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PubMed1998

[Use of meropenem in patients with neutropenia].

Meropenem was used in the treatment of 14 infectious complications in 11 patients including 8 with acute myeloid leukemia due to the cytostatic therapy, 1 with chronic myeloid leukemia, 1 with aplastic anemia and 1 with acute intermittent porphyria. At the moment of the meropenem use critical neutropenia (less than 500 granulocytes per 1 ml) in 11 cases (79 per cent) was stated. The drug was administered as intravenous infusions in a dose of 1 g every 8 hours for 4 to 41 days (the median of 11 days). 9 out of the 14 infectious complications were cured (the body temperature normalized and all the inflammation foci were eliminated), among them 6 out of 8 pyocyanic sepsis. Eradication of gram-negative bacteria was observed in 8 out of 10 cultures of the biological materials. No toxic complications or electrolytic disorders due to the drug use were recorded. The drug tolerance was good.

Adolescent↗
PubMed1998

[Prospective randomized trial of meropenem versus cefotaxime and metronidazole in the treatment of intraabdominal infections].

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

Abdomen↗
PubMed1998

[Clinical experience with meropenem in the treatment of severe infections in critically ill patients].

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

APACHE↗
PubMed1998

[Comparison of the in vitro and in vivo effects of meropenem and ciprofloxacin on the morphology of Escherichia coli and Staphylococcus aureus].

In the treatment of infections, subinhibitory concentrations are commonly present and induce a wide range of effects. Some of these effects have been reported to improve the efficacy of these compounds. One of these effects, the change of the bacterial morphology, was assayed in this study both in vitro and in vivo, and their results were compared. Two antimicrobial agents (meropenem and ciprofloxacin) and two standard Gram-positive and Gram-negative strains (S. aureus y E. coli) were used. The methods employed included the in vitro exposure of microorganisms on Mueller-Hinton agar plates, and the in vivo intraperitoneal infection model in mice. With all the sub-MICs tested, the in vitro results showed that meropenem induced the formation of round cells (spheroplasts) on E. coli, while ciprofloxacin produced filaments. With S. aureus, the two antimicrobial agents induced the formation of cellular aggregates (clusters) with a diameter greater than 1 mm. The in vivo results confirmed those observed in vitro, but to a lesser extent. These results agree with those expected in relation with the mechanisms of action of each drug, and could be important in order to prevent a lost in efficacy when the levels of the drug are below the MIC.

Animals↗
PubMed2006

Clonal occurrences of multidrug-resistant Gram-negative bacilli: report from the Meropenem Yearly Susceptibility Test Information Collection Surveillance Program in the United States (2004).

The Meropenem Yearly Susceptibility Test Information Collection Program is a global, longitudinal resistance surveillance network of more than 100 medical centers worldwide monitoring the susceptibility of bacterial pathogens to carbapenems and other broad-spectrum agents. Between 1999 and 2004, a total of 10-16 US medical centers referred up to 200 nonduplicate isolates from clinical infections to a central processing laboratory. Over this 6-year period, the antimicrobial activity of 12 broad-spectrum agents was assessed against 15990 bacterial isolates using Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards) reference methods. Analysis of the MIC results by year within organism species and/or organism groups revealed a continued decrease in fluoroquinolone susceptibility (ciprofloxacin and levofloxacin), especially among indole-positive Proteae (-22.1%), Escherichia coli (-17.0%), Enterobacter species (-10.0%), and Proteus mirabilis (-7.6%) isolates. Antibiogram analysis of strains demonstrating multidrug resistance from the same institutions were further characterized by automated ribotyping and pulsed-field gel electrophoresis to determine clonality. In 2004, a total of 165 selected multidrug-resistant (MDR) strains produced 64 different ribotypes with the largest representing 31 Escherichia coli isolates from 6 medical centers. Other clusters were also identified within single medical centers among Enterobacter cloacae (6 strains), Providencia stuartii (5 strains), and Morganella morganii (4 strains). A significant clonal outbreak encompassing 40 Acinetobacter baumannii isolates from 3 centers in a single endemic region was identified in 1999 and has persisted through 2004. Continued surveillance of these broad-spectrum antimicrobial agents against MDR pathogens appears warranted to monitor the incidence and spread of resistant clones causing serious infections. Possible emergence of resistance mechanisms via clonal dissemination proves to be among the principle threats that compromise carbapenem therapy, where meropenem maintains the broadest spectrum of coverage.

Anti-Bacterial Agents↗
PubMed1996

In vitro activity of trovafloxacin in combination with ceftazidime, meropenem, and amikacin.

The in vitro activity of trovafloxacin alone and in combination with ceftazidime, meropenem, and amikacin was studied by determining the minimal inhibitory concentrations (MICs) for 111 gram-negative and 71 gram-positive bacteria. In addition, the synergy of these combinations against 46 strains of gram-negative and gram-positive organisms was studied by checkerboard titration and time-kill kinetics. Trovafloxacin exhibited excellent in vitro activity against all strains tested. Synergism was observed in 17% of the gram-negative strains and in 32% of the gram-positive strains. No antagonism was observed with any of the combinations tested.

Amikacin↗
PubMed1994

Imipenem and meropenem induced resistance to beta-lactam antibiotics in Pseudomonas aeruginosa.

The ability of imipenem and meropenem in subinhibitory concentrations to influence the results of disk diffusion susceptibility tests was assessed. Selection of stably derepressed mutants resistant to beta-lactam antibiotics other than carbapenems was also investigated. Beta-lactams were shown to be subject to carbapenem-mediated antagonism in the disk diffusion test. On the other hand in vitro selection of stably derepressed mutants resistant to other beta-lactams could not be demonstrated.

Anti-Bacterial Agents↗
PubMed1989

Antibacterial activity of the new carbapenem meropenem (SM-7338) against clinical isolates.

The in vitro antibacterial activity of the new carbapenem antibiotic meropenem (SM-7338) against 567 clinical isolates was evaluated. SM-7338 exhibited activity against a broad spectrum of organisms, including aerobes and anaerobes, and was superior to the other beta-lactam drugs tested (piperacillin, cefotaxime, ceftazidime, ceftriaxone, cefoxitin). SM-7338 was more active than imipenem, gentamicin and amikacin against Enterobacter cloacae and Pseudomonas aeruginosa. SM-7338 was less potent than imipenem against staphylococci and enterococci, but the activity of the two antibiotics against anaerobes was similar. SM-7338 and imipenem showed a high bactericidal activity at a concentration of 2-4 x MIC.

Anti-Bacterial Agents↗
PubMed1992

In vitro activity of meropenem and imipenem against mycobacteria: development of a daily antibiotic dosing schedule.

The activity of two carbapenem antibiotics, meropenem and imipenem, against Mycobacterium species was assessed by means of the Bactec 460 radiometric apparatus. This system allowed a result to be read in 4-10 days. The instability of imipenem, particularly, in the test system necessitated the development of a regimen of daily addition of antibiotic to permit a more accurate assessment of antibiotic activity to be made. When antibiotic-containing media are incubated for long periods, as is the case when determining antimycobacterial activity, the stability of test antibiotics is an important factor that must be considered.

Culture Media↗
PubMed2004

Chromatographic determination of polymerized impurities in meropenem.

A method for the separation of polymerized impurities in meropenem has been developed by gel filtration chromatography (GFC). The chromatographic conditions included a Superdex peptide HR 10/30 column and the mobile phase consisting of 0.01 mol L(-1) sodium phosphate buffer (pH 7.0), at a flow rate of 0.8 mL min(-1). The wavelength of UV detector was set at 220 nm. The linear range was 0.08-10 microg (r=0.9998); relative standard deviation (R.S.D.)=0.5-1.5%; the LOD and LOQ were 2.4 and 12.4 ng, respectively. Specificity of the GFC was checked by switching the effluent of each peak on the GFC to a C18 trap column and analyzing the effluent by LC-MS. The result shows that for the determination of polymers, the gel filtration chromatography is a rather simple separation mode as compared to RPLC.

Chromatography, Gel↗
PubMed2003

Mutation prevention concentration of ceftriaxone, meropenem, imipenem, and ertapenem against three strains of Streptococcus pneumoniae.

This investigation tested the mutation prevention concentration (MPC) concept using imipenem, meropenem, ceftriaxone, and ertapenem against three strains of Streptococcus pneumoniae (PCN MIC = 0.012, 1, 8 mg/L, respectively). MIC, MBC, and MPC values for each of the beta-lactams did not differ by more than one tube dilution. While an interesting concept, MPC may not apply to antimicrobials that do not utilize a dual targeting system, such as beta-lactams, or to bacteria that exhibit multiple mechanisms of resistance and/or mutate at a rate where the frequency would likely be captured by the standard inoculum size used in routine MIC testing.

Anti-Bacterial Agents↗
PubMed1995

Meropenem (meronem, zeneca).

Meropenem is the latest in a series of antibiotics noted for their broad spectrum of activity. Is it an alternative to established antibiotic regimen in the treatment of infections in hospitalized patients?

Drug Costs↗
PubMed2006

[Pharmacokinetic interaction between valproic acid and meropenem].

Several reports have described a decrease in valproic acid (VPA) serum concentrations when carbapenem therapy is administered. The exact mechanism of this pharmacokinetic interaction is unknown, although several experimental studies have been carried out in animals. Because of these interactions, plasma concentrations of VPA in these patients should be monitored and, whenever possible, VPA or carbapenem therapy should be substituted by other drugs. We describe the cases of two epileptic children who simultaneously received meropenem and VPA. Concentrations of VPA decreased to subtherapeutic levels. We review the various mechanisms for this interaction proposed to date, as well as all reported cases.

Anti-Bacterial Agents↗
PubMed2001

Effect of meropenem on disposition kinetics of valproate and its metabolites in rabbits.

PURPOSE: We investigated the effect of meropenem (MEPM) on the disposition kinetics of valproate (VPA) and its metabolites in rabbits. METHODS: Rabbits were given 75 mg/kg VPA intravenously with or without 300 mg/kg MEPM. RESULTS: The plamsa total clearance of VPA was significantly increased to about 1.5 times the control (6.09 mL/min/kg vs. 4.28 mL/min/kg) by MEPM (P < 0.05). The values of the area under the plasma concentration-time curve (AUC) of 2-en-VPA, a product of beta-oxidation, and VPA-glucuronide (VPA-G) were significantly decreased to about 55% and 78% of the control, respectively (P < 0.05). The cumulative urinary excretions of VPA in the control and MEPM-treated groups were 0.54% and 0.62% of the dose, respectively, whereas those of VPA-G were 45.6% and 62.5%, respectively. The urinary excretion of VPA-G was significantly increased by MEPM (P < 0.05). Further, in the case of 33.8 mg/kg VPA-G administered intravenously the AUC value of VPA-G was unchanged by MEPM, whereas that of the generated VPA was significantly decreased to about half of the control. CONCLUSIONS: The increase of the total clearance of VPA caused by MEPM appears to be a consequence of increased renal clearance of VPA-G, as well as suppression of VPA-G hydrolysis in the liver.

Animals↗
PubMed2004

Development of a standardized susceptibility test for campylobacter with quality-control ranges for ciprofloxacin, doxycycline, erythromycin, gentamicin, and meropenem.

A standardized agar dilution susceptibility testing method was developed for Campylobacter that consisted of testing on Mueller-Hinton medium supplemented with 5% defibrinated sheep blood in an atmosphere of 10% CO2, 5% O2, and 85% N2. Campylobacter jejuni ATCC 33560 was identified as a quality-control (QC) strain. Minimal inhibitory concentration (MIC) QC ranges were determined for two incubation time/temperature combinations: 36 degrees C for 48 hr and 42 degrees C for 24 hr. Quality-control ranges were determined for ciprofloxacin, doxycycline, erythromycin, gentamicin, and meropenem. For all antimicrobial agents tested at both temperatures, 95-100% of the QC MIC results fell within recommended QC ranges. Twenty-one Campylobacter clinical isolates, encompassing five species of Campylobacter (C. jejuni, C. coli, C. jejuni, subsp. doylei, C. fetus, and C. lari) were tested in conjunction with the C. jejuni QC strain. While C. jejuni and C. coli could be reliably tested under both test conditions, growth of C. jejuni subsp. doylei, C. fetus, and C. lari isolates was inconsistent when incubated at 42 degrees C. Therefore, it is recommended that these species only be tested at 36 degrees C.

Campylobacter↗
PubMed2026

Meropenem-Colistin Combination Mitigates Porin-Associated Carbapenem Resistance Development in Ertapenem-Mono-Resistant Enterobacterales.

BACKGROUND: Non-carbapenemase-producing Enterobacterales with isolated ertapenem resistance (ETP-mono-R) may represent an early stage in the evolution toward broader carbapenem resistance, but whether further resistance induction occurs and its underlying mechanisms remain poorly understood. METHODS: Resistance induction was assessed in three Escherichia coli, four Klebsiella pneumoniae, and two Enterobacter cloacae isolates through serial exposure to subinhibitory concentrations of meropenem (MEM), imipenem, ceftazidime-avibactam, or colistin (COL), with antibiotic-free passaging for reversion. Resistance induction under MEM+COL was evaluated separately. Whole-genome sequencing (WGS), targeted porin-gene Sanger sequencing, and transcriptional analysis were used to characterize resistance mechanisms across induction stages. RESULTS: Subinhibitory MEM exposure rapidly selected for carbapenem resistance through porin-associated alterations in a species-specific manner. E. coli accumulated loop-region mutations in ompC, while K. pneumoniae predominantly developed disruptive mutations in ompK36, both accompanied by marked transcriptional downregulation. In contrast, E. cloacae retained wild-type porins but showed increased MEM MICs, suggesting a non-porin-mediated mechanism. Subinhibitory exposure to COL alone rapidly induced colistin resistance but was associated with decreased carbapenem MICs. Co-exposure to MEM and COL significantly delayed resistance development and reduced MIC increases (all P < 0.05). Targeted sequencing of 26 non-carbapenemase-producing K. pneumoniae isolates resistant to all carbapenems revealed widespread disruptive ompK36 alterations, including the S337P substitution identified experimentally, consistent with a shared permeability-loss pathway. CONCLUSIONS: In ETP-mono-R Enterobacterales, subinhibitory carbapenem exposure promotes carbapenem resistance, with porin-associated mechanisms predominating in E. coli and K. pneumoniae. Co-exposure to COL attenuates this process, suggesting a potential strategy to delay the emergence of carbapenem resistance.

Enterobacterales↗