meropenem and Infections

Meropenem exhibits time-dependent antimicrobial activity and prolonged infusion (PI) (extended infusion or continuous infusion, EI or CI) of meropenem can better achieve pharmacodynamics target when comparing with intermittent bolus (IB). However, the clinical outcomes between two groups remain inconclusive.. To evaluate current published literatures by meta-analysis to ascertain whether PI of meropenem can improve clinical outcomes.. Medline, Cochrane database and EMBASE were searched. Randomized control trails (RCT) and observational studies which compared the clinical outcomes of PI and IB groups were included and evaluated for quality. The data of studies were extracted and meta-analysis was performed using Revman 5.3 software.. Six RCTs and 4 observation studies with relatively high quality were included in this analysis. Compared to IB group, PI group had a higher clinical success rate (odd ratio 2.10, 95% confidence interval 1.31-3.38) and a lower mortality (risk ratio 0.66, 95% confidence interval 0.50-0.88). The sensitivity analysis showed the results were stable.. PI of meropenem was associated with a higher clinical improvement rate and a lower mortality. It is recommended for patients with severe infection or infected by less sensitive microbial.

Topics: Anti-Bacterial Agents; Drug Administration Schedule; Humans; Infections; Infusions, Intravenous; Meropenem; Observational Studies as Topic; Randomized Controlled Trials as Topic; Severity of Illness Index; Time Factors; Treatment Outcome

Several reports have shown marked heterogeneity of antibiotic pharmacokinetics (PK) in patients admitted to ICUs, which might potentially affect outcomes. Therefore, the pharmacodynamic (PD) parameter of the efficacy of β-lactam antibiotics, that is, the time that its concentration is above the bacteria minimal inhibitory concentration (T > MIC), cannot be safely extrapolated from data derived from the PK of healthy volunteers.. We performed a full review of published studies addressing the PK of intravenous β-lactam antibiotics given to infected ICU patients. Study selection comprised a comprehensive bibliographic search of the PubMed database and bibliographic references in relevant reviews from January 1966 to December 2010. We selected only English-language articles reporting studies addressing β-lactam antibiotics that had been described in at least five previously published studies. Studies of the PK of patients undergoing renal replacement therapy were excluded.. A total of 57 studies addressing six different β-lactam antibiotics (meropenem, imipenem, piperacillin, cefpirome, cefepime and ceftazidime) were selected. Significant PK heterogeneity was noted, with a broad, more than twofold variation both of volume of distribution and of drug clearance (Cl). The correlation of antibiotic Cl with creatinine clearance was usually reported. Consequently, in ICU patients, β-lactam antibiotic half-life and T > MIC were virtually unpredictable, especially in those patients with normal renal function. A better PD profile was usually obtained by prolonged or even continuous infusion. Tissue penetration was also found to be compromised in critically ill patients with septic shock.. The PK of β-lactam antibiotics are heterogeneous and largely unpredictable in ICU patients. Consequently, the dosing of antibiotics should be supported by PK concepts, including data derived from studies of the PK of ICU patients and therapeutic drug monitoring.

Topics: Anti-Bacterial Agents; beta-Lactams; Cefepime; Cefpirome; Ceftazidime; Cephalosporins; Critical Illness; Humans; Imipenem; Infections; Meropenem; Piperacillin; Thienamycins

The aim of this study was to evaluate the efficacy and safety of meropenem plus amikacin compared with piperacillin-tazobactam plus netilmicin for initial empirical antibiotic treatment of high-risk febrile neutropenia in children with cancer. Patients with hematologic malignancy (leukemia or stage III/IV non-Hodgkin lymphoma) who presented with fever and neutropenia (ANC < 500/mm3) and patients with solid tumors who presented with fever and severe neutropenia (ANC < 100/mm3) were considered to be at high risk and eligible for this study. In this prospective study, 33 patients with 50 febrile neutropenic episodes received i.v. neropenem (20 mg/kg every 8 h) plus amikacin (15 mg/kg/d in 2 divided doses) (in 31 episodes) or piperacillin/tazobactam (100 mg/4 mg/kg every 8 h) plus netilmicin (7 mg/kg every 24 h) (in 19 episodes). Clinical response was determined at 72 h and at completion of the therapy. The groups were comparable in terms of age, sex, initial ANC, use of growth factors, and classification of the infections. An infection was documented microbiologically in 12 episodes (39%) in the meropenem plus amikacin group and in 8 episodes (42%) in the piperacillin/tazobactam plus netilmicin group. Of the 22 microbiological isolates, 37% were gram-positives, 45% were gram-negatives, and 18% were fungi. Most of the clinically documented infections were of lower respiratory tract, gastrointestinal mucosa, or urinary tract origin. The mean duration of neutropenia was 9 days in both groups. Fever persisted for 1-30 days (mean 3 vs. 5 days). The success rate with initial empiric therapy was 52% in the meropenem plus amikacin and 42% in the piperacillin/tazobactam plus netilmicin group, respectively (p = .5). Total success rate (with or without modification) was 97% vs. 90% in the episodes. Three patients died due to infection (1 vs. 2 patients). No major adverse effects were observed in each group. Empirical therapy with meropenem plus amikacin or piperacillin/tazobactam plus netilmicin for high-risk febrile neutropenia is equally effective and safe in pediatric cancer patients.

Topics: Amikacin; Anti-Bacterial Agents; Drug Therapy, Combination; Fever; Fungi; Gram-Negative Bacteria; Gram-Positive Bacteria; Hematologic Neoplasms; Humans; Infections; Meropenem; Neoplasms; Netilmicin; Neutropenia; Penicillanic Acid; Piperacillin; Tazobactam; Thienamycins

The objective of this study was to evaluate the clinical efficacy, dose and tolerability of treatment with meropenem in children with moderate to severe infections. An observational, multicenter, prospective study of 258 children was conducted. Two cohorts (81 under the age of 1 year, and 177 aged 1 to 14 years) were followed up at 48 hours, at the end of treatment, and 1 week later. Nosocomial infections were present in 37.5% of the children aged 1 to 14 years, and in 79.7% of those younger than 1 year of age (p < 0.001). A total of 79% received 20 mg/kg/8 h of meropenem; 43.8% received combination treatment with antifungal agents, glycopeptides or both. At 48 hours, 77.4% showed a clinical improvement; 74.2% were clinically cured at the end of treatment, and 77.5% at 1 week after the end of treatment. The clinical outcome was similar in both groups. Eradication or negative control cultures were found in 76.8%, with no difference between the two age groups. No major adverse events were reported, except for one case of pancytopenia after 2 days of treatment in a patient with a transplanted liver.

Topics: Adolescent; Child; Child, Preschool; Female; Hospitalization; Humans; Infant; Infections; Male; Meropenem; Prospective Studies; Severity of Illness Index; Thienamycins

The efficacy of two carbapenems, imipenem/cilastatin (I/C, 1.5 g daily) versus meropenem (3 g daily) in intra-abdominal infections was assessed in a recent multicenter randomized clinical trial. The aim of this article is to perform a cost-effectiveness analysis as in real-world practice according to the findings of this clinical trial.. A decision tree was used to estimate the clinical outcomes and direct costs of treating intra-abdominal infections using the two carbapenems from the perspective of the Italian National Health Service (INHS) or a private insurance company (PIC).. In a population of 30,000 patients with intra-abdominal infections in Italy, it was estimated that 97 potential deaths/year could be avoided if these patients were treated with I/C versus meropenem. In addition, from the perspective of INHS, the total costs of treatment were estimated as ITL 106,874 million and 134,042 million for I/C and meropenem, respectively. In favor of the PIC point of view, the total costs were estimated as ITL 110,500 million and 135,899 million for I/C and meropenem, respectively.. The treatment of intra-abdominal infections with I/C is shown to be more effective (97 deaths avoided/year) and less costly than with meropenem (with a saving of ITL 27,168 and 25,399 million/year for INHS and PIC, respectively).

Topics: APACHE; Cilastatin; Cost-Benefit Analysis; Decision Trees; Drug Combinations; Female; Health Care Costs; Humans; Imipenem; Infections; Male; Meropenem; Middle Aged; Peritoneal Diseases; Protease Inhibitors; Thienamycins

Most of the hospitalized patients are on a number of drugs for comorbidities and/or to prevent nosocomial infections. This necessitates a careful consideration of drug interactions not only to avoid possible toxicities but also to reach the highest efficiency with drug treatment. We aimed to investigate drug interactions related to systemic antibiotic use and compare three different databases to check for drug interactions while characterizing the main differences between medical and surgical departments.. This point prevalence study covered data on 927 orders for patients hospitalized between June 3 and 10, 2018 in Ankara University Hospitals. Systemic antibiotic use and related drug interactions were documented using UptoDate, Drugs, and Medscape and comparisons between the departments of medical and surgical sciences were made.. The number of orders, or the number of drugs or antibiotics per order were not different between the medical and surgical sciences departments. A total of 1335 antibiotic-related drug interactions of all levels were reported by one, two, or all three databases. UptoDate reported all common and major interactions. Pantoprazole was the most commonly prescribed drug and appeared in 63% of all orders. Among 75 different molecules, ceftriaxone and meropenem were the two most prescribed antibiotics by the surgical and medical departments, respectively.. A dramatic variance existed amongst antibiotics prescribed by different departments. This indicated the requirement for a centralized role of an infectious diseases specialist. Especially for the hospitalized patient, prophylactic coverage with at least one antibiotic brought about a number of drug interactions. A precise evaluation of orders in terms of drug interactions by a clinical pharmacist (currently none on duty) will reduce possible drug-related hazards.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Ceftriaxone; Child; Comorbidity; Cross Infection; Cross-Sectional Studies; Databases, Factual; Drug Interactions; Drug Prescriptions; Hospital Departments; Hospitals, University; Humans; Infections; Meropenem; Middle Aged; Pantoprazole; Pharmaceutical Preparations; Practice Patterns, Physicians'; Prevalence; Turkey

Antimicrobial resistance is one of the greatest public health threats worldwide. The improper prescription of antibiotics is one factor that promotes antibiotic resistance. Access to antimicrobial surveillance data is essential when assessing the pattern and appropriateness of antimicrobial prescriptions in hospitals and for the establishment of an antimicrobial stewardship program. This study aimed to describe the rate of antimicrobial use and the pattern of prescriptions in a tertiary care pediatric unit in Thailand.. A point prevalence survey on antimicrobial use was conducted monthly between January and June 2016, using standardized tools. The survey included all inpatient pediatric beds and identified all children receiving antimicrobial treatment on the day of the survey.. The study included 644 children, 43.3% of whom received antimicrobial treatment during hospitalization. In general wards, the rate of antimicrobial prescriptions was 37.2%; in oncology wards it was 47.0%; in intensive care units it was 38.7%, and in surgical wards it was 67.7%. Meropenem was the most prescribed antimicrobial in the general wards (24.5%) and intensive care units (28.6%), whereas antipseudomonas was the most commonly prescribed antimicrobial in the oncology ward (26.6%). For the surgical ward, the most prescribed antimicrobial was third-generation cephalosporin for both prophylaxis and treatment (39.0%). The most common reason for antimicrobial use was the treatment of infections.. Nearly half of hospitalized children received at least one antimicrobial. This was comparable with other pediatric tertiary care centers, although the high use of meropenem was different. This study provides important baseline information on antimicrobial use in a large tertiary-care pediatric unit and could lead to a nationwide survey in the future.

Topics: Adolescent; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotic Prophylaxis; Antimicrobial Stewardship; Cephalosporins; Child; Child, Preschool; Cross-Sectional Studies; Drug Prescriptions; Drug Resistance, Microbial; Drug Utilization; Hospitalization; Humans; Infant; Infections; Meropenem; Prevalence; Surveys and Questionnaires; Tertiary Care Centers; Thailand

The widespread prevalence of metallo-β-lactamase (MβL)-mediated pathogens has seriously caused a loss of efficacy of carbapenem antibacterials, the last resort for the treatment of severe infectious diseases. The development of effective MβL inhibitors is an ideal alternative to restore the efficacy of carbapenems. Here we report that Ru complexes can irreversibly inhibit clinically relevant B1 subclass MβLs (NDM-1, IMP-1 and VIM-2) and potentiate meropenem efficacy against MβL-expressing bacteria in vitro and in a mice infection model. The Cys208 residue at the Zn(ii)-binding site and Met67 residue at the β-hairpin loop of an enzyme active pocket are critical for Ru complexes to inhibit NDM-1, which was verified by enzyme kinetics, thermodynamics, NDM-1-C208A mutation and MALDI-TOF-MS analysis. This study will undoubtedly aid efforts to develop metal-based MβL inhibitors in combination with carbapenems to deal with the clinical crisis of carbapenem-resistant E. coli harboring MβLs.

Topics: Amino Acid Sequence; Animals; Anti-Bacterial Agents; beta-Lactamase Inhibitors; beta-Lactamases; Binding Sites; Carbapenems; Coordination Complexes; Disease Models, Animal; Drug Development; Drug Resistance, Microbial; Escherichia coli; Infections; Meropenem; Mice; Microbial Sensitivity Tests; Prospective Studies; Protein Binding; Protein Conformation; Ruthenium; Structure-Activity Relationship; Zinc

The post-marketing surveillance of meropenem (Meropen®) administered over 2g/day for serious infectious diseases was conducted between August 2011 and June 2013 to evaluate safety and efficacy under actual clinical use. There were 382 and 322 evaluable cases for safety and efficacy respectively, of 399 case cards collected from 87 institutions. In safety analysis, the incidence of adverse drug reactions (ADRs) associated with use of meropenem (including abnormal laboratory findings) was 19.1% (73/382 cases), and the main ADRs were hepatic function abnormal, aspartate aminotransferase increased, alanine aminotransferase increased, liver disorder, and diarrhoea, which were similar to these observed in the post-marketing surveillances of meropenem conducted before. In efficacy analysis, the efficacy was 73.6% (237/322 cases), which is as same as 71.4% (3214/4504 cases) of post-marketing surveillance of meropenem conducted after first approval under 2 g/day for infectious diseases. These results confirmed meropenem (Meropen®) is one of the useful antimicrobial agents for serious infectious diseases.

Topics: Anti-Bacterial Agents; Chemical and Drug Induced Liver Injury; Diarrhea; Humans; Infections; Meropenem; Product Surveillance, Postmarketing; Thienamycins

Topics: Anti-Infective Agents; Drug Repositioning; Drug Substitution; Foscarnet; Humans; Infections; Meropenem; Thienamycins; Trimethoprim, Sulfamethoxazole Drug Combination

Meropenem is an effective β-lactam antibiotic that is frequently used to treat serious infections in both intensive care unit (ICU) and febrile neutropenic hematology/oncology (Hem/Onc) patients. Studies suggest that to be effective, meropenem concentrations must be maintained above the inhibitory concentrations for the majority of a dosing interval. However, the pharmacokinetics (PK) of meropenem seem to differ in critically ill patients compared with healthy or less ill subjects used to select labeled dosing regimens.. This study was designed to investigate meropenem PK in critically ill patients and to see how often standard dosing regimens produced adequate plasma concentrations. A secondary objective was to investigate how achieved concentrations were related to outcomes (morbidity and mortality) in these patients.. Meropenem plasma concentrations over time were measured using a high pressure liquid chromatography assay in febrile Hem/Onc and ICU patients who were treated with standard meropenem dosing schedules. Outcomes such as fever control and survival were assessed in these patients and compared with individual meropenem PK data and with recommended target concentrations.. A total of 25 subjects including 10 febrile Hem/Onc and 15 ICU patients with a variety of serious illnesses and baseline renal function were studied. Mean peak concentrations were less variable than were pre-dose concentrations. Post peak and trough concentrations were often below recommended minimum inhibitory concentrations. Both clearance and volumes of distribution were greater than reported in less ill subjects, only in part explained by increased renal clearance. Therefore, serum concentrations often did not exceed recommended concentration targets even for moderately sensitive organisms. Inadequate concentrations were especially common in the mostly ill, febrile neutropenic Hem/Onc subjects and seemed to explain at least some therapeutic failures. Conversely, drug accumulation occurred in ICU subjects with decreased renal function.. Standard meropenem dosing regimens were inadequate in many critically ill febrile, neutropenic Hem/Onc, and septic ICU patients. These data suggest a role for meropenem concentration monitoring in such patients.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Critical Illness; Female; Humans; Infections; Intensive Care Units; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Prospective Studies; Retrospective Studies; Thienamycins

The case of a 57-year-old woman who suffered a fall is presented. After a polymethyl malacrylate revision cranioplasty, she presented with signs, symptoms, and intraoperative findings consistent with postneurosurgical infection. Dural foreign-body reaction was diagnosed, and parenteral antibiotic therapy was discontinued successfully.

Topics: Anti-Bacterial Agents; Brain Diseases; Craniotomy; Female; Foreign Bodies; Foreign-Body Reaction; Humans; Infections; Meropenem; Middle Aged; Postoperative Complications; Thienamycins; Time Factors; Vancomycin

Procalcitonin (PCT) is an early marker of bacterial infection but little is known about its value in neutropenic allogeneic bone marrow transplant (BMT) recipients. We collected plasma from 12 recipients of T-cell-depleted HLA-matched related BMT recipients who had been treated preemptively with meropenem from the day after BMT for at least 15 days. PCT and C-reactive protein (CRP) concentrations were determined on BMT days 1, 5, 8, 12, and 15, and their relationship to inflammatory events (IE), including mucositis, microbiologically and clinically defined infections, acute graft-versus-host disease (GVDH), and unexplained fever, was then determined. The PCT concentrations were all low and never exceeded 4 microg/liter, unlike CRP concentrations, which spanned the full range up to 350 mg/liter. All patients had mucositis, and there was no significant difference between PCT concentrations associated with mucositis alone and those associated with an additional IE on BMT days 1 to 12. However, on BMT day 15, the mean concentrations of PCT were 0.37 +/- 0.05 microg/liter for the 10 patients that had an additional IE, compared with 0.11 +/- 0.03 microg/liter for the 2 patients with mucositis only (P = 0.012), and GVHD rather than infection was involved in six cases. PCT was also not a sensitive marker of gram-positive bacteremia or pulmonary aspergillosis. Thus, PCT is of little value in discriminating infections from other inflammatory complications that occur following allogeneic BMT.

Topics: Adult; Biomarkers; Bone Marrow Transplantation; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Female; Graft vs Host Disease; Humans; Infections; Inflammation; Male; Meropenem; Protein Precursors; Thienamycins; Transplantation, Homologous