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PubMed1995

[Multicenter comparative study of meropenem vs. imipenem in the intramuscular treatment of hospital infections of the urinary tract].

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.

Adult↗

PubMed1997

[Pharmacoeconomics of meropenem versus imipenem/cilastatin].

The Pharmacy and Therapeutics Committee of our hospital regulates the use of antimicrobial drugs every year. With the coming into the market of the new antibiotic carbapenem meropenem, comparative meropenem, it was assigned to the Drug Information Center the elaboration of comparative report on the two antibiotics, including as well cost analysis. We have analyzed the activities to be made since an antimicrobial drug is purchased until it is administered. We have only assessed on the direct costs that differ in the two antibiotics that are: the pre-use preparation in the pharmacy service and the preparation and administration in hospital floors. We have classified the direct cost in: goods and services, purchases and supplies costs costs and staff costs. We have calculated the daily cost of both antibiotics in the treatment of serious infections and even in more serious, life threatening infections. On top of that, we have a reviewed the use of imipenem/cilastatin and meropenem in our hospital. The information obtained shows that the saving in serious infections is of 34.6% and of 4.5% in more serious infections with vital compromise. The Pharmacy and Therapeutic Commission taking into account the report elaborated, has considered convenient the choice of meropenem as a representative of carbapenem drugs.

Cilastatin↗

PubMed1989

In-vitro activity of meropenem imipenem, the penem HRE 664 and ceftazidine against clinical isolates from West Germany.

The antibacterial activity in vitro of meropenem was compared with another carbapenem, imipenem, the penem HRE 664, and ceftazidime. MICs were not influenced by pH nor by inoculum size below 5 X 10(5) cfu/ml: higher inocula caused a modest increase in MIC. Cation supplementation of Mueller-Hinton broth was without effect. Meropenem was more active than imipenem and the other comparative agents against the majority of Gram-negative species (in particular proteus, providencia, morganella, haemophilus, neisseria and Pseudomonas aeruginosa, including isolates from patients with cystic fibrosis). Against Gram-positive organisms, the activity of meropenem was equal to or slightly less that of imipenem. Neither meropenem nor imipenem were influenced by the extended spectrum beta-lactamases that confer resistance to third generation cephalosporins produced by Escherichia coli, Klebsiella pneumoniae, K. oxytoca or Serratia marcescens.

Anti-Bacterial Agents↗

PubMed2000

MYSTIC (Meropenem Yearly Susceptibility Test Information Collection): a global overview.

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) is a global, multicentre surveillance study that compares the activity of meropenem in centres that are prescribers with that of imipenem, ceftazidime, piperacillin/tazobactam, ciprofloxacin and gentamicin. Of the 46 centres (intensive care units, cystic fibrosis units, neutropenia units and general wards) contributing to this study, 29 were in Europe, 14 in the Americas and three in the Middle East and Asia. The results for the most common isolates obtained in the first year of the study from these three regions show that meropenem has a broad spectrum of activity and potency in these centres, with 89% of the 6890 strains tested having an MIC 4 mg/L. The overall susceptibility was lower for the comparator antibiotics. There was evidence in all regions of strains producing beta-lactamases and other resistance mechanisms against the other beta-lactams tested, fluoroquinolones and aminoglycosides. Future years' results from this surveillance study will show whether meropenem will continue to exhibit such activity.

Journal Article↗

PubMed2000

MYSTIC (Meropenem Yearly Susceptibility Test Information Collection) results from Europe: comparison of antibiotic susceptibilities between countries and centre types.

The activity of meropenem and five comparators has been studied against 7886 isolates from 29 centres in 10 European countries from 1997 to 1999 as part of the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) surveillance study. Gram-positive and Gram-negative isolates from intensive care units (ICUs), neutropenia centres, cystic fibrosis (CF) centres and general wards were investigated in Belgium (1 year), Czech Republic (2 years), Germany (3 years), Italy (3 years), Poland (2 years), Russia (2 years), Sweden (2 years), Switzerland (1 year), Turkey (1 year) and UK (3 years). Resistance to quinolones and aminoglycosides was observed, as was resistance to the cephalosporins and penicillins via extended-spectrum beta-lactamases (ESBLs) and AmpC beta-lactamases. Meropenem showed good activity against the pathogens tested, particularly in CF and neutropenia centres, over the 3 year period. The overall order of potency of the six antimicrobial agents tested was: meropenem > imipenem > piperacillin/tazobactam and ciprofloxacin > ceftazidime > gentamicin. No increase in resistance to the carbapenems, to date, has been detected in any of the European centres included in this study.

Journal Article↗

PubMed1998

Changes in outer membrane protein profiles of bacteria after meropenem-induced postantibiotic effect studied by capillary electrophoresis.

Persistent inhibition of bacterial growth, called postantibiotic effect (PAE), after a short exposure to a new carbapenem, meropenem, was determined in different strains of the Enterobacteriaceae family. Capillary electrophoresis (CE), as well as sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) were used to study the outer membrane protein (OMP) profiles before and after meropenem treatment. CE proved to be suitable for the characterization of the OMP profiles of bacteria. Significant changes in the electrophoretic patterns were observed, showing the consequential effect of meropenem on bacteria.

Bacterial Outer Membrane Proteins↗

PubMed1998

Pharmacokinetics of meropenem in patients with cystic fibrosis.

The pharmacokinetics of meropenem were studied after single i.v. infusions of 15 mg meropenem/kg body weight in eight subjects with cystic fibrosis (CF) and eight healthy volunteers matched for age, sex, and weight. Significantly shorter terminal half-lives (mean, 0.74 h vs. 0.99 h) and mean residence times (mean, 1.09 h vs. 1.39 h) were noted in CF subjects. Plasma and renal clearances tended to be higher and distribution volumes smaller among the patients, but differences were not statistically significant. The results are consistent with the findings for many other beta-lactam agents used in CF patients. Assuming a MIC90 of 4 mg/l for meropenem against Pseudomonas aeruginosa, the time above the MIC was less than 3.3 h in six of the eight CF patients. This finding should be kept in mind when designing treatment regimens with meropenem in CF subjects.

Adult↗

PubMed1995

Correlation between in vitro and in vivo models of proconvulsive activity with the carbapenem antibiotics, biapenem, imipenem/cilastatin and meropenem.

The present study evaluated the proconvulsant liability of biapenem, a novel carbapenem antibiotic, in in vitro and in vivo experiments, in comparison with the carbapenems, imipenem/cilastatin and meropenem. Imipenem/cilastatin is a carbapenem antibiotic with known proconvulsive liability in man and in animal experiments. In in vivo studies imipenem/cilastatin, at doses of 400/400 mg/kg i.v., significantly lowered the convulsive threshold of pentylenetetrazol (PTZ) in mice and shifted the dose-response curve of PTZ. The effects of biapenem (400 mg/kg i.v.) and another reference carbapenem, meropenem (400 mg/kg i.v.), in the mouse PTZ model were not significantly different from control. In in vitro experiments the carbapenems were tested for their ability to inhibit [3H]muscimol (1.3 mM) binding to rat brain homogenates at concentrations of 1-10 mM. Similar to in vivo results, when compared to imipenem/cilastatin, biapenem and meropenem did not inhibit [3H]muscimol binding to the GABAA receptor complex in brain homogenates while imipenem/cilastatin exhibited significant inhibition (IC50 = 4.6 mM). These results further confirm the correlation between in vitro GABAA binding and in vivo PTZ convulsive testing with carbapenem antibiotics, and suggest that biapenem possesses a low proconvulsive liability.

Analysis of Variance↗

PubMed2004

Susceptibility of meropenem and comparators tested against 30,634 Enterobacteriaceae isolated in the MYSTIC Programme (1997-2003).

A total of 30,634 global Enterobacteriaceae isolates collected from the MYSTIC (Meropenem Yearly Surveillance Test Information Collection) Programme were tested using a reference methodology against meropenem and seven other broad-spectrum agents commonly used in the hospital setting (1997-2003). The most active compound was meropenem (99.6% susceptible), followed by imipenem (98.4%), cefepime (94.0%), gentamicin (86.8%), piperacillin/tazobactam (85.8%), ceftazidime (85.0%), ciprofloxacin (84.6%), and tobramycin (84.5%). Continued surveillance of antimicrobial compounds' in vitro activity is necessary to recommend regimens that are likely to be effective in clinical practice.

Anti-Bacterial Agents↗

PubMed2005

Use of a program-specific website to disseminate surveillance data obtained from the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Study.

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program is a multicenter, longitudinal surveillance study initiated in 1997 that compares the activity of meropenem and comparator antimicrobials in centers that are actively prescribing meropenem. Antimicrobial surveillance programs, such as MYSTIC, provide important information on the emergence of bacterial resistance and the nature of the underlying mechanisms in different geographical regions. Data concerning these mechanisms and patterns of antimicrobial resistance allow the implementation of changes in antimicrobial prescribing practices and infection control interventions. Therefore, it is important that data from surveillance programs be analyzed and accessible to clinicians within reasonable, clinically useful, intervals. In this article, the use of a website designed to disseminate data collected from the MYSTIC program is described. This web-based program allows specific surveillance data to be examined in a timely manner and can assist the clinician when choosing the most appropriate antibiotic for the situation encountered and hopefully maximize successful clinical outcomes.

Anti-Bacterial Agents↗

PubMed2004

Susceptibility of the Acinetobacter calcoaceticus-A. baumannii complex to imipenem, meropenem, sulbactam and colistin.

The Acinetobacter calcoaceticus-Acinetobacter baumannii complex includes some of the most clinically relevant species of the genus Acinetobacter due to their capacity to cause epidemic nosocomial outbreaks as well as their increasing resistance to antibiotics. Susceptibility of Acinetobacter strains varies greatly depending on origin, thus highlighting the importance of local analyses of susceptibility profiles. Two hundred twenty-one strains of the A. calcoaceticus-A. baumannii complex were identified using biochemical tests and were biotyped. Strain susceptibility to imipenem, meropenem, colistin and sulbactam was studied using agar dilution. Eight different biotypes were found, type 1 accounting for 69.2% of the strains. MIC(50) and MIC(90) to imipenem, meropenem, colistin and sulbactam were 4 and 8 mg/l, 16 and 32 mg/l, 0.5 and 1mg/l, and 8 and 16 mg/l, with susceptibility rates of 64.3, 22.6, 98.2 and 73.8%, respectively. Biotype 1 was the most resistant. A statistically significant difference was observed for the mean MIC of the four predominant biotypes to imipenem, meropenem and sulbactam but not to colistin.

Acinetobacter↗

PubMed2006

In vitro antimicrobial activity of liposomal meropenem against Pseudomonas aeruginosa strains.

Twelve lipid formulations of liposomal meropenem were tested on six drug-susceptible and two drug-resistant Pseudomonas aeruginosa strains to determine their antibacterial activity. Cationic liposomes, especially PC/DOPE/SA 4:4:2 and PC/DOTAP/Chol 5:2:3, were more effective than anionic ones against sensitive isolates as the MICs of those formulations were two to four times lower than those of the free drug. None of the studied liposomal forms of meropenem exhibited bactericidal activity against isolates, which are drug-resistant due to low permeability. Even Fluidosomes (liposomes made of DPPC/DMPG 18:1), which demonstrated fusion with P. aeruginosa membranes, showed 4-16 times higher MICs for sensitive and resistant strains than did the free meropenem.

Anti-Infective Agents↗

PubMed1996

High-performance liquid chromatographic assay for meropenem in serum.

High-performance liquid chromatographic procedures have been developed for the measurement of meropenem in serum. The separation was performed on an Ultrasphere XL-ODS analytical column (75 x 4.6 min I.D.). The mobile phase consisted of 10.53 mmol/l ammonium acetate-acetonitrile (95:5, v/v) (pH 4). The UV detection was at 298 nm. The quantitation limit both in serum and water was 0.25 micrograms/ml. The method was validated in serum and aqueous solution over the concentration range 0.25-50 micrograms/ml. The extraction recovery from serum spiked with meropenem was 99.7 +/- 3.4%. The intra- and inter-assay coefficients of variation were below 6%. Stored at -80 degrees C for three months at various concentrations in serum and in aqueous solution, meropenem did not reveal any appreciable degradation. After 24 h, it was also stable at 4 degrees C in serum, aqueous solution and supernatant of extraction but not at room temperature. The stability of the drug was also confirmed in serum after repeated freezing-thawing cycles at -80 degrees C on four consecutive days.

Animals↗

PubMed2003

Validation of HPLC and UV spectrophotometric methods for the determination of meropenem in pharmaceutical dosage form.

A high-performance liquid chromatographic method and a UV spectrophotometric method for the quantitative determination of meropenem, a highly active carbapenem antibiotic, in powder for injection were developed in present work. The parameters linearity, precision, accuracy, specificity, robustness, limit of detection and limit of quantitation were studied according to International Conference on Harmonization guidelines. Chromatography was carried out by reversed-phase technique on an RP-18 column with a mobile phase composed of 30 mM monobasic phosphate buffer and acetonitrile (90:10; v/v), adjusted to pH 3.0 with orthophosphoric acid. The UV spectrophotometric method was performed at 298 nm. The samples were prepared in water and the stability of meropenem in aqueous solution at 4 and 25 degrees C was studied. The results were satisfactory with good stability after 24 h at 4 degrees C. Statistical analysis by Student's t-test showed no significant difference between the results obtained by the two methods. The proposed methods are highly sensitive, precise and accurate and can be used for the reliable quantitation of meropenem in pharmaceutical dosage form.

Chromatography, High Pressure Liquid↗

PubMed1999

Capillary zone electrophoresis determination of meropenem in biological media using a high sensitivity cell.

A capillary electrophoresis method with a high sensitivity cell (Z-cell) has been developed for the determination of meropenem in aqueous solution and in biological media (urine, plasma). Water samples were analysed using two calibration curves of meropenem with standard capillary and a capillary with a high sensitivity cell. In urine, the samples were only diluted in buffer and were injected without any further sample preparation. For the analysis of plasma samples, a calibration curve was utilized covering the meropenem concentration range of 0.5-200 microg/ml. The detection limit and the relative standard deviation of the migration times and of the peak areas were determined.

Electrophoresis, Capillary↗

PubMed2002

Antimicrobial susceptibility of inducible AmpC beta-lactamase-producing Enterobacteriaceae from the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Programme, Europe 1997-2000.

Among 11345 clinical isolates from 31 European centres in the MYSTIC (Meropenem Yearly Susceptibility Test Information Collection) Programme (1997-2000), the potential AmpC-producing pathogens were Enterobacter spp. (904 cases), Citrobacter spp. (144) and Serratia marcescens (288). Resistance to ceftazidime or cefotaxime (11-34%) and piperacillin/tazobactam (12%) was observed, indicating stably derepressed expression of AmpC cephalosporinases. Meropenem (MIC(90), 0.25 mg/l; >99% susceptible) and imipenem (MIC(90), 2 mg/l; 98% susceptible) were active, even against these stably derepressed AmpC-producers: Enterobacter spp. (305 strains), Citrobacter spp. (29) and S. marcescens (35). The overall rank order of spectrum (% susceptible) versus the stably derepressed subset of isolates was: meropenem=imipenem (98%)>cefepime (89%)>gentamicin (73%)>ciprofloxacin (62%)>tobramycin (60%) >piperacillin/tazobactam (21%). We suggest increased attention in Europe to: (1) the recognition of these resistant phenotypes, (2) infection control practices, and (3) limiting the overuse of certain selecting extended-spectrum beta-lactam agents (e.g. ceftazidime).

Anti-Bacterial Agents↗

PubMed2002

The comparison of in the vitro effect of imipenem or meropenem combined with ciprofloxacin or levofloxacin against multidrug-resistant Pseudomonas aeruginosa strains.

This study evaluated the in vitro effects of the combination of a carbapenem (imipenem or meropenem) with a quinolone (ciprofloxacin or levofloxacin) using a microbroth dilution chequerboard technique and multidrug-resistant Pseudomonas aeruginosa strains. The ciprofloxacin and meropenem combination was only synergistic against 2 strains (6.2%) and ciprofloxacin and imipenem against 1 strain (3.1%). Levofloxacin and imipenem or meropenem were not synergistic for against any strain. None of the combinations showed an antagonistic effect.

Anti-Bacterial Agents↗

PubMed1999

The MYSTIC (meropenem yearly susceptibility test information collection) programme.

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

Bacteria↗