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PubMedDate not supplied

Combination effect of meropenem with aminoglycosides and teicoplanin on Pseudomonas and enterococci.

The in vitro activity of meropenem, a new carbapenem, and the combination effect with netilmicin, tobramycin, gentamicin, and teicoplanin against Pseudomonas spp. and enterococci was studied. Meropenem showed very good in vitro activity against Pseudomonas aeruginosa (MIC90 2 mg/l) and good to moderate activity against Pseudomonas putida (MIC90 4 mg/l) and Enterococcus faecalis (MIC90 8 mg/l). Aminoglycosides were highly active against P. putida (MIC90 0.5 mg/l), but showed only moderate activity against P. aeruginosa. The synergistic effect of meropenem was shown in combination with teicoplanin against E. faecalis (40%). No Pseudomonas strains were inhibited by the synergistic effect of meropenem with aminoglycosides. No antagonism occurred with any of the combinations.

Aminoglycosides↗

PubMed1991

Effect of meropenem on the intestinal microflora.

Ten healthy volunteers were given 500 mg of meropenem by intravenous infusion over 30 min three times daily for seven days. Stool specimens were collected before, during and after meropenem administration. The numbers of enterobacteria and streptococci decreased during the administration period, while the numbers of enterococci increased. There was a decrease in the numbers of clostridia, bacteroides and gram-negative cocci, while the numbers of gram-positive cocci and rods were not changed by the administration of meropenem. The intestinal flora returned to normal in all volunteers within two weeks after the termination of meropenem administration.

Adult↗

PubMed1992

Comparative activity of meropenem (SM-7338) against major respiratory pathogens and amikacin-resistant nosocomial isolates.

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.

Amikacin↗

PubMed1989

Comparative in vitro antibacterial activity of the new carbapenem meropenem (SM-7338).

The in vitro antimicrobial activity of the new carbapenem meropenem (SM-7338) was determined by an agar dilution method in comparison with imipenem, ticarcillin/calvulanic acid, ceftazidime and the fourth-generation cephalosporin cefepime (BMY 28142). Meropenem showed superior activity against Enterobacteriaceae (MIC90 less than or equal to 0.06 mg/l) and against non-fermentative gram-negative rods, with the exception of Xanthomonas maltophilia. Meropenem had excellent activity against beta-lactamase-producing Haemophilus influenzae and Neisseria gonorrhoeae, and against the Bacteroides fragilis group. Imipenem was slightly more active then meropenem against gram-positive cocci especially Enterococcus faecalis.

Anti-Bacterial Agents↗

PubMed1999

Alterations in surface hydrophobicity of Acinetobacter baumannii induced by meropenem.

Six strains of Acinetobacter baumannii out of eleven strains tested revealed a strong hydrophobic character. This was demonstrated by adherence of bacteria to xylene in the range of 90-94%. Changes in surface hydrophobicity of these strains were studied after treatment with meropenem at subinhibitory concentrations (sub-MICs) (1/4, 1/8, 1/16 or 1/32 of the MICs). All strains showed a reduced adherence to xylene after the action of meropenem at 1/4 or 1/16 of the MICs. Hydrophobicity of the treated bacteria was decreased to 1.3-70% (1/16 of the MICs) or to 12-86% (1/4 of the MICs), depending on the strain. A decrease in surface hydrophobicity of three strains was also observed after their exposure to meropenem at 1/8 of the MICs (to 18-71% of the control values). Meropenem at 1/32 of the MICs practically did not affect bacterial hydrophobic properties, with the exception of one strain.

Acinetobacter↗

PubMedDate not supplied

A comparison of the pharmacokinetics of meropenem after intravenous administration by injection over 2, 3 and 5 minutes.

The pharmacokinetics of meropenem were determined in 9 healthy volunteers after the administration of 1 g dose by injection over 2, 3 or 5 min. Peak plasma concentrations were not significantly different across the three rates of administration and, due to the finite time required for complete mixing of the blood in the central compartment, did not always occur at the end of the injection. Overall exposure to meropenem was unchanged by the more rapid rates of administration. Plasma clearance, terminal half-life and volume of distribution were virtually unchanged. Within 10 min after the start of the injection, the plasma concentrations from all three injections were very similar indicating that dosing over 2, 3 or 5 min would result in similar antimicrobial cover and, therefore, comparable efficacy. Comparison of the data derived from the three injections indicated that rapid administration of meropenem did not appreciably alter its disposition pharmacokinetics. Tolerability of meropenem was unchanged with the more rapid administration rate.

Adolescent↗

PubMed2002

Cellular and molecular aspects of drugs of the future: meropenem.

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

Animals↗

PubMed1992

Antibiotic susceptibilities of the Vibrionaceae to meropenem and other antimicrobial agents.

The in vitro activity of meropenem was compared with imipenem and other selected antimicrobial agents against 115 isolates from the family Vibrionaceae. No resistance was observed with meropenem or imipenem against these isolates. However, meropenem was generally four- to 16-fold more active than imipenem against the aeromonads and Vibrio cholerae. Meropenem showed excellent in vitro activity against the Vibrionaceae and may be useful for eradicating infections produced by these organisms.

Aeromonas↗

PubMed2004

Antimicrobial resistance rates and clonality results from the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) programme: report of year five (2003).

The U.S. Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Programme in the fifth year continues to monitor the spectrum of activity and potency of meropenem within medical centers where carbapenems are used for the treatment of serious infections. The antimicrobial activity of 11 broad-spectrum agents (including initial comparisons for levofloxacin) was assessed against 2,848 isolates in 2003. The minimum inhibitory concentration (MIC) results demonstrate the continued high potency of meropenem against all monitored pathogens. Against all Gram-negative bacilli tested, the overall rank order of susceptibility was meropenem (96.3%) > imipenem (95.6%) > cefepime (93.7%) > tobramycin (91.9%) > piperacillin/tazobactam (90.2%) > ceftazidime (90.1%) > gentamicin (89.6%) > levofloxacin (82.8%) > ciprofloxacin (82.5%) > aztreonam (81.8%) > ceftriaxone (72.3%). Clonal-based resistances were observed that adversely influenced carbapenem resistance rates, particularly among Klebsiella spp. and Acinetobacter baumannii isolates. Continued surveillance of the carbapenem class and other broad-spectrum agents is warranted to monitor activity against pathogens causing serious infections in hospitalized patients.

Academic Medical Centers↗

PubMed2006

Antimicrobial susceptibility pattern comparisons among intensive care unit and general ward Gram-negative isolates from the Meropenem Yearly Susceptibility Test Information Collection Program (USA).

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program is a global, longitudinal antimicrobial resistance surveillance network of greater than 100 medical centers worldwide monitoring the susceptibility of bacterial pathogens to carbapenems and other broad-spectrum agents. Between 1999 and 2002, 15 US medical centers referred up to 200 nonduplicate isolates from clinical infections to a central processing laboratory. During this 4-year period, the antimicrobial activity of 11 broad-spectrum agents was assessed against 5389 bacterial isolates using Clinical and Laboratory Standards Institute (formerly National Committee for Clinical Laboratory Standards)-recommended methods with interpretive criteria. Analysis of the MIC results for pathogens isolated from patients hospitalized in intensive care units (ICUs) were compared to results from pathogens isolated in non-ICU settings. Among Enterobacteriaceae (3884 strains), the carbapenems (imipenem and meropenem) demonstrated the highest susceptibility rates (> or =98.7%) and with only a 1% increase in resistance for ICU isolates compared to non-ICU organisms. Other antimicrobial agents tested demonstrated consistently higher susceptibility rates against Enterobacteriaceae isolates from ICU (89.7-98.7%) and non-ICU (93.2-99.9%) areas. For the nonfermentative Gram-negative bacilli, the rank order of the most active agents having lowest percentage resistance rates were tobramycin (15.5%) < cefepime < imipenem < piperacillin/tazobactam < ceftazidime < meropenem (21.9%) for ICU isolates, and meropenem (7.8%) < cefepime < imipenem < piperacillin/tazobactam < ceftazidime < tobramycin (12.9%) among non-ICU strains. All tested agents showed lower susceptibility rates (range, 1.0-15.3%) and higher resistance rates (range, 0.1-15.1%) for both Enterobacteriaceae and nonfermentative Gram-negative bacilli among the ICU isolates compared to the non-ICU isolates (except for ciprofloxacin against Enterobacteriaceae). Continued surveillance of these broad-spectrum antimicrobial agents in both ICU and general hospital wards appears warranted to monitor the occurrence and spread of antimicrobial resistance in pathogens causing serious infections in these care areas and the possible emergence of resistance mechanisms that could compromise empiric carbapenem therapy.

Anti-Bacterial Agents↗

PubMed2006

Contemporary activity of meropenem and comparator broad-spectrum agents: MYSTIC program report from the United States component (2005).

The Meropenem Yearly Susceptibility Test Information Collection Program is a 9-year-old antimicrobial resistance surveillance network of more than 100 medical centers worldwide, including 15 sites in the United States (US) that monitors the susceptibility of Gram-negative and Gram-positive bacterial pathogens especially to carbapenems. In 2005, the antimicrobial activity of 11 broad-spectrum agents was assessed against 2910 bacterial isolates (2493 Gram-negative and 417 staphylococci) submitted from the US medical centers to a reference laboratory using Clinical and Laboratory Standards Institute susceptibility testing methods and interpretative criteria. Meropenem continued to demonstrate 1) high potency with MIC(90) values 4- to 16-fold lower than imipenem against the Enterobacteriaceae, 2) equal activity against Pseudomonas aeruginosa, 3) 2-fold less activity compared with imipenem against Acinetobacter spp., and 4) 4- to 8-fold less activity compared with imipenem against the oxacillin-susceptible staphylococci. The wide spectrum of activity for carbapenems against Enterobacteriaceae (1657 strains) was confirmed by the overall rank order by percentage susceptibility at breakpoint criteria: imipenem (98.9%) > meropenem (98.7%) > cefepime (97.6%) > piperacillin/tazobactam (92.0%) > ceftriaxone (91.2%) > aztreonam (90.6%) > gentamicin = tobramycin (90.5%) > ceftazidime (90.4%) > levofloxacin (84.9%) > ciprofloxacin (83.9%). Against Acinetobacter spp. isolates, only tobramycin (92.0% susceptible) and carbapenems (92.0-85.6%) exhibited acceptable levels of activity. A continued increase in the resistance rate for both ciprofloxacin and levofloxacin was observed with highest rates found among indole-positive Proteae species (36.5-33.3%) and Escherichia coli (21.6-20.4%) isolates, some documented by molecular typing methods as clonally related. Ongoing surveillance of meropenem and other broad-spectrum antimicrobial agents appears warranted to monitor the potency and spectrum of activity against indicated Gram-negative and-positive pathogens causing serious infections in the hospital setting, and to detect the emergence of new or novel resistance mechanisms that could compromise clinical utility (serine and metallo-carbapenemases).

Anti-Bacterial Agents↗

PubMed2006

Meropenem and imipenem activity against Pseudomonas aeruginosa isolates from the MYSTIC Program.

This article examines the activity of meropenem and imipenem against Pseudomonas aeruginosa isolates from the Meropenem Yearly Susceptibility Test Information Collection program between 1997 and 2005. In particular, it examines the activity of meropenem against imipenem-resistant strains and vice versa. Meropenem proved to be active against up to a 3rd of imipenem-resistant strains.

Anti-Bacterial Agents↗

PubMed2005

Intrapulmonary pharmacokinetics and pharmacodynamics of meropenem.

The objective of this study was to determine the plasma and intrapulmonary pharmacokinetic parameters of intravenously administered meropenem in healthy volunteers. Four doses of 0.5 g, 1.0 g or 2.0 g meropenem were administered intravenously to 20, 20 and 8 healthy adult subjects, respectively. Standardised bronchoscopy and timed bronchoalveolar lavage (BAL) were performed following administration of the last dose. Blood was obtained for drug assay prior to drug administration and at the time of BAL. Meropenem was measured in plasma, BAL fluid and alveolar cells (ACs) using a combined high pressure liquid chromatographic-mass spectrometric technique. Plasma, epithelial lining fluid (ELF) and AC pharmacokinetics were derived using non-compartmental methods. Cmax/MIC90 (where Cmax is the maximum plasma concentration and MIC90 is the minimum inhibitory concentration required to inhibit 90% of the pathogen), AUC/MIC90 (where AUC is the area under the curve for the mean concentration-time data), intrapulmonary drug exposure ratios and percent time above MIC90 during the dosing interval (%T > MIC90) were calculated for common respiratory pathogens with MIC90 values of 0.12-4 microg/mL. In the 0.5 g dose group, the Cmax (mean+/-S.D.), AUC(0-8 h) and half-life for plasma were, respectively, 25.8+/-5.8 microg/mL, 28.57 microg h/mL and 0.77 h; for ELF the values were 5.3+/-2.5 microg/mL, 12.27 microg h/mL and 1.51 h; and for ACs the values were 1.0+/-0.5 microg/mL, 4.30 microg h/mL and 2.61 h. In the 1.0 g dose group, the Cmax, AUC(0-8 h) and half-life for plasma were, respectively, 53.5+/-19.7 microg/mL, 55.49 microg h/mL and 1.31 h; for ELF the values were 7.7+/-3.1 microg/mL, 15.34 microg h/mL and 0.95 h; and for ACs the values were 5.0+/-3.4 microg/mL, 14.07 microg h/mL and 2.17 h. In the 2.0 g dose group, the Cmax, AUC(0-8 h) and half-life for plasma were, respectively 131.7+/-18.2 microg/mL, 156.7 microg h/mL and 0.89 h. The time above MIC in plasma ranged between 28% and 78% for the 0.5 g dose and between 45% and 100% for the 1.0 g and 2.0 g doses. In ELF, the time above MIC ranged from 18% to 100% for the 0.5 g dose and from 25% to 88% for the 1.0 g dose. In ACs, the time above MIC ranged from 0% to 100% for the 0.5 g dose and from 24% to 100% for the 1.0 g dose. Time above MIC in ELF and ACs for the 2.0 g dose was not calculated because of sample degradation. The prolonged T > MIC90 and high intrapulmonary drug concentrations following every 8 h administration of 0.5-2.0 g doses of meropenem are favourable for the treatment of common respiratory pathogens.

Adult↗

PubMed2006

Population pharmacokinetics of meropenem in febrile neutropenic patients in Korea.

Population pharmacokinetic parameters of meropenem in 57 febrile neutropenic patients and minimal inhibitory concentration (MIC) data for clinically isolated Pseudomonas aeruginosa and Escherichia coli were applied to estimate the time above the MIC (T>MIC) using the Monte Carlo simulation method. Mean population clearance (CL) and volume of distribution (V(d)) of meropenem were proportional to creatinine clearance (CL(Cr)) and body weight, respectively: CL (L/h)=9.7 x (CL(Cr)(mL/min)/120); V(d) (L)=14.6 x (body weight (kg)/61). In 1000 simulated patients treated with meropenem 0.5g or 1g every 8h, the proportions of patients who had a T>MIC less than 40% of the dosing interval were 46.3% and 39.5% for P. aeruginosa and 5.8% and 5.6% for E. coli, respectively. The overwhelming resistance of the pathogenic microorganisms, especially P. aeruginosa, in our data compared with that reported in North America suggests the importance of regions or countries as a critical factor for determining the dosage regimen of meropenem in addition to patient characteristics and pharmacokinetics.

Adult↗

PubMed1997

Imipenem and meropenem activity against mecA-positive homogeneously and heterogeneously oxacillin-resistant and mecA-negative oxacillin-borderline-susceptible staphylococci.

Microbroth dilution and disk-diffusion testing of imipenem and meropenem was performed at 35 and 30 degrees C against 61 phenotypic expression class 3,4 and 9 phenotypic expression class 1,2 oxacillin-resistant isolates of Staphylococcus aureus (ORSA), 51 oxacillin-borderline-susceptible isolates of S. aureus (BORSA), and 37 phenotypic expression class 3,4 and 9 phenotypic expression class 1,2 isolates of Staphylococcus epidermidis (ORSE). Imipenem MIC ranges at 35 degree C were 0.6 to > 64 micrograms/ml for class 3,4 ORSA, 0.03 to 0.25 micrograms/ml for class 1,2 ORSA, 0.015 to 0.12 micrograms/ml for BORSA, 0.03 to 64 micrograms/ml for class 3,4 ORSE, and 0.12 to 8 micrograms/ml for class 1,2 ORSE. Corresponding values for meropenem were 0.5 to 64 micrograms/ml, 0.12 to 4 micrograms/ml, 0.06 to 1 microgram/ml, 0.5 to 64 micrograms/ml, and 1 to 8 microgram/ml. MIC ranges at 30 degrees C did not differ by more than 1 log2 dilution from those at 35 degrees C. After 24 h incubation of disk-diffusion tests at 35 degrees C, 44% of class 3,4 and 100% of class 1,2 ORSA isolates were imipenem-susceptible; after an additional 24 h at 25 degrees C, 39 and 100% of these isolates, respectively, remained susceptible to imipenem. Similar values were obtained with 24 h incubation at 30 degrees C followed by 24 h at 25 degrees C. All BORSA isolates were susceptible to imipenem. Of the ORSE isolates, 22 and 78% of isolates in classes 3,4 and 1,2, respectively, were susceptible at 24 h with little change after an additional 24 h at 25 degrees C. Similar trends were observed with meropenem. In parallel disk-diffusion studies with oxacillin, false-susceptibility rates of 5% of class 3,4 and 44% class 1,2 ORSA isolates after 24 h of incubation at 35 degrees C were reduced to 3 and 0%, respectively, after an additional 24 h of incubation at 25 degrees C. Imipenem- and meropenem-resistant subpopulations of oxacillin-resistant staphylococci did not seem to be detected by altered susceptibility testing conditions.

Anti-Bacterial Agents↗

PubMed1999

Meropenem (1.5 g/day) is as effective as imipenem/cilastatin (2 g/day) for the treatment of moderately severe intra-abdominal infections.

This multicentre, open-label, randomised trial compared meropenem (0.5 g/8 h) and imipenem/cilastatin (at the commonly used dosage of 0.5 g/6 h) in monotherapy in patients with moderately severe intra-abdominal infections (IAIs). In total, 161 patients were randomised (82 meropenem, 79 imipenem/cilastatin). The mean APACHE II scores in the two groups were 5.8 and 6.4, respectively. At the end of therapy, 65/71 (91.6%) evaluable meropenem recipients were clinically cured or improved, compared to 60/64 (93.8%) imipenem/cilastatin recipients. This difference and that in an intention-to-treat analysis (82.1 vs 86.1%, respectively), were not statistically significant. Both drugs were generally well tolerated. Thus, meropenem 0.5 g/8 h is as clinically effective and well tolerated as imipenem/cilastatin 0.5 g/6 h in moderately severe IAIs.

APACHE↗

PubMed2003

The activity of meropenem and comparators against Acinetobacter strains isolated from European hospitals, 1997-2000.

In vitro susceptibilities to meropenem and comparators of Acinetobacter strains isolated from serious infections in 37 European hospital centers participating in the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program (1997-2000) were tested. There were 635 Acinetobacter strains collected: 490 A. baumannii; 51 A. calcoaceticus var. lwoffii; and 94 other Acinetobacter strains. Overall, meropenem and imipenem were the most effective agents tested. Resistance to the antimicrobials was: 14%, meropenem; 16%, imipenem; 39%, piperacillin-tazobactam; 41%, tobramycin; 45%, ceftazidime; and 53%, ciprofloxacin. Thus, the carbapenems have useful activity against Acinetobacter spp. and represent a viable choice for treating infections caused by these organisms.

Acinetobacter↗

PubMed2004

Meropenem plus amikacin versus piperacillin-tazobactam plus netilmicin as empiric therapy for high-risk febrile neutropenia in children.

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

Amikacin↗