meropenem and Bacterial-Infections

Bacteroides fragilis is an important etiological agent of serious infections in humans. Rapid methods, readily adaptable to use in medical laboratories, are needed to detect antibiotic resistance and decrease the likelihood of therapy failure. The aim of this study was to determine the prevalence of B. fragilis cfiA-positive isolates. The second purpose was to investigate the carbapenemase activity in B. fragilis strains by Carba NP test. In the study, 5.2% of B. fragilis isolates are phenotypically resistant to meropenem. The cfiA gene was identified in 6.1% of B. fragilis isolates. The MICs of meropenem were significantly higher in cfiA-positive strains. The presence of the cfiA gene along with the IS1186 was detected in one B. fragilis strain which was resistant to meropenem (MIC 1.5 mg/L). The Carba NP test results were positive for all the cfiA-positive strains, including those susceptible to carbapenems based on their MIC values. A review of the literature revealed that the rate of B. fragilis with the cfiA gene varies from 7.6 to 38.9% worldwide. Presented results are in line with the other European studies. Phenotypic testing with the Carba NP test, it seems to be a viable alternative for the cfiA gene detection in B. fragilis isolates. The positive result obtained is of greater clinical importance than the detection of the gene cfiA.

Topics: Anti-Bacterial Agents; Bacterial Infections; Bacterial Proteins; Bacteroides fragilis; Carbapenems; Humans; Meropenem; Microbial Sensitivity Tests

An increase in the number of multidrug-resistant microbial strains is the biggest threat to global health and is projected to cause >10 million deaths by 2055. The carbapenem family of antibacterial drugs are an important class of last-resort treatment of infections caused by drug-resistant bacteria and are only available as an injectable formulation. Given their instability within the gut and poor permeability across the gut wall, oral carbapenem formulations show poor bioavailability. Meropenem (MER), a carbapenem antibiotic, has broad-spectrum antibacterial activity, but suffers from the above-mentioned issues. In this review, we discuss strategies for improving the oral bioavailability of MER, such as inhibiting tubular secretion, prodrug formulations, and use of nanomedicine. We also highlight challenges and emerging approaches for the development of oral MER.

Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Bacterial Infections; Biological Availability; Drug Development; Drug Resistance, Multiple, Bacterial; Global Health; Humans; Meropenem

β-Lactam antibiotics are one of the most relevant drug classes of antibacterial agents worldwide. The discovery and the market of first β-lactam antibiotic (Penicillin G) is a symbolic landmark of modern chemotherapy. Since then, several other β-lactam antibiotics have been introduced in the therapy, revolutionizing the treatment of bacterial infections. Their antibacterial efficacy has been kept in check by the emergence of bacterial resistance. Among the resistance mechanisms, the expression of β-lactamase enzymes is one of the most studied and prevalent. The combined use of beta-lactamase inhibitors with broad spectrum activity β-lactam antibiotics has been an effective strategy to circumvent the resistance issue. This review discusses, with a focus on structural aspects, the different classes of beta-lactam antibiotics (penicillins, cephalosporins, carbapenems, monobactams and penems) in light of their stability, sensitivity to β-lactamases, mechanism of action and spectrum of antimicrobial activity. β-Lactamase inhibitors (structurally correlated and non-correlated to the β-lactam system) and their proposed inhibition mechanisms are also discussed.

Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; beta-Lactamase Inhibitors; beta-Lactamases; beta-Lactams; Chemistry, Pharmaceutical; Humans; Hydrolysis; Models, Chemical; Molecular Structure

Carbapenems are broad-spectrum antibacterial molecules. Imipenem-cilastatin and meropenem are the two main molecules used in French healthcare services.. We aimed to evaluate the relative strengths and weaknesses of these two molecules by considering their pharmacokinetic, pharmacodynamic, microbiological, and clinical properties. We demonstrated that imipenem-cilastatin and meropenem are not alike.. Review of the literature by querying the MEDLINE network.. Imipenem-cilastatin is the first marketed molecule of the carbapenem class. It is more effective against Gram-positive cocci. Its stability does not allow for long infusions and its main adverse effect on the central nervous system limits its use. Meropenem is more effective against Gram-negative bacilli. Its stability and its milder adverse effects distinguish it from imipenem-cilastatin.. Meropenem is preferred for daily use in healthcare services when carbapenems are to be used.

Topics: Anti-Bacterial Agents; Bacterial Infections; Biotransformation; Child; Child, Preschool; Cilastatin, Imipenem Drug Combination; Contraindications, Drug; Drug Resistance, Microbial; Drug Resistance, Multiple, Bacterial; Drug Stability; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Infant; Liver Failure; Meropenem; Molecular Structure; Organ Specificity; Pregnancy; Pregnancy Complications, Infectious; Protein Binding

Beta-lactam dose optimization in critical care is a current priority. We aimed to review the pharmacokinetics (PK) of three commonly used beta-lactams (amoxicillin ± clavulanate, piperacillin-tazobactam and meropenem) to compare PK parameters reported in critically and noncritically ill neonates, children and adults, and to investigate whether allometric and maturation scaling principles could be applied to describe changes in PK parameters through life.. A systematic review of PK studies of the three drugs was undertaken using MEDLINE and EMBASE. PK parameters and summary statistics were extracted and scaled using allometric principles to 70 kg individual for comparison. Pooled data were used to model clearance maturation and decline using a sigmoidal (Hill) function.. A total of 130 papers were identified. Age ranged from 29 weeks to 82 years and weight from 0.9-200 kg. PK parameters from critically ill populations were reported with wider confidence intervals than those in healthy volunteers, indicating greater PK variability in critical illness. The standard allometric size and sigmoidal maturation model adequately described increasing clearance in neonates, and a sigmoidal model was also used to describe decline in older age. Adult weight-adjusted clearance was achieved at approximately 2 years postmenstrual age. Changes in volume of distribution were well described by the standard allometric model, although amoxicillin data suggested a relatively higher volume of distribution in neonates.. Critical illness is associated with greater PK variability than in healthy volunteers. The maturation models presented will be useful for optimizing beta-lactam dosing, although a prospective, age-inclusive study is warranted for external validation.

Topics: Adult; Age Factors; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bacterial Infections; beta-Lactamase Inhibitors; Biological Variation, Population; Child; Critical Illness; Dose-Response Relationship, Drug; Healthy Volunteers; Humans; Infant, Newborn; Meropenem; Microbial Sensitivity Tests; Piperacillin, Tazobactam Drug Combination

To review the pharmacology, spectrum of activity, pharmacokinetics, pharmacodynamics, safety, efficacy, administration, and considerations for clinical use of meropenem/vaborbactam (M/V).. A literature search using PubMed and clinicaltrials.gov (June 2013 to December 2017) was conducted using the search terms meropenem, vaborbactam, RPX7009, biapenem, RPX2003, and carbavance. References from relevant articles and conference abstracts were also reviewed.. Preclinical, phase I studies, and phase III studies written in the English language were evaluated.. M/V is a novel carbapenem/β-lactamase inhibitor antimicrobial with in vitro activity against nearly 99% of Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae. M/V is approved for the treatment of adults with complicated urinary tract infections (cUTIs), including pyelonephritis. In a phase III cUTI trial (TANGO I), 98.4% of patients treated with M/V experienced overall clinical success compared with 94% of patients treated with piperacillin/tazobactam (95% CI = 0.7 to 9.1). When compared with best available therapy for carbapenem-resistant Enterobacteriaceae (CRE) infections in TANGO II, patients receiving M/V were more likely to achieve clinical cure at both the end of therapy (64.3% vs 33.3%, P = 0.04) as well as at the test of cure (57.1% vs 26.7%, P = 0.04). The most common adverse effects associated with M/V were headache, infusion-site reactions, and diarrhea.. M/V has a valuable role in the treatment of CRE and should be used judiciously to preserve its use for resistant infections.

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Boronic Acids; Humans; Meropenem

To prevent the devastating consequences of infection, most infants admitted to the neonatal intensive care unit are exposed to antibiotics. However, dosing regimens are often extrapolated from data in adults and older children, increasing the risk for drug toxicity and lack of clinical efficacy because they fail to account for developmental changes in infant physiology. However, newer technologies are emerging with minimal-risk study designs, including ultra-low-volume assays, pharmacokinetic modeling and simulation, and opportunistic drug protocols. With minimal-risk study designs, pharmacokinetic data and dosing regimens for infants are now available for ampicillin, clindamycin, meropenem, metronidazole, and piperacillin/tazobactam.

Topics: Ampicillin; Anti-Bacterial Agents; Bacterial Infections; Clindamycin; Humans; Infant; Infant, Newborn; Infant, Premature; Intensive Care Units, Neonatal; Meropenem; Metronidazole; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Practice Guidelines as Topic; Thienamycins

Meropenem is the first representative of carbapenem analogues with methyl group, which has been applied in medicine. This drug has been approved by FDA (Food and Drug Administration) in 1996. Available results of clinical trials and scientific reports point surprising synergism of combination of meropenem with other chemotherapeutics, in the treatment of bacterial diseases. Present study based on available information presents indications for use the mentioned antibiotic in pharmacotherapy of infectious diseases. Meropenem is the first representative of carbapenem analogues, which contains methyl group. Introduction of a methyl group at the system of coupled rings: β-lactam and pyrrolidine, solved the problem of degradation by the dehydropeptidase-I (DHP-I). In the consequence it is not necessary to use meropenem in the connection with specific DHP-I inhibitors. Meropenem, similarly to other carbapanem analogues, is intended for the treatment of severe inpatient and outpatient infections. Bacterial resistance to meropenem may be the result of: carbapenemases activity, decreased affinity to Penicillin Binding Proteins--PBP (mainly PBP 2 and PBP 3) and activation of efflux pump (antibiotic ejection outside the cell). Twenty-year period of application of meropenem in pharmacotherapy may cause the spread of methyl-β-lactamases.

Topics: Anti-Bacterial Agents; Bacterial Infections; Child; Drug Synergism; Humans; Meropenem; Thienamycins; Tuberculosis; United States

To systematically review evidence comparing traditional and alternative dosing strategies for meropenem, based on clinical and pharmacoeconomic outcomes.. MEDLINE (1950-September 2009), EMBASE (1980-September 2009), and International Pharmaceutical Abstracts (1970-September 2009) were searched, using the terms meropenem, carbapenems, pharmacodynamics, and pharmacokinetics. Reference citations from publications identified were reviewed.. Articles discussing administration of meropenem to adults with normal renal function and comparing at least 2 regimens, 1 of which included the manufacturer-recommended regimen of 0.5 g or 1 g every 8 hours infused over 30 minutes, with clinical, pharmacodynamic, or pharmacoeconomic endpoints, were included. The pharmacodynamic endpoint of interest was percent time that the unbound drug concentration exceeded the minimal inhibitory concentration for a bacterial pathogen.. Sixteen studies were reviewed, which included 13 pharmacokinetic and dynamic assessments using Monte Carlo simulations, 5 clinical evaluations, and 3 pharmacoeconomic appraisals. Data on clinical and economic outcomes are largely nonrandomized retrospective analyses and case reports. Meropenem via intermittent prolonged infusion potentially increases the likelihood of achieving pharmacodynamic targets. However, a strong link with improved clinical outcomes is lacking. Smaller doses with shorter intervals appear to provide pharmacodynamic target attainment rates and clinical outcomes similar to those with traditional dosing, with potential pharmacoeconomic benefits. Meropenem via continuous infusion appears to increase the likelihood of achieving pharmacodynamic targets, compared with intermittent infusions. The sparsity of clinical evidence supporting this practice limits its broad application to practice. No studies have formally examined adverse effects with alternative dosing regimens.. Meropenem alternative dosing strategies provide similar pharmacodynamic target attainment rates compared with traditional dosing strategies. Small doses with shorter interval dosing provide additional pharmacoeconomic benefits and similar clinical outcomes. Alternative dosing strategies for meropenem were largely studied in healthy subjects; individuals with pharmacokinetic parameters that differ significantly may be ideal subjects for empiric dose modification.

Topics: Adult; Animals; Anti-Bacterial Agents; Bacterial Infections; Dose-Response Relationship, Drug; Drug Administration Schedule; Economics, Pharmaceutical; Humans; Meropenem; Thienamycins; Treatment Outcome

Increasing frequency of infections due to multi-drug resistant organisms is currently observed in the adult and pediatric population. Therapeutic options are unfortunately limited to treat such infections. It is the clinician's responsibility to use wide-spectrum antibiotics when appropriate, but also to limit the use of these drugs to the sole situations where such a potent treatment is required. Carbapenems are the most efficient beta-lactams, especially against gram-negative bacilli, and the most preserved from resistance so far. This review summarizes microbiological, pharmacokinetic and pharmacodynamic characteristics of currently available cabapenems. Their clinical use in different pediatric settings is then discussed, based on available published evidence. In order to maintain their microbiological efficiency and to limit the emergence of carbapem-resistant strains, carbapenems should be exclusively used for infections due to gram-negative bacilli showing resistance to other beta-lactams. In the next years meropenem should logically replace imipenem indications regarding its superior pharmacokinetic-pharmacodynamic properties, its higher tolerance and its easier use in the pediatric population.

Topics: Adult; Anti-Bacterial Agents; Bacterial Infections; Carbapenems; Child; Drug Tolerance; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Meropenem; Thienamycins

Meropenem is a carbapenem antibiotic approved by the US Food and Drug Administration for the treatment of complicated skin and skin-structure infections, complicated intra-abdominal infections, and pediatric bacterial meningitis (in patients >or=3 months of age). In clinical trials, it also has shown efficacy as initial empirical therapy for the treatment of nosocomial pneumonia. Unlike other beta-lactam antibiotics, including third-generation cephalosporins, carbapenems have shown activity against extended-spectrum beta-lactamase-producing and AmpC chromosomal beta-lactamase-producing bacteria. Compared with imipenem, meropenem is more active against gram-negative pathogens and somewhat less active against gram-positive pathogens, and it does not require coadministration of a renal dehydropeptidase inhibitor. In most comparative trials, clinical and bacteriological response rates with imipenem and meropenem were similar. Compared with clindamycin/tobramycin, meropenem is associated with a reduced length of hospital stay and a shorter duration of therapy among patients with complicated intra-abdominal infections. Meropenem is well tolerated by children and adults and has an acceptable safety profile. Alternative meropenem dosing strategies for the optimization of outcomes are under investigation.

Topics: Abdominal Abscess; Bacteria; Bacterial Infections; Cross Infection; Humans; Infant; Meningitis, Bacterial; Meropenem; Pneumonia; Skin Diseases, Bacterial; Thienamycins

Meropenem (Merrem, Meronem) is a broad-spectrum antibacterial agent of the carbapenem family, indicated as empirical therapy prior to the identification of causative organisms, or for disease caused by single or multiple susceptible bacteria in both adults and children with a broad range of serious infections. Meropenem is approved for use in complicated intra-abdominal infection (cIAI), complicated skin and skin structure infection (cSSSI) and bacterial meningitis (in paediatric patients aged > or = 3 months) in the US, and in most other countries for nosocomial pneumonia, cIAI, septicaemia, febrile neutropenia, cSSSI, bacterial meningitis, complicated urinary tract infection (UTI), obstetric and gynaecological infections, in cystic fibrosis patients with pulmonary exacerbations, and for the treatment of severe community-acquired pneumonia (CAP). Meropenem has a broad spectrum of in vitro activity against Gram-positive and Gram-negative pathogens, including extended-spectrum beta-lactamase (ESBL)- and AmpC-producing Enterobacteriaceae. It has similar efficacy to comparator antibacterial agents, including: imipenem/cilastatin in cIAI, cSSSI, febrile neutropenia, complicated UTI, obstetric or gynaecological infections and severe CAP; clindamycin plus tobramycin or gentamicin in cIAI or obstetric/gynaecological infections; cefotaxime plus metronidazole in cIAI; cefepime and ceftazidime plus amikacin in septicaemia or febrile neutropenia; and ceftazidime, clarithromycin plus ceftriaxone or amikacin in severe CAP. Meropenem has also shown similar efficacy to cefotaxime in paediatric and adult patients with bacterial meningitis, and to ceftazidime when both agents were administered with or without tobramycin in patients with cystic fibrosis experiencing acute pulmonary exacerbations. Meropenem showed greater efficacy than ceftazidime or piperacillin/tazobactam in febrile neutropenia, and greater efficacy than ceftazidime plus amikacin or tobramycin in patients with nosocomial pneumonia. Meropenem is well tolerated and has the advantage of being suitable for administration as an intravenous bolus or infusion. Its low propensity for inducing seizures means that it is suitable for treating bacterial meningitis and is the only carbapenem approved in this indication. Thus, meropenem continues to be an important option for the empirical treatment of serious bacterial infections in hospitalized patients.

Topics: Anti-Bacterial Agents; Bacterial Infections; Cost-Benefit Analysis; Drug Costs; Humans; Meropenem; Severity of Illness Index; Thienamycins; Treatment Outcome

The carbapenems are beta-lactam antimicrobial agents with an exceptionally broad spectrum of activity. Older carbapenems, such as imipenem, were often susceptible to degradation by the enzyme dehydropeptidase-1 (DHP-1) located in renal tubules and required co-administration with a DHP-1 inhibitor such as cilastatin. Later additions to the class such as meropenem, ertapenem and doripenem demonstrated increased stability to DHP-1 and are administered without a DHP-1 inhibitor. Like all beta-lactam antimicrobial agents, carbapenems act by inhibiting bacterial cell wall synthesis by binding to and inactivating penicillin-binding proteins (PBPs). Carbapenems are stable to most beta-lactamases including AmpC beta-lactamases and extended-spectrum beta-lactamases. Resistance to carbapenems develops when bacteria acquire or develop structural changes within their PBPs, when they acquire metallo-beta-lactamases that are capable of rapidly degrading carbapenems, or when changes in membrane permeability arise as a result of loss of specific outer membrane porins. Carbapenems (imipenem, meropenem, doripenem) possess broad-spectrum in vitro activity, which includes activity against many Gram-positive, Gram-negative and anaerobic bacteria; carbapenems lack activity against Enterococcus faecium, methicillin-resistant Staphylococcus aureus and Stenotrophomonas maltophilia. Compared with imipenem, meropenem and doripenem, the spectrum of activity of ertapenem is more limited primarily because it lacks activity against Pseudomonas aeruginosa and Enterococcus spp. Imipenem, meropenem and doripenem have in vivo half lives of approximately 1 hour, while ertapenem has a half-life of approximately 4 hours making it suitable for once-daily administration. As with other beta-lactam antimicrobial agents, the most important pharmacodynamic parameter predicting in vivo efficacy is the time that the plasma drug concentration is maintained above the minimum inhibitory concentration (T>MIC). Imipenem/cilastatin and meropenem have been studied in comparative clinical trials establishing their efficacy in the treatment of a variety of infections including complicated intra-abdominal infections, skin and skin structure infections, community-acquired pneumonia, nosocomial pneumonia, complicated urinary tract infections, meningitis (meropenem only) and febrile neutropenia. The current role for imipenem/cilastatin and meropenem in therapy remains for use in moderate to severe nosocomial and p

Topics: Anti-Bacterial Agents; Bacterial Infections; beta-Lactams; Carbapenems; Doripenem; Ertapenem; Humans; Imipenem; Meropenem; Thienamycins

Meropenem is a broad-spectrum carbapenem antibacterial with potent antimicrobial activity against a broad range of Gram-negative, Gram-positive and anaerobic bacteria. The second parenteral carbapenem to be introduced worldwide, meropenem has been in clinical use since 1994. Two previous safety reviews have established that meropenem has a favourable and acceptable safety profile. This new review was conducted after the approval of meropenem in the US in 2005 for the treatment of patients with complicated skin and skin-structure infections, in addition to the previously approved indications of intra-abdominal infections and paediatric bacterial meningitis. The analysis includes the clinical trial data from the previous safety reviews, updated with expanded experience across a number of serious bacterial infections, including a large international study in patients with skin or skin-structure infections and further experience in patients with intra-abdominal infections and bacterial meningitis. A total of 6154 patients with 6308 meropenem exposures were compared with 4483 patients treated with comparator agents (4593 exposures), and the paediatric population base for which safety data are available has doubled to over 1000 patients. The data presented reinforce the favourable safety profile of meropenem. In general, the incidence and pattern of adverse events occurring with meropenem were similar to those of the first carbapenem, imipenem/cilastatin, and to those of the cephalosporin- and clindamycin-based regimens to which it had been compared. The most common adverse events reported for meropenem were diarrhoea (2.5%), rash (1.4%) and nausea/vomiting (1.2%). No adverse event occurred in more than 3% of patient exposures to meropenem, indicating a low overall frequency of adverse events as well as excellent gastrointestinal tolerability. Furthermore, no unexpected adverse events were identified, and the very low incidence of seizures in patients with meningitis was not considered to be drug related. In infections other than meningitis, the incidence of seizures considered by investigators to be related to meropenem treatment was 0.07%. In the new studies that updated the earlier safety data, no new cases of drug-related seizure were reported for any treatment or patient group (meningitis/non-meningitis infections). In conclusion, meropenem is well tolerated and has good CNS and gastrointestinal tolerability when used for the treatment of serious bacterial

Topics: Anti-Bacterial Agents; Bacterial Infections; Clinical Trials as Topic; Humans; Meropenem; Thienamycins

The threat of antibacterial resistance continues to increase globally, and therapeutic options for the treatment of some serious infectious diseases are diminishing. The carbapenems are a potent class of broad-spectrum drugs, and their stability against hydrolysis by many important beta-lactamases make them an important weapon in the treatment of beta-lactamase-producing bacterial pathogens. This review focuses on four carbapenems of clinical importance in the USA: imipenem, meropenem, ertapenem and doripenem. After a historical review of carbapenem development, these four carbapenems are evaluated based on their mechanism of action, spectrum of activity, potency, pharmacodynamics, clinical pharmacokinetics, clinical profiles and toxicity issues.

Topics: Anti-Bacterial Agents; Bacterial Infections; beta-Lactams; Carbapenems; Clinical Trials as Topic; Doripenem; Drug Resistance, Multiple, Bacterial; Ertapenem; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Structure-Activity Relationship; Thienamycins; United States

Meropenem is a new carbapenem antibacterial agent with wide spectrum of activity against gram-negative, gram-positive and anaerobic organisms. It is stable against most beta-lactamases produced by gram-negative bacteria and has greatest utility in treating severe infections in hospitalized children. It has good CSF penetrability and useful in treatment of childhood meningitis and infections in neutropenic children. Due to concern relating to emergence of resistance, it should be used as a reserve drug in difficult-to-treat infections caused by resistant organisms or when conventional treatment fails.

Topics: Bacterial Infections; Central Nervous System Bacterial Infections; Child; Child, Preschool; Drug Resistance, Bacterial; Humans; Infant; Infant, Newborn; Intensive Care Units; Meropenem; Neutropenia; Thienamycins

To compare the effectiveness of meropenem with imipenem plus cilastatin in the treatment of severe infections.. CENTRAL, EMBASE and MEDLINE were searched for abstracts and papers. All searching was completed in March 2004. No restriction was placed on language.. Randomized controlled trials of adult patients with severe infections treated with meropenem or imipenem plus cilastatin at an equal dose, on a gram-for-gram basis, and with the same dosing regimen.. Two reviewers independently assessed papers against the inclusion/exclusion criteria and for methodological quality with differences in opinion adjudicated by a third party. Data were extracted on clinical response, bacteriologic response, mortality and adverse events.. A total of 27 trials met the inclusion criteria. Meta-analyses were carried out using a Fixed Effects model. Results demonstrated that when compared to imipenem plus cilastatin, meropenem is associated with a significantly greater clinical response (Relative Risk 1.04; 95% Confidence Interval: 1.01-1.06), a significantly greater bacteriologic response (RR 1.05; 95% CI: 1.01-1.08), a non-significant reduction in mortality (RR 0.98; 95% CI: 0.71-1.35), and a significantly lower adverse event rate (RR 0.87; 95% CI: 0.77-0.97).. This systematic review demonstrates that meropenem compared to imipenem plus cilastatin has a significantly greater clinical and bacteriologic response with a significant reduction in adverse events. There was no evidence of heterogeneity or publication bias and the analyses were robust to changes in the inclusion/exclusion criteria and use of a Random Effects model.

Topics: Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Drug Therapy, Combination; Humans; Imipenem; Meropenem; Protease Inhibitors; Randomized Controlled Trials as Topic; Risk; Thienamycins

This overview provides a summary of the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program over an 8-year period from 1997 to 2004. The evolution of the MYSTIC Program is described, as well as its design compared with other surveillance programs. In addition, the global MYSTIC Program data, published to date, are summarized, and the empiric use of carbapenems, their current indications, and meropenem usage versus resistance was discussed. From 1997 to 2004, 120 medical centers that were actively prescribing meropenem in 32 countries worldwide participated in the program. The MYSTIC Program results demonstrate the sustained potency and continued effectiveness of meropenem globally against clinically relevant Gram-negative and Gram-positive pathogens including extended spectrum beta-lactamase- and AmpC beta-lactamase-producing organisms, which may also display resistance to the fluoroquinolones and/or aminoglycosides. Furthermore, in centers actively prescribing meropenem, resistance to meropenem is not increasing despite greater resistance among the comparator antimicrobial agents. Thus, antipseudomonal carbapenems such as meropenem and imipenem remain an effective treatment option.

Topics: Anti-Bacterial Agents; Bacterial Infections; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Meropenem; Microbial Sensitivity Tests; Population Surveillance; Thienamycins

The carbapenems are a group of broad-spectrum beta-lactam antibiotic agents of which there are three parenteral preparations currently available in South Africa, namely imimpenem/cilastatin, meropenem and ertapenem. Owing to the fact that imipenem/cilastatin and meropenem have a broad spectrum of activity that includes Pseudomonas and Acinetobacter species, they are ideal antibiotics for treatment of severe nosocomial infections. In contrast, ertapenem has limited in vitro activity against the latter non-fermentative gram-negative bacteria and is therefore more suitable for the treatment of certain severe community-acquired infections. This statement arises out of concerns about the general abuse of antibiotics such as the carbapenems, with the primary intention of highlighting the appropriate use of these agents.

Topics: Anti-Bacterial Agents; Bacterial Infections; beta-Lactams; Carbapenems; Cilastatin; Community-Acquired Infections; Cross Infection; Drug Resistance, Bacterial; Drug Utilization; Ertapenem; Humans; Imipenem; Lactams; Meropenem; Patient Selection; Pneumonia, Bacterial; Practice Patterns, Physicians'; Protease Inhibitors; South Africa; Surgical Wound Infection; Thienamycins; Urinary Tract Infections

Meropenem, first synthesized in the late eighties, has become one of the most important beta-lactam antibiotics of the carbapenem subclass used for the treatment of a variety of life-threatening infections. Due to its unique chemical structure, meropenem is not inactivated by the kidney dehydropeptidase I and the majority of microbial beta-lactamases. Its antimicrobial activity is based on its high affinity for the majority of cell wall-synthesizing enzymes, the so-called penicillin-binding proteins, of Gram-positive and -negative bacteria. However, bacteria have evolved several approaches to resist meropenem: (i) by reducing the affinity of the penicillin-binding proteins for the antibiotics, (ii) by decreasing the permeability of the outer membrane of Gram-negative bacteria, (iii) by using efflux pumps, and (iv) by activating zinc-dependent carbapenemases. Meropenem has a low toxicity profile and, in contrast to imipenem, no central nervous system toxicity.

Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Bacterial Outer Membrane Proteins; beta-Lactam Resistance; Forecasting; Humans; Meropenem; Protein Binding; Thienamycins

Topics: Adolescent; Bacterial Infections; Carbapenems; Child; Child, Preschool; Clinical Trials as Topic; Humans; Imipenem; Infant; Infant, Newborn; Meropenem; Postoperative Complications; Thienamycins

Meropenem is a carbapenem antibacterial agent that has antimicrobial activity against gram-negative, gram-positive and anaerobic micro-organisms. In vitro studies involving isolates from patients in intensive care units (ICUs) indicate that meropenem is more active against most gram-negative pathogens than other comparators (including imipenem), although, compared with imipenem, meropenem is less active against most gram-positive organisms. Resistance to meropenem is uncommon in most bacteria. Treatment with meropenem as initial empirical monotherapy was effective in a range of serious infections in adult and paediatric ICU patients. Meropenem monotherapy was as effective as imipenem/cilastatin in 4 comparative trials in terms of satisfactory clinical and bacteriological responses. Meropenem monotherapy was significantly more effective than ceftazidime-based combination treatments in 2 trials in patients with nosocomial lower respiratory tract infections (LRTIs) in terms of both clinical and bacteriological responses. Meropenem was also more active than ceftazidime-based treatments against both gram-positive and gram-negative organisms. However, 2 studies in patients with a range of serious infections found no significant differences between meropenem and cephalosporin-based treatments in terms of clinical or bacteriological response. Meropenem was also as effective as cephalosporin-based treatments in comparative trials in children with serious infections. Meropenem is well tolerated as either a bolus or an infusion, and clinical trials have shown similar incidences of adverse events to those observed with cephalosporin-based treatments. It is well tolerated by the CNS, with seizures reported infrequently, and can therefore be used at high doses and in patients with meningitis. The incidence of drug-related nausea and vomiting is low and, in contrast to imipenem/cilastatin, does not increase with dose or speed of administration.. Meropenem is a well tolerated broad spectrum antibacterial agent that, when used as initial empirical monotherapy, is as effective as imipenem/cilastatin in the treatment of a range of serious infections (including nosocomial) in adults and children in ICUs. Compared with cephalosporin-based combination treatments, meropenem monotherapy may be more effective in the treatment of nosocomial LRTIs and can be used as monotherapy. Meropenem has an important role in the empirical treatment of serious infections in adults and children in ICUs.

Topics: Adult; Aged; Aging; Animals; Anti-Bacterial Agents; Area Under Curve; Bacterial Infections; Child; Cross Infection; Humans; Infant, Newborn; Intensive Care Units; Meropenem; Metabolic Clearance Rate; Microbial Sensitivity Tests; Randomized Controlled Trials as Topic; Thienamycins; Tissue Distribution

To collate the clinical response and pathogen eradication rates for meropenem monotherapy with in vitro susceptibility of the causative pathogens.. Data were compiled from 17 randomized clinical studies that compared meropenem monotherapy with standard treatment options, often combinations. A total of 4906 pathogens from lower respiratory tract, intra-abdominal, obstetric/gynecological, skin/soft tissue, meningitis, or pediatric infections were assessed. Of these, 3713 pathogens (1963 meropenem, 1750 comparators) were evaluable.. The overall rates of satisfactory clinical response (cure or improvement) and pathogen eradication (eradication or presumed eradication) at the end of therapy were similar with meropenem (93% for both responses) and the comparators (92%), as were the rates in each infection type. For each pathogen, the clinical response and eradication rates with meropenem were similar across the minimum inhibitory concentration (MIC) range of < or = 0.25 to 4 mg/L. Overall, a satisfactory clinical response occurred in 93% (1580 of 1708) of infections caused by nonfastidious pathogens with MICs < or = 4 mg/L and in 84% (16 of 19) of those with an MIC of 8 mg/L. Pathogen eradication rates were similar (93 and 79%, respectively). A similar profile was observed for fastidious pathogens. The high rates of satisfactory clinical response and pathogen eradication produced by meropenem in each type of infection were generally independent of the causative pathogen, whether Gram-positive or -negative aerobe or anaerobe or when occurring as mono- or polymicrobial infections.. The attractive in vitro profile of meropenem translates into good clinical efficacy. The National Committee for Clinical Laboratory Standards has now defined meropenem MIC breakpoints for nonfastidious aerobes or anaerobes as < or = 4 (susceptible), 8 (intermediate) and > or = 16 mg/L (resistant), respectively. The susceptibility breakpoint for Streptococcus spp. (excluding Streptococcus pneumoniae) is < or = 0.5 mg/L and, since meropenem is indicated for the treatment of meningitis, the susceptibility breakpoint for S. pneumoniae and Haemophilus influenzae is < or = 0.25 and < or = 0.5 mg/L, respectively. Meropenem monotherapy is therefore a valid option for the initial empirical treatment of a range of serious infections caused by single or multiple bacterial pathogens.

Topics: Bacteria; Bacterial Infections; Drug Therapy, Combination; Meropenem; Microbial Sensitivity Tests; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Thienamycins; Treatment Outcome

Anti-infectious drugs are among the most-prescribed medications in the community, in 1997 being more than 9% of all drugs prescribed by the Spanish National Health System. In the particular case of the treatment of patients with moderate or severe intra-abdominal infection, economic aspects are important. Antimicrobial therapy is responsible for as much as 50% of the drug budget in some Spanish hospitals. On the other hand, as more options become available for the treatment of intra-abdominal infection, it is important to know their clinical and economic consequences. Imipenem/cilastatin (IC) is a broad-spectrum beta-lactam antibiotic that has demonstrated its effectiveness in the treatment of nosocomial and community-acquired bacterial infections.. The objective of this study was to determine if IC has a favorable cost-effectiveness relation compared to other antibiotic therapies for the treatment of intra-abdominal infections.. A cost-effectiveness analysis was made based on retrospective information on the treatment of patients over 18 with clinical suspicion of moderate-to-severe intra-abdominal infection. Health-care results were measured in natural health units (percentage of clinically favorable cases) in a systematic review of the literature. Direct health-care costs associated with the treatments compared were calculated. The other options studied, apart from IC, included the most common and least expensive option (a combination of an aminoglycoside and an anaerobicide [AA]) and an antibiotic from the same family as IC, meropenem (M).. The results, in terms of the percentage of patients with clinically favorable results, showed that the effectiveness of IC was equivalent to that of M (95.2% vs. 96.4%) and the AA association (88.0% vs. 86.6%). Analysis of cost minimization showed that the total cost per patient treated with the IC and M options was similar, but that the lower price of IC slightly reduced the total cost per patient treated (ptas. 455,320 IC and ptas. 483,404 M). In the comparison of IC and AA, the higher price of IC was compensated for by the lower cost associated with the duration of hospitalization in patients treated with IC (total cost per patients treated ptas. 844,678 IC and ptas. 1,009,180 AA).. The results of the meta-analysis showed that imipenem/cilastatin was highly effective (more than 90% clinically favorable results) and that it can be considered a minimum equivalent to meropenem and to the combination of an aminoglycoside and anaerobicide for the treatment of patients with moderate or severe intra-abdominal infection. Given the equivalence in effectiveness of the options studied, analysis of cost minimization was used to study their relative effectiveness. This analysis showed that IC was accompanied by lower costs per patient than M and AA. The most relevant variables in the study of the efficiency of the treatment of intra-abdominal infections were, in conditions of equivalent effectiveness, days of hospitalization (and associated costs) and drug price.

Topics: Abdomen; Adult; Aged; Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Child; Cilastatin; Clinical Trials as Topic; Cost-Benefit Analysis; Double-Blind Method; Drug Costs; Drug Therapy, Combination; Evidence-Based Medicine; Health Care Costs; Hospital Costs; Humans; Imipenem; Meropenem; Middle Aged; Odds Ratio; Prospective Studies; Single-Blind Method; Spain; Thienamycins; Treatment Outcome

The safety profile of meropenem in the elderly (aged > 65 years, n=843) and/or renally impaired (creatinine clearance < 51 ml/min, n=436) was assessed by evaluating data from 26 phase III studies which compared the use of meropenem (0.5 or 1.0 g, i.v. every 8 h) with other antimicrobial agents in patients with bacterial infections. The overall pattern and frequency of adverse events following meropenem therapy in the elderly and/or renally impaired were similar to those in younger and/or non-renally impaired cohorts and to imipenem/cilastatin and injectable third generation cephalosporins. Both dosages of meropenem (0.5 and 1.0 g, i.v. every 8 h) were generally well tolerated. There was no clinically significant mean change in indicators of renal flux between baseline and the end of treatment in any patient sub-group. Importantly, meropenem-related seizures were rare (0.1%), even in patients with renal impairment. In summary, meropenem has an excellent safety profile and is therefore suitable for use in elderly and/or renally impaired patients.

Topics: Aged; Bacterial Infections; Humans; Kidney Failure, Chronic; Meropenem; Seizures; Thienamycins

Meropenem is a new beta-lactam carbapenem antibiotic that appears to be promising in the treatment of hospitalized infants and children with serious infections. It has broad-spectrum activity against microorganisms, including most of the major aerobic (gram-negative and gram-positive) and anaerobic pathogens that cause serious bacterial infections in neonates and children. In addition, its pharmacokinetic profile makes possible parenteral administration every 8 hours. Several studies have demonstrated that meropenem is an effective and safe treatment for infants and children with serious pediatric infections (e.g., urinary tract infections, pneumonia, sepsis, intraabdominal infections, and skin and soft-tissue infections), bacterial meningitis, and cystic fibrosis. The results of further studies of the use of meropenem in the treatment of high-risk seriously ill infants and children are awaited with interest.

Topics: Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Clinical Trials as Topic; Cystic Fibrosis; Female; Hospitalization; Humans; Infant; Infant, Newborn; Male; Meningitis, Bacterial; Meropenem; Microbial Sensitivity Tests; Thienamycins

Administration of empirical antibiotic therapy is now standard practice in the management of febrile neutropenia, but there has been considerable debate about the selection of an efficacious empirical antimicrobial regimen over the past 2 decades. A variety of approaches, including both monotherapeutic and multidrug regimens, have been demonstrated to be effective, although no one regimen has been proven to be superior to another. Changes in the epidemiology of infectious organisms and the growing emergence of highly drug-resistant strains make it necessary to continually reevaluate the therapeutic options. Fortunately, the number of therapeutic options has also been broadening as new antimicrobial agents, including third-generation cephalosporins and carbapenem antibiotics such as imipenem and meropenem, become available. Optimal management is directed by the findings of a clinical evaluation of the patient as well as an awareness of institutional patterns of infection and susceptibility of likely infecting organisms.

Topics: Anti-Bacterial Agents; Bacterial Infections; Cephalosporins; Clinical Trials as Topic; Drug Resistance, Microbial; Drug Therapy, Combination; Fever; Humans; Imipenem; Meropenem; Neutropenia; Thienamycins

Meropenem is a carbapenem antibiotic that appears to be widely distributed in tissues and is eliminated by both excretion and metabolism. Approximately 70% of meropenem is excreted via the kidneys, thus dosage adjustments are required for patients with renal impairment. The pharmacokinetic parameters for meropenem are similar to those for imipenem/cilastatin, with the exception of meropenem's smaller volume of distribution. The urinary recovery of meropenem is as high as that of imipenem in combination with cilastatin, an inhibitor of renal dehydropeptidase. Therefore, unlike imipenem, meropenem can be used without dehydropeptidase inhibitors to obtain a consistently high concentration in the urine without nephrotoxic effects.

Topics: Adult; Aged; Animals; Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Cilastatin; Drug Therapy, Combination; Humans; Imipenem; Infant; Kidney; Meropenem; Molecular Structure; Protease Inhibitors; Rabbits; Rats; Thienamycins; Urine

Meropenem, a new carbapenem antibiotic, is more active against gram-negative bacilli and less active against gram-positive cocci than is imipenem, and there are several important structural differences between meropenem and the older carbapenem. These differences may be responsible for the lower potential for the induction of epileptogenic activity observed with meropenem as well as for its increased stability to degradation by dehydropeptidase-I. The pharmacokinetics of meropenem are typical of those of a parenteral beta-lactam antibiotic with low protein binding and predominantly renal excretion. Dosage reduction is required in patients with reduced renal function; no dosage adjustment is required for patients with hepatic impairment. Meropenem has excellent penetration in abdominal tissues, bile, blister fluid, inflammatory exudate, cerebrospinal fluid (in the presence of inflammation), gynecologic tissues, respiratory tract tissues, and urinary tract tissues; tissue levels are generally equal to or above the levels needed for the treatment of patients with susceptible pathogens.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteria, Anaerobic; Bacterial Infections; Child; Child, Preschool; Cilastatin; Clinical Trials as Topic; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Imipenem; Infant; Infant, Newborn; Kidney; Male; Meropenem; Microbial Sensitivity Tests; Molecular Structure; Renal Insufficiency; Thienamycins

The carbapenems, a class of beta-lactam antimicrobials with efficacy against both aerobic and anaerobic organisms, have demonstrated potential as monotherapeutic regimens in the treatment of serious intra-abdominal infections. Clinical trials have been conducted in the past decade to compare carbapenem monotherapy versus combinations of antibiotic therapy. We report here a meta-analysis of 10 such trials.. An 11-year Medline search (from 1985 through 1996) of the English-language literature identified clinical trials that compared the outcomes of carbapenem monotherapy, either imipenem/cilastatin or meropenem, versus another antibiotic regimen in intra-abdominal infections in human subjects. Ten randomized, prospective trials were found, with a total of 1,227 clinically evaluable patients. A meta-analysis of these clinical trials was performed to determine the difference in clinical outcomes between carbapenem monotherapy versus other antibiotic regimens. We found a difference in response rates of -1.6% (95% confidence interval [CI] -5.7% to 2.5%) and a response ratio of 0.99 (95% CI, 0.90 to 1.09), indicating no statistical significant difference.. A meta-analysis of 10 clinical trials from 1985 through 1996 has revealed no statistical significant difference in clinical response between carbapenem monotherapy and combinations of antibiotic therapy in intra-abdominal infections. We noted, however, that the earlier studies reported more favorable response ratios for carbapenems than later publications. This may have been due to the selection of less effective comparators in earlier studies. We conclude that carbapenem monotherapy is as effective as combinations of antimicrobials for the treatment of intra-abdominal infections.

Topics: Abdomen; Bacterial Infections; Carbapenems; Drug Therapy, Combination; Humans; Imipenem; Meropenem; Randomized Controlled Trials as Topic; Thienamycins

Carbapenems are active beta-lactam antibiotics versus most of the gram positive and gram negative microorganisms and anaerobes although their activity is lacking in the case of Staphylococcus sp. resistant to methicillin, Enterococcus faecium and Streptococcus pneumoniae with high resistance to penicillin and some gram negative bacilli which naturally produce an methaloenzyme able to hydrolyze them such as Stenotrophomonas maltophilia. Imipenem, the first synthetized carbapenem requires administration with cilastatin to avoid inactivation by renal dehydropeptidase 1. Meropenem does not require being taken with the renal enzyme inhibitor, with its activity being similar to that of imipenem. In abdominal infection the carbapenems have shown to be the authentic monotherapy in this type of infections being as effective as the different schedules of antibiotic associations normally used. Treatment with carbapenems in bacterial meningitis should be currently limited to the cases produced by gram negative bacilli producers of wide spectrum beta-lactamases (WSBL), cases of meningitis by Pseudomonas aeruginosa or gram negative bacilli producers of inducible cephalosporinase. Meropenem is the carbapenem of choice probably in these cases because the carbapenems are often the only active antibiotics and meropenem, specifically, does not have the risk of convulsions observed with imipenem-cilastatin. The carbapenems have shown to be useful in skin and soft tissue infections as well as in obstetric and gynecologic infections as monotherapy similar to the schedules of the currently used antibiotic associations. In the case of nosocomial pneumonias, all the studies have evaluated the carbapenems in monotherapy as useful and effective, specially in the case of pneumonia by gram negative bacilli. Finally, in non filiated nosocomial sepsis and specially in the case of neutropenic patients, the use of carbapenems is particularly attractive in gram negative sepsis in intensive care units. The appearance in the last few years of strains of gram negative bacilli, producers of wide spectrum beta-lactamase or stable repressed hyperproducers of class I chromosomic cephalosporinase, as well as other multiresistant gram negative bacilli, such as Acinetobacter baumanii make the carbapenems, in many cases, the only effective antibiotic in this type of infections.

Topics: Anti-Bacterial Agents; Bacterial Infections; Carbapenems; Cross Infection; Drug Therapy, Combination; Humans; Imipenem; Meningitis, Bacterial; Meropenem; Pneumonia, Bacterial; Skin Diseases, Infectious; Thienamycins

Monotherapy with ceftazidime, cefepime, imipenem or meropenem for the empiric treatment of febrile neutropenia appears as effective as the combination therapy involving aminoglycosides. However, empiric therapy with a combination of a beta-lactam plus an aminoglycoside is a reasonable decision under circumstances where Gram negative sepsis is very likely. Monotherapy is usually associated with a modest rate of response in infections caused by Gram positive organisms. In about 30% of the patients, a glycopeptide will be added at some point, because the response to the initial therapy is not considered optimal.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Cefepime; Ceftazidime; Cephalosporins; Drug Therapy, Combination; Fever; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Imipenem; Meropenem; Neutropenia; Sepsis; Thienamycins

Topics: Abdomen; Anti-Bacterial Agents; Bacterial Infections; Clinical Trials as Topic; Humans; Meningitis; Meropenem; Thienamycins

Topics: Bacterial Infections; Child; Child, Preschool; Clinical Trials as Topic; Hospitalization; Humans; Infant; Meropenem; Thienamycins

The parenteral carbapenem meropenem is relatively stable to inactivation by human renal dehydropeptidase (DHP-1) and does not require concomitant administration of a DHP-1 inhibitor such as cilastatin. It has a broad spectrum of antibacterial activity in vitro, the majority of Gram-negative, Gram-positive and anaerobic pathogens being highly susceptible to the drug. Meropenem has shown clinical and bacteriological efficacy in the treatment of a wide range of serious infections in adults and children which is at least comparable with that of currently available treatment options. Its clinical and bacteriological efficacy is similar to that of imipenem/cilastatin, clindamycin plus tobramycin and cefotaxime plus metronidazole in the treatment of intraabdominal infections; cefotaxime or ceftriaxone in the treatment of meningitis; imipenem/cilastatin, and ceftazidime with or without an aminoglycoside, in lower respiratory tract infections; and imipenem/cilastatin or ceftazidime in the treatment of urinary tract infections. Satisfactory clinical and bacteriological response rates have also been achieved in patients with skin and skin structure infections, obstetric and gynaecological infections or septicaemia, and in immunocompromised patients with febrile episodes. Preliminary findings also indicate efficacy in the treatment of respiratory tract infections in patients with cystic fibrosis. The tolerability profile of meropenem is generally similar to that of comparator agents, although it is associated with a lower incidence of adverse gastrointestinal effects (nausea and vomiting) than imipenem/cilastatin. Importantly, the incidence of seizures in patients with meningitis is not increased following administration of meropenem. Thus, meropenem is an effective broad spectrum antibacterial drug for the treatment of a wide range of infections including polymicrobial infections in both adults and children, with comparable efficacy to imipenem/cilastatin and various other treatment regimens. Meropenem is likely to be of greatest value as empiric monotherapy in the treatment of serious infections for those caused by multiply-resistant pathogens. Further clinical experience is necessary, however, to ultimately define its place in therapy.

Topics: Absorption; Aging; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Child; Child, Preschool; Drug Evaluation; Drug Resistance, Microbial; Drug Therapy, Combination; Humans; Meropenem; Thienamycins; Tissue Distribution

Infection remains the major cause of morbidity and mortality for cancer patients who become granulocytopenic as a result of chemotherapy. Treatment is instituted at the first sign of infection and before the identification of the causative pathogen (empiric treatment). For many years, standard empiric treatment has been combination therapy with beta-lactams and aminoglycosides. The advent of new broad spectrum antibiotics, such as ceftazidime, has introduced the possibility of empiric monotherapy. However, ceftazidime has only modest activity against infections due to Gram-positive organisms, which presently account for at least 50% of infections in neutropenic patients, and resistance to ceftazidime in Gram-negative organisms has been documented. Meropenem is a new carbapenem with a broad antibacterial spectrum with greater in vitro activity than ceftazidime against staphylococci, streptococci and many Gram-negative bacteria. A comparative study of intravenous meropenem (1 g 8-hourly) and ceftazidime (2 g 8-hourly) in the empiric treatment of febrile neutropenic patients with haematological malignancies has been conducted. In an open, randomised trial of the treatment of 338 febrile episodes, all patients survived to 72 hours on both treatments, and meropenem was found to be at least as clinically effective as ceftazidime in eradicating both Gram-positive and Gram-negative infections. Early modification of treatment (48-72 hours) was required for approximately 40% of patients but occurred less frequently in patients treated with meropenem than with ceftazidime. Tolerability of both treatments was good. Meropenem should be compared with standard combination therapy in a large randomised trial before adopting it as empiric monotherapy for febrile neutropenic patients.

Topics: Bacterial Infections; Ceftazidime; Clinical Trials as Topic; Fever; Humans; Infusions, Intravenous; Meropenem; Neutropenia; Randomized Controlled Trials as Topic; Thienamycins

Serious infections in paediatric patients pose some unique challenges to clinicians. Children represent a dynamic group of patients in whom there are age-related changes as well as age-related alterations in the biodisposition of various antimicrobial agents. In infants and children with serious infections multidrug therapy is generally employed. This occurs because most antibiotic therapy in these patients is initiated and continued on an empiric basis and few, if any, of the currently available agents may be employed confidently as monotherapy. When the agents currently available are compared on a pharmacokinetic and pharmacodynamic basis the carbapenems emerge as close to ideal for the treatment of serious infections in infants and children. Imipenem is the only member of this group currently available. It lacks paediatric labelling in the USA and its efficacy has not been compared directly with that of antibiotic regimens commonly employed in children. Meropenem is a new carbapenem currently under evaluation of the treatment of moderate to severe infections in children and adults. In 2 multicentre, randomised evaluations of the treatment of a variety of infections including lower respiratory tract infections, urinary tract infections, intra-abdominal infections, infections of the skin and skin structures, and septicaemia, the efficacy and safety of meropenem monotherapy were compared with those of cefotaxime-based regimens. Meropenem had an overall clinical efficacy rate of 98% compared with a rate of 95% for cefotaxime-based regimens. Neither regimen was associated with any significant clinical or laboratory adverse events. The carbapenem, meropenem, appears to be a reasonable choice for empiric therapy in infants and children with serious infections. Meropenem monotherapy has been evaluated and has been found to be as well tolerated and as effective as cefotaxime-based regimens in these patients.

Topics: Bacterial Infections; Cefotaxime; Child; Child, Preschool; Clinical Trials as Topic; Female; Humans; Infant; Infant, Newborn; Male; Meropenem; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Thienamycins

Meropenem is a parenteral carbapenem antibiotic which has excellent bactericidal activity in vitro against almost all clinically significant aerobes and anaerobes. Its high activity is explained by ease of entry into bacteria combined with good affinity for essential penicillin binding proteins, including those associated with cell lysis. Breadth of spectrum is due, in part, to stability to all serine-based beta-lactamases, including those which hydrolyse third-generation cephalosporins. Meropenem has an antibacterial spectrum which is broadly similar to that of imipenem but, whilst slightly less active against staphylococci and enterococci, it is more active against Pseudomonas aeruginosa, all Enterobacteriaceae and Haemophilus influenzae. Amongst common human pathogens, only methicillin-resistant staphylococci and Enterococcus faecium are uniformly resistant to meropenem. The meropenem MICs for penicillin-resistant Streptococcus pneumoniae are higher than for penicillin-susceptible strains but the organisms remain susceptible. Clinical susceptibility in vitro to meropenem is defined by MICs of < or = 4 mg/L, intermediate susceptibility by MICs of 8 mg/L and MICs of > or = 16 mg/L define resistance; equivalent figures for zones of growth inhibition are > or = 14 (susceptible), 12-13 (intermediate) and < or = 11 (resistant) mm. Studies in guinea pig models of systemic infection and infections localised to the lungs, urinary tract and the central nervous system, some of which used immunocompromised animals, confirm the potential of meropenem demonstrated in vitro. These factors, combined with the human plasma, tissue or urinary concentrations of meropenem which exceed modal MICs for the pathogens isolated in clinical trials for most or all of the recommended 8 h dosing interval, predict that meropenem should be efficacious in the treatment of infections at many body sites.

Topics: Animals; Bacterial Infections; Carbapenems; Humans; Meropenem; Thienamycins

Data from 3125 patients (3220 patient exposures) treated with meropenem were compared with those from 2886 patients (2960 patient exposures) treated with a variety of comparator agents including cephalosporins (alone or in combination with aminoglycosides or an anti-anaerobe agent) and imipenem/cilastatin. Patients treated included those with bacterial infections of the lower respiratory tract, urinary tract and skin and soft tissues, abdominal, obstetric and gynaecological infections, meningitis, febrile episodes in neutropenic patients and paediatric patients with infections. In three studies, meropenem was administered intramuscularly; in the remainder, meropenem was given by 15-30 min iv infusion or by bolus injection over approximately 5 min. The usual dosages were 500 mg or 1 g 8 hourly in adults and 10 or 20 mg/kg 8 hourly in children. In bacterial meningitis, the meropenem dosage in adults was 2 g 8 hourly and 40 mg/kg 8 hourly in children. The overall pattern and frequency of adverse events with meropenem were similar to those of the other beta-lactam antibiotics with which it was compared. The most frequently reported adverse events were diarrhoea, rash, nausea and vomiting, thrombocytosis, eosinophilia and changes in hepatic biochemistry. Abnormal laboratory tests occurred with similar frequencies between meropenem and the comparator agents. The safety profile of meropenem was similar in adults and children, and the presence of renal impairment did not alter the safety profile of meropenem. Experience in clinical studies in 3220 patient exposures has revealed no unusual or unexpected toxicity. The possibility of administration by either iv infusion or bolus injection with a low incidence of nausea and vomiting also provides flexibility in the clinical management of patients. Moreover, the low incidence of reported seizures and good tolerability at high doses, make meropenem particularly useful for the treatment of meningitis and other indications which carry a risk of seizures, or in the treatment of serious infections where high doses of antibiotics are frequently indicated.

Topics: Bacterial Infections; Carbapenems; Child; Clinical Trials, Phase III as Topic; Humans; Meropenem; Prospective Studies; Randomized Controlled Trials as Topic; Thienamycins; Treatment Outcome

Patients with cirrhosis and treatment non-responsive spontaneous bacterial peritonitis (SBP) have high mortality. We aimed to investigate whether GM-CSF can improve SBP response rates.. In this open-label RCT, 131 cirrhosis patients with difficult-to-treat SBP (DTT SBP) were randomized to receive meropenem alone (1 g IV thrice daily for 5 days) (MERO Group, n = 66) or in combination with GM-CSF (1.5 mcg/Kg daily IV till resolution or till 5d) (MEROGM Group, n = 65). The primary end-point was SBP early-response (reduction in absolute neutrophil count (ANC) by >25% after 48 h). Secondary end-points included SBP resolution at day 5.. Patients in MEROGM group in comparison to MERO group had higher SBP early-response (60% vs. 31.8%; p = .001) and SBP resolution rates (55.4% vs. 24.2%; p = .0003). Patients in the combination arm also had better resolution of pneumonia {8/17 (47.05%) vs. 2/19 (10.5%), p = .02} and lower incidence of new-onset AKI (15.4% vs. 31.8%, p = .02), HE (18.5% vs. 34.8%, p = .04) and infections (21.5% vs. 37.9%, p = .05). In comparison to MERO group, 7-day survival was higher in MEROGM group (89.2% vs. 78.7%, p = .03), though the 28-day survival was comparable (78.4% vs. 71.2%; p = .66). None of the patients developed treatment-related severe adverse effects requiring discontinuation of therapy.. The addition of GM-CSF to meropenem significantly improves response rates in DTT SBP patients within 48 h. Early use of GMCSF modulates host immune response, and enhances antibiotic response with higher SBP resolution. The use of GMCSF needs to be considered in combating difficult SBP in cirrhosis patients.

Topics: Anti-Bacterial Agents; Bacterial Infections; Carbapenems; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Liver Cirrhosis; Meropenem; Peritonitis

Bloodstream infections (BSIs) adversely affect clinical outcome in children with cancer. Over 1 decade, this retrospective cohort study describes pathogen distribution in BSIs and antimicrobial susceptibility against empirical antibiotics frequently prescribed in children with cancer. The antibiotic efficacy was evaluated through the determination of minimal inhibitory concentrations for piperacillin-tazobactam and meropenem and by disk diffusion for remaining antibiotics. From 2004 to 2013, 398 BSIs occurred in 196 children with cancer (median age: 5.4 y), resulting in 457 bacteria. Overall, 266 (58.2%) were Gram-positive, and 191 (41.8%) were Gram-negative with a significant Gram-positive increase over time (P=0.032). Coagulase-negative staphylococci (74, 16.2%), viridans group streptococci (67, 14.7%), Escherichia coli (52, 11.4%), and Staphylococcus aureus (39, 8.5%) were the most common pathogens. Susceptibility to piperacillin-tazobactam (95.9%, P=0.419) and meropenem (98.9%, P=0.752) was stable over time, and resistance was observed among viridans group streptococci against piperacillin-tazobactam (18%) and meropenem (7%) and among Enterobacterales against piperacillin-tazobactam (3%). Vancomycin showed 98% Gram-positive activity, gentamicin 82% Gram-negative activity and ampicillin, cefotaxime, and cefuroxime were active in 50%, 72%, and 69% of pathogens, respectively, and BSI-related mortality was 0%. In conclusion, over 1 decade, we report an increase in Gram-positive BSIs, and stable, low-resistance rates against currently recommended empirical antibiotics, piperacillin-tazobactam and meropenem.

Topics: Adolescent; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Male; Meropenem; Microbial Sensitivity Tests; Neoplasms; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Sepsis

In Norway, initial treatment of febrile neutropenia (FN) has traditionally been benzylpenicillin plus an aminoglycoside. Internationally, FN is often treated with a broad-spectrum β-lactam antibiotic. We aimed to compare these two regimens in a prospective, randomized, trial in patients with lymphoma or leukaemia with an expected period of neutropenia ≥7 days, and a suspected bacterial infection.. Adult neutropenic patients with lymphoma or leukaemia, and a suspected bacterial infection, were randomized for treatment with benzylpenicillin plus an aminoglycoside or meropenem. The primary endpoint was clinical success, defined as no modification of antibiotics and clinical stability 72 h after randomization.. Among 322 randomized patients, 297 proved evaluable for analyses. Fifty-nine per cent (95% CI 51%-66%), (87/148) of the patients given benzylpenicillin plus an aminoglycoside were clinically stable, and had no antibiotic modifications 72 h after randomization, compared with 82% (95% CI 75%-87%), (122/149) of the patients given meropenem (p <0.001). When the antibiotic therapy was stopped, 24% (95% CI 18%-32%), (36/148) of the patients given benzylpenicillin plus an aminoglycoside, compared with 52% (95% CI 44%-60%), (78/149) of the patients given meropenem, had no modifications of their regimens (p <0.001). In the benzylpenicillin plus an aminoglycoside arm, the all-cause fatality within 30 days of randomization was 3.4% (95% CI 1.2%-7.9%), (5/148) of the patients, compared with 0% (95% CI 0.0%-3.0%), (0/149) of the patients in the meropenem arm (p 0.03).. Clinical success was more common in FN patients randomized to meropenem compared with the patients randomized to benzylpenicillin plus an aminoglycoside. The all-cause fatality was higher among the patients given benzylpenicillin plus an aminoglycoside.

Topics: Adolescent; Adult; Aged; Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Female; Humans; Leukemia; Lymphoma; Male; Meropenem; Middle Aged; Mortality; Neutropenia; Norway; Penicillin G; Prospective Studies; Thienamycins; Treatment Outcome; Young Adult

Pneumonia is the third leading cause of mortality in Japan. In 2011, the use of meropenem (MEPM) at 3 g daily was approved to treat refractory infections in Japan. However, little has been reported on the clinical efficacy and safety of this regimen in Japanese patients with refractory infections.. This study prospectively assessed the clinical efficacy and safety of MEPM (3 g daily) in Japanese patients with refractory pneumonia and/or intrapleural infections.. This study was performed at our university hospital and affiliated hospitals. The plasma concentrations of MEPM before and one and four hours after MEPM administration were also evaluated.. A total of 48 patients were enrolled for the efficacy and safety evaluations. The response rate to MEPM (3 g daily) treatment was 90.9% (40/44). Adverse drug reactions were observed in 17 of the 48 patients (20.8%), and all improved after the cessation of MEPM. The plasma MEPM concentration one hour after administering 1 g of MEPM was 44.9 ± 12.0 μg/ml. A pharmacokinetic analysis revealed that the percentage of time above the MIC/24 h for an MIC of 4 μg/ml or 8 μg/ml was more than 50% in 12 of 13 (92%) and in nine of the 13 patients (69%), respectively, indicating sufficient efficacy of 3 g daily of MEPM.. Treatment with MEPM (3 g daily) in Japanese patients with refractory pneumonia and/or intrapleural infections is effective, with sufficient plasma concentrations of MEPM, and the treatment has a relatively good safety profile.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Drug Administration Schedule; Female; Humans; Japan; Male; Meropenem; Middle Aged; Prospective Studies; Respiratory Tract Infections; Thienamycins

Biapenem is a newly developed carbapenem to treat moderate and severe bacterial infections. This multicenter, randomized, parallel-controlled clinical trial was conducted to compare the clinical efficacy, bacterial eradication rates and safety of biapenem and meropenem in the treatment of bacterial lower respiratory tract infections and urinary tract infections (UTIs) at nine centres in China.. Patients diagnosed with bacterial lower respiratory tract infections or UTIs were randomly assigned to receive either biapenem (300 mg every 12 h) or meropenem (500 mg every 8 h) by intravenous infusion for 7 to 14 days according to their disease severity. The overall clinical efficacy, bacterial eradication rates and drug-related adverse reactions of biapenem and meropenem were analyzed.. A total of 272 enrolled cases were included in the intent-to-treat (ITT) analysis and safety analysis. There were no differences in demographics and baseline medical characteristics between biapenem group and meropenem group. The overall clinical efficacies of biapenem and meropenem were not significantly different, 94.70 per cent (125/132) vs. 93.94 per cent (124/132). The overall bacterial eradication rates of biapenem and meropenem showed no significant difference, 96.39 per cent (80/83) vs. 93.75 per cent (75/80). Drug-related adverse reactions were comparable in biapenem and meropenem groups with the incidence of 11.76 per cent (16/136) and 15.44 per cent (21/136), respectively. The most common symptoms of biapenem-related adverse reactions were rash (2.2%) and gastrointestinal distress (1.5%).. Biapenem was non-inferior to meropenem and was well-tolerated in the treatment of moderate and severe lower respiratory tract infections and UTIs.

Topics: Adult; Aged; Bacteria; Bacterial Infections; China; Female; Humans; Infusions, Intravenous; Male; Meropenem; Middle Aged; Respiratory Tract Infections; Thienamycins; Urinary Tract Infections

Therapeutic options for postoperative infection in gastrointestinal surgery are limited. To identify new treatment alternatives, the Japan Society for Surgical Infection conducted a multicenter prospective, randomized, controlled clinical trial comparing the efficacy of intravenous ciprofloxacin (CIP IV) and intravenous meropenem (MEM IV). Between July 2005 and May 2008, the trial recruited patients who developed postoperative infection or had suspected infectious systemic inflammatory response syndrome after elective clean-contaminated gastrointestinal surgery. All patients had received prophylactic postoperative antibiotic treatment. Patients received either intravenous CIP IV 300 mg b.i.d. or MEM IV 500 mg b.i.d. A total of 205 patients from 31 institutions were enrolled. Of these, 101 were randomized to CIP IV and 104 to MEM IV. There were 100 and 102 in the intent-to-treat (ITT)/safety population and 75 and 77 in the per-protocol (PP) population. There was no significant difference between CIP IV and MEM IV in terms of clinical efficacy, bacteriological efficacy, incidence of adverse drug reactions, duration of antimicrobial treatment, or relapse/reactivation. Overall clinical success PP population) was high in both treatment groups: 85.3% (64/75) for CIP IV and 89.6% (69/77) for MEM IV, although the non-inferiority of CIP IV was not demonstrated (difference -4.3%, 95% CI -14.8, 6.2). In patients who had undergone upper gastrointestinal surgery, success was 88.5% (23/26) for CIP IV and 85.2% (23/27) for MEM IV. Intravenous ciprofloxacin is as effective as intravenous meropenem in the empiric therapy of postoperative infection after gastrointestinal surgery.

Topics: Aged; Anti-Bacterial Agents; Bacterial Infections; Ciprofloxacin; Digestive System Surgical Procedures; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Injections, Intravenous; Japan; Male; Meropenem; Middle Aged; Prospective Studies; Surgical Wound Infection; Thienamycins; Treatment Outcome

Many patients with hematologic malignancies show immunosuppression and/or neutropenia, and are at a high risk of developing a serious infection that would require empiric therapy with broad-spectrum antibiotics. However, a thorough comparison of the efficacies of different carbapenems has not been carried out. To compare the efficacies of meropenem (MEPM) and doripenem (DRPM) in febrile patients with hematologic neoplasms, we retrospectively reviewed data of 149 consecutive febrile patients with acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome (MDS) who were treated empirically with MEPM or DRPM. The duration from the start of carbapenem administration to decline of fever was not significantly different between the MEPM and DRPM groups (median, 3 versus 4 days; P = 0.79). Multivariate analysis showed that a diagnosis of MDS and the use of liposomal amphotericin-B or voriconazole are statistically significant risk factors for sustained fever. In conclusion, MEPM and DRPM showed similar efficacies in febrile patients with acute leukemia and MDS.

Topics: Aged; Anti-Bacterial Agents; Bacterial Infections; Carbapenems; Doripenem; Female; Fever; Hematologic Neoplasms; Humans; Male; Meropenem; Middle Aged; Retrospective Studies; Risk Factors; Thienamycins; Treatment Outcome

Complicated intra-abdominal infections (cIAIs) require surgical intervention and empiric antibacterial therapy. Doripenem, a broad-spectrum carbapenem, provides coverage of key gram-negative and -positive aerobes and anaerobes encountered in cIAI.. This study was designed to compare the efficacy and safety profile of doripenem and meropenem in hospitalized adult patients with cIAI.. In this prospective, multicenter, doubleblind, noninferiority study, hospitalized adults with cIAI were randomly assigned to receive doripenem 500 mg IV q8h or meropenem 1 g IV q8h. After a minimum of 9 doses and adequate clinical improvement (relative to before the start of IV study drug, decreased body temperature and white blood cell count, improved or absent signs and symptoms of cIAI, and return of normal bowel function), patients could be switched to oral amoxicillin/clavulanate. Antibacterial therapy (IV plus subsequent oral) was given for a total of 5 to 14 days. The coprimary efficacy end points were the clinical cure rate (complete resolution or significant improvement of signs or symptoms of the index infection) in patients microbiologically evaluable (>or=1 baseline pathogen isolated from an intra-abdominal culture that was susceptible to both IV study drug therapies) at the test-of-cure (TOC) visit (21-60 days after the completion of study drug therapy) and the clinical cure rate in the microbiological modified intent-to-treat (mMITT) population (a bacterial pathogen identified at baseline, regardless of its susceptibility to the study drug). Noninferiority was concluded if the lower limit of the 2-sided 95% CI for the difference (doripenem minus meropenem) in the proportion of patients classified as clinical cures was >or=-15%.. A total of 476 patients were enrolled. The microbiologically evaluable population (319 patients) was 62.7% male and 67.7% white, with a mean age and weight of 46.7 years and 77.2 kg, respectively. In this population, doripenem and meropenem were associated with clinical cure rates at the TOC visit of 85.9% and 85.3%, respectively. The corresponding treatment difference was 0.6% (95% CI, -7.7% to 9.0%); this difference was not statistically significant. Similarly, in the mMITT population (385 patients), the clinical cure rates were 77.9% and 78.9%, respectively, and the corresponding 1.0% treatment difference was not statistically significant (95% CI, -9.7% to 7.7%). Clinical cure rates were not significantly different between the 2 treatment arms in key subgroups (eg, age, sex, race, baseline Acute Physiology and Chronic Health Evaluation II score, primary infection site). Microbiological eradication rates for common pathogens isolated at study entry were not significantly different between the 2 treatment groups. Doripenem was well tolerated in the population studied. In the intent-to-treat population (471 patients), 83.0% and 78.0% of patients experienced >or=1 adverse event (AE) and 13.2% and 14.0% experienced >or=1 serious AE in the doripenem and meropenem treatment arms, respectively. In the doripenem and meropenem treatment arms, AEs resulted in study drug discontinuation in 5.1% and 2.1% of patients and death in 2.1% and 3.0% of patients, respectively.. The present study found that doripenem (500 mg q8h) was effective in the treatment of cIAI, was therapeutically noninferior to meropenem (1 g q8h), with a safety profile not significantly different from that of meropenem in this selected population of patients with cIAI.

Topics: Abdominal Abscess; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Carbapenems; Doripenem; Double-Blind Method; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Injections, Intravenous; Male; Meropenem; Middle Aged; Prospective Studies; Thienamycins

Cystic fibrosis (CF) is characterized by chronic bacterial broncho-pulmonary infection. Although intravenous (i.v.) antibiotic therapy is regarded as standard treatment in CF, only few randomised trials comparing different antibiotic compounds exist.. We report on a prospective multicenter interventional trial of i.v. meropenem (120 mg/kg/day) or i.v. ceftazidime (200-400 mg/kg/day), each administered together with i.v. tobramycin (9-12 mg/kg/day). Outcome measures were changes in lung function, microbiological sputum burden and blood inflammatory marker. Liver and renal function values were measured to assess safety.. One hundred eighteen patients (59/59) were included into the study with the following indications: first infection of P. aeruginosa (n=6), acute pulmonary exacerbation (n=34) and suppression therapy of chronic P. aeruginosa colonization (n=78). Both treatments improved lung function measures, bacterial sputum burden and CRP levels with no differences between treatment groups observed. A significant higher elevation for alkaline phosphatase (p<0.0001) was observed for patients in the meropenem/tobramycin group.. i.v. antibiotic therapy in CF patients with meropenem/tobramycin is as effective as with ceftazidime/tobramycin regarding lung function, microbiological sputum burden and systemic inflammatory status. Hepato-biliary function should be monitored carefully during i.v. treatment, possibly important in CF patients with pre-existing liver disease.

Topics: Adolescent; Anti-Bacterial Agents; Bacterial Infections; C-Reactive Protein; Ceftazidime; Child; Child, Preschool; Cystic Fibrosis; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Infusions, Intravenous; Male; Meropenem; Prospective Studies; Thienamycins; Tobramycin; Treatment Outcome

In patients with severe, necrotizing pancreatitis, it is common to administer early, broad-spectrum antibiotics, often a carbapenem, in the hope of reducing the incidence of pancreatic and peripancreatic infections, although the benefits of doing so have not been proved.. A multicenter, prospective, double-blind, placebo-controlled randomized study set in 32 centers within North America and Europe.. One hundred patients with clinically severe, confirmed necrotizing pancreatitis: 50 received meropenem and 50 received placebo.. Meropenem (1 g intravenously every 8 hours) or placebo within 5 days of the onset of symptoms for 7 to 21 days.. Primary endpoint: development of pancreatic or peripancreatic infection within 42 days following randomization. Other endpoints: time between onset of pancreatitis and the development of pancreatic or peripancreatic infection; all-cause mortality; requirement for surgical intervention; development of nonpancreatic infections within 42 days following randomization.. Pancreatic or peripancreatic infections developed in 18% (9 of 50) of patients in the meropenem group compared with 12% (6 of 50) in the placebo group (P = 0.401). Overall mortality rate was 20% (10 of 50) in the meropenem group and 18% (9 of 50) in the placebo group (P = 0.799). Surgical intervention was required in 26% (13 of 50) and 20% (10 of 50) of the meropenem and placebo groups, respectively (P = 0.476).. This study demonstrated no statistically significant difference between the treatment groups for pancreatic or peripancreatic infection, mortality, or requirement for surgical intervention, and did not support early prophylactic antimicrobial use in patients with severe acute necrotizing pancreatitis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Cohort Studies; Double-Blind Method; Drug Administration Schedule; Female; Humans; Infusions, Intravenous; Male; Meropenem; Middle Aged; Pancreatitis, Acute Necrotizing; Thienamycins; Treatment Outcome

Monte Carlo simulation is often used to predict the cumulative fraction of response (CFR) for antibiotics, but the relevance of these predictions to outcomes in humans has not been well studied. We compared the CFR for meropenem 500 mg every 8h against pathogens causing complicated skin and skin structure infections from a randomised, multicentre clinical trial with clinical response (CR) and microbiological response (MR). A population pharmacokinetic model was utilised to estimate pharmacokinetic parameters for 96 clinically evaluable patients with pathogen and minimum inhibitory concentration (MIC) data available. A 1000-subject Monte Carlo simulation was performed to estimate bacteriostatic (20% of time serum concentration above the MIC (T>MIC)) and bactericidal (40% T>MIC) exposures for comparison. Only the bactericidal CFR versus the CR was not statistically different (92% CR versus 91.9% CFR; 95% confidence interval of the difference, -7.7% to 4.2%), whilst bacteriostatic CFRs overestimated actual CR and MR. This study demonstrates that the use of Monte Carlo simulation to predict the CR of meropenem in complicated skin and skin structures is accurate.

Topics: Anti-Infective Agents; Bacterial Infections; Humans; Meropenem; Microbial Sensitivity Tests; Monte Carlo Method; Outcome Assessment, Health Care; Skin Diseases; Thienamycins

In the present study, we analyze the efficacy of prophylaxis with meropenem in patients receiving a matched related donor allogeneic transplant. In total, 38 patients were sequentially treated with meropenem starting on the day of the first febrile episode (n=17, group A) vs prophylactic meropenem starting on the first day with <500/mm(3) granulocytes (n=21, group B), and maintained until resolution of fever or after granulocyte count >500/mm(3). Of these, 16 (94%) patients in group A developed fever as compared to 16 (76%) in group B (P=0.02). While only one patient in group A did not require first-line antibiotherapy, there were seven (33%) in group B who did not require it (P=0.01) since fever lasted less than 72 h. In addition, 52% patients in group B did not require second-line antibiotics as compared to 11% among patients in group A (P=0.04). In multivariate analysis prophylaxis with meropenem (HR=2.83, 95% CI (1-8.02); P=0.04) and disease status at transplant (HR for early stage=0.15, 95% CI (0.04-0.62); P=0.04) significantly influenced the development of fever. In conclusion, the current pilot study suggests that the use of prophylaxis with meropenem during the period of neutropenia in patients undergoing allogeneic transplantation favorably affects the morbidity of the procedure by reducing febrile episodes.

Topics: Acute Disease; Adult; Bacterial Infections; Chronic Disease; Cohort Studies; Female; Fever; Hematopoietic Stem Cell Transplantation; Humans; Incidence; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myeloid; Male; Meropenem; Middle Aged; Pilot Projects; Thienamycins

We performed a retrospective, comparative study to evaluate efficacy, safety and economic outcomes of empiric cefoperazone/sulbactam monotherapy compared with the meropenem, imipenem/cilastatine and combination of cefepime plus metroindazol in patients with intra-abdominal infection. A total of 468 patients diagnosed with intra-abdominal abscess, peritonitis, pancreatitis were included in the study (the severity of infection according to scale APACHE II was less than 15). Patients were randomized to be treated with either 500 mg meropemen i.v. every 8 hours or 500 mg imipenem/cilastatine i.v. every 8 hours or 2 g cefepime i.v. every 12 hours plus 500 mg metronidazol twice daily or cefoperazone/sulbactam 2 g daily administered every 12 hours. Overall positive clinical responses (cure or improvement) were achieved at the end of treatment for 87.5 patients in meropenem group, 86.6% in the imipenem/cilastatin group, 85.3% in the cefepime group and 86.8% in cefoperazone/sulbactam group. Total cost of the treatment per 100 patients with intra-abdominal infections for cefoperazone/sulbactam was 1957031 roubles, for combinations of cefepime with metronidazol--2497815 roubles. For carbapenem group cost achieved for meropenem--3085291 rub., for imipenem/cilastatin--2653388 roubles. Rate "cost-effectiveness" in total: 784.47$ for cefepime, and 834.39$ for imipenem/cilastatine, 970.21$ for meropenem and 615.4$ for cefoperazone/sulbactam. The most expensive treatment was considered to be with meropenem and imipenem/cilastatine, main share is determined by initial cost of preparations. Less expensive was treatment by cefoperazone/sulbactam with cefepime and by metronidazol.

Topics: Abdomen; Anti-Bacterial Agents; Bacterial Infections; Cefepime; Cefoperazone; Cephalosporins; Clinical Trials as Topic; Costs and Cost Analysis; Drug Combinations; Humans; Imipenem; Meropenem; Models, Economic; Sulbactam; Thienamycins

In patients with acute renal failure, the pharmacokinetics of meropenem depend on the operational characteristics of the renal replacement therapy. Dosage recommendations are based on the correlation of plasma levels with pharmacodynamic requirements.. Eight critically ill patients with acute renal failure were treated by continuous veno-venous hemofiltration with a filtrate flow of 1,600 ml/h and received 500 mg of meropenem every 12 h. Plasma and hemofiltrate concentrations of meropenem at steady state were determined by HPLC.. Peak levels in plasma amounted to 39.5 +/- 10.5 mg/l (mean +/- SD) and trough levels were 2.4 +/- 1.5 mg/l. The minimal inhibitory concentration (MIC) for susceptible bacteria (4 mg/l) was covered for 40% of the dosing interval or longer in all patients. The MIC for intermediately susceptible organisms (8 mg/l) was covered for 33% in 6 of the 8 patients. The elimination half-life was prolonged to 3.63 +/- 0.77 h. The sieving coefficient of meropenem was 0.91 +/- 0.10 and the recovery in hemofiltrate amounted to 30.9 +/- 11.5% of the dose.. A dosage of 500 mg twice daily provides appropriate serum levels for the treatment of infections caused by susceptible bacteria. A higher dosage is adequate for infections by intermediately susceptible bacteria or for renal replacement therapies with markedly higher filtrate flow rates.

Topics: Acute Kidney Injury; Aged; Bacterial Infections; Critical Illness; Drug Administration Schedule; Female; Half-Life; Hemofiltration; Humans; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Thienamycins

To determine which carbapenem (imipenem/cilastatin or meropenem) was the preferable empiric antibiotic monotherapy in pre-engrafted pediatric bone marrow transplant (BMT) patients in terms of patient tolerance, therapeutic efficacy, and cost.. We prospectively analyzed 16 pediatric BMT patients who received meropenem, and retrospectively analyzed 16 matched patients who had received imipenem/cilastatin for BMT procedures during the prior 2-year period. We evaluated the patients for evidence of bacterial infection, necessity for concurrent antibiotics, vomiting episodes, duration of concurrent total parenteral nutrition (TPN), and cost of therapy.. We found no differences in the number of culture proven or clinically suspected breakthrough bacterial infections or the need for concurrent additional antibiotics between the groups. Our analysis found that patients who received meropenem experienced significantly less vomiting than those in the imipenem/cilastatin cohort. Our data showed both direct and indirect cost savings for the meropenem group. The statistical and clinical differences in the number of vomiting episodes between these groups impacted other aspects of patient care, antiemetic use, and TPN duration.. By switching to meropenem, we reduced the cost of antiemetic therapy per patient treatment course, and also showed a trend toward reduced duration of TPN. We found that meropenem provided both clinical and fiscal advantages over imipenem/cilastatin as empiric antibiotic monotherapy in neutropenic pediatric BMT patients.

Topics: Adolescent; Bacterial Infections; Bone Marrow Transplantation; Carbapenems; Child; Child, Preschool; Cilastatin; Drug Costs; Female; Humans; Imipenem; Male; Meropenem; Postoperative Complications; Prospective Studies; Protease Inhibitors; Thienamycins; Vomiting

The efficacy and the safety of meropenem (MEPM) were examined in obstetric and gynecological infections and the results shown below were obtained. 1. The subjects were patients with infectious diseases during a non-pregnant period (n = 14), a pregnant period (n = 13) and a puerperal period (n = 11). After intravenous drip infusion of MEPM at 1-2 g/day, the response rate was 38/39 (97.4%) (Excellent: 13/39 (33.3%), Effective: 25/39 (64.1%)). 2. The response rates in a group receiving 1 g/day, a group receiving 2 g/day and a group receiving a combination of both were, respectively, 25/26 (96.2%), 9/9 (100%) and 4/4 (100%). 3. In cases that did not respond to previous treatments, the response rate to MEPM was 20/20 (100%). 4. In clinical efficacy classified by causative organisms, the rate of Excellent was 10/23 (43.5%) and the rate of Effective was 13/23 (56.5%), and the bacterial eradication rate was 21/23 (91.3%). 5. No subjective and objective adverse reactions or abnormalities in clinical laboratory tests due to administration of MEPM were observed.

Topics: Adult; Bacterial Infections; Female; Genital Diseases, Female; Humans; Infusions, Intravenous; Meropenem; Pregnancy; Pregnancy Complications, Infectious; Thienamycins; Treatment Outcome

This trial assessed the efficacy and safety of meropenem versus ceftazidime as empirical monotherapy for febrile neutropenia in paediatric cancer patients. In a prospective randomized study, 172 evaluable febrile episodes in the meropenem arm and 170 episodes in the ceftazidime arm were analysed for the clinical and microbiological response dependent on the kind of infection. About half the episodes were classified as fever of unknown origin (FUO) and the remainder as microbiologically or clinically documented infections. The most frequently documented infections in both arms were bacteraemias (22.1 versus 26.5%), predominantly caused by Gram-positive organisms (57.9 versus 71.1%). The success rate of the initial monotherapy differed significantly between the two arms and was 55.8% in the meropenem and 40.0% in the ceftazidime arm (P = 0.003). In addition, a significantly longer duration of fever and of antimicrobial therapy was observed in the ceftazidime arm than in the meropenem arm (median 5 versus 4 days, P = 0.022, and 7 versus 6 days, P = 0.009, respectively). With respect to the kind of infection, differences between the two arms were significant only in episodes classified as FUO but not in documented infections. In both arms, side effects were minimal. Despite the greater response rate for meropenem in FUO, the fact that ceftazidime has been proven to be as effective as meropenem in documented infections in the present study suggests that both drugs are useful as empirical monotherapy in febrile paediatric cancer patients.

Topics: Bacterial Infections; Ceftazidime; Cephalosporins; Child; Child, Preschool; Escherichia coli; Female; Fever; Humans; Infant; Infant, Newborn; Klebsiella pneumoniae; Male; Meropenem; Neoplasms; Neutropenia; Prospective Studies; Relapsing Fever; Thienamycins; Time Factors; Treatment Outcome

The efficacy and safety profile of meropenem were analyzed according to data collected from hospitalized pediatric patients aged 4 days to 20 years who had serious bacterial infections and were treated in a major teaching hospital in Taipei. Of the 53 patients enrolled, 47 were analyzed for clinical efficacy and 53 for safety. The satisfactory clinical response rate was 57% in lower respiratory tract infection, 58% in septicemia, 100% in complicated urinary tract infection, osteomyelitis, and central nervous system infection, 83% in skin and soft tissue infection, and 93% in intra-abdominal infection. Eleven (21%) patients experienced adverse events related to meropenem. The most commonly observed adverse reactions were elevated hepatic enzymes (7.5%), increased alkaline phosphatase (3.8%), and thrombocytosis (3.8%). There was no meropenem-related seizure, withdrawal, or death. The results of this study suggested that meropenem is well tolerated even in young infants, and is effective in treating serious childhood bacterial infection. However, this study also identified a proportion of hospitalized pediatric patients with isolates that were resistant to meropenem. The trends in meropenem resistance among nosocomially acquired bacteria should be monitored closely.

Topics: Adult; Bacterial Infections; Child; Drug Evaluation; Female; Humans; Infant, Newborn; Male; Meropenem; Prospective Studies; Respiratory Tract Infections; Sepsis; Thienamycins; Treatment Outcome

To study the pharmacokinetics of meropenem in critically ill patients with acute renal failure receiving continuous venovenous hemofiltration (CWHF).. Prospective, open-labeled study.. Medical intensive care unit of the University Medical Center Utrecht.. Five critically ill patients receiving CWHF for acute renal failure treated with meropenem for documented or suspected bacterial infection.. All patients received meropenem (500 mg) administered intravenously every 12 hrs. Plasma samples and ultrafiltrate aliquots were collected during one dosing interval.. Mean age and body weight of the patients studied were 46.6 yrs (range, 28-61 yrs) and 85.8 kg (range, 70-100 kg), respectively. The following pharmacokinetic variables for meropenem were obtained: mean peak plasma concentration was 24.5 +/- 7.2 mg/L, mean trough plasma concentration was 3.0 +/- 0.9 mg/L, mean terminal elimination half-life was 6.37 +/- 1.96 hrs, mean total plasma clearance was 4.57 +/- 0.89 L/hr, mean CWHF clearance was 1.03 +/- 0.42 L/hr, mean nonrenal clearance was 3.54 +/- 1.06 L/hr, and mean volume of distribution was 0.37 +/- 0.15 L/kg.. In critically ill patients with acute renal failure, nonrenal clearance became the main elimination route. CWHF substantially contributed to the clearance of meropenem (23% of mean total plasma clearance). We recommend meropenem to be dosed at 500 mg intravenously every 12 hrs in patients receiving CWHF, according to our operational characteristics. This dosing regimen resulted in adequate trough plasma levels for susceptible microorganisms.

Topics: Acute Kidney Injury; Adult; Bacterial Infections; Critical Illness; Drug Monitoring; Female; Hemofiltration; Humans; Infusions, Intravenous; Least-Squares Analysis; Male; Meropenem; Metabolic Clearance Rate; Middle Aged; Prospective Studies; Thienamycins; Time Factors; Tissue Distribution

To compare the efficacy and tolerability of meropenem and imipenem/cilastatin as empirical monotherapy in intensive care unit (ICU) patients with serious bacterial infections.. A multicenter, open-label, randomized, parallel-group trial was conducted in Belgium, evaluating empirical monotherapy with meropenem or imipenem/cilastatin (both 1 g/8 h intravenously) in ICU patients with one or more of the following infections caused by sensitive pathogens: lower respiratory tract infection (LRTI) in ventilated patients, intra-abdominal infection or sepsis.. The overall satisfactory clinical response rate at the end of randomized treatment was 77.0% (67/87) with meropenem and 68.1% (62/91) with imipenem/cilastatin (difference 8.9%; 95% confidence interval -4.2% to 21.9%; P = 0.185). The two drugs produced similar satisfactory clinical response rates against LRTIs: 68.3% (41/60) with meropenem versus 68.6% (35/51) with imipenem/cilastatin. Meropenem appeared to be slightly more effective against intra-abdominal infections: 95.5% (21/22) versus 76.7% (23/30), respectively. All five meropenem recipients with sepsis had a satisfactory clinical response, compared to 40.0% (4/10) of those who received imipenem/cilastatin. The overall satisfactory bacteriologic response rate was 67.1% (49/73) with meropenem and 60.3% (44/73) with imipenem/cilastatin (difference 6.9%; 95% confidence interval -8.7% to 22.4%; P = 0.389). The predominant pathogens were Escherichia coli, Enterobacter spp. and Pseudomonas aeruginosa. No incidences of drug-related nausea and vomiting were reported, but one probable drug-related seizure occurred in the imipenem/cilastatin group.. Meropenem is at least as efficacious (clinically and bacteriologically) as imipenem/cilastatin for the empirical monotherapy of serious bacterial infections in ICU patients, and it can therefore be considered a useful option in this setting. Moreover, meropenem is well tolerated and offers several potential advantages, including greater in vitro activity against Gram-negative pathogens and the option of bolus administration.

Topics: Adult; Aged; Aged, 80 and over; Bacterial Infections; Belgium; Cilastatin; Drug Combinations; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Imipenem; Infusions, Intravenous; Intensive Care Units; Male; Meropenem; Middle Aged; Protease Inhibitors; Thienamycins; Treatment Outcome

This prospective crossover study compared the pharmacokinetics of meropenem by continuous infusion and by intermittent administration in critically ill patients. Fifteen patients were randomized to receive meropenem either as a 2 g iv loading dose, followed by a 3 g continuous infusion (CI) over 24 h, or by intermittent administration (IA) of 2 g iv every 8 h (q8h). Each regimen was followed for a period of 2 days, succeeded by crossover to the alternative regimen for the same period. Pharmacokinetic parameters (mean +/- SD) of CI included the following: concentration at steady state (Css) was 11.9+/-5.0 mg/L; area under the curve (AUC) was 117.5+/-12.9 mg/L x h. The maximum and minimum serum concentrations of meropenem (Cmax, Cmin) and total meropenem clearance (CItot) for IA were 110.1+/-6.9 mg/L, 8.5+/-1.0 mg/L and 9.4+/-1.2 L/h, respectively. The AUC during the IA regimen was larger than the AUC during CI (P < 0.001). In both treatment groups, meropenem serum concentrations remained above the MICs for the most common bacterial pathogens. We conclude that CI of meropenem is equivalent to the IA regimen and is therefore suitable for treating critically ill patients. Further studies are necessary to compare the clinical effects of CI and IA in this patient group.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Critical Illness; Cross-Over Studies; Drug Administration Schedule; Female; Humans; Infusions, Intravenous; Intensive Care Units; Male; Meropenem; Middle Aged; Pneumonia; Sepsis; Thienamycins

Meropenem was used in the treatment of 15 newborns (8 preterm) with sepsis, pneumonia or meningitis by intravenous infusion of 15-20 mg/kg daily divided to 3 equal doses. Clinical improvement was achieved in all the cases. No side effects were recorded.

Topics: Bacterial Infections; Dose-Response Relationship, Drug; Humans; Infant, Newborn; Infant, Premature, Diseases; Meningitis, Bacterial; Meropenem; Pneumonia, Bacterial; Sepsis; Thienamycins

Infections remain the major cause of morbidity and mortality among neutropenic cancer patients. The current study addresses the question whether monotherapy with the new broad-spectrum carbapenem meropenem exhibits efficacy comparable to that of the standard combination therapy with ceftazidime and amikacin for empirical treatment of febrile neutropenic patients. Seventy-one patients with hematological malignancies (55%) or solid tumors (45%), neutropenia < 500/microliter, and fever > 38.5 degrees C were randomly assigned to either meropenem (1 g every 8 h) or ceftazidime (2 g every 8 h) and amikacin (15 mg/kg/day) intravenously. Meropenem (n = 34) and ceftazidime/amikacin (n = 37) were equivalent with respect to the clinical response at 72 h (62% versus 68%) (p > 0.05) and at the end of unmodified therapy (59% versus 62%). Gram-positive bacteremia responded poorly in the meropenem and ceftazidime/amikacin group (29% versus 25%), whereas all gram-negative bacteremias responded except for one in the meropenem group caused by Pseudomonas aeruginosa. All patients survived to 72 h. One patient in each group died of gram-positive sepsis resistant to study medication. No significant side effects occurred in any regimen. This study suggests that meropenem monotherapy might be as effective as combination therapy with ceftazidime and amikacin for the empirical treatment of febrile neutropenic patients.

Topics: Adolescent; Adult; Aged; Amikacin; Anti-Bacterial Agents; Bacteremia; Bacterial Infections; Ceftazidime; Cephalosporins; Drug Therapy, Combination; Female; Fever; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Male; Meropenem; Middle Aged; Neutropenia; Thienamycins

The clinical and bacteriological results of treatment for 429 patients who had intra-abdominal infection were analyzed to determine whether the anatomical origin of peritonitis influenced outcome. All patients had received effective broad spectrum antimicrobial therapy and operation in four multicenter trials. The diagnoses of infection were categorized into three sites: upper gastrointestinal tract, complicated appendicitis, and lower gastrointestinal tract. Clinical response rates were excellent for complicated appendicitis and were lowest for infections related to the upper gastrointestinal tract. Bacteriological response rates were also lower for upper gastrointestinal tract organisms and were highest for isolates associated with complicated appendicitis. There were no deaths in the 213 patients who had infection associated with appendicitis. Seven deaths occurred in the 86 patients (81%) with an upper gastrointestinal site of infection, and nine deaths occurred in the 130 patients (6.5%) with lower gastrointestinal site of infection. Mortality was related to recurrent intra-abdominal infection after an unsuccessful primary operation and a serum albumin less than 25 g/l. Clinical trails of antimicrobials for intra-abdominal infection should consider stratification of patients according to these three levels of alimentary tract perforation when the site is known preoperatively. Patients who have infection secondary to previous surgery or who are malnourished represent a higher risk group even with appropriate antibiotics.

Topics: Adult; Aged; Anti-Bacterial Agents; Appendicitis; Bacterial Infections; Bacteriological Techniques; Cause of Death; Cilastatin; Clindamycin; Combined Modality Therapy; Drug Therapy, Combination; Female; Gastrointestinal Diseases; Humans; Imipenem; Male; Meropenem; Middle Aged; Peritonitis; Risk Factors; Survival Rate; Thienamycins; Tobramycin; Treatment Outcome

In this multicenter study, the efficacy of and tolerability for meropenem were compared with those for the combination of cefuroxime-gentamicin (+/- metronidazole) for the treatment of serious bacterial infections in patients > or = 65 years of age. A total of 79 patients were randomized; thirty-nine received meropenem (1 g/8 h), and 40 received cefuroxime (1.5 g/8 h) plus gentamicin (4 mg/kg of body weight daily) for 5 to 10 days. Metronidazole (500 mg/6 h) could be added to the cefuroxime-gentamicin regimen for the treatment of intra-abdominal infections (n = 10). Seventy patients were evaluable for clinical efficacy; the primary diagnoses were as follows: pneumonia in 41 patients (20 treated with meropenem, 21 treated with cefuroxime-gentamicin), intra-abdominal infection in 10 patients (7 meropenem, 3 cefuroxime-gentamicin-metronidazole), urinary tract infection (UTI) in 11 patients (6 meropenem, 5 cefuroxime-gentamicin), sepsis syndrome in 7 patients (4 meropenem, 3 cefuroxime-gentamicin), and "other" in 1 patient (cefuroxime-gentamicin). The pathogens isolated from 18 patients with bacteremia were as follows: Staphylococcus spp. (n = 2), Streptococcus spp. (n = 2), members of the family Enterobacteriaceae (n = 11), and Bacteroides spp. (n = 3). A satisfactory clinical response at the end of therapy was achieved in 26 of 37 (70%) and 24 of 33 (73%) evaluable patients treated with meropenem and combination therapy, respectively. Clinical success was achieved in 23 of 31 (74%) and 21 of 28 (75%) evaluable patients with infections other than UTIs, respectively. A satisfactory microbiological response occurred in 15 of 22 (68%) patients in the meropenem group compared with 12 of 19 (63%) treated with combination therapy. Renal failure occurred during therapy in 2 of 39 (5%) meropenem recipients compared with 5 of 40 (13%) of those treated with combination therapy. The findings in this small study indicate that meropenem is as efficacious for and as well tolerated by elderly patients as the combination of cefuroxime-gentamicin (+/- metronidazole).

Topics: Aged; Aged, 80 and over; Bacterial Infections; Cefuroxime; Double-Blind Method; Drug Therapy, Combination; Female; Gentamicins; Humans; Male; Meropenem; Thienamycins; Treatment Outcome

In a multicenter, randomized, open comparison of meropenem to ceftazidime as empiric treatment of severe acute infections, 185 children (1 mo-15 years old, mean 65.4 mo) were enrolled. Meropenem (20 mg/kg t.i.d. i.v.) was given to 98 and ceftazidime (10-30 mg/kg t.i.d. i.v.) to 87 children, generally for 5 to 10 days (mean: 6.9 for meropenem and 7.5 for ceftazidime). Clinical response was evaluated at the beginning and at the end of therapy and 4 weeks later (follow-up). Clinical response was deemed satisfactory at the end of therapy in 96.7% of the patients treated with meropenem and in 95.3% of those who received ceftazidime without any statistically significant difference. One relapse occurred in a meropenem-treated patient at the follow-up clinical assessment. The baseline infecting organism was eradicated or presumed eradicated at the end of therapy in 14/16 patients treated with meropenem and in 14/15 treated with ceftazidime. The incidence of drug-related adverse events (mostly a slight increase in liver enzymes) was 9.2% in the meropenem group and 4.6% in the ceftazidime group. Our data show that meropenem is as effective as ceftazidime in the empiric treatment of severe infections in infants and children.

Topics: Adolescent; Bacterial Infections; Ceftazidime; Cephalosporins; Child; Child, Preschool; Drug Monitoring; Hospitalization; Humans; Infant; Infant, Newborn; Liver; Meropenem; Respiratory Tract Infections; Sepsis; Skin Diseases, Infectious; Thienamycins; Treatment Outcome; Urinary Tract Infections

The aim of this study was to compare the clinical and bacteriologic efficacy of meropenem with imipenem/cilastatin in the treatment of obstetric and gynecologic infections. This was a controlled, multicenter, randomized study with two parallel groups and a follow-up period of up to 4 weeks. A total of 105 hospital in-patients requiring antibacterial parenteral therapy were enrolled, 52 in the meropenem group and 53 in the imipenem/cilastatin group. Both drugs were administered at 0.5 g every 8 hours, by slow intravenous infusion over 20-30 minutes; for meropenem the administration by intravenous bolus injection (over approximately 5 minutes) was allowed. The mean duration of therapy was 5 days for both treatments. At the end of treatment, all 46 evaluable patients in the meropenem treatment group had a satisfactory clinical response, while in the imipenem/cilastatin group 5/49 patients were clinical failures. The difference between the treatment groups in clinical response was statistically significant (100% vs 89.8%; p=.026). A similar result was seen in the intention-to-treat analysis (98% vs 84.6%; p=0.017). Both treatments were well tolerated, but fewer meropenem patients experienced treatment-related adverse events in comparison with imipenem/cilastatin (11.5% vs 15.1%).

Topics: Adolescent; Adult; Aged; Bacterial Infections; Cilastatin; Drug Therapy, Combination; Female; Follow-Up Studies; Genital Diseases, Female; Humans; Imipenem; Infusions, Intravenous; Injections, Intravenous; Meropenem; Middle Aged; Protease Inhibitors; Thienamycins; Treatment Outcome

The empiric antibiotic treatment of intraabdominal infections is in constant evolution. Monotherapy appears to be a desirable goal because of the simplicity of its administration, lack of toxic effects and wide spectrum.. A multicentre, prospective, randomized, open study was carried out to compare two antibiotic regimens in the treatment of intraabdominal infections in patients undergoing surgery. Ninety-eight consecutive patients were randomly allocated into two groups. One group (GM, n = 51) received meropenem (1 g/8 h) and the other (GCM, n = 47) a combination of cefotaxime (2 g/8 h) plus metronidazol (0.5 g/8 h). Clinical and bacteriological responses were assessed at the end of treatment and at 2-4 weeks.. The severity of patients as assessed by the APACHE II score was similar in both groups (GM: 7.2 and GCM: 8.1). Three patients in each group could not be evaluated due to premature interruption of treatment or deviation from the protocol. The mean duration of treatment was 7.4 days in GM and 7.9 days in GCM. A satisfactory clinical response was obtained in 95% of patients in both groups. 31 patients (61%) in GM and 26 patients (55%) in GCM were bacteriologically evaluable. Bacteriological erradication was achieved in 94% of patients in GM and in 92% of patients in GCM.. Meropenem is a good alternative for single antibiotic therapy in intraabdominal infections of moderate severity.

Topics: Abdomen; Abdominal Abscess; Adult; Aged; Bacterial Infections; Cefotaxime; Drug Therapy, Combination; Female; Humans; Male; Meropenem; Metronidazole; Middle Aged; Peritonitis; Prospective Studies; Thienamycins

We conducted a multicenter trial to compare the efficacy and safety of meropenem with the efficacy and safety of clindamycin plus gentamicin in the treatment of 515 hospitalized patients with acute gynecologic and obstetric pelvic infections. At the end of treatment, the rates of satisfactory clinical and bacteriologic response were high (88%) in both treatment groups: the rates of response were 90% for the meropenem group and 86% for the clindamycin/gentamicin group. No serious adverse events occurred. The most frequently reported drug-related adverse clinical events in the meropenem group were nausea and injection-site reactions (> 1% of patients), and the most common drug-related laboratory abnormality was thrombocythemia. Similar patterns of adverse events occurred in the clindamycin/gentamicin group; however, the incidence of diarrhea and eosinophilia was higher in this group. In summary, this trial demonstrated that meropenem is an effective and safe alternative to the combination of clindamycin plus gentamicin for the treatment of women with acute gynecologic and obstetric pelvic infections.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Clindamycin; Diarrhea; Drug Therapy, Combination; Eosinophilia; Female; Genital Diseases, Female; Gentamicins; Hospitalization; Humans; Meropenem; Microbial Sensitivity Tests; Pelvic Inflammatory Disease; Pregnancy; Pregnancy Complications, Infectious; Thienamycins; Thrombocytopenia

To determine clinical and bacteriological efficacy and tolerability of meropenem and imipenem/cilastatin, given intravenously, in the treatment of intra-abdominal infections in hospitalized patients.. Open multicentre, randomized, parallel groups clinical trial, comparing meropenem and imipenem/cilastatin.. Six Italian hospitals.. Eighty-six hospitalized patients, aged 16 or more, with intra-abdominal infections requiring parenteral antibiotic therapy, were randomized to two treatment groups (43 on meropenem, 43 on imipenem/cilastatin). Eighty-four patients completed the study and 2 were excluded from efficacy analysis.. Meropenem and imipenem/cilastatin were administered intravenously at 1 g TID. Dosage was reduced in patients with renal impairment. Mean treatment duration in clinically evaluable patients was 7.0 days in meropenem group and 7.6 days in imipenem/cilastatin group.. Clinical efficacy evaluated at the end of the therapy and 2-4 weeks after. Bacteriological efficacy before, during, and immediately after the end or the modification of the experimental treatment. All adverse events were recorded.. 42/43 (98%) patients on meropenem and 39/41 (95%) on imipenem/cilastatin had satisfactory clinical response. In both groups bacteriological response was satisfactory in 26/27 (96%) evaluable patients. No statistically significant differences were found, both for clinical and bacteriological efficacy. Only two adverse reaction to study drug were observed (1 rash per treatment group).. Meropenem, broad spectrum antibiotic with high stability to human renal DHP-1, given alone for the treatment of intra-abdominal infections is as effective and well tolerated as imipenem/cilastatin.

Topics: Abdomen; Adolescent; Adult; Aged; Bacterial Infections; Cilastatin; Female; Follow-Up Studies; Humans; Imipenem; Infusions, Intravenous; Male; Meropenem; Middle Aged; Protease Inhibitors; Thienamycins; Time Factors

We conducted a prospective, multi-centre, open, randomized study in 11 UK hospitals to compare iv meropenem 1 g tds with the combination of iv cefotaxime 1 g tds and iv metronidazole 500 mg tds in patients with serious infections. One hundred and sixty-one patients were enrolled, of whom 131 were clinically evaluable (meropenem, n = 68; cefotaxime/metronidazole, n = 63). The most common infections were subsequent to intra-abdominal pathology (meropenem, n = 77%; cefotaxime/metronidazole, n = 75%), and were usually accompanied by septicaemia (meropenem, n = 61%; cefotaxime/metronidazole, n = 53%). The incidence of a satisfactory clinical response was similar in the two groups at the end of treatment (93% for meropenem; 92% for cefotaxime/metronidazole) and up to 8 weeks later (96% for meropenem; 93% for cefotaxime/metronidazole). Satisfactory bacteriological response (success or presumed success) was recorded at the end of therapy in 86% of meropenem and 88% of cefotaxime/metronidazole patients. Adverse events were reported in 32% of meropenem and 25% of cefotaxime/metronidazole patients, and most were mild or moderate and did not require discontinuation of therapy. Twenty-one patients (ten meropenem and 11 cefotaxime/metronidazole) died during the trial, underlining the severity of the infections being treated in this group of patients. None of the deaths was thought to be related to study therapy.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Cefotaxime; Female; Hospitalization; Humans; Male; Meropenem; Metronidazole; Middle Aged; Prospective Studies; Thienamycins; Treatment Outcome

An open-label prospective, randomized, parallel multicentre study was undertaken to compare the efficacy and tolerability of 1.5 g/day intravenous imipenem/cilastatin with 3 g/day intravenous meropenem in the treatment of intra-abdominal infections. A total of 287 patients were enrolled: 201 patients, divided between the 2 treatment groups, were evaluable. Clinical outcome, bacteriological outcome, untoward microbiological effects, and clinical and laboratory adverse experiences were evaluated. 98% of patients receiving imipenem/cilastatin therapy were cured, with 96% showing eradication of infection. 95% of those on meropenem were cured, with 98% showing eradication. These differences in clinical and bacteriological outcome between the 2 treatments were not statistically significant. Two patients receiving imipenem/cilastatin and 5 receiving meropenem had untoward microbiological effects. There was a 0.7% frequency (1/139 patients) of possibly or probably drug-related clinical or laboratory adverse experiences with imipenem/cilastatin and a 2.7% frequency (4/148) with meropenem. The mean time to defervescence was significantly less for patients in the imipenem/cilastatin treatment group than for those receiving meropenem. This study shows that 1.5 g/day of imipenem/cilastatin is equivalent to 3.0 g/day meropenem in clinical and bacteriological outcome, as well as in incidence of side effects.

Topics: Abdomen; Adult; Aged; Anti-Bacterial Agents; APACHE; Bacterial Infections; Cilastatin; Female; Humans; Imipenem; Infusions, Intravenous; Male; Meropenem; Middle Aged; Prospective Studies; Protease Inhibitors; Thienamycins; Treatment Outcome

Meropenem was compared with imipenem/cilastatin for the treatment of serious bacterial infections in a randomized, prospective multicentre study. Both study drugs were given intravenously 1 g every 8 h and no other antimicrobial agents were permitted concomitantly. Of the 204 patients enrolled, the treatment of 177 was evaluable for clinical efficacy and 115 for bacteriological efficacy. In the clinically evaluable treatment population, 75 (83%) of the 90 patients in the meropenem group and 78 (90%) of the 87 in the imipenem/cilastatin group had a single site of infection whereas the remainder had two or more sites of infection. Infections of the lower respiratory tract and peritoneal cavity predominated accounting for 95 and 75 cases respectively. Other infections included skin and soft tissue infections, complicated urinary tract infections, bacteraemia and a case of meningitis treated with meropenem and one of mediastinitis treated with imipenem/cilastatin. One hundred and nineteen (67%) patients were in an intensive care unit, 105 (59%) were receiving assisted ventilation and 93 (53%) of the patients had failed previous antibiotic therapy. One hundred and ten organisms were identified as pathogens in the meropenem group and 109 in the imipenem/cilastatin group. Overall, treatment with meropenem was clinically successful in 68 (76%) of 90 cases and imipenem/cilastatin in 67 (77%) of 87 cases and the corresponding eradication rates of bacteria were 85 of 110 (77%) and 90 of 109 (83%) respectively. Superinfections due to resistant bacteria occurred in two patients treated with meropenem and three cases given imipenem/cilastatin. No statistically significant differences in the clinical or bacteriological outcome were observed between the treatment groups for any of the infection sites analysed. Both drugs were well tolerated with adverse events considered to be related to therapy being recorded for 10 (9%) of 106 patients treated with meropenem and 12 (12%) of 98 of those who had been given imipenem/cilastatin. Empirical monotherapy with meropenem was therefore as effective and as well tolerated as that with imipenem/cilastatin for the treatment of serious bacterial infections.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacterial Infections; Cilastatin; Drug Therapy, Combination; Female; Hospitals; Humans; Imipenem; Infusions, Intravenous; Injections, Intravenous; Male; Meropenem; Middle Aged; Peritonitis; Protease Inhibitors; Respiratory Tract Infections; Thienamycins; Time Factors; Treatment Outcome; Urinary Tract Infections

Meropenem, a new carbapenem with improved stability in the presence of human dehydropeptidase-I[1], was evaluated in three prospective, multicenter, randomized, controlled clinical trials in North America. We compared the in vitro activity of meropenem and conventional antimicrobial agents for the treatment of intraabdominal, obstetric/gynecologic, and skin or soft tissue infections as well as the responses of pathogens to all of these agents. The trials of the drug for intraabdominal infection were double blind, and those for the obstetric/gynecologic and soft tissue infections were open labeled. Overall, MICs of meropenem for pathogens were lower, and the pathogen response rates were at least comparable to those for the following comparative agents: clindamycin plus tobramycin (for intraabdominal infections); clindamycin plus gentamicin (for obstetric/gynecologic infections); and imipenem and cilastatin (for skin or soft tissue infections). Meropenem has high in vitro potency and covers a broad spectrum of anaerobic and aerobic pathogens.

Topics: Abdomen; Anti-Bacterial Agents; Bacterial Infections; Double-Blind Method; Female; Genital Diseases, Female; Humans; Meropenem; Microbial Sensitivity Tests; Prospective Studies; Skin Diseases, Bacterial; Soft Tissue Infections; Thienamycins

The safety and efficacy of meropenem and imipenem/cilastatin were compared in the treatment of hospitalized patients with complicated urinary tract infections (UTIs) in a prospective, multicenter, open, parallel-group trial. Patients were randomized to receive 500-mg intravenous doses of either meropenem every 8 hours (n = 116) or imipenem/cilastatin every 6 hours (n = 119). Data from 95 patients given meropenem and 82 patients given imipenem/cilastatin were included in the evaluation of efficacy. Meropenem produced satisfactory clinical and bacteriologic responses in 99% and 90% of cases, respectively. These results were similar to those obtained with imipenem/cilastatin, which produced clinical improvement in 99% of cases and bacteriologic improvement in 81%. Two patients given meropenem and five patients given imipenem/cilastatin developed superinfections. The rate of relapse was similar in the two groups. Patients who received meropenem had fewer drug-related adverse reactions than did recipients of imipenem/cilastatin (8% vs. 19%). The results of this study demonstrate that meropenem is a safe and effective alternative to imipenem/cilastatin in the treatment of hospitalized patients with complicated UTIs.

Topics: Bacteria; Bacterial Infections; Cilastatin; Drug Therapy, Combination; Female; Hospitalization; Humans; Imipenem; Infusions, Intravenous; Male; Meropenem; Middle Aged; Prospective Studies; Protease Inhibitors; Thienamycins; Urinary Tract Infections

Meropenem is a new carbapenem antibiotic shown to resist degradation by renal dehydropeptidase I. In a multicenter, open-label, prospective trial, we compared the efficacy and safety of meropenem with imipenem/cilastatin in patients with skin and soft tissue infections. Patients received either 500 mg of meropenem every 8 hours (n = 184) or 500 mg of imipenem/cilastatin every 6 hours (n = 193), by intravenous infusion for an average of 6 to 7 days. Satisfactory clinical responses were achieved in 120 (98%) of 123 assessable meropenem-treated patients and in 120 (95%) of 126 assessable imipenem/cilastatin-treated patients. Satisfactory bacteriologic responses were achieved in 120 (98%) of 123 assessable meropenem-treated patients and in 120 (95%) of 126 assessable imipenem/cilastatin-treated patients. Satisfactory bacteriologic response rates were high as well: 94% with meropenem and 91% with imipenem/cilastatin. Between-group differences in satisfactory response rates were not significant (95% confidence interval, -2.29 to 6.93 [clinical]; -2.73 to 10.39 [bacteriologic]). Overall pathogen eradication rates (for aerobes and anaerobes) were slightly higher for meropenem. Elevated liver enzymes were the most frequent adverse events in each treatment group. Meropenem was well tolerated and as effective as imipenem/cilastatin in treatment of hospitalized patients with skin and soft tissue infections.

Topics: Abscess; Adolescent; Adult; Aged; Aged, 80 and over; Bacterial Infections; Cellulitis; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Female; Hospitalization; Humans; Imipenem; Infusions, Intravenous; Male; Meropenem; Middle Aged; Prospective Studies; Skin Diseases, Infectious; Soft Tissue Infections; Thienamycins; Ulcer

In order to compare the clinical and microbiological efficacy and safety of meropenem with imipenem/cilastatin, 249 patients with intra-abdominal infections participated in an open randomised comparative multicentre trial. Seventy-five men and 57 women (mean age 51 years) were enrolled in the meropenem group and 67 men and 50 women (mean age 52 years) in the imipenem/cilastatin group. The patients received either meropenem, 500 mg q 8 h, or imipenem/cilastatin, 500 mg/500 mg q 8 h by intravenous infusion for up to 17 days (mean 5 days). Ninety-seven of 99 patients (98%) receiving meropenem were clinically cured while 86 of 90 patients (96%) in the imipenem/cilastatin group were clinically cured. The microbiological response was satisfactory in 89 of 94 evaluable patients (95%) receiving meropenem and in 78 of 81 evaluable patients (96%) receiving imipenem/cilastatin. There was no significant difference in clinical and microbiological efficacy between the two treatment groups. Adverse reactions were noted in 26 patients receiving meropenem and in 36 patients receiving imipenem/cilastatin. The present study shows that meropenem is effective and well tolerated in the treatment of intra-abdominal infections.

Topics: Abdomen; Adolescent; Adult; Aged; Aged, 80 and over; APACHE; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Female; Humans; Imipenem; Infusions, Intravenous; Male; Meropenem; Middle Aged; Thienamycins

The efficacy of meropenem was compared to that of the combination of tobramycin plus clindamycin (T/C) in a multiinstitutional clinical trial of treatment for patients suffering intraabdominal infection. Among the 177 patients enrolled and randomized, 127 were clinically evaluable and 86 were microbiologically evaluable. Analysis of data on an intent-to-treat basis for all randomized patients and on the basis of a successful outcome (absence of any infection) for clinically evaluable patients failed to detect any difference in efficacy between the two treatments. Infection was cleared in 92% of meropenem- and 89% of T/C-treated clinically evaluable patients. Eradication of pathogens also was similar in the two treatment groups. Overall, adverse drug experiences were comparable between the two treatment groups, with the exception of an increase in serum creatinine level (which occurred more frequently in patients receiving T/C). Meropenem appears to be efficacious for the treatment of intraabdominal infections.

Topics: Abdomen; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Clindamycin; Diarrhea; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Meropenem; Middle Aged; Prospective Studies; Thienamycins; Tobramycin

The pharmacokinetics of meropenem were studied in a group of 11 surgical patients (four male, seven female; mean age 63 years; mean weight 72 kg) all of whom had moderate or severe infection and who received a mean dose of 14.5 mg/kg +/- 2.7 meropenem 8-hourly iv for a minimum of 4 days. Venous blood samples were collected at timed intervals after the first dose on day 1 and the second dose on the fourth or fifth day of therapy. Serum meropenem concentrations were assayed by HPLC and fitted to a two compartment pharmacokinetic model. The mean pharmacokinetic parameters (+/- standard deviation) on day 1 were T1/2 84.6 +/- 24.1 min, Vdss 0.22 +/- 0.06 L/kg, AUC 6028 +/- 1983.2 mg.min/L, Cltot 188 +/- 67 mL/min and MRT 89.1 +/- 67.8 min. On the fourth or fifth days of therapy the values were T1/2 79.9 +/- 18.2 min, Vdss 0.17 +/- 0.8 L/kg, AUC 6000.7 +/- 2417 mg.min/L, Cltot 190 +/- 60 mL/min and MRT 67.8 +/- 30.4 min. Although the T1/2, Vdss and MRT decreased from day 1 to day 4 or 5 these changes were not statistically significant (Student's t-test, P > 0.05). Total clearance of meropenem was linearly related to creatinine clearance or patient age on the first day of therapy. Although the T1/2 and MRT were longer and the Cltot lower than those reported for young healthy volunteers, they were similar to those found in elderly volunteers.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aged, 80 and over; Bacterial Infections; Chromatography, High Pressure Liquid; Female; Humans; Male; Meropenem; Middle Aged; Models, Biological; Spectrophotometry, Ultraviolet; Surgical Procedures, Operative; Thienamycins

The efficacies of meropenem, a novel carbapenem, and ceftazidime, as empirical therapy of febrile neutropenic patients, were compared in a prospective, randomized clinical trial. One hundred and twelve adult patients were given meropenem 1 g tds iv for 153 episodes of fever, while 109 patients received ceftazidime 2 g tds iv for 151 episodes. All patients survived the first 3 days of therapy and, by the end of the treatment courses, 67 (44%) episodes had responded to meropenem, compared with 62 (41%) to ceftazidime. Eighty (53%) episodes initially treated with ceftazidime and 63 (41%) episodes treated with meropenem were considered to have failed treatment because it was thought necessary to administer additional antibacterial agents; however, modifications were made twice as often because of fever that persisted beyond 2-3 days than because of obvious causes of failure such as persistent infection. Three patients in the ceftazidime group and five in the meropenem group died. Meropenem was well tolerated, with no reports of nausea or toxicity to the central nervous system. Although ceftazidime was shown in the present study to be as effective as meropenem, the broader spectrum of activity of meropenem against Gram-positive cocci suggests that it might be more appropriate as empirical therapy of febrile neutropenic patients who are at high risk of acquiring infections caused by these bacteria.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Ceftazidime; Cephalosporins; Female; Fever; Humans; Leukemia; Leukocyte Count; Male; Meropenem; Middle Aged; Neutropenia; Prospective Studies; Thienamycins; Treatment Failure

In three open, multicentre, prospective randomised studies, the efficacy and safety of meropenem were assessed and compared with ceftazidime (Study 1) and imipenem/cilastatin (Studies 2 and 3) in 864 patients; 417 with urinary tract infections (UTI) and 447 with community acquired lower respiratory tract infections (LRTI). All the antibiotics were administered by intramuscular injection. Clinical and bacteriological responses were assessed at the end of therapy and at follow-up (2-4 weeks for LRTI, 4-6 weeks for UTI). The clinical response rate in UTI at the end of therapy was 93-100% for meropenem 500 mg tds compared with 94-95% for ceftazidime 500 mg tds; for meropenem 500 mg bd it was 97%, significantly higher than that for imipenem/cilastatin 500 mg bd which was 90% (P = 0.03). At follow-up, the response rates were 90% for meropenem tds compared with 81-85% for ceftazidime 500 mg tds and 81% for meropenem bd compared with 78% for imipenem/cilastatin 500 mg bd. The clinical response rate in LRTI at end of therapy was 93% for meropenem 500 mg tds, compared with 92% for ceftazidime 1 g tds; for meropenem 500 mg bd the clinical response rate was 96%, compared with 91% for imipenem/cilastatin 500 mg bd (P = 0.054). At follow-up, the clinical response rates were 96%, 89%, 93% and 96%, respectively. The bacteriological response rates at 5-9 days post-therapy in UTI were 61-84% in patients treated with meropenem 500 mg tds, compared to 73-82% in patients treated with ceftazidime 500 mg tds; the rates for meropenem 500 mg bd and imipenem/cilastatin 500 mg bd were each 75%. At follow-up, the response rates were 40-72%, 57-70%, 51% and 49%, respectively. In LRTI, bacteriological response rates at the end of therapy were 91% for both meropenem 500 mg tds and ceftazidime 1 g tds, and 91% for meropenem 500 mg bd compared with 86% for imipenem/cilastatin 500 mg bd. At follow-up, the response rates were 87%, 77%, 84% and 79%, respectively. All treatments were well tolerated. In these studies, intramuscular meropenem proved to be an effective and well tolerated treatment for LRTI and UTI.

Topics: Bacterial Infections; Carbapenems; Ceftazidime; Cilastatin; Humans; Imipenem; Injections, Intramuscular; Meropenem; Respiratory Tract Infections; Thienamycins; Treatment Outcome; Urinary Tract Infections

Meropenem and imipenem/cilastatin were compared in an open, randomised prospective multicentre study in the treatment of acute exacerbations of severe chronic obstructive pulmonary disease in hospitalised patients. One-hundred-and-seventy-three patients were enrolled; 164 were evaluable for clinical efficacy and 98 for bacteriological efficacy, with 144 pathogens isolated. The predominant pathogens were Haemophilus influenzae (n = 30), Streptococcus pneumoniae (18), Staphylococcus aureus (12), Pseudomonas aeruginosa (11), Moraxella catarrhalis (8), other Gram-negative bacteria (Neisseria, Klebsiella, Proteus, and Enterobacter spp.) (53) and other Gram-positive bacteria (12). A single bacterial pathogen was identified in 61 patients, whereas two bacterial pathogens were isolated in 31 patients and three in six patients. The clinical response at the end of treatment was very high in both groups with a satisfactory outcome (cured or improved) in 97.6% of the meropenem patients and in 96.3% of the imipenem/cilastatin patients; at follow-up the rates were 89.1% and 89.8%, respectively. The bacterial success (eradication or presumed eradication) was 88.2% in the meropenem group and 89.4% in the comparator group. Nausea or vomiting were reported more frequently in patients treated with imipenem/cilastatin, whereas in the meropenem group an increase in aminotransferases was reported. One patient treated with imipenem/cilastatin was withdrawn from the study due to seizures. Meropenem and imipenem/cilastatin were highly effective for the treatment of severe bacterial exacerbations of chronic bronchitis but meropenem was better tolerated.

Topics: Bacterial Infections; Bronchitis; Carbapenems; Cilastatin; Drug Therapy, Combination; Drug Tolerance; Hospitalization; Humans; Imipenem; Lung Diseases, Obstructive; Meropenem; Prospective Studies; Thienamycins; Treatment Outcome

A multicentre, open, randomised, parallel group study was carried out to assess the efficacy and safety of meropenem monotherapy versus the combination of ceftazidime plus amikacin in the treatment of serious bacterial infections. Adult, hospitalised patients (n = 237) were included if they had infections at one or more of the following sites: lower respiratory tract (89 community-acquired; 84 hospital-acquired), urinary tract (59 complicated; 3 uncomplicated), skin and skin structures (n = 8), or septicaemia (n = 29). Patients were randomised to receive either iv meropenem (1 g every 8 h) as monotherapy or iv ceftazidime (2 g every 8 h) plus iv amikacin (15 mg/kg/day in two or three divided doses). Meropenem had comparable clinical efficacy to ceftazidime plus amikacin in: community-acquired lower respiratory tract infection (LRTI) (40/43, 93% vs 31/39, 79% cured or improved); hospital-acquired LRTI (30/37, 81% vs 23/32, 72%); septicaemia (10/12, 83% vs 16/17, 94%) and complicated urinary tract infection (UTI) (13/15, 87% vs 25/25, 100%). A similar proportion of patients in each treatment group experienced adverse events, the most frequent being transient elevations in serum transaminases. Seven patients in the meropenem group and eight patients in the ceftazidime plus amikacin group died during the study period from reasons unrelated to study medication, and seven patients (five meropenem, two ceftazidime plus amikacin) were withdrawn due to adverse events. Empirical monotherapy with meropenem is as well tolerated and as effective as the combination of ceftazidime plus amikacin in the treatment of serious infections.

Topics: Adolescent; Adult; Aged; Amikacin; Bacterial Infections; Carbapenems; Ceftazidime; Community-Acquired Infections; Cross Infection; Drug Therapy, Combination; Drug Tolerance; Hospitalization; Humans; Meropenem; Middle Aged; Respiratory Tract Infections; Sepsis; Thienamycins; Time Factors; Treatment Outcome; Urinary Tract Infections

In an open, multicentre, randomised study, the efficacy and safety of meropenem monotherapy as adjuvant antibiotic therapy in the surgical management of intra-abdominal infection was compared with that of the combination of cefotaxime and metronidazole. A total of 160 hospitalised adult patients with intra-abdominal infection requiring surgery were treated intravenously with either meropenem 1 g every 8 h (by bolus injection or infusion; n = 77) or cefotaxime 2 g and metronidazole 500 mg every 8 h (n = 83). Clinical and bacteriological responses to antibiotic therapy were assessed at the end of treatment and at 2-4 weeks' follow-up after treatment. The clinical response rates at the end of treatment and follow-up were 91% and 96%, respectively, for meropenem and 100% and 97%, respectively, for cefotaxime plus metronidazole. The bacteriological response rates were 90% and 93%, respectively, for meropenem and 92% at both time points for cefotaxime plus metronidazole. Both treatments were well tolerated. In this study, meropenem monotherapy was effective and as well tolerated as cefotaxime plus metronidazole. Meropenem monotherapy should, therefore, prove a useful alternative to standard combination therapy for the empirical treatment of intra-abdominal infections.

Topics: Abdomen; Adolescent; Adult; Aged; Anti-Infective Agents; Bacterial Infections; Carbapenems; Cefotaxime; Drug Therapy, Combination; Drug Tolerance; Humans; Meropenem; Metronidazole; Middle Aged; Thienamycins; Treatment Outcome

In a multicentre, open, randomised study, the efficacy and tolerability of intravenous meropenem (1 g every 8 h, infusion or bolus) was compared with that of intravenous imipenem/cilastatin (1 g every 8 h, infusion) in 232 hospitalised patients with moderate to severe intra-abdominal infections. At the end of therapy, a satisfactory clinical response (cure or improvement) was seen in 79/82 (96%) evaluable meropenem patients and 83/88 (94%) imipenem/cilastatin patients; this was still seen at follow-up (57/63; 90% and 58/66; 88%, respectively). A satisfactory bacteriological response (elimination or presumed elimination) was seen in 69/82 (84%) meropenem patients and 71/88 (81%) imipenem/cilastatin patients at the end of therapy and in 52/62 (84%) and 55/70 (79%), respectively, at follow-up. There was a high level of clinical cure or improvement (95% for both treatment groups) in the 120 patients (60 in each group) who had polymicrobial infections. A similar incidence of adverse events was seen in each group: 45/116 patients in the meropenem group (72 events) and 42/116 patients in the imipenem/cilastatin group (65 events); the adverse event profiles were also similar, with injection site inflammation and elevated transaminases the most frequent in both groups. The results of this study indicate that monotherapy with meropenem was as effective and as well tolerated as the combination of imipenem/cilastatin in the treatment of moderate to severe intra-abdominal infections.

Topics: Abdomen; Adolescent; Adult; Aged; Bacterial Infections; Carbapenems; Cilastatin; Drug Therapy, Combination; Humans; Imipenem; Injections, Intravenous; Meropenem; Middle Aged; Thienamycins; Treatment Outcome

Data from 3125 patients (3220 patient exposures) treated with meropenem were compared with those from 2886 patients (2960 patient exposures) treated with a variety of comparator agents including cephalosporins (alone or in combination with aminoglycosides or an anti-anaerobe agent) and imipenem/cilastatin. Patients treated included those with bacterial infections of the lower respiratory tract, urinary tract and skin and soft tissues, abdominal, obstetric and gynaecological infections, meningitis, febrile episodes in neutropenic patients and paediatric patients with infections. In three studies, meropenem was administered intramuscularly; in the remainder, meropenem was given by 15-30 min iv infusion or by bolus injection over approximately 5 min. The usual dosages were 500 mg or 1 g 8 hourly in adults and 10 or 20 mg/kg 8 hourly in children. In bacterial meningitis, the meropenem dosage in adults was 2 g 8 hourly and 40 mg/kg 8 hourly in children. The overall pattern and frequency of adverse events with meropenem were similar to those of the other beta-lactam antibiotics with which it was compared. The most frequently reported adverse events were diarrhoea, rash, nausea and vomiting, thrombocytosis, eosinophilia and changes in hepatic biochemistry. Abnormal laboratory tests occurred with similar frequencies between meropenem and the comparator agents. The safety profile of meropenem was similar in adults and children, and the presence of renal impairment did not alter the safety profile of meropenem. Experience in clinical studies in 3220 patient exposures has revealed no unusual or unexpected toxicity. The possibility of administration by either iv infusion or bolus injection with a low incidence of nausea and vomiting also provides flexibility in the clinical management of patients. Moreover, the low incidence of reported seizures and good tolerability at high doses, make meropenem particularly useful for the treatment of meningitis and other indications which carry a risk of seizures, or in the treatment of serious infections where high doses of antibiotics are frequently indicated.

Topics: Bacterial Infections; Carbapenems; Child; Clinical Trials, Phase III as Topic; Humans; Meropenem; Prospective Studies; Randomized Controlled Trials as Topic; Thienamycins; Treatment Outcome

In this multicentre, randomised study of 170 children hospitalised with bacterial infections, meropenem (10 to 20 mg/kg every 8 h) was found to be as effective and as well tolerated as cefotaxime (100 to 150 mg/kg/day), with or without amikacin or metronidazole. Most drug-related adverse events were mild and self-limiting. Neither regimen was associated with seizures. The overall incidence of clinically significant laboratory changes was similar in the two treatment groups. Satisfactory clinical responses were obtained in 94/96 (98%) patients treated with meropenem monotherapy and 43/46 (93%) children treated with cefotaxime regimens, while satisfactory bacteriological responses were obtained in 25/28 (89%) and 9/10 (90%) patients, respectively. Meropenem monotherapy appears to be a well-tolerated and effective drug for paediatric infections.

Topics: Amikacin; Anti-Bacterial Agents; Bacterial Infections; Carbapenems; Cefotaxime; Cephalosporins; Child; Child, Preschool; Drug Therapy, Combination; Drug Tolerance; Humans; Infant; Meropenem; Metronidazole; Thienamycins

Noncompartmental and compartmental analyses of meropenem disposition in patients receiving 1-g intravenous intermittent infusions every 8 h were performed. Twelve patients (one woman and 11 men) participated in the meropenem pharmacokinetic analysis. Operative findings included perforated appendicitis (five patients), gangrenous appendicitis (five patients), peri-appendical abscess (one patient), and gunshot wound to the abdomen (one patient). The most common associated adverse drug reactions to meropenem were diarrhea and increased liver enzymes. The estimated noncompartmental pharmacokinetic parameters, mean +/- standard deviation, are as follows: maximum drug concentration in plasma, 47.58 +/- 17.59 micrograms/ml; half-life, 1.04 +/- 0.19 h; elimination rate constant, 0.68 +/- 0.12 h-1; area under the concentration-time curve from 0 h to infinity, 57.5 +/- 20.12 micrograms x ml/h; total plasma clearance, 315.40 +/- 71.94 ml/min; renal clearance, 136.7 +/- 89.20 ml/min; volume of distribution at steady state, 26.68 +/- 6.88 liters; and mean residence time, 1.47 +/- 0.28 h. The two-compartment model best described meropenem disposition in our patients. Our findings differed from estimates for healthy volunteers possibly because of the physiologic changes as a result of surgery. Our findings suggest that meropenem (1,000 mg) administered intravenously every 8 h provides adequate concentrations for most intra-abdominal infections.

Topics: Abdomen; Adolescent; Adult; Bacterial Infections; Double-Blind Method; Female; Half-Life; Humans; Infusions, Intravenous; Male; Meropenem; Middle Aged; Models, Biological; Thienamycins

Meropenem (MEPM), a novel parenteral carbapenem antibiotic, was examined in a cooperative study involving 12 pediatric and 1 neonatologic facilities. The results are summarized as follows. 1. Antibacterial activity Antibacterial activity of MEPM against stock organisms including 31 strains of Streptococcus agalactiae, 14 of Listeria monocytogenes, 4 of Bordetella pertussis and 3 of Neisseria meningitidis ranged from 0.025 to 0.10 micrograms/ml in MIC90's, which were equal or lower than those of control drugs such as imipenem cefazolin, cefotiam, cefotaxime, ceftazidime and latamoxef. MICs against clinical isolates were as follows: In Gram-positive bacteria, MICs were 0.20 micrograms/ml to 6.25 micrograms/ml against 3 strains of Staphylococcus aureus, and 0.025 micrograms/ml or less against 4 of Streptococcus pneumoniae. In Gram-negative bacilli, MICs were 0.10 micrograms/ml to 0.20 micrograms/ml against 3 strains of Haemophilus influenzae and 0.78, 0.10 and 0.78 micrograms/ml, respectively, against one strain each of Enterobacter cloacae, Morganella morganii and Pseudomonas aeruginosa. MIC against 1 strain of Peptococcus saccharolyticus was < or = 0.025 micrograms/ml. 2. Pharmacokinetics Maximum plasma concentrations after intravenous infusion of MEPM over 30 minutes at doses of 10, 20 and 40 mg/kg, respectively, to 3 different groups of 3 children (total 9 cases) were observed at the completion of the treatment. Mean maximum concentrations in the 3 groups were 36.3, 69.5 and 129.8 micrograms/ml, respectively, exhibiting clear dose response. Mean plasma half lives in beta phase were 0.94, 0.86 and 0.94 hours, respectively, exhibiting no difference by doses, and this trend was observed also by HPLC. Urinary excretion rates in the first 6 hours after dose in the 10, 20 and 40 mg/kg groups were 67.3, 65.6 and 68.4%, respectively. Concentrations of MEPM in cerebrospinal fluid were determined in 2 cases of pyogenic meningitis. In 1 case, 500 mg (5.9 mg/kg) of MEPM was infused intravenously over 30 minutes and concentrations on Days 6, 8 and 15 observed at 190, 60 and 100 minutes after respective doses were 0.13, 0.10 micrograms/ml and less than the detection limit. Cerebrospinal fluid-plasma concentration ratio was determinable only on Day 8 and was 2.8%. In another case to which 250 mg (38.5 mg/kg) of MEPM was infused intravenously over 30 minutes, the concentration at Days 6, 7 and 10, 1 hour after the dose were less than the detection limit on day 6, and 2.

Topics: Adolescent; Age Factors; Bacteria; Bacterial Infections; Child; Child, Preschool; Drug Resistance, Microbial; Female; Humans; Infant; Male; Meropenem; Thienamycins

The efficacy and the safety of meropenem (MEPM), a newly developed carbapenem antibiotic, were investigated in 150 patients with severe infections complicated with hematopoietic disorders. 1. Clinical responses in 132 patients who were evaluable for effectiveness were excellent in 33 patients, good in 45, fair in 10 and poor in 44, with an efficacy rate of 59.1%. 2. The efficacy rate in patients who had previously been treated with the other antibiotics was 51.2%, while that in patients who had not been thus treated was 62.9%. 3. The efficacy rate in patients whose neutrophil counts increased during the therapy with MEPM was higher than that in patients whose neutrophil counts did not increase. The efficacy rate in patients whose neutrophil counts during the therapy were below 100/mm3 was 48.1%. 4. Out of 150 cases, side effects were observed in 4 patients, 3 with eruption and 1 with jaundice. Abnormalities in laboratory test results on liver functions were noted in 8 patients. These results indicate that MEPM is an effective and safe antibiotic for the treatment of severe infections in patients with hematopoietic disorders.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Female; Hematologic Diseases; Humans; Leukemia, T-Cell; Lymphatic Diseases; Lymphoma, Non-Hodgkin; Male; Meropenem; Middle Aged; Myelodysplastic Syndromes; Thienamycins

Pharmacokinetic and clinical evaluations in pediatrics were made on meropenem (SM-7338, MEPM), a new parenteral dehydropeptidase-1 stable carbapenem used without any inhibitors, at 33 medical institutions. The results are summarized as follows. 1. Pharmacokinetic studies. MEPM at a dose of 10, 20, or 40 mg/kg was administered to 53 children by 30-minute drip infusion. Peak plasma concentrations (Cmax's) and plasma half-lives (T1/2's) of these doses were 28.5, 47.2 and 130.0 micrograms/ml, and 0.80, 0.93 and 0.94 hours, respectively. A clear dose response was observed in Cmax's and T1/2 values were quite similar to those observed in adults. In the first 6 hours after administration, 54.4 to 68.1% of the administered drug was recovered in urine. The cerebrospinal fluid (CSF) levels of MEPM in patients with purulent meningitis were 0.13 microgram/ml at a dose of 6 mg/kg, and 0.64 to 4.22 micrograms/ml at a dose of 29 to 44 mg/kg within day 4 of onset. The penetration rate of MEPM showed an intermediate value among those for other cephalosporin antibiotics. 2. Clinical study. Clinical efficacies of MEPM were evaluated in 389 cases. The most common doses used were 10 to 20 mg/kg/once, 2 to 3 times a day. The maximum dose was 173 mg/kg/day q.i.d. MEPM gave "excellent" or "good" responses in 242 (97.6%) out of 248 cases in which causative organisms were documented and in 134 (95.0%) out of 141 cases in which causative organisms were not identified. Clinical efficacy rates were 100% in 11 patients with purulent meningitis, 85.7% in 7 with septicemia, 98.8% in 173 with pneumonia, and 100% in 65 with UTI. Bacteriologically, 260 strains (96.7%) out of 269 strains were eradicated by MEPM treatment. Eradication rates were 89.2% for Staphylococcus aureus (37 strains) and 100% for Streptococcus pneumoniae (35 strains). The overall eradication rate for Gram-positive bacteria was 94.6%. Among Gram-negative bacteria, 98.3% out of 172 strains were eradicated. The eradication rate of Haemophilus influenzae (73 strains) was 98.6% and Pseudomonas aeruginosa (11 strains) was 90.9%, and all of Branhamella catarrhalis (15 strains), Escherichia coli (42 strains), and Klebsiella pneumoniae (6 strains) were eradicated. Out of 84 cases for which previous antibiotic therapies of 3 days or longer were not successful, MEPM gave "excellent" or "good" responses in 77 cases (91.7%) and excellent bacteriological responses (95.7%).(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Bacterial Infections; Child; Child, Preschool; Escherichia coli Infections; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Moraxella catarrhalis; Neisseriaceae Infections; Pseudomonas Infections; Staphylococcal Infections; Streptococcal Infections; Thienamycins

The authors report three trials of B-lactams and carbapenems for soft tissue infections treated on a surgical service: 1) cefmetazole versus cefoperazone, n = 44; 2) cefotetan versus cefoxitin, n = 24; and 3) meropenem versus imipenem, n = 44. A total of 138 hospitalized patients were enrolled with 112 meeting evaluability criteria. Four hundred twenty-three isolates were cultured (mean, three/patient) of which 67 per cent were aerobes and 33 per cent anaerobes. Cure rates for each trial were: 1) 93 per cent; 2) 92 per cent; 3) 100 per cent. Failures were caused by resistant organisms (Streptococcus group D, Bacteroides fragilis and Pseudomonas) appearing in incompletely drained infection sites. Three patients receiving meropenem had adverse effects (headache, nausea) and one receiving cefoxitin (truncal rash). Operative drainage and debridement remain the critical elements in therapy. Agents with longer half lives allowing twice daily dosing (cefmetazole and cefotetan) were as effective and less expensive than multiple doses of short-acting agents. The extended spectrum carbapenems are most useful for severe infections or resistant organisms.

Topics: Adult; Aged; Bacterial Infections; Carbapenems; Cefmetazole; Cefoperazone; Cefotetan; Cefoxitin; Cephalosporins; Drug Combinations; Drug Resistance, Microbial; Escherichia coli Infections; Female; Humans; Imipenem; Male; Meropenem; Middle Aged; Prospective Studies; Remission Induction; Skin Diseases, Infectious; Staphylococcal Infections; Streptococcal Infections; Thienamycins

A multicentre in-vitro study was undertaken to evaluate the susceptibility of bacterial pathogens isolated in different Italian hospitals to meropenem. A total of 1399 aerobic and 452 anaerobic strains was analysed. Comparative agents were imipenem, cefotaxime, ceftazidime, ceftriaxone, piperacillin, ciprofloxacin, gentamicin, amikacin, plus vancomycin when appropriate. The MIC ranges (mg/l) of meropenem were: 0.015-2 for Klebsiella spp., Proteus spp., Morganella morganii and Providencia spp.; less than 0.008-1 for Escherichia coli; 0.016-32 for Serratia spp.; 0.03-2 for Enterobacter spp. and Citrobacter spp.; 0.03- greater than 128 for Acinetobacter anitratus; 0.03-32 for Pseudomonas spp.; less than 0.008-0.5 for Haemophilus spp. and Neisseria spp.; 0.015-64 for Staphylococcus spp.; 0.06- greater than 128 for Enterococcus spp.; less than 0.008-0.25 for Streptococcus spp.; 0.016-8 for Fusobacterium spp.; 0.03-8 for Bacteroides spp.; less than 0.06-0.5 for anaerobic Gram-positive cocci; 0.08-2 for Clostridium spp. Meropenem exhibited superior antibacterial activity against the aerobic and anaerobic strains tested when compared to the other beta-lactam drugs. The new carbapenem was as active as ciprofloxacin and more active than imipenem and the aminoglycosides against Enterobacteriaceae and Ps. aeruginosa. It was also more active than ciprofloxacin against most strains of Gram-positive cocci. Meropenem was slightly less potent than imipenem against staphylococci and enterococci, with the exception of oxacillin-susceptible Staph. aureus against which meropenem and imipenem exhibited similar antibacterial activity.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Carbapenems; Ciprofloxacin; Gram-Negative Aerobic Bacteria; Gram-Negative Anaerobic Bacteria; Humans; Italy; Meropenem; Microbial Sensitivity Tests; Multicenter Studies as Topic; Thienamycins

The investigation on antibiotic stewardship in neonatal intensive care unit in China is scarce. This study aimed to analyze the effect of a comprehensive 2-year antibiotic stewardship in a level 4 NICU. During this baseline period from October 1st 2017 to October 1st 2019, continuation of empirical antibiotic therapy for ruled-out sepsis courses was beyond 72 h and for pneumonia was more than 7 days. Meropenem or vancomycin was used even if they were not the only bacterial sensitive antibiotics. The intervention period was from October 2nd 2019 to August 23rd 2021. Three areas for quality improvement were targeted in our center: discontinuation of antibiotic use in ruled-out sepsis within 72 h, treatment duration for culture-negative pneumonia less than 7 days, and vancomycin or meropenem was not used unless the cultured bacteria was only susceptible to them. The total antibiotic consumption decreased from 791.1 to 466.3 days of therapy per 1000 patient days from baseline to intervention period. Antibiotics were stopped within 72 h for 47.48% patients with rule-out sepsis and within 7 days for 75.70% patients with pneumonia compared with 11.56% and 37.69% during the baseline period respectively. The prevalence of multi-drug resistance bacteria decreased from 67.20 to 48.90%. The total use rate of meropenem or vancomycin decreased from 7.6 to 1.8%. Our quality improvement approach on antibiotic strategy significantly reduced antibiotic use and prevalence of multi-drug resistance bacteria in our NICU.

Topics: Anti-Bacterial Agents; Bacterial Infections; Drug Resistance, Multiple, Bacterial; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Meropenem; Sepsis; Vancomycin

To understand the changes of resistance of major clinical isolates to commonly used antibiotics in a comprehensive teaching hospital from 2015 to 2017 and to provide a basis for rational clinical use of antibiotics in the hospital. Antimicrobial susceptibility testing of all clinical isolates from 2015 to 2017 was carried out according to a unified protocol using Kirby-Bauer method or automated systems according to the unified plan. A total of 28715 non-repetitive clinical isolates were collected from 2015 to 2017. Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii were the top three most common isolates for three consecutive years. Escherichia coli is still highly sensitive to carbapenems, with the drug resistance rate less than 1%. Klebsiella pneumoniae's resistance to carbapenems increases year by year, reaching about 18% in 2017. The resistance rate of Acinetobacter baumannii to meropenem was above 70%, and that of Pseudomonas aeruginosa to meropenem was about 30%. Staphylococcus is more sensitive to linezolid and vancomycin. Enterococcus faecalis had lower drug resistance to most tested antibiotics (except tetracycline) than Enterococcus faecalis, and both were sensitive to linezolid and vancomycin. Bacterial resistance to commonly used antibiotics is still on the rise. We should strengthen the management of clinical use of antimicrobial agents and maintain good practice in surveillance of bacterial resistance.

Topics: Anti-Bacterial Agents; Bacterial Infections; Drug Resistance, Bacterial; Escherichia coli; Gram-Negative Bacteria; Hospitals, Teaching; Humans; Linezolid; Meropenem; Microbial Sensitivity Tests; Vancomycin

There are reports of high rates of antibiotic prescribing among hospitalized patients with COVID-19 around the world. To date, however, there are few reports of prescribing in relation to COVID-19 in Pakistan. Herein, we describe a point prevalence survey of antibiotic prescribing amongst patients hospitalized with suspected or proven COVID-19 in Pakistan. A Point Prevalence Survey (PPS) was undertaken in seven tertiary care health facilities in Punjab Provence, Pakistan. Baseline information about antimicrobial use according to the World Health Organization (WHO) standardized methodology was collected on a single day between 5

Topics: Adult; Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Bacterial Infections; Ceftriaxone; Coinfection; COVID-19; COVID-19 Drug Treatment; Drug Prescriptions; Female; Humans; Male; Meropenem; Pakistan; Prevalence

Consumption trends of four broad-spectrum antimicrobials and their correlation with antimicrobial resistance in Gram-negative bacilli (GNB) from 2013-2017 within intensive care units (ICUs) were explored.. Consumption of meropenem (MEM), polymyxin B (PMB), piperacillin/tazobactam (TZP) and cefepime (FEP) in defined daily doses per 1000 patient-days (DDD/1000PD) was measured. Infection-related GNB isolates were grouped according to specific resistance profiles. Time series of antimicrobial consumption and their parametric correlation with each grouped resistant GNB were explored.. A total of 1423 GNB were evaluated. A significant linear decline in consumption was observed for MEM [slope -3.88, 95% confidence interval (CI) -4.96 to -2.81; P < 0.0001] and PMB (slope -3.51, 95% CI -5.528 to -1.495; P = 0.0009). A significant decline in MEM-non-susceptible Acinetobacter spp. (R. Reduction in the consumption of broad-spectrum antimicrobials may alter the frequency of infection-related isolates and their antimicrobial resistance profiles.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Bacterial Infections; Drug Resistance, Bacterial; Gram-Negative Bacteria; Humans; Meropenem; Microbial Sensitivity Tests

The continued rise of Klebsiella pneumoniae resistance to antibiotics is precipitating a medical crisis. Bacteriophages have been hailed as one possible therapeutic option to enhance the efficacy of antibiotics. This study describes the genomic characterization and biological property of a new bacteriophage vB_1086 and its potential for phage therapy application against Klebsiella pneumoniae.. In our study, the double-layer agar plate method isolated a lytic bacteriophage named vB_1086. Besides, we analyzed its biological characteristics and genetic background. Then the antibacterial ability of the bacteriophage vB_1086 combined with antibiotics were analyzed by the combined checkerboard method. The impact on the formation of biofilms was analyzed by crystal violet staining method.. vB_1086 is a lytic bacteriophage with stable biological characteristics and clear genetic background, showing good antibacterial activity in combination with ceftriaxone, and the combination of phage and meropenem can effectively inhibit the formation of biofilm. Besides, the combination of bacteriophage and antimicrobials can effectively alleviate the generation of bacterial resistance and reduce the dosage of antimicrobials.. vB_1086 is a novel phage. To some extent, these results provide valuable information that phage vB_1086 can be combined with antibiotics to reduce the dosage of antimicrobials and alleviate the generation of bacterial resistance.

Topics: Agar; Anti-Bacterial Agents; Bacterial Infections; Bacteriophages; Ceftriaxone; Gentian Violet; Humans; Klebsiella pneumoniae; Meropenem

Topics: Ascites; Bacterial Infections; Humans; Liver Cirrhosis; Meropenem; Peritonitis

Meropenem is a broad-spectrum carbapenem widely used to treat both Gram-positive and negative bacterial infections, including extended-spectrum beta-lactamase-producing microbes. We describe the occurrence of thrombocytopenia and hypersensitivity in a boy receiving intravenous meropenem for intra-abdominal sepsis secondary to perforated appendicitis. The patient developed a pruritic maculopapular rash with occasional petechiae, associated with severe thrombocytopenia, after 7 days of meropenem administration. Investigations for other causes of thrombocytopenia, including possible line sepsis, were unfruitful, and the thrombocytopenia did not resolve until cessation of meropenem. Drug-induced reactions should be considered in children receiving meropenem who present with a rash and thrombocytopenia.

Topics: Anti-Bacterial Agents; Bacterial Infections; Child; Humans; Male; Meropenem; Thienamycins; Thrombocytopenia

The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. Bacterial co-infections are associated with unfavourable outcomes in respiratory viral infections; however, microbiological and antibiotic data related to COVID-19 are sparse. Adequate use of antibiotics in line with antibiotic stewardship (ABS) principles is warranted during the pandemic. We performed a retrospective study of clinical and microbiological characteristics of 140 COVID-19 patients admitted between February and April 2020 to a German University hospital, with a focus on bacterial co-infections and antimicrobial therapy. The final date of follow-up was 6 May 2020. Clinical data of 140 COVID-19 patients were recorded: The median age was 63.5 (range 17-99) years; 64% were males. According to the implemented local ABS guidelines, the most commonly used antibiotic regimen was ampicillin/sulbactam (41.5%) with a median duration of 6 (range 1-13) days. Urinary antigen tests for Legionella pneumophila and Streptococcus peumoniae were negative in all cases. In critically ill patients admitted to intensive care units (n = 50), co-infections with Enterobacterales (34.0%) and Aspergillus fumigatus (18.0%) were detected. Blood cultures collected at admission showed a diagnostic yield of 4.2%. Bacterial and fungal co-infections are rare in COVID-19 patients and are mainly prevalent in critically ill patients. Further studies are needed to assess the impact of antimicrobial therapy on therapeutic outcome in COVID-19 patients to prevent antimicrobial overuse. ABS guidelines could help in optimising the management of COVID-19. Investigation of microbial patterns of infectious complications in critically ill COVID-19 patients is also required.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ampicillin; Anti-Bacterial Agents; Antifungal Agents; Antimicrobial Stewardship; Aspergillosis; Azithromycin; Bacterial Infections; Cohort Studies; Coinfection; COVID-19; Enterobacteriaceae Infections; Escherichia coli Infections; Female; Germany; Humans; Klebsiella Infections; Linezolid; Male; Meropenem; Middle Aged; Piperacillin, Tazobactam Drug Combination; Practice Patterns, Physicians'; Retrospective Studies; SARS-CoV-2; Staphylococcal Infections; Streptococcal Infections; Sulbactam; Vancomycin; Young Adult

Meropenem is frequently used for the treatment of severe bacterial infections in critically ill patients. Because critically ill patients are more prone to pharmacokinetic variability than other patients, ensuring an effective blood concentration can be complex. Therefore, describing this variability to ensure a proper use of this antibiotic drug limits the rise and dissemination of antimicrobial resistance, and helps preserve the current antibiotic arsenal. The aims of this study were to describe the pharmacokinetics of meropenem in critically ill patients, to identify and quantify the patients' characteristics responsible for the observed pharmacokinetic variability, and to perform different dosing simulations in order to determine optimal individually adapted dosing regimens.. A total of 58 patients hospitalized in the medical intensive care unit and receiving meropenem were enrolled, including 26 patients with renal replacement therapy. A population pharmacokinetic model was developed (using NONMEM software) and Monte Carlo simulations were performed with different dosing scenarios (bolus-like, extended, and continuous infusion) exploring the impact of clinical categories of residual diuresis (anuria, oliguria, and preserved diuresis) on the probability of target attainment (MIC: 1-45 mg/L).. The population pharmacokinetic model included five covariates with a significant impact on clearance: glomerular filtration rate, dialysis (continuous and semi-continuous), renal function status, and volume of residual diuresis. The clearance for a typical patient in our population is 4.20 L/h and volume of distribution approximately 44 L. Performed dosing regimen simulations suggested that, for equivalent doses, the continuous infusion mode (with loading dose) allowed the obtaining of the pharmacokinetic/pharmacodynamic target for a larger number of patients (100% for MIC ≤ 20 mg/L). Nevertheless, for the treatment of susceptible bacteria (MIC ≤ 2 mg/L), differences in the probability of target attainment between bolus-like, extended, and continuous infusions were negligible.. Identified covariates in the model are easily accessible information in patient health records. The model highlighted the importance of considering the patient's overall condition (renal function and dialysis) and the pathogen's characteristics (MIC target) during the establishment of a patient's dosing regimen.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Critical Illness; Drug Administration Schedule; Female; Humans; Intensive Care Units; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Models, Biological; Monte Carlo Method; Retrospective Studies; Tissue Distribution; Young Adult

A major resistance mechanism in Gram-negative bacteria is the production of β-lactamase enzymes. Originally recognized for their ability to hydrolyze penicillins, emergent β-lactamases can now confer resistance to other β-lactam drugs, including both cephalosporins and carbapenems. The emergence and global spread of β-lactamase-producing multi-drug-resistant "superbugs" has caused increased alarm within the medical community due to the high mortality rate associated with these difficult-to-treat bacterial infections. To address this unmet medical need, we initiated an iterative program combining medicinal chemistry, structural biology, biochemical testing, and microbiological profiling to identify broad-spectrum inhibitors of both serine- and metallo-β-lactamase enzymes. Lead optimization, beginning with narrower-spectrum, weakly active compounds, provided

Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; beta-Lactam Resistance; beta-Lactamase Inhibitors; Borinic Acids; Carbapenems; Carboxylic Acids; Humans; Mice; Models, Molecular

Topics: Bacterial Infections; Humans; Intraabdominal Infections; Meropenem; Prospective Studies; Tetracyclines

The management of patients with brain abscess poses a significant challenge to clinicians in patients with chronic kidney disease. Obtaining a biopsy sample from the affected area is the mainstay in the diagnosis, but it is often unavailable. In most cases, therapy is guided by clinical findings and imaging alone. We discuss three cases of brain abscess- each with a different scenario and discuss the issues faced in management. The first case was a 32-year-old post-renal transplant male patient with a brain abscess due to dematiaceous fungi and was treated with amphotericin. The second case was a 42-year-old female patient with stage 5 chronic kidney disease on maintenance hemodialysis who presented with a brain abscess due to suspected fungal infection based on imaging findings and was managed with antibiotics and voriconazole. The third case was a 42-year-old post-renal transplant male patient who presented with a brain abscess due to nocardiosis and was managed with cotrimoxazole, meropenem and linezolid. We also summarize the approach to the management of brain abscess in resource-limited settings.

Topics: Adult; Anti-Bacterial Agents; Antifungal Agents; Bacterial Infections; Brain Abscess; Female; Humans; Kidney Transplantation; Linezolid; Male; Meropenem; Mycoses; Renal Insufficiency, Chronic; Trimethoprim, Sulfamethoxazole Drug Combination; Voriconazole

The mortality rate of patients with a drug-resistant bacterial infection is high, as are the associated treatment costs. To overcome these issues, optimization of the available therapeutic options is required. Beta-lactams are time-dependent antibiotics and their efficacy is determined by the amount of time the free concentration remains above the minimum inhibitory concentration. Therefore, the aim of this study was to assess the extent and variability of protein binding for meropenem, cefepime, and piperacillin.. Plasma samples for the analysis of meropenem, cefepime, and piperacillin were collected from patients admitted to a tertiary care hospital as part of the standard care. The bound and unbound drug fractions in the samples were separated by ultrafiltration. Validated liquid chromatography-tandem mass spectrometry assays were used to quantify the total and free plasma concentrations, and the protein binding was determined.. Samples from 95 patients were analyzed. The median (range) age of patients was 56 years (17-87) and the median (range) body mass index was 25.7 kg/m (14.7-74.2). Approximately 59% of the patients were men. The median (range) unbound fraction (fu) was 62.5% (41.6-99.1) for meropenem, 61.4% (51.6-99.2) for cefepime, and 48.3% (39.4-71.3) for piperacillin. In the bivariate analysis, as the total meropenem concentration increased, the fu increased (r = 0.37, P = 0.045). A decrease in piperacillin fu was observed as the albumin concentration increased (r = -0.56, P = 0.005).. The average fu values were lower than those reported in the literature. There was also a large variability in fu; hence, it should be considered when managing patients administered with these drugs through direct measurements of free drug concentrations.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Cefepime; Drug Monitoring; Female; Humans; Male; Meropenem; Middle Aged; Piperacillin; Protein Binding; Young Adult

The rising incidence of resistance to currently available antibiotics among pathogens, particularly Gram-negative pathogens, in complicated intra-abdominal infections (cIAIs) has become a challenge for clinicians. Ceftazidime/avibactam (CAZ-AVI) is a fixed-dose antibiotic approved in Europe and the United States for treating (in combination with metronidazole) cIAI in adult hospitalised patients who have limited or no alternative treatment options. The approval was based on the results of RECLAIM, a Phase III, parallel-group, comparative study (RECLAIM 1 [NCT01499290] and RECLAIM 2 [NCT01500239]). The objective of our study was to assess the cost-effectiveness of CAZ-AVI plus metronidazole compared with 1) ceftolozane/tazobactam plus metronidazole and 2) meropenem, as an empiric treatment for the management of cIAI in Italy.. A sequential, patient-level simulation model, with a 5-year time horizon and 3% annual discount rate (applied to both costs and health benefits), was developed using Microsoft Excel® to demonstrate the clinical course of the disease. The impact of resistant pathogens was included as an additional factor.. In the base-case analysis, the CAZ-AVI sequence (CAZ-AVI plus metronidazole followed by a colistin + tigecycline + high-dose meropenem combination after treatment failure), when compared to sequences for ceftolozane/tazobactam (ceftolozane/tazobactam plus metronidazole followed by colistin + tigecycline + high-dose meropenem after treatment failure) and meropenem (meropenem followed by colistin + tigecycline + high-dose meropenem after treatment failure), had better clinical outcomes with higher cure rates (93.04% vs. 91.52%; 92.98% vs. 90.24%, respectively), shorter hospital stays (∆ = - 0.38 and ∆ = - 1.24 days per patient, respectively), and higher quality-adjusted life years (QALYs) gained per patient (4.021 vs. 3.982; 4.019 vs. 3.960, respectively). The incremental cost effectiveness ratio in the CAZ-AVI sequence was €4099 and €15,574 per QALY gained versus each comparator sequence, respectively, well below the willingness-to-pay threshold of €30,000 per QALY accepted in Italy.. The model results demonstrated that CAZ-AVI plus metronidazole could be a cost-effective alternative when compared with other antibiotic treatment options, as it is expected to provide better clinical benefits in hospitalised patients with cIAI in Italy.

Topics: Adult; Anti-Bacterial Agents; Azabicyclo Compounds; Bacterial Infections; Ceftazidime; Cephalosporins; Cost-Benefit Analysis; Drug Combinations; Hospitalization; Humans; Intraabdominal Infections; Italy; Meropenem; Models, Economic; Tazobactam

The modified carbapenem inactivation method (mCIM) is a simple phenotypic screening method for detecting carbapenemase production by Enterobacteriaceae and Pseudomonas aeruginosa. We recently developed another modified carbapenem inactivation method (CIMTris), in which carbapenemase is extracted from bacteria with Tris-HCl buffer, to detect carbapenemase production by Acinetobacter and Pseudomonas species. This study describes an improved carbapenem inactivation method, CIMTrisII, for detecting carbapenemase production by Gram-negative pathogens, including Enterobacteriaceae, Acinetobacter and Pseudomonas species. CIMTrisII was different from CIMTris in the concentration of Meropenem disks (5-µg MEM disks vs. 10-µg MEM disks), the inoculum volume of the bacteria (a 5-µl loopful vs. a 10 µl loopful) and the incubation time (1 vs. 2 h). CIMTrisII showed an overall sensitivity of 99.3 % and an overall specificity of 95.0 % for tested isolates. In comparison, CIMTris showed a sensitivity of 96.1 % and a specificity of 96.3 %, and mCIM showed a sensitivity of 67.1 % and a specificity of 100 %. CIMTrisII is thus deemed useful for detecting carbapenemase production by Gram-negative pathogens.

Topics: Acinetobacter; Anti-Bacterial Agents; Asia, Southeastern; Bacterial Infections; Bacterial Proteins; beta-Lactamases; Carbapenems; DNA, Bacterial; Enterobacteriaceae; Humans; Imipenem; Japan; Meropenem; Microbial Sensitivity Tests; Nepal; Pseudomonas; Sensitivity and Specificity; Sequence Analysis, DNA; Time Factors

The recently described proportion of carbapenem consumption metric was used to assess the effectiveness of formulary restriction for carbapenems for 2 units housing predominantly immunocompromised patients at a large academic medical center. Interrupted time series analysis revealed a significant decrease in meropenem use for hematology-oncology and bone marrow transplant units after restriction.

Topics: Academic Medical Centers; Anti-Bacterial Agents; Antimicrobial Stewardship; Bacterial Infections; Drug Resistance, Multiple, Bacterial; Drug Utilization; Guideline Adherence; Hospitals; Humans; Immunocompromised Host; Interrupted Time Series Analysis; Meropenem; Practice Patterns, Physicians'

In older adults, few studies confirm that adequate concentrations of antibiotics are achieved using current dosage regimens of intravenous β-lactam antibiotics. Our objective was to investigate trough concentrations of cefotaxime, meropenem, and piperacillin in older adults hospitalized with infection. We included 102 patients above 70 years of age. Total trough antibiotic concentrations were measured and related to suggested target intervals. Information on antibiotic dose, patient characteristics, and 28-day outcomes were collected from medical records and regression models were fitted. Trough concentrations for all three antibiotics exhibited considerable variation. Mean total trough concentrations for cefotaxime, meropenem, and piperacillin were 6.5 mg/L (range 0-44), 3.4 mg/L (range 0-11), and 30.2 mg/L (range 1.2-131), respectively. When a target range of non-species-related breakpoint - 5× non-species-related breakpoint was applied, only 36% of patients had both values within the target range. Regression models revealed that severe sepsis was associated with varying concentration levels and increasing age and diminishing kidney function with high concentration levels. The study was not powered to demonstrate consequences in clinical outcomes. Conclusively, in older adults treated with cefotaxime, meropenem, or piperacillin-tazobactam, trough antibiotic concentrations varied considerably. Better predictors to guide dosing regimens of β-lactam antibiotics or increased use of therapeutic drug monitoring are potential ways to address such variations.

Topics: Aged; Aged, 80 and over; Analysis of Variance; Bacterial Infections; beta-Lactams; Cefotaxime; Drug Monitoring; Female; Humans; Length of Stay; Male; Meropenem; Patient Readmission; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Sepsis; Sweden; Thienamycins

Patients often receive broad-spectrum antibiotics for nosocomial infections commonly with activity against Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus. Previous retrospective and/or single-center studies have suggested that the combination of vancomycin and piperacillin/tazobactam might be associated with an increased risk of acute kidney injury.. To compare the incidence of nephrotoxicity in patients receiving intravenous vancomycin in combination with cefepime, meropenem, or piperacillin/tazobactam.. This was a prospective, multicenter observational study of patients receiving vancomycin in combination with piperacillin/tazobactam versus cefepime or meropenem. Adult patients 18 years of age or older who were hospitalized and received 72 or more hours of intravenous vancomycin and 72 hours or more of cefepime, meropenem, or piperacillin/tazobactam were eligible. Patient and medication characteristics were examined for the 242 patients included.. The incidence of acute kidney injury for patients treated with vancomycin and piperacillin/tazobactam was significantly higher than for those treated with vancomycin and cefepime or meropenem, 29.8% versus 8.8%, respectively, P < 0.001. Binary logistic regression demonstrated that patients receiving vancomycin and piperacillin/tazobactam were 6.7 times more likely to develop acute kidney injury compared with the other cohort.. The combination of vancomycin with piperacillin/tazobactam significantly increases the risk of acute kidney injury compared with other broad-spectrum antibiotic combinations. Clinicians should be vigilant when employing this regimen.

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Cefepime; Drug Therapy, Combination; Female; Humans; Male; Meropenem; Middle Aged; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Vancomycin

Data on antimicrobial use among hospitalized children in Africa are very limited due to the absence of electronic prescription tracking.. This study evaluated antimicrobial consumption rates, the antimicrobial spectrum used, and the indications for therapy on a paediatric ward and in the paediatric intensive care unit (PICU) at Tygerberg Hospital, Cape Town, South Africa. Antimicrobial prescription and patient demographic data were collected prospectively from May 10, 2015 to November 11, 2015. For the same period, data on antimicrobials dispensed and costs were extracted from the pharmacy electronic medicine management system. The volume of antimicrobials dispensed (dispensing data) was compared with observed antimicrobial use (prescription data).. Of the 703 patients admitted, 415/451 (92%) paediatric ward admissions and 233/252 (92%) PICU admissions received ≥1 antimicrobials. On the ward, 89% of prescriptions were for community-acquired infections; 29% of PICU antimicrobials were prescribed for healthcare-associated infections. Ampicillin and third-generation cephalosporins were the most commonly prescribed agents. Antimicrobial costs were 67541 South African Rand (ZAR) (5680 United States Dollars (USD)) on the ward and 210484 ZAR (17702 USD) in the PICU. Ertapenem and meropenem were the single largest contributors to antimicrobial costs on the ward (43%) and PICU (30%), respectively. The volume of antimicrobials dispensed by the pharmacy (dispensing data) differed considerably from observed antimicrobial use (prescription data).. High rates of antimicrobial consumption were documented. Community-acquired infections were the main indication for prescription. Although pharmacy dispensing data did not closely approximate observed use, this represents a promising method for antimicrobial usage tracking in the future.

Topics: Ampicillin; Anti-Bacterial Agents; Bacterial Infections; Child; Community-Acquired Infections; Cross Infection; Ertapenem; Female; Hospitalization; Hospitals; Humans; Infant; Intensive Care Units, Pediatric; Male; Medical Overuse; Meropenem; Pediatrics; Pharmacies; South Africa

Meropenem plasma concentration above a pathogen's MIC over the whole dosing interval (100% ƒT>MIC) is a determinant of outcome in severe infections. Significant variability of meropenem pharmacokinetics is reported in ICU patients.. To characterize meropenem pharmacokinetics in variable CLCR or renal replacement therapy and assess the appropriateness of recommended regimens for MIC coverage.. A pharmacokinetic analysis (NONMEM) was conducted with external model validation. Patient characteristics were tested on meropenem clearance estimates, differentiated according to the presence/absence of continuous renal replacement therapy (CRRT, CLCRRT or CLno-CRRT). Simulations evaluated the appropriateness of recommended dosing for achieving 100% fT>MIC in 90% of patients.. A total of 101 patients were studied: median 63 years (range 49-70), 56% male, SAPS II 38 (27-48). 32% had a CLCR >60 mL/min, 49% underwent CRRT and 32% presented severe sepsis or septic shock. A total of 127 pathogens were documented: 76% Gram-negatives, 24% Gram-positives (meropenem MIC90 2 mg/L, corresponding to EUCAST susceptibility breakpoint). Three hundred and eighty plasma and 129 filtrate-dialysate meropenem concentrations were analysed: two-compartment modelling best described the data. Predicted meropenem CLno-CRRT was 59% lower in impaired (CLCR 30 mL/min) compared to normal (CLCR 100 mL/min) renal function. Simulations showed that recommended regimens appropriately cover MIC90 in patients with CLCR <60 mL/min. Patients with CLCR of 60 to <90 mL/min need 6 g/day to achieve appropriate coverage. In patients with CLCR ≥90 mL/min, appropriate exposure is achieved with increased dose, frequency of administration and infusion duration, or continuous infusion.. Recommended meropenem regimens are suboptimal in ICU patients with normal or augmented renal clearance. Modified dosing or infusion modalities achieve appropriate MIC coverage for optimized antibacterial efficacy in meropenem-susceptible life-threatening infections.

Topics: Aged; Anti-Bacterial Agents; Bacterial Infections; Computer Simulation; Critical Illness; Female; Humans; Male; Meropenem; Metabolic Clearance Rate; Middle Aged; Plasma; Prospective Studies; Renal Insufficiency; Renal Replacement Therapy

Introduction: The Colombian national pharmaceutical policy establishes as a strategy the generation of greater pharmaco-epidemiological research at the national level, especially in the case of antibiotic drugs.\ Objective: To provide local pharmaco-epidemiological evidence regarding the effectiveness, conditions of use and safety of generic meropenem and cefepime in a tertiary hospital in Bogotá. \ Materials and methods: We conducted a descriptive, longitudinal and retrospective drug utilization study. The data were collected from the medical histories of all the patients who had cefepime or meropenem prescribed.\ Results: We included 82 patients treated with cefepime and 91 treated with meropenem in the study. Most of the patients were in services different from the intensive care unit (taking cefepime: 59.8%, and meropenem: 52.7%). Only 21.9% of the patients treated with cefepime and 49% of those treated with meropenem were seen by an infectious disease specialist. The antibiogram was performed for 47% and 60% of the patients treated with cefepime and meropenem, respectively. The most frequent\ indication for cefepime were respiratory infections and for meropenem, genitourinary ones. Therapeutic success rates were 61.7% for cefepime and 63.0% for meropenem.\ Conclusions: This study contributes evidence regarding the therapeutic performance of two generic antibiotics used in tertiary hospitals. There were no reports of therapeutic failure during the study period. In the cases of non-response, pharmacokinetic alterations, unfavorable clinical conditions, and inappropriate choice of antimicrobial treatment were identified as frequent factors.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Cefepime; Child; Child, Preschool; Colombia; Diagnosis-Related Groups; Drug Prescriptions; Drug Utilization; Drugs, Generic; Female; Humans; Infant; Infant, Newborn; Male; Meropenem; Middle Aged; Retrospective Studies; Tertiary Care Centers; Treatment Outcome; Young Adult

The effects of i.v. push administration on the pharmacodynamic exposures of meropenem, cefepime, and aztreonam were evaluated.. Pharmacokinetic and pharmacodynamic analyses were conducted using previously published pharmacokinetic data for meropenem, cefepime, and aztreonam. The probability of target attainment (PTA) was assessed using Monte Carlo simulations for 30-minute and 5-minute infusions of approved dosing regimens and alternative dosing schemes often used in clinical practice, including 500 mg every 6 hours and 1 g every 8 hours for meropenem, 1 g every 6 hours and 2 g every 8 hours for cefepime, and 2 g every 8 hours for aztreonam. For each regimen examined, means and standard deviations for the percentage of the dosing interval that the free drug concentration remained above the minimum inhibitory concentration (MIC) were calculated and reported.. No or only minor differences were noted between 30-minute and 5-minute infusions. The largest differences were observed at an MIC of 4 mg/L for meropenem and an MIC of 16 mg/L for aztreonam. At an MIC of 4 mg/L, meropenem 500 mg every 6 hours as a 30-minute infusion had an 8% greater PTA compared with the 5-minute infusion. At an MIC of 16 mg/L, a 30-minute infusion of aztreonam 2 g every 8 hours had a 12% greater PTA compared with the 5-minute infusion.. Simulations of meropenem, cefepime, and aztreonam by i.v. push over 5 minutes indicated that there would be minimal or no effect on pharmacodynamic exposures compared with the effect when administered by 30-minute infusions.

Topics: Anti-Bacterial Agents; Aztreonam; Bacterial Infections; Cefepime; Drug Administration Schedule; Healthy Volunteers; Humans; Infusions, Intravenous; Meropenem; Microbial Sensitivity Tests; Models, Biological; Monte Carlo Method; Time Factors

Topics: Administration, Intravenous; Aged; Amputation, Surgical; Anti-Bacterial Agents; Bacterial Infections; Clindamycin; Debridement; Escherichia coli; Fasciitis, Necrotizing; Female; Humans; Immunosuppressive Agents; Leg; Lupus Erythematosus, Systemic; Magnetic Resonance Imaging; Meropenem; Spondylitis; Staphylococcus epidermidis; Staphylococcus hominis; Thienamycins; Tomography, X-Ray Computed; Treatment Outcome

To determine the existence of concentration-toxicity relationships for common β-lactam antibiotic adverse effects and define thresholds above which toxicity is more likely.. Retrospective review of consecutive patients treated with piperacillin, meropenem or flucloxacillin who underwent therapeutic drug monitoring (TDM) at St Vincent's Hospital (Sydney, Australia) between January 2013 and December 2015. Adverse events investigated included neurotoxicity, nephrotoxicity, hepatotoxicity and opportunistic Clostridium difficile infection. Toxicity was measured using observational grading criteria, clinical assessment and relevant serum biomarkers. These findings were correlated with trough TDM measurements at the time of toxicity presentation.. TDM results from 378 patients (piperacillin = 223, meropenem = 94 and flucloxacillin = 61) were investigated. There was no difference in baseline patient characteristics across antibiotic groups. A statistically significant elevation in mean serum trough concentrations (Cmin) was found in patients diagnosed with neurotoxicity (piperacillin, P < 0.01; meropenem, P = 0.04; flucloxacillin, P = 0.01) and those who developed nephrotoxicity whilst being treated with piperacillin (P < 0.01) or meropenem (P < 0.01). Incidence of hepatotoxicity and C. difficile was not related to Cmin. Threshold concentrations for which there is 50% risk of developing a neurotoxicity event (piperacillin, Cmin >361.4 mg/L; meropenem, Cmin >64.2 mg/L; flucloxacillin, Cmin >125.1 mg/L) or nephrotoxicity (piperacillin, Cmin >452.65 mg/L; meropenem, Cmin >44.45 mg/L) varied across antibiotics.. Our data reveal an association between toxic concentrations for a number of β-lactam agents and neurotoxic/nephrotoxic effects. We have defined threshold concentrations above which these toxicities become more likely. Clinicians should balance concerns for therapeutic efficacy with potential toxicity when considering aggressive therapy.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; beta-Lactams; Clostridium Infections; Cohort Studies; Drug Monitoring; Drug-Related Side Effects and Adverse Reactions; Female; Floxacillin; Humans; Incidence; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Neurotoxicity Syndromes; Piperacillin; Retrospective Studies; Thienamycins

Since 2013, wounded and ill children from Syria have received treatment in Israel. Screening cultures indicated that multidrug-resistant (MDR) pathogens colonized 89 (83%) of 107 children. For 58% of MDR infections, the pathogen was similar to that identified during screening. MDR screening of these children is valuable for purposes of isolation and treatment.

Topics: Adolescent; Amikacin; Anti-Bacterial Agents; Armed Conflicts; Bacterial Infections; Child; Child, Preschool; Colistin; Critical Illness; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Hospitalization; Humans; Infant; Infant, Newborn; Israel; Male; Meropenem; Multiple Trauma; Syria; Thienamycins

Spontaneous bacterial peritonitis (SBP) can be life threatening in patients with liver cirrhosis. In contrast to community-acquired SBP, no standard treatment has been established for healthcare-related and nosocomial SBP.. We prospectively collected healthcare-related and nosocomial SBP cases from March 2012 till February 2016 at the Department of Internal Medicine I of the University of Bonn and analysed the prevalence of antibiotic resistance among the isolated bacteria. SBP was diagnosed according to international guidelines. Ciprofloxacin, ceftriaxone and meropenem were used as reference substance for resistance to quinolones, third-generation cephalosporins and carbapenems, respectively.. Ninety-two SBP episodes in 86 patients were identified: 63 episodes (69%) were nosocomial. Escherichia coli, Klebsiella species, enterococci and streptococci were most frequently isolated. Frequencies of these microorganisms were comparable for healthcare-related and nosocomial SBP (14% vs. 11%, 14% vs. 8%, 14% vs. 5% and 10% vs. 6%, respectively). In general, antibiotic resistance was higher in isolates from nosocomial than from healthcare-related SBP (50% vs. 18% for quinolones, 30% vs. 11% for piperacillin-tazobactam; P > 0·05), but comparable concerning third-generation cephalosporins (30% vs. 33%). All microorganisms were sensitive to carbapenems apart from nosocomial infections with Enterococcus faecium (n = 3) and Candida albicans (n = 1) due to intrinsic resistance or lack of microbiological efficacy, respectively. No multidrug-resistant microorganisms were detected. Resistance to initial antibiotic treatment affected 30-day survival negatively (18% vs. 68%; P = 0·002).. Resistance to initial antibiotic treatment was associated with increased mortality. With resistance to cephalosporins being frequent, piperacillin-tazobactam or carbapenems might be preferred as treatment of SBP.

Topics: Aged; Anti-Bacterial Agents; Bacterial Infections; Ceftriaxone; Ciprofloxacin; Cross Infection; Drug Resistance, Bacterial; Enterococcus; Escherichia coli Infections; Female; Gram-Positive Bacterial Infections; Humans; Klebsiella Infections; Liver Cirrhosis; Male; Meropenem; Middle Aged; Peritonitis; Prospective Studies; Streptococcal Infections; Thienamycins

To study the distribution characteristics and drug resistance of non-fermenting bacterial infection in intensive care unit (ICU) at a tertiary hospital during seven consecutive years, and to provide evidence for rational use of antibiotics in ICU.. A retrospective analysis was conducted. The related data about non-fermentative bacteria obtained from clinical specimens, collected from lower respiratory tract, blood, urine, bile and other secretions of ICU patients admitted to Binzhou Medical University Hospital from January 2009 to December 2015 were retrospectively analyzed. The distribution characteristics and drug resistance of non-fermentative bacteria, and isolation rate of multiple drug resistance (MDR) strains were analyzed.. 2 672 strains of nonfermentative bacteria were isolated during seven consecutive years, accounting for 57.9％ gram negative (G-) bacilli (2 672/4 613),and 35.2％ of all bacteria (2 672/7 587).The top five were Acinetobacter baumannii (38.4％),Pseudomonas aeruginosa (34.6％),Onion burkholderia cepacia (9.9％),Stenotrophomonas maltophilia (6.2％),and Pseudomonas fluorescens (5.6％).Non-fermentative bacteria were mainly isolated from the lower respiratory tract (60.9％).Isolation of the non-fermentative bacteria accounted for over 50％ of G-bacilli during seven consecutive years, and the isolation rate of the top five types of bacteria showed no obvious change, while positive rate of Acinetobacter baumannii showed a tendency to increase (obviously from 26.5％ in 2009 to 50.2％ in 2015),and a lowering trend of positive rate of Onion burkholderia cepacia,Stenotrophomonas maltophilia, and Pseudomonas fluorescens was obvious (from 15.6％,10.6％,13.0％ in 2009 to 5.6％,7.4％,1.4％ in 2015 respectively) was observed. The isolation rate of Pseudomonas aeruginosa was stable (about 30％) during seven consecutive years. The drug susceptibility results showed that the resistant rates of Acinetobacter baumannii against imipenem, meropenem, aminoglycosides and third-generation cephalmsporins were all higher than 70％,while its resistant rate to cefoperazone-sulbactam was relatively lower (40.2％-68.1％)with relatively higher sensitivity rate (23.6％-46.0％).In contrast, the resistant rates of Pseudomonas aeruginosa against antibiotics were low,while the sensitivity rate to fourth-generation cephalmsporins cefepime (58.3％-87.7％)and third-generation cephalmsporins was high (ceftazidime:55.6％-79.3％,piperacillin-tazobactam:62.5％-86.2％,cefoperazone-sulbactam:46.0％-89.8％).From 2009 to 2015,the incidence of MDR strains of Acinetobacter baumannii showed an obvious increasing tendency (from 68.0％ to 84.1％);in contrast, the incidence of MDR strains of Pseudomonas aeruginosa did not show an obviously increase in incidence from 2009 to 2012,on the other hand, it showed a decreasing tendency from a peak 68.6％ in 2012 to 23.5％ in 2015.. The isolation rate of non-fermentative bacteria was high and the drug resistance situation was serious. Therefore,it is important to grasp the knowledge regarding distribution characteristics, drug resistance and variation of non-fermentative bacteria in ICU. It is not only beneficial for both rational use of antibiotics, improve efficacy but also helpful in reducing the emergence of drug resistance stains.

Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Bacterial Infections; Cefepime; Cefoperazone; Cephalosporins; Cross Infection; Drug Resistance; Drug Resistance, Bacterial; Gram-Negative Bacteria; Humans; Imipenem; Intensive Care Units; Meropenem; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Retrospective Studies; Thienamycins

To find the most prevalent organism in diabetic foot ulcers and its drug sensitivity and resistance to different standard antibiotics.. Adescriptive and cross-sectional study.. Ward 7, Jinnah Postgraduate Medical Center, Karachi, from December 2010 to December 2012.. Ninety-five diabetic patients with infected foot wounds of Wegener grade 2 - 5 who had not received any previous antibiotics were included in the study by consecutive sampling. Pus culture specimen from wounds was taken and the organism isolated was identified. Also the most sensitive group of antibiotics and the most resistant one to that organism was noted.. Staphylococcus aureuswas the most prevalent organism constituting 23.16% (n=22) of the organisms isolated; Escherichia coli with 17.89% (n=17) and Klebsiella with 12.63% (n=12) followed. Males presented more with diabetic foot (n=52) out of 95 patients. The most common age group affected was 41 - 60 years (73 patients). The organisms were most sensitive to Meropenem, effective in 90 (95%) patients and most resistant to Cotrimoxazole (80, 84% patients). Out of the 95 patients, 39 (41%) patients were hypertensive, 30 (31.5%) were obese and 14 (15%) were smokers. Staphylococcus aureus was the most prevalent organism overall irrespective to gender, age groups and co-morbidity of the patients.. Staphylococcus aureuswas the most frequent organism in diabetic foot ulcers; the most effective antibiotic is Meropenem and least effective is Cotrimoxazole.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Cross-Sectional Studies; Diabetic Foot; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Humans; Klebsiella; Klebsiella Infections; Meropenem; Microbial Sensitivity Tests; Middle Aged; Pakistan; Prevalence; Staphylococcal Infections; Staphylococcus aureus; Thienamycins; Trimethoprim, Sulfamethoxazole Drug Combination; Wound Infection

Misuse of antibiotics can provoke increased bacterial resistance. There are no immediate prospects of any new broad-spectrum antibiotics, especially any with activity against enterobacteria, coming onto the market. Therefore, programmes should be implemented to optimise antimicrobial therapy. In a quasi-experimental study, the results for the pre-intervention year were compared with those for the 3 years following the application of an antimicrobial stewardship programme. We describe 862 interventions carried out as part of the stewardship programme at the Hospital Costa del Sol from 2009 to 2011. We examined the compliance of the empirical antimicrobial treatment with the programme recommendations and the treatment optimisation achieved by reducing the antibiotic spectrum and adjusting the dose, dosing interval and duration of treatment. In addition, we analysed the evolution of the sensitivity profile of the principal microorganisms and the financial savings achieved. 93 % of the treatment recommendations were accepted. The treatment actions taken were to corroborate the empirical treatment (46 % in 2009 and 31 % in 2011) and to reduce the antimicrobial spectrum taking into account the antibiogram results (37 % in 2009 and 58 % in 2011). The main drugs assessed were imipenem/meropenem, used in 38.6 % of the cases, and cefepime (20.1 %). The sensitivity profile of imipenem against Pseudomonas aeruginosa increased by 10 % in 2011. Savings in annual drug spending (direct costs) of 30,000 Euros were obtained. Stewardship programmes are useful tools for optimising antimicrobial therapy. They may contribute to preventing increased bacterial resistance and to reducing the long-term financial cost of antibiotic treatment.

Topics: Anti-Bacterial Agents; Bacterial Infections; Cefepime; Cephalosporins; Drug Resistance, Microbial; Drug Utilization; Humans; Imipenem; Klebsiella pneumoniae; Meropenem; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Pharmacy Service, Hospital; Practice Patterns, Physicians'; Program Evaluation; Pseudomonas aeruginosa; Spain; Thienamycins

To develop a population model to describe the pharmacokinetics (PK) of intravenous meropenem in adult patients with severe burns and investigate potential relationships between dosage regimens and antimicrobial efficacy.. A dose of 1 g every 8 h was administered to adult patients with total body surface area burns of ≥15%. Doses for subsequent courses were determined using results from the initial course and the patient's clinical condition. Five plasma meropenem concentrations were typically measured over the dosage interval on one to four occasions. An open, two-compartment PK model was fitted to the meropenem concentrations using NONMEM and the effect of covariates on meropenem PK was investigated. Monte Carlo simulations investigated dosage regimens to achieve a target T>MIC for ≥40%, ≥60% or ≥80% of the dose interval.. Data comprised 113 meropenem concentration measurements from 20 dosage intervals in 12 patients. The parameters were CL (L/h) = 0.196 L/h/kg × [1 - 0.023 × (age - 46)] × [1 - 0.049 × (albumin - 15)], V1 = 0.273 L/kg × [1 - 0.049 × (albumin - 15)], Q = 0.199 L/h/kg and V2 = 0.309 L/kg × [1 - 0.049 × (albumin - 15)]. For a target of ≥80% T>MIC, the breakpoint was 8 mg/L for doses of 1 g every 4 h and 2 g every 8 h given over 3 h, but only 4 mg/L if given over 5 min.. Although 1 g 8 hourly should be effective against Escherichia coli and CoNS, higher doses, ideally with a longer infusion time, would be more appropriate for empirical therapy, mixed infections and bacteria with MIC values ≥4 mg/L.

Topics: Administration, Intravenous; Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Burns; Female; Humans; Male; Meropenem; Middle Aged; Monte Carlo Method; Plasma; Thienamycins; Time Factors

Adequate empirical antibiotic dose selection for critically ill burn patients is difficult due to extreme variability in drug pharmacokinetics. Therapeutic drug monitoring (TDM) may aid antibiotic prescription and implementation of initial empirical antimicrobial dosage recommendations. This study evaluated how gradual TDM introduction altered empirical dosages of meropenem and imipenem/cilastatin in our burn ICU.. Imipenem/cilastatin and meropenem use and daily empirical dosage at a five-bed burn ICU were analyzed retrospectively. Data for all burn admissions between 2001 and 2011 were extracted from the hospital's computerized information system. For each patient receiving a carbapenem, episodes of infection were reviewed and scored according to predefined criteria. Carbapenem trough serum levels were characterized. Prior to May 2007, TDM was available only by special request. Real-time carbapenem TDM was introduced in June 2007; it was initially available weekly and has been available 4 days a week since 2010.. Of 365 patients, 229 (63%) received antibiotics (109 received carbapenems). Of 23 TDM determinations for imipenem/cilastatin, none exceeded the predefined upper limit and 11 (47.8%) were insufficient; the number of TDM requests was correlated with daily dose (r=0.7). Similar numbers of inappropriate meropenem trough levels (30.4%) were below and above the upper limit. Real-time TDM introduction increased the empirical dose of imipenem/cilastatin, but not meropenem.. Real-time carbapenem TDM availability significantly altered the empirical daily dosage of imipenem/cilastatin at our burn ICU. Further studies are needed to evaluate the individual impact of TDM-based antibiotic adjustment on infection outcomes in these patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Body Surface Area; Burn Units; Burns; Carbapenems; Cilastatin; Cilastatin, Imipenem Drug Combination; Cohort Studies; Computer Systems; Critical Illness; Drug Combinations; Drug Monitoring; Female; Humans; Imipenem; Length of Stay; Male; Meropenem; Middle Aged; Retrospective Studies; Thienamycins; Young Adult

Meropenem is a restricted, broad spectrum and expensive antibiotic. The major consequences of irrational use of restricted antibiotics are increase drug resistance and drug expenditure. The use of antibiotics, specifically restricted antibiotics, must be monitored continuously to increase its adherence to the standard guidelines to avoid such problems. The objective of this study was to evaluate the appropriateness of meropenem use with respect to renal status of patients in a teaching based hospital. A retrospective study was carried out from 1st January 2013 to 30th June 2013 to determine the evaluation of meropenem use in accordance to the criteria developed through national (Infectious disease society of Pakistan) and international guidelines (Health care infection control practices advisory committee). The data was recorded on data collection form by thorough reviewing of patients' medical records. Main outcomes measured were indication, dose, interval, duration, creatinine clearance, complete blood count and culture sensitivity test. Correlation of different variable (side effects and generalized health) was also observed with reference to renal status of patients. Statistical analyses were performed using descriptive statistics. A total of 201 cases of meropenem prescription were identified during the study period. The variable, which was most consistent with the criteria was 'indication', in which 97.52% of meropenem prescription was indicated in diseases encouraged by guidelines. However, the use of meropenem as an empirical therapy was the major problem reported in this study as it adhered to in only 43% of the cases. It was also noted that prevalence of side effects increased when meropenem was prescribed in renal compromised patients, and also observed that generalized health of patients decreased with meronem use in renal unstable patients. Thrombocytopenia was the major problem associated with the meropenem use (37.81%). The study detected various areas where use of meropenem was not according to the standards. Strict policies and procedures need to be implemented to use meropenem in line with the standard guidelines.

Topics: Anti-Bacterial Agents; Bacterial Infections; Comorbidity; Drug Prescriptions; Drug Utilization Review; Guideline Adherence; Hospitals, Teaching; Humans; Kidney; Kidney Diseases; Meropenem; Patient Selection; Practice Guidelines as Topic; Practice Patterns, Physicians'; Retrospective Studies; Risk Assessment; Risk Factors; Thienamycins; Time Factors; Treatment Outcome

Management of pancreatic ascites poses significant therapeutic challenges. Treatment usually consists of either conservative management or interventional therapy with little consensus between the two options. Conservative therapy is the most common initial treatment option but has high failure rates hence arguing for interventional therapy as a preferred primary treatment option. Endoscopic treatment is particularly appealing due to lower failure rates and mortality than conservative therapy or surgery. We describe a patient with recurrent pancreatic ascites who was successfully managed with endoscopic transpapillary stenting. This report contributes to the limited but growing literature on the management of pancreatic ascites.

Topics: Adult; Anti-Bacterial Agents; Ascites; Bacterial Infections; Cholangiopancreatography, Endoscopic Retrograde; Humans; Male; Meropenem; Pancreatic Diseases; Recurrence; Stents; Thienamycins; Treatment Outcome

The acquisition of blaNDM-1 gene by Gram negative bacteria has emerged as critical threat to human health as these organisms display high resistance to available antibiotics. The presence of this gene has been observed in both clinical as well as environmental settings. The present study was carried out to evaluate the prevalence of blaNDM-1 containing microorganisms in water sources. A total of 241 water samples were collected from different sites in Islamabad, Rawalpindi and areas of Khyber Pakhtunkhwa. Meropenem resistant organisms were isolated and PCR was used for the detection of the blaNDM-1 gene among the resistant isolates of all the water samples, 43 meropenem resistant bacteria were isolated among which 12 isolates were found to carry blaNDM-1 gene. The blaNDM-1 isolates were resistant to most of the antibiotics but sensitive to colistin and polymyxin B. The presence of blaNDM-1 gene harboring organisms in aquatic environment is concerning and poses public health threat.

Topics: Anti-Bacterial Agents; Bacterial Infections; Bacterial Load; beta-Lactamases; Environmental Monitoring; Gram-Negative Bacteria; Humans; Meropenem; Microbial Sensitivity Tests; Polymerase Chain Reaction; Prevalence; Thienamycins; Water Microbiology; Water Pollutants; Water Quality

Two different series of N-substituted imidazolium oximes and their monoquaternary salts were synthesized and biologically tested with respect to their ability to inhibit growth a diverse panel of antibiotic susceptible Gram-positive and antibiotic resistant Gram-negative bacteria as well fungal strains. The newly synthesized compounds were analyzed by spectral studies to confirm their structure. The preliminary results showed that all compounds tested possess promising antimicrobial potential against both susceptible Gram-positive and antibiotic resistant Gram-negative isolates, exhibiting a wide range of MIC values from 0.14 to 100.0 μg/mL. The structure-activity relationship demonstrates that the p-methylphenyl and p-fluorophenyl groups in monoquaternary salts 6 and 7 attached directly to the imidazolium ring could be essential for observed remarkable inhibitory profiles against clinically important pathogens Pseudomonas aeruginosa (MIC=0.14 μg/mL) and Klebsiella pneumoniae (MIC=1.56 μg/mL). Furthermore, the broth microdilution assay was then used to investigate the antiresistance efficacy of compound 7 against fourteen extended-spectrum β-lactamase (ESBL)-producing strains in comparison to eight clinically relevant antibiotics. Compound 7 exhibited a remarkable antiresistance profiles ranging between 0.39 and 12.50 μg/mL against all of ESBL-producing strains, which leads to the suggestion that may be interesting candidate for development of new antimicrobials to combat multidrug resistant Gram-negative bacteria.

Topics: Anti-Infective Agents; Bacterial Infections; Drug Resistance, Multiple; Fungi; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Imidazoles; Microbial Sensitivity Tests; Mycoses; Oximes

We describe here a rare case in which valproic acid (VPA) levels were affected by ertapenem but not by meropenem even though ertapenem and meropenem are in the same carbapenem class. A 68-year-old Filipino male treated with valproate for epilepsy and ertapenem for an infectious disease had decreased VPA levels during the first day of ertapenem therapy. His VPA level increased soon after terminating ertapenem therapy. Two types of carbapenems had different drug reactions with concomitant use of VPA in this patient.. Closer monitoring of VPA concentrations are necessitated using carbapenems for treating infection in patients being administered VPA. Another option is the use of anti-epileptic drugs other than VPA if concomitant use with a carbapenem is warranted.

Topics: Aged; Anti-Bacterial Agents; Anticonvulsants; Bacterial Infections; beta-Lactams; Drug Interactions; Drug Monitoring; Epilepsy; Ertapenem; Humans; Male; Meropenem; Thienamycins; Valproic Acid

Acinetobacter baumannii and Pseudomonas aeruginosa pathogens are the most common causes of fatal pneumonia among patients treated in Intensive Care Units (ICU). Carbapenems remain a group of antibiotics characterized by the highest effectiveness in treatment of heavy infections of the lower respiratory tract. This study compared in vitro sensitivity of A. baumannii and P. aeruginosa to three carbapenems: imipenem, meropenem and doripenem. The material was collected from 71 patients treated in the ICU from April 2009 to January 2010. Bronchial tree was the predominant source of samples. Fifty-four strains of A. baumannii and 17 strains of P. aeruginosa were analyzed. Sensitivity to carbapenems was interpreted in line with Clinical and Laboratory Standard Institute (CLSI) and European Committee for Antimicrobial Susceptibility Testing (EUCAST) criteria (imipenem and meropenem) or in compliance with the Food and Drug Administration (FDA) and CLSI guidelines (doripenem). We found that A. baumannii was significantly more often sensitive to imipenem than to doripenem and meropenem, but only according to the CLSI and FDA and not EUCAST criteria. The sensitivity of P. aeruginosa was higher to imipenem than to doripenem and meropenem, according to both CLSI and EUCAST criteria (64.7 %). We conclude that the EUCAST criteria demonstrate a higher rigor than those of CLSI and FDA in the determination of carbapenems sensitivity. Imipenem appears more effective than doripenem and meropenem in treatment of A. baumannii and P. aeruginosa infections.

Topics: Acinetobacter baumannii; Bacterial Infections; Carbapenems; Doripenem; Electrophoresis, Gel, Pulsed-Field; Europe; Humans; Imipenem; Intensive Care Units; Meropenem; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Sensitivity and Specificity; Species Specificity; Thienamycins; United States; United States Food and Drug Administration

Appendicitis is a frequent clinical condition in normal children that may be complicated by community-acquired secondary peritonitis (CASP). We evaluated the potential efficacy of different drugs for initial treatment of this condition, as recommended by recent Consensus Conference and Guidelines for paediatric patients. Susceptibility to ampicillin-sulbactam, ertapenem, gentamycin, piperacillin, piperacillin-tazobactam, vancomycin, and teicoplanin was evaluated according to EUCST 2012 recommendations in aerobic bacteria isolated from peritoneal fluid in CASP diagnosed from 2005 to 2011 at 'Istituto Giannina Gaslini', Genoa, Italy. A total of 114 strains were analysed: 83 E. coli, 15 P. aeruginosa, 6 Enterococci, and 10 other Gram-negatives. Resistance to ampicillin-sulbactam was detected in 37% of strains, while ertapenem showed a potential resistance of 13% (all P. aeruginosa strains). However, the combination of these drugs with gentamicin would have been increased the efficacy of the treatment to 99 and 100%, respectively. Resistance to piperacillin-tazobactam was 3%, while no strain was resistant to meropenem. Our data suggest that monotherapy with ampicillin-sulbactam or ertapenem for community-acquired secondary peritonitis would present a non-negligible rate of failure, but the addition of gentamycin to these drugs could reset to zero this risk. On the contrary, monotherapy with piperacillin-tazobactam or meropenem is highly effective.

Topics: Ampicillin; Anti-Bacterial Agents; Bacterial Infections; beta-Lactams; Child; Community-Acquired Infections; Drug Resistance, Bacterial; Drug Therapy, Combination; Ertapenem; Gentamicins; Hospitals, Pediatric; Humans; Italy; Meropenem; Microbial Sensitivity Tests; Penicillanic Acid; Peritonitis; Piperacillin; Piperacillin, Tazobactam Drug Combination; Practice Guidelines as Topic; Sulbactam; Thienamycins

Carbapenems are broad spectrum antibiotics considered as a "last resort" medicine to treat bacterial infections. Carbapenem-hydrolyzing β-lactamases (also called carbapenemases), however, can confer bacterial resistance and represent a serious health threat. Here, we report a novel approach using (18)O labeling and selected reaction monitoring to detect carbapenemase activity from pathogenic microorganisms in a rapid and quantitative manner. Four model bacterial strains bearing various classes of β-lactamases were tested for their capability to hydrolyze Meropenem, an FDA-approved carbapenem drug. We were able to predict the Meropenem resistance of these bacteria on the basis of their carbapenemase activity, suggesting the great potential of our method in clinical diagnostics.

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Bacterial Proteins; beta-Lactamases; Carbapenems; Chromatography, Liquid; Drug Resistance, Neoplasm; Meropenem; Oxygen Radioisotopes; Tandem Mass Spectrometry; Thienamycins

Severe sepsis and septic shock can alter the pharmacokinetics of broad-spectrum β-lactams (meropenem, ceftazidime/cefepime, and piperacillin-tazobactam), resulting in inappropriate serum concentrations. Obesity may further modify the pharmacokinetics of these agents. We reviewed our data on critically ill obese patients (body mass index of ≥ 30 kg/m(2)) treated with a broad-spectrum β-lactam in whom therapeutic drug monitoring was performed and compared the data to those obtained in critically nonobese patients (body mass index of <25 kg/m(2)) to assess whether there were differences in reaching optimal drug concentrations for the treatment of nosocomial infections. Sixty-eight serum levels were obtained from 49 obese patients. There was considerable variability in β-lactam serum concentrations (coefficient of variation of 50% to 92% for the three drugs). Standard drug regimens of β-lactams resulted in insufficient serum concentrations in 32% of the patients and overdosed concentrations in 25%. Continuous renal replacement therapy was identified by multivariable analysis as a risk factor for overdosage and a protective factor for insufficient β-lactam serum concentrations. The serum drug levels from the obese cohort were well matched for age, gender, renal function, and sequential organ failure assessment (SOFA) score to 68 serum levels measured in 59 nonobese patients. The only difference observed between the two cohorts was in the subgroup of patients treated with meropenem and who were not receiving continuous renal replacement therapy: serum concentrations were lower in the obese cohort. No differences were observed in pharmacokinetic variables between the two groups. Routine therapeutic drug monitoring of β-lactams should be continued in obese critically ill patients.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; beta-Lactams; Case-Control Studies; Cefepime; Ceftazidime; Cephalosporins; Drug Monitoring; Enzyme Inhibitors; Female; Humans; Male; Meropenem; Middle Aged; Obesity; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Renal Replacement Therapy; Sepsis; Shock, Septic; Tazobactam; Thienamycins; Young Adult

Surveys of bacterial infections among neutropenic cancer patients frequently report pooled antibiotic susceptibility data. Management guidelines address initial antibiotic regimens for febrile neutropenia. In this study, rates of bacterial infection and antibiotic susceptibilities among initial and subsequent or breakthrough episodes of fever were analysed. Prospective surveillance of fever of unknown origin (FUO), clinically documented infection and microbiologically documented infection (MDI) was conducted in the haemato-oncology and haematopoietic stem cell transplantation wards in a single cancer centre in Israel. Subsequent infections were defined as those developing during or after broad-spectrum antibiotic treatment. A total of 567 febrile episodes were documented among 271 patients. Bacterial MDIs were documented in 104/162 (64%) initial febrile episodes and 75/405 (19%) subsequent episodes and Gram-negative bacteria predominated (64% and 71%, respectively). Escherichia coli was the most common species isolated. Higher antibiotic susceptibilities were observed for initial compared with subsequent MDIs for Gram-negative bacteria [ceftazidime 80% vs. 45%, piperacillin/tazobactam (TZP) 86% vs. 40% and meropenem 95% vs.76%] and Gram-positive bacteria. TZP monotherapy was the most commonly used antibiotic and its susceptibility decreased to 22.2% following its use. Appropriate empirical antibiotic treatment was administered in 71/97 (73%) initial and 40/74 (54%) subsequent episodes (P=0.009) and was significantly associated with mortality (adjusted odds ratio=0.4, 95% confidence interval 0.18-0.87). We conclude that previous antibiotic exposure significantly impacts antibiotic susceptibility and that pooled reporting of all infections can be misleading. Treatment guidelines should address the antibiotic treatment of breakthrough fever.

Topics: Adult; Aged; Aged, 80 and over; Bacteremia; Bacterial Infections; Ceftazidime; Drug Resistance, Bacterial; Escherichia coli; Fever; Gram-Positive Bacteria; Hematologic Diseases; Hematopoietic Stem Cell Transplantation; Hospitalization; Humans; Israel; Meropenem; Middle Aged; Odds Ratio; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Thienamycins; Treatment Outcome; Young Adult

To compare treatment effectiveness and tolerability between generic meropenem (Mapenem, Siam Pharmaceutical) and the original formulation.. A retrospective review using historical control of children hospitalized at Queen Sirikit National Institute of Child Health was conducted. The demographics, clinical, and treatment outcomes of 180 children receiving generic meropenem were compared with that of 180 children receiving original meropenem.. Baseline demographics, clinical characteristics were comparable between both groups. The treatment outcomes on day 3, 7, and 14 of treatment were comparable between the two groups with overall improvement rates of 73.9% and 71.7% for generic and original meropenem, respectively (absolute difference: 2.2%, 95% CI: -6.9%, 11.4%). Both drugs were well tolerated, with only 1.6% of patients in each group who experienced adverse reactions.. Mapenem exhibited comparable therapeutic effectiveness and tolerability with that of the brand-name formulation in the treatment of moderate to severe infections in a pediatric population.

Topics: Adolescent; Anti-Bacterial Agents; Bacterial Infections; Case-Control Studies; Child; Child, Preschool; Drugs, Generic; Female; Humans; Infant; Infant, Newborn; Male; Meropenem; Retrospective Studies; Severity of Illness Index; Thailand; Thienamycins

In recent years, owing to the presence of multi-drug resistant nosocomial bacteria, combination therapies are more frequently applied. Thus there is more need to investigate the in vitro activity of drug combinations against multi-drug resistant bacteria. Checkerboard synergy testing is among the most widely used standard technique to determine the activity of antibiotic combinations. It is based on microdilution susceptibility testing of antibiotic combinations. Although this test has a standardised procedure, there are many different methods for interpreting the results. In many previous studies carried out with multi-drug resistant bacteria, different rates of synergy have been reported with various antibiotic combinations using checkerboard technique. These differences might be attributed to the different features of the strains. However, different synergy rates detected by checkerboard method have also been reported in other studies using the same drug combinations and same types of bacteria. It was thought that these differences in synergy rates might be due to the different methods of interpretation of synergy test results. In recent years, multi-drug resistant Acinetobacter baumannii has been the most commonly encountered nosocomial pathogen especially in intensive-care units. For this reason, multidrug resistant A.baumannii has been the subject of a considerable amount of research about antimicrobial combinations. In the present study, the in vitro activities of frequently preferred combinations in A.baumannii infections like imipenem plus ampicillin/sulbactam, and meropenem plus ampicillin/sulbactam were tested by checkerboard synergy method against 34 multi-drug resistant A.baumannii isolates. Minimum inhibitory concentration (MIC) values for imipenem, meropenem and ampicillin/sulbactam were determined by the broth microdilution method. Subsequently the activity of two different combinations were tested in the dilution range of 4 x MIC and 0.03 x MIC in 96-well checkerboard plates. The results were obtained separately using the four different interpretation methods frequently preferred by researchers. Thus, it was aimed to detect to what extent the rates of synergistic, indifferent and antagonistic interactions were affected by different interpretation methods. The differences between the interpretation methods were tested by chi-square analysis for each combination used. Statistically significant differences were detected between the four diff

Topics: Acinetobacter baumannii; Acinetobacter Infections; Ampicillin; Anti-Bacterial Agents; Bacterial Infections; Cross Infection; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Sulbactam; Thienamycins

Meropenem plays a significant role in the current antimicrobial treatment of serious infections. Recently, generic meropenems have become widely available in Thailand.. Compare the effectiveness and safety ofa generic meropenem (Mapenem) with the original meropenem (Meronem) in clinical practice.. A retrospective cohort study was conducted in hospitalized patients with serious infections that had been treated with either the generic or the original meropenem in nine secondary- and tertiary-care hospitals nationwide. The treatment outcomes at days 3, 7, and 14 after the use ofmeropenem between the two groups were compared.. Three hundred ninety seven patients with a mean (SD) age of 66.4 +/- 16.9 years were included. There were 228 (57.4%) males and 169 (42.6%) females. Two hundred and seven (52.1%) and 190 (47.9%) cases fell into the generic and original groups respectively. There were no significant differences regarding age, gender history of underlying disease, body weight, and ward of admission between the two groups. The majority ofpatients had presented with the respiratory tract (48.6%) and bloodstream infections (29.5%). The three most common causative bacteria were Pseudomonas aeruginosa, Acinetobacter baumannii, and extended-spectrum beta-lactamase (ESBL) producing Escherichia coli. The distribution ofthe sites of infection, causative microorganisms, the dosage ofmeropenem, and duration oftreatment were similar between the two groups. The distribution of patients with complete resolution, improvement, stable, worse, diedfrom infection, and died from other causes were similar between the two groups at day 3, 7, and 14 ofmeropenem use (p > 0.05). The drugs were well-tolerated, and less than 2% of patients in both groups discontinued meropenem due to the adverse drug effects.. The generic meropenem has a similar effectiveness in the treatment of serious bacterial infections when compared with original meropenem. Both formulations are well tolerated among patients with substantial comorbidities. Adverse drug effects that lead to drug discontinuation are uncommon.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Cohort Studies; Drugs, Generic; Female; Hospitals, University; Humans; Inpatients; Male; Meropenem; Middle Aged; Retrospective Studies; Thailand; Thienamycins; Time Factors; Treatment Outcome

The post-marketing surveillance of meropenem for children was conducted between May 2004 and September 2006. The safety and the efficacy were analyzed in 1210 cases and 1004 cases, respectively. The results of this surveillance were as follows: The incidence of adverse drug reactions (ADRs) associated with use of meropenem (including abnormal laboratory findings) was 14.3% (173 cases), and the main ADRs were hepatic function abnormal, alanine aminotransferase increased, and aspartate aminotransferase increased, which were similar to these observed in the clinical study. And the efficacy was 88.6% (890 cases).

Topics: Adolescent; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Child; Child, Preschool; Drug Resistance, Bacterial; Female; Humans; Infant; Male; Meropenem; Product Surveillance, Postmarketing; Prospective Studies; Sex Factors; Thienamycins; Treatment Outcome

The antibacterial activity of meropenem (MEPM) and other parenteral antibiotics against clinical isolates of 2655 strains including 810 strains of Gram-positive bacteria, 1635 strains of Gram-negative bacteria, and 210 strains of anaerobic bacteria obtained from 30 medical institutions during 2009 was examined. The results were as follows; (1) MEPM was more active than the other carbapenem antibiotics tested against Gram-negative bacteria, especially against enterobacteriaceae and Haemophilus influenzae. MEPM was also active against most of the species tested in Gram-positive and anaerobic bacteria, except for multidrug resistant strains including methicillin-resistant Staphylococcus aureus (MRSA). (2) MEPM maintained potent and stable antibacterial activity against Pseudomonas aeruginosa. The proportion of MEPM-resistant strains to ciprofloxacin-resistant strains or imipenem-resistant strains were 53.1% and 58.0% respectively. (3) The proportion of extended-spectrum beta-lactamase (ESBL) strains was 3.1% (26 strains) in enterobacteriaceae. And the proportion of metallo-beta-lactamase strains was 2.0% (6 strains) in P. aeruginosa. (4) Of all species tested, there were no species except for Bacteroides fragilis group, which MIC90 of MEPM was more than 4-fold higher than those in our previous study. Therefore, there is almost no significant decrease in susceptibility of clinical isolates to meropenem. In conclusion, the results from this surveillance study suggest that MEPM retains its potent and broad antibacterial activity and therefore is a clinically useful carbapenem for serious infections treatment at present, 14 years passed after available for commercial use in Japan.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteria, Anaerobic; Bacterial Infections; Child; Child, Preschool; Dosage Forms; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Infant; Infant, Newborn; Japan; Meropenem; Middle Aged; Respiratory System; Thienamycins; Time Factors; Urine; Young Adult

In Siriraj Hospital, generic meropenem (Monem) has been available and was substituted for original meropenem, but the effectiveness and safety of using generic meropenem in a clinical setting are the main concern.. From July 2007 to June 2009, hospitalized patients aged 18 or older who received meropenem for 48 hours were identified from the pharmacy database of Siriraj hospital. A retrospective study was conducted. Three hundred patients in each of original and generic meropenem groups were required to demonstrate non-inferiority of generic to original meropenem.. The mean age of all patients was 63 years. Most of the patients had co-morbidities. Approximately 90% of the infections were health-care associated. Drug-resistant gram-negative bacteria including ESBL producing E. coli and K. pneumoniae, P. aeruginosa and A. baumannii account for nearly 50% of all organisms. No significant difference was found regarding characteristics, type or site of infection and pathogen between generic and original groups but for more patients in the original group having cardiovascular disease and more patients in the generic group receiving immunosuppressive agents. Eighty-two to 85% received meropenem with one of appropriate indications. No statistically significant difference occurred either in an overall favorable outcome (63% vs.70.4%, p = 0.07) or in overall mortality (38% vs. 32%, p = 0.17), as well as adverse effects between the original and the generic groups.. Generic meropenem (Monem) was not inferior to original meropenem for therapy of infections in the hospitalized patients at Siriraj Hospital.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Cross Infection; Drugs, Generic; Female; Hospitalization; Hospitals, Teaching; Humans; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Retrospective Studies; Thailand; Thienamycins; Treatment Outcome

To test the hypothesis that treatment with cefepime hydrochloride leads to higher incidence of periodic epileptiform discharges compared with treatment with other β-lactams.. Data from hospital pharmacy databases of patients treated with cefepime or meropenem during a 42-month period (from January 1, 2007, through June 30, 2010) were retrospectively crossed with data from the electroencephalography database for the same period.. Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.. Patients who underwent electroencephalographic testing while taking cefepime or meropenem were selected. Only electroencephalographic tests performed during the antibiotic treatment period were considered. Matches were compared with nurses' medication records to ensure that the antibiotic considered was effectively given.. Proportions of patients with continuous epileptiform discharges in the 2 groups were compared using the Fisher exact test.. A total of 1120 patients were treated with cefepime and 1572 patients with meropenem. Electroencephalographic testing was performed during treatment in 59 patients treated with cefepime and 80 treated with meropenem (5.26% vs 5.08%, P = .85). Continuous epileptiform discharges were present in 14 patients in the cefepime group and 3 in the meropenem group (1.25% vs 0.19%, P < .001). Blood creatinine concentration was elevated in 5 of the 17 patients (range, 1.5-4.2 mg/dL; reference range, 0.7-1.2 mg/dL), and liver enzyme levels were elevated in 5 patients. No patient had major electrolyte disturbances.. Our study showed a prevalence of electroencephalographic test results with continuous epileptiform discharges in 14 of 1120 patients receiving cefepime (1.25%) but only 3 of 1572 patients receiving meropenem (0.19%). Contrary to the results of previous case series, these electroencephalographic patterns occurred, in most cases, in patients with normal renal function. These results suggest that cefepime may be an independent risk factor for periodic epileptiform discharges, which are associated with worse outcomes. This finding could provide a partial explanation for the higher mortality rates reported in patients treated with cefepime compared with other β-lactams.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Belgium; Cefepime; Cephalosporins; Cross-Over Studies; Electroencephalography; Epilepsy; Female; Humans; Male; Meropenem; Middle Aged; Pharmacy Service, Hospital; Retrospective Studies; Thienamycins

The microbiological tests of 769 blood samples from 220 patients, treated in 4 intensive care units of the N.V. Sklifosovsky Research Institute for Emergency Medical Service within a period from January 2009 to June 2010, were analysed. Etiologically significant microorganisms were detected in 323 samples (42%). 253 isolates were used in the analysis. Grampositive and gramnegative pathogens were detected in 47 and 42% of the cases respectively. Candida and anaerobic organisms were isolated in 8 and 3% of the cases respectively. Staphylococcus aureus and enterococci were isolated in 24 and 15% of the cases respectively. Nonfermenting gramnegative bacteria and enterobacteria were revealed in 25 and 17% of the cases respectively. Differences in the spectrum of the sepsis pathogens depending on the patients contingent were shown. The maximum summary susceptibility of the grampositive cocci was observed with respect to vancomycin and linezolid and that of the gramnegative bacteria was stated with respect to imipenem and meropenem.

Topics: Acetamides; Anti-Bacterial Agents; Bacteria, Anaerobic; Bacterial Infections; Candida; Cross Infection; Drug Resistance, Microbial; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Imipenem; Infection Control; Intensive Care Units; Linezolid; Meropenem; Moscow; Oxazolidinones; Sepsis; Thienamycins; Vancomycin

The experience of meropenem (Mepenam, manufactured by 'Arterium", Ukraine Corporation) application as a measure for conduction of empirical therapy and for prophylaxis of an acute destructive pancreatitis complications, was summarized. Efficacy of the preparation on different stages of the purulent complications treatment (while applied solely as well as in combination with various kinds of miniinvasive and open operative interventions) was estimated. The recommendations, concerning Mepenam application for various forms of an acute pancreatitis, were elaborated.

Topics: Anti-Bacterial Agents; Bacterial Infections; Humans; Meropenem; Pancreatitis, Acute Necrotizing; Thienamycins

We investigated antimicrobial activities of meropenem and other antibiotics against 164 isolates (41 Escherichia coli, 16 Klebsiella pneumoniae, 7 Enterobacter cloacae, 21 Pseudomonas aeruginosa, 14 methicillin-susceptible Staphylococcus aureus (MSSA), 18 methicillin-resistant Staphylococcus aureus (MRSA), 47 Staphylococcus epidermidis) from blood of the patients admitted to Keio University Hospital between January and October in 2010. Meropenem showed the potent antibacterial activity against Gram-negative bacteria especially and it maintained good broad spectrum antimicrobial activity including resistant strains through 13 years since when we started the investigation. These results indicated the validity of choosing meropenem as a first line antimicrobial agent for serious infectious diseases.

Topics: Anti-Bacterial Agents; Bacterial Infections; Blood; Drug Resistance, Bacterial; Gram-Negative Bacteria; Humans; Meropenem; Thienamycins; Time Factors

This study was a pharmacokinetic (PK)-pharmacodynamic (PD) target attainment analysis of meropenem in Japanese adult patients. Plasma drug concentration data (265 samples from 42 patients) were used for population PK modeling and Monte Carlo simulation to assess the probability of attaining the PK-PD target (40% of the time above the MIC for the bacterium). The final population PK model identified creatinine clearance (Cl(cr), ml/min) and body weight (BW, kg) as the most significant covariates: Cl (l/h) = 0.0905 × Cl(cr) + 2.03, V(c)(l) = 0.199 9 BW, Q (l/h) = 4.02, and V(p) (l) = 4.55, where Cl is the clearance, Vc and Vp are the volumes of distribution of the central and peripheral compartments, respectively, and Q is the intercompartmental clearance. The Monte Carlo simulation developed the PK-PD breakpoints (the highest MIC values at which the probabilities of target attainment in plasma are 80% or more) for meropenem regimens, the values of which varied with the Cl(cr) and BW of the patient. The simulation also demonstrated that 0.25 g every 12 h (0.5-h infusion) achieved a target attainment probability of 82.4-100% against Escherichia coli, methicillin-susceptible Staphylococcus aureus, Haemophilus influenzae, and Streptococcus pneumoniae isolates. However, against Pseudomonas aeruginosa isolates, 0.5 g every 8 h or 1 g every 8 h was required to achieve 80% or more probability in most typical patients. These results provide a PK-PD-based strategy for tailoring a meropenem regimen according to Clcr and BW of a Japanese adult patient and susceptibility of the causative bacteria.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Female; Gram-Negative Bacteria; Gram-Positive Cocci; Humans; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Models, Biological; Monte Carlo Method; Thienamycins; Young Adult

The aims of this study were to develop a population pharmacokinetic model for meropenem in Japanese pediatric patients, and to use this model to assess the pharmacodynamics of meropenem regimens against common bacterial populations. Pharmacokinetic data were pooled from nine separate studies (229 plasma samples and 61 urine samples from 40 infected children), modeled using the NONMEM program, and used for a pharmacodynamic simulation to estimate the probabilities of attaining the bactericidal target (40% of the time above the MIC for the bacterium). In the final population pharmacokinetic model, body weight (BW, kg) was the most significant covariate: Cl(r) (l/h) = 0.254 x BW, Cl(nr) (l/h) = 3.45, V (c) (l) = 0.272 x BW, Q (l/h) = 1.65, and V (p) (l) = 0.228 x BW, where Cl(r) and Cl(nr) are the renal and non-renal clearances, V (p) and V (c) are the volumes of distribution of the central and peripheral compartments, and Q is the intercompartmental (central-peripheral) clearance. In most typical patients (BW = 10, 20, and 30 kg), the approved regimens of 10-40 mg/kg, three times a day (0.5-h infusions), achieved a target attainment probability of >80% against Escherichia coli, Streptococcus pneumoniae, methicillin-susceptible Staphylococcus aureus, Haemophilus influenzae, and Pseudomonas aeruginosa isolates. The results of this study provide a better understanding of the pharmacokinetics and pharmacodynamics of meropenem in Japanese pediatric patients.

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Body Weight; Child; Humans; Japan; Meropenem; Microbial Sensitivity Tests; Models, Biological; Monte Carlo Method; Thienamycins

Our aim was to determine the prevalence of multidrug resistance of Acinetobacter baumannii and other pathogens at a tertiary-care teaching hospital in Mexico over a 3-year period. Clinical isolates of A. baumannii (n = 550), Pseudomonas aeruginosa (n = 250), some Enterobacteriaceae species (n = 500) and Staphylococcus aureus (n = 250) collected over a 3-year period were included. Susceptibility tests were performed by the broth microdilution method. 74% of A. baumannii, 40% of Escherichia coli, 34% of P. aeruginosa, 22% of Klebsiella pneumoniae, 9% of Enterobacter cloacae, and 7% of Serratia sp. were multidrug resistant. 59% of A. baumannii clinical isolates were meropenem-resistant. A. baumannii isolates from the lower respiratory tract were the most susceptible, followed by urine clinical isolates. Species from Enterobacteriaceae showed susceptibility rates higher than 90% to meropenem and tigecycline and Serratia sp. showed the highest susceptibility to the drugs evaluated. For P. aeruginosa, the most potent drug was levofloxacin, followed by meropenem and piperacillin-tazobactam. With regard to S. aureus, 96% of the isolates were susceptible to vancomycin, followed by tigecycline and minocycline (91% of strains susceptible). The high multidrug resistance observed underscores the need for surveillance of bacterial drug resistance.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Hospitals, Teaching; Humans; Klebsiella pneumoniae; Meropenem; Mexico; Microbial Sensitivity Tests; Minocycline; Prevalence; Pseudomonas aeruginosa; Pseudomonas Infections; Staphylococcus aureus; Thienamycins; Tigecycline

To develop a population pharmacokinetic model of meropenem in burn patients and to explore the appropriateness of current dosage regimens.. Fifty-nine patients with burns ranging from 3% to 97% of total body surface area treated with meropenem were analysed. The population pharmacokinetic parameters of meropenem in 59 burn patients were estimated, and concentrations were simulated by using a mixed effect method (NONMEM, ver. 6.2).. The final model was a two-compartment model with first-order elimination where creatinine clearance (CL(CR)) and oedema contributed. The mean population pharmacokinetic parameters were clearance (L/h) =4.45 +10.5 × CL(CR) (mL/min)/138, V1 (central volume) =17.0+11.1 × presence of oedema (0 or 1) L, V2 (peripheral volume) =10.1 L and Q (intercompartmental clearance) =5.25 L/h with interindividual variability (CV%) of 31.5%, 44.4%, 67.2% and 0% (not estimated), respectively.. The population clearance and volume of distribution in our burn patients were significantly greater than those reported in non-burn patients. The simulation of 1000 virtual patients' plasma meropenem concentration treated with 1000 mg (30 min infusion) every 8 h based upon the model predicted the probability of achieving the time above MIC >40% of the dosing interval as 58.9% for Pseudomonas aeruginosa isolated from three university hospitals in Korea.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Burns; Female; Humans; Korea; Male; Meropenem; Metabolic Clearance Rate; Microbial Sensitivity Tests; Middle Aged; Pseudomonas aeruginosa; Thienamycins

Doripenem is a new carbapenem with broad spectrum antibacterial activity indicated for the treatment of nosocomial pneumonia and complicated urinary and intraabdominal infections.. Isolates of Pseudomonas aeruginosa, Acinetobacter and Enterobacteriaceae from patients with nosocomial pneumonia, bacteremia and complicated intraabdominal infections attended in 16 Spanish hospitals were included (October 2008-May 2009). Susceptibility to imipenem, meropenem and doripenem was studied with the Etest method, and the results were interpreted according to the EUCAST criteria.. Considering all the isolates, doripenem (MIC(50) 0.12 mg/L) was 2- to 8-fold more active than meropenem (0.25 mg/L) and imipenem (1 mg/L). In relation to Enterobacteriaceae, the MIC(50) and MIC(90) values of doripenem and meropenem were similar (0.03 and 0.12 mg/L, respectively) and clearly superior to those of imipenem (0.25 and 1 mg/L). In the case of P. aeruginosa, MIC(50) and MIC(90) were more favorable to doripenem (0.25 and 16 mg/L) than to meropenem (0.5 and ≥64 mg/L) or imipenem (2 and ≥64 mg/L). In this species, the percentage of strains with lower MIC values for doripenem among those exhibiting intermediate susceptibility and resistance to meropenem was 63.0% (29/46) and 61.7% (63/102), respectively, versus only 4.3% (2/46) and 1.9% (2/102) with higher MIC values for doripenem.. The results obtained in this study are similar to those reported in other countries, and reinforce the superior in vitro activity of doripenem versus the other carbapenems and its position in the treatment guidelines regarding the nosocomial infections for which it is indicated.

Topics: Acinetobacter Infections; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Carbapenems; Doripenem; Enterobacteriaceae Infections; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Pseudomonas Infections; Spain; Thienamycins

The clinical course in acute necrotizing pancreatitis is mainly influenced by bacterial infection of pancreatic and peripancreatic necrosis. The effect of two antibiotic treatments for early prophylaxis was studied in the taurocholate model of necrotizing pancreatitis in the rat.. Sixty male Sprague-Dawley rats were divided into three pancreatitis groups (15 animals each) and a sham-operated group (15 animals, control group). Pancreatitis was induced by intraductal infusion of 3% taurocholate under sterile conditions. Animals were placed on one of two different antibiotic regimens (15 mg/kg ertapenem or 20 mg/kg meropenem, one shot) after the induction of pancreatitis or received no antibiotics (control). All animals were sacrificed after 24 h to study pancreatic and extrapancreatic infection.. Early antibiotic prophylaxis with either erapenam or meropenem significantly decreased pancreatic infection from 12/15 (control group) to 4/15 (ertapenem antibiotic group) and 3/15 (meropenem antibiotic group) (P < 0.05).. In our animal model of necrotizing pancreatitis, early antibiotic prophylaxis with ertapenem and meropenem reduced bacterial infection of the pancreas. The efficacy of early antibiotic prophylaxis with ertapenem in the clinical setting should be subject to further research.

Topics: Animals; Antibiotic Prophylaxis; Bacterial Infections; beta-Lactams; Colony Count, Microbial; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Ertapenem; Male; Meropenem; Pancreatitis, Acute Necrotizing; Probability; Random Allocation; Rats; Rats, Sprague-Dawley; Reference Values; Risk Factors; Sensitivity and Specificity; Severity of Illness Index; Thienamycins

Topics: ABO Blood-Group System; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Bacterial Infections; Caspofungin; Drug Therapy, Combination; Echinocandins; Female; Fungemia; Fusarium; Graft Rejection; Histocompatibility; Humans; Immunocompromised Host; Immunosuppressive Agents; Lipopeptides; Liver Transplantation; Meropenem; Middle Aged; Teicoplanin; Thienamycins

Topics: Adolescent; Anti-Bacterial Agents; Bacteria, Anaerobic; Bacterial Infections; Bronchopneumonia; Child; Cystic Fibrosis; Humans; Meropenem; Thienamycins

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program was a global, longitudinal antimicrobial resistance surveillance network of more than 100 medical centers worldwide monitoring the susceptibility of meropenem and selected other broad-spectrum comparator agents. In 1999, and from 2000 through 2008, a total of 10 or 15 United States (USA) medical centers each forwarded 200 nonduplicate clinical isolates from serious infections to a central processing laboratory. Over the 10-year period of this surveillance program, the activity of meropenem and an average of 11 other antimicrobial agents were assessed against a total of 27 289 bacterial isolates using Clinical and Laboratory Standards Institute reference methods. Meropenem consistently demonstrated low resistance rates against Enterobacteriaceae species isolates through 2008 and did not exhibit a widespread change in resistance rates over the monitored interval. In fact, the incidence of emerging carbapenemase-producing (KPC-type) Klebsiella spp. showed a decline in 2008 compared to the steeply increasing rates observed from 2004 to 2007. Moreover, the KPC serine carbapenemases have spread to other Enterobacteriaceae species monitored by the MYSTIC Program. Greatest increases in antimicrobial resistance rates were observed for the fluoroquinolones (ciprofloxacin, levofloxacin) among all species monitored by the MYSTIC Program. Current susceptibility rates for meropenem when tested against prevalent pathogens were Pseudomonas aeruginosa (439 strains, 85.4% susceptible), Enterobacteriaceae (1537 strains, 97.3% susceptible), methicillin-susceptible staphylococci (460 strains, 100.0% susceptible), Streptococcus pneumoniae (125 strains, 80.2% at meningitis susceptibility breakpoints), other streptococci (159 strains, 90.0-100.0% susceptible), and Acinetobacter spp. (127 strains, 45.7% susceptible), the widest spectrum among beta-lactams tested in 2008 and throughout the last decade. Continued local surveillance of broad-spectrum agents following the completion of the MYSTIC Program (USA) appears critical to detect emerging resistances among pathogens causing the most serious infections requiring carbapenem agents.

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Resistance, Bacterial; Humans; Longitudinal Studies; Meropenem; Microbial Sensitivity Tests; Prevalence; Thienamycins; United States

We examined the antimicrobial activities of meropenem and other antibiotics against main bacteria isolated from patient blood in Keio university hospital between January and November in 2008. A total of 187 isolates, including 43 Escherichia coli, 23 Klebsiella pneumoniae, 9 Enterobacter cloacae, 22 Pseudomonas aeruginosa, 16 methicillin-susceptible Staphylococcus aureus (MSSA), 24 methicillin-resistant Staphylococcus aureus (MRSA), 50 Staphylococcus epidermidis were tested. Meropenem showed the potent and stable antibacterial activity against Gram-negative bacteria especially compared with our previous testing data. These results suggested that meropenem was first-line antibiotic for serious infections, although over 12 years passed after meropenem was approved in Japan.

Topics: Anti-Bacterial Agents; Bacterial Infections; Blood; Dose-Response Relationship, Drug; Drug Resistance, Bacterial; Gram-Negative Bacteria; Humans; Meropenem; Thienamycins; Time Factors

Against 182 anaerobe and 241 aerobe strains obtained from diabetic foot infections, doripenem was the most active carbapenem against Pseudomonas aeruginosa (MIC(90), 2 microg/ml), more active than imipenem against Proteus mirabilis, and ertapenem was more active against Escherichia coli and Klebsiella spp. The MIC(50) and MIC(90) values were < or =0.125 microg/ml for methicillin-sensitive Staphylococcus aureus and all streptococci and 0.25/1 for Bacteroides fragilis.

Topics: Anti-Bacterial Agents; Bacteria, Aerobic; Bacteria, Anaerobic; Bacterial Infections; Carbapenems; Diabetic Foot; Doripenem; Humans; Microbial Sensitivity Tests

There have been few clinical reports on pharmacokinetics-pharmacodynamics (PK-PD) theory, although many basic or fundamental researches on appropriate use for the antimicrobials based on the PK-PD theory have been performed. We evaluated the target T>MIC values on meropenem and biapenem which have been obtained by basic researches. While we investigated whether the target T>MIC values were also useful for anaerobic infections. Clinical and bacteriological efficacies of meropenem and biapenem were about 70% in T>MIC over 25% or over 80% in T>MIC over 30%. When monomicrobial infections by anaerobes were occurred as abscesses, there have been no correlation between target T>MIC values and clinical effect. When polymicrobial infections between aerobes and anaerobes were occurred, we have achieved over 90% clinical efficacy when over 20% T>MIC values. These results supported the data by Craig, W. A. and Drusano, G. L. The regimen based on PK-PD theory would be useful in clinical practice including against anaerobic infections.

Topics: Adult; Bacteria, Aerobic; Bacteria, Anaerobic; Bacterial Infections; Carbapenems; Drug Administration Schedule; Drug Resistance, Microbial; Escherichia coli; Female; Humans; Meropenem; Middle Aged; Pelvic Inflammatory Disease; Staphylococcus aureus; Thienamycins

Topics: Anti-Bacterial Agents; Bacterial Infections; Humans; Meropenem; Thienamycins

Topics: Abdominal Abscess; Anti-Bacterial Agents; Bacterial Infections; Carbapenems; Doripenem; Humans; Imipenem; Meropenem; Thienamycins

A pharmacokinetic (PK)/pharmacodynamic (PD) modeling strategy to simulate in vivo bactericidal effects for three carbapenem antibiotics, doripenem (DRPM), meropenem (MEPM)/cilastatin (CS), and imipenem (IPM)/CS, against a Pseudomonas aeruginosa (P. aeruginosa) strain is proposed. The PD model we have already developed to explain in vitro time-kill profiles was modified to incorporate the growth rate, bactericidal activities, and PK profiles in murine lung infection models. Plasma concentration data and bacterial time-kill data for each antibiotic consist of six and eight time points, respectively, at one dose regimen (four or five mouse/point). In vivo time-kill curves could be well simulated for each antibiotic by the PK/PD model. Simulated bacterial counts at 24 h and PK/PD indices derived from total drug concentrations (time above the minimum inhibitory concentration (MIC) (T > MIC), C(max)/MIC, and AUC/MIC) for various dose regimens were examined for MEPM/CS and IPM/CS. Simulated bacterial counts correlated only with T > MIC (correlation coefficient: 0.951 for MEPM/CS, 0.982 for IPM/CS) and T > MIC values to achieve a bacteriostatic effect and a 2-log killing effect for both antibiotics were estimated to be approximately 15 and 20%, respectively, which are similar to previously reported results. These findings suggested that the proposed PK/PD model is a good tool for predicting in vivo bactericidal effects.

Topics: Animals; Anti-Bacterial Agents; Area Under Curve; Bacterial Infections; Carbapenems; Cilastatin; Disease Models, Animal; Doripenem; Female; Imipenem; Meropenem; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Models, Biological; Thienamycins

Surveillance studies conducted in the United States over the last decade have revealed increasing resistance among community-acquired respiratory pathogens, especially Streptococcus pneumoniae, that may limit future options for empirical therapy. The objective of this study was to assess the scope and magnitude of the problem at the national and regional levels during the 2005-2006 respiratory season (the season when community-acquired respiratory pathogens are prevalent) in the United States. Also, since faropenem is an oral penem being developed for the treatment of community-acquired respiratory tract infections, another study objective was to provide baseline data to benchmark changes in the susceptibility of U.S. respiratory pathogens to the drug in the future. The in vitro activities of faropenem and other agents were determined against 1,543 S. pneumoniae isolates, 978 Haemophilus influenzae isolates, and 489 Moraxella catarrhalis isolates collected from 104 U.S. laboratories across six geographic regions during the 2005-2006 respiratory season. Among S. pneumoniae isolates, the rates of resistance to penicillin, amoxicillin-clavulanate, and cefdinir were 16, 6.4, and 19.2%, respectively. The least effective agents were trimethoprim-sulfamethoxazole (SXT) and azithromycin, with resistance rates of 23.5 and 34%, respectively. Penicillin resistance rates for S. pneumoniae varied by region (from 8.7 to 22.5%), as did multidrug resistance rates for S. pneumoniae (from 8.8 to 24.9%). Resistance to beta-lactams, azithromycin, and SXT was higher among S. pneumoniae isolates from children than those from adults. beta-Lactamase production rates among H. influenzae and M. catarrhalis isolates were 27.4 and 91.6%, respectively. Faropenem MICs at which 90% of isolates are inhibited were 0.5 mug/ml for S. pneumoniae, 1 mug/ml for H. influenzae, and 0.5 mug/ml for M. catarrhalis, suggesting that faropenem shows promise as a treatment option for respiratory infections caused by contemporary resistant phenotypes.

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Infections; beta-Lactams; Community-Acquired Infections; Drug Resistance, Multiple, Bacterial; Geography; Haemophilus influenzae; Health Surveys; Humans; Moraxella catarrhalis; Penicillin Resistance; Respiratory Tract Infections; Streptococcus pneumoniae; Trimethoprim, Sulfamethoxazole Drug Combination; United States

CW-270033, an injectable carbapenem, is a novel, synthesized pyrrolidinyl-thio carbapenem. In the present study, the in-vitro and in-vivo antibacterial activities of CW-270033 against wild-type strains and clinical isolates were compared with those of imipenem and meropenem. CW-270033 was more active than imipenem against Gram-negative (Escherichia coli and Pseudomonas aeruginosa) clinical isolates, but was slightly less active than meropenem. Against the Gram-positive clinical isolates methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE), CW-270033 was slightly more active than meropenem, but was less active than imipenem. CW-270033 displayed potent in-vivo activity against E. coli ATCC 25922, P. aeruginosa ATCC 27853, and S. aureus SMITH in the mouse systemic infection model; the efficacy of CW-270033 in this model was 2--7 fold higher than that of meropenem. This activity was comparable to the in-vitro activity of CW-270033. An intravenous injection of CW-270033 showed that the half-life of CW-270033 in serum in mice was about 20 min, which was about two times that of meropenem. CW-270033 was also found to be resistant to hydrolysis by the mouse renal dehydropeptidase I (DHP-I) enzyme.

Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Carbapenems; Cilastatin; Dose-Response Relationship, Drug; Enterococcus faecalis; Escherichia coli; Injections, Intravenous; Meropenem; Methicillin Resistance; Mice; Microbial Sensitivity Tests; Molecular Structure; Protease Inhibitors; Pseudomonas aeruginosa; Pyrrolidines; Staphylococcus aureus; Thienamycins; Vancomycin Resistance

To compare outcomes and cost for the traditional United States Food and Drug Administration-approved dosing regimen for meropenem versus an alternative dosing regimen providing similar pharmacodynamic exposure with a lower total daily dose.. Retrospective cohort study with a cost-minimization analysis.. A 417-bed, privately owned community hospital.. One hundred patients who received meropenem 1 g every 8 or 12 hours (traditional dosing regimen) between January 1 and September 30, 2004 (historical controls), and 192 patients who received meropenem 500 mg every 6 or 8 hours (alternative dosing regimen) between October 1, 2004, and September 30, 2005.. Demographic and clinical data were collected for all patients. Cost-minimization analysis was performed by using the drug acquisition cost for meropenem. Demographics, sources of infection, distributions of organisms, and Charlson Comorbidity Index scores were similar between patients in the traditionally and alternatively dosed groups. Concomitant therapy, duration of therapy, success rates, lengths of stay, and in-hospital mortality rates were also similar between groups. Median time to the resolution of symptoms was 3 days for traditional dosing and 1.5 days for alternative dosing (p<0.0001). A logistic regression model including the dosing strategy showed that only polymicrobial infections and sepsis were associated with increased failure rates. The median cost for antibiotics was $439.05/patient for traditional dosing and $234.08/patient for alternative dosing (p<0.0001).. An alternative dosing regimen for meropenem with a lower total daily dose yielded patient outcomes, including success rates and duration of therapy, equivalent to those of the traditional dosing regimen. Alternative dosing decreased total drug exposure, costs for antibiotics, and time to the resolution of infections.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Cohort Studies; Costs and Cost Analysis; Drug Administration Schedule; Drug Costs; Hospitals, Community; Humans; Logistic Models; Meropenem; Middle Aged; Retrospective Studies; Sepsis; Thienamycins; Treatment Outcome

This study compared the cost-effectiveness of meropenem with that of imipenem plus cilastatin in the treatment of severe infections in hospital intensive care in the UK. A Markov model was constructed to model lifetime costs and quality-adjusted life years (QALYs) of using meropenem and imipenem plus cilastatin for the treatment of severe infections in intensive care. Estimates of effectiveness, utility weights and costs were obtained from the published literature. Probabilistic sensitivity analysis was conducted to assess the robustness of the results. Estimated treatment costs for the patient cohort were pound 14,938 with meropenem and pound 15,585 with imipenem plus cilastatin. QALYs gained were 7,495 with meropenem and 7,413 with imipenem plus cilastatin. Probabilistic sensitivity analysis showed meropenem to be significantly less costly (-pound 636.47, 95% CI -pound 132.33 to -pound 1,140.62) and more effective (0.084, 95% CI 0.023 to 0.144). Meropenem thus appears significantly more effective and less expensive than imipenem plus cilastatin and should therefore be considered the dominant treatment strategy.

Topics: Aged; Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cohort Studies; Cost-Benefit Analysis; Decision Support Techniques; Dipeptidases; Drug Combinations; Female; Humans; Intensive Care Units; Male; Markov Chains; Meropenem; Middle Aged; Quality-Adjusted Life Years; Sensitivity and Specificity; Thienamycins

The reasonable data on the basis of a PK/PD theory in clinical practice would be provided by the analysis in consideration of renal function because the excretion of meropenem mainly occurs from kidney. We carried out the simulation with pharmacokinetics of meropenem in consideration of renal function, and investigated whether renal function would affect Time above MIC (T>MIC). The % T>MICs were 18.9%, 35.0%, 49.4%, 61.1% in serum creatinine level 0.5, 1.0, 1.5, and 2.0 mg/dL, respectively, when MIC of causative organism was assumed to 4microg/mL. Furthermore, we investigated the association between renal function and clinical efficacy in three patients with peritonitis, who received meropenem. We conclude that the simulation in consideration of renal function would be useful in PK/PD-based analysis, and would give the clinically useful data in clinical practices.

Topics: Aged; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Biomarkers; Creatinine; Drug Administration Schedule; Drug Resistance, Bacterial; Female; Humans; Kidney; Kidney Function Tests; Meropenem; Middle Aged; Peritonitis; Thienamycins

A Monte Carlo simulation demonstrated that 1 g of meropenem (MEM) every 8 h (q8h) (3-h infusion) has a higher target attainment rate against Pseudomonas aeruginosa than either 500 mg of MEM q8h (3-h infusion) or 0.5 g of imipenem-cilastatin (I-C) q6h (1-h infusion). For other pathogens, 500 mg of MEM q8h was equivalent or superior to I-C.

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Models, Biological; Monte Carlo Method; Pseudomonas aeruginosa; Thienamycins; Time Factors

The bactericidal exposures necessary for positive clinical outcomes among skin and soft tissue infections are largely dependent on interpatient pharmacokinetic variability and pathogen drug susceptibility. By simulating the probability of achieving target bactericidal exposures, the pharmacodynamics of three beta-lactam agents were compared against a range of pathogens implicated commonly in complicated skin and soft tissue infections.. Using Monte Carlo simulation, pharmacodynamic target attainment expressed as the percentage of the time interval during which the antibiotic concentration exceeded the minimal inhibitory concentration (%T > MIC) in serum and blister fluid was calculated for 5,000 simulated patients receiving imipenem-cilastatin 0.5 g q8h, meropenem 0.5 g q8h, piperacillin-tazobactam 3.375 g q6h, and piperacillin-tazobactam 4.5 g q8h. The pharmacokinetics for each antibiotic were derived from previously published healthy volunteer studies. The MICs for Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Enterobacter sp., Klebsiella sp., coagulase-negative staphylococci, Proteus sp., beta-hemolytic streptococci, and Serratia sp. were taken from the MYSTIC 2003 surveillance study and weighted by the prevalence of each pathogen among 1,404 isolates collected from skin and soft tissue infections during the 2000 SENTRY study. The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) was added into the model at increasing resistance rates.. Imipenem-cilastatin, meropenem, and piperacillin-tazobactam 3.375 g q6h achieved greater than 90% likelihood of achieving bactericidal exposure in serum and blister fluid until the prevalence of MRSA increased beyond 10%. Piperacillin-tazobactam 4.5 g q8h achieved a lower probability of achieving bactericidal exposure than the other regimens (88.7%, p < 0.001).. When the incidence of MRSA is low, imipenem-cilastatin, meropenem and piperacillin-tazobactam 3.375 g q6h would be optimal choices for the empiric treatment of complicated skin and soft tissue infections among the regimens studied. When MRSA is suspected, a drug that retains activity against this pathogen should be considered.

Topics: Anti-Bacterial Agents; Bacterial Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Dose-Response Relationship, Drug; Drug Combinations; Gram-Negative Bacteria; Gram-Positive Cocci; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Models, Biological; Monte Carlo Method; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Population Surveillance; Prevalence; Soft Tissue Infections; Thienamycins

Topics: Bacterial Infections; Cohort Studies; Drug Resistance; Fever; Hematopoietic Stem Cell Transplantation; Humans; Meropenem; Multivariate Analysis; Neutropenia; Odds Ratio; Research Design; Risk Factors; Thienamycins; Transplantation, Homologous; Treatment Outcome

Topics: Bacteria; Bacterial Infections; beta-Alanine; Carbapenems; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Administration Schedule; Drug Combinations; Drug Resistance, Bacterial; Humans; Imipenem; Meropenem; Thienamycins; Treatment Failure

The antibacterial activity of meropenem (MEPM) and other parenteral antibiotics against clinical isolates of 899 strains of Gram-positive bacteria, 1500 strains of Gram-negative bacteria, and 158 strains of anaerobic bacteria obtained from 28 medical institutions during 2002 was measured. The results were as follows; 1. MEPM was more active than other carbapenem antibiotics against Gram-negative bacteria, especially against enterobacteriaceae and Haemophilus influenzae. MIC90 of MEPM against Pseudomonas aeruginosa was the lowest of the drugs tested. MEPM showed low cross-resistant rate against both imipenem-resistant P. aeruginosa and ciprofloxacin-resistant P. aeruginosa. MEPM was active against most of the species tested in Gram-positive and anaerobic bacteria, except for multi-drug resistant strains including methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE). 2. The proportion of extended-spectrum beta-lactamase (ESBL) strains was 3.1% (4 strains) in Escherichia coli and 1.9% (2 strains) in Klebsiella pneumoniae. Carbapenems including MEPM were active against these ESBL strains. In conclusion, the results from this surveillance study suggest that MEPM retains its potent and broad antibacterial activity and therefore is a clinically useful carbapenem; at present, 7 years after available for commercial use.

Topics: Bacteria; Bacterial Infections; Carbapenems; Drug Resistance, Bacterial; Humans; Japan; Meropenem; Product Surveillance, Postmarketing; Thienamycins; Time Factors

Topics: Adolescent; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Catheterization, Central Venous; Child; Child, Preschool; Drug Resistance, Bacterial; Fever; Humans; Infant; Meropenem; Neoplasms; Neutropenia; Prospective Studies; Thienamycins; Vancomycin

The clinical and economic outcomes of a meropenem dosage strategy based on pharmacodynamic concepts are retrospectively reviewed.. The medical records of all patients receiving at least one day of meropenem at a large teaching hospital during 2002 were reviewed. Patients were included if they were clinically evaluable, had no prior successful antibiotic therapy, and received a meropenem dosage appropriate for renal function. Clinical outcomes were evaluated by the rate of response (days to normalization of temperature or lymphocyte count) and success rate. A cost-minimization analysis was performed from the hospital's perspective for level 1, 2, and 3 costs. The average wholesale price of meropenem for 2002 and the cost for one hospital day at our institution were used to calculate economic outcomes.. Of the 136 patients identified as receiving at least one dose of meropenem, 85 met inclusion criteria, of whom 45 received meropenem 500 mg every six hours and 40 received meropenem 1000 mg every eight hours. No significant differences in demographics, site of infection, meropenem-related length of stay, or rate of response were found. Clinical success rates were similar between groups (p = 0.862). Patients taking the 500-mg regimen received less meropenem during treatment than those in the 1000-mg group (13 g versus 18 g, respectively) (p = 0.012). Median level 1 and 2 costs were significantly lower for the 500-mg regimen (p = 0.009 and p = 0.008, respectively). Level 3 costs were not significantly different.. A pharmacodynamically designed meropenem dosage strategy of 500 mg every six hours yielded similar clinical outcomes to a regimen of 1000 mg every eight hours and reduced the daily drug acquisition costs associated with antibiotic therapy.

Topics: Adult; Bacteria; Bacterial Infections; Connecticut; Drug Utilization Review; Economics, Pharmaceutical; Female; Hospital Costs; Hospitals, Teaching; Humans; Length of Stay; Male; Medical Records; Meropenem; Middle Aged; Retrospective Studies; Thienamycins; Treatment Outcome

Ciprofloxacin and meropenem have effects on intestinal bacteria that are responsible for pancreatic infection, and on the basis of recent data it has been argued that probiotics, especially those used in the food industry, could improve efforts to prevent and treat secondary pancreatic infections by inhibiting bacterial translocation.. To evaluate the effects of probiotic treatment alone or in combination with early administration of two different antibiotics on serum amylase, pancreatic histopathology, bacterial translocation, and oxidative markers.. Acute pancreatitis was induced in rats with 3% sodium taurocholate (1 mL/kg intraductally), except in group VI (sham group). After the stabilization period, the rats were divided into seven groups (n = 20) randomly. At hour 6 after injection, group I rats received probiotic Saccharomyces boulardii (25 mg/d orally q.d.), group II received meropenem (60 mg/kg intraperitoneally b.i.d.), group III received ciprofloxacin (40 mg/kg intraperitoneally b.i.d.), group IV received the same dose of probiotic plus meropenem, and group V received probiotic plus ciprofloxacin. Treatment was not given to group VI (sham group) and group VII (pancreatitis group). At hour 48 after induction, specimens were collected.. Although histopathologic scores in treatment groups were found to be lower than in group VII, the difference was statistically significant only in group V (p < 0.001). In evaluation of oxidative stress, we found that MDA levels decreased and SOD levels increased in treatment groups in comparison with levels in group VII. Probiotic treatment alone reduced bacterial translocation. Probiotic-antibiotic combination therapy was shown to improve histopathologic scores and oxidative parameters.

Topics: Analysis of Variance; Animals; Anti-Bacterial Agents; Bacterial Infections; Bacterial Translocation; Ciprofloxacin; Combined Modality Therapy; Male; Malondialdehyde; Meropenem; Oxidative Stress; Pancreatitis, Acute Necrotizing; Probiotics; Rats; Rats, Sprague-Dawley; Saccharomyces; Superoxide Dismutase; Taurocholic Acid; Thienamycins

Antibacterial activity of biapenem (BIPM) against clinical isolates of 8 species between 2000 and 2002 was compared with those of imipenem/cilastatin (IPM/CS), meropenem (MEPM), panipenem/betamipron (PAPM/BP) and ceftazidime (CAZ). The MICs of biapenem for Gram-positive bacteria were higher than those of IPM/CS and PAPM/BP, equal to those of MEPM and lower than those of CAZ. The MICs of BIPM for Gram-negative bacteria were higher than those of MEPM, equal to those of IPM/CS and PAPM/BP, and lower than those of CAZ. Antibacterial activity of BIPM against Pseudomonas aeruginosa was equal to those of IPM/CS and MEPM and superior to those of PAPM/BP and CAZ. In conclusion, BIPM showed broad antibacterial activity against both Gram-positive and Gram-negative clinical isolates. These results suggest that BIPM is useful for the treatment of various bacterial infections.

Topics: Bacteria; Bacterial Infections; beta-Alanine; Carbapenems; Ceftazidime; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Resistance, Bacterial; Humans; Imipenem; Meropenem; Thienamycins

Recent data from the experimental clinical studies suggest that antibiotics having good penetration to pancreas may reduce mortality by preventing pancreatic infection, which is the most important prognostic factor in acute pancreatitis (AP). Deferoxamine is an active free oxygen radical scavenger, which has been shown to have a protective role in development of acute pancreatitis.. To determine the effects of combination of deferoxamine and meropenem in acute necrotizing pancreatitis.. One hundred male Sprague-Dawley rats were randomly divided into 5 groups. All rats underwent laparotomy with cannulation of biliopancreatic duct. Group 1 received intraductal saline injection. Acute necrotizing pancreatitis was induced in group 2, 3, 4, and 5 by intraductal injection of 3% taurocholate. Group 1 (sham operated) and group 2 were injected with saline of 0.3 mL/kg intraperitoneally (i.p). Group 3 was injected with meropenem 60 mg/kg/d i.p, group 4 with deferoxamine 80 mg/kg/d s.c and group 5 with combination of these 2 agents at the same doses. While meropenem was started 2 hours later, all treatments were started immediately after the induction of pancreatitis. All rats were killed at the 48th hour of the treatment and blood and tissue samples were collected for amylase determinations, pathologic examinations, and culture.. There was no difference in serum amylase levels between AP induced groups (P > 0.05). Pancreatic histology scores were significantly low in rats treated with deferoxamine (group 4), and combination regimen (group 5) (P < 0.001). Meropenem significantly reduced the incidence of pancreatic infection. Although combination of deferoxamine with meropenem showed better effects than meropenem alone in terms of pancreatic infection, the difference did not reach to statistical significance.. Meropenem treatment reduces secondary pancreatic infections in acute pancreatitis. Treatment with deferoxamine and meropenem combination may be more beneficial than single therapies in reducing the severity of pancreatitis. Further studies investigating the effects of this combination on survival are needed.

Topics: Acute Disease; Animals; Bacteria; Bacterial Infections; Catheterization; Deferoxamine; Drug Therapy, Combination; Laparotomy; Male; Meropenem; Pancreatitis, Acute Necrotizing; Rats; Rats, Sprague-Dawley; Thienamycins

Secondary infection of the inflamed pancreas is the principal cause of death after severe acute pancreatitis (AP). Although patients are not always managed early in the course of AP in clinical practice, prophylactic antibiotics that were used in experimental studies in rats were always initiated early after induction of pancreatitis. The effectiveness of antibiotics initiated later is unknown.. The aim of this study was to compare the effectiveness of ciprofloxacin and meropenem initiated early versus later in the course of acute necrotizing pancreatitis (ANP) in rats.. 100 Sprague-Dawley rats were studied. ANP was induced in rats by intraductal injection of 3% taurocholate. Rats were divided randomly into five groups: group I rats received normal saline as a placebo, group II and IV rats received three times daily meropenem 60 mg/kg i.p. at 2 and 24 h, respectively and group III and V rats received twice daily ciprofloxacin 50 mg/kg i.p. at 2 and 24 h, respectively, after induction. At 96 h, all rats were killed for quantitative bacteriologic study. A point-scoring system of histological features was used to evaluate the severity of pancreatitis.. Meropenem and ciprofloxacin initiated 2 h after induction of pancreatitis significantly reduced the prevalence of pancreatic infection (p < 0.001 and p < 0.04, respectively) as compared to controls. Neither of the antibiotics initiated later during the course of AP caused a significant decrease in pancreatic infection in rats (p > 0.05). Although the rats treated early infected less frequently than the rats treated later, the comparison reached statistical significance only in the meropenem group (p < 0.02).. Early antibiotic treatment reduces pancreatic infection more efficiently than late antibiotic treatment in ANP in rats.

Topics: Animals; Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacterial Infections; Ciprofloxacin; Drug Administration Schedule; Male; Meropenem; Pancreatitis; Pancreatitis, Acute Necrotizing; Random Allocation; Rats; Rats, Sprague-Dawley; Thienamycins

Infectious complications are the major causes of morbidity and mortality in children receiving chemotherapy for malignant diseases. Granulocytopenia carries the risk of bacterial infection, and also, if prolonged, of fungal infection. The aim of this study was to evaluate the clinical effectiveness of meropenem in immunocompromised children in association with isolated bacteria from blood cultures and clinical background.. Retrospective study of all febrile episodes when meropenem was used in neutropenic children between January 1998 and December 2002 in the haemato-oncological units of the authors hospital. During the study period meropenem was used in 87 febrile events diagnosed in 55 patients (mean age 10 years 5 months), and 328 bacterial cultures were performed. Blood samples were taken from each patient with granulocytopenia (< 0.5 G/l) and fever (> or = 38 degrees C), prior to the start of any antibiotic therapy. For the microbiological process Bactec 9050 (Becton Dickinson) blood culture systems were used.. Microorganisms were detected and identified in 64 (19.5%) from the 328 hemocultures. There was a predominance of Gram-positive strains, 67% (43/64)--the most common bacteria being coagulase negative Staphylococcus (cnS). From the 87 periods in 43 cases (49.4%) the infection was documented microbiologically. In 16 additional cases the infection was proven clinically (based on the clinical course, laboratory and radiologic results) and 32.2% (28/87) of the febrile neutropenic episodes were considered to be fever of unknown origin. Meropenem was used in a mean dose of 60.8 (30-120) mg/kg/die, for 9.3 (2-24) days. The success rate of the meropenem therapy -excluding the proven fungal (n = 13) or cnS (n = 15) infections-was 72.9%. No severe side effects occurred in any regimens.. The results demonstrate that meropenem is effective and well-tolerated when used for the treatment of feverish neutropenic cancer children.

Topics: Adolescent; Adult; Anti-Infective Agents; Antineoplastic Agents; Bacteremia; Bacterial Infections; Child; Child, Preschool; Female; Fever; Humans; Infant; Male; Meropenem; Mycoses; Neoplasms; Neutropenia; Retrospective Studies; Thienamycins; Treatment Outcome

The safety profile of meropenem in the elderly (aged > 65 years, n = 843) and/or renally impaired (creatinine clearance < 51 ml/min, n = 436) was assessed by evaluating data from 26 phase III studies which compared the use of meropenem (0.5 or 1.0 g, i.v. every 8 h) with other antimicrobial agents in patients with bacterial infections. The overall pattern and frequency of adverse events following meropenem therapy in the elderly and/or renally impaired were similar to those in younger and/or non-renally impaired cohorts and to imipenem/cilastatin and injectable third generation cephalosporins. Both dosages of meropenem (0.5 and 1.0 g, i.v. every 8 h) were generally well tolerated. There was no clinically significant mean change in indicators of renal flux between baseline and the end of treatment in any patient sub-group. Importantly, meropenem-related seizures were rare (0.1%), even in patients with renal impairment. In summary, meropenem has an excellent safety profile and is therefore suitable for use in elderly and/or renally impaired patients.

Topics: Aged; Bacterial Infections; Humans; Kidney Failure, Chronic; Meropenem; Seizures; Thienamycins

The primary objective of the MYSTIC study is to monitor the performance of meropenem over a period of at least 3 years during which this carbapenem is prescribed in different hospital units thus allowing profiles to be established within individual hospitals. Monitoring is being carried out by assessing the antibiotic susceptibility of bacterial pathogens isolated from patients with a predominate problem of intraabdominal infections (IAI) and/or lower respiratory tract infections (LRTI), treated in specialist centres (haematology wards, the Intensive Care Unit [ICU], cystic fibrosis units) and non-specialised centres. Samples will be collected over each year and tested against meropenem and a set of comparators. The data obtained from the first year of the study (1997) come from 33 centres spread mainly throughout Europe but also in Israel and Mexico. The results shows that meropenem retains its broad spectrum and potency whilst there is evidence that the activity of comparator antibiotics is being eroded by a variety of resistance mechanisms. Data from subsequent years of the programme will determine whether these trends continue and will allow a series of individual centre profiles to be compiled and presented.

Topics: Bacteria; Bacterial Infections; Data Collection; Drug Resistance, Microbial; Hospital Departments; Humans; Meropenem; Microbial Sensitivity Tests; Thienamycins

Topics: Adolescent; Adult; Aged; Bacterial Infections; Female; Genital Diseases, Female; Humans; Meropenem; Middle Aged; Thienamycins

The use of meropenem, a new antibiotic from the carbapenemic family, was analyzed in the treatment of all types of serious infections in patients in critical condition. The global clinical response was satisfactory in 85.4% of the 178 assessable cases, with no significant differences being found in the form of treatment (monotherapy or combination therapy with aminoglycosides and/or glycopeptides) or in the type of infection treated, although the patients that received three or more antibiotics had more treatment failure. In the case of pneumonia, a better clinical response was observed with the use of monotherapy (38/40, 95% vs. 38/47, 80.8%, p = 0.049). The microbiological response was satisfactory in 72.7% of the 110 assessable cases. Initial pathogens persisted in just 8.2% of the cases, with superinfection in 12.7% and colonization in 6.4%. Differences relating to the form of treatment or the area of infection were not detected. The severity of the patient's condition influenced the choice of the form of meropenem treatment (monotherapy or combined therapy). Such factors as the patient's severity, the presence of hypotension or shock, and the need for mechanical ventilation were indicators for the use of two or more antibiotics. The severity also influenced the use of a larger average daily dose, as well as the length of treatment. Adverse reactions were detected in 6 of the 178 (3.37%) assessable patients, with 4 cases of nephrotoxicity, and 2 of hepatotoxicity. Global mortality was 14%, while infection-related mortality was 8.43%.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aminoglycosides; Anti-Bacterial Agents; APACHE; Bacterial Infections; Child; Child, Preschool; Critical Illness; Data Interpretation, Statistical; Drug Therapy, Combination; Female; Glycopeptides; Humans; Male; Meropenem; Middle Aged; Sepsis; Shock, Septic; Thienamycins

The in vitro antibacterial activity of meropenem and up to 26 other antibiotics was compared under routine conditions at 92 German centers from March to June 1995 with use of the agar diffusion method against 18632 recent isolates from ICU--hemato-oncology--and pediatric patients. Overall, meropenem was the most active drug exhibiting a higher activity against gram-negative aerobes than imipenem, but somewhat less active against staphylococci and enterocooci. The overall resistance rates of most antibiotics tested was higher compared to the recently published surveillance data of the Paul-Ehrlich-Society in Germany. The main reason for this discrepancy is the higher percentage of test strains which were recovered from intensive care unit patients in the present study. These data confirm similar results from the USA and underscore the pressing need for the implementation of a nationwide antimicrobial surveillance system which is risk-stratified by hospital size, ICU- versus non-ICU-patients, and body site from which the isolates are recovered.

Topics: Anti-Bacterial Agents; Bacteria, Aerobic; Bacterial Infections; beta-Lactam Resistance; Drug Resistance, Microbial; Germany; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Lactams; Meropenem; Thienamycins

Meropenem is a carbapenem antibiotic which is active against the majority of aerobic and anaerobic bacteria implicated in serious infections. Its therapeutic efficacy in a wide range of serious infections is similar to that of imipenem/cilastatin and standard combination drug regimens. Hence, meropenem is suitable for use as monotherapy. Although the acquisition cost of meropenem is likely to be higher than that of aminoglycoside- and metronidazole-containing combination regimens, the latter incur additional drug administration costs and potentially higher costs for treatment of adverse effects. In addition, aminoglycoside-containing regimens also incur assay and toxicity monitoring costs. Economic analyses are required to compare overall treatment costs with combination therapy and meropenem. Cost analyses indicate that the ability to give meropenem, but not imipenem/cilastatin, by rapid intravenous bolus injection results in lower drug administration costs than with the standard infusion method. More comprehensive pharmacoeconomic data on meropenem are required. However, assuming that meropenem and imipenem/cilastatin have similar acquisition costs, the option of administering meropenem by bolus injection and its lower epileptogenic potential at high dosages (thus permitting its use in meningitis) should be considered potentially important attributes when choosing a carbapenem antibiotic for inclusion in a hospital formulary.

Topics: Bacterial Infections; Cost-Benefit Analysis; Economics, Pharmaceutical; Humans; Meropenem; Thienamycins

The choice of an antibiotic for the treatment of a serious paediatric infection is generally a difficult problem. The arrival of Carbapenem resulted an important advance in the field of medicine due to its broad-spectrum, low incidence of resistances and good safety profile. Among Carbapenems, Meropenem introduction represents a progress because of its pharmacokinetics characteristics and blood-brain barrier penetration. Meropenem dosage depends on the patient weight, and the way of administration is potentially easier. Meropenem has been compared with the most used paediatric antimicrobial in controlled and randomised clinical trials, showing a high efficacy in the treatment of several infections (respiratory, urinary, intraabdominal, dermatological, septicemia) and in neutropenic and cystic fibrosis patients aged between one month and twelve years old. Meropenem is specially useful in the bacterial meningitis treatment because it penetrates into the cerebrospinal fluid of patients with inflamed meninges and reaches therapeutic concentrations, and because appearance of seizures is low. Adverse reactions produced by Meropenem show a poor incidence and its severity is usually mild. With regard to this characteristics, it can be concluded that Meropenem is an antimicrobial which efficacy and safety profiles guarantee its use in the treatment of severe paediatric infections.

Topics: Bacterial Infections; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Infant, Premature; Meningitis, Bacterial; Meropenem; Neutropenia; Respiratory Tract Infections; Thienamycins; Urinary Tract Infections

Intraabdominal infections are severe with a high morbidity and mortality which may be produced by multiple causes: perforation of the empty viscera, intestinal inflammatory processes, vascular pictures, abdominal traumatisms as a consequence of surgery. From a microbiologic point of view, different types of gram positive and gram negative aerobes such as anaerobe microorganisms or fungi may be isolated as causes. Polymicrobial infections are usually observed. The main treatment policy is to correctly eliminate the causing foci of the bacterial contamination whether surgically of by percutaneous drainage. Parallelly, it is essential for the surgeon to use appropriate antibiotic treatment. Meropenem, a carbapenem, has a wide spectrum antibacterial activity which cover gram positive and gram negative aerobes in addition to anaerobes leading to scarce adverse reactions. All the above leads meropenem to be a very effective alternative in both the treatment of these infections as monotherapy and for initiating empiric therapy.

Topics: Abdomen; Bacterial Infections; Cilastatin; Drug Combinations; Humans; Imipenem; Meropenem; Postoperative Complications; Thienamycins

The critical concentrations of sensitivity and resistance for meropenem versus anaerobic bacterias were analyzed. It is demonstrated the meropenem is a powerful inhibitor of the microorganisms of the Bacteroides groups (MIC90 < 1 mg/l), Prevotella > Porphyromonas, Fusobacterium, Veillonella, Clostridium perfringens is inhibited at a MIC < 0.06 mg/l. The MIC of meropenem versus C. difficile is 2 mg/l. They are also highly susceptible to the Propionibacterium, Peptostreptococcus and Peptococcus type microorganisms. Meropenem is comparable to imipenem and is more active than piperacillin, metronidazole and clindamycin. The mechanism of action and acquisition of resistance versus meropenem is evaluated and discussed. The percentage of highly resistant strains (MIC > 256 mg/l) isolated in the Hospital Gregorio Marañón in Madrid (Spain) is low (1.2%). The influence of pH on the in vitro activity of the carbapenémicos is also analyzed providing experimental data suggesting that meropenem maintains its bactericide activity more effectively in low pH conditions (5.6). Finally, the authors analyze the literature and the evidence reported regarding the use of meropenem in clinical practice, as a treatment of intraabdominal infections with a clinical response of 91%-100% and bacteriologic efficacy of 84%-95%.

Topics: Bacteria, Anaerobic; Bacterial Infections; Carbapenems; Cross Infection; Drug Resistance, Microbial; Humans; Hydrogen-Ion Concentration; Meropenem; Microbial Sensitivity Tests; Thienamycins

In order to evaluate antimicrobial activity of meropenem (MEPM), minimum inhibitory concentrations (MICs) of MEPM and control drugs were determined against clinical isolates in 1993. The results were as follows; 1. Antimicrobial activities of MEPM against Gram-positive bacteria were stronger than those of cephems (CEPs), were approximately equal to those of panipenem (PAPM), and were weaker than those of imipenem (IPM). 2. Carbapenems showed strong antimicrobial activities against Enterobacteriaccae, glucose non-fermentative Gram-negative rods and Bacteroides fragilis group that were multiple drug resistant including the third generation CEPs. Antimicrobial activities of MEPM against these organisms were stronger than those of IPM and PAPM. 3. MIC-ranges of MEPM against Enterobacteriaceae and Haemophilus influenzae were lower than those of IPM and PAPM. We observed that MEPM had better permeability into the cells of H. influenzae, higher affinities to 3 to 5 different penicillin-binding protein and high stability against beta-lactamase than those of IPM and PAPM.

Topics: Bacteria; Bacterial Infections; Carbapenems; Drug Resistance, Microbial; Humans; Meropenem; Thienamycins

The in vitro and in vivo antibacterial activities of sulopenem, a new penem, were evaluated in comparison with imipenem (IPM), meropenem (MEPM), ceftazidime (CAZ) and flomoxef (FMOX). Sulopenem had broad and potent antibacterial spectra against Gram-positive and Gram-negative bacteria, including Enterococcus faecalis, Proteus vulgaris, Morganella morganii, Enterobacter spp. and Citrobacter freundii. Sulopenem showed concentration-dependent bactericidal activities against Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae and Acinetobacter calcoaceticus. Morphological observation using phase-contrast microscope revealed that sulopenem induced spherical cell formation with E. coli and K. pneumoniae at lower concentrations and bacteriolysis at higher concentrations. Therapeutic efficacies of sulopenem against systemic infections in mice were almost equal to those of imipenem against Streptococcus pneumoniae. While its therapeutic efficacies were superior to those of meropenem, ceftazidime and flomoxef against S. aureus and S. pneumoniae, they were inferior to those of imipenem/cilastatin against S. aureus, K. pneumoniae and A. calcoaceticus.

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Ceftazidime; Cephalosporins; Gram-Negative Bacteria; Gram-Positive Bacteria; Imipenem; Lactams; Male; Meropenem; Mice; Thienamycins

Topics: Abdomen; Bacterial Infections; Drug Approval; Humans; Meningitis, Bacterial; Meropenem; Thienamycins; United States; United States Food and Drug Administration

Topics: Bacterial Infections; Humans; Meropenem; Thienamycins

Plasma meropenem concentration versus time data collected during a single dose, pharmacokinetic study in infants and children were analysed using the population pharmacokinetics program NONMEM. A total of 300 meropenem concentrations was obtained from 65 patients ranging from 2 months to 12 years of age; weighing between 3.7 and 46 kg. A two-compartment open pharmacokinetic model with a zero-order infusion over 30 min was fitted to the data. The most important determinant of meropenem clearance was the creatinine clearance but an additional improvement occurred when a nonlinear dependence upon age was included. The most important determinant of the volume of distribution in the central and peripheral compartments was the body weight. The distributional clearance showed a nonlinear dependence on body weight. Demographic factors other than weight and age were not found to be influential in the model. Both clearance and distributional clearance were markedly different in the younger (< 2 years) or lighter (< 10 kg) patients, respectively. Thereafter the parameter values slowly approached those found in adults. In this study, a mean of 4.6 samples per patient was used to provide information on the pharmacokinetics and the determinants of the pharmacokinetic variability in infants and children. The findings in the younger, lighter patients, if generally applicable, might have significance for the dosage recommendations for drugs with narrow therapeutic indices.

Topics: Age Factors; Analysis of Variance; Bacterial Infections; Body Weight; Carbapenems; Child; Child, Preschool; Creatinine; Humans; Infant; Meropenem; Models, Biological; Thienamycins

Topics: Bacteria; Bacterial Infections; Carbapenems; Clinical Trials as Topic; Drug Resistance, Microbial; Humans; Meropenem; Thienamycins

Meropenem is a new carbapenem antibiotic that is stable to human renal dehydropeptidase-I (DHP-I) and exhibits potent bactericidal activity against almost all clinically significant aerobic and anaerobic bacteria. Activity is achieved through rapid entry into bacteria, resisting hydrolysis by all serine-based beta-lactamases, both of chromosomal or plasmid origin, and high affinity for vital penicillin binding proteins. The antibacterial spectrum of meropenem has been investigated extensively in a world-wide programme of studies. The results from all of these studies are consistent and identify in vitro differences between meropenem and imipenem. Both agents demonstrate high activity against Gram-positive aerobes with meropenem slightly less active than imipenem but significantly more potent than imipenem against Haemophilus influenza, all Enterobacteriaceae and 2-4 fold more active against Pseudomonas aeruginosa and most other pseudomonas. The spectrum of carbapenems is superior to that of all other beta-lactams. This is achieved, in part, by stability to the chromosomal beta-lactamases which hydrolyse ceftazidime, cefotaxime and ceftriaxone and against which newer agents like cefpirome and cefepime are not fully stable. Meropenem is also stable to the new plasmid-mediated enzymes which are responsible for significant elevation of MIC's of all cephalosporins and penicillins. When tested against P. Aeruginosa which have become resistant to imipenem therapy, these strains remained susceptible to meropenem. The activity of meropenem against anaerobes is at least as potent as metronidazole and clindamycin. These impressive in vitro data have been the basis for an extensive clinical evaluation programme in many indications including infections caused by single or multiple pathogens.

Topics: Animals; Anti-Bacterial Agents; Bacteria, Aerobic; Bacteria, Anaerobic; Bacterial Infections; beta-Lactamases; Dipeptidases; Gram-Negative Bacteria; Gram-Positive Bacteria; Guinea Pigs; Humans; Imipenem; Meropenem; Mice; Microbial Sensitivity Tests; Molecular Structure; Penicillin Resistance; Penicillins; Thienamycins

The aim of the present study was to compare the in vitro activity of meropenem (ICI 194660, CAS 96036-03-2) with imipenem, metronidazole, clindamycin, ampicillin and ampicillin/sulbactam against a variety of anaerobic bacteria using an agar dilution method. 423 clinical isolates were tested belonging to 70 species of 15 anaerobic genera. They included Bacteroides fragilis (n = 62), Bacteroides thetaiotaomicron (n = 45), Prevotella bivia (n = 11), Fusobacterium nucleatum (n = 12), Clostridium perfringens (n = 15) and several rarely isolated species and genera, e.g. Selenomonas sputigena and Clostridium symbiosum. Bacteroides species were inhibited by meropenem at < or = 2.0 micrograms/ml, Clostridium species, including C. difficile, at < or = 4.0 micrograms/ml and all the other anaerobes at < or = 0.5 microgram/ml. Meropenem and imipenem were the most active substances, but often equal to, or only slightly better than, metronidazole, clindamycin or ampicillin/sulbactam, dependent on species. Meropenem was especially active against Bacteroides gracilis (MIC90 0.015 microgram/ml), Prevotella disiens (MIC90 0.03 microgram/ml), Fusobacterium nucleatum (MIC90 0.015 microgram/ml), Clostridium perfringens (MIC90 0.015 microgram/ml) and Veillonella parvula (MIC90 0.03 microgram/ml). The results obtained indicate that meropenem might be a useful adjunct to chemotherapy of anaerobic and mixed aerobic and anaerobic infections.

Topics: Ampicillin; Bacteria, Anaerobic; Bacterial Infections; Clindamycin; Humans; Imipenem; Meropenem; Metronidazole; Microbial Sensitivity Tests; Sulbactam; Thienamycins

Topics: Animals; Bacteria; Bacterial Infections; Escherichia coli; Meropenem; Mice; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Staphylococcus aureus; Thienamycins; Time Factors

The antibacterial activity of meropenem and comparative agents against approximately 1,000 anaerobes was determined using the disk dilution methods recommended by the National Committee for Clinical Laboratory Standards (NCCLS). The organisms represented 27 species of six genera and included the most common pathogens. Meropenem and imipenem were the most active drugs and were comparable in overall activity, generally exhibiting an MIC90 of < or = 1 micrograms/mL. In contrast, the MICs of cefoxitin, clindamycin, and metronidazole were 32, 16, and 2 micrograms/mL, respectively. Meropenem was two- to fourfold more active than imipenem against selected Bacteroides species, Clostridium species, and Fusobacterium species. At a concentration of 1 microgram/mL, meropenem was more active than imipenem against cefoxitin-resistant Bacteroides fragilis or Bacteroides thetaiotaomicron. At a concentration of < or = 0.5 micrograms/mL, meropenem was more active than imipenem against clindamycin-resistant Bacteroides distasonis. At a concentration of 2 micrograms/mL, meropenem was more active than imipenem against cefoxitin-resistant or clindamycin-resistant Clostridium difficile. Thus, meropenem's high potency and broad-spectrum activity against common, rare, and drug-resistant anaerobes confirms its utility in the treatment of mixed anaerobic and aerobic infections.

Topics: Anti-Bacterial Agents; Bacteria, Anaerobic; Bacterial Infections; Drug Resistance, Microbial; Humans; Imipenem; In Vitro Techniques; Meropenem; Microbial Sensitivity Tests; North America; Thienamycins

The antimicrobial activity of meropenem, a new parenteral carbapenem, was tested in vitro by an agar dilution method against 200 clinical isolates (gram-negative/positive aerobes and anaerobes). Meropenem was compared with imipenem, ceftazidime, cefotaxime, piperacillin, ciprofloxacin, gentamicin; and metronidazole, cefoxitin, chloramphenicol, clindamycin, vancomycin when appropriate. Meropenem and imipenem exhibited an extended spectrum of activity with low minimal inhibitory concentrations (MICs). Only one strain each of Enterococcus faecium and Pseudomonas (Xanthomonas) maltophilia were resistant. Of the carbapenems, imipenem was slightly more active against Enterococcus faecalis, Streptococcus agalactiae, and staphylococci, but meropenem was obviously more active against enterobacteriaceae and Clostridium perfringens. Both, meropenem and imipenem had similar activities towards Pseudomonas aeruginosa, Acinetobacter calcoaceticus, Streptococcus pyogenes and Bacteroides sp. All other antibiotics tested were less potent than the carbapenems with the exception of ciprofloxacin which generally exhibited similar antibacterial activities, except for anaerob microorganisms.

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Resistance, Microbial; Humans; In Vitro Techniques; Meropenem; Microbial Sensitivity Tests; Thienamycins

Meropenem (MEPM, SM-7338), a novel parenteral carbapenem antibiotic, was examined for its effect on intestinal flora in children. Seven children with infectious diseases (3 male and 4 female children of age's ranging from 4 months to 8 years and 9 months weighing from 7.3 to 23.0 kg) were treated with MEPM at doses ranging 10.3 to 40.5 mg/kg 3 or 4 times a day for 6 to 12 days. Before, during and after the treatment, identities and numbers of various bacteria contained in 1 g of feces were determined and fecal beta-lactamase activity and Clostridium difficile D-1 antigen were also assayed. Changes in fecal flora during MEPM treatment was somewhat different depending on cases. Regarding Enterobacteriaceae among aerobes, all of 7 cases exhibited moderate or pronounced reductions in Escherichia coli. Some of the cases exhibited the tendency to increase in Klebsiella oxytoca. Enterobacter cloacae and Citrobacter freundii. E. coli which was reduced during the treatment increased rapidly after the treatment in 5 out of 7 cases, and the initial bacterial counts were restored. Diverse strains were observed within the genus Enterococcus, while the overall bacterial counts of this genus exhibited the tendency to increase during the treatment. As a result, no significant change in total aerobe count was observed in any case except 1 case where Enterococcus count was somewhat reduced. Among anaerobes, major bacteria such as Bacteroides, Bifidobacterium, Eubacterium and Peptococcaceae exhibited tendencies to decrease in some cases during the antibiotic treatment. Two infants and 1 child exhibited significant decreases in total anaerobe counts. In most of the cases, such changes in major anaerobes were transient and bacterial counts recovered to their initial values rapidly after completion of the treatment. In no cases, glucose non-fermentative Gram-negative bacilli or fungus became predominant. Although C. difficile D-1 antigen was observed in 4 cases, its changes had no relationship with characteristics of feces. C. difficile was not detected in any of the cases. MEPM was detected in feces in 4 cases being treatment, in concentrations ranging from 0.35 to 66.0 micrograms/g. Fecal MEPM levels were very low except in 1 case in which beta-lactamase was negative. From these results, effects of MEPM on intestinal flora in children were relatively minor compared to other new beta-lactam drugs. However, a care should be taken to minimize diarrhea and bacterial turnover whe

Topics: Age Factors; Bacteria; Bacterial Infections; Child; Child, Preschool; Feces; Female; Humans; Infant; Infusions, Intravenous; Male; Meropenem; Thienamycins

We performed laboratory and clinical evaluation of meropenem (SM-7338, MEPM), a new carbapenem antibiotics, in pediatric field. Pharmacokinetics of MEPM was examined with 5 patients, at a dose of 10 mg/kg via 30 minutes drip infusion. Mean plasma concentrations at 30 minutes, 1, 1.5, 2.5, 3.5 and 5.5 hours after dose were 18.8, 6.97, 3.62, 1.14, 0.43 and 0.12 micrograms/ml, respectively, with a half life of 0.96 hour. The urine recovery rate in 6 hours was 70.4%. Clinical efficacy of MEPM was evaluated in 36 patients with various infectious diseases. MEPM was administered at doses ranging 9.5 to 30.6 mg/kg/dosage, 3 to 4 times a day, 21/3 to 10 days. Clinical effects were excellent in 24, good in 11, fair in 1, with an efficacy rate of 97.2%. Bacteriologically, all causative organisms except one each of Haemophilus influenzae and Salmonella enteritidis were eradicated, an eradication rate for Gram-positive and Gram-negative bacteria were 100% and 93.3%, respectively. No side effects were observed. Elevations of GOT and/or GPT were noted in 2 patients. From the above results, we believe that MEPM is a highly effective and safe drug for patients with various infectious diseases in pediatric fields.

Topics: Age Factors; Bacterial Infections; Child; Child, Preschool; Drug Evaluation; Female; Humans; Infusions, Intravenous; Male; Meropenem; Thienamycins

One gram of meropenem was administered as prophylaxis to patients undergoing endoscopic retrograde cholangiography (ERC) in a study of the bile pharmacokinetics of this agent. Twenty-four patients were evaluated and a single bile sample was collected from each one during ERC at different time intervals following intravenous infusion. Bile concentrations after the dose ranged from 0.7 to 25.7 mg/L (mean 11.1) and exceeded the MIC90s for the pathogens most commonly associated with biliary tract infections for up to 203 mins. The bile concentrations of 13 patients with biliary tree obstruction were compared with those of 11 patients without obstruction. Bile concentrations in excess of the MIC90s for the predominant pathogens were achieved in both groups; a positive correlation between meropenem bile concentration and the time of dose administration was demonstrable only for the obstructed group. ERC may be a useful technique for biliary pharmacokinetic studies.

Topics: Adult; Aged; Aged, 80 and over; Bacterial Infections; Bile; Cholangiopancreatography, Endoscopic Retrograde; Chromatography, High Pressure Liquid; Female; Humans; Male; Meropenem; Middle Aged; Thienamycins

We studied a newly developed carbapenem, meropenem (MEPM), and obtained the following results. 1. Pharmacokinetics of MEPM in pediatrics was examined in 3 patients. MEPM was injected intravenously at a dose of 16-22 mg/kg by drip infusion for 30 minutes, and its concentrations in serum and urine were determined using bioassay. The average peak value of serum levels of MEPM was 38.4 micrograms/ml and T1/2 beta of MEPM was 1.26 hours. The urinary recovery rate for the first 6 hours after administration was 65.6%. 2. Clinical evaluations of MEPM in pediatrics were done in 14 patients with ages ranging, 1 month to 14 years, with various bacterial infections. Excellent or good clinical responses were observed in all patients, and bacteriological eradication were obtained in 7 out of 8 cases. No serious side effects were observed in any cases, but 2 showed mild and transient GOT, GPT elevations.

Topics: Adolescent; Bacterial Infections; Child; Child, Preschool; Citrobacter freundii; Enterobacteriaceae Infections; Female; Humans; Infant; Male; Meropenem; Pseudomonas Infections; Staphylococcal Infections; Staphylococcus epidermidis; Thienamycins

Forty-five children were treated with meropenem (MEPM) and the clinical efficacy and side effects were evaluated. The ages of the patients ranged from 1 month to 9 years and their body weights from 5.2 to 25 kg. Doses given were 17.2-45.5 mg/kg every 6 to 8 hours for 2 to 24.5 days. Those patients who responded to the MEPM treatment included 15 children with pneumonia, 7 with pharyngitis, 3 with cervical lymphadenitis, 3 with cellulitis, 10 with urinary tract infections and 4 with other infections. Among 42 children, the results were excellent in 29, good in 12 and fair in 1. The drug was well tolerated, although slightly elevated serum concentrations of transaminases occurred in 5 patients, eosinophilia in 2 patients, and neutropenia in 1 patient among 45 patients examined. The pharmacokinetic studies on MEPM were done in 6 patients. Their ages ranged from 2 to 9 years and body weights from 14.5 to 23.2 kg. In 4 patients, plasma concentrations at the end of 30 minutes drip infusion of 20 mg/kg were 29.28 +/- 10.29 micrograms/ml and those 3 hours later were 0.49 +/- 0.26 micrograms/ml. Serum elimination half-lives of the drug were 0.66 +/- 0.12 hours in these patients. Excretion rates of this drug into urine in the first 6 hours after initiation of drug administration were 53 and 40% in 2 of these patients. In 2 patients with 35 and 44 mg/kg of drug administration, plasma concentrations were higher than those given 20 mg/kg of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Bacterial Infections; Bifidobacterium; Child; Child, Preschool; Enterobacteriaceae; Escherichia coli Infections; Feces; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Male; Meropenem; Staphylococcal Infections; Streptococcal Infections; Streptococcus pyogenes; Thienamycins

We studied the clinical efficacy of meropenem (SM-7338, MEPM), a new parenteral carbapenem beta-lactam antibiotic, in pediatric field. Thirteen patients with 2 months to 8 years and 8 months of ages, with acute infectious diseases were administered with doses at 39.3 to 76.7 mg/kg/day of MEPM intravenously. The diagnoses consisted of 7 respiratory tract infections, 1 sepsis, 2 orbital cellulitis, 1 parotid abscess, 1 lymphadenitis and 1 pyoderma. The clinical efficacy rate was 84.6% (11/13), and the bacteriological eradication rate was 71.4% (5/7). Clinical laboratory examinations revealed 1 patient with eosinophilia and another with anemia. No other side effects attributable to this drug were observed. It appears that MEPM is a useful antibiotic for moderate to severe acute bacterial infections in children.

Topics: Bacterial Infections; Child; Child, Preschool; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Meropenem; Moraxella catarrhalis; Neisseriaceae Infections; Pneumococcal Infections; Respiratory Tract Infections; Staphylococcal Infections; Thienamycins

Bacteriological and clinical studies have been performed on meropenem (MEPM, SM-7338), a newly developed carbapenem antibiotic, in the pediatric field. 1. Antibacterial activities of MEPM against 24 clinical isolates were determined. MEPM showed excellent activity against Gram-positive bacteria including Staphylococcus aureus and Gram-negative bacteria, especially Escherichia coli and Branhamella catarrhalis. Against Haemophilus influenzae, MEPM had a higher activity than imipenem and flomoxef, but had a lower activity than piperacillin and cefoperazone. 2. Clinical efficacies of MEPM were evaluated in 32 cases with bacterial infections. A poor efficacy was observed in 1 patient with phlegmon but excellent or good efficacies were obtained in other 31 patients with tonsillitis (1), pneumonia (17), UTI (12), or SSSS (1). The overall efficacy rate was 96.9%. All strains except 1 of S. aureus were eradicated by the administration of MEPM, and a high eradication rate of 95.8% (23 out of 24 strains) was obtained. 3. No side effects were observed in 35 evaluated cases. As abnormal laboratory test results, elevated GOT, elevated GPT, eosinophilia and neutropenia were noted in 4, 4, 4 and 2 patients, respectively. 4. Influences on blood coagulation parameters were studied. PIVKA II was elevated upon administration of MEPM in some cases, but no changes in ATT, TT, HPT or Fbg were observed during the treatment. Based on the above results, it has been concluded that MEPM is a safe and effective drug to use in the treatment of pediatric infections. The usual recommended dosage and administration should be 10 to 20 mg/kg of MEPM at a time, using intravenous drip infusion, 3 times a day.

Topics: Adolescent; Bacterial Infections; Child; Child, Preschool; Escherichia coli Infections; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Male; Meropenem; Moraxella catarrhalis; Neisseriaceae Infections; Pneumococcal Infections; Staphylococcal Infections; Streptococcal Infections; Streptococcus pyogenes; Thienamycins

Twenty-five children were treated with meropenem (MEPM, SM-7338) and the clinical efficacy and side effects were evaluated. Ages of the patients ranged from 9 months to 11 years. Dose levels of MEPM ranged from 50.4 to 108 mg/kg/day for 4 to 8 days. The 25 patients included 11 pneumonia cases, 4 bronchitis, 6 tonsillitis, 3 urinary tract infections and 1 gingivitis, and they were evaluated for the clinical efficacy of MEPM. Results were excellent in 13 and good in 12 patients. No side effects nor abnormal clinical laboratory test results were observed. The pharmacokinetics of MEPM was studied in 7 patients with ages ranging from 9 to 15 years. The mean plasma peak concentration of MEPM in 5 patients was 36.7 micrograms/ml after dosing 10 mg/kg, and that of 2 patients was 70.0 micrograms/ml after administering 20 mg/kg. These data showed that plasma concentrations of drug depended on dose levels. Average half-life values for the 2 groups (10 and 20 mg/kg) were 0.83 and 0.85 hour, respectively. Urinary recovery rates for the 2 groups (10 and 20 mg/kg) were 64.3% and 81.3%, respectively, in the first 5 hours after administration.

Topics: Absorption; Adolescent; Bacterial Infections; Child; Child, Preschool; Drug Evaluation; Female; Half-Life; Humans; Infant; Male; Meropenem; Thienamycins

A clinical study on a new carbapenem antibiotic, meropenem (MEPM), was carried out in acute pediatric infections. MEPM was administered to 8 patients including 3 patients with acute pneumonia, 2 with cervical lymphadenitis, 1 with acute tonsillitis, and 1 with cellulitis and 1 with sepsis. The overall efficacy rate was 100%. As an adverse reaction, diarrhea was observed in 1 patient. In clinical laboratory tests 1 patient was found to have S-GPT elevation which normalized after discontinuation of MEPM. MEPM appears to be effective and safe drug for pediatric acute infections.

Topics: Adolescent; Bacterial Infections; Child; Child, Preschool; Drug Evaluation; Female; Humans; Infant; Male; Meropenem; Microbial Sensitivity Tests; Thienamycins

Pharmacokinetic, bacteriological and clinical studies on meropenem (MEPM) were performed in children. The results are summarized as follows: 1. A total of 16 patients was treated with MEPM. Each dose was 20 mg/kg, and administration was made 3 times daily using 30-minute intravenous drip infusion for 5-28 days. Clinical efficacies of MEPM in 16 patients with bacterial infections (1 with purulent meningitis, 1 with suspected subdural abscess, 2 with suspected sepsis, 4 with pneumonia, 1 with acute maxillar sinusitis, 2 with cervical abscess, 1 with acute gastroenteritis, 2 with skin soft tissue infection and 2 with urinary tract infection) were evaluated as excellent in 7 patients, good in 8 patients and fair in 1 patient with an efficacy rate of 93.8%. Fourteen causative organisms found in 11 patients (Streptococcus pneumoniae in 4, Branhamella catarrhalis in 3, Staphylococcus aureus in 3, Group B Streptococcus in 1, Escherichia coli in 3) were all eradicated. No adverse reactions were observed in any of the 16 patients. 2. MICs of MEPM against 6 clinically isolated bacteria (B. catarrhalis 2, S. pneumoniae 3 and S. aureus 1) from children with bacterial infections were examined. MEPM showed good antibacterial activities. 3. Pharmacokinetic studies: Peak plasma concentrations of MEPM averaged 43.07 micrograms/ml (37.20-46.30 micrograms/ml) at dose of 20 mg/kg administered by 30-minute drip infusion. In the first 8 hours after administration, the urinary excretion rates of MEPM averaged 39.9% of the administered dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Bacteria; Bacterial Infections; Child; Child, Preschool; Drug Evaluation; Female; Half-Life; Humans; Infant; Male; Meropenem; Microbial Sensitivity Tests; Thienamycins

Pharmacokinetic and clinical evaluations of meropenem (SM-7338, MEPM) were carried out in pediatric patients. The following results were obtained. 1. After 30-minute intravenous drip infusion at a dose of 20 mg/kg, plasma concentrations of MEPM reached their peaks at the end of drip infusion with an average value of 48.8 +/- 3.64 micrograms/ml, and the average plasma half-life was 0.93 +/- 0.21 hour in the beta-phase. After 30-minute intravenous drip infusion at a dose of 10 mg/kg, the average peak plasma concentration was 27.7 +/- 4.33 micrograms/ml and the average plasma half-life was 0.78 +/- 0.20 hour. 2. Urinary excretion rates of MEPM after 30-minute intravenous drip infusion at doses of 20 and 10 mg/kg were 44.8 +/- 4.54% and 40.9 +/- 1.78%, respectively. 3. MEPM was administered to 13 cases (upper and lower respiratory infections, pneumonia and lymphadenitis) at daily doses between 60-90 mg/kg/day divided into 3 dosages using 30-minute intravenous drip infusion. Clinical responses were "excellent" in 12 patients, "good" in 1, hence an efficacy rate of 100% was obtained. 4. Bacteria identified in various disease cases included 12 strains of 5 species, and the eradication rate was 100%. 5. No side effects were observed in any children. Laboratory test results showed abnormalities in 2 cases with elevations of GOT and GPT. These results suggest that MEPM may be a very useful and safe drug for the treatment of pediatric infections.

Topics: Bacterial Infections; Child; Child, Preschool; Drug Evaluation; Female; Half-Life; Humans; Infant; Infusions, Intravenous; Male; Meropenem; Thienamycins

We studied clinical effects of meropenem (MEPM, SM-7338), a newly developed parenteral carbapenem beta-lactam drug, and following results were obtained. The patients were administered with 16-20 mg/kg of MEPM every 8 hours using 1 hour drip infusion. 1. Clinical effects of MEPM were studied in 10 children with various infectious diseases: 1 with acute bronchitis, and 2 each with acute tonsillitis, acute bronchopneumonia, acute pneumonia, acute urinary infection, and 1 with pertussis pneumonia. The case of pertussis pneumonia later developed bronchiolitis obliterans, hence a steroid and gamma-globulin were used. This case was excluded from the clinical evaluation. The efficacy rate was 100% (9/9), and the bacteriological eradication rate was 100% (6/6). 2. No side effects were noted. Clinical laboratory test values were investigated in 10 patients. There was a case of abnormal laboratory test findings with mild elevations of liver functions such as GOT, GPT, and gamma-GTP. These abnormalities disappeared in 1 week after the end of therapy.

Topics: Bacterial Infections; Child; Child, Preschool; Drug Evaluation; Female; Humans; Infant; Liver; Liver Function Tests; Male; Meropenem; Thienamycins

Pharmacokinetic and clinical studies on meropenem (MEPM, SM-7338), a new developed carbapenem, were performed and the following results were obtained. 1. Absorption/excretion: Pharmacokinetics of MEPM was studied in 9 children using doses of 10 mg/kg and 20 mg/kg by a 30 minute-drip infusion. Peak plasma levels and plasma half-lives of the 2 doses were 28.4 and 43.0 micrograms/ml, and 0.70 and 0.80 hours, respectively. Their urinary recovery rates were 42.5 to 67.6% and 29.9 to 62.6%, respectively. Cerebrospinal fluid levels and penetration rates of MEPM in a patient with purulent meningitis were 0.66 to 4.01 micrograms/ml and 1.6 to 12.2%, respectively. 2. Clinical study: Forty-nine patients were treated with MEPM at doses exceeding 100 mg/kg/day with purulent meningitis and 30 to 60 mg/kg/day with other infections. MEPM gave "excellent" or "good" responses in 48 cases, an efficacy rate of 98.0%. Only one patient with subdural abscess showed fair response. Diarrhea and rash were observed in 1 case each. Abnormal laboratory test results were noted in 5 patients including elevation of GOT, GPT and eosinophils. In no cases the treatment had to be discontinued.

Topics: Absorption; Adolescent; Bacterial Infections; Child; Child, Preschool; Drug Evaluation; Female; Half-Life; Humans; Infant; Liver; Male; Meningitis, Bacterial; Meropenem; Thienamycins

A new carbapenem antibiotic, meropenem (MEPM), was evaluated for its safety and efficacy in 33 infants and children. MEPM was effective in all the 32 evaluable cases including 4 cases of bacterial meningitis and 5 cases of Pseudomonas aeruginosa infections. The mean half life of plasma concentrations of MEPM was 0.84 +/- 0.09 hours after 30 minutes intravenous drip infusion. Mild diarrhea (2 cases), transient elevation of transaminases (8 cases), and transient eosinophilia (2 cases) were associated with the MEPM therapy, but none of them was problematic. These data suggest that MEPM is safe in infants and children and could be one of the therapeutic agents for severe infections or infections in compromised hosts.

Topics: Adolescent; Bacterial Infections; Child; Child, Preschool; Drug Evaluation; Female; Half-Life; Humans; Infant; Male; Meningitis, Bacterial; Meropenem; Pseudomonas Infections; Thienamycins

Laboratory and clinical studies on meropenem (MEPM), a new carbapenem antibiotic, were carried out in the field of pediatrics. The results obtained are summarized below. 1. The antibacterial activities of MEPM against clinically isolated organisms in our department were generally high. 2. After 30 minutes intravenous drip infusion of MEPM at a dose of 20 mg/kg to 2 children, the mean peak plasma level of MEPM was 32.7 micrograms/ml at the end of infusion with a mean half-life of 1.45 hours. The mean cumulative urinary recovery rate in the first 6 hours after infusion was 43.6%. 3. Fifteen patients with various bacterial infections were treated with MEPM. The clinical efficacy rate was 100% and the bacteriological efficacy rate was 95.2%. 4. No side effects were observed except in 1 case of mild diarrhea. Some abnormal laboratory test results were obtained, but they were mild with slight elevations of GOT and GPT in 2 cases.

Topics: Bacteria; Bacterial Infections; Child; Child, Preschool; Drug Evaluation; Female; Half-Life; Humans; Infant; Male; Meropenem; Microbial Sensitivity Tests; Thienamycins

We have carried out clinical studies on meropenem (MEPM, SM-7338), the results are summarized as follows. Treatment with MEPM was made in 13 cases of pediatric bacterial infections including 9 cases of pneumonia and 2 cases of colitis and 1 case each of purulent tonsillitis, and pharyngitis. Results obtained were excellent in 10 cases, good in 3 cases. No significant side effects due to the drug were observed in any cases, except in 1 case each of eosinophilia, elevated gamma-GTP, elevated total bilirubin and elevated GPT.

Topics: Adolescent; Bacterial Infections; Child; Child, Preschool; Drug Evaluation; Female; Humans; Infant; Liver; Male; Meropenem; Pneumonia; Thienamycins

The pharmacokinetics and the clinical effectiveness of meropenem (MEPM) were examined in the field of pediatrics. The results are summarized as follows. 1. A 4-year-6-month-old girl with suppurative meningitis (Haemophilus influenzae) was treated by intravenous drip infusion of MEPM in a daily dose of 29 mg/kg which was divided into 4 dosages, each dosage being infused over 30 minutes, and the drug concentration in cerebrospinal fluid was determined. Upon completion of infusion on the 2nd day of treatment, the drug concentration was 2.52 micrograms/ml, which corresponded to 3.6% of the drug concentration in the blood. 2. MEPM was used in 10 patients, including 3 with suppurative lymphnoditis, 2 with staphylococcal scalded skin syndrome (SSSS) and 1 each with pneumonia, suppurative meningitis, suppurative knee arthritis, facial phlegmon and pyelonephritis. The daily doses ranged from 30 to 117.6 mg/kg, divided into 3 to 4 dosages and administered via intravenous drip infusion over 30 minutes. Clinical responses were evaluated as very good in 7 patients, good in 2 patients and fair in 1 patient, with an efficacy rate of 90%. 3. Isolated pathogens were 2 strains of Staphylococcus aureus, 1 strain of Klebsiella pneumoniae and 3 strains of Haemopilus influenzae. All of the 6 strains were eradicated, with an eradication rate of 100%. 4. In the safety evaluation, none of the patients was observed to have any side effects. Furthermore, no abnormal variations were found in laboratory test data possibly attributable to administration of MEPM.

Topics: Bacterial Infections; Child; Child, Preschool; Drug Evaluation; Female; Humans; Infant; Infusions, Intravenous; Male; Meningitis, Haemophilus; Meropenem; Thienamycins

The in vitro and in vivo antibacterial activities of meropenem were compared with those of imipenem, ceftazidime, flomoxef, cefuzonam and cefotiam. Meropenem showed a broad antibacterial spectrum against clinical isolates of Gram-positive and Gram-negative bacteria. Against Gram-negative bacteria, with the exception of Acinetobacter calcoaceticus, meropenem exhibited the most potent activity among the drugs tested. It inhibited all 330 strains of Enterobacteriaceae at 0.78 mg/l. Meropenem was sensitive against several cephem-resistant strains of Enterobacteriaceae. Against Pseudomonas aeruginosa, meropenem was four-fold more active than imipenem and eight-fold more active than ceftazidime, with an MIC90 of 0.78 mg/l. The therapeutic effect of meropenem on systemic infection in mice was ten to twenty-fold less than that of imipenem against Staphylococcus aureus, Streptococcus pyogenes and Streptococcus pneumoniae. However, meropenem was as effective as imipenem on infections of Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, Acinetobacter calcoaceticus and Pseudomonas aeruginosa. Meropenem was eliminated from mice plasma two-fold faster than imipenem, with a plasma half-life of 7.6 min. From the above results the authors concluded that meropenem is a promising drug for clinical use.

Topics: Animals; Bacterial Infections; Cephalosporins; Gram-Negative Bacteria; Gram-Positive Bacteria; Imipenem; Male; Meropenem; Mice; Mice, Inbred Strains; Microbial Sensitivity Tests; Thienamycins

The activity of meropenem was determined against 350 strains of anaerobic bacteria by an agar dilution method. It was compared with those of piperacillin, cefoxitin, imipenem, clindamycin, metronidazole and chloramphenicol. Meropenem and imipenem were the most active agents tested. On the basis of these results, meropenem appears to be a promising antimicrobial agent for anaerobic infections and warrants further clinical investigation.

Topics: Anti-Bacterial Agents; Bacteria, Anaerobic; Bacterial Infections; Bacteroides fragilis; Carbapenems; Clostridium; Clostridium perfringens; Fusobacterium; Humans; Meropenem; Microbial Sensitivity Tests; Propionibacterium acnes; Thienamycins

SM-7338, a new carbapenem antibiotic, was demonstrated to have potent antibacterial activity against a broad spectrum of aerobes, including Staphylococcus aureus, beta-hemolytic streptococci, Streptococcus pneumoniae, Haemophilus influenzae, Neisseria spp., members of the family Enterobacteriaceae, Pseudomonas spp., and gram-positive and gram-negative anaerobes in a collection of 1,102 unselected clinical isolates. At a concentration of 0.5 micrograms/ml, SM-7338 inhibited 90% of these strains. The spectrum of activity of ceftazidime and cefotaxime was more limited, and many of the Enterobacteriaceae and Pseudomonas spp. were resistant to these agents, piperacillin, or gentamicin. A collection of ofloxacin-resistant strains was inhibited by SM-7338 or imipenem at 4 micrograms/ml. SM-7338 was more active than metronidazole and clindamycin against anaerobes. Of the carbapenems, imipenem had greater activity against staphylococci but SM-7338 was much more active against Haemophilus, Branhamella, and Neisseria spp. and all genera of Enterobacteriaceae tested. The MIC of SM-7338 for 90% of these strains ranged from less than or equal to 0.008 to 0.13 micrograms/ml. When tested against 124 strains of Pseudomonas aeruginosa, SM-7338 inhibited 76% at 0.5 microgram/ml but imipenem inhibited only 15% at this concentration. Both carbapenems exhibited similar activities against Bacteroides spp., but SM-7338 was more active than imipenem against Clostridium spp. The MBC of SM-7338 was most commonly the same as or twice the MIC. SM-7338 and imipenem showed excellent activities against bacteria elaborating chromosome- or plasmid-mediated beta-lactamases, including those conferring resistance to broad-spectrum cephalosporins. The activity of SM-7338 was generally unaffected by the culture medium used, pH, 25% human serum, and inoculum size, but the susceptibility of Xanthomonas maltophilia was medium dependent.

Topics: Bacteria; Bacterial Infections; beta-Lactamases; Ceftazidime; Dipeptidases; Humans; Imipenem; Meropenem; Plasmids; Thienamycins

Meropenem and comparative antibiotics were evaluated in five models of infection. All antibiotics were administered parenterally; imipenem was used in combination with cilastatin but meropenem and other agents were given alone. Generalized infections in mice caused by Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Serratia marcescens, Proteus mirabilis or Pseudomonas aeruginosa all responded to low doses of meropenem or imipenem. Immunocompromised mice infected with Ps. aeruginosa responded to slightly higher doses of meropenem or gentamicin but required four to seven times the dose of other agents. Those given a greater challenge of Ps. aeruginosa were treated most successfully by meropenem. Treatment with meropenem, imipenem or ceftazidime caused significant reductions of E. coli in the urinary bladder and kidneys of mice challenged per urethram. Infection with Ps. (Xanthomonas) maltophilia localized to the subcutaneous neck tissue of guinea pigs was also treated successfully. Lung infections caused by Ps. aeruginosa in guinea pigs were treated effectively by meropenem, imipenem, and ceftazidime at the dose of 10 mg/kg but only meropenem eradicated bacteria from all the tissues examined. These results demonstrate that meropenem has excellent antibacterial activity in vivo in both normal and immunocompromised animals and in some models of infection is superior to imipenem.

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Carbapenems; Escherichia coli Infections; Guinea Pigs; Immunosuppression Therapy; Lung Diseases; Male; Meropenem; Mice; Mice, Inbred Strains; Microbial Sensitivity Tests; Pseudomonas Infections; Respiratory Tract Infections; Thienamycins; Urinary Tract Infections

The in-vitro activity of meropenem against anaerobic bacteria was assessed by an agar dilution procedure. MICs were measured for 449 clinical isolates and reference strains. Meropenem showed excellent activity against both Gram-negative anaerobes, including Bacteroides fragilis (MIC90 0.25 mg/l), and Gram-positive anaerobes. The MIC90 for Clostridium perfringens was 0.01 mg/l. Meropenem had comparable activity to imipenem against Gram-negative anaerobes but was more active than imipenem against clostridia, including C. difficile (MIC90 2 mg/l compared with 8 mg/l). Meropenem was more active against anaerobes than was cefoxitin, metronidazole or clindamycin.

Topics: Anti-Bacterial Agents; Bacteria, Anaerobic; Bacterial Infections; Carbapenems; Clindamycin; Gram-Negative Anaerobic Bacteria; Gram-Positive Bacteria; Humans; Imipenem; Meropenem; Metronidazole; Microbial Sensitivity Tests; Thienamycins

Meropenem, a new parenteral carbapenem, was tested in vitro by an agar-dilution method against 373 standard strains (aerobes and anaerobes) and against nine expanded-spectrum beta-lactamase-producing strains and their transconjugants (5 CTX-1, 2 CAZ-1, 2 CAZ-2). Meropenem was compared with methicillin, imipenem, piperacillin, cefoxitin, cefotaxime, ceftazidime, gentamicin, chloramphenicol, clindamycin, ciprofloxacin, vancomycin and metronidazole. Meropenem and imipenem exhibited an extended spectrum of activity, with low MICs. Only methicillin-resistant staphylococci, and Pseudomonas (Xanthomonas) maltophilia were resistant. Of the carbapenems, imipenem was more active against methicillin-susceptible staphylococci, streptococci and Enterococcus faecalis, but meropenem was markedly more active against all the Enterobacteriaceae and some pseudomonads. Both had similar activity against Ps. aeruginosa, Acinetobacter spp. and anaerobes. The carbapenem MICs were very low for Enterol acteriaceae producing the expanded-spectrum beta-lactamases. Against CTX-1-producing strains resistant to cefotaxime and ceftazidime and against CAZ-1 or CAZ-2-producers highly resistant to ceftazidime meropenem was the most active, with MICs lower (0.03-0.12 mg/l) than those of imipenem (0.06-0.5 mg/l), for wild type producers and their transconjugants.

Topics: Bacteria; Bacteria, Anaerobic; Bacterial Infections; beta-Lactamases; Carbapenems; Enterobacteriaceae; Enterobacteriaceae Infections; Gram-Positive Bacteria; Humans; Meropenem; Microbial Sensitivity Tests; Thienamycins

MICs of meropenem were determined for a wide range of common bacteria of clinical importance. For Enterobacteriaceae, Aeromonas spp., Haemophilus influenzae, Branhamella catarrhalis, Neisseria gonorrhoeae, Gardnerella vaginalis, Campylobacter coli/jejuni, beta-haemolytic streptococci and anaerobes other than Clostridium difficile, MICs were almost always within the range 0.002-0.5 mg/l. The activity of meropenem for these organisms was always greater than that of imipenem and piperacillin, and was similar to that of ceftazidime and cefotaxime except that strains resistant to these latter, and to piperacillin, were usually sensitive to imipenem and meropenem. Meropenem was also active against most non-fermentative Gram-negative bacilli, with MICs in the range 0.12-4 mg/l but Pseudomonas (Xanthomonas) maltophilia was often resistant, as it was to all the other drugs tested. Staphylococci, Strreptococcus pneumoniae and other alpha-haemolytic streptococci were usually more sensitive to imipenem than to meropenem, but even methicillin-resistant staphylococci were sensitive to both drugs (MICs less than 4 mg/l). Enterococci were also less sensitive to meropenem than to imipenem, and Enterococcus faecium was invariably highly resistant to all the drugs tested except ciprofloxacin, which had marginal activity. Results for Ps. maltophilia and Haem. influenzae were affected by media used for sensitivity testing.

Topics: Bacteria; Bacterial Infections; Carbapenems; Culture Media; Enterobacteriaceae; Gram-Negative Aerobic Bacteria; Gram-Positive Bacteria; Humans; Meropenem; Microbial Sensitivity Tests; Thienamycins; United Kingdom

The in-vitro activity of meropenem, a new parenteral carbapenem, was compared with that of imipenem, ceftazidime, cefotaxime, piperacillin, gentamicin and, where appropriate, other antibiotics against recent clinical isolates and characterized beta-lactamase producers. MICs were determined by a standard agar dilution procedure and two inocula (10(4) and 10(6) cfu) were used throughout. Meropenem inhibited 90% of isolates of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, indole-positive Proteus spp., Enterobacter spp., Serratia marcescens and Providencia stuartii at less than or equal to 0.25 mg/l and was four- to 16-fold more active than imipenem against these species. Against the enteric pathogens Salmonella typhi, Shigella sonnei, Yersinia enterocolitica and Campylobacter jejuni, meropenem was four- to eight-fold more active than imipenem, inhibiting all isolates at less than or equal to 0.03 mg/l. Meropenem was also more active than imipenem against Haemophilus influenzae (MIC90 0.06 mg/l) but had similar activity against the Bacteroides fragilis group (MIC90 0.25 mg/l), against Pseudomonas aeruginosa (MIC90 2 mg/l) and against streptococci. Imipenem was four-fold more active than meropenem against Acinetobacter spp. and two- to eight-fold more active against all species of staphylococci tested. Both meropenem and imipenem were inactive against Ps. (Xanthomonas) maltophilia.

Topics: Bacteria; Bacterial Infections; Canada; Carbapenems; Drug Resistance, Microbial; Humans; Meropenem; Microbial Sensitivity Tests; Thienamycins

For clinical isolates the MICs of meropenem were significantly lower than the MICs of imipenem, especially against Pseudomonas aeruginosa. Furthermore, meropenem was bactericidal for Pseudomonas spp., including Ps. (Xanthomonas) maltophilia, and staphylococci, with MBCs on average only two-fold above the respective MICs. The bactericidal activity was confirmed by killing curve assays. Strains with high meropenem MICs (greater than or equal to 8 mg/l) were killed by a combination of the carbapenem and amikacin, with kinetics that indicated synergism between the two antimicrobial agents.

Topics: Amikacin; Bacteria; Bacterial Infections; Carbapenems; Drug Synergism; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Meropenem; Microbial Sensitivity Tests; Mycobacterium avium Complex; Thienamycins