meropenem and Cross-Infection

Treatment of Acinetobacter baumannii has become a medical challenge because of the increasing incidence of multiresistant strains and a lack of viable treatment alternatives. This systematic review attempts to investigate the changes in resistance of A. baumannii to different classes of antibiotics in Iran, with emphasis on the antimicrobial activity of polymyxin B (PMB) and colistin (COL). Biomedical databases were searched for English-published articles evaluating microbiological activity of various antimicrobial agents, including PMB and COL. Then, the available data were extracted and analyzed. Thirty-one studies, published from 2009 to 2015, were identified which contain data for 3,018 A. baumannii clinical isolates. With the exception of polymyxins and tigecycline (TIG), there was a high rate of resistance to various groups of antibiotics, including carbapenems. The minimum inhibitory concentration (MIC) ranges for PMB and COL on A. baumannii isolates tested were 0.12-64 μg/ml and 0.001-128 μg/ml, respectively. Polymyxins showed adequate activity with no significant trends in the resistance rate during most of the study period. The incidence of resistance to TIG was estimated low from 2% to 38.4% among the majority of A. baumannii. The present systematic review of the published literatures revealed that multidrug-resistant (including carbapenem-resistant) strains of A. baumannii have increased in Iran. In these circumstances, the older antibiotics, such as COL or PMB, preferably in combination with other antimicrobials (rifampicin, meropenem), could be considered as the therapeutic solution against the healthcare-associated infections. Designing rational dosage regimens for patients to maximize the antimicrobial activity and minimize the emergence and prevalence of resistance is recommended.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Humans; Iran; Meropenem; Microbial Sensitivity Tests; Minocycline; Polymyxin B; Rifampin; Thienamycins; Tigecycline

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

The prevalence of antibiotic-resistant bacteria continues to increase, particularly in patients in the intensive care unit with nosocomial pneumonia. The intention of this review is to provide an overview of severe nosocomial pneumonia, carbapenems and the problem of bacterial resistance to antimicrobial agents. Attention was focused on the efficacy, safety and pharmacodynamics of imipenem, meropenem, ertapenem and doripenem. Issues on the impact of appropriate empiric antibiotic therapy for nosocomial pneumonia patients considered at risk for resistant pathogens are discussed. Critical decision making regarding the use of carbapenems for treating severe nosocomial pneumonia requires careful consideration of the four Ds of optimal antimicrobial therapy: right Drug, right Dose, De-escalated to pathogen-directed therapy and right Duration of therapy.

Topics: Anti-Bacterial Agents; beta-Lactams; Carbapenems; Cross Infection; Doripenem; Drug Administration Schedule; Drug Resistance, Multiple, Bacterial; Ertapenem; Humans; Imipenem; Meropenem; Patient Selection; Pneumonia, Bacterial; Respiratory Tract Infections; Severity of Illness Index; Thienamycins; Treatment Outcome

We report a case of a nosocomial Capnocytophaga spp. DF-1 pneumonia in an intubated 56-year-old man following coronary artery bypass grafting. We review Capnocytophaga spp., including the infections they produce and antibiotic susceptibilities.

Topics: Anti-Bacterial Agents; Capnocytophaga; Coronary Artery Bypass; Cross Infection; Gram-Negative Bacterial Infections; Humans; Immunocompetence; Male; Meropenem; Middle Aged; Pneumonia, Bacterial; Postoperative Complications; Respiration, Artificial; Thienamycins

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Cross Infection; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Humans

The comparative effectiveness and safety of carbapenems with other beta-lactams and fluoroquinolones for the empirical treatment of patients with hospital-acquired pneumonia remains controversial. In the present study, a meta-analysis of 12 relevant randomised controlled trials was performed. Overall, carbapenems were associated with lower mortality than fluoroquinolones or beta-lactams, alone or in combination with aminoglycosides (odds ratio 0.72, 95% confidence interval 0.55-0.95). There was no difference between the compared antibiotics regarding treatment success (1.08, 0.91-1.29), microbiological success (1.04, 0.72-1.50) or development of adverse effects (0.81, 0.46-1.43). In the subset of patients with Pseudomonas aeruginosa pneumonia, carbapenems were associated with lower treatment success (0.42, 0.22-0.82) and lower eradication of P. strains (0.50, 0.24-0.89). Carbapenems are equivalent to fluoroquinolones or beta-lactams, alone or in combination with aminoglycosides, for the empirical treatment of immunocompetent adult patients with hospital-acquired pneumonia. However, there is limited evidence, based predominantly on unblinded randomised controlled trials, that carbapenems are associated with lower mortality than the comparators; this association was not observed in a subset analysis of randomised controlled trials with a high methodological quality score. In patients with Pseudomonas aeruginosa pneumonia, carbapenems are associated with worse outcomes than the comparators.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aminoglycosides; beta-Lactams; Carbapenems; Cross Infection; Drug Resistance, Multiple; Drug Therapy, Combination; Fluoroquinolones; Humans; Immunocompetence; Intensive Care Units; Meropenem; Pneumonia, Bacterial; Pseudomonas Infections; Randomized Controlled Trials as Topic; Respiration, Artificial; Survival Rate; Thienamycins; Treatment Outcome

A rare case of prosthetic valve endocarditis from Acinetobacter spp occurring 9 months postoperatively is described. The patient initially received empirical therapy against pathogens commonly associated with prosthetic valve endocarditis, but his condition did not improve. Identification of bacteremia due to Acinetobacter spp was not attributed to any of the classic nosocomial factors such as presence of a catheter or a recent invasive procedure. The patient did well with an intravenous regimen of meropenem and tobramycin instituted according to susceptibility testing. Physicians should be aware of this rare association of a nosocomial pathogen such as Acinetobacter spp with prosthetic valve endocarditis occurring long after the initial cardiothoracic procedure.

Topics: Acinetobacter; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Cross Infection; Echocardiography, Transesophageal; Endocarditis, Bacterial; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Male; Meropenem; Reoperation; Thienamycins; Tobramycin

Pseudomonas aeruginosa is one of the leading gram-negative organisms associated with nosocomial infections. The increasing frequency of multi-drug-resistant Pseudomonas aeruginosa (MDRPA) strains is concerning as efficacious antimicrobial options are severely limited. By searching MEDLINE from January 1966-February 2005 and relevant journals for abstracts, we reviewed the frequency, risk factors, and patient outcomes of MDRPA nosocomial infections in critically ill patients, determined the available antimicrobial therapies, and then provided recommendations for clinicians. The definition of MDRPA was established as isolates intermediate or resistant to at least three drugs in the following classes: beta-lactams, carbapenems, aminoglycosides, and fluoroquinolones. Reported rates of MDRPA varied from 0.6-32% according to geographic location and type of surveillance study. Risk factors for MDRPA infection included prolonged hospitalization, exposure to antimicrobial therapy, and immunocompromised states such as human immunodeficiency virus infection. Emergence of MDRPA isolates during therapy was reported in 27-72% of patients with initially susceptible P. aeruginosa isolates. Patients with severe MDRPA infections should be treated with combination therapy, consisting of an antipseudomonal beta-lactam with an aminoglycoside or fluoroquinolone rather than aminoglycoside and fluoroquinolone combinations, to provide adequate therapy and improve patient outcomes. Synergy has been observed when resistant antipseudomonal drugs were combined in vitro against MDRPA with successful clinical application reported in two centers. Colistin with adjunctive therapy, such as a beta-lactam or rifampin, may be a useful agent in MDRPA when antimicrobial options are limited, but patients should be monitored closely for toxicities associated with this agent. Standardization of terminology for MDRPA isolates is needed for consistency and comparability of surveillance and institutional reports. Clinical studies are needed to identify risk factors for MDRPA development and to determine the economic impact of these infections, as well as to determine the most efficacious antimicrobial regimens and duration of therapy to maximize outcomes in the treatment of MDRPA infections.

Topics: Anti-Bacterial Agents; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Meropenem; Polymyxin B; Pseudomonas aeruginosa; Pseudomonas Infections; 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 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

Increasing prevalence of multidrug-resistant gram-negative organisms has led to a rise in clinically significant infections with these organisms and an increasing therapeutic dilemma. We present a case of a neurosurgical patient who developed ventriculoperitoneal shunt-associated ventriculitis due to ceftazidime-resistant Klebsiella pneumoniae susceptible to cefepime, imipenem, meropenem, and polymyxin B only. Successful management was accomplished by removal of the shunt and therapy with systemic meropenem and intraventricular polymyxin B. Rapid cerebrospinal fluid (CSF) sterilization occurred, with CSF bactericidal titers of 1:32 to 1:128. Polymyxin B should be considered as adjunctive therapy for life-threatening multidrug-resistant gram-negative infections. Prior literature on use of intrathecal polymyxin B in therapy for meningitis supports its potential efficacy.

Topics: Anti-Bacterial Agents; Ceftazidime; Cerebrospinal Fluid; Cross Infection; Drug Resistance, Microbial; Female; Humans; Injections, Intravenous; Injections, Intraventricular; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Middle Aged; Polymyxin B; 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

The acquisition of antibiotic-resistance genes by virtually all major bacterial pathogens is currently a world-wide phenomenon. This problem is especially evident in nosocomial lower respiratory tract infections (LRTI). Carbapenems like imipenem and meropenem offer interesting antibacterial activities and beta-lactamase-stability, as well as adequate pharmacokinetic characteristics, to cover most of the pathogens involved in moderate to severe community-acquired and nosocomial LRTI. In contrast to imipenem, meropenem is not nephrotoxic and offers the advantage of greater stability against renal dehydropeptidase-I, so no concomitant application of an enzyme inhibitor is necessary. Meropenem can also be given by intravenous infusion or injection without the nausea and vomiting often associated with the administration of imipenem/cilastatin. Preliminary results with meropenem in LRTI show excellent cure rates and good tolerance for this new carbapenem.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ceftazidime; Cilastatin; Clinical Trials as Topic; Community-Acquired Infections; Cross Infection; Drug Therapy, Combination; Female; Humans; Imipenem; Male; Meropenem; Middle Aged; Respiratory Tract Infections; Thienamycins

A clinical, multicentre, randomised, comparative study in 283 adult hospitalized patients was carried out to assess efficacy of meropenem in the treatment of complicated and non-complicated urinary tract infections, in comparison to imipenem/cilastatin. Both antibiotics were administered intramuscularly, at a dose of 500 mg bid. The two groups were homogeneous, as regards the distribution between male and female, the mean age of the patients, the severity of infections and the mean duration of treatment. Clinical results were assessed at the end of therapy and follow-up (4-6 weeks). Bacteriological results were assessed at 5-9 days post-treatment and at follow-up. As regards clinical and bacteriological results patients showing a satisfactory response rate were compared, at the end of the treatments using a Chi square test. With both treatments high satisfactory clinical and bacteriological response rates were seen. As regards clinical satisfactory responses (97% of meropenem assessable patients versus 90% of imipenem/cilastatin assessable patients), there was a statistically significant difference in favor of meropenem. The bacteriological outcome was successful (eradication) for 75% of assessable patients in each group. Most failures were seen in the complicated infections, even when pathogens usually sensitives to carbapenemics were initially isolated. Safety was good with both drugs; no withdrawals in any group of treatment was seen because of side effects. The local tolerance of meropenem was globally rated as good.

Topics: Adult; Aged; Carbapenems; Chi-Square Distribution; Cilastatin; Cross Infection; Female; Humans; Imipenem; Male; Meropenem; Middle Aged; Protease Inhibitors; Thienamycins; Urinary Tract Infections

As resistance to antibiotics is increasing among microbes, rational use of these drugs is important both in the community and in hospitals. Many infections with resistant microorganisms may be fatal. For a long time, carbapenems have been the last resort for treatment of resistant microorganisms. Unfortunately, resistance to these drugs is increasing. It appears that use of higher doses of antibiotics may help in some cases. However, the potential harm caused by higher doses is a problem. In this primary study, higher doses of meropenem, a common carbapenem, were found to be safe.

Topics: Anti-Bacterial Agents; Cross Infection; Humans; Meropenem; Pilot Projects; Sepsis

Treatment of aspiration pneumonia is an important problem due to aging of populations worldwide. However, the effectiveness of cefepime in aspiration pneumonia has not yet been evaluated.. To compare the clinical efficacy and safety of cefepime and meropenem in patients with moderate-to-severe aspiration pneumonia.. In this open-label, randomized study, either cefepime 1 g or meropenem 0.5 g was administered intravenously every 8 h to patients with moderate-to-severe community-acquired or nursing-home acquired pneumonia at risk for aspiration for an average of 10.5 days. The primary outcome was the clinical response rate at the end of treatment (EOT) in the validated per-protocol (VPP)-population. Secondary outcomes were clinical response during treatment (days 4 and 7) and at the end of study (EOS) in the VPP-population, and survival at day 30 in the modified intention-to-treat (MITT)-population.. There was no difference between the groups in the primary or secondary outcomes or safety. Significant improvement was observed in each group on day 4.. Cefepime is as effective and safe as meropenem in the treatment of moderate-to-severe aspiration pneumonia.. UMIN000001349.

Topics: Administration, Intravenous; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cefepime; Community-Acquired Infections; Cross Infection; Female; Humans; Male; Meropenem; Pneumonia, Aspiration; Prospective Studies; Severity of Illness Index; Treatment Outcome

Optimal antimicrobial drug exposure in the lung is required for successful treatment outcomes for nosocomial pneumonia. Little is known about the intrapulmonary pharmacokinetics (PK) of meropenem when administered by continuous infusion (CI). The aim of this study was to evaluate the PK of two dosages of meropenem (3 g vs 6 g/day by CI) in the plasma and epithelial lining fluid (ELF) in critically ill patients with nosocomial pneumonia.. Thirty-one patients (81% male, median (IQR) age 72 (22) years) were enrolled in a prospective, randomized, clinical trial. Sixteen patients received 1 g/8 h and 15 2 g/8 h by CI (8 h infusion). Plasma and ELF meropenem concentrations were modeled using a population methodology, and Monte Carlo simulations were performed to estimate the probability of attaining (PTA) a free ELF concentration of 50% of time above MIC (50% fT>MIC), which results in logarithmic killing and the suppression of resistance in experimental models of pneumonia.. An increase in the dose of meropenem administered by CI achieved a higher exposure in the plasma and ELF. The use of the highest licensed dose of 6 g/day may be necessary to achieve an optimal coverage in ELF for all susceptible isolates (MIC ≤ 2 mg/L) in patients with conserved renal function. An alternative therapy should be considered when the presence of microorganisms with a MIC greater than 2 mg/L is suspected.. The trial was registered in the European Union Drug Regulating Authorities Clinical Trials Database (EudraCT-no. 2016-002796-10). Registered on 27 December 2016.

Topics: Aged; Anti-Bacterial Agents; Cross Infection; Female; Healthcare-Associated Pneumonia; Humans; Infusions, Intravenous; Male; Meropenem; Middle Aged; Prospective Studies

In vitro models showing synergism between polymyxins and carbapenems support combination treatment for carbapenem-resistant Gram-negative (CRGN) infections. We tested the association between the presence of in vitro synergism and clinical outcomes in patients treated with colistin plus meropenem.. This was a secondary analysis of AIDA, a randomized controlled trial comparing colistin with colistin-meropenem for severe CRGN infections. We tested in vitro synergism using a checkerboard assay. Based on the fractional inhibitory concentration (ΣFIC) index for each colistin-meropenem combination, we categorized results as synergistic, antagonistic or additive/indifferent. The primary outcome was clinical failure at 14 days. Secondary outcomes were 14- and 28-day mortality and microbiological failure.. The sample included 171 patients with infections caused by carbapenem-resistant Acinetobacter baumannii (n = 131), Enterobacteriaceae (n = 37) and Pseudomonas aeuruginosa (n = 3). In vitro testing showed synergism for 73 isolates, antagonism for 20 and additivism/indifference for 78. In patients who received any colistin plus meropenem, clinical failure at 14 days was 59/78 (75.6%) in the additivism/indifference group (reference category), 54/73 (74.0%) in the synergism group (adjusted odds ratio (aOR) 0.76, 95% CI 0.31-1.83), and 11/20 (55%) in the antagonism group (aOR 0.77, 95% CI 0.22-2.73). There was no significant difference between groups for any secondary outcome. Comparing the synergism group to patients treated with colistin monotherapy, synergism was not protective against 14-day clinical failure (aOR 0.52, 95% CI 0.26-1.04) or 14-day mortality (aOR1.09, 95% CI 0.60-1.96).. In vitro synergism between colistin and meropenem via checkerboard method did not translate into clinical benefit.

Topics: Aged; Aged, 80 and over; Carbapenems; Colistin; Cross Infection; Drug Resistance, Bacterial; Drug Synergism; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Pneumonia, Bacterial; Treatment Outcome

Nosocomial pneumonia due to antimicrobial-resistant pathogens is associated with high mortality. We assessed the efficacy and safety of the combination antibacterial drug ceftolozane-tazobactam versus meropenem for treatment of Gram-negative nosocomial pneumonia.. We conducted a randomised, controlled, double-blind, non-inferiority trial at 263 hospitals in 34 countries. Eligible patients were aged 18 years or older, were undergoing mechanical ventilation, and had nosocomial pneumonia (either ventilator-associated pneumonia or ventilated hospital-acquired pneumonia). Patients were randomly assigned (1:1) with block randomisation (block size four), stratified by type of nosocomial pneumonia and age (<65 years vs ≥65 years), to receive either 3 g ceftolozane-tazobactam or 1 g meropenem intravenously every 8 h for 8-14 days. The primary endpoint was 28-day all-cause mortality (at a 10% non-inferiority margin). The key secondary endpoint was clinical response at the test-of-cure visit (7-14 days after the end of therapy; 12·5% non-inferiority margin). Both endpoints were assessed in the intention-to-treat population. Investigators, study staff, patients, and patients' representatives were masked to treatment assignment. Safety was assessed in all randomly assigned patients who received study treatment. This trial was registered with ClinicalTrials.gov, NCT02070757.. Between Jan 16, 2015, and April 27, 2018, 726 patients were enrolled and randomly assigned, 362 to the ceftolozane-tazobactam group and 364 to the meropenem group. Overall, 519 (71%) patients had ventilator-associated pneumonia, 239 (33%) had Acute Physiology and Chronic Health Evaluation II scores of at least 20, and 668 (92%) were in the intensive care unit. At 28 days, 87 (24·0%) patients in the ceftolozane-tazobactam group and 92 (25·3%) in the meropenem group had died (weighted treatment difference 1·1% [95% CI -5·1 to 7·4]). At the test-of-cure visit 197 (54%) patients in the ceftolozane-tazobactam group and 194 (53%) in the meropenem group were clinically cured (weighted treatment difference 1·1% [95% CI -6·2 to 8·3]). Ceftolozane-tazobactam was thus non-inferior to meropenem in terms of both 28-day all-cause mortality and clinical cure at test of cure. Treatment-related adverse events occurred in 38 (11%) of 361 patients in the ceftolozane-tazobactam group and 27 (8%) of 359 in the meropenem group. Eight (2%) patients in the ceftolozane-tazobactam group and two (1%) in the meropenem group had serious treatment-related adverse events. There were no treatment-related deaths.. High-dose ceftolozane-tazobactam is an efficacious and well tolerated treatment for Gram-negative nosocomial pneumonia in mechanically ventilated patients, a high-risk, critically ill population.. Merck & Co.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Cephalosporins; Cross Infection; Female; Humans; Male; Meropenem; Middle Aged; Pneumonia, Bacterial; Tazobactam; Treatment Outcome

Spontaneous bacterial peritonitis (SBP) is a common, life-threatening complication of liver cirrhosis. Third-generation cephalosporins have been considered the first-line treatment of SBP. In 2014, a panel of experts suggested a broader spectrum antibiotic regimen for nosocomial SBP, according to the high rate of bacteria resistant to third-generation cephalosporins found in these patients. However, a broader-spectrum antibiotic regimen has never been compared to third-generation cephalosporins in the treatment of nosocomial SBP. The aim of our study was to compare meropenem plus daptomycin versus ceftazidime in the treatment of nosocomial SBP. Patients with cirrhosis and nosocomial SBP were randomized to receive meropenem (1 g/8 hours) plus daptomycin (6 mg/kg/day) or ceftazidime (2 g/8 hours). A paracentesis was performed after 48 hours of treatment. A reduction in ascitic fluid neutrophil count <25% of pretreatment value was considered a treatment failure. The primary outcome was the efficacy of treatment defined by the resolution of SBP after 7 days of treatment. Thirty-two patients were randomized and 31 were analyzed. The combination of meropenem plus daptomycin was significantly more effective than ceftazidime in the treatment of nosocomial SBP (86.7 vs. 25%; P < 0.001). Ninety-day transplant-free survival (TFS) was not significantly different between the two groups. In the multivariate analysis, ineffective response to first-line treatment (hazard ratio [HR]: 20.6; P = 0.01), development of acute kidney injury during hospitalization (HR: 23.2; P = 0.01), and baseline mean arterial pressure (HR: 0.92; P = 0.01) were found to be independent predictors of 90-day TFS.. The combination of meropenem plus daptomycin is more effective than ceftazidime as empirical antibiotic treatment of nosocomial SBP. Efficacy of the empirical antibiotic treatment is a strong predictor of 90-day survival in patients with nosocomial SBP.

Topics: Adult; Aged; Anti-Bacterial Agents; Ascites; Ceftazidime; Cross Infection; Daptomycin; Drug Therapy, Combination; Female; Hospital Mortality; Hospitals, University; Humans; Italy; Liver Cirrhosis; Male; Meropenem; Middle Aged; Multivariate Analysis; Peritonitis; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Prospective Studies; Risk Assessment; Severity of Illness Index; Survival Analysis; Thienamycins; Treatment Outcome; Young Adult

Patients admitted to intensive care unit (ICU) with Klebsiella pneumoniae infections are characterized by high mortality. The aims of the present study were to investigate the population pharmacokinetics parameters and to assess the probability of target attainment of meropenem in critically ill patients to provide information for more effective regimens.. Twenty-seven consecutive patients were included in the study. Meropenem was administered as 3-h intravenous (i.v.) infusions at doses of 1-2 g every 8 or 12 h. Meropenem plasma concentrations were measured by a high-performance liquid chromatography (HPLC) method, and a population pharmacokinetics analysis was performed using NONMEM software. Meropenem plasma disposition was simulated for extended (3 h; 5 h) or continuous i.v. infusions, and the following parameters were calculated: time during which free drug concentrations were above minimum inhibitory concentration (MIC) (fT > MIC), free minimum plasma concentrations above 4× MIC (fCmin > 4× MIC), probability of target attainment (PTA), and cumulative fraction of response (CFR).. Gender and severity of sepsis affected meropenem clearance, whose typical population values ranged from 6.22 up to 12.04 L/h (mean ± standard deviation (SD) value, 9.38 ± 4.47 L/h). Mean C min value was 7.90 ± 7.91 mg/L, suggesting a high interindividual variability. The simulation confirmed that 88 and 97.5 % of patients achieved effective C min > 4× MIC values after 3- and 5-h i.v. infusions of meropenem 2 g × 3/day, respectively. On the contrary, the same total daily doses reached the target C min > 4× MIC values in 100 % of patients when administered as continuous i.v. infusions.. Several factors may influence meropenem pharmacokinetics in ICU patients. Continuous i.v. infusions of meropenem seem to be more effective than standard regimens to achieve optimal therapeutic targets.

Topics: Adult; Aged; Anti-Bacterial Agents; Critical Illness; Cross Infection; Female; Humans; Infusions, Intravenous; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Models, Biological; Sepsis; Thienamycins

An analysis of subjects with concurrent bacteraemia and either nosocomial pneumonia, complicated intra-abdominal infection or complicated urinary tract infection from six phase 3 clinical trials demonstrated similar cure rates and clearance of bacteraemia in patients treated with doripenem and comparator agents.

Topics: Anti-Bacterial Agents; Bacteremia; Carbapenems; Cross Infection; Doripenem; Female; Humans; Imipenem; Intraabdominal Infections; Male; Meropenem; Ofloxacin; Pneumonia; Thienamycins; Treatment Outcome; Urinary Tract Infections

ß-Lactam antibiotics demonstrate time-dependent killing. Prolonged infusion of these agents is commonly performed to optimize the time the unbound concentration of an antibiotic remains greater than the minimum inhibitory concentration and decrease costs, despite limited evidence suggesting improved clinical results.. To determine whether prolonged infusion of ß-lactam antibiotics improves outcomes in critically ill patients with suspected gram-negative infection.. We conducted a single-center, before-after, comparative effectiveness trial between January 2010 and January 2011 in the intensive care units at Barnes-Jewish Hospital, an urban teaching hospital affiliated with the Washington University School of Medicine in St. Louis, MO. Outcomes were compared between patients who received standardized dosing of meropenem, piperacillin-tazobactam, or cefepime as an intermittent infusion over 30 minutes (January 1, 2010, to June 30, 2010) and patients who received prolonged infusion over 3 hours (August 1, 2010, to January 31, 2011).. A total of 503 patients (intermittent infusion, n = 242; prolonged infusion, n = 261) treated for gram-negative infection were included in the clinically evaluable population. Approximately 50% of patients in each group received cefepime and 20% received piperacillin-tazobactam. More patients in the intermittent infusion group received meropenem (35.5% vs 24.5%; p = 0.007). Baseline characteristics were similar between groups, with the exception of a greater occurrence of chronic obstructive pulmonary disease (COPD) in the intermittent infusion group. Treatment success rates in the clinically evaluable group were 56.6% for intermittent infusion and 51.0% for prolonged infusion (p = 0.204), and in the microbiologically evaluable population, 55.2% for intermittent infusion and 49.5% for prolonged infusion (p = 0.486). Fourteen-day, 30-day, and inhospital mortality rates in the clinically evaluable population for the intermittent and prolonged infusion groups were 13.2% versus 18.0% (p = 0.141), 23.6% versus 25.7% (p = 0.582), and 19.4% versus 23.0% (p = 0.329).. Routine use of prolonged infusion of time-dependent antibiotics for the empiric treatment of gram-negative bacterial infections offers no advantage over intermittent infusion antibiotic therapy with regard to treatment success, mortality, or hospital length of stay. These results were confirmed after controlling for potential confounders in a multivariate analysis.

Topics: Aged; Anti-Bacterial Agents; beta-Lactams; Cefepime; Cephalosporins; Cohort Studies; Cross Infection; Drug Administration Schedule; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Hospitals, Teaching; Hospitals, Urban; Humans; Infusions, Intravenous; Intensive Care Units; Length of Stay; Male; Meropenem; Middle Aged; Missouri; Penicillanic Acid; Pilot Projects; Piperacillin; Piperacillin, Tazobactam Drug Combination; Thienamycins

Healthcare-associated pneumonia (HCAP) may have a more severe course than community-acquired pneumonia (CAP); hence, it is more likely to be caused by drug-resistant bacterial pathogens and anaerobes involved in aspiration pneumonia. We compared the efficacy and safety of initial empiric therapy with piperacillin/tazobactam (PIPC/TAZ, 13.5 g/day) with that of meropenem (MEPM, 1.5 g/day) as single broad-spectrum regimens with gram-negative and anaerobic coverage in patients with HCAP in Japan. The clinical cure rate was 75.9 % (22/29 cases) in the PIPC/TAZ group and 64.3 % (18/28 cases) in the MEPM group. The clinical efficacy rate was 87.9 % (29/33 cases) in the PIPC/TAZ group and 74.2 % (23/31 cases) in the MEPM group. The bacteriological eradication rate was 94.4 % (17/18) in the PIPC/TAZ group and 87.5 % (14/16) in the MEPM group. Adverse drug reactions were seen in 22.4 % (11/49 cases) of patients in the PIPC/TAZ group and 17.4 % (8/46 cases) of patients in the MEPM group. Although not statistically different, the PIPC/TAZ group had a slightly higher efficacy rate than the MEPM group. Both treatment regimens are tolerable and might be appropriate to use as initial empiric therapy for HCAP in Japan. To investigate the differences in efficacy profiles of those two regimens, a further confirmatory study with a larger cohort as determined by a power analysis is recommended.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Cross Infection; Female; Humans; Japan; Male; Meropenem; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Prospective Studies; Statistics, Nonparametric; Thienamycins; Treatment Outcome

Adequacy and effectiveness of empirical antibacterial therapy of severe nosocomial infections with meropenem vs. combined regimens of antibacterial therapy were investigated and the ratio of the cost and effectiveness of the compared regimens was evaluated. A prospective, randomized, open, comparative study of two initiative regimens of empirical antibacterial therapy of severe nosocomial infections was performed: meropenem in a daily dose of 1.5-3 g and the standard regimen with the use of betalactams and fluoroquinolones in combination with aminoglycosides and/or metronidazole. Patients with recorded diagnosis of nosocomial pneumonia (including the ventilator-associated one) or abdominal infection with the signs of severe sepsis and severity of APACHE II > 14 were enrolled. The patients were stratified into 2 groups subject to the disease severity, i.e. APACHE II 15-20 and APACHE II 21-25. One hundred thirty five out of 166 patients with recorded nosocomial infection were included into the final estimate of the therapy adequacy and effectiveness (Protocol Analysis): 62 patients were treated with meropenem and in the treatment of 73 patients the standard antibacterial therapy was used. In the group of the patients treated with meropenem there were stated significantly higher clinical effectiveness (recovery in 80.6% of the patients vs. the control of 46.6%, p < 0.01) and pathogen eradication (89.6 and 48.1% respectively, p < 0.01). The difference in the clinical and bacteriological effectiveness of meropenem and the standard therapy was more evident in the subgroups of more severe patients (APACHE > 20). With the use of meropenem the probability of recovery from nosocomial infection was significantly higher (RR 1.73-1.94, p < 0.001) vs. the control. Meropenem provided significantly higher eradication of the pathogens: P. aeruginosa (88 and 40% respectively, p = 0.007), E. coli (100 and 46.7%, p = 0.003), Acinetobacter spp. (90.9 and 40%, p = 0.02). The antibacterial therapy with the use of meropenem was assessed as adequate in 51 out of 56 patients (91.1%), that was 3 times as frequent as with the use of the standard antibacterial therapy (33.9%). The cost-effectiveness coefficient with the use of meropenem was 2.2 times lower vs. the control. Therefore, the empirical therapy of severe nosocomial infections with meropenem proved to be more adequate and from the economic viewpoint more advantageous vs. the standard combined regimens of antibacterial thera

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aminoglycosides; Anti-Bacterial Agents; Anti-Infective Agents; beta-Lactams; Costs and Cost Analysis; Cross Infection; Drug Therapy, Combination; Female; Fluoroquinolones; Humans; Male; Meropenem; Metronidazole; Middle Aged; Pneumonia, Bacterial; Prospective Studies; Russia; Thienamycins; Treatment Outcome

The efficacy and tolerability of meropenem as empirical treatment in patients with hospital-acquired pneumonia was determined in a prospective, open-label, non-randomized trial. Patients from 28 centers in the USA received meropenem 1 g every 8 h intravenously. Of 255 patients enrolled, 111 were evaluable for efficacy, including 60 patients with ventilator-associated pneumonia. At end of treatment 74% of patients had a satisfactory clinical response and 64% had this response at follow-up, which could last up to 28 days after treatment. In patients with ventilator-associated pneumonia, a satisfactory clinical response was observed in 68% at the end of treatment and 63% at follow-up. The overall satisfactory response rate for individual pretreatment pathogens ranged from 65% to 100%. This study demonstrates that meropenem monotherapy is effective and well tolerated for patients with hospital-acquired pneumonia, including a subgroup of patients with ventilator-associated pneumonia.

Topics: Adolescent; Adult; Aged; Cross Infection; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Infusions, Intravenous; Male; Meropenem; Middle Aged; Pneumonia, Bacterial; Probability; Prospective Studies; Respiration, Artificial; Risk Assessment; Thienamycins; Treatment Outcome

Recently, new broad spectrum carbapenem has been investigated on a world-wide scale for the treatment of moderate to severe infections. In the neonatal intensive care units the extensive use of third generation cephalosporins for therapy of neonatal sepsis may lead to rapid emergence of multiresistant gram-negative organisms. We report the use of meropenem in 35 infants with severe infections due to Acinetobacter baumanii and Klebsiella pneumoniae. All gram negative bacteria were resistant to ampicillin, amoxicillin, ticarcilin, cefazoline, cefotaxime, ceftazidime, ceftriaxone and aminoglycosides. Eighty two percent of the cases (29/35) were born prematurely. Assisted ventilation was needed in 85.7% (30/35). All infants deteriorated during their conventional treatment and were changed to meropenem monotherapy. Six percent (2/35) died. The incidence of drug-related adverse events (mostly a slight increase in liver enzymes) was 8.5%. No adverse effects such as diarrhea, vomiting, rash, glossitis, oral or diaper area moniliasis, thrombocytosis, thrombocytopenia, eosinophilia and seizures were observed. At the end of therapy, overall satisfactory clinical and bacterial response was obtained in 33/35 (94.3%) of the newborns treated with meropenem. Clinical and bacterial response rates for meropenem were 100% for sepsis and 87.5% for nosocomial pneumonia. This report suggests that meropenem may be a useful antimicrobial agent in neonatal infections caused by multiresistant gram negative bacilli. Further studies are needed to confirm these results: Meropenem, newborn, sepsis and nosocomial infection.

Topics: Acinetobacter Infections; Cross Infection; Drug Resistance, Multiple; Female; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Klebsiella Infections; Male; Meropenem; Prospective Studies; Thienamycins

This study aimed at evaluating the efficacy and safety of meropenem as first choice treatment for nosocomial pneumonia (NP) in intensive care units (ICU) in Hospital das Clínicas (HC) - University of São Paulo; a hospital with high incidence of antimicrobial resistance. Prospective, open, and non-comparative trial with meropenem were done in patients with ventilator-associated or aspiration NP in 2 ICUs at HC - University of São Paulo. Etiologic investigation was done through bronchoalveolar lavage and blood cultures prior to study entry. Twenty-five (25) critically ill patients with NP were enrolled (mean age 40 years). Ventilator-acquired pneumonia was responsible for 76% of cases and aspiration NP for 24%. Specific etiologic agents were identified and considered to be clinically and temporally responsible for NP in 11 (44%) patients. A. baumanii was responsible for 6 cases (55%), P. aeruginosa for 3 (27%), and S. aureus for 2 (18%). At completion of treatment, 19 patients (76%) showed either cure (48%) or improvement (28%) after use of meropenem therapy. Mortality was 12% at the end of therapy (8% after excluding 1 non-evaluable patient). After 4 to 6 weeks of follow-up, 12 (48%) patients had improved or been totally cured, and overall mortality was 24%. Clinical complications were observed in 11 patients (44%), with none of them definitely related to the study drug. Meropenem as monotherapy was effective and well-tolerated in most NP patients in our ICU. The low mortality rate in this study might have been due to first choice use of this drug. Controlled, drug comparative clinical trials are needed to support this preliminary observation.

Topics: Adult; Aged; Cross Infection; Female; Humans; Intensive Care Units; Male; Meropenem; Middle Aged; Pneumonia, Bacterial; Prospective Studies; Thienamycins; Ventilators, Mechanical

We performed a prospective, open label, randomized study in intensive care unit patients with ventilator-associated pneumonia (VAP) to determine the efficacy and safety of empiric intravenous (i.v.) meropenem monotherapy compared with the combination of ceftazidime plus amikacin. A total of 140 patients receiving mechanical ventilation and diagnosed with pneumonia were included in the study. Patients were randomized to receive either 1 g meropenem i.v. every 8 hours or 2 g ceftazidime i.v. every 8 hours plus 15 mg/kg amikacin daily, administered to patients with normal renal function as two daily doses. Satisfactory clinical responses (cure or improvement) were achieved at the end of treatment in 68.1% of meropenem-treated patients and 54.9% in the ceftazidime/amikacin treated group (relative risk 1.25; 95% confidence interval > 1.00, 1.55). When non-evaluable patients were excluded from the analysis, the satisfactory clinical response was 82.5% and 66.1% for the meropenem and ceftazidime/amikacin patients, respectively (p = 0.044). Logistic regression demonstrated that treatment with meropenem and both the basic traumatic and medical pathologies were significantly associated with a satisfactory response. Adverse events judged to be possible or probably related to treatment were reported by seven (10.1%) patients in the meropenem group and by eight patients (11.3%) in the ceftazidime/amikacin group. The results of this study confirm that monotherapy with meropenem is well tolerated and provides superior efficacy to the conventional combination of ceftazidime and amikacin in combating VAP.

Topics: Amikacin; Ceftazidime; Cross Infection; Drug Therapy, Combination; Female; Humans; Male; Meropenem; Middle Aged; Pneumonia, Bacterial; Prospective Studies; Respiration, Artificial; Superinfection; Thienamycins

Clinical efficacy and tolerance of meropenem were estimated by comparison with those of ceftazidime and amikacin used in combination in the therapy of hospital infections of the lower respiratory tract, skin and soft tissues, intraabdominal and gynecologic infections, urinary tract infection and sepsis. 48 patients were given meropenem in a dose of 1 g every 8 hours for 3-14 days (the average of 9 days). 47 patients were subjected to the routine combined therapy: ceftazidime in a dose of 1 g every 8 hours and amikacin in a dose of 0.5 g every 12 hours for 2-14 days (the average of 9 days). The patient groups were comparable by the age, nature and severity of the infection and the condition (the mean APACHE II of 9.1 and 8.9). By the end of the treatment a positive clinical effect (recovery and improvement) was observed in 47 patients (97.9 per cent) treated with meropenem and in 41 patients (89.1 per cent) subjected to the combined therapy. The infection relapse within 4 weeks after the treatment completion was recorded in 3 patients in every group. Before the treatment 133 microbial strains were isolated from the patients. 121 of them were susceptible to meropenem (91.1 per cent), 111 to amikacin (83.4 per cent) and 90 to ceftazidime (67.7 per cent). The difference between meropenem and ceftazidime was significant (p = 0.0005). Eradication of the primary pathogens at the background of the meropenem therapy was stated in 41 out of 44 patients (93.2 per cent) and that of the combined therapy in 38 out of 43 patients (88.4 per cent). The microbiological relapse after the treatment completion was recorded in 3 and 2 patients, respectively. Side effects were observed in 8.3 per cent of the patients treated with meropenem and in 10.6 per cent of the patients subjected to the combined therapy. The trial results were indicative of the meropenem high efficacy and good tolerance and of the possible use of the drug in the monotherapy as an alternative of the routine combined therapy of severe hospital infections.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amikacin; Ceftazidime; Cross Infection; Drug Therapy, Combination; Female; Humans; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Thienamycins; Treatment Outcome

To evaluate the efficacy and tolerability of intravenous empiric treatment with meropenem compared with ceftazidime-tobramycin in patients with hospital-acquired lower respiratory tract infections.. Prospective, nonblind, randomized trial.. Multicenter trial conducted at 22 centers.. Two hundred eleven patients were enrolled and 121 were evaluable for the analysis of both clinical and bacteriologic efficacy.. One hundred four patients were randomized to receive intravenous meropenem (1000 mg) every 8 hrs and 107 patients were randomized to receive intravenous ceftazidime (2000 mg) plus tobramycin (1 mg/kg) every 8 hrs. Sixty-three meropenem-treated patients and 58 ceftazidime-tobramycin-treated patients were eligible for the analysis of clinical and bacteriologic efficacy. In the ceftazidime-tobramycin group, 32 (55%) evaluable patients received more than six doses of tobramycin, 24 (41%) received six doses or fewer, and two (3%) did not receive any tobramycin.. The analysis of efficacy was based on the clinical and bacteriologic responses at the end of treatment. Satisfactory clinical responses occurred in 56 (89%) of 63 of the meropenem-treated patients and in 42 (72%) of 58 of the ceftazidime-tobramycin-treated patients (p = .04). Corresponding bacteriologic response rates were 89% and 67%, respectively (p = .006). The frequency and profile of drug-related adverse events was similar across treatment groups. Seizures were reported in three meropenem-treated patients, but these seizures were considered by the investigator to be unrelated to treatment.. Meropenem is well tolerated and more efficacious than the combination of ceftazidime and tobramycin for the initial empiric treatment of hospital-acquired bacterial pneumonia.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Ceftazidime; Cephalosporins; Cross Infection; Drug Therapy, Combination; Female; Humans; Male; Meropenem; Middle Aged; Prospective Studies; Respiratory Tract Infections; Thienamycins; Time Factors; Tobramycin

The clinical and bacteriological efficacy and the tolerability of meropenem versus imipenem/cilastatin (both 1 g t.i.d.) in severe nosocomial infections were compared in a multicentre, randomised, nonblinded study. A total of 151 patients were recruited; 133 (66 meropenem, 67 imipenem/cilastatin) were clinically evaluable and 84 (42 meropenem, 42 imipenem/cilastatin) bacteriologically evaluable. Most clinically evaluable patients (90%) were in intensive care units, required mechanical ventilation (72%), and had received previous antibiotic therapy (62%). The mean (+/- SD) APACHE II score was 15.2 (+/- 6.6) in the meropenem group and 17.8 (+/- 6.8) in the imipenem/cilastatin group. The primary infections were nosocomial lower respiratory tract infections (56% of patients), intra-abdominal infections (15%), septicaemia (21%), skin/skin structure infections (5%), and complicated urinary tract infections (3%); 35% of the patients had two or more infections. There was no significant difference between the meropenem and imipenem/cilastatin groups in the rates of satisfactory clinical (weighted percentage 87% vs. 74%) or bacteriological (weighted percentage 79% vs. 71%) response. There was a slightly higher rate of clinical success with meropenem against primary or secondary lower respiratory tract infection (89% vs. 76%). Drug-related adverse events occurred in 17% and 15% of meropenem and imipenem/cilastatin patients, respectively. Meropenem (1 g t.i.d.) was as efficacious as the same dose of imipenem/cilastatin in this setting, and both drugs were well tolerated.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Carbapenems; Cilastatin; Cilastatin, Imipenem Drug Combination; Cross Infection; Drug Combinations; Drug Therapy, Combination; Female; Humans; Imipenem; Male; Meropenem; Middle Aged; Prospective Studies; Thienamycins

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

A clinical, multicentre, randomised, comparative study in 283 adult hospitalized patients was carried out to assess efficacy of meropenem in the treatment of complicated and non-complicated urinary tract infections, in comparison to imipenem/cilastatin. Both antibiotics were administered intramuscularly, at a dose of 500 mg bid. The two groups were homogeneous, as regards the distribution between male and female, the mean age of the patients, the severity of infections and the mean duration of treatment. Clinical results were assessed at the end of therapy and follow-up (4-6 weeks). Bacteriological results were assessed at 5-9 days post-treatment and at follow-up. As regards clinical and bacteriological results patients showing a satisfactory response rate were compared, at the end of the treatments using a Chi square test. With both treatments high satisfactory clinical and bacteriological response rates were seen. As regards clinical satisfactory responses (97% of meropenem assessable patients versus 90% of imipenem/cilastatin assessable patients), there was a statistically significant difference in favor of meropenem. The bacteriological outcome was successful (eradication) for 75% of assessable patients in each group. Most failures were seen in the complicated infections, even when pathogens usually sensitives to carbapenemics were initially isolated. Safety was good with both drugs; no withdrawals in any group of treatment was seen because of side effects. The local tolerance of meropenem was globally rated as good.

Topics: Adult; Aged; Carbapenems; Chi-Square Distribution; Cilastatin; Cross Infection; Female; Humans; Imipenem; Male; Meropenem; Middle Aged; Protease Inhibitors; Thienamycins; Urinary Tract Infections

Gram-negative bacillary meningitis remains a rare occurrence, even in patients with human immunodeficiency virus. Current literature only describes anecdotal cases of spontaneous nosocomial Proteus mirabilis meningitis. This report describes the clinical manifestations and management of a patient with healthcare-associated spontaneous Gram-negative bacillary meningitis in a patient with advanced human immunodeficiency virus disease.. A 23-year-old Congolese female was hospitalized in a human immunodeficiency virus specialized center for ongoing weight loss, chronic abdominal pain, and vomiting 9 months after initiation of treatment for tuberculosis meningitis. Hospitalization was complicated by healthcare-associated Gram-negative bacillary meningitis on day 18. Blood and cerebrospinal fluid cultures confirmed Proteus mirabilis. Antibiotic susceptibility testing showed extended spectrum beta-lactamase resistant to common antibiotics, and sensitive to meropenem. Despite initiation of high-dose meropenem by intravenous infusion (2 g every 8 hours), the patient did not improve, and died after 4 days of meropenem treatment. Gram-negative bacillary meningitis remains rare and is associated with an unfavorable prognosis.. This case report highlights the importance of microbiological identification of pathogens in resource-limited settings. As Gram-negative bacillary meningitis does not present with pleocytosis in patients with advanced human immunodeficiency virus, a negative lumbar puncture cannot exclude this diagnosis. Access to clinical bacteriology in resource-limited settings is essential to enable correct antibiotic treatment and avoid overuse of antibiotics to which there is already resistance. It further plays an essential role in public health by identifying antibiotic susceptibilities. Infection prevention and control measures must be reinforced in order to protect patients from such avoidable healthcare-associated infections.

Topics: Adult; Anti-Bacterial Agents; Cross Infection; Female; Gram-Negative Bacteria; HIV; HIV Infections; Humans; Meningitis; Meningitis, Bacterial; Meropenem; Proteus mirabilis; Young Adult

The aim of this study was to analyze and identify documented infections and possible risk factors for Clostridioides difficile infections in children with cancer.. This is a retrospective case-control study, carried out in a pediatric cancer hospital, covering the years 2016-2019. Matching was performed by age and underlying disease, and for each case, the number of controls varied from 1 to 3. Logistic regression models were used to assess risk factors.. We analyzed 63 cases of documented infection by C. difficile and 125 controls. Diarrhea was present in all cases, accompanied by fever higher than 38°C in 52.4% of the patients. Mortality was similar among cases (n=4; 6.3%) and controls (n=6; 4.8%; p=0.7). In all, 71% of patients in the case group and 53% in the control group received broad-spectrum antibiotics prior to the infection. For previous use of vancomycin, the Odds Ratio for C. difficile infection was 5.4 (95% confidence interval [95%CI] 2.3-12.5); for meropenem, 4.41 (95%CI 2.1-9.2); and for cefepime, 2.6 (95%CI 1.3-5.1). For the antineoplastic agents, the Odds Ratio for carboplatin was 2.7 (95%CI 1.2-6.2), melphalan 9.04 (95%CI 1.9-42.3), busulfan 16.7 (95%CI 2.1-134.9), and asparaginase 8.97 (95%CI 1.9-42.9).. C. difficile symptomatic infection in children with cancer was associated with previous hospitalization and the use of common antibiotics in cancer patients, such as vancomycin, meropenem, and cefepime, in the last 3 months. Chemotherapy drugs, such as carboplatin, melphalan, busulfan, and asparaginase, were also risk factors.

Topics: Anti-Bacterial Agents; Asparaginase; Busulfan; Cancer Care Facilities; Carboplatin; Case-Control Studies; Cefepime; Child; Clostridioides difficile; Clostridium Infections; Cross Infection; Humans; Melphalan; Meropenem; Neoplasms; Retrospective Studies; Risk Factors; Vancomycin

Healthcare-associated infections (HAIs) are often caused by multidrug-resistant (MDR) bacteria contaminating hospital environments which can cause outbreaks as well as sporadic transmission.. This study systematically sampled and utilized standard bacteriological culture methods to determine the numbers and types of MDR Enterococcus faecalis/faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species, and Escherichia coli (ESKAPEE) from high-touch environments of five Kenyan hospitals; level 6 and 5 hospitals (A, B, and C), and level 4 hospitals (D and E), in 2018. Six hundred and seventeen high-touch surfaces across six hospital departments; surgical, general, maternity, newborn, outpatient and pediatric were sampled.. 78/617 (12.6%) of the sampled high-touch surfaces were contaminated with MDR ESKAPEE; A. baumannii, 23/617 (3.7%), K. pneumoniae, 22/617 (3.6%), Enterobacter species, 19/617 (3.1%), methicillin resistant S. aureus (MRSA), 5/617 (0.8%), E. coli, 5/617 (0.8%), P. aeruginosa, 2/617 (0.3%), and E. faecalis and faecium, 2/617 (0.3%). Items found in patient areas, such as beddings, newborn incubators, baby cots, and sinks were the most frequently contaminated. Level 6 and 5 hospitals, B, 21/122 (17.2%), A, 21/122 (17.2%), and C, 18/136 (13.2%), were more frequently contaminated with MDR ESKAPEE than level 4 hospitals; D, 6/101 (5.9%), and E, 8/131 (6.1%). All the sampled hospital departments were contaminated with MDR ESKAPEE, with high levels observed in newborn, surgical and maternity. All the A. baumannii, Enterobacter species, and K. pneumoniae isolates were non-susceptible to piperacillin, ceftriaxone and cefepime. 22/23 (95.6%) of the A. baumannii isolates were non-susceptible to meropenem. In addition, 5 K. pneumoniae isolates were resistant to all the antibiotics tested except for colistin.. The presence of MDR ESKAPEE across all the hospitals demonstrated gaps in infection prevention practices (IPCs) that should be addressed. Non-susceptibility to last-line antibiotics such as meropenem threatens the ability to treat infections.

Topics: Anti-Bacterial Agents; Child; Cross Infection; Delivery of Health Care; Escherichia coli; Female; Hospital Departments; Hospitals; Humans; Infant, Newborn; Kenya; Meropenem; Methicillin-Resistant Staphylococcus aureus; Pregnancy

Combined prescription of the antimicrobial drugs linezolid and meropenem is a common strategy to treat multidrug-resistant nosocomial infections. We propose an innovative method to determine these two drugs in plasma and urine, based on micellar liquid chromatography. Both biological fluids were diluted in mobile phase, filtered and directly injected, without any extraction step. Using a C18 column and a mobile phase of 0.1 M sodium dodecyl sulfate - 10 % methanol, phosphate buffered at pH 3, running under isocratic mode, both antibiotics were eluted without overlapping in<15 min. Detection was by absorbance: 255 nm for linezolid and 310 nm for meropenem. The influence of sodium dodecyl sulfate and methanol concentration on retention factor was established for both drugs using an interpretative approach assisted by chemometrics. The procedure was successfully validated following the guidelines of 2018 Bioanalytical Method Validation Guidance for Industry in terms of: linearity (determination coefficients over 0.99990), calibration range (1 - 50 mg/L), instrumental and method sensitivity, trueness (bias of -10.8 to + 2.4%), precision (relative standard deviation of < 10.2%), dilution integrity, carry-over effect, robustness and stability. It should be emphasized that the method uses low volumes of toxic and volatile solvents and can be achieved in a short period. The procedure was found useful for routine analysis, as it was cost-affordable, more eco-friendly and safer than hydroorganic HPLC, easy-to-handle and highly sample-throughput. Finally, it was applied to incurred samples of patients taking this medication.

Topics: Anti-Bacterial Agents; Chromatography, High Pressure Liquid; Chromatography, Liquid; Cross Infection; Humans; Linezolid; Meropenem; Methanol; Micelles; Sodium Dodecyl Sulfate

It is well documented that inappropriate use of antimicrobials is the major driver of antimicrobial resistance. To combat this, antibiotic stewardship has been demonstrated to reduce antibiotic usage, decrease the prevalence of resistance, lead to significant economic gains and better patients' outcomes. In Nigeria, antimicrobial guidelines for critically ill patients in intensive care units (ICUs), with infections are scarce. We set out to develop antimicrobial guidelines for this category of patients.. A committee of 12 experts, consisting of Clinical Microbiologists, Intensivists, Infectious Disease Physicians, Surgeons, and Anesthesiologists, collaborated to develop guidelines for managing infections in critically ill patients in Nigerian ICUs. The guidelines were based on evidence from published data and local prospective antibiograms from three ICUs in Lagos, Nigeria. The committee considered the availability of appropriate antimicrobial drugs in hospital formularies. Proposed recommendations were approved by consensus agreement among committee members.. Candida albicans and Pseudomonas aeruginosa were the most common microorganisms isolated from the 3 ICUs, followed by Klebsiella pneumoniae, Acinetobacter baumannii, and Escherichia coli. Targeted therapy is recognized as the best approach in patient management. Based on various antibiograms and publications from different hospitals across the country, amikacin is recommended as the most effective empiric antibiotic against Enterobacterales and A. baumannii, while colistin and polymixin B showed high efficacy against all bacteria. Amoxicillin-clavulanate or ceftriaxone was recommended as the first-choice drug for community-acquired (CA) CA-pneumonia while piperacillin-tazobactam + amikacin was recommended as first choice for the treatment of healthcare-associated (HA) HA-pneumonia. For ventilatorassociated pneumonia (VAP), the consensus for the drug of first choice was agreed as meropenem. Amoxycillin-clavulanate +clindamycin was the consensus choice for CAskin and soft tissue infection (SSIS) and piperacillin-tazobactam + metronidazole ±vancomycin for HA-SSIS. Ceftriaxone-tazobactam or piperacillin-tazobactam + gentamicin was consensus for CA-blood stream infections (BSI) with first choice+regimen for HA-BSI being meropenem/piperacillin-tazobactam +amikacin +fluconazole. For community-acquired urinary tract infection (UTI), first choice antibiotic was ciprofloxacin or ceftriaxone with a catheter-associated UTI (CAUTI) regimen of first choice being meropenem + fluconazole.. Data from a multicenter three ICU surveillance and antibiograms and publications from different hospitals in the country was used to produce this evidence-based Nigerian-specific antimicrobial treatment guidelines of critically ill patients in ICUs by a group of experts from different specialties in Nigeria. The implementation of this guideline will facilitate learning, continuous improvement of stewardship activities and provide a baseline for updating of guidelines to reflect evolving antibiotic needs.. Il est bien établi que l’utilisation inappropriée des antimicrobiens est le principal moteur de la résistance aux antimicrobiens. Pour lutter contre ce phénomène, il a été démontré que la bonne gestion des antibiotiques permettait de réduire l’utilisation des antibiotiques, de diminuer la prévalence de la résistance, de réaliser des gains économiques significatifs et d’améliorer les résultats pour les patients. Au Nigéria, les directives antimicrobiennes pour les patients gravement malades dans les unités de soins intensifs (USI), souffrant d’infections, sont rares. Nous avons entrepris d’élaborer des lignes directrices sur les antimicrobiens pour cette catégorie de patients.. Un comité de 12 experts, composé de microbiologistes cliniques, d’intensivistes, de médecins spécialistes des maladies infectieuses, de chirurgiens et d’anesthésistes, a collaboré à l’élaboration de lignes directrices pour la prise en charge des infections chez les patients gravement malades dans les unités de soins intensifs nigérianes. Les lignes directrices sont basées sur des données publiées et des antibiogrammes prospectifs locaux provenant de trois unités de soins intensifs de Lagos, au Nigeria. Le comité a pris en compte la disponibilité des médicaments antimicrobiens appropriés dans les formulaires des hôpitaux. Les recommandations proposées ont été approuvées par consensus entre les membres du comité.. Candida albicans et Pseudomonas aeruginosa étaient les microorganismes les plus fréquemment isolés dans les trois unités de soins intensifs, suivis par Klebsiella pneumoniae, Acinetobacter baumannii et Escherichia coli. La thérapie ciblée est reconnue comme la meilleure approche pour la prise en charge des patients. Sur la base de divers antibiogrammes et publications provenant de différents hôpitaux du pays, l'amikacine est recommandée comme l'antibiotique empirique le plus efficace contre les entérobactéries et A. baumannii, tandis que la colistine et la polymixine B se sont révélées très efficaces contre toutes les bactéries. L'amoxicilline-clavulanate ou la ceftriaxone ont été recommandées comme médicaments de premier choix pour les pneumonies communautaires, tandis que la pipéracilline-tazobactam + amikacine ont été recommandées comme médicaments de premier choix pour le traitement des pneumonies associées aux soins. Pour les pneumonies acquises sous ventilation mécanique (PAV), le consensus sur le médicament de premier choix est le méropénem. L'amoxycilline-clavulanate +clindamycine était le choix consensuel pour les infections de la peau et des tissus mous et la pipéracilline-tazobactam + métronidazole ±vancomycine pour les infections de la peau et des tissus mous. HA-SSIS. Ceftriaxone-tazobactam ou pipéracilline-tazobactam + gentamicine a fait l'objet d'un consensus pour les infections de la circulation sanguine de l'AC (BSI), le premier choix de régime pour les HA-BSI étant le méropénem/pipéracilline-tazobactam +amikacine +fluconazole. Pour les infections urinaires communautaires, l'antibiotique de premier choix était la ciprofloxacine ou la ceftriaxone, le régime de premier choix pour les infections urinaires associées à un cathéter étant le meropenem +fluconazole.. Les données issues d’une surveillance multicentrique de trois unités de soins intensifs, d’antibiogrammes et de publications de différents hôpitaux du pays ont été utilisées par un groupe d’experts de différentes spécialités nigérianes pour élaborer ces lignes directrices sur le traitement antimicrobien des patients gravement malades dans les unités de soins intensifs, fondées sur des données probantes et spécifiques au Nigeria. La mise en œuvre de ces lignes directrices facilitera l’apprentissage, l’amélioration continue des activités de gestion et fournira une base de référence pour la mise à jour des lignes directrices afin de refléter l’évolution des besoins en antibiotiques.. Antimicrobiens, Résistance aux antimicrobiens, Gestion des antibiotiques, Lignes directrices, Soins intensifs, Unité de soins intensifs, Infections associées aux soins de santé.

Topics: Amikacin; Anti-Bacterial Agents; Anti-Infective Agents; Ceftriaxone; Clavulanic Acid; Community-Acquired Infections; Critical Illness; Cross Infection; Fluconazole; Humans; Meropenem; Microbial Sensitivity Tests; Nigeria; Piperacillin, Tazobactam Drug Combination; Pneumonia; Prospective Studies; Urinary Tract Infections

Topics: Adult; Amikacin; Anti-Bacterial Agents; Brain Abscess; Carbapenem-Resistant Enterobacteriaceae; Cross Infection; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meningitis; Meropenem; Microbial Sensitivity Tests; Pneumonia; Sulfamethoxazole

Carbapenem-resistant Enterobacteriales has become a threat in Taiwan. This is the first local study focusing on the association between carbapenem-resistant Enterobacteriales and antimicrobial consumption. From January 2012 to December 2020, data were collected in a tertiary care hospital in Taipei, Taiwan. Antimicrobial consumption was estimated by the defined daily dose/1,000 patient-days. During the same period, the prevalence of carbapenem-resistant Escherichia coli (CREC) and carbapenem-resistant Klebsiella pneumoniae (CRKP) were collected through routine surveillance data. The following retrospective analyses were conducted: 1) analysis of antimicrobial consumption over time, (2) analysis and forecast of CREC and CRKP prevalence over time, and 3) analysis of correlation between antimicrobial consumption and the prevalence of CREC and CRKP. The consumption of piperacillin/tazobactam (β = 0.615), fluoroquinolones (β = 0.856), meropenem (β = 0.819), and doripenem (β = 0.891) increased during the observation period (P < 0.001), and the consumption of aminoglycosides (β = -0.852) and imipenem/cilastatin (β = -0.851) decreased (P < 0.001). The prevalence of CRKP rose over time (β = 0.522, P = 0.001) and correlated positively with the consumption of fluoroquinolones, levofloxacin, penicillin/β-lactamase inhibitor, piperacillin/tazobactam, meropenem, and doripenem (P < 0.05). The prevalence of CRKP and CREC both correlated negatively with consumption of aminoglycosides (P < 0.01). The prevalence of CRKP in our hospital increased as the forecast predicted based on an autoregressive integrated moving average model. This study provides alarming messages for members participating in antimicrobial stewardship programs, including the increasing prevalence of CRKP, the increasing consumption of broad-spectrum antibiotics, and the positive correlation between them.

Topics: Aminoglycosides; Anti-Bacterial Agents; Anti-Infective Agents; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Cross Infection; Doripenem; Escherichia coli; Fluoroquinolones; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Piperacillin, Tazobactam Drug Combination; Prevalence; Retrospective Studies; Taiwan; Tertiary Care Centers

Hospital admitted patients are at increased risk of nosocomial infections (NIs) with multi-drug resistant (MDR) pathogens which are prevalent in the hospital environment. Pseudomonas aeruginosa (P. aeruginosa) and Acinetobacter baumannii (A. baumannii) are common causes of NIs worldwide. The objective of this study is to determine antimicrobial resistance profiles and associated factors of Acinetobacter spp and P. aeruginosa NIs among hospitalized patients.. A cross-sectional study was conducted at Dessie comprehensive specialized hospital, North-East Ethiopia, from February 1 to April 30, 2020. A total of 254 patients who were suspected of the bloodstream, urinary tract, or surgical site nosocomial infections were enrolled consecutively. Socio-demographic and other variables of interest were collected using a structured questionnaire. Specimens were collected and processed following standard microbiological procedures. Antimicrobial susceptibility was determined using the Kirby-Bauer disk diffusion method following Clinical and Laboratory Standards Institute guidelines. Data were analyzed with SPSS version 23 and p-value < 0.05 was considered statistically significant.. Overall, 13% of patients had nosocomial Acinetobacter spp and/or P. aeruginosa infections. The culture positivity rate was 16(6.3%) for Acinetobacter spp and 18(7.1%) for P. aeruginosa. Patients admitted in the surgical ward (Adjusted odds ratio (AOR):10.66;95% confidence interval (CI):1.22-93.23), pediatric ward (AOR:14.37;95%CI:1.4-148.5), intensive care unit (AOR:41.93;95%CI:4.7-374.7) and orthopedics (AOR:52.21;95%CI:7.5-365) were significantly at risk to develop NIs compared to patients admitted in the medical ward. Patients who took more than two antimicrobial types at admission were 94% (AOR:0.06; 95% CI:0.004-0.84) times more protected from NIs compared to those who did not take any antimicrobial. About 81% of Acinetobacter spp and 83% of P. aeruginosa isolates were MDR. Amikacin and meropenem showed promising activity against Acinetobacter spp and P. aeruginosa isolates.. The high prevalence of MDR Acinetobacter spp and P. aeruginosa nosocomial isolates enforce treating of patients with NIs based on antimicrobial susceptibility testing results.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Amikacin; Anti-Bacterial Agents; Child; Child, Preschool; Cross Infection; Cross-Sectional Studies; Drug Resistance, Multiple, Bacterial; Ethiopia; Female; Hospitals, Special; Humans; Infant; Infant, Newborn; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Patient Admission; Pseudomonas aeruginosa; Pseudomonas Infections; Risk Factors; Treatment Outcome; Young Adult

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

The aim of this study was to characterise metallo-β-lactamase (MBL)-harbouring plasmids, their change in copy number in respect to different antibiotic pressure, and the efficiency of different curing agents in eliminating these resistance plasmids from nosocomial Pseudomonas aeruginosa isolates.. Plasmids were extracted from four isolates harbouring bla. Conjugatively transferable MBL genes (bla. The spread of multidrug resistance plasmids has been noted as a key factor associated with increasing carbapenem resistance. Successful curing of resistance plasmids can reverse the bacterial phenotype back to susceptible. This study revealed that different antibiotic pressure induces a change in copy number of MBL-encoding plasmids. SDS can be successfully used as an eliminating agent for these resistance determinants, although therapeutic application of this agent is not possible due to its high toxicity and mutagenic nature.

Topics: Anti-Bacterial Agents; Aztreonam; beta-Lactamases; Cefotaxime; Cross Infection; DNA Copy Number Variations; Drug Resistance, Multiple, Bacterial; Ertapenem; Gene Expression Regulation, Bacterial; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Plasmids; Pseudomonas aeruginosa; Pseudomonas Infections; Sodium Dodecyl Sulfate; Suppuration; Urine

Hospital-acquired infections caused by K pneumoniae are difficult to eradicate since K pneumoniae carries resistance genes for many antimicrobials, including carbapenems. The study aimed to determine the prevalence of hospital-acquired infections caused by multiple drug-resistant K pneumoniae and identify carbapenem and fluoroquinolone resistance by phenotypic and genotypic methods amongst hospitalised patients.. Two hundred and fifty samples from patients with hospital-acquired infections were included. Identification and susceptibility testing for K pneumoniae isolates was performed by standard methods. The detection of carbapenemase resistance (bla. Out of 250 samples, 42 (16.8%) were multiple drug-resistant K pneumoniae, and the frequency of K Pneumoniae isolation was higher in urine samples, in the age group (<10 years), in ICU and in patients with longer hospital stay. Twenty-four (57%) of the isolates were resistant to Meropenem, 13 (31%) were resistant to Imipenem and 35 (83.3%) were resistant to Ciprofloxacin. bla. Multidrug-resistant K pneumoniae isolates harbouring bla

Topics: Adolescent; Adult; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Child; Ciprofloxacin; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Genotype; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Length of Stay; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Phenotype; Young Adult

There have historically been concerns of acute kidney injury (AKI) with the use of aminoglycosides. The present study aimed to compare the AKI incidence and mortality rate between critically ill patients treated with aminoglycoside or meropenem in the intensive care unit setting using a propensity score matching approach. This cross-sectional study was conducted at two university hospitals from January 2011 to October 2017. Clinical and laboratorial data were evaluated to exclude potential confounders and to calculate the Charlson index. AKI was classified according to the Acute Kidney Injury Network criteria. All tests were two-tailed, and a p value ≤ 0.05 was considered significant in the univariate and multivariate analyses. We included 494 patients, 95 and 399 of whom used meropenem and aminoglycoside, respectively. Patients in the subgroup that used meropenem were matched with controls (aminoglycoside). Among the 494 patients, 120 developed any grade of AKI (24.2%). After propensity score matching, there were no significant differences in AKI incidence and mortality rate between the aminoglycoside and meropenem groups (p = 0.324 and 0.464, respectively). Patients on the aminoglycoside regimen neither presented a higher AKI incidence nor mortality rate when compared with those on the meropenem regimen. Aminoglycosides may be a safe option for the treatment of critically ill patients on carbapenem sparing antimicrobial stewardship programs.

Topics: Acute Kidney Injury; Aged; Aminoglycosides; Anti-Bacterial Agents; Critical Illness; Cross Infection; Cross-Sectional Studies; Female; Hospitals, University; Humans; Incidence; Intensive Care Units; Male; Meropenem; Middle Aged; Propensity Score; Retrospective Studies; Risk Factors

Topics: Cephalosporins; Cross Infection; Doripenem; Double-Blind Method; Humans; Meropenem; Pneumonia, Ventilator-Associated; Tazobactam

Topics: Cephalosporins; Cross Infection; Doripenem; Double-Blind Method; Humans; Meropenem; Pneumonia, Ventilator-Associated; Tazobactam

Pseudomonas aeruginosa (PA) is a major cause of healthcare-associated infections. Antipseudomonal carbapenems are among the antimicrobial agents used to treat PA infections, but several mechanisms of resistance, including the production of a carbapenemase (CP), may compromise their clinical efficacy. The objectives of this study were to determine: (i) the dissemination of carbapenem-resistant CP-negative and CP-positive PA isolates; and (ii) the in-vitro activity of ceftolozane-tazobactam (CTT) against carbapenem-susceptible and carbapenem-resistant isolates. Isolates were collected prospectively from January 2016 to April 2017 at 20 German medical laboratories. Each centre was asked to provide 50 consecutive isolates from hospitalized patients. Overall, 985 isolates were collected, of which 34% were obtained from intensive care patients. Seven hundred and thirty-eight (74.9%) isolates were susceptible to both imipenem and meropenem (Subgroup I), and 247 (25.1%) isolates were resistant to carbapenems (Subgroup II): 125 (12.7%) were imipenem-resistant but meropenem-susceptible, 12 (1.2%) were meropenem-resistant but imipenem-susceptible, and 110 (11.2%) were resistant to both carbapenems (Subgroup III). A CP was detected in 28 (2.8%) isolates (predominantly VIM-2). Nine hundred and fifty (96.4%) isolates were CTT-susceptible. Susceptibility to CTT was seen in 99.6% of Subgroup I isolates, 87% of Subgroup II isolates and 74.5% of Subgroup III isolates. Overall, 2.8% of PA produced a CP, while 22.2% were carbapenem-resistant, CP-non-producing isolates. Based on these findings, CTT may be considered for treatment of PA infections, particularly those caused by multi-drug-resistant CP-non-producing isolates.

Topics: Aged; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Cephalosporins; Cross Infection; Drug Resistance, Multiple, Bacterial; Germany; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Tazobactam

Topics: Anti-Bacterial Agents; Critical Illness; Cross Infection; Humans; Meropenem; Pneumonia; Thienamycins

To determine the percentage of patients given standard doses of piperacillin/tazobactam or meropenem by continuous  infusion who achieved the target pharmacokinetic/pharmacodynamic  (PK/PD) index, which was defined as free concentrations four times  more than the minimum inhibitory concentration (CMI) for 100% of the  dosing interval (100% fT≥ 4 x MIC).. Preliminary data from a larger prospective clinical study  analysing the PK/PD behaviour of β-lactams antibiotics continuous  infusion (CI) in critical patients. The study was conducted in the  intensive care units of a tertiary university hospital for adults (June  2015-May 2017). Inclusion criteria: normal renal function (glomerular  renal function (GFR) CKD-EPI formula ≥ 60 mL/min/1.73 m2) and  treatment with standard dose β-lactams CI. Concentrations at steady  state (Css) conditions were determined using UHPLC-MS/MS. We  selected the highest susceptible MIC for all likely organisms according to  European Commitee on Antimicrobial Susceptibility Testing's (i.e.  piperacillin/tazobactam: 8 mg/L for enterobacteriaceae and 16 mg/L for  Pseudomonas aeruginosa; meropenem: 2 mg/L for any  microorganism). In addition, a subanalysis of patients was conducted using actual MIC values.. 61 patients were enrolled (25 to meropenem and 36 to  piperacillin/tazobactam). Average age was 59 (15) years and median  GFR rate was 95 mL/min/1.73 m2 (83-115). Median meropenem and  piperacillin free concentrations were 16 mg/L (11-29) and 40 mg/L (21- 51), respectively. 88% of patients treated with meropenem reached the  PK/PD target, without differences between both microorganisms. For  piperacillin/tazobactam, 61% and 11% of patients reached the target,  with enterobacteriaceae and Pseudomonas as suspected  microorganisms, respectively. The pathogen was isolated in 35 (57%)  patients: 94% reached the target PK/PD, without differences between  both antibiotic therapies.. Standard doses of meropenem CI are sufficient to  achieve a PK/PD target of 100% fT≥ 4 x MIC in suspected infections  with high MICs (Pseudomonas aeruginosa or enterobacteriaceae).  However, higher doses of piperacillin/tazobactam could be considered to  achieve this goal. In patients with isolated microorganisms, a  standard dose of both antibiotic therapies would be sufficient to achieve  the target. Therapeutic drug monitoring is highly recommended for  therapeutic optimization.. Objetivo: Determinar el porcentaje de pacientes, a los que se les  administró dosis estándar de piperacilina/tazobactam o meropenem en  perfusión continua, que alcanzaban el índice  farmacocinético/farmacodinámico diana definido como el 100% del  intervalo de administración en que las concentraciones de antibiótico  libre fueron cuatro veces iguales o superiores a la concentración mínima  inhibitoria (100% fT ≥ 4 x CMI).Método: Datos preliminares obtenidos de un estudio clínico prospectivo que analiza el comportamiento  farmacocinético/farmacodinámico de los antibióticos betalactámicos  administrados en perfusión continua en pacientes críticos. Se realizó en  unidades de cuidados intensivos de un hospital universitario de tercer  nivel, desde junio de 2015 a mayo de 2017. Criterios de inclusión:  adultos con función renal correcta (filtrado glomerular según la fórmula  CKD-EPI ≥ 60 ml/min/1,73 m2) y tratados con dosis estándar de  antibióticos betalactámicos en perfusión continua. Las concentraciones  en estado de equilibrio estacionario fueron determinadas mediante  cromatografía líquida acoplada a espectrometría de masas (UHPLC- MS/MS). Se utilizaron valores de concentración mínima  inhibitoria  teóricos para microorganismos más resistentes (piperacilina/ tazobactam: 16 mg/l para Pseudomonas aeruginosa y 8 mg/l para Enterobacteriaceae; meropenem: 2 mg/l, independientemente del  microorganismo). Además, se realizó un subanálisis de los pacientes con aislamiento microbiológico (concentraciones mínimas inhibitorias  reales).Resultados: Se incluyeron 61 pacientes (25 meropenem y 36  piperacilina/ tazobactam). Edad media 59 años (15), mediana de  filtrado glomerular 95 ml/min/1,73 m2 (83-115). Mediana de  concentraciones en estado de equilibrio estacionario libre: 16 mg/l (11- 29) meropenem y 40 mg/l (21-51) piperacilina. El 88% de los pacientes  tratados con meropenem alcanzaron el objetivo  farmacocinético/farmacodinámico, sin diferencias entre Enterobacteriaceae y Pseudomonas. En el caso de  piperacilina/tazobactam, el 61% y el 11% de los pacientes alcanzaron la  diana, considerando Enterobacteriaceae y Pseudomonas como  microorganismo sospechoso. Un total de 35 (57%) pacientes  presentaron aislamiento microbiológico. El 94% de ellos alcanzaron la  diana, sin diferencias entre los dos antibióticos.Conclusiones: Ante la sospecha de infecciones por microorganismos con concentraciones mínimas inhibitorias elevadas  (Pseudomonas aeruginosa o enterobacterias),

Topics: Adult; Aged; Anti-Bacterial Agents; Clinical Studies as Topic; Critical Illness; Cross Infection; Enterobacteriaceae Infections; Female; Hospitals, University; Humans; Infusions, Intravenous; Intensive Care Units; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Pseudomonas Infections; Tertiary Care Centers

Acinetobacter baumanii is a pathogenic bacterium that is the cause of many nosocomial infections. This study aimed to determine metallo-β-lactamases (MBL) produced by the A. baumanii isolates obtained from clinical samples in Shahrekord, southwest Iran.. A total of 100 A. baumanii were isolated from 250 clinical samples between June 2013 and June 2014. Then, the isolates were identified by biochemical tests, and MBL screening was conducted by the phenotypic tests modified Hodge, EDTA-disk synergy (EDS), combined disk (CD) and AmpC disc after antibiotic sensitivity test. Using PCR technique the bla genes were detected. Eighty-five (85%) isolates were resistant to meropenem and imipenem. Phenotypic tests showed that out of the 100 isolates, 46, 59, 50, 65 and 65 isolates were positive: AmpC disk, CD, EDS, Modified Hodge and E-test MBL respectively. Gene detection by PCR showed that 23 isolates carried the VIM-1 gene and only three isolates carried the IMP-1 gene. The prevalence of metallo-β-lactamases isolates containing A. baumanii is increasing. Furthermore, the coexistence of various carbapenemases is dominantly act as a major problem. Continuous monitoring of the infections related to these bacteria should be considered to plan an alternative and new therapeutic strategies.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Cross Infection; Drug Resistance, Multiple, Bacterial; Genotype; Imipenem; Iran; Meropenem; Metalloproteins; Microbial Sensitivity Tests; Phenotype

Topics: Cephalosporins; Cross Infection; Double-Blind Method; Humans; Meropenem; Pneumonia; Tazobactam

There are few prospective studies with sufficient duration in time to evaluate clinical and antibiotic resistance impact of antibiotic stewardship programs (ASP). This is a descriptive study between January 2012 and December 2017, pre-post intervention. A meropenem ASP was initiated in January 2015; in patients who started treatment with meropenem, an infectious disease physician performed treatment recommendations to prescribers. Prospective information was collected to evaluate adequacy of meropenem prescription to local guidelines and to compare results between cases with accepted or rejected intervention. Analysis was performed to verify variables associated with intervention acceptance and with any significant change in meropenem consumption, hospital-acquired multidrug-resistant (MDR) bloodstream infections (BSIs), and 30-day all-cause crude death in MDR BSIs. Adequacy of meropenem prescription and de-escalation from meropenem treatment to narrower-spectrum antibiotic improved progressively over time, after ASP implementation (p < 0.001). Interventions on prescription were performed in 330 (38.7%) patients without meropenem justified treatment; in 269, intervention was accepted and in 61 not. Intervention acceptance was associated with shorter duration of treatment, cost, and inpatient days (p < 0.05); intervention rejection was not associated with severity of patient. During the period 2015-2017, meropenem consumption decreased compared with 2012-2014 (rate ratio [RR] 0.67; 95% CI 0.58-0.77, p < 0.001). Also decreased were hospital-acquired MDR BSI rate (RR 0.63; 95% CI 0.38-1.02, p = 0,048) and 30-day all-cause crude death in MDR BSIs (RR 0.45; 95% CI 0.14-1.24, p = 0.096), coinciding in time with ASP start-up. The decrease and better use of meropenem achieved had a sustained clinical, economic, and ecological impact, reducing costs and mortality of hospital-acquired MDR BSIs.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antimicrobial Stewardship; Bacteremia; Child; Cross Infection; Female; Humans; Length of Stay; Male; Meropenem; Middle Aged; Prospective Studies; Young Adult

Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Chromatography, High Pressure Liquid; Ciprofloxacin; Cross Infection; Humans; Limit of Detection; Linear Models; Meropenem; Reproducibility of Results; Solid Phase Extraction; Stomach Neoplasms

Doripenem shows good in vitro activity against common nosocomial pathogens, such as extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii. However, the use of doripenem for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) remains controversial. The aim of this study was to compare the efficacy and safety between doripenem and meropenem for patients with HAP or VAP.. Adult patients diagnosed with HAP and VAP at National Taiwan University Hospital, who received doripenem or meropenem for more than 48 h between January 2015 and November 2017, were retrospectively reviewed. All-cause mortality on the 30th day was used as the primary outcome measurements.. Fifty-seven patients with doripenem and 252 patients with meropenem were analyzed. Compared to the meropenem group, the doripenem group was younger and had a higher Sequential Organ Failure Assessment (SOFA) score. Multivariable Cox regression analysis revealed that presence of solid organ malignancies (adjusted hazard ratio [AHR], 1.82; 95% CI, 1.04-3.19, p = 0.003) and SOFA score (AHR, 1.10; 95% CI, 1.03-1.17, p = 0.003) were independent factors associated with mortality. There was no survival difference of 30-day mortality between patients receiving doripenem and meropenem for HAP or VAP (log-rank p = 0.113). However, a poorer outcome was observed among patients with hematological disease in the doripenem group (log-rank p = 0.012).. Our results demonstrate that doripenem has similar efficacy as meropenem in HAP or VAP patients. With an aim to enhance antibiotic diversity, doripenem could be an alternative choice for patients with HAP or VAP, except for those with hematological malignancies.

Topics: Acinetobacter baumannii; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cross Infection; Doripenem; Drug Resistance, Multiple, Bacterial; Female; Hospitals; Humans; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Multivariate Analysis; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Regression Analysis; Retrospective Studies; Taiwan

Intestinal colonization resistance is mainly exerted by commensal anaerobes.. To assess whether exposure to non-carbapenem antibiotics with activity against intestinal anaerobes (namely, piperacillin/tazobactam, amoxicillin/clavulanate and metronidazole) may promote the acquisition of gut colonization with ceftriaxone-resistant Gram-negative bacteria (CFR-GNB) in ICU patients.. All patients with a first stay >3 days in a single surgical ICU over a 30 month period were retrospectively included. Rectal carriage of CFR-GNB (i.e. ESBL-producing Enterobacteriaceae, AmpC-hyperproducing Enterobacteriaceae, Pseudomonas aeruginosa, Stenotrophomonas maltophilia and CFR Acinetobacter baumannii) was routinely screened for at admission then weekly. The impact of anti-anaerobe antibiotics was investigated in propensity score (PS)-matched cohorts of patients exposed and not exposed to these drugs and through PS-based inverse probability of treatment weighting on the whole study cohort, treating in-ICU death or discharge as competing risks for CFR-GNB acquisition.. Among the 352 included patients [median ICU stay 16 (9-30) days, in-ICU mortality 12.2%], 120 (34.1%) acquired one or more CFR-GNB, mostly AmpC-hyperproducing Enterobacteriaceae (17.6%) and P. aeruginosa (14.8%). Exposure to anti-anaerobe antibiotics was the main predictor of CFR-GNB acquisition in both the PS-matched cohorts [adjusted HR (aHR) 3.92, 95% CI 1.12-13.7, P = 0.03] and the whole study cohort (aHR 4.30, 95% CI 1.46-12.63, P = 0.01). Exposure to other antimicrobials-especially ceftriaxone and imipenem/meropenem-exerted no independent impact on the likelihood of CFR-GNB acquisition.. Exposure to non-carbapenem antibiotics with activity against intestinal anaerobes may predispose to CFR-GNB acquisition in ICU patients. Restricting the use of these drugs appears to be an antibiotic stewardship opportunity.

Topics: Aged; Anti-Bacterial Agents; Bacteria, Anaerobic; Carbapenems; Ceftriaxone; Cross Infection; Drug Resistance, Bacterial; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Imipenem; Intensive Care Units; Intestines; Male; Meropenem; Middle Aged; Propensity Score; Retrospective Studies

Topics: Azabicyclo Compounds; Ceftazidime; Cross Infection; Double-Blind Method; Drug Combinations; Humans; Meropenem; Pneumonia, Ventilator-Associated

Acinetobacter baumannii is a common causative agent of hospital-acquired infections and a leading cause of infection in burns patients. Carbapenem-resistant A. baumannii is considered a major public-health threat and has been identified by the World Health Organization as the top priority organism requiring new antimicrobials. The most common mechanism for carbapenem resistance in A. baumannii is via horizontal acquisition of carbapenemase genes. In this study, we sampled 20 A. baumannii isolates from a patient with extensive burns, and characterized the evolution of carbapenem resistance over a 45 day period via Illumina and Oxford Nanopore sequencing. All isolates were multidrug resistant, carrying two genomic islands that harboured several antibiotic-resistance genes. Most isolates were genetically identical and represented a single founder genotype. We identified three novel non-synonymous substitutions associated with meropenem resistance: F136L and G288S in AdeB (part of the AdeABC efflux pump) associated with an increase in meropenem MIC to ≥8 µg ml

Topics: Acinetobacter baumannii; Bacterial Proteins; beta-Lactamases; Carbapenems; Ciprofloxacin; Cross Infection; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Humans; Membrane Transport Proteins; Meropenem; Microbial Sensitivity Tests; Multilocus Sequence Typing; Polymorphism, Single Nucleotide; Protein Conformation; Sequence Analysis, DNA

Six cases of cutaneous melioidosis from southwestern Australia, a non-endemic region occurred as a result of Burkholderia pseudomallei contamination of normal saline that was used for irrigating superficial wounds. Treatment with parenteral meropenem, given by continuous infusion for 2 weeks, followed by oral antibiotics was successful in all cases.

Topics: Aged, 80 and over; Anti-Bacterial Agents; Burkholderia pseudomallei; Cross Infection; Disease Outbreaks; Female; Humans; Infusions, Intravenous; Male; Melioidosis; Meropenem; Middle Aged; Thienamycins; Treatment Outcome; Western Australia

The spread of antibiotic resistance is rapidly threatening the effectiveness of antibiotics in the clinical setting. Many infections are being caused by known and unknown pathogenic bacteria that are resistant to many or all antibiotics currently available. Empedobacter falsenii is a nosocomial pathogen that can cause human infections. E. falsenii Wf282 strain was found to be resistant to many antibiotics, including carbapenems and colistin. Whole-genome shotgun sequencing of the strain was performed, and distinct features were identified. A novel metallo-β-lactamase, named EBR-2, was found, suggesting a potential role of E. falsenii as a reservoir of β-lactamases and other resistance determinants also found in its genome. The EBR-2 protein showed the highest catalytic efficiency for penicillin G as compared to meropenem and ampicillin and was unable to hydrolyze cefepime. The results described in this work broaden the current understanding of the role of β-lactamases in the Flavobacteriaceae family and suggest that E. falsenii Wf282 may be a reservoir of these novel resistance determinants.

Topics: Amino Acid Sequence; Ampicillin; Anti-Bacterial Agents; beta-Lactamases; Cefepime; Cephalosporins; Cross Infection; Drug Resistance, Multiple, Bacterial; Flavobacteriaceae; Genome, Bacterial; Humans; Meropenem; Microbial Sensitivity Tests; Penicillin G; Thienamycins

A total of 18,656 Enterobacteriaceae and 4,175 Pseudomonas aeruginosa were consecutively collected from 85 US hospitals and tested for susceptibility by broth microdilution methods in a central monitoring laboratory (JMI Laboratories). The antimicrobial susceptibility and frequency of key resistance phenotypes were assessed and stratified by infection type as follows: bloodstream (BSI; 3,434 isolates; 15.0%), pneumonia (6,439; 28.2%), skin and skin structure (SSSI; 4,134; 18.1%), intra-abdominal (IAI; 951; 4.2%), and urinary tract (UTI; 7,873; 34.5%). Ceftazidime-avibactam was active against 99.9% to 100.0% of Enterobacteriaceae and 97.0% (pneumonia) to 99.4% (UTI) of P. aeruginosa isolates. Susceptibility rates were consistently lower for β-lactams, such as ceftazidime (82.3% vs. 87.1-90.8%), piperacillin-tazobactam (87.5% vs. 90.2-95.6%), and meropenem (96.8% vs. 98.4-99.4%) among Enterobacteriaceae from pneumonia compared to other infection types. Susceptibility to gentamicin was also generally lower among isolates from pneumonia, whereas susceptibility to levofloxacin and colistin were lowest among BSI and SSSI isolates, respectively. The occurrence of multidrug-resistance (MDR; 8.2% overall), extensively drug-resistance (XDR; 1.1% overall), and carbapenem-resistant Enterobacteriaceae (CRE; 1.3% overall) phenotypes were markedly higher among isolates from patients with pneumonia compared to other infection types. Among P. aeruginosa, susceptibility rates for ceftazidime, piperacillin-tazobactam, and gentamicin were lowest among isolates from pneumonia, whereas susceptibility to meropenem was similar among isolates from BSI, pneumonia, and IAI (77.3-77.9%), and susceptibility to levofloxacin was markedly lower among UTI isolates (67.1%). The frequencies of P. aeruginosa isolates with MDR and XDR phenotypes were highest among isolates from patients with pneumonia.

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Ceftazidime; Colistin; Cross Infection; Drug Combinations; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Meropenem; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Pseudomonas Infections; Thienamycins; United States

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

Acinetobacter baumannii (A. baumannii) is one of the leading pathogens in hospital infections. To characterize the epidemiology of A. baumannii in a burn ward, we collected all A. baumannii isolates though 18 months. Antibiotic susceptibility and antibiotic resistant genes were tested. Multilocus sequence typing (MLST) was further used to molecularly subtype these isolates. These isolates showed a severe multidrug resistant phenotype with 85% resistance to imipenem and meropenem. Along with the resistant phenotype, antibiotic resistant genes were widely found among these isolates. The prevalences of OXA23, AmpC, PER and VIM were 65.1%, 84%, 37.7% and 53%, respectively. Fifteen reported STs and sixteen novel STs were found in this study. ST368 (35%) was the dominant type, followed by ST195 (15%), ST191 (12%), ST369 (10%) and ST208 (10%). Majority (82.8%) of these isolates belong to clonal group 92, indicating the nosocomial spreading of A. baumannii. Further monitoring and control measures for A. baumannii spreading are necessary.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Burn Units; Burns; Cross Infection; Drug Resistance, Multiple, Bacterial; Humans; Imipenem; Meropenem; Molecular Epidemiology; Multilocus Sequence Typing; Thienamycins; Wound Infection

Ventilator associated pneumonia (VAP) is one of the most serious nosocomial infections in Intensive Care Unit (ICU). The aim of this study was to evaluate a new approach to spare the carbapenems for the management of patients diagnosed with VAP due to Acinetobacter baumannii (A. baumannii).. This retrospective study was conducted on VAP patients presenting for treatment at tertiary care centre between May 2014 and March 2016. The case sheets of patients who have been treated for VAP with meropenem, antibiotic adjuvant entity (AAE) and colistin were analysed.. Out of 113 patients analysed, 24 (21.3%) patients were having VAP due to MDR A. baumannii. Microbial sensitivity has shown that 87.5% of patients were sensitive to AAE and colistin whereas all of them were resistant to meropenem, imipenem and gentamycin. The mean treatment durations were 12.4±2.1, 13.2±2.4 and 14.3±2.1days for AAE, meropenem+colistin and AAE+colistin treatment groups. In AAE susceptible patients, the mean treatment duration and cost could be reduced by 23-24% and 43-53% if AAE is used empirically. In AAE-resistant patients, the mean treatment duration and cost could be reduced by 21% and 26% if AAE+colistin regime is used empirically instead of meropenem followed by AAE+colistin.. Clinical assessment with microbial eradication and pharmaco-economic evaluation clearly shows benefits in using AAE empirically in the management of A. baumannii infected VAP cases.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Anti-Bacterial Agents; Ceftriaxone; Chemotherapy, Adjuvant; Colistin; Cross Infection; Drug Therapy, Combination; Edetic Acid; Female; Humans; Intensive Care Units; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Pneumonia, Ventilator-Associated; Retrospective Studies; Sulbactam; Thienamycins

To assess risk factors for recurrent carbapenem-resistant Klebsiella pneumoniae bloodstream-infection (CR-KP BSI), we performed a prospective observational cohort study of all consecutive adult patients cured of a CR-KP BSI at our hospital over a six-year period (June 2010 to June 2016). Maximum follow-up per patient was 180 days from the index blood cultures (BCs). Recurrent CR-KP BSI was defined as new evidence of positive BCs in patients with documented clinical response after completing a course of anti-CR-KP therapy. Univariate and multivariate cause-specific Cox proportional hazards analysis were performed. During the study period 249 patients were diagnosed with a CR-KP BSI, 193 were deemed as cured within 14 days after index BCs and were analysed. Recurrence occurred in 32/193 patients (16.6%) within a median of 35 (IQR 25-45) days after index BCs. All but one of the recurrences occurred within 60 days after the index BCs. Comparison of recurrent and non-recurrent cases showed significant differences for colistin use (84.4% vs. 62.2%, p = 0.01), meropenem-colistin-tigecycline regimen (43.8% vs. 24.8%, p = 0.03) and length of therapy for the index BSI episode (median 18 vs. 14 days, p = 0.004). All-cause 180-day mortality (34.4% vs. 16.1%, p = 0.02) was higher in recurrent cases. In the multivariate analysis, the only independent variable was source control as a protective factor for recurrence. Recurrence is frequent among patients cured of a CR-KP BSI and is associated with higher long-term mortality. When feasible, source control is mandatory to avoid recurrence. The role of antibiotic treatment should be further investigated in large multicentre studies.

Topics: Aged; Anti-Bacterial Agents; beta-Lactam Resistance; Colistin; Cross Infection; Female; Hospitals; Humans; Incidence; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Minocycline; Prospective Studies; Recurrence; Risk Factors; Sepsis; Thienamycins; Tigecycline; Time Factors

Nosocomial pneumonia (NP) is a frequent complication among patients with intracerebral hemorrhage (ICH). However, there are currently no pharmacokinetic (PK) and pharmacodynamic (PD) data to guide meropenem dosing in these patients.. To investigate the PK/PD properties of meropenem in these patients and whether the usual dosing regimens of meropenem (2-hour infusion, 1 g, every 8 hours) was suitable.. A total of 11 patients with a diagnosis of ICH complicated with NP were selected in the emergency internal medicine and treated with a 1-g/2-hours extended infusion model. The plasma concentrations of meropenem were determined by high-performance liquid chromatography. PK parameters were estimated by plasma concentration versus time profile using WinNonlin software. The probability of target attainments (PTAs) of meropenem at different minimum inhibitory concentrations (MICs) based on percentage time that concentrations were above the minimum inhibitory concentration (%T>MIC) value were performed by Monte Carlo simulation.. The volume of distribution and total body clearance of meropenem were 55.55 L/kg and 22.89 L/h, respectively. Using 40%T>MIC, PTA was >90% at MICs ≤4 µg/mL. Using 80% or 100%T>MIC, PTA was >90% only at MICs ≤1 µg/mL.. The PK/PD profile of dosing regimens tested will assist in selecting the appropriate meropenem regimens for these patients. At a target of 40%T>MIC, the usual dosing regimens can provide good coverage for pathogens with MICs of ≤4 µg/mL. However, when a higher target (80% or 100%) is desired for difficult-to-treat infections, larger doses, prolonged infusions, shorter intervals, and/or combination therapy may be required.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Cerebral Hemorrhage; Cross Infection; Female; Humans; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Monte Carlo Method; Pneumonia; Thienamycins

In critical burn patients, the pharmacokinetic parameters (absorption, distribution, metabolism, and excretion) of many classes of drugs, including antibiotics, are altered. The aim of this study was to compare 2 groups of burn patients undergoing treatment for health care-associated infections with and without therapeutic drug monitoring.. A retrospective analysis of a clinical intervention (ie, a before/after study) was conducted with patients with health care-associated pneumonia, burn infection, bloodstream infection, and urinary tract infection in the burn intensive care unit of a tertiary care hospital. The patients were divided into 2 groups: (1) those admitted from May 2005 to October 2008 who received conventional antimicrobial dose regimens; and (2) those admitted from November 2008 to June 2011 who received antibiotics (imipenem, meropenem, piperacillin, and vancomycin) with doses adjusted according to plasma monitoring and pharmacokinetic modeling. General characteristics of the groups were analyzed, as were clinical outcomes and 14-day and in-hospital mortality.. Sixty-three patients formed the conventional treatment group, and 77 comprised the monitored treatment group. The groups were homogeneous, median age was 31 years (range: 1-90) and 66% were male. Improvement occurred in 60% of the patients under monitored treatment (vs 52% with conventional treatment); 14-day mortality was 16% vs 14%; and the in-hospital mortality was similar between groups (39% vs 36%). In the final multivariate models, variables significantly associated with in-hospital mortality were total burn surface area ≥30%, older age, and male sex. Treatment group did not affect the prognosis.. Therapeutic drug monitoring of antimicrobial treatment did not alter the prognosis of these burn patients. More trials are needed to support the use of therapeutic drug monitoring to optimize treatment in burn patients.

Topics: Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Burns; Child; Child, Preschool; Cross Infection; Drug Monitoring; Female; Humans; Imipenem; Infant; Intensive Care Units; Male; Meropenem; Middle Aged; Piperacillin; Pneumonia; Prognosis; Tertiary Care Centers; Thienamycins; Urinary Tract Infections; Vancomycin; Young Adult

The recent escalation of occurrences of carbapenem-resistant

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; beta-Lactamase Inhibitors; Catheter-Related Infections; Ceftazidime; Cephalosporins; Cross Infection; Drug Combinations; Humans; Meropenem; Microbial Sensitivity Tests; Penicillanic Acid; Pseudomonas aeruginosa; Pseudomonas Infections; Tazobactam; Thienamycins

Burkholderia sp. infections are extremely complex in cystic fibrosis (CF) patients, especially considering the lack of knowledge regarding its behavior, its relationship with prognosis, as well as its transmissibility and multidrug resistance features. This study evaluated the frequency of chronic infection by Burkholderia, using microbiological and clinical data. Ninety-eight patients with CF attended from July 2011 to April 2014 in a Brazilian reference hospital were included. Antimicrobial activity, molecular epidemiology, Shwachman score, body mass index, exacerbations, and lung function were analyzed. Nine patients had chronic colonization, and all of them showed preserved pulmonary function levels, body mass index, and Shwachman score. Meropenem was the most effective antibiotic; however, divergent results were shown by other studies. Cross-contamination may have occurred in only two unrelated patients of different ages, who were colonized by B. vietnamiensis, which does not occur frequently. Twelve new sequence types (STs) were identified and three STs have presented intercontinental distribution. None of the patients presented known epidemic strains. In conclusion, a relatively low number of patients with chronic colonization and suspected cross-infection were identified. Different from other studies that have found CF patients chronically colonized with Burkholderia sp. having a greater deterioration of lung function, more frequent antibiotic therapy, and increased mortality, in the current study, the patients showed good clinical outcomes and favorable options for antibiotics therapy. This study also updated the epidemiological database, which facilitates the multicentric collaborative analysis and assists in the control of global infection by these pathogens.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Brazil; Burkholderia cepacia complex; Burkholderia Infections; Ceftazidime; Child; Child, Preschool; Cross Infection; Cystic Fibrosis; Electrophoresis, Gel, Pulsed-Field; Female; Hospitals; Humans; Infant; Lung; Male; Meropenem; Microbial Sensitivity Tests; Molecular Typing; Respiratory Function Tests; Thienamycins; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Quinolones are frequently used classes of antimicrobials in hospitals, crucial for the treatment of infections caused by Gram-negative bacteria. The inappropriate use of quinolones and other antimicrobial agents for the treatment of bacterial infections leads to a significant increase of resistant isolates. The acquisition of antimicrobial resistance may be related to achievement of resistance determinant genes mediated by plasmids, transposons and gene cassettes in integrons. The objective of this cross-sectional study, conducted from December 2015 to July 2016 at two teaching hospitals in Ahvaz, southern Iran, was to screen for the presence of class 1 integrons and quinolone resistance genes in clinical isolates of Enterobacter spp. In all, 152 non-duplicated Enterobacter isolates were collected from clinical specimens and identified as Enterobacter spp. using standard microbiological methods. Antimicrobial susceptibility test was determined using the disc diffusion method according to the CLSI recommendation. Determination of class 1 integrons and PMQR genes was assessed by PCR. Analysis of antibiotic susceptibility tests showed that the highest antibiotic resistance was toward ciprofloxacin (55.3%), while the lowest level was observed against meropenem (34.9%). Moreover, 47.4% (72/152) and 29% (44/152) of isolates were positive for class 1 integron and quinolone resistance genes, respectively. The relative frequencies of antibiotic resistance were significantly higher among class 1 integron-positive isolates. In summary, our results highlight the importance of PMQR genes in the emergence of quinolone-resistant Enterobacter isolates. Moreover, it seems that class 1 integrons have a widespread distribution among Enterobacter isolates and have clinical relevance to multiple-drug-resistant isolates.

Topics: Anti-Bacterial Agents; Cross Infection; Cross-Sectional Studies; Drug Resistance, Multiple, Bacterial; Enterobacter; Enterobacteriaceae Infections; Fluoroquinolones; Genes, Bacterial; Humans; Imipenem; Integrons; Iran; Meropenem; Microbial Sensitivity Tests; Plasmids; Thienamycins

Carbapenem-resistant Pseudomonas aeruginosa infections have been a challenge and issue in hospital settings. However, the clinical impact of P. aeruginosa blood isolates resistant only to carbapenems has never been discussed previously.. To assess the risk factors and clinical significance of bacteremia caused by carbapenem resistance only P. aeruginosa (CROPA), a 6-year retrospective case-control study was conducted. The CROPA strains were defined as isolates susceptible to ciprofloxacin, antipseudomonal penicillins and cephalosporins, and aminoglycosides but resistant to one antipseudomonal carbapenem (imipenem or meropenem) or both. The controls were selected among patients with bacteremia due to P. aeruginosa susceptible to all above classes of antipseudomonal antibiotics, which was defined as all-susceptible P. aeruginosa.. Twenty-five patients had at least one blood culture positive for CROPA, and 50 controls had all-susceptible P. aeruginosa bacteremia. CROPA bacteremia had a high 30-day mortality rate (72.0%), as compared to 26.0% for the controls (p < 0.001). Through multivariate analysis, carbapenem exposure was the only risk factor for developing CROPA bacteremia (p = 0.002). A comparison between the surviving and deceased patients with CROPA bacteremia showed that nine (50%) of those who died, but none of the survivors, received carbapenems as the initial empirical therapy (p = 0.027).. Carbapenem exposure was associated with emergence of CROPA infections. Repeated carbapenem use in such patients might increase rates of inappropriate initial empirical treatment and mortality. Prudent carbapenem use is important to reduce the emergence of CROPA.

Topics: Adult; Aged; Aminoglycosides; Anti-Bacterial Agents; Bacteremia; Blood Culture; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Case-Control Studies; Cephalosporins; Ciprofloxacin; Cross Infection; Female; Hospitals; Humans; Imipenem; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Mortality; Multivariate Analysis; Odds Ratio; Penicillins; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Risk Factors; Severity of Illness Index; Taiwan; Thienamycins

Topics: beta-Lactamases; Cross Infection; Genotype; Hospitals; Humans; Hungary; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Molecular Typing; 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

The objective of the present study was to evaluate the prevalence of intestinal colonization with extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E) and carbapenemase-producing Enterobacteriaceae (CPE) in non-selected hospitalized and non-hospitalized patients from the same geographic area of Madrid.. A total of 501 fecal samples were screened. Diluted samples in saline were cultured in MacConkey agar plates with ceftazidime, cefotaxime, imipenem and meropenem disks. Colonies growing within the inhibition zone of either disk were selected. Characterization of ESBLs and CPEs were performed by PCR and sequencing. The Wider system was used for the bacterial identification. In addition, clonal analysis was carried out for species predominant among the fecal carriage.. Among the 501 patients enrolled, 43 (8.6 %) carried ESBL-E and 8 (1.6 %) patients exhibited CPE. The main intestinal colonizer among ESBL-E was CTX-M-producing Escherichia coli isolates in both settings (community and hospital). ST131 clonal complex was the most common among faecal ESBL-producing E. coli. All gut carriers of CPE were hospitalized patients, Klebsiella pneumoniae being the most prevalent species. Two OXA-48-producing K. pneumoniae isolates belonging to ST15 were detected.. Present study reveals that faecal carriage of ESBL is common among inpatients and outpatients, whereas carbapenemase producers are only present in the hospital setting. Therefore, active surveillance will be useful for reducing transmission of antimicrobial-resistant bacteria and preventing infection.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacterial Proteins; beta-Lactamases; Carrier State; Cefotaxime; Ceftazidime; Child; Child, Preschool; Cross Infection; Culture Media; Drug Resistance, Multiple, Bacterial; Escherichia coli; Feces; Female; Gastrointestinal Microbiome; Hospitalization; Humans; Imipenem; Infant; Intestines; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Spain; Thienamycins; Young Adult

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

Available therapeutic options against carbapenem-resistant Klebsiella pneumoniae (CR-Kp) are limited because of the high level of resistance to other antimicrobial classes including polymyxins. The double-carbapenem regimen has been recently considered a possible therapeutic strategy. In the present study, we evaluated the in vitro bactericidal and synergistic activity of a double-carbapenem regimen consisting of ertapenem plus high-dose meropenem in a series of patients with healthcare-associated CR-Kp infections in whom the use of colistin was not indicated because of potential nephrotoxicity and/or resistance. In vitro synergy was evaluated using checkerboard and killing studies. A total of 15 patients were included in the study, with sepsis, severe sepsis and septic shock found in two (13.3%), five (33.3%) and one (6.7%) patients, respectively. Overall, the clinical/microbiological response was 12/15 (80%). Synergy was observed in 11/14 (78.6%) isolates using the checkerboard method whereas in killing studies 12/14 (85.7%) and 14/14 (100%) strains were synergistic and bactericidal at 24 h at concentrations of 1 × MIC MEM+1 × MIC ERT and 2 × MEM+1 × MIC ERT, respectively, with a significant decrease of log CFU/mL compared with other combinations (p <0.0001). The double-carbapenem regimen showed clinical and in vitro effectiveness in patients with CR-Kp infections.

Topics: Aged; Anti-Bacterial Agents; beta-Lactams; Cross Infection; Dose-Response Relationship, Drug; Drug Resistance, Multiple, Bacterial; Drug Synergism; Ertapenem; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Sepsis; Thienamycins

Transplant recipients are at high risk of infections caused by multidrug resistant microorganisms. Due to the limited therapeutic options, innovative antimicrobial combinations against carbapenem-resistant Enterobacteriaceae causing severe infections are necessary.A 61-year-old woman with a history of congenital solitary kidney underwent renal transplantation. The postoperative course was complicated by nosocomial pneumonia due to Stenotrophomonas maltophilia and pan-sensitive Escherichia coli, successfully treated with antimicrobial therapy. On postoperative day 22, diagnosis of surgical site infection and nosocomial pneumonia with concomitant bacteremia due to a Klebisella pneumoniae carbapenemase-producer E coli was made. The patient was treated with the double-carbapenem regimen (high dose of meropenem plus ertapenem) and a potent synergistic and bactericidal activity of this un-conventional therapeutic strategy was observed in vitro. Despite a microbiological response with prompt negativity of blood cultures, the patient faced a worse outcome because of severe hemorrhagic shock.The double-carbapenem regimen might be considered as a rescue therapy in those subjects, including transplant recipients, in whom previous antimicrobial combinations failed or when colistin use might be discouraged. Performing in vitro synergy testing should be strongly encouraged in cases of infections caused by pan-drug resistant strains, especially in high-risk patients.

Topics: Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; beta-Lactams; Carbapenems; Cross Infection; Drug Resistance, Bacterial; Drug Synergism; Ertapenem; Escherichia coli; Escherichia coli Infections; Female; Humans; Kidney Transplantation; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Middle Aged; Surgical Wound Infection; Thienamycins

The aim of this multi-hospital study was to assess the in vitro activity of doripenem and its comparators, imipenem and meropenem, using the new CLSI breakpoints against a large population of a frequently isolated nosocomial pathogen, Acinetobacter baumannii.. During a 2-year period, four referral or tertiary hospitals submitted 400 isolates of Ac. baumannii for susceptibility testing using imipenem, meropenem and doripenem via disc diffusion and E-test methods. A subset of 390 isolates was resistant to all three tested carbapenems. Doripenem and meropenem (MIC50 , 32 μg ml(-1) ) had comparable activity, albeit doripenem's activity was greater than imipenem (MIC50 , >32 μg ml(-1) ). A significantly higher proportion of the isolates were inhibited by doripenem than by imipenem at MIC values of 12, 16, 24 and 32 μg ml(-1) (P < 0·05). The cumulative percentage of imipenem MICs was lower compared to its comparators. The comparison of resistance rate to imipenem and meropenem based on old and new breakpoints showed <1% difference. The overall agreement between the two susceptibility testing methods was ≥95%.. Doripenem has a slightly greater in vitro activity than imipenem in terms of zone breakpoints and MIC values, but its activity is comparable to meropenem.. Doripenem should be considered as a therapeutic option for monotherapy or combination therapy, particularly when the therapeutic options are limited.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; beta-Lactam Resistance; Carbapenems; Cross Infection; Doripenem; Humans; Imipenem; Iran; Meropenem; Microbial Sensitivity Tests; Thienamycins

Infection is a major determinant of clinical outcome among patients in the intensive care unit. However, these data are lacking in most developing countries; hence, we set out to describe the profile of nosocomial infection in one of the major tertiary hospitals in northern Nigeria.. Case records of patients who were admitted into the intensive care unit over a 4-year period were retrospectively reviewed. A preformed questionnaire was administered, and data on clinical and microbiological profile of patients with documented infection were obtained.. Eighty-our episodes of nosocomial infections were identified in 76 patients. Road traffic accident (29/76, 38.2%) was the leading cause of admission. The most common infections were skin and soft tissue infections (30/84, 35.7%) followed by urinary tract infection (23/84, 27.4%). The most frequent isolates were Staphylococcus aureus (35/84, 41.7%), Klebsiella pneumoniae (18/84, 21.4%), and Escherichia coli (13/84, 15.5%). High rate of resistance to cloxacillin (19/35, 54.3%) and cotrimoxazole (17/26, 65.4%) was noted among the S aureus isolates. All the Enterobacteriaceae isolates were susceptible to meropenem, whereas resistance rate to ceftriaxone was high (E coli, 55.6%; K pneumoniae, 71.4%; Proteus spp, 50%).. Infection control practice and measures to curtail the emergence of antimicrobial resistance need to be improved.

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Catheter-Related Infections; Ceftriaxone; Cloxacillin; Cross Infection; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Humans; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Nigeria; Pneumonia, Bacterial; Retrospective Studies; Staphylococcal Infections; Staphylococcus aureus; Surgical Wound Infection; Tertiary Care Centers; Thienamycins; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections; Young Adult

The ultrastructural alterations caused by polymyxin B and meropenem and by the association between polymyxin B and meropenem were investigated in two multiresistant isolates of Klebsiella pneumoniae (K3-A2 and K12-A2) carriers of blaKPC-2, coming from infection and colonization in patients in a public hospital in Recife, Brazil. The ultrastructural changes were detected by transmission electron microscopy and scanning. The susceptibility of the isolates to antimicrobials was tested by the disc diffusion method and microdilution in broth. The analysis by electron microscopy showed that the isolates presented morphological and ultrastructural cellular changes when subjected to a clinically relevant concentration of antimicrobials alone or in combination. When subjected to meropenem, they presented retraction of the cytoplasmic material, rupture of the cell wall and extravasation of the cytoplasmic content. When submitted to polymyxin B, the isolates showed condensation of the ribosomes, DNA clotting, cell wall thickening and the presence of membrane compartment. When subjected to polymyxin B and meropenem in combination, the isolates showed a higher intensity of the ultrastructural changes visualized. This is the first report of the ultrastructural changes caused by polymyxin B and meropenem in multiresistant isolates of K. pneumoniae carriers of the blaKPC-2 gene. It should be noted that even when the K. pneumoniae isolates were multiresistant carriers of the blaKPC-2 gene, they underwent important structural change owing to the action of polymyxin B and meropenem.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Brazil; Cross Infection; Drug Resistance, Multiple, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Microscopy, Electron; Microscopy, Electron, Scanning; Middle Aged; Polymyxin B; Thienamycins

In this study the ability for biofilm production among meropenem (MEM)-resistant and -susceptible Acinetobacter baumannii isolates was verified. MEM susceptibility and biofilm production were screened in 116 isolates. Meropenem-resistant A. baumannii isolates showed a reduced ability to produce biofilms compared to those susceptible to MEM (P<0.0001). The results suggest an inverse relationship between biofilm production and MEM resistance in nosocomial A. baumanni isolates.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Biofilms; Cross Infection; Drug Resistance, Multiple, Bacterial; Humans; Meropenem; Microbial Sensitivity Tests; Thienamycins

The objective of this study was to propose an optimal treatment regimen of meropenem in critically ill patients with severe nosocomial pneumonia.. Among 55 patients in intensive care treated with 1 g of meropenem every 8 h for severe nosocomial pneumonia, 30 were assigned to intermittent infusion (II; over 0.5 h) and 25 to extended infusion (EI; over 3 h) groups. Based on plasma and epithelial lining fluid (ELF) concentrations determined at steady-state, pharmacokinetic modelling and Monte Carlo simulations were undertaken to assess the probability of attaining drug concentrations above the MIC for 40%-100% of the time between doses (%T > 1-fold and 4-fold MIC), for 1 or 2 g administered by either method.. Penetration ratio, measured by the ELF/plasma ratio of AUCs, was statistically higher in the EI group than in the II group (mean ± SEM: 0.29 ± 0.030 versus 0.20 ± 0.033, P = 0.047). Considering a maximum susceptibility breakpoint of 2 mg/L, all dosages and modes of infusions achieved 40%-100% T > 1-fold MIC in plasma, but none did so in ELF, and only the 2 g dose over EI achieved 40%-100% T > 4-fold MIC in plasma.. The optimum regimen to treat severe nosocomial pneumonia was 2 g of meropenem infused over 3 h every 8 h. This regimen achieved the highest pharmacodynamic targets both in plasma and in ELF.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Critical Illness; Cross Infection; Female; Humans; Infusions, Intravenous; Male; Meropenem; Middle Aged; Plasma; Pneumonia, Bacterial; Prospective Studies; Respiratory Mucosa; Thienamycins; Young Adult

A novel New Delhi metallo-β-lactamase (NDM) variant, NDM-14, was identified in clinical isolate Acinetobacter lwoffii JN49-1, which was recovered from an intensive care unit patient at a local hospital in China. NDM-14, which differs from other existing enzymes by an amino acid substitution at position 130 (Asp130Gly), possesses enzymatic activity toward carbapenems that is greater than that of NDM-1. Kinetic data indicate that NDM-14 has a higher affinity for imipenem and meropenem.

Topics: Acinetobacter; Acinetobacter Infections; Amino Acid Substitution; Anti-Bacterial Agents; beta-Lactamases; Carbapenems; China; Cross Infection; Drug Resistance, Bacterial; Humans; Imipenem; Intensive Care Units; Kinetics; Meropenem; Molecular Sequence Data; Plasmids; Thienamycins

A total of 1085 strains of Acinetobacter sp. obtained from 280 medical institutions in the Chugoku and Shikoku areas of Japan were investigated between 2011 and 2013. Among these strains, 20 (1.84 %) showing meropenem or imipenem resistance with a MIC of >4 μg ml- 1 were detected. Of these 20 strains, the bla(OXA-23) gene was detected in 17 strains isolated from the same institution. The PFGE patterns of the 17 strains were separated into two clusters, and multi-locus sequence typing showed the sequence types (STs) to be ST2 and ST246. This investigation demonstrated that A. baumannii ST2 of international clone II, which has rarely been isolated in Japan, has not yet spread nationwide.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; beta-Lactamases; Cross Infection; Drug Resistance, Multiple, Bacterial; Hospitals; Humans; Imipenem; Japan; Meropenem; Microbial Sensitivity Tests; Multilocus Sequence Typing; Thienamycins

Nosocomial pathogens can be associated with a variety of infections, particularly in intensive care units (ICUs) and in immunocompromised patients. Usually these pathogens are resistant to multiple drugs and pose therapeutic challenges. Among these organisms, Acinetobacter baumannii is one of the most frequent being encountered in the clinical setting. Carbapenems are very useful to treat infections caused by these drug-resistant Gram-negative bacilli, but carbapenem resistance is increasing globally. Combination therapy is frequently given empirically for hospital-acquired infections in critically ill patients and is usually composed of an adequate beta-lactam and an aminoglycoside. The purpose of this study was to evaluate the in vitro activity of plazomicin against carbapenem-resistant Acinetobacter baumannii. Amikacin was used as a comparator. The activity of plazomicin in combination with several different antibiotics was tested by disk diffusion, the checkerboard method, and time-kill studies. Synergy was consistently observed with carbapenems (meropenem and/or imipenem) along with plazomicin or amikacin. When the aminoglycosides were combined with other classes of antibiotics, synergy was observed in some cases, depending on the strain and the antibiotic combination; importantly, there was no antagonism observed in any case. These findings indicate the potential utility of plazomicin in combination with other antibiotics (mainly carbapenems) for the treatment of A. baumannii infections, including those caused by carbapenem-resistant isolates.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Amikacin; Anti-Bacterial Agents; beta-Lactam Resistance; Cross Infection; Drug Synergism; Drug Therapy, Combination; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Sisomicin; Thienamycins

Extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae are the leading causes of hospital-associated infections, but community-acquired cases are increasingly being reported. This study determined the prevalence of ESBL-producing E. coli and K. pneumoniae carriers, their bla genes and risk factors of 452 patients admitted to the emergency room (ER) of Ramathibodi Hospital, Mahidol University, Bangkok, Thailand between April and August 2011. Prevalence of ESBL-producing E. coli and K. pneumoniae from rectal swabs was 16.5% and 1.0%, respectively. Factors associated with ESBL-producing carriers were a previous history of hospital admission (p = 0.001) and visits to health care facilities (p = 0.002) during the previous 3 months. All ESBL-producing isolates were susceptible to imipenem, meropenem and ertapenem. The majority (78%) of ESBL-producing E. coli isolates showed very high resistance to cefotaxime and ceftriaxone (MIC50 and MIC90 > 256 µg/ml). ESBL-producing E. coli harbored chromosomal blaTEM (96%), blaCTX-M (70%) and blaSHV (1%), while 8%, 73% and 3%, respectively, were located on plasmid. The prevalence of these genes in ESBL-producing K. pneumoniae was 75%, 50% and 25%, respectively on chromosome; and 100%, 25% and 50%, respectively on plasmid. Nucleotide sequence analysis revealed that these bla genes were of the type blaTEM-1' blaTEM-116' blaCTX-M-15' blaCTX-M-161' blaSHV-12, blaSHV-28 and blaSHV-148. Detailed epidemiologic and clinical characteristics of ER patients with history of prior hospital visits should be carried out to identify the ESBL-producing organisms they have acquired in order to institute appropriate treatment for these patients as well as control measures against further dissemination of these life-threatening organisms.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; beta-Lactamases; beta-Lactams; Cross Infection; Emergency Service, Hospital; Ertapenem; Escherichia coli; Escherichia coli Infections; Female; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Plasmids; Thailand; Thienamycins; Young Adult

Chromobacterium violaceum is sensitive to temperature and the infection is usually confined to tropical or subtropical regions. Since Japan has a warm climate, C. violaceum has been scarcely isolated from clinical specimens. With global warming, however, the geographical distribution of C. violaceum infection is likely to change. We report two cases of C. violaceum nosocomial pneumonia that occurred at an intensive care center in Japan. C. violaceum was first detected from a patient in the same center as a pathogenic organism of pneumonia. Later, the organism was isolated from sputum and a ventilator circuit tube of another patient in the center. The two patients were admitted to the center in nearby beds for several days. All of the pathogens were confirmed to be C. violaceum by the nucleic acid sequence of the 16S rRNA gene and were proven to be genetically identical organisms by pulsed field gel electrophoresis. Both patients were managed with well-humidified and heated oxygen using a venturi mask and ventilator to promote excretion of sputum. It was thought that the medical respiratory care devices that provide a humid and warm environment, an optimal condition for proliferation of C. violaceum, can contribute to C. violaceum infection in a hospital environment.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Chromobacterium; Cross Infection; Gram-Negative Bacterial Infections; Humans; Male; Meropenem; Pneumonia, Bacterial; Sputum; Thienamycins

To investigate control of an outbreak due to orthopedic infections caused by Enterobacteriaceae producing IMP carbapenemases.. The sporadic orthopedic infections with Enterobacteriaceae producing carbapenemase (CPE) were retrospectively analyzed in a Chinese tertiary care hospital from November 2010 to September 2012.. The CPE were isolated from four distinct orthopedic patients, three patients infected with Enterobacter cloacae while the other with Klebsiella oxytoca. All strains were resistant to almost all the conventional antimicrobial. The strains produced IMP-4 type detected in the two early patients, while other strains could produce IMP-8 type. All of the four patients had ever undergoing invasive surgical procedure, and three of them were given fluoroquinolones for anti-infection treatment while the other patients was treated with meropenem. Ultimately, all patients were cured and discharged, without outbreak of nosocomial infection caused by CPE.. Our study shows that strict infection control plays an important role in limiting dissemination of Enterobacteriaceae producing IMP carbapenemase. In addition, reasonable supporting treatment and disinfection protection seems to be more effective for the infection of strains.

Topics: Adolescent; Anti-Bacterial Agents; Arthritis, Infectious; beta-Lactam Resistance; beta-Lactamases; China; Cross Infection; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Enterobacter cloacae; Enterobacteriaceae Infections; Female; Fluoroquinolones; Fracture Fixation, Internal; Humans; Infection Control; Klebsiella Infections; Klebsiella oxytoca; Levofloxacin; Male; Meropenem; Middle Aged; Osteitis; Patient Isolation; Protective Clothing; Retrospective Studies; Surgical Wound Infection; Thienamycins; Universal Precautions; Wound Infection

Acinetobacter baumannii has been reported increasingly as a significant causative organism of various nosocomial infections, including hospital-acquired pneumonia (HAP). The aim of this study was to investigate the clinical characteristics of HAP induced by carbapenem-resistant A. baumannii (CRAB) in elderly patients and the in vitro antimicrobial effects of cefoperazone/sulbactam combination therapy.. Seventy-one elderly patients in the geriatric ward of the General Hospital of the People's Liberation Army (PLAGH) with CRAB-induced HAP were analyzed retrospectively. The checkerboard method was used to determine the in vitro drug sensitivity of 60 CRAB strains to antimicrobial combinations (cefoperazone/sulbactam with meropenem, minocycline, or levofloxacin). The occurrence of carbapenemase genes was detected by PCR.. CRAB-induced HAP occurred mostly in patients with underlying diseases. Prior to onset, most patients had received antimicrobial therapies including broad-spectrum β-lactams, invasive mechanical ventilation, and catheterization. The 30-day survival rate was 95.1% in patients using cefoperazone/sulbactam, with or without combination with antimicrobial drugs, and 73.3% in patients not using cefoperazone/sulbactam (p<0.05). When cefoperazone/sulbactam was used in combination with minocycline, levofloxacin, and meropenem, minimum inhibitory concentrations MIC50 and MIC90 were reduced for each drug. The genes OXA-23 and OXA-51 were amplified in 96.7% of the strains, but the genes OXA-24, OXA-58, SIM, VIM, and IMP were not amplified.. CRAB-induced HAP occurred mostly in patients with anemia or decreased levels of serum albumin, but with elevated levels of C-reactive protein and creatinine. Cefoperazone/sulbactam in combination with minocycline, meropenem, and levofloxacin had a synergistic and additive in vitro bacteriostatic action on CRAB.

Topics: Acinetobacter baumannii; Aged; Aged, 80 and over; Anti-Bacterial Agents; C-Reactive Protein; Carbapenems; Cefoperazone; Cross Infection; Drug Combinations; Drug Resistance, Multiple, Bacterial; Drug Synergism; Female; Humans; Levofloxacin; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Bacterial; Retrospective Studies; Sulbactam; Thienamycins

Acinetobacter baumannii which is an opportunistic pathogen leading to nosocomial epidemics, exhibit high rates of antimicrobial resistance. Treatment of Acinetobacter infections is a challenge since most of the isolates are multiple antibiotic resistant. The aim of this study was to investigate minimum inhibitory concentrations (MICs) of sulbactam, imipenem, meropenem, and cefoperazone and in vitro synergistic activity of sulbactam in combination with imipenem, meropenem and cefoperazone against A.baumannii isolates of hospitalized patients. Forty A.baumannii strains isolated from various clinical specimens and found to be resistant to carbapenems by disc diffusion method, were included in the study. The isolates were identified by conventional methods and VITEK 2 (bioMerieux, France) automated identification system. MICs of sulbactam, imipenem, meropenem, and cefoperazone were determined by the broth microdilution method according to the standards of CLSI and in vitro synergy test was performed using the checkerboard microdilution method. Synergistic, partial synergistic, additive, indifferent and antagonistic effects of drug combinations were evaluated with the fractional inhibitory concentration index (FICI). Interpretation of the FICI was as follows: ≤ 0.5 synergy; > 0.5 to < 1 partial synergy; 1 additive; > 1 to < 4 indifference; and ≥ 4 antagonism. Forty A.baumannii isolates were resistant to imipenem and cefoperazone, but two were susceptible, seven were moderately susceptible and 31 were resistant to meropenem with the microdilution method. MIC values of the isolates for sulbactam were found to be 4 μg/ml in two, 8 μg/ml in five, 16 μg/ml in three, 32 μg/ml in 13, 64 μg/ml in three, 128 μg/ml in six and > 128 μg/ml in eight isolates. According to the FICI; imipenem/sulbactam combination exhibited synergy in 18 (45%), partial synergy in 4 (10%) and indifferent effect in 2 (5%) isolates, the combination of meropenem and sulbactam showed synergy in 19 (48%), partial synergy in 3 (7.5%), and indifferent effect in 3 (7.5%) isolates, the combination of cefoperazone/sulbactam demonstrated synergy in 18 (45%), partial synergy in 2 (5%), and indifferent effect in 2 (5%) isolates. There was no antagonistic effect with the tested combinations. In conclusion, MIC values of sulbactam were generally high in carbapenem-resistant A.baumannii strains. However, synergistic effect was detected in approximately half of the strains with the sulbactam/carbapenem combin

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; beta-Lactam Resistance; Carbapenems; Cefoperazone; Cross Infection; Drug Combinations; Drug Synergism; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Sulbactam; Thienamycins

The role of Acinetobacter nosocomialis and Acinetobacter pittii, which belong to the A. calcoaceticus-A. baumannii complex, in hospital-acquired infections is increasingly recognized. Here we describe a retrospective cohort study of hospital-acquired A. calcoaceticus-A. baumannii complex infections at a university hospital in Thailand. A total of 222 unique cases were identified between January 2010 and December 2011. The genomospecies of the A. calcoaceticus-A. baumannii complex isolates were classified as follows: A. baumannii, 197 (89%); A. nosocomialis, 18 (8%); and A. pittii, 7 (3%). All A. nosocomialis and A. pittii isolates were susceptible to imipenem and meropenem. The patients infected with A. nosocomialis and A. pittii had lower 30-day mortality than those infected with carbapenem-susceptible A. baumannii (P = 0.025) and carbapenem-resistant A. baumannii (P = 0.013). The factors influencing 30-day mortality were infection with non-baumannii A. calcoaceticus-A. baumannii complex (hazard ratio [HR], 0.12; 95% confidence interval [CI], 0.03 to 0.51; P = 0.004), infection with carbapenem-resistant A. baumannii (HR, 1.57; 95% CI, 0.89 to 2.79; P = 0.105), appropriate empirical antimicrobial therapy (HR, 0.38; 95% CI, 0.23 to 0.61; P < 0.001), and higher acute physiology and chronic health evaluation II (APACHE II) score (HR, 1.15; 95% CI, 1.10 to 1.19; P < 0.001). In Galleria mellonella assays, the survival rates were significantly higher for the larvae infected with A. nosocomialis or A. pittii than for those infected with either carbapenem-susceptible A. baumannii or carbapenem-resistant A. baumannii, but no differences in survival rates were observed between carbapenem-susceptible A. baumannii and carbapenem-resistant A. baumannii. These findings suggest intrinsic differences in virulence between non-baumannii A. calcoaceticus-A. baumannii complex species and A. baumannii but not between carbapenem-susceptible and resistant A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Animals; Anti-Bacterial Agents; Cohort Studies; Cross Infection; Drug Resistance, Bacterial; Female; Humans; Imipenem; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Moths; Retrospective Studies; Thienamycins; Treatment Outcome

Pantoea calida, a recently described environmental Enterobacteriaceae organism, has not yet been associated with human infection.. We report a case of postoperative meningitis caused by P. calida. After pituitary adenoma resection, a 52-year-old Caucasian woman developed febrile meningitis confirmed by cerebrospinal fluid analysis. P. calida was grown in pure culture from this fluid and was firmly identified with partial rpoB gene sequencing. She was cured by a 14-day course of meropenem.. P. calida must be added to the list of opportunistic Enterobacteriaceae pathogens responsible for postsurgical meningitis. It is easily identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

Topics: Adenoma; Anti-Bacterial Agents; Cross Infection; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Meningitis, Bacterial; Meropenem; Middle Aged; Pituitary Neoplasms; Thienamycins

The molecular epidemiology of 66 NDM-producing isolates from 2 Pakistani hospitals was investigated, with their genetic relatedness determined using repetitive sequence-based PCR (Rep-PCR). PCR-based replicon typing and screening for antibiotic resistance genes encoding carbapenemases, other β-lactamases, and 16S methylases were also performed. Rep-PCR suggested a clonal spread of Enterobacter cloacae and Escherichia coli. A number of plasmid replicon types were identified, with the incompatibility A/C group (IncA/C) being the most common (78%). 16S methylase-encoding genes were coharbored in 81% of NDM-producing Enterobacteriaceae.

Topics: Acinetobacter baumannii; Amdinocillin; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Cross Infection; DNA, Bacterial; Doripenem; Enterobacteriaceae; Fosfomycin; Humans; Meropenem; Methyltransferases; Microbial Sensitivity Tests; Molecular Epidemiology; Multilocus Sequence Typing; Pakistan; Thienamycins

Acinetobacter baumannii is a Gram-negative coccobacillus that has emerged as a troublesome pathogen causing institutional outbreaks. Environmental contamination is a distinctive characteristic of this microorganism, which brings a further difficulty in infection control. During A. baumannii outbreaks in intensive care units, a common contaminated object can be found as a reservoir. Finding out this source by epidemiological investigations is of particular importance in order to develop effective interventions. We describe an outbreak of A. baumannii and the results of epidemiological investigations in a neonatal intensive care unit. The outbreak strain was isolated from the outer surface of a breastmilk pump. We have successfully controlled the outbreak by careful reviewing of our milk collection process.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Ampicillin; Anti-Bacterial Agents; Breast Milk Expression; Cross Infection; Disease Outbreaks; Disease Reservoirs; Equipment Contamination; Humans; Incidence; Infant, Newborn; Infection Control; Intensive Care Units, Neonatal; Male; Meropenem; Microbial Sensitivity Tests; Respiratory Distress Syndrome, Newborn; Sulbactam; Thienamycins

Acinetobacter baumannii is an emerging pathogen worldwide that is most commonly associated with nosocomial infections and multi-drug resistance. In the present study we determined the mechanisms of carbapenem resistance and clonal diversity of A. baumannii nosocomial isolates in Hospital Civil de Guadalajara, Mexico.. A total of 303 clinical isolates of A. baumannii identified during a period expanding from 2004-2011 were analyzed for carbapenem resistance using several microbiological and molecular methods. Clonal relatedness of these isolates was determined using pulsed-field gel electrophoresis.. Of the 303 isolates, 84% were resistant to meropenem, 71.3% to imipenem and 78.3% the resistant isolates were positive for metallo-β-lactamases as determined by the phenotypic assay. In addition, 49.6% of carbapenem-intermediate or -resistant isolates carried the blaOXA-72 gene and 1.2% carried the blaVIM-1 gene. Efflux pump phenotype was responsible for reduced susceptibility to meropenem in 14.5% and to imipenem in 31.6% of the resistant isolates, respectively in the presence of the efflux pump inhibitor, carbonyl cyanide 3-chlorophenylhydrazone. Strains representing different carbapenem-resistant patterns exhibited reduced expression of 22, 29, 33, and 43 kDa OMPs. Among the bacterial collection studied, 48 different clones were identified, two of which were predominant and persistently transmitted.. Carbapenemase production in combination with efflux pump expression, reduction in OMPs expression and the cross-transmission of clones appear to be major contributors to the high frequency of carbapenem-resistance observed in A. baumannii. To our knowledge, this is the first study to define the molecular mechanisms associated with carbapenem-resistance in A. baumannii in Mexico.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Biological Transport; Carbapenems; Cross Infection; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Hospitals; Humans; Hydrazones; Imipenem; Meropenem; Mexico; Microbial Sensitivity Tests; Thienamycins

Carbapenem-resistant Enterobacteriaceae (CRE) are a growing problem worldwide. Guidelines focus on carbapenemase-producing organisms, and little is known about whether strict adherence to infection control measures is effective for CRE without carbapenemase. During 2009, CRE increased markedly in a tertiary hospital, and enhanced infection control measures without active surveillance were adopted.. Beginning in April 2010, enhanced antimicrobial stewardship, strict contact precautions, and cohort isolation were adopted. After September 2010, hand hygiene performance was prospectively monitored by active surveillance, and results were monthly fed back to medical personnel. Available carbapenem-resistant Escherichia coli (ECO) and carbapenem-resistant Klebsiella pneumoniae (KPN) isolated during 2008-2010 were characterized. Imipenem and meropenem minimal inhibitory concentrations were confirmed by E-test (AB biodisk, Solna, Sweden). Phenotypic screening assays and polymerase chain reaction (PCR) amplification of known β-lactamase and carbapenemase genes were performed.. From 3,511 ECO and 2,279 KPN, 44 (0.76%) were CRE (3 ECO, 41 KPN). CRE incidence rates rose from 1.61 in 2008 to 5.49 in 2009; they rose further to 9.81 per 100,000 patient days in early 2010. After adoption of strict infection control measures, CRE frequency fell back in 2011 and remained at baseline afterward. Phenotypic screening and PCR showed AmpC β-lactamase and extended spectrum β-lactamases with or without loss of porins; carbapenemases were not detected.. Enhanced infection control measures, even without active surveillance, seem effective to prevent further spread of CRE in a low-prevalence setting with mainly carbapenemase-nonproducing CRE.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Carbapenems; Containment of Biohazards; Cross Infection; Enterobacteriaceae; Enterobacteriaceae Infections; Hospitals, Teaching; Humans; Imipenem; Incidence; Infection Control; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Phenotype; Prevalence; Prospective Studies; Republic of Korea; Retrospective Studies; Thienamycins

To investigate the change of the antibiotic resistance profiles of the nosocomial Acinetobacter baumannii isolates in intensive care units (ICUs) between the years 2008 and 2011.. A. baumannii isolates that were responsible for ICU-acquired nosocomial infections between 2008 and 2011 were included in the study. The susceptibility rates of the antibiotics that are mainly used in the treatment of Acinetobacter infections were compared by years. Clinical and Laboratory Standards Institute criteria were used to determine antimicrobial susceptibility.. There were 252 infection episodes detected in 229 hospitalized patients in the ICU that were caused by A. baumannii. Imipenem resistance was found as 98.9% in 2011 whereas it was 54% in 2008. A significant increase was observed for meropenem resistance from 2008 (73.5%) to 2011 (98.9%). Colistin resistance, confirmed by E-test, was found in 4 strains. The resistance rates of other antimicrobial agents were as follows: ampicillin/sulbactam 95.7% and 93.5%, cefoperazone/sulbactam 45.7% and 90.3%, netilmicin 41.7% and 53%, gentamicin 96% and 87.2%, and trimethoprimsulfamethoxazole 91.7% and 72%, in 2008 and 2011, respectively. The resistance rate to tigecycline increased to 81.3% in 2011 from 12.5% in 2008.

Topics: Acinetobacter baumannii; Cross Infection; Drug Resistance, Bacterial; Imipenem; Intensive Care Units; Meropenem; Microbial Sensitivity Tests; Thienamycins; Time Factors

In the context of the substantial increase in antibiotic resistance rates of Acinetobacter baumannii, we aimed to evaluate the susceptibility rate changes of A. baumannii strains for carbapenems. A. baumannii strains isolated from patients diagnosed with healthcare-associated infections between 2007-2010 were included. A total of 127 A. baumannii strains [53 (42%) from the intensive care unit and 74 (58%) from the non-intensive care unit] were isolated. Conventional methods and an automated microbiology system were used for identification. Susceptibility testing was studied by Kirby-Bauer disk diffusion method. In 2007, five of 26 strains, in 2008, 18 of 31, in 2009, 10 of 35, in 2010, and 20 of 35 were obtained from intensive care unit patients. The susceptibility rate for imipenem was 50% in 2007 but 20% in 2010, while for meropenem it was 55% in 2007 but 12% in 2010. Prevention and control of antibiotic resistance among Acinetobacter species needs antibiotic usage restrictions and infection control precautions.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; beta-Lactam Resistance; Carbapenems; Cross Infection; Hospitals, University; Humans; Imipenem; Intensive Care Units; Meropenem; Microbial Sensitivity Tests; Prognosis; Risk Factors; Thienamycins; Turkey

Resistance to carbapenems is a significant therapeutic threat. The increasing frequency of car bapenemase enzymes among Gram-negative bacilli makes their early detection and differentiation urgent. Carbapenemases belonging to Class A are most commonly produced by members of family Enterobacteriaceae and are inhibited to various degrees by clavulanic acid. The present study is aimed to determine the occurrence and phenotypic detection of Class A carbapenemases in Escherichia coli and Klebsiella pneumoniae blood isolates from septicemic patients.. A total of 75 isolates of K. pneumoniae and 25 E. coli were screened for resistance to carbapenems by using meropenem and imipenem discs and meropenem E-test. Positive strains were then subjected to a modified Hodge test combined with carbapenemase inhibition tests to phenotypically detect and differentiate Class A serine carbapenemases from other classes of carbapenem hydrolyzing enzymes.. The screening test showing the number of isolates resistant to meropenem and imipenem were 41 and 35 for K. pneumoniae and nine and four for E. coli, respectively. A total of 25 (33.3%) K. pneumoniae isolates and two (8.0%) E. coli isolates were classified as Class A carbapenemase producers. Multidrug resistance with coexistence of extended spectrum-beta-lactamases occurred in 44.4% isolates. However, all of the isolates were susceptible to colistin, polymyxin B, and tigecycline by disc diffusion test.. We conclude from the present study that Class A carbapenemases appear to be the predominant cause of resistance to carbapenems in Enterobacteriaceae at our center and, thus, phenotypic detection based on simple methods should be employed routinely in clinical microbiology laboratories.

Topics: Adult; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Cross Infection; Escherichia coli; Escherichia coli Infections; Female; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Prevalence; Sepsis; Tertiary Care Centers; Thienamycins

Topics: Aged; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colombia; Cross Infection; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Pneumonia, Bacterial; Stroke; Thienamycins

Newborns are rarely infected by extended-spectrum β-lactamase (ESBL)-producing members of the Enterobacteriaceae. In a neonatal intensive care unit, 14 newborns were infected or colonized by CTX-M-15-producing Enterobacter cloacae. All seven infected patients had underlying medical conditions, and five of them were treated successfully with meropenem, whilst one untreated patient died. Paediatric infections caused by multidrug-resistant ESBL-producing Enterobacter cloacae constitute a critical clinical and epidemiological issue.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cluster Analysis; Cross Infection; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Enterobacter cloacae; Enterobacteriaceae Infections; Female; Genotype; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Male; Meropenem; Microbial Sensitivity Tests; Molecular Typing; Thienamycins; Treatment Outcome

Carbapenem-resistant Acinetobacter baumannii (CRAB) are an increasing infectious threat in hospitals. We investigated the clinical epidemiology of CRAB infections vs. colonization in patients, and examined the mechanisms of resistance associated with elevated minimum inhibitory concentrations (MICs) for carbapenems. From January to June 2009, 75 CRAB strains were collected. CRAB infection was significantly associated with malignancy and a high APACHE II score. The most dominant resistance mechanism was ISAba1 preceding OXA-51, producing strains with overexpression of efflux pump. Strains carrying blaOXA-23-like enzymes had higher carbapenem MICs than those carrying blaOXA-51-like enzymes; however, the presence of multiple mechanisms did not result in increased resistance to carbapenems. There was no difference in the resistance mechanisms in strains from infected and colonized patients. The majority of strains were genetically diverse by DNA macrorestriction although there was evidence of clonal spread of four clusters of strains in patients.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactam Resistance; Carbapenems; Chi-Square Distribution; Cluster Analysis; Cross Infection; Electrophoresis, Gel, Pulsed-Field; Female; Humans; Imipenem; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Molecular Epidemiology; Republic of Korea; Risk Factors; Statistics, Nonparametric; Thienamycins

Acinetobacter species have emerged as opportunistic nosocomial pathogens in intensive care units. Epidemic spread and outbreaks of multidrug-resistant or carbapenem-resistant Acinetobacter baumannii infections have been described worldwide. Species distribution, antimicrobial resistance and genotypes were investigated for Acinetobacter species isolates collected from a single institution in Korea over 7 years. Two hundred and eighty-seven Acinetobacter species isolates were collected from patients with bloodstream infections in one Korean hospital from 2003 to 2010. Most of them belonged to the Acinetobacter calcoaceticus-baumannii complex (94.4 %). The most frequently isolated species was A. baumannii (44.2 %), followed by Acinetobacter nosocomialis (formerly Acinetobacter genomic species 13TU) (34.1 %). The proportion of A. baumannii increased significantly from 2008 to 2010 (40.4 to 50.0 %). From 2008, imipenem and meropenem resistance rates increased significantly compared with 2003-2007 (12.9 % and 20.5 %, respectively, to 41.4 % and 41.5 %, respectively). An increased carbapenem resistance rate between the two periods was identified more clearly amongst A. baumannii isolates. Polymyxin-resistant A. baumannii isolates emerged in 2008-2010, despite the availability of few isolates. The increase of carbapenem resistance in A. baumannii might be due to the substitution of main clones. Although ST92 and ST69 were the most prevalent clones amongst A. baumannii in 2003-2007 (47.8 % and 15.9 %, respectively), ST75 and ST138 had increased in 2008-2010 (39.7 % and 25.9 %, respectively). Although ST92 showed moderate resistance to carbapenems, most ST75 and ST138 isolates were resistant to carbapenems. All ST75 and ST138 isolates, but only one ST92 isolate, contained the bla(OXA-23-like) gene. Increased carbapenem resistance in Acinetobacter species and A. baumannii isolates might be due to the expansion of specific carbapenem-resistant clones.

Topics: Acinetobacter; Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteremia; Carbapenems; Cross Infection; Drug Resistance, Bacterial; Genotype; Hospitals; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Republic of Korea; Species Specificity; Thienamycins

The aim of this study was to determine the current susceptibility of hospital isolates of contemporary Gram-negative pathogens to the carbapenems doripenem, imipenem and meropenem. Between May and October 2008, seven centres in Germany were invited to collect and submit Pseudomonas aeruginosa, Enterobacteriaceae and other Gram-negative bacterial Intensive Care Unit (ICU)/non-ICU isolates from patients with complicated intra-abdominal infections (cIAIs), bloodstream infections (BSIs) or nosocomial pneumonia (NP). Susceptibility was determined at each centre by Etest. A central laboratory performed species confirmation as well as limited susceptibility and quality control testing. In total, 363 isolates were collected, comprising 46.0% Enterobacteriaceae, 45.2% P. aeruginosa, 4.7% Acinetobacter spp. and 4.1% other Gram-negatives. Most isolates (47.9%) were collected from NP, 32.8% were from cIAIs and 19.3% from BSIs; 57.3% were obtained from ICU patients. The MIC(90) values (minimum inhibitory concentration for 90% of the isolates) for doripenem, meropenem and imipenem were, respectively, 4, 16 and 32 mg/L against P. aeruginosa, 0.06, 0.06 and 0.5mg/L against Enterobacteriaceae and ≥ 64 mg/L for each carbapenem against other Gram-negative isolates. Using European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints, 81.1%, 75.6% and 79.3% of P. aeruginosa were susceptible to doripenem, imipenem and meropenem, respectively. Against all pathogens combined, MIC(90) values for ICU versus non-ICU isolates, respectively, were 4 mg/L vs. 1mg/L for doripenem, 8 mg/L vs. 1mg/L for meropenem and ≥ 64 mg/L vs. 8 mg/L for imipenem. Doripenem showed comparable activity against P. aeruginosa from patients with BSIs, cIAIs or NP. Similar findings were observed for Enterobacteriaceae and other Gram-negatives, including Acinetobacter spp. Doripenem generally showed similar or slightly better activity than meropenem and better activity than imipenem against Gram-negative pathogens collected in Germany.

Topics: Bacteremia; Carbapenems; Cross Infection; Doripenem; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Germany; Humans; Imipenem; Intensive Care Units; Intraabdominal Infections; Meropenem; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Quality Control; 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

The majority of nosocomial infections in Taiwan hospitals are caused by drug-resistant Gram-negative bacteria (GNB), including Pseudomonas aeruginosa, Acinetobacter baumannii, and various species of Enterobacteriaceae. Carbapenems are important agents for treating infections caused by these GNB. Recently, doripenem was approved for use in Taiwan in August 2009. However, data on its in vitro activity against nosocomial GNB isolated from Taiwan remain limited. The study was designed to look into this clinical issue.. A total of 400 nonduplicated nosocomial blood isolates isolated in 2009, inclusive of P. aeruginosa (n = 100), A. baumannii (n = 100), and Enterobacteriaceae (n = 200), were randomly selected from the bacterial bank preserved at National Taiwan University Hospital. Susceptibilities of these 400 isolates to various antibiotics, including doripenem, imipenem, meropenem, ceftazidime, amikacin, ciprofloxacin, colistin, and tigecycline were determined by using Etest.. Doripenem demonstrated similar in vitro activity to imipenem and meropenem against P. aeruginosa (87%, vs. 85% and 89%), A. baumannii (56%, vs. 60% and 60%), and Enterobacteriaceae (100%, vs. 98.5% and 99.5%). The prevalence of carbapenem-resistant (any one of three tested carbapenems) P. aeruginosa, A. baumannii, and Enterobacteriaceae isolates was 15%, 44%, and 0.5%, respectively.. Doripenem was as effective as imipenem and meropenem in our study. However, there was a significant proportion of carbapenem resistance among the tested isolates. Hence, longitudinal surveillance is necessary to monitor the resistance trend.

Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Bacteremia; Carbapenems; Cross Infection; Doripenem; Drug Resistance, Bacterial; Enterobacteriaceae; Gram-Negative Bacteria; Hospitals, University; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Taiwan; Thienamycins

Seven carbapenem-resistant NDM-1-positive Klebsiella pneumoniae isolates were recovered from patients hospitalized between 2007 and 2009 in different wards at a referral and tertiary care center in Nairobi. Most of the isolates were obtained from urine. All isolates carried the bla(NDM-1) carbapenemase gene previously reported from India, Pakistan, and the United Kingdom. These isolates were clonally related and expressed many other resistance determinants, including β-lactamases CTX-M-15, OXA-1, OXA-9, CMY-6, and aminoglycoside resistance methylase RmtC. This work corresponds to the first report of NDM-1 producers in Africa.

Topics: Adult; Aged; Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Cross Infection; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Humans; Kenya; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Polymerase Chain Reaction

Carbapenem-resistant Klebsiella pneumoniae (CRKP) has been increasingly reported all over the world. In this study, we aimed to investigate the risk factors for the acquisition of nosocomial CRKP infections.. We conducted a case-control study with data collected from thirty-nine patients with nosocomially acquired CRKP infection between July 2006 and July 2008. Controls were selected at a ratio of 1:2 from patients with nosocomial carbapenem-susceptible Klebsiella pneumoniae (CSKP) infection and were matched with CRKP cases for site of infection and the date of hospital admission (± within 5 days). T test, chi-square test, and logistic regression were used for statistical analysis.. Bivariable analysis showed that the age of the patients (P=0.038), days of hospital stay prior to isolation of Klebsiella pneumoniae (K. pneumoniae) (P=0.043), altered consciousness (P=0.007), intensive care unit (ICU) admission within two weeks (P=0.003), tracheal intubation (P=0.027), mechanical ventilation (P=0.009), number of changes in antibiotics≥4 (P=0.001), exposure to carbapenems (P = 0.002), exposure to fourth-generation cephalosporins (P=0.027), and exposure to piperacillin-tazobactams/cefoperazone-sulbactams (P=0.043) and glycopeptides (P=0.042) were related to CRKP infection. The multivariable analysis showed that ICU admission (within two weeks) [odds ratio (OR):4.68, 95% confidence intervals (CI):1.15-19.09, P=0.031], exposure to carbapenems (OR: 12.69, 95% CI: 2.09-77.10, P=0.006) and exposure to glycopeptides (OR: 3.57, 95% CI: 1.11-11.42, P=0.032) were independent risk factors for nosocomial CRKP infections.. Several factors are related to CRKP infections. ICU admission (within two weeks) or prior exposure to carbapenems or glycopeptides are independent risk factors for the acquisition of nosocomial CRKP infections.

Topics: Age Factors; Anti-Bacterial Agents; beta-Lactams; Carbapenems; Case-Control Studies; Chi-Square Distribution; Confidence Intervals; Cross Infection; Drug Resistance, Bacterial; Ertapenem; Female; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Length of Stay; Logistic Models; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Multivariate Analysis; Odds Ratio; Risk Factors; Thienamycins

Doripenem is a new carbapenem recently introduced into Europe. The COMParative Activity of Carbapenem Testing (COMPACT) study compared the susceptibility of common Gram-negative bacilli causing serious infections in hospitalized patients with doripenem, imipenem and meropenem.. Gram-negative isolates (4498 total: 2171 Pseudomonas species; 1910 Enterobacteriaceae; and 417 other Gram-negative bacilli) were collected from 80 centres in 16 countries in Europe, the Middle East and Africa during 2008-09. The MICs of doripenem, imipenem and meropenem were determined using Etest methodology and broth microdilution. Susceptibility was interpreted according to CLSI, EUCAST and FDA breakpoints.. The MIC(90)s of doripenem, imipenem and meropenem for all isolates were 8, ≥64 and 32 mg/L, respectively. Doripenem had the lowest MIC(90) for Pseudomonas species at 16 mg/L, with imipenem and meropenem values of ≥64 mg/L. Enterobacteriaceae were highly susceptible to all three carbapenems, with MIC(90)s of doripenem, imipenem and meropenem of 0.06, 0.5 and 0.12 mg/L, respectively. Other Gram-negative isolates, predominantly Acinetobacter baumannii, were resistant to all three carbapenems (MIC(90) ≥64 mg/L). Susceptibility to doripenem was observed in 14.9% of isolates resistant to imipenem and/or meropenem.. Doripenem showed excellent activity against Gram-negative isolates; generally it was more active than imipenem and at least as good as meropenem. Against Pseudomonas species, doripenem was more active than both imipenem and meropenem, with doripenem susceptibility observed for some imipenem- and/or meropenem-resistant isolates.

Topics: Africa; Anti-Bacterial Agents; Carbapenems; Cross Infection; Doripenem; Europe; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Middle East; Thienamycins

The aim of this study was to determine the in vitro activities of doripenem, imipenem, and meropenem against clinical gram-negative isolates. A total of 596 clinical isolates were obtained from intensive care unit (ICU) and non-ICU patients in 10 centers over Turkey between September-December 2008. The origin of the isolates was patients with nosocomial pneumonia (42.4%), bloodstream infections (%40.4), and complicated intraabdominal infections (17.1%). Of the isolates, 51.8% were obtained from ICU patients. The study isolates consisted of Pseudomonas spp. in 49.8%, Enterobacteriaceae in 40.3%, and other gram-negative agents in 9.9%. The minimum inhibitory concentrations (MIC) for doripenem, imipenem and meropenem were determined for all isolates in each center using Etest® strips (AB Biodisk, Solna, Sweden). Of the isolates, 188 (31.5%) were resistant to at least one of the carbapenems. MIC50 of doripenem against Pseudomonas spp. Was 1 mg/L which was similar to that of meropenem and two-fold lower than imipenem. Susceptibility to carbapenems in P.aeruginosa was 64% for doripenem at an MIC level of 2 mg/L, 53.9% and 63% for imipenem and meropenem at an MIC level of 4 mg/L, respectively. Doripenem and meropenem showed similar activity with the MIC90 of 0.12 mg/L whereas imipenem was four-fold less active at 0.5 mg/L. Against other gramnegative pathogens, mostly Acinetobacter spp., MIC50 was 8 mg/L for doripenem and 32 mg/L for other two carbapenems. P.aeruginosa isolates were inhibited 84.2% with doripenem and 72.1% with meropenem at the MIC level of 8 mg/L. Doripenem generally showed similar or slightly better activity than meropenem and better activity than imipenem against pathogens collected in this study. Against Pseudomonas spp., doripenem was the most active of the three carbapenems. Doripenem and meropenem were equally active against Enterobacteriaceae and at least four-fold more active than imipenem. It was concluded that doripenem seemed to be a promising agent in the treatment of nosocomial pneumonia, blood stream infections and intraabdominal infections particularly in patients who were under risk of developing antimicrobial resistance.

Topics: Anti-Bacterial Agents; Bacteremia; Carbapenems; Cross Infection; Doripenem; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Imipenem; Intensive Care Units; Meropenem; Microbial Sensitivity Tests; Pneumonia, Bacterial; Thienamycins; Turkey

Antimicrobial resistance among microorganisms is a global concern. In 2003, a nationwide antibiotic restriction program (NARP) was released in Turkey. In this study we evaluated the effect of NARP on antibiotic consumption, antimicrobial resistance, and cost.. The data obtained from all of the four university hospitals, and one referral tertiary-care educational state hospital in Ankara. Antimicrobial resistance profiles of 14,233 selected microorganisms all grown in blood cultures and antibiotic consumption from 2001 to 2005 were analyzed retrospectively.. A negative correlation was observed between the ceftriaxone consumption and the prevalence of ceftriaxone resistant E.coli and Klebsiella spp. (rho:-0.395, p:0.332 and rho:-0.627, p:0.037, respectively). The decreased usage of carbapenems was correlated with decreased carbapenems-resistant Pseudomonas spp. and Acinetobacter spp (rho:0.155, p:0.712 and rho:0.180, p:0.668, respectively for imipenem). Methicillin resistance rates of S.aureus were decreased from 44% to 41%. After two years of NARP 5,389,155.82 USD saving occurred.. NARP is effective in lowering the costs and antibiotic resistance.

Topics: Acinetobacter; Anti-Bacterial Agents; Cefepime; Ceftazidime; Ceftriaxone; Cephalosporins; Cost Savings; Cross Infection; Drug Costs; Drug Prescriptions; Drug Resistance, Bacterial; Drug Utilization; Escherichia; Health Policy; Hospitals; Humans; Imipenem; Klebsiella; Meropenem; Methicillin Resistance; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas; Staphylococcus aureus; Teicoplanin; Thienamycins; Turkey; Vancomycin

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 devise a local strategy for eradication of a hospital-wide outbreak caused by carbapenem-resistant Klebsiella pneumoniae (CRKP).. Quasi-experimental, before-and-after, interrupted time-series study.. A 1,000-bed tertiary-care university teaching hospital.. Retrospectively, all relevant data were collected from the medical records of patients with CRKP infections from May 2006 through April 2007, the preintervention period. From May 1, 2007, through May 1, 2010, the postintervention period, the intervention was applied and prospectively followed. The 5 key elements of this strategy were an emergency department flagging system, the building of a cohort ward, the eradication of clusters, environmental and personnel hand cultures, and a carbapenem-restriction policy. The demographic and clinical parameters of patients colonized by and/or infected with CRKP were collected from medical records.. A total of 10,680 rectal cultures were performed for 8,376 patients; 433 (5.16%) and 370 (4.4%) were CRKP-colonized and CRKP-infected patients, respectively, and 789 (98%) of 803 patients were admitted to the CRKP cohort ward. The CRKP infection density was reduced from 5.26 to 0.18 per 10,000 patient-days (P ≤ .001), and no nosocomial CRKP infections were diagnosed. Twenty-three percent of environmental cultures were found to be positive. Meropenem use was reduced from 283 ± 70.92 to 118 ± 74.32 defined daily doses per 1,000 patient-days (P ≤ .001).. This intervention produced an enormous impact on patient location, surveillance cultures, and antibiotic policies and a massive investment in infection control resources.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Carbapenems; Cross Infection; Drug Resistance, Bacterial; Feces; Female; Humans; Infection Control; Israel; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Nursing Homes; Patient Isolation; Thienamycins; Young Adult

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 Corporation ARTERIUM, Ukraine) application as empirical therapy in severe intraabdominal infections was presented. The diseases outcome and the preparation efficacy were estimated, recommendations concerning its application in the treatment of severe intraabdominal infections were done.

Topics: Adult; Aged; Anti-Bacterial Agents; APACHE; Cross Infection; Humans; Intraabdominal Infections; Meropenem; Middle Aged; Thienamycins; Treatment Outcome

The resistance mechanism of 49 Enterobacteriaceae isolates with decreased susceptibility to carbapenems collected from 2004 to 2008 at 16 teaching hospitals in China was investigated. Moderate- to high-level carbapenem resistance in most isolates was more closely associated with loss or decreased expression of both major porins combined with production of AmpC or extended-spectrum beta-lactamase enzymes, while KPC-2, IMP-4, and IMP-8 carbapenemase production may lead to a low to moderate level of carbapenem resistance in Enterobacteriaceae in China.

Topics: Anti-Bacterial Agents; Bacterial Outer Membrane Proteins; Bacterial Proteins; beta-Lactamases; Carbapenems; China; Cross Infection; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Enterobacteriaceae; Enterobacteriaceae Infections; Genotype; Integrons; Microbial Sensitivity Tests; Phenotype; Population Surveillance; Porins; Reverse Transcriptase Polymerase Chain Reaction

We describe the activity of a novel cephalosporin, CXA-101 (FR26 4205), against a panel of highly resistant Pseudomonas aeruginosa isolates collected from U.S. hospitals. CXA-101 demonstrated increased potency against this population of resistant isolates, with activity that is 4- to 10-fold higher than that of comparator agents in each phenotypic category. The addition of tazobactam did not improve its activity. CXA-101 appears to be a promising addition to the category of antipseudomonal beta-lactams.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Cephalosporins; Child; Child, Preschool; Cross Infection; Drug Combinations; Drug Resistance, Multiple, Bacterial; Humans; Infant; Microbial Sensitivity Tests; Middle Aged; Penicillanic Acid; Pseudomonas aeruginosa; Tazobactam; Young Adult

CXA-101, previously designated FR264205, is a new antipseudomonal cephalosporin. We evaluated the activity of CXA-101 against a highly challenging collection of beta-lactam-resistant Pseudomonas aeruginosa mutants selected in vitro and after antipseudomonal treatment of intensive care unit (ICU) patients. The in vitro mutants investigated included strains with multiple combinations of mutations leading to several degrees of AmpC overexpression (ampD, ampDh2, ampDh3, and dacB [PBP4]) and porin loss (oprD). CXA-101 remained active against even the AmpD-PBP4 double mutant (MIC = 2 microg/ml), which shows extremely high levels of AmpC expression. Indeed, this mutant showed high-level resistance to all tested beta-lactams, except carbapenems, including piperacillin-tazobactam (PTZ), aztreonam (ATM), ceftazidime (CAZ), and cefepime (FEP), a cephalosporin considered to be relatively stable against hydrolysis by AmpC. Moreover, CXA-101 was the only beta-lactam tested (including the carbapenems imipenem [IMP] and meropenem [MER]) that remained fully active against the OprD-AmpD and OprD-PBP4 double mutants (MIC = 0.5 microg/ml). Additionally, we tested a collection of 50 sequential isolates that were susceptible or resistant to penicillicins, cephalosporins, carbapenems, or fluoroquinolones that emerged during treatment of ICU patients. All of the mutants resistant to CAZ, FEP, PTZ, IMP, MER, or ciprofloxacin showed relatively low CXA-101 MICs (range, 0.12 to 4 microg/ml; mean, 1 to 2 microg/ml). CXA-101 MICs of pan-beta-lactam-resistant strains ranged from 1 to 4 microg/ml (mean, 2.5 microg/ml). As described for the in vitro mutants, CXA-101 retained activity against the natural AmpD-PBP4 double mutants, even when these exhibited additional overexpression of the MexAB-OprM efflux pump. Therefore, clinical trials are needed to evaluate the usefulness of CXA-101 for the treatment of P. aeruginosa nosocomial infections, particularly those caused by multidrug-resistant isolates that emerge during antipseudomonal treatments.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Cephalosporins; Cross Infection; Humans; Intensive Care Units; Microbial Sensitivity Tests; Mutation; Pseudomonas aeruginosa; Pseudomonas Infections

A clinical strain of Acinetobacter calcoaceticus resistant to carbapenems was isolated from a blood culture sample from an inpatient in a hospital in Madrid (Spain) during a large outbreak of infection (affecting more than 300 inpatients), caused by a multidrug-resistant Acinetobacter baumannii clone. The carbapenem resistance in both the A. calcoaceticus and A. baumannii clones was due to a bla(OXA-24) gene harbored in different plasmids. The plasmids were fully sequenced, revealing the presence of site-specific recombination binding sites putatively involved in mobilization of the bla(OXA-24) gene. Comparison of plasmids contained in the two strains revealed possible horizontal transmission of resistance genes between the Acinetobacter species.

Topics: Acinetobacter; Acinetobacter baumannii; Acinetobacter calcoaceticus; Acinetobacter Infections; Bacterial Proteins; Base Sequence; beta-Lactam Resistance; beta-Lactamases; Cross Infection; Disease Outbreaks; DNA-Binding Proteins; Drug Resistance, Multiple, Bacterial; Gene Transfer, Horizontal; Genes, Bacterial; Humans; In Vitro Techniques; Molecular Epidemiology; Molecular Sequence Data; Plasmids; Recombination, Genetic; Spain; Species Specificity

The Chinese Meropenem Surveillance Study (CMSS) programme was initiated in 2003 with the aim of monitoring the antimicrobial activity of broad-spectrum agents against nosocomial Gram-negative bacilli in China. From 2003 to 2008, a total of 3892 isolates were collected from 10 teaching hospitals. The minimum inhibitory concentrations (MICs) of 11 antimicrobial agents were determined by the agar dilution method. During the study period, a marked decrease in the susceptibility of Acinetobacter spp. to meropenem and imipenem was noticed, from 94.6% to 60.7% and from 92.5% to 62.1%, respectively. However, for Pseudomonas aeruginosa the susceptibility was relatively stable, with susceptibility rates of 86.2% to 76.0% for meropenem and 74.8% to 70.5% for imipenem. Meropenem and imipenem exhibited the highest activities against enterobacterial organisms, with ranges of MIC(90) values (MIC for 90% of the organisms) from 0.064mg/L to 0.25mg/L and 0.25 to 4mg/L, respectively. Except for Acinetobacter spp., the next most active agent against the majority of isolates was amikacin, with susceptibility ranging from 78.8% to 93.3%, followed by piperacillin/tazobactam (73.7% to 98.2%), cefoperazone/sulbactam (63.9% to 99.1%), cefepime (67.0% to 95.4%) and ceftazidime (54.5% to 93.3%). The percentage of isolates positive for extended-spectrum beta-lactamases among Escherichia coli, Klebsiella spp. and Proteus mirabilis ranged from 50.9% to 66.7%, 25.4% to 42.4% and 8.9% to 24.2%, respectively. These CMSS results have demonstrated increasing resistance of Acinetobacter spp. to carbapenems, resulting from the spread of highly resistant clones. Continued surveillance studies, including CMSS, as well as potent measures for controlling the spread of resistant clones are required.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; China; Cross Infection; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Meropenem; Microbial Sensitivity Tests; Thienamycins

Topics: Anti-Bacterial Agents; Critical Care; Cross Infection; Drug Resistance, Bacterial; Humans; Infection Control; Intensive Care Units; Meropenem; Pseudomonas aeruginosa; Pseudomonas Infections; Thienamycins

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Cross Infection; Disease Outbreaks; Greece; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Thienamycins

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Cross Infection; Drug Resistance, Bacterial; Drug Synergism; Humans; Intensive Care Units; Meropenem; Microbial Sensitivity Tests; Minocycline; Sulbactam; Thienamycins; Tigecycline

A significant increase in the rate of vancomycin-resistant Enterococcus faecium (VREfm) bacteremia at our health service, despite improved infection control, prompted us to investigate the cause.. E. faecium bacteremia (including VREfm) over a 12-year period (1998-2009) was investigated using multilocus sequence typing, antibiotic and antiseptic susceptibility profiles, optical mapping, and whole genome sequencing of historical and recent isolates.. For 10 years, the rate of bacteremia due to vanB VREfm remained stable and sequence type (ST) 17 was predominant. In 2005, ST203 vancomycin-susceptible E. faecium first appeared at our institution, and from March 2007, coinciding with the appearance of a vanB VREfm ST203, the rate of VRE bacteremia has increased exponentially. Although we found no difference in antiseptic susceptibility or presence of genes encoding putative virulence determinants (esp(Efm), hyl(Efm), and fms genes), comparative genomics revealed almost 500 kb of unique sequence when an ST17 and an ST203 VREfm isolate were compared, suggesting that other genomic factors are responsible for the apparent success of E. faecium.. The application of multilocus sequence typing has uncovered the emergence of an epidemic clone of E. faecium ST203 that appears to have acquired the vanB locus and has caused a sustained outbreak of VRE bacteremia.

Topics: Anti-Bacterial Agents; Australia; Bacteremia; Bacterial Proteins; Bacterial Typing Techniques; Communicable Diseases, Emerging; Cross Infection; Disease Outbreaks; Electrophoresis, Gel, Pulsed-Field; Enterococcus faecium; Genomics; Gram-Positive Bacterial Infections; Humans; Incidence; Meropenem; Microbial Sensitivity Tests; Phylogeny; Thienamycins; Vancomycin; Vancomycin Resistance

The incidence of fungal infections such as Aspergillosis is increasing among immunocompromised patients. Demand for diagnosis of mycotic diseases is steadily raising among clinicians and treatment of these patients represents a continually growing challenge. The authors present a case of a 53-year-old male patient with Aspergillus peritonitis. This case deserves attention because its extreme rarity in the medical literature and complex therapy of coinfections during the hospital stay which was difficult and relatively expensive. The importance of consultation and microbiological sampling is emphasized.

Topics: Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Aspergillosis; Clindamycin; Cross Infection; Humans; Immunocompromised Host; Male; Meropenem; Middle Aged; Peritonitis; Subphrenic Abscess; Thienamycins

The mechanisms responsible for the increasing prevalence of colistin-only-sensitive (COS) Pseudomonas aeruginosa isolates in a Spanish hospital were investigated. Pulsed-field gel electrophoresis revealed that 24 (50%) of the studied isolates belonged to the same clone, identified as the internationally spread sequence type 235 (ST235) through multilocus sequence typing. In addition to several mutational resistance mechanisms, an integron containing seven resistance determinants was detected. Remarkably, the extended-spectrum beta-lactamase GES-1 and its Gly170Ser carbapenem-hydrolyzing derivative GES-5 were first documented to be encoded in a single integron. This work is the first to describe GES enzymes in Spain and adds them to the growing list of beta-lactamases of concern (PER, VIM, and OXA) detected in ST235 clone isolates.

Topics: Anti-Bacterial Agents; Base Sequence; beta-Lactamases; Colistin; Cross Infection; Humans; Molecular Sequence Data; Pseudomonas aeruginosa

The carbapenems are broad-spectrum beta-lactam antibiotics with activity against most organisms encountered in the pediatric intensive care unit (PICU). In anticipation of their increased use in critically ill children, we measured the effect of sustained meropenem use on the pattern of Gram-negative bacillus colonization in patients admitted to a tertiary care PICU.. : Prospective preintervention/postintervention comparison.. Medical/surgical PICU.. Consecutive PICU admissions over 2.5 yrs.. After a 6-mo baseline period, all children with serious infections admitted to the PICU during the subsequent 2 yrs were administered meropenem. The incidence of colonization by Gram-negative bacilli resistant to one of a battery of broad-spectrum parenteral agents, and by organisms resistant specifically to meropenem, during the baseline period was compared with the period of preferred meropenem use.. During the period of preferred meropenem use, the amount of meropenem used increased >seven-fold, whereas the use of other advanced generation beta-lactams was reduced by nearly 80%. The mean prevalence of colonization by antibiotic-resistant bacilli in general was not statistically altered during the period of meropenem preference (7.3 organisms/100 patient-days, vs. 9.4 organisms/100 patient-days at baseline, p < 0.09). The prevalence of colonization by Gram-negative organisms resistant specifically to meropenem was 0.61 organisms/100 patient-days during the baseline period vs. 1.04 organisms/100 patient-days during the period of meropenem preference (p < 0.30). The incidence of nosocomial infections did not change, and the prevalence of nosocomial infections caused by meropenem-resistant organisms was always <1% of all admissions during the period of meropenem preference.. There was no statistically detectable effect on the prevalence of colonization by Gram-negative organisms resistant to one or more classes of broad-spectrum parenteral antibiotics, or to colonization by organisms resistant specifically to meropenem, when meropenem was the preferred antibiotic in a PICU.

Topics: Antibiotic Prophylaxis; Child; Child, Preschool; Colony Count, Microbial; Cross Infection; Drug Resistance, Microbial; Female; Follow-Up Studies; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Incidence; Infant; Intensive Care Units, Pediatric; Male; Meropenem; Microbial Sensitivity Tests; Probability; Prospective Studies; Risk Assessment; Thienamycins; Treatment Outcome

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program is a longitudinal antimicrobial surveillance study that has been in existence since 1997 in centers that are actively prescribing meropenem. This report examines the results from the study in Europe in 2007. A total of 5208 isolates were examined for activity (MIC) of meropenem and other broad-spectrum antibacterial comparators. Cumulative susceptibility rates using Clinical and Laboratory Standards Institute criteria against all methicillin-susceptible staphylococci were imipenem (97.7%) > meropenem (97.3%) > piperacillin/tazobactam (96.2%) > tobramycin (94.2%) > gentamicin (92.0%) > ciprofloxacin (84.0%) > ceftazidime (39.8%). Against all species of Enterobacteriaceae, the rates were meropenem (99.4%) > imipenem (98.3%) > tobramycin (92.0%) > gentamicin (89.5%) > ceftazidime (86.2%) > piperacillin/tazobactam (85.5%) > ciprofloxacin (84.2%). Meropenem was most effective against the nonfermenters, although multidrug-resistant Acinetobacter spp. and imipenem-resistant Pseudomonas aeruginosa strains were reported. The continued need for surveillance studies such as MYSTIC is exemplified, and results from these types of surveillance can, hopefully, help in the correct choice of empiric therapy.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Cross Infection; Drug Resistance, Bacterial; Enterobacteriaceae; Europe; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Longitudinal Studies; Meropenem; Microbial Sensitivity Tests; Population Surveillance; Thienamycins

Topics: Antibiotic Prophylaxis; Child; Child, Preschool; Critical Illness; Cross Infection; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Incidence; Infant; Intensive Care Units, Pediatric; Male; Meropenem; Risk Assessment; Sensitivity and Specificity; Survival Analysis; Thienamycins

Serratia marcescens is a well recognized nosocomial pathogen. We report an outbreak with this organism in 8 neonates in a neonatal intensive care unit (NICU). Seven cases were treated successfully with meropenem after the failure of imipenem treatment. Although they have similar anti-microbial effects, meropenem can effectively treat the S. marcescens sepsis resistant to imipenem.

Topics: Anti-Bacterial Agents; Cross Infection; Disease Outbreaks; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Meropenem; Serratia Infections; Serratia marcescens; Thienamycins; Turkey

To analyze an outbreak caused by a multiple resistant strain of S. typhimurium in a newborn unit in Turkey.. The outbreak occurred during the period 15 to 29 March,2005. A newborn infected with S. typhimurium was defined as a case. Newborns who were hospitalized during the outbreak period with no diagnosis of S. typhimurium infections (n=50) constituted the control group I (CG I). The matched patients of the control group II (CG II) (n=20) were selected from neonates without S. typhimurium infections during the period.. Of 22 infants who were affected two died. Cases developed diarrhea (n=20), septicemia (n=5) and meningitis (n=1). The strain was resistant to ampicillin, ceftriaxone, ceftazidime, amikacin, trimethoprim-sulfamethoxasole and chloramphenicol, susceptible to meropenem. All of the infected neonates were treated with meropenem. The surveillance cultures were negative. The outbreak was controlled by appropriate therapy and institution of effective control measures. The cases were more exposed to mechanical ventilation than CG I (p<0.05). The mean additional length of stay in cases was significantly different from CG II (14.9 days vs. 5.1 days, p<0.05). The mean charges was $1588.78 for a case and $506.94 for a control (P<0.05). Accommodation accounted for 44.5% of these extra charges.. This study increases the understanding of the burden of multidrug-resistant S. typhimurium infection. Nosocomial outbreaks have a major effect on healthcare delivery, costs and outcomes.

Topics: Anti-Bacterial Agents; Cross Infection; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Female; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Length of Stay; Male; Meropenem; Salmonella Infections; Salmonella typhimurium; Thienamycins; Treatment Outcome; Turkey

To determine risk factors and outcomes for patients with meropenem high-level-resistant Pseudomonas aeruginosa (MRPA) (minimum inhibitory concentration [MIC] > or = 32 microg/mL).. Case-control-control.. An 867-bed urban, teaching hospital.. Fifty-eight MRPA case patients identified from an earlier P. aeruginosa study; 125 randomly selected control patients with meropenem-susceptible P. aeruginosa (MSPA) (MIC < or = 4 microg/mL), and 57 control patients without P. aeruginosa (sampled by case date/location).. Patient data, outcomes, and costs were obtained via administrative database. Cases were compared to each control group while controlling for time at risk (days between admission and culture, or entire length of stay [LOS] for patients without P. aeruginosa).. A multivariable model predicted risks for MRPA versus MSPA (odds ratio [95% confidence interval]): more admissions (in the prior 12 months) (1.41 [1.15, 1.74]), congestive heart failure (2.19 [1.03, 4.68]), and Foley catheter (2.53 [1.18, 5.45]) (adj. R(2) = 0.28). For MRPA versus no P. aeruginosa, risks were age (in 5-year increments) (1.17 [1.03, 1.33]), more prior admissions (1.40 [1.08, 1.81]), and more days in the intensive care unit (1.10 [1.03, 1.18]) (adj. R(2) = 0.32). Other invasive devices (including mechanical ventilation) and previous antibiotic use (including carbapenems) were nonsignificant. MRPA mortality (31%) did not differ from that of MSPA (15%) when adjusted for time at risk (P = .15) but did from mortality without P. aeruginosa (9%) (P = .01). Median LOS and costs were greater for MRPA patients versus MSPA patients and patients without P. aeruginosa: 30 days versus 16 and 10 (P<.01) and $88,425 versus $28,620 and $22,605 (P<.01).. Although antibiotic use has been shown to promote resistance, our data found that prior antibiotic use was not associated with MRPA acquisition. However, admission frequency and Foley catheters were, suggesting that infection control measures are essential to reducing MRPA transmission.

Topics: Adolescent; Age Factors; Anti-Bacterial Agents; Case-Control Studies; Catheterization; Child; Cross Infection; Drug Resistance, Bacterial; Female; Health Care Costs; Hospitalization; Hospitals, Teaching; Hospitals, Urban; Humans; Length of Stay; Male; Meropenem; Microbial Sensitivity Tests; Multivariate Analysis; Odds Ratio; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Risk Factors; Thienamycins; Treatment Outcome; Young Adult

The MICs of imipenem, meropenem, piperacillin-tazobactam, cefotaxime, polymixin B and tigecycline against 80 isolates of Acintobacter baumanii from 6 hospitals were determined. A multiplex-PCR was used to detect the genes encoding carbapenemases. Field Inversion Gel Electrophoresis (FIGE) was then used to investigate the genetic relationships among the carbapenem-resistant isolates. Only 7 isolates were resistant to polymixin B and tigecycline (MIC = 16). All isolates were positive for at least 2 carbapenemase genes. At least 10 distinct clones were detected by FIGE. A dominant pattern designated as pulsotype A consisting of 23 isolates was detected from 4 hospitals. The majority of isolates in this pulsotype had a bla(OXA-51/23-like) and bla(OXA-51/24-like) carbapenemase genes and cultured from the patients at burns and ICU. The pan drug resistant isolates belonged to different FIGE patterns. Nosocomial infections with different clones of Acintobacter baumanii occur at Tehran hospitals. However, inter-hospital transmission with certain pulsotypes is likely.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Cefotaxime; Cross Infection; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Genes, Bacterial; Hospitals; Humans; Imipenem; Iran; Meropenem; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Thienamycins

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Chromosomes, Bacterial; Cross Infection; Disease Outbreaks; DNA, Bacterial; Drug Resistance, Bacterial; Edetic Acid; Greece; Humans; Imipenem; Integrons; Isoelectric Focusing; Microbial Sensitivity Tests; Molecular Sequence Data; Sequence Analysis, DNA

The basis of the beta-lactam resistance of 39 multidrug-resistant Acinetobacter baumannii isolates recovered from hospitalized patients was studied. These isolates were collected from 2001 to 2005 at the Sahloul Hospital in Sousse, Tunisia. They belonged to two distinct clones. One clone that grouped 19 isolates produced a carbapenem-hydrolyzing oxacillinase, OXA-97, that differed from OXA-58 by a single amino acid substitution and conferred the same beta-lactam resistance profile as OXA-58. The bla(OXA-97) gene was located on plasmids that varied in size in 18 isolates and was chromosomally located in a single isolate. Cloning and sequencing identified genetic structures surrounding the bla(OXA-97) gene similar to those reported to be adjacent to the bla(OXA-58) gene. In addition, the novel ISAba8 element (which is of the IS21 family) was identified. This is the first report of the nosocomial spread of carbapenemase producers in A. baumannii isolates in Africa.

Topics: Acinetobacter baumannii; Africa; Bacterial Proteins; beta-Lactamases; Blotting, Southern; Carbapenems; Cross Infection; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Models, Genetic; Molecular Sequence Data; Polymerase Chain Reaction; Tunisia

The oxacillinase gene was reported to confer limited resistance to carbapenem in Acinetobacter baumannii. In this study, we have demonstrated that an A. baumannii clinical isolate harboring a plasmid, pTVICU53, has 11,037 bp encoding 13 open reading frames. A bla(OXA-58) gene with an upstream insertion of truncated ISAba3 (DeltaISAba3) and IS1008 was found in this plasmid. DeltaISAba3and IS1008 provided two independent promoters for the transcription control of the bla(OXA-58) gene. The transformation of pTVICU53 or a shuttle vector bearing IS1008-DeltaISAba3-bla(OXA-58) to different A. baumannii recipients can increase their MICs of carbapenem 64- to 256-fold. The deletion of promoters provided by IS1008 resulted in dramatic decreases in bla(OXA-58) transcription and a 32- to 64-fold reduction in the carbapenem MIC. These findings highlight that A. baumannii might develop carbapenem resistance with a single transformation step, taking up a plasmid containing a genetic construct with a potentially high level of transcription of the bla(OXA-58) gene.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Base Sequence; beta-Lactam Resistance; beta-Lactamases; Carbapenems; Cross Infection; DNA Primers; DNA Transposable Elements; DNA, Bacterial; Genes, Bacterial; Humans; Microbial Sensitivity Tests; Molecular Sequence Data; Plasmids; Promoter Regions, Genetic; Transformation, Genetic

During 2003, 40 carbapenem-resistant Pseudomonas aeruginosa clinical isolates collected in a Mexican tertiary-care hospital were screened for metallo-beta-lactamase production. Thirteen isolates produced IMP-15, and 12 had a single pulsed-field gel electrophoresis pattern. The bla(IMP-15) gene cassette was inserted in a plasmid-borne integron with a unique array of gene cassettes and was named In95.

Topics: Bacterial Proteins; beta-Lactamases; Cross Infection; Electrophoresis, Gel, Pulsed-Field; Humans; Integrons; Mexico; Models, Genetic; Molecular Sequence Data; Pseudomonas aeruginosa; Pseudomonas Infections

The first outbreak of carbapenem-resistant Klebsiella pneumoniae isolates producing the plasmid-encoded carbapenem-hydrolyzing oxacillinase OXA-48 is reported. The 39 isolates belonged to two different clones and were collected at the University Hospital of Istanbul, Turkey, from May 2006 to February 2007, and they coproduced various beta-lactamases (SHV-12, OXA-9, and TEM-1 for clone A and CTX-M-15, TEM-1, and OXA-1 for clone B).

Topics: Bacterial Proteins; beta-Lactamases; Carbapenems; Cross Infection; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Models, Genetic; Turkey

This study reports data on the susceptibilities to five commonly used antianaerobic agents of five clinically frequently encountered anaerobes from 2000 to 2007 and to Bacteroides fragilis isolates causing nosocomial infections from 1990 to 2006. There was a trend of decreasing susceptibilities of these anaerobes to ampicillin-sulbactam, cefmetazole, chloramphenicol, and clindamycin with time during the study period. The rates of susceptibility to clindamycin and cefmetazole for all clinical isolates of Bacteroides fragilis isolates were higher than those of isolates associated with nosocomial infections. The MICs of 207 anaerobic blood isolates collected in 2006 to 14 antimicrobial agents were determined by the agar dilution method. The rates of nonsusceptibility to imipenem and meropenem were 7% and 12% for B. fragilis isolates (n = 60), 7% and 3% for Bacteroides thetaiotamicron isolates (n = 30), 4% and 4% for Fusobacterium species (n = 27), 6% and 0% for Prevotella species (n = 16), 15% and 0% for Clostridium species (n = 28), and 0% and 0% for Peptostreptococcus species (n = 32). The rates of susceptibility to moxifloxacin were 90% for B. fragilis isolates, 87% for B. thetaiotaomicron isolates, 81% for Fusobacterium species, 75% for Prevotella species, 93% for Clostridium species, and 78% for Peptostreptococcus species. Thirty-six percent of Clostridium species and 12% of Peptostreptococcus species were not susceptible to metronidazole. Comparison of the data with the data from a previous survey from the same institute in 2002 revealed higher rates of nonsusceptibility to carbapenems, especially for B. fragilis, Fusobacterium species, and Prevotella species isolates. The high rates of nonsusceptibility to commonly used antianaerobic agents mandate our attention, and periodic monitoring of the trend of the resistance is crucial.

Topics: Anti-Bacterial Agents; Bacteria, Anaerobic; Bacteroides fragilis; Bacteroides Infections; Blood; Carbapenems; Cross Infection; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Microbial Sensitivity Tests; Taiwan

Agar dilution antimicrobial susceptibility testing (CLSI, M11-A7, 2007) performed for 208 toxin-producing clinical isolates of Clostridium difficile resulted in OPT-80 MICs ranging from 0.06 to 1 microg/ml, with 90% of the isolates inhibited by a concentration of 0.5 microg/ml. The in vitro activity of OPT-80 was independent of the susceptibilities of isolates to nine other antimicrobial agents.

Topics: Anti-Bacterial Agents; Bacterial Toxins; Clostridioides difficile; Cross Infection; Enterocolitis, Pseudomembranous; Glycosides; Humans; In Vitro Techniques; Microbial Sensitivity Tests

We investigated the basis of the carbapenem resistance of 17 multidrug-resistant Acinetobacter baumannii clinical isolates collected from 2004 to 2005 at the Saint George University Hospital in Beirut, Lebanon. A. baumannii isolates were clonally related and were susceptible to colistin and trimethoprim-sulfamethoxazole, susceptible or intermediate to ampicillin-sulbactam and meropenem, and resistant to all other antimicrobials. Conjugation experiments demonstrated that resistance to imipenem could be transferred along with a plasmid containing the carbapenem-hydrolyzing oxacillinase bla(OXA-58) gene. The plasmid that we called pABIR was 29,823 bp in size and showed a novel mosaic structure composed of two origins of replication, four insertion sequence (IS) elements, and 28 open reading frames. The bla(OXA-58) gene was flanked by IS18 and ISAba3 elements at the 5' and 3' ends, respectively. The production of the carbapenem-hydrolyzing oxacillinase OXA-58 was apparently the only mechanism for carbapenem resistance in A. baumannii isolates causing the outbreak at the Lebanese Hospital.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Conjugation, Genetic; Cross Infection; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Genes, Bacterial; Hospitals, University; Humans; Imipenem; Lebanon; Molecular Epidemiology; Molecular Sequence Data; Plasmids

A total of 49 unique clinical isolates of multidrug-resistant (MDR) Acinetobacter baumannii identified at a tertiary medical center in Pittsburgh, Pennsylvania, between August 2006 and September 2007 were studied for the genetic basis of their MDR phenotype. Approximately half of all A. baumannii clinical isolates identified during this period qualified as MDR, defined by nonsusceptibility to three or more of the antimicrobials routinely tested in the clinical microbiology laboratory. Among the MDR isolates, 18.4% were resistant to imipenem. The frequencies of resistance to amikacin and ciprofloxacin were high at 36.7% and 95.9%, respectively. None of the isolates was resistant to colistin or tigecycline. The presence of the carbapenemase gene bla(OXA-23) and the 16S rRNA methylase gene armA predicted high-level resistance to imipenem and amikacin, respectively. bla(OXA-23) was preceded by insertion sequence ISAba1, which likely provided a potent promoter activity for the expression of the carbapenemase gene. The structure of the transposon defined by ISAba1 differed from those reported in Europe, suggesting that ISAba1-mediated acquisition of bla(OXA-23) may occur as an independent event. Typical substitutions in the quinolone resistance-determining regions of the gyrA and parC genes were observed in the ciprofloxacin-resistant isolates. Plasmid-mediated quinolone resistance genes, including the qnr genes, were not identified. Fifty-nine percent of the MDR isolates belonged to a single clonal group over the course of the study period, as demonstrated by pulsed-field gel electrophoresis.

Topics: Academic Medical Centers; Acinetobacter baumannii; Acinetobacter Infections; Amikacin; Base Sequence; beta-Lactamases; Cross Infection; DNA Primers; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Genes, Bacterial; Humans; Microbial Sensitivity Tests; Molecular Epidemiology; Pennsylvania; Polymerase Chain Reaction

Nosocomial spreading of extensive drug-resistant Acinetobacter baumannii (EDRAB) is an emerging problem. To clarify the association between prior antibiotic usage and subsequent EDRAB acquisition, we conducted a one-to-one matched case-control study among patients in all intensive care units (ICUs) at the National Taiwan University Hospital, Taipei, Taiwan, during a 1-year period. A total of 113 pairs of patients were identified. We measured prior antibiotics exposure in 4 perspectives: usage, overall treatment duration, accumulated dosage, and treatment potency. We found positive associations between EDRAB acquisition and prior usage of imipenem and meropenem across 4 measures, especially in usage and average treatment potency (usage, odds ratio [OR](imipenem) = 3.7 with 95% confidence interval [CI] = 1.2-11.0, OR(meropenem) = 5.4 with 95% CI = 1.2-20.0; average treatment potency, OR(imipenem) = 5.3 with 95% CI = 1.3-22.0, OR(meropenem) = 3.4 with 95% CI = 1.0-12.0). Ceftazidime use with stronger treatment potency was also strongly associated with subsequent nosocomial EDRAB acquisition (OR = 5.5, 95% CI = 1.5-21.0). The OR of EDRAB acquisition greatly increased in patients who had previously been exposed to any 1 (OR = 5.5, 95% CI = 2.3-13.2) or to any 2 or 3 (OR = 11.1, 95% CI = 2.7-46.4) of the abovementioned antibiotics. Based on these findings, we conclude that usage of imipenem, meropenem, and/or ceftazidime is associated with subsequent acquisition of EDRAB in critically ill patients in ICUs.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Case-Control Studies; Ceftazidime; Chi-Square Distribution; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Humans; Imipenem; Intensive Care Units; Male; Meropenem; Middle Aged; Regression Analysis; Thienamycins

To describe the effectiveness and tolerability of the dose adjustment of meropenem in empirical treatment of nosocomial infections in critically-ill patients admitted to intensive care medicine services.. Prospective, observational and multicenter study in patients admitted to 17 intensive care medicine services with nosocomial infection, who were initially treated with meropenem, 1 g every 8 h, were eligible. The initial dose was adjusted to 0.5 g every 8 h if there were: a) a favorable clinical course, and b) microbiological isolation of meropenem-susceptible pathogens or absence of pathogens in cultures.. Ninety-two patients in whom meropenem doses were adjusted to 0.5 g every 8 h were included. Ventilator-associated pneumonia followed by bacteremia was the most frequently treated infections. Microbiological studies were positive in 53 patients, with a predominance of gram-positive bacteria (53.7%), especially methicillin-susceptible Staphylococcus aureus, followed by gram-negative bacteria (42.7 %). A total of 18 patients were not evaluable at the end of treatment. Sixty-seven (90.5 %) of the 74 evaluable patients had a favorable clinical course (54 patients cured and 13 improved). In 50 out of 53 microbiologically evaluable cases, eradication or apparent eradication of initial microorganisms was achieved. In 3 cases, the initial pathogen persisted: Acinetobacter baumannii (2 cases) and Pseudomonas aeruginosa (1 case). On three occasions, new pathogens developed during treatment: A. baumannii (2 cases) and methicillin-resistant S. aureus (1 case). Adverse events occurred in 3 patients (4%), none of which was considered severe, and withdrawal of meropenem was not necessary. A total of 25 (27.2 %) patients died, three of them in relation to the infectious process.. Dose adjustment of meropenem to 0.5 g every 8 h is a useful tool in the treatment of severe nosocomial infections in patients admitted to services of intensive care medicine except in cases in which causative pathogens are non-fermenting Gram-negative bacteria.

Topics: Anti-Bacterial Agents; Critical Illness; Cross Infection; Female; Humans; Male; Meropenem; Middle Aged; Prospective Studies; Severity of Illness Index; Thienamycins

In order to study the enzymatic carbapenem resistance mechanisms in Acinetobacter baumannii isolates from Argentina, we performed molecular characterization on 41 epidemiologically unrelated strains isolated from 1995 to 2006 with diminished susceptibilities to imipenem and meropenem.. Acinetobacter baumannii isolates were identified with the ARDRA technique. The total genomic DNA was used to detect each carbapenem beta-lactamase gene described so far in this species and those insertion sequences usually associated to carbapenem beta-lactamase genes (ISAba1, 2, 3, 4 and IS18) by the PCR technique with specific primers.. 26 out of 41 Acinetobacter baumannii isolates with diminished susceptibilities to carbapenems harboured the bla(OXA-23) gene. The bla(OXA-58) was detected in 13 out of 41 isolates. ISAba1 was always located upstream bla(OXA-23). All isolates containing the bla(OXA-58) gene showed ISAba3 downstream of the carbapenemase, while 4 isolates had a second copy of the ISAba3 upstream of the gene.. Enzymatic carbapenem resistance in Acinetobacter baumannii was found in 88% of 41 non-epidemiologically-related strains mediated by the polyclonal spread of the bla(OXA-23) and bla(OXA-58) genes. The genetic structures surrounding the oxacillinase genes found in our bacterial isolates revealed a particular epidemiology in our geographical region. This data suggests the need of local molecular surveillance to help control multirresistance Acinetobacter baumannii infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Argentina; beta-Lactamases; Cross Infection; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Genes, Bacterial; Humans; Imipenem; Meropenem; Polymerase Chain Reaction; Sequence Analysis, DNA; Thienamycins

VIM-type metallo-betalactamases (MBLs) exhibit hydrolytic activity against most betalactam antibiotics, including carbapenems. So far, VIM-type-producing Klebsiella pneumoniae isolates had not been reported in Latin America.. In July 2005, a carbapenem-resistant Klebsiella pneumoniae was isolated from a urine sample collected from a 7-year-old girl hospitalized at the Hospital de Niños "J. M. de los Ríos" in Caracas, Venezuela. This strain was identified using conventional biochemical tests. The susceptibility analysis was conducted by disk diffusion, and MICs for Imipenem and Meropenem were performed by agar dilution. For the phenotypic detection of MBL we used the Imipenem-EDTA/SMA double-disk diffusion method. The hydrolytic activity against carbapenems was determined by the Masuda microbiological method. Purified protein was subjected to isoelectric focusing (IEF). Detection of antimicrobial resistance genes was performed by PCR amplification with specific VIM primers.. The strain showed resistance to most betalactam antibiotics, quinolones and amynoglicosides, but remained susceptible to Aztreonam and Cefepime. The use of phenotypic and microbiological methods detected the presence of a metallobetalactamase. By IEF we visualized three bands at pI 5.4, 7.6 and 7.9, corresponding to reduced-spectrum betalactamases, and a band at pI 5.8 that corresponded to the metallobetalactamase. PCR screening of bla genes revealed the presence of blaVIM, with an amplicon of 261 bp.. This is the first report of a MBL-mediated carbapenem-resistant Klebsiella pneumoniae in Latin America, which constitutes a public health concern in our region since their transference to other microorganisms with multiple antibiotic resistance mechanisms will increase the antimicrobial resistance problem.

Topics: Anti-Bacterial Agents; Aztreonam; beta-Lactam Resistance; beta-Lactamases; Cefepime; Cephalosporins; Child; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Quinolones; Thienamycins; Urine; Venezuela

Acinetobacter baumannii is a prolific nosocomial pathogen renowned for its multidrug-resistant nature. We report a case of community-acquired meningitis due to A. baumannii. The case highlights the potential pathogenicity of this organism and raises concerns that this highly adaptable organism may soon evolve into a significant community pathogen, too.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Anti-Inflammatory Agents; Ceftriaxone; Community-Acquired Infections; Cross Infection; Dexamethasone; Humans; Male; Meningitis, Bacterial; Meropenem; Middle Aged; Thienamycins

Of the 181 unduplicated Escherichia coli strains isolated in nine different hospitals in three Portuguese regions, 119 were extended-spectrum beta-lactamase (ESBL)-CTX-M producers and were selected for phenotype and genotype characterization. CTX-M producer strains were prevalent among community-acquired infections (56%), urinary tract infections (76%), and patients >/=60 years old (76%). In MIC tests, all strains were resistant to cefotaxime, 92% were resistant to ceftazidime, 93% were resistant to quinolones, 89% were resistant to aminoglycoside, and 26% were resistant to trimethoprim-sulfamethoxazole; all strains were sensitive to carbapenems, and 92% of the strains had a multidrug resistance phenotype. Molecular methods identified 109 isolates harboring a bla(CTX-M-15) gene, 1 harboring the bla(CTX-M-32) gene (first identification in the country), and 9 harboring the bla(CTX-M-14) gene. All isolates presented the ISEcp1 element upstream from the bla(CTX-M) genes; one presented the IS903 element (downstream of bla(CTX-M-14) gene), and none had the IS26 element; 85% carried bla(TEM-1B), and 84% also carried a bla(OXA-30). Genetic relatedness analysis based on pulsed-field gel electrophoresis defined five clusters and indicated that 76% of all isolates (from cluster IV) corresponded to a single epidemic strain. Of the 47 strains from one hospital, 41 belonged to cluster IV and were disseminated in three main wards. CTX-M-producing E. coli strains are currently a problem in Portugal, with CTX-M-15 particularly common. This study suggests that the horizontal transfer of bla(CTX-M) genes, mediated by plasmids and/or mobile elements, contributes to the dissemination of CTX-M enzymes to community and hospital environments. The use of extended-spectrum cephalosporins, quinolones, and aminoglycosides is compromised, leaving carbapenems as the therapeutic option for severe infections caused by ESBL producers.

Topics: Aged; Anti-Bacterial Agents; beta-Lactamases; Community-Acquired Infections; Cross Infection; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Humans; Microbial Sensitivity Tests; Middle Aged; Portugal

Bloodstream infections (BSI) caused by extended-spectrum beta-lactamase (ESBL)-producing organisms markedly increase the rates of treatment failure and death. We conducted a retrospective cohort analysis to identify risk factors for mortality in adult in-patients with BSI caused by ESBL-producing Enterobacteriaceae (ESBL-BSI). Particular attention was focused on defining the impact on the mortality of inadequate initial antimicrobial therapy (defined as the initiation of treatment with active antimicrobial agents >72 h after collection of the first positive blood culture). A total of 186 patients with ESBL-BSI caused by Escherichia coli (n = 104), Klebsiella pneumoniae (n = 58), or Proteus mirabilis (n = 24) were identified by our microbiology laboratory from 1 January 1999 through 31 December 2004. The overall 21-day mortality rate was 38.2% (71 of 186). In multivariate analysis, significant predictors of mortality were inadequate initial antimicrobial therapy (odds ratio [OR] = 6.28; 95% confidence interval [CI] = 3.18 to 12.42; P < 0.001) and unidentified primary infection site (OR = 2.69; 95% CI = 1.38 to 5.27; P = 0.004). The inadequately treated patients (89 of 186 [47.8%]) had a threefold increase in mortality compared to the adequately treated group (59.5% versus 18.5%; OR = 2.38; 95% CI = 1.76 to 3.22; P < 0.001). The regimens most commonly classified as inadequate were based on oxyimino cephalosporin or fluoroquinolone therapy. Prompt initiation of effective antimicrobial treatment is essential in patients with ESBL-BSI, and empirical decisions must be based on a sound knowledge of the local distribution of pathogens and their susceptibility patterns.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Cross Infection; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Female; Humans; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Predictive Value of Tests; Proteus mirabilis; Risk Factors; Survival Analysis; Treatment Outcome

Clinical isolates of Acinetobacter baumannii (n = 470) were collected during a 7-year period and investigated for the genetic determinants of resistance to expanded-spectrum beta-lactams. Thirty-one isolates produced the TEM-92 extended-spectrum beta-lactamase (ESBL) and were clonally related. This is the first report of A. baumannii producing a TEM-type ESBL.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; beta-Lactams; Cross Infection; Humans; Italy; Microbial Sensitivity Tests

A prospective observational study was conducted to identify factors associated with bloodstream infections (BSIs) caused by integron-carrying Enterobacteriaceae and to evaluate the clinical significance of integron carriage. Consecutive patients with Enterobacteriaceae BSIs were identified and followed up until discharge or death. Identification of blood isolates and susceptibility testing were performed by the Wider I automated system. int-1-specific PCR, conserved-segment PCR, and DNA sequencing were used to determine the presence, length, and content of integrons. The relatedness among the isolates was examined by pulsed-field gel electrophoresis. Two hundred fifty episodes of Enterobacteriaceae BSI occurred in 233 patients; 109 (43.6%) were nosocomial, 82 (32.8%) were community acquired, and 59 (23.6%) were health care associated. Integrons were detected in 11 (13.4%) community-acquired, 24 (40.7%) health care-associated, and 46 (42.2%) nosocomial isolates. Integron-carrying organisms were more likely to exhibit resistance to three or more classes of antimicrobials (odds ratio [OR], 9.84; 95% confidence interval [95% CI], 5.31 to 18.23; P < 0.001) or to produce extended-spectrum beta-lactamases (OR, 5.75; 95% CI, 2.38 to 13.89; P < 0.001) or a VIM-type metallo-beta-lactamase (P, 0.003). Inter- or intraspecies integron transfer and cross-transmission of integron-carrying clones were observed. Use of cotrimoxazole (OR, 4.77; 95% CI, 1.81 to 12.54; P < 0.001) and a nosocomial or other health care setting (OR, 3.07; 95% CI, 1.30 to 7.22; P, 0.01) were independently associated with BSIs caused by integron-carrying Enterobacteriaceae. Patients with a nonurinary source of bacteremia (OR, 9.46; 95% CI, 2.77 to 32.32; P < 0.001) and a Pitt bacteremia score of > or =4 (OR, 23.36; 95% CI, 7.97 to 68.44; P < 0.001) had a significantly higher 14-day mortality rate, whereas integron carriage did not affect clinical outcomes. These findings may have implications affecting antibiotic policies and infection control measures.

Topics: Bacteremia; Community-Acquired Infections; Cross Infection; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Enterobacteriaceae Infections; Gene Transfer, Horizontal; Humans; Infectious Disease Transmission, Professional-to-Patient; Integrons; Microbial Sensitivity Tests; Nucleic Acid Amplification Techniques; Polymerase Chain Reaction; Prospective Studies; Risk Factors; Sequence Analysis, DNA; Treatment Outcome

Seven bla(IMP-1)-harboring Acinetobacter sp. isolates and one Pseudomonas putida clinical isolate were recovered from hospitalized patients. All isolates possessed a class 1 integron, named In86, carrying the same cassette array [bla(IMP1), aac(6')-31, and aadA1], which was plasmid located in five of the isolates. This report describes the ability of nonfermentative nosocomial pathogens to acquire and disseminate antimicrobial resistance determinants.

Topics: Acinetobacter; Amino Acid Sequence; Aminoglycosides; Anti-Bacterial Agents; Base Sequence; Brazil; Codon, Terminator; Cross Infection; Drug Resistance, Multiple, Bacterial; Gene Transfer, Horizontal; Genes, Bacterial; Hospitals; Humans; Integrons; Microbial Sensitivity Tests; Molecular Sequence Data; Open Reading Frames; Plasmids; Pseudomonas putida; Transcription, Genetic

Topics: Acinetobacter; Acinetobacter baumannii; Acinetobacter Infections; Bacterial Proteins; beta-Lactamases; Cross Infection; Humans; Plasmids; Portugal

Carbapenem resistance in Acinetobacter spp. is an emerging problem in China. We investigated the molecular epidemiology and carbapenemase genes of 221 nonrepetitive imipenem-resistant clinical isolates of Acinetobacter spp. collected from 1999 to 2005 at 11 teaching hospitals in China. Genotyping by pulsed-field gel electrophoresis (PFGE) found 15 PFGE patterns. Of these, one (clone P) was identified at four hospitals in Beijing and another (clone A) at four geographically disparate cities. Most imipenem-resistant isolates exhibited high-level resistance to all beta-lactams and were only susceptible to colistin. bla(OXA-23)-like genes were found in 97.7% of isolates. Sequencing performed on 60 representative isolates confirmed the presence of the bla(OXA-23) carbapenemase gene. Analysis of the genetic context of bla(OXA-23) showed the presence of ISAba1 upstream of bla(OXA-23). All of the 187 A. baumannii isolates identified by amplified RNA gene restriction analysis carried a bla(OXA-51)-like oxacillinase gene, while this gene was absent from isolates of other species. Sequencing indicated the presence of bla(OXA-66) for 18 representative isolates. Seven isolates of one clone (clone T) carried the plasmid-mediated bla(OXA-58) carbapenemase gene, while one isolate of another clone (clone L) carried the bla(OXA-72) carbapenemase gene. Only 1 isolate of clone Q carried the bla(IMP-8) metallo-beta-lactamase gene, located in a class 1 integron. Of 221 isolates, 77.8% carried bla(PER-1)-like genes. Eleven different structures of class 1 integrons were detected, and most integrons carried genes mediating resistance to aminoglycosides, rifampin, and chloramphenicol. These findings indicated clonal spread of imipenem-resistant Acinetobacter spp. and wide dissemination of the OXA-23 carbapenemase in China.

Topics: Acinetobacter; Acinetobacter Infections; Aminoglycosides; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; beta-Lactams; Blotting, Southern; Carbapenems; China; Chloramphenicol; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Hospitals; Humans; Imipenem; Integrons; Microbial Sensitivity Tests; Molecular Epidemiology; Molecular Sequence Data; Rifampin; Sequence Analysis, DNA

All (236) Pseudomonas aeruginosa isolates resistant to imipenem and/or meropenem collected during a multicenter (127-hospital) study in Spain were analyzed. Carbapenem-resistant isolates were found to be more frequently resistant to all beta-lactams and non-beta-lactam antibiotics than carbapenem-susceptible isolates (P < 0.001), and up to 46% of the carbapenem-resistant isolates met the criteria used to define multidrug resistance (MDR). Pulsed-field gel electrophoresis revealed remarkable clonal diversity (165 different clones were identified), and with few exceptions, the levels of intra- and interhospital dissemination of clones were found to be low. Carbapenem resistance was driven mainly by the mutational inactivation of OprD, accompanied or not by the hyperexpression of AmpC or MexAB-OprM. Class B carbapenemases (metallo-beta-lactamases [MBLs]) were detected in a single isolate, although interestingly, this isolate belonged to one of the few epidemic clones documented. The MBL-encoding gene (bla(VIM-2)), along with the aminoglycoside resistance determinants, was transferred to strain PAO1 by electroporation, demonstrating its plasmid location. The class 1 integron harboring bla(VIM-2) was characterized as well, and two interesting features were revealed: intI1 was found to be disrupted by a 1.1-kb insertion sequence, and a previously undescribed aminoglycoside acetyltransferase-encoding gene [designated aac(6')-32] preceded bla(VIM-2). AAC(6')-32 showed 80% identity to AAC(6')-Ib' and the recently described AAC(6')-31, and when aac(6')-32 was cloned into Escherichia coli, it conferred resistance to tobramycin and reduced susceptibility to gentamicin and amikacin. Despite the currently low prevalence of epidemic clones with MDR, active surveillance is needed to detect and prevent the dissemination of these clones, particularly those producing integron- and plasmid-encoded MBLs, given their additional capacity for the intra- and interspecies spread of MDR.

Topics: Amino Acid Sequence; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Carbapenems; Chromosomes, Bacterial; Cross Infection; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Integrons; Molecular Epidemiology; Molecular Sequence Data; Mutation; Plasmids; Polymerase Chain Reaction; Porins; Pseudomonas aeruginosa; Sequence Analysis, DNA; Sequence Homology, Amino Acid; Spain

Risk factors, therapy and outcome of 15 cases of nosocomial meningitis due to Pseudomonas aeruginosa is reviewed. No difference in risk factors was found, however mortality for Ps. aeruginosa was significantly higher (33.3 vs 15.1% p<0.04).

Topics: Adolescent; Anti-Bacterial Agents; Cefotaxime; Ceftazidime; Chi-Square Distribution; Child, Preschool; Chloramphenicol; Cross Infection; Drug Therapy, Combination; Female; Gentamicins; Humans; Infant; Infant, Newborn; Male; Meningitis, Bacterial; Meropenem; Pseudomonas Infections; Retrospective Studies; Risk Factors; Survival Analysis; Thienamycins

Within last 15 years, analyzing patterns of etiology and resistance in organisms causing neuroinfections, emergence of resistance has been observed in Slovakia in S. haemolyticus to teicoplanin (11%), Ps. aeruginosa and A. baumannii to meropenem (20%) and Candida spp. (non-albicans Candida spp.) to fluconazol (20%). There are no new antibiotics against carbapenem resistant Ps. aeruginosa and Acinetobacter baumannii.

Topics: Anti-Infective Agents; Brain Diseases; Candidiasis; Cross Infection; Drug Resistance, Microbial; Fluconazole; Humans; Meningitis; Meropenem; Pseudomonas Infections; Staphylococcal Infections; Teicoplanin; Thienamycins

500 strains of Serratia marcescens isolated in 2003-2005 were examined for drug susceptibility. By using several phenotypic methods it was shown that 67.6% of these strains produced ESBLs. Strains ESBL(-) and ESBL(+) were compared, paying special attention to their susceptibility to various antibiotics. It was revealed that strains ESBL(+) were much more resistant to majority of the investigated drugs. The biggest differences were in the case of amikacin and gentamicin, sensitive about 50% of ESBL(-) and 10% of ESBL(+), ciprofloxacin, sensitive 42% of ESBL(-) and 6.3% of ESBL(+) and trimethoprim/ sulphametoxazole, sensitive 45.8% of ESBL(-) and 9.4% of ESBL(+). Strains ESBL(-) retained a high susceptibility to ceftazidime (68.9%) and cefepime (71%). All strains ESBL(-) as well as ESBL(+) were susceptible to imipenem and meropenem. 78.9% of ESBL(-) and 67.3% of investigated ESBL(+) were susceptible to piperacillin/ tazobactam.

Topics: Amikacin; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Ciprofloxacin; Cross Infection; Disk Diffusion Antimicrobial Tests; Drug Resistance, Multiple, Bacterial; Gentamicins; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Poland; Serratia marcescens; Thienamycins

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program is a global study that provides antimicrobial susceptibility data in centers prescribing meropenem. The activity of meropenem and 7 broad-spectrum antimicrobials have been examined against 5208 bacterial isolates from 9 Turkish centers between 2000 and 2003. Cumulative susceptibility rates against all species of Enterobacteriaceae combined were ranked as follows: meropenem (99.3%), imipenem (97.6%), cefepime (80.0%), piperacillin-tazobactam (73.6%), ceftazidime (70.3%), ciprofloxacin (70.1%), cefotaxime (66.9%), and tobramycin (67.2%). The production of extended-spectrum beta-lactamases (ESBLs) was detected in 48.7% of Klebsiella pneumoniae and in 19.5% of Escherichia coli isolates. Of ESBL producing K. pneumoniae isolates, 75.7% were resistant to tobramycin, 40.3% to ciprofloxacin, and 48.3% to piperacillin-tazobactam. Only piperacillin/tazobactam and carbapenems were active against more than 50% of Pseudomonas aeruginosa at the National Committee for Clinical Laboratory Standards-susceptible breakpoint, and the carbapenems were the most active compounds against Acinetobacter spp. These data confirm the continued potency of meropenem against Enterobacteriaceae in units where it is actively being prescribed.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cross Infection; Drug Resistance, Bacterial; Enterobacteriaceae; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Meropenem; Microbial Sensitivity Tests; Population Surveillance; Thienamycins; Turkey

The aim of this study was to determine the frequency of PER-1 type extended-spectrum beta-lactamase (ESBL) in nosocomial Pseudomonas aeruginosa strains isolated in Hacettepe University Adult Hospital. Sixty-seven non-duplicate P. aeruginosa isolates from patients with nosocomial infections between January 2002 and December 2004 were included in the study. The isolates were identified at species-level by Sceptor (Becton Dickinson, USA) system, and all the strains were stored at -80 degrees C until further testing. Polymerase chain reaction (PCR) was performed for the detection of (bla)PER-1 genes, and PFGE analysis was used to investigate their genetic relatedness. The antimicrobial susceptibilities of the PER-1 positive isolates were determined by Etest (AB Biodisk, Solna, Sweden) method. According to the results of PCR, 22.7% (15/67) of the isolates were positive for PER-1 enzyme. Those 15 (bla)PER-1 positive isolates showed eight different PFGE patterns, indicating the presence of multiple clones. Of the PER-1 positive P. aeruginosa isolates, nine were resistant to imipenem/meropenem, and 11 were resistant to piperacillin-tazobactam and tobramycin. The epidemiological investigation of multidrug resistant P. aeruginosa should give important clues for the initial empirical therapy, especially in certain geographic locations where ESBL-producing P. aeruginosa strains seemed to be highly prevalent.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cross Infection; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Humans; Imipenem; Meropenem; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Polymerase Chain Reaction; Pseudomonas aeruginosa; Pseudomonas Infections; Thienamycins; Tobramycin

Ochrobactrum anthropi (formerly Achromobacter spp.) is an aerobic, motile, oxidase positive and lactose negative gram negative bacillus which is widely distributed in the environment and water sources. In recent publications, O. anthropi has an increasing importance as a nosocomial infection agent. The aim of this report was to present a case of O. anthropi bacteremia developed after endoscopic retrograde cholangiopancreatography (ERCP). A 89-year old female patient presented with high fever one day after ERCP performed due to klatskin tumour. O. anthropi had been grown in blood culture (BacT/ALERT 3D, bioMérieux, Durham, USA), and the isolate was identified by automatized system (VITEK, bioMerieux, Marcy l'Etoile, France). Since there was no clinical response to empirical ceftriaxone therapy, it was switched to meropenem, which was found effective by VITEK antibiotic susceptibility detection system. The patient was treated successfully with meropenem therapy (3 x 1 gr/day, 10 days). As a result, in case of suspected post-ERCP bacteremia, unconventional microorganisms such as O. anthropi should be taken into consideration.

Topics: Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Cholangiopancreatography, Endoscopic Retrograde; Cross Infection; Female; Gram-Negative Bacterial Infections; Humans; Meropenem; Microbial Sensitivity Tests; Ochrobactrum anthropi; Thienamycins

The aim of this paper was to evaluate usefulness and safety of Meropenem in severe infections in neonatal intensive care unit (NICU) patients. New broad spectrum carbapenem class of -lactam antibiotics has been investigated for the treatment of a wide range of infections, including nosocomial infections with cephalosporin-resistant pathogens, an emergent problem in NICU, and meningitis. Meropenem represents the first cabapenem-class that has received Food and Drug Administration (FDA) approval for use in children 3 months of age and older. The pharmacokinetics of Meropenem has been well studied in preterm neonates.. We report the use of Meropenem in 26 neonates with median gestational age (GA) of 27 weeks (25-32) and median birth weight of 940 g (510-1900), with severe infections due to Gram-negative or Gram-positive organisms, from 2001 to 2004. The median postnatal age was 21 days (4-75). Meropenem was administrated intravenously in 30 min at dosage of 20 mg/kg every 12 h (every 8 h in Pseudomonas Aeruginosa infections).. In all cases Meropenem has been used as second choice. No adverse effects (eosinophilia, trombocytosis or thrombocytopenia, increase in liver enzyme, increase in creatinine, diarrhea, vomiting and seizures) were observed. Clinical and bacterial response was ontaine in all cases but one.. This report suggests that Meropenem may be a useful and safe antimicrobial agent in neonatal infections caused by resistant organisms and in meningitis. Further studies are needed to confirm these results.

Topics: Anti-Bacterial Agents; Cross Infection; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature; Intensive Care Units, Neonatal; Liver Function Tests; Meropenem; Severity of Illness Index; Thienamycins; Treatment Outcome

The study monitored the susceptibility of nosocomial pathogens to meropenem and comparator antimicrobial agents isolated as part of the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program from Turkish university hospitals. In terms of minimum inhibitory concentration 90% (MIC(90)) values, meropenem was two- and eight-fold more active than imipenem against Escherichia coli and Klebsiella pneumoniae, respectively. 40.5% of K. pneumoniae, 23.1% of Klebsiella oxytoca and 15.3% of E. coli isolates were extended-spectrum beta-lactamase (ESBL) producers. Piperacillin/tazobactam was the most active agent against isolates of Pseudomonas aeruginosa, followed by meropenem and imipenem. Against Acinetobacter baumannii isolates, meropenem and imipenem were the most active agents. Continued surveillance by the MYSTIC Program appears to be prudent to help focus on effective empiric treatment regimens.

Topics: Anti-Bacterial Agents; Cross Infection; Drug Resistance, Bacterial; Escherichia coli; Humans; Imipenem; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Thienamycins; Turkey

The epidemiological impact of Acinetobacter baumannii nosocomial infections in a Sicilian intensive care unit (ICU) was investigated to determine the Acinetobacter-specific infection rates, to estimate the preventable proportion of Acinetobacter infections, i.e., those resulting from cross-transmission, and to investigate the molecular epidemiology of antimicrobial resistance in Acinetobacter. The impact of Acinetobacter nosocomial infection in the ICU was determined to be 3.0 new cases per 100 admissions. Site-specific rates confirmed that ICU-acquired pneumonia was the most important infection type. The incidence rate, adjusted by the number of patient-days, was 3.3 infections/1000 patient-days. The estimated preventable proportion of A. baumannii nosocomial infections in the ICU was 66.7%. A class 1 integron, characterised by its gene cassette content, was present in all A. baumannii isolates of four different pulsed-field gel electrophoresis types, and was associated significantly with clones implicated in cross-transmission episodes. Furthermore, the same integron was detected in two genetically distinct isolates responsible for recurrent infection in the same patient, suggesting the occurrence of horizontal gene transfer in vivo. Even in an endemic setting with low infection rates, spread of A. baumannii was caused mainly by infection control shortcomings that require appropriate surveillance and control policies.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Cross Infection; Drug Resistance, Microbial; Electrophoresis, Gel, Pulsed-Field; Gene Transfer, Horizontal; Humans; Imipenem; Integrons; Intensive Care Units; Italy; Meropenem; Morbidity; Pneumonia, Bacterial; Thienamycins

We studied the clinical effect of continuous infusion over 24 hours of meropenem (MEPM) on bacterial pneumonia in the elderly (over 65). The subjects were 26 patients (community-acquired pneumonia: moderate, n = 9; severe, n= 4; hospital-acquired pneumonia: group III, n = 13) whose performance status was 3 or 4. MEPM 1.0g/day was infused continuously for 7-14 days, and its clinical efficacy, bacteriological efficacy, and side effects were examined prospectively. It was effective in 23 of the 26 patients (community-acquired pneumonia: moderate, 8/9; severe, 3/4; hospital-acquired pneumonia: group III, 12/13; efficacy rate: 88.5%). Bactericidal effects were obtained in 3 strains of Klebsiella pneumoniae, 2 strains of Streptococcus pneumoniae, 2 strains of methicillin-sensitive Staphlococcus aureus, 1 strain of Streptococcus agalactiae and 1 strain of Proteus mirabilis, but not in 2 strains of methicillin-resistant S. aureus, 1 strain of Pseudomonas aeruginosa and 1 strain of Serratia marcescens. Mild abnormal laboratory findings were observed in 2 patients: elevation of GPT, gamma-GTP, BUN and elevation of ALP. Based on the above, continuous infusion of MEPM on bacterial pneumonia in the elderly obtained excellent clinical effects. Further study is needed to compare the efficacy of continuous versus intermittent administration of MEPM.

Topics: Aged; Aged, 80 and over; Community-Acquired Infections; Cross Infection; Drug Administration Schedule; Female; Humans; Infusions, Intravenous; Male; Meropenem; Pneumonia, Bacterial; Prospective Studies; Thienamycins

Nosocomial infections after spinal surgery are relatively uncommon but potentially serious. The goal of diagnostic evaluation is to determine the extent of infection and identify the microorganism involved. Neuroimaging provides accurate information on correct topography, localization and propagation of the infection. Microbiological data are able to give aetiological causes. In this patient with severe, chronic polymicrobial spine infection with epidural abscess and CSF fistula due to multidrug-resistant organisms, the cure was achieved with long-term antimicrobial specific therapy with quinupristin-dalfopristin (50 days) and linezolid (100 days) with mild side effects. This positive result was due to combined medical and surgical treatment.

Topics: Acetamides; Anti-Bacterial Agents; Bacteria; Cerebrospinal Fluid; Combined Modality Therapy; Cross Infection; Curettage; Device Removal; Discitis; Epidural Abscess; Female; Fistula; Fluconazole; Fungi; Humans; Internal Fixators; Laminectomy; Linezolid; Lumbar Vertebrae; Meropenem; Methicillin Resistance; Middle Aged; Osteomyelitis; Oxazolidinones; Parkinson Disease; Prosthesis-Related Infections; Reoperation; Skin Diseases; Spinal Diseases; Spinal Stenosis; Staphylococcal Infections; Thienamycins; Virginiamycin

Antibiotic susceptibility of nosocomial Klebsiella isolates from inpatients of 30 medical centres in 15 various regions of Russia was studied. In total 212 strains were tested. The Klebsiella genus was represented by the following species: Klebsiella pmeumoniae ss. pneumoniae (182 isolates, 85.8%), Klebsiella pneumonia ss. ozaenae (1 isolate, 0.5%), Klebsiella oxytoca (29 isolates, 13.7%). The susceptibility was determined by the broth microdilution method. Carbapenems (imipenem and meropenem) remained to be the most active antibacterial agents. However, 1 imipenem resistant strain and 2 meropenem resistant strains were isolated. As for the 3rd generation cephalosporins, the lowest MICs were observed with the use of the inhibitor-protected agents, such as ceftazidime/clavulanic acid (MIC50 0.25 mcg/ml, MIC90 64 mcg/ml). 48.8%, 16.9%, 29.7% and only 10.5% of the isolates was susceptible to cefepime, cefotaxime, ceftazidime and cefoperazone respectively. Detecting of the beta-lactamase genes (TEM, SHV and CTX) was performed by PCR in 42 strains of Klebsiella pneumoniae ss. pneumoniae. Alone or in various combination the TEM type beta-lactamases were detected in 16 (38.1%) isolates. SHV and CTX were detected in 29 (69%) and 27 (64.3%) isolates respectively. Combinations of 2 and 3 different determinants of resistance to beta-lactams were revealed in 23.8% and 26.2% of the isolates respectively. No isolates producing class B MBL among the carbapenem resistant nosocomial Klebsiella strains were detected.

Topics: Anti-Bacterial Agents; Carbapenems; Cephalosporin Resistance; Cross Infection; Humans; Imipenem; Klebsiella; Klebsiella Infections; Meropenem; Thienamycins

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program provides antimicrobial susceptibility data. The activity of meropenem and 7 broad-spectrum antimicrobials have been examined against 12645 bacterial isolates from 14 European centers between 1997 and 2002. Cumulative susceptibility rates against all species of Enterobacteriaceae combined were ranked as follows: meropenem (99.9%) > imipenem (97.7%) > ciprofloxacin (86.0%) > piperacillin-tazobactam (85.6%) > ceftazidime (85.4%) > gentamicin (85.4%) > tobramycin (85.0%) > cefotaxime (83.8%). The carbapenems were also found to be the most active of the classes tested against nonfermentative Gram-negative bacilli. Against methicillin-susceptible Staphylococcus aureus and coagulase-negative staphylococci, all beta-lactams tested (except ceftazidime) had susceptibility rates of > or = 99.0% and > or = 94.3%, respectively. Over the 6-year period, there was no loss of activity or increase in resistance rate for either carbapenem against any of the species tested. These data confirm the continued potency and broad-spectrum activity of meropenem in units where it is actively being prescribed.

Topics: Academic Medical Centers; Anti-Bacterial Agents; Cross Infection; Drug Resistance, Bacterial; Europe; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Hospitalization; Humans; Meropenem; Microbial Sensitivity Tests; Population Surveillance; Thienamycins

Antimicrobial resistance of isolates and risk factors for mortality were retrospectively investigated in 71 adult patients with Serratia marcescens bacteremia. During the 4-year study period, 78 clinically significant episodes of S. marcescens bacteremia occurred in 71 patients. The mean age of the patients was 65 years (range, 25-86 years) with a male predominance (45 patients, 63%). Most of the bacteremic episodes were nosocomial (78%), and 34% were polymicrobial. The overall mortality rate within 2 weeks after the onset of bacteremia was 41%. The presence of malignancy and critical illness at initial presentation were independent risk factors for mortality. By disk susceptibility test, 72 isolates were resistant to cefotaxime (92%) but susceptible to ceftazidime (99%). All isolates were susceptible to meropenem. Among the 47 patients with monomicrobial S. marcescens bacteremia, the mortality rate within 5 days of onset in patients receiving appropriate empirical antimicrobial therapy was lower than that in patients receiving inappropriate therapy although this difference was not significant (14% vs 28%, p = 0.27). Among the patients with cefotaxime-resistant but ceftazidime-susceptible S. marcescens bacteremia treated with ceftazidime, 6 of 7 patients (86%) survived for more than 2 weeks, suggesting the potential effectiveness of ceftazidime in the treatment of cefotaxime-resistant Serratia infections. Further clinical studies are required to delineate the clinical role of ceftazidime therapy for infections caused by S. marcescens with this resistant phenotype.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; Cefotaxime; Ceftazidime; Critical Illness; Cross Infection; Drug Resistance, Bacterial; Female; Humans; Male; Meropenem; Middle Aged; Neoplasms; Retrospective Studies; Risk Factors; Serratia Infections; Serratia marcescens; Taiwan; Thienamycins

To compare the probability of achieving specific pharmacodynamic exposures of commonly used intravenous antibiotics for the empirical treatment of nosocomial pneumonia against those pathogens most commonly implicated in the disease.. Ten thousand-subject Monte Carlo simulation.. Research center.. None.. Pharmacodynamic analysis was conducted for the following antimicrobials at standard doses: meropenem, imipenem-cilastatin, ceftazidime, cefepime, piperacillin/tazobactam, and ciprofloxacin. Prevalence of causative pathogens was based on the 2000 SENTRY Antimicrobial Surveillance Study, and minimum inhibitory concentration (MIC) values were obtained using the 2003 US MYSTIC database. The probabilities of each drug and dosing regimen in achieving pharmacodynamic targets were calculated. Bactericidal targets were defined as 40% T>MIC for the carbapenems, 50% T>MIC for other beta-lactams, and an area under the curve (AUC)/MIC ratio of 125 for ciprofloxacin. A sensitivity analysis was performed using two alternate models to determine the impact of varying pathogen prevalence on target attainment.. Meropenem and imipenem provided high probabilities of achieving their bactericidal target of 40% T>MIC, with target attainments of 98% for all regimens. At the bactericidal end point of 50% T>MIC, cefepime 2 g every 8 hrs displayed the highest target attainment at 99.9%, followed by cefepime 2 g every 12 hrs, ceftazidime 2 g every 8 hrs, piperacillin/tazobactam 4.5 g every 6 hrs and 3.375 g every 6 hrs, cefepime 1 g every 12 hrs, and ceftazidime 1 g every 8 hrs with target attainments of 95.0%, 92.5%, 92.3%, 91.3%, 90.3%, and 67.9%, respectively. Ciprofloxacin presented the lowest probability of achieving its bactericidal target of an AUC/MIC ratio of 125, with target attainments of 54.7% and 12.0% when given as 400 mg every 8 hrs and 400 mg every 12 hrs, respectively.. Meropenem, imipenem, cefepime, ceftazidime (2 g every 8 hrs), and piperacillin/tazobactam have high probabilities of achieving adequate pharmacodynamic exposures when given for the empirical treatment of nosocomial pneumonia in the absence of methicillin-resistant S. aureus. Ceftazidime 1g every 8 hrs and ciprofloxacin produce low target attainment rates and will not likely result in high clinical success rates when given as monotherapy.

Topics: Anti-Bacterial Agents; Cefepime; Ceftazidime; Cephalosporins; Ciprofloxacin; Cross Infection; Dose-Response Relationship, Drug; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Monte Carlo Method; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Thienamycins

An outbreak of extended-spectrum beta-lactamase (ESBL) producing Klebsiella pneumoniae (ESBL-Kp) in a neonatal intensive care unit prompted a prospective surveillance study between 12th September and 6th October 2003. Surveillance was carried out by obtaining stool samples twice a week. The DNA relatedness of the isolates was shown by random amplified polymorphic DNA comparison (ERIC-PCR). ESBL production was identified by clavulanate synergy, isoelectric focusing, PCR and sequence analysis. During the study period, 49 neonates were hospitalized in the neonatal intensive care unit (NICU). In the first 20-day period, five neonates were infected with ESBL-Kp. The first patient treated with third generation cephalosporin and the second patient treated with meropenem died. While all three infected survivors were clinically improving, the digestive tracts were being colonized by SHV-5 producing Klebsiella. In the next period of the study, five neonates were colonized by ESBL-Kp as well. Univariate comparison of risk factors between colonized and non-colonized neonates was not significant. A total of 24 colonally related ESBL-Kp have been recovered from clinical materials and stool samples. This study demonstrated that parenterally applied meropenem, though successful in treating the systemic illness, might fail to protect the digestive tract from colonization of ESBL-Kp.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cephalosporins; Cohort Studies; Cross Infection; Disease Outbreaks; DNA Fingerprinting; DNA, Bacterial; Feces; Female; Genes, Bacterial; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Isoelectric Focusing; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Molecular Epidemiology; Polymerase Chain Reaction; Random Amplified Polymorphic DNA Technique; Sequence Analysis, DNA; Thienamycins

This study examines the susceptibilities of meropenem and other broad-spectrum antimicrobials tested against bacterial isolates collected from hospitalized patients during 2002-2004 from worldwide medical centers participating in the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program. The in vitro activity of meropenem and 5 comparator antimicrobial agents was assessed against Pseudomonas aeruginosa and Acinetobacter spp. Generally, the susceptibility of Australasian and North American isolates was higher than that of the European and South American isolates. The rank order of activity of the antimicrobial agents tested against a worldwide collection of P. aeruginosa was piperacillin/tazobactam (77.7% susceptible) > meropenem (75.4%) > ceftazidime (70.0%) > imipenem (69.7%) > gentamicin (66.1%) > ciprofloxacin (62.0%). Against a worldwide collection of Acinetobacter spp. meropenem (76.1% susceptible) was the most active compound followed by imipenem (74.7%) > gentamicin (51.9%) > ciprofloxacin (40.5%) > piperacillin/tazobactam (39.8%) > ceftazidime (38.1%). The carbapenems appear to be a valuable option for the treatment of serious nosocomial infections caused by P. aeruginosa or Acinetobacter spp. over a broad geographical region.

Topics: Acinetobacter; Acinetobacter Infections; Anti-Bacterial Agents; Asia; Australia; Cross Infection; Drug Resistance, Bacterial; Europe; Humans; Inpatients; Meropenem; Microbial Sensitivity Tests; North America; Population Surveillance; Pseudomonas aeruginosa; Pseudomonas Infections; South America; Thienamycins

Antibiotic surveillance studies lack consideration of pharmacodynamics and provide little information about optimal dosing. By using minimum inhibitory concentration (MIC) data derived from a global surveillance study and Monte Carlo simulation, the Optimizing Pharmacodynamic Target Attainment using the MYSTIC Antibiogram (OPTAMA) Program was established to impart greater understanding of the ability to attain pharmacodynamic exposure for specific dosing regimens and their relationship with percent susceptibility. Early OPTAMA studies focused on determining the cumulative fraction of response (CFR) for various antibiotics against Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa regionally in Europe and the Americas. Later reports considered the prevalence of specific bacteria causing infections to estimate the CFR for empiric therapy of pneumonia, bloodstream, complicated skin/skin structure, and intra-abdominal infections. Collectively, the approach of the OPTAMA Program provides a novel tool that complements susceptibility data to help in the selection of appropriate empirical antibiotic therapy at the national, regional, and institutional level.

Topics: Anti-Bacterial Agents; Cross Infection; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Meropenem; Microbial Sensitivity Tests; Monte Carlo Method; Thienamycins

The antimicrobial susceptibility of 103 clinical isolates of Enterobacteriaceae to 11 antibiotics, was investigated, using a conventional inoculum size (5 x 10(5) CFU) and a higher inoculum size (5 x 10(8) CFU). All the isolates produced complex beta-lactamase patterns, including an extended-spectrum beta-lactamase (ESBL) of the TEM- or SHV-type plus other enzymes (a TEM-type or an SHV-type non-ESBL and/or a class C enzyme). The following repertoire of ESBLs was produced by the isolates: TEM-15, TEM-19, TEM-26, TEM-52, TEM-72, TEM-87, TEM-92, SHV-2a, SHV-5 and SHV-12, as assessed by sequencing. Production of the other enzymes was showed by analytical isoelectric focusing. Overall, meropenem was the most active agent and less influenced by inoculum size, while other beta-lactams showed a lower activity and a significant inoculum size effect. In conclusion, from its in vitro performance, meropenem could be considered as the last resource drug against strains producing complex beta-lactamase patterns including an ESBL.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; beta-Lactams; Colony Count, Microbial; Cross Infection; DNA, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Genes, Bacterial; Humans; Italy; Meropenem; Microbial Sensitivity Tests; Sequence Analysis, DNA; Thienamycins

Listeria monocytogenes is highly susceptible to meropenem in vitro, but data on the efficacy of meropenem in clinical cases of listeriosis are scarce. Described here is the case of a child with aplastic anemia who acquired nosocomial listeriosis and failed to respond to initial meropenem therapy. Resolution of fever was not noted after 5 days of therapy with meropenem and, more importantly, clinical worsening was observed during this period. The patient began to improve after ampicillin was introduced to the therapeutic regimen. In total, meropenem was administered for 15 days and ampicillin for 10 days.

Topics: Ampicillin; Anemia, Aplastic; Child, Preschool; Cross Infection; Drug Therapy, Combination; Follow-Up Studies; Humans; Immunocompromised Host; Listeria monocytogenes; Listeriosis; Male; Meropenem; Risk Assessment; Severity of Illness Index; Thienamycins; Treatment Failure

Risk factors for multi-drug resistant Pseudomonas aeruginosa (MDRP) infections were investigated using a case-control study design involving MDRP patients (N = 44) and controls (N = 68). A retrospective cohort study was performed to study the predictive factors of clinical outcome in MDRP patients. Multivariate analysis demonstrated that previous exposure to imipenem/meropenem [odds ratio (OR), 44.8] and mechanical ventilation (OR 8.2) were risk factors for nosocomial infections of MDRP. Of 44 cases of MDRP infections, 20 patients died directly from P. aeruginosa infections. Pulsed-field gel electrophoresis (PFGE) analysis on serial isolates from three patients showed that profiles of isolates from the same patient were closely related or indistinguishable. Multivariate analysis demonstrated that patients with adverse clinical outcomes were more likely to have been treated with mechanical ventilation (OR 12.8), and more likely to have MDRP resistance patterns that did not change during treatments (OR 26.5). We concluded that mechanical ventilation and previous exposure to imipenem/meropenem were independent risk factors for MDRP infections, while mechanical ventilation and antibiotic resistance switch were predictive factors of outcomes of MDRP infections.

Topics: Adult; Age Factors; Aged; Anti-Bacterial Agents; Case-Control Studies; China; Comorbidity; Cross Infection; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Hospitals, University; Humans; Imipenem; Logistic Models; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Respiration, Artificial; Risk Factors; Thienamycins; Treatment Outcome

The aim of this study was to detect carbapenemases in imipenem-resistant Acinetobacter baumannii isolates obtained in the microbiology department of a Basque Country Public Health Service hospital over a period of 19 months, and to genetically characterize the resistant clones.. Susceptibility tests to imipenem, meropenem, ticarcillin, ceftazidime, cefotaxime, cefepime and aztreonam were done by determining the minimum inhibitory concentration on agar plates. A tRNA technique was used for species identification and PCR with primers ERIC2, AP3 and M13 for genetic typing of resistant isolates. Carbapenemase production was detected by the Hodge test and metallo-beta-lactamase by the EDTA test and Etest MBL.. A total of 76 isolates were resistant to imipenem and 49 of these were resistant to all the betalactam antibiotics tested. Genetic typing showed three predominant clones, denominated I (9 isolates), II (48 isolates) and III (8 isolates). Hodge and EDTA tests were positive in 45 and 8 isolates belonging to clone II, 8 and 4 belonging to clone I and 7 and 3 belonging to clone III, respectively. The Etest confirmed 7 results (45% of the 17 positive EDTA test isolates).. Our results show that one factor contributing to the high level of imipenem resistance in the isolates analyzed is dissemination of a predominant, multiresistant clone able to produce OXA-type carbapenemases and metallo-beta-lactamases.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; beta-Lactams; Carbapenems; Cross Infection; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Genotype; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Multicenter Studies as Topic; Spain; Thienamycins

The treatment of gram-negative infection of the central nervous system (CNS) presents a clinical challenge due to antibiotic resistance and difficulties with penetration into the cerebrospinal fluid (CSF). Two patients with gram-negative CNS infections were treated successfully with high-dose, prolonged infusions of meropenem. The CSF meropenem concentrations exceeded the minimum inhibitory concentration of the pathogen for virtually the entire dosing interval in both cases. Our experience demonstrates that dosage modification to maximize pharmacodynamic targets and bactericidal activity may be practically applied to optimize antibiotic treatment for difficult-to-treat CNS infections.

Topics: Adult; Cross Infection; Female; Gram-Negative Bacterial Infections; Humans; Infusions, Intravenous; Male; Meningitis, Bacterial; Meropenem; Middle Aged; Pseudomonas aeruginosa; Serratia marcescens; Thienamycins; Time Factors

Outbreaks of Acinetobacter baumannii demonstrating multiple antibiotic resistance, including meropenem resistance, have been described as severe therapeutic problems. Here we describe a monoclonal outbreak of infection and colonization with multidrug-resistant A. baumannii over a two-month period. Resistance to meropenem was mediated by expression of a metallo-beta-lactamase enzyme. Four of 14 patients showed clinical signs of infection and two died. Contamination of the environment, water, or instruments were excluded as causes of the outbreak. All patients, except one, underwent surgery in a specific operation theatre where surgery of contamination class IV (infected, dirty) was performed. Although individual surgeon error was eliminated, analyses of the patients' histories suggested that bacterial transmission had occurred during surgery. Five patients showed signs of A. baumannii infection and two of these patients suffered from large abdominal wounds infected with a high density of A. baumannii requiring repeated revisions. Presumably, these revisions favoured the transmission of A. baumannii, which is remarkably resistant to various environmental stresses including soaps, disinfectants and dry conditions. No case of meropenem-resistant A. baumannii had been observed in the hospital before the outbreak. Interestingly, the resistant bacteria appear to have been imported by a patient returning from West Africa. This indicates that, similar to MRSA, multiresistant A. baumannii may be introduced by patients from foreign hospitals. The outbreak was stopped in the following months by reinforcing standard procedures and by taking all necessary precautions such as patient isolation, and finally only one new case was detected.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; beta-Lactamases; Cameroon; Carrier State; Cross Infection; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Environmental Monitoring; Epidemiological Monitoring; Female; Gene Expression Regulation, Bacterial; Germany; Hospitals, University; Humans; Infection Control; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Operating Rooms; Prevalence; Retrospective Studies; Risk Factors; Thienamycins; Travel

Abstract Sub-inhibitory concentrations of imipenem and meropenem were evaluated for their ability to induce morphological changes with six strains of Acinetobacter baumannii isolated from patients with nosocomial pneumonia. Three strains were susceptible and three were resistant to carbapenems. The strains were grown in the presence of 0 (controls), 0.25x, 0.5x and 1x the MIC of both carbapenems for 4 h, and then examined after Gram's stain. Cells > or = 3 microm in size (spheroplasts) were considered to be altered. Both carbapenems induced significant numbers of spheroplasts compared to controls. Imipenem had more effect against susceptible strains, while meropenem had a greater effect against resistant strains.

Topics: Acinetobacter baumannii; Carbapenems; Cross Infection; Histocytochemistry; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Pneumonia; Thienamycins

The incidence of candiduria is increasing in teaching hospitals. We examined the hypothesis that this trend was correlated with the amount of departmental antibiotic consumption. In the setting of a large teaching hospital in Israel, the correlation coefficient between departmental intravenous antibiotic consumption (expressed as daily defined dose (DDD)/1000 patient-days) and the incidence of candiduria per 1000 patient-days was 0.47 (P=0.03). For broad-spectrum antibiotics, the corresponding correlation coefficient was 0.66 (P=0.001). The strongest correlation with candiduria was shown for the use of meropenem (r=0.79, P<0.001) and ceftazidime (r=0.66, P=0.001). This is the first time that departmental habits of antibiotic use have been shown to be strongly correlated with the incidence of candiduria in hospitalized patients. These results add an important new dimension to the strategy of restricting broad-spectrum antibiotics.

Topics: Anti-Bacterial Agents; Candida; Candidiasis; Ceftazidime; Cross Infection; Drug Utilization; Hospital Bed Capacity, 500 and over; Hospital Departments; Hospitals, Teaching; Humans; Incidence; Infection Control; Infusions, Intravenous; Internal Medicine; Israel; Meropenem; Organizational Policy; Practice Patterns, Physicians'; Retrospective Studies; Risk Factors; Surgery Department, Hospital; Thienamycins; Urinary Tract Infections

We describe a case of empyema with infected ascites caused by Stenotrophomonas maltophilia, which has rarely been reported as pathogenic. The source was determined to a disinfectant solution. The isolate was sensitive to a newer carbapenem-meropenem, and the patient was treated successfully. This case represents a novel dual presentation of a nosocomial infection by the isolate in question.

Topics: Aged; Anti-Bacterial Agents; Cross Infection; Disinfectants; Female; Gram-Negative Bacterial Infections; Humans; India; Meropenem; Stenotrophomonas maltophilia; Thienamycins

The MYSTIC program is an international, multicenter surveillance study that compares the activity of meropenem, in centers that are prescribers, with that of imipenem, ceftazidime, piperacillin/tazobactam, ciprofloxacin and gentamicin. These Italian data are from 3 centers (neutropenia, cystic fibrosis and intensive care units). A total of 2,072 (238 Gram-positive and 1,834 Gram-negative) aerobic microorganisms were collected during the study. Pseudomonas aeruginosa (33.4%) was the most isolated species followed by Escherichia coli (14.4%). All except one Enterobacteriaceae strain isolated were fully susceptible to meropenem. Moreover, the activity of meropenem against Enterobacteriaceae was about eight-fold greater than that of imipenem and four- to eight-fold more active than that of ceftazidime. Meropenem was highly active against non-fermentative Gram-negative microorganisms, exceeding the activity of most of the other antimicrobial agents tested. Moreover, meropenem showed increasing activity during the 4 years of study (starting from 86.2% in 1997 to 94.0% in 2000). In conclusion, our results indicate that meropenem has excellent potency and spectrum of activity despite being prescribed for the treatment of seriously ill patients, and appears to be a reliable option for the initial empirical treatment of serious nosocomial infections.

Topics: Anti-Bacterial Agents; Bacteria; Cross Infection; Data Collection; Disease Susceptibility; Drug Resistance, Bacterial; Humans; Italy; Meropenem; Microbial Sensitivity Tests; Population Surveillance; Thienamycins

Topics: Anti-Bacterial Agents; Ceftazidime; Cross Infection; Drug Therapy, Combination; Humans; Meropenem; Pneumonia, Bacterial; Respiration, Artificial; Thienamycins

From February to November 1997, 29 inpatients at Ramón y Cajal Hospital, Madrid, Spain, were determined to be either colonized or infected with imipenem- and meropenem-resistant Acinetobacter baumannii (IMRAB) strains (MICs, 128 to 256 microg/ml). A wide antibiotic multiresistance profile was observed with IMRAB strains. For typing IMRAB isolates, pulsed-field gel electrophoresis was used. For comparative purposes, 30 imipenem- and meropenem-susceptible A. baumannii (IMSAB) strains isolated before, during, and after the outbreak were included in this study. The molecular-typing results showed that the outbreak was caused by a single IMRAB strain (genotype A). By cloning experiments we identified a class D beta-lactamase (OXA-24) encoded in the chromosomal DNA of this IMRAB strain which showed carbapenem hydrolysis. Moreover, the outer membrane profile of the IMRAB strain showed a reduction in the expression of two porins at 22 and 33 kDa when compared with genetically related IMSAB isolates. In addition no efflux mechanisms were identified in the IMRAB strains. In summary, we report here the molecular characterization of a nosocomial outbreak caused by one multiresistant A. baumannii epidemic strain that harbors a carbapenem-hydrolyzing enzyme. Although alterations in the penicillin-binding proteins cannot be ruled out, the reduction in the expression of two porins and the presence of this OXA-derived beta-lactamase are involved in the carbapenem resistance of the epidemic nosocomial IMRAB strain.

Topics: Acinetobacter; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Bacterial Outer Membrane Proteins; beta-Lactamases; Carbapenems; Child; Cross Infection; Disease Outbreaks; Drug Resistance, Microbial; Drug Resistance, Multiple; Electrophoresis, Gel, Pulsed-Field; Humans; Hydrolysis; Imipenem; Meropenem; Microbial Sensitivity Tests; Polymerase Chain Reaction; Thienamycins

A proficiency testing project was conducted among 48 microbiology laboratories participating in Project ICARE (Intensive Care Antimicrobial Resistance Epidemiology). All laboratories correctly identified the Staphylococcus aureus challenge strain as oxacillin- resistant and an Enterococcus faecium strain as vancomycin-resistant. Thirty-one (97%) of 32 laboratories correctly reported the Streptococcus pneumoniae strain as erythromycin-resistant. All laboratories testing the Pseudomonas aeruginosa strain against ciprofloxacin or ofloxacin correctly reported the organism as resistant. Of 40 laboratories, 30 (75%) correctly reported resistant MICs or zone sizes for the imipenem- and meropenem-resistant Serratia marcescens. For the extended-spectrum beta-lactamase (ESBL)-producing strain of Klebsiella pneumoniae, 18 (42%) of 43 laboratories testing ceftazidime correctly reported ceftazidime MICs in the resistant range. These results suggest that current testing generally produces accurate results, although some laboratories have difficulty detecting resistance to carbapenems and extended-spectrum cephalosporins. This highlights the need for monitoring how well susceptibility test systems in clinical laboratories detect emerging resistance.

Topics: Aminoglycosides; Anti-Bacterial Agents; Anti-Infective Agents; Ciprofloxacin; Cross Infection; Drug Resistance, Microbial; Enterococcus faecium; Erythromycin; Humans; Imipenem; Laboratories, Hospital; Meropenem; Ofloxacin; Oxacillin; Penicillins; Pseudomonas aeruginosa; Reproducibility of Results; Serratia marcescens; Staphylococcus aureus; Streptococcus pneumoniae; Thienamycins; Vancomycin

To demonstrate the usefulness of REP-PCR and AP-PCR on molecular typing of A. baumannii isolates.. From February to November 1997, 29 inpatients at Ramón y Cajal Hospital, Madrid-23 in five intensive care units (ICUs) and six at two different medical departments-were either colonized or infected with imipenem- and meropenem-resistant Acinetobacter baumannii (IMRAB) strains (MICs of 64-256 mg/L). A wide antibiotic multiresistance profile was observed with IMRAB strains, and only tobramycin, sulbactam and colistin displayed valuable activity. For typing IMRAB isolates, repetitive extragenic palindromic sequence-based polymerase chain reaction (REP-PCR) and arbitrary primer sequence-based polymerase chain reaction (AP-PCR) methods were used and compared with pulsed-field gel electrophoresis (PFGE) as reference technique. For comparative purposes, 30 imipenem- and meropenem-susceptible A. baumannii (IMSAB) strains isolated before, during and after the outbreak were included in this study.. The molecular typing results showed that the outbreak was caused by a single IMRAB strain (genotype 1). On the other hand, seven different genotypes were observed in the pre-, at- and post-outbreak strains tested by REP-PCR. Regarding AP-PCR, three of four at-outbreak IMSAB strains were indistinguishable from the IMRAB profile. Thus, with AP-PCR, only six genotypes were obtained, apart from the IMRAB genotype.. Under our experimental conditions, REP-PCR had a higher discriminatory power than AP-PCR, with PFGE as reference technique. The REP-PCR technique is a useful and expeditious method for the epidemiologic characterization of A. baumannii nosocomial outbreaks, the results being comparable to those obtained with the PFGE technique.

Topics: Acinetobacter; Acinetobacter Infections; Cross Infection; Disease Outbreaks; DNA Fingerprinting; DNA, Bacterial; Drug Resistance, Microbial; Drug Resistance, Multiple; Electrophoresis, Gel, Pulsed-Field; Humans; Imipenem; Meropenem; Polymerase Chain Reaction; Polymorphism, Genetic; Spain; Thienamycins

The activity of two carbapenem compounds, imipenem and meropenem, against 447 strains of Acinetobacter baumannii isolated between 1990 and 1998 in different Chilean hospitals was determined. MIC ranges, MIC(50) and MIC(90), were determined by an agar dilution method. Similar antibacterial activities were observed for both antibacterials; however, a slight increase in the MIC(50) of imipenem and meropenem, and in the MIC(90) of meropenem was found among strains isolated from 1997-1998. Although A. baumannii remains susceptible to these antibiotics, the MIC(50) and MIC(90) have increased in recent years.

Topics: Acinetobacter; Acinetobacter Infections; Chile; Cross Infection; Humans; Imipenem; Meropenem; Thienamycins

Comparative activity of meropenem and other antibacterial drugs against isolates from intensive care and reanimation units of various profiles was estimated. It was shown that the recommendations for the combined therapy with the 3rd generation cephalosporins and aminoglycosides should be revised, since none of the isolates resistant to ceftazidime or cefotaxime was susceptible to gentamicin or tobramycin. At present the most promising agents of empirical therapy are carbapenems (meropenem and imipenem). However, the resistance of methicillin resistant staphylococci and Enterococcus faecium to carbapenems and the intrinsic resistance of some gram-negative bacteria to carbapenems are indicative of the necessity of microbiological diagnosis, especially when the treatment with meropenem fails.

Topics: Anti-Bacterial Agents; Cephalosporins; Cross Infection; Drug Therapy, Combination; Gentamicins; Gram-Negative Bacteria; Gram-Positive Bacteria; Imipenem; Meropenem; Microbial Sensitivity Tests; Thienamycins; Tobramycin

Topics: Anti-Bacterial Agents; Ceftazidime; Cephalosporins; Critical Illness; Cross Infection; Drug Therapy, Combination; Humans; Meropenem; Pneumonia, Bacterial; Severity of Illness Index; Thienamycins; Tobramycin; Treatment Outcome

In 1997 in western Austria, 9.9% of Pseudomonas aeruginosa strains from patients of general practitioners were resistant to imipenem as well as 18.2% of the isolates from hospitals and 20.2% of the strains at a university teaching hospital. Within the hospital the imipenem resistance varied from 9.9% among out-patients to 28.7% in isolates from intensive care units. In medical/surgical words, up to 15.1% of P. aeruginosa strains were resistant to imipenem. The incidence of imipenem-resistant P. aeruginosa strains correlates to the use of carbapenems. In June 1997, 10 consecutive isolates from 8 patients were obtained and typed using restriction fragment length polymorphism analysis (RFLP) and Pyocin typing. All 10 isolates were resistant to meropenem as well as to imipenem. The finding (by RFLP and Pyocin typing) of individual bacterial types in each isolate strongly contradicts the spread of infection by cross infection. However, all patients were proven to have been treated with imipenem during the 3 months prior to testing. In 1997, 13,880 g of imipenem were used at the university hospital in Innsbruck. The use of carbapenems appears to be the main cause for the increased incidence of imipenem-resistant P. aeruginosa strains.

Topics: Austria; Bacterial Typing Techniques; Cross Infection; Drug Resistance, Microbial; Humans; Imipenem; Meropenem; Polymorphism, Restriction Fragment Length; Pseudomonas Infections; Thienamycins

The aim of the study was to determine the activity of four beta-lactam antibiotics against nosocomial strains of Gram-positive bacteria. Two antibiotics combined with beta-lactamase inhibitors: timentin (TIC/CLAV) and tazocin (PIP/TZB) and two carbapenems: imipenem and meropenem were applied. The clinical strains were isolated from patients hospitalized in surgical ward of the National Clinical Hospital No 1 in Warsaw. The strains were identified in the automatic ATB system using ID 32 STAPH, API STREP, API CORYNE and API 20 A strips. The susceptibility of isolates to antibacterial agents was determined in the automatic ATB system using ATB STAPH, ATB STREP and ATB ANA strips. The susceptibility of strains to timentin, tazocin, imipenem and meropenem was tested with disc diffusion method. 111 strains of Gram-positive bacteria were cultured. Staphylococci (49) and enterococci (44) dominated among isolated strains. 33 Staphylococcus spp. strains were identified as methicillin-resistant. The obtained results indicate a significant role of Gram-positive cocci (staphylococci and enterococci) in the aetiology of nosocomial infections. Antibiotics combined with beta-lactamase inhibitors and carbapenems demonstrate broad antibacterial spectrum against clinical strains of Gram-positive bacteria except E. faecium strains.

Topics: Anti-Bacterial Agents; beta-Lactamase Inhibitors; Clavulanic Acids; Cross Infection; Drug Resistance, Microbial; Drug Therapy, Combination; Gram-Positive Bacteria; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Species Specificity; Thienamycins; Ticarcillin

Topics: Cefepime; Ceftazidime; Cephalosporins; Cross Infection; Drug Resistance, Microbial; Drug Resistance, Multiple; Flavobacterium; Gram-Negative Bacterial Infections; Humans; Hydrolysis; Imipenem; Meropenem; Microbial Sensitivity Tests; Thienamycins

Meropenem is a new carbapenem antibiotic of with an antibacterian spectrum similar to that of imipenem, but from which it may mainly be differentiated by the possibility of its administration at high doses and it has no demonstrated proconvulsive effect, properties which make it applicable in the treatment of bacterial meningitis. The clinical and experimental experience in the treatment of bacterial meningitis with this antibiotic is herein reviewed. It has been observed that the efficacy and safety of meropenem in meningitis caused by N. meningitidis, H. influenzae and pneumococci sensitive to penicillin may be similar to that of cefotaxime or ceftriaxone in both the pediatric and adult population. There are very few reports on the treatment of meningitis caused by pneumococci resistant to penicillin. However, given that the activity of meropenem on these pneumococci is similar to that of cefotaxime and that the doses administered are much lower, it does not appear to be recommendable in the treatment of this indication, although it should be tested in all meningeal strain to these characteristics isolated. It may currently be considered that the main indication of meropenem in the infections of the central nervous system is in nosocomial meningitis by multiresistant gram negative bacilli such as those of the Klebsiella-Serratia-Enterobacter and Acinetobacter sp. group. Therefore a limited, albeit favorable, report on the clinical experience with meropenem is herein presented. Meropenem may also be useful in the treatment of meningitis by Pseudomonas aeruginosa in which other treatments have failed.

Topics: Adult; Animals; Blood-Brain Barrier; Child; Cross Infection; Disease Models, Animal; Humans; Meningitis, Bacterial; Meropenem; Rabbits; 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 compare the in vitro killing activity of meropenem and imipenem against multiresistant P.aeruginosa 14 strains were used. All nosocomial isolates were susceptible to meropenem and imipenem minimum inhibitory concentration (MIC < or = 4 micrograms/ml) and resistant to at least two other antimicrobial agents of diverse chemical class with antipseudomonal activity. Forty-two killing curves were performed by exposing a 5 x 10(5) CFU/ml log-phase inoculum to 1x minimum bactericidal concentration (MBC) of each carbapenem. Meropenem was found to possess a slower killing rate than imipenem over the first 5 hours of P.aeruginosa exposure, but to be equally effective as imipenem after 24 hours of incubation. Forty percent and 11.1% of P.aeruginosa strains developed resistance to imipenem and meropenem respectively after a 24-hour exposure to carbapenem. The authors speculate about the underlying mechanisms explaining the higher rate of resistance development to imipenem than to meropenem.

Topics: Cross Infection; Drug Resistance, Microbial; Drug Resistance, Multiple; Humans; Imipenem; In Vitro Techniques; Meropenem; Pseudomonas Infections; Thienamycins; Time Factors

Topics: Cancer Care Facilities; Cross Infection; Disease Outbreaks; Drug Resistance, Microbial; Humans; Infection Control; Meropenem; Pseudomonas aeruginosa; Pseudomonas Infections; Serotyping; Thienamycins

Topics: Accidental Falls; Adult; Brain Injuries; Cross Infection; Humans; Male; Meningitis, Bacterial; Meropenem; Pseudomonas aeruginosa; Pseudomonas Infections; Thienamycins

Meropenem, a new broad-spectrum carbapenem antibiotic, demonstrated excellent in vitro activity against major respiratory pathogens including Moraxella catarrhalis, Haemophilus influenzae and Streptococcus pneumoniae. Minimal inhibitory concentrations of meropenem for Moraxella catarrhalis and Haemophilus influenzae isolates were frequently less than those of imipenem. For nosocomial amikacin-resistant gram-negative bacilli, meropenem had eightfold lower MIC90 values compared to imipenem against strains of Serratia marcescens, Enterobacter cloacae and Escherichia coli; it was 32-fold more active than imipenem against Proteus mirabilis isolates. Activity was similar to that of imipenem against Pseudomonas aeruginosa isolates. Overall, meropenem showed excellent activity against common community-acquired pathogens as well as amikacin-resistant nosocomial pathogens.

Topics: Amikacin; Bacteria; Cross Infection; Drug Resistance, Microbial; Humans; Meropenem; Microbial Sensitivity Tests; Respiratory Tract Infections; Thienamycins