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PubMed2006

Cure of persistent, post-appendectomy Klebsiella pneumoniae septicaemia with continuous intravenous administration of meropenem.

A 15-year-old girl developed a persistent bacteraemia with Klebsiella pneumoniae accompanied by systemic symptoms including high fever and rigors after appendectomy. Extensive laboratory and imaging work-up, including tests for an intra-vascular source of infection, did not reveal the origin of the persistent bacteraemia. The Klebsiella pneumoniae isolates were susceptible to gentamicin and colistin and intermediately susceptible to meropenem. The septicaemia persisted despite the intravenous administration of meropenem 1 g and later 2 g every 8 h in combination with intravenous gentamicin and later colistin. The patient was cured only after the continuous intravenous administration of meropenem of 6 g/d.

Adolescent↗

PubMed1998

Appearance of resistance to meropenem during the treatment of a patient with meningitis by Acinetobacter.

A case is reported of a patient who developed Acinetobacter meningitis after an external ventricular drainage system had been fitted for control of intracranial pressure. During the process, nine strains of Acinetobacter isolated from her cerebrospinal fluid were indistinguishable by analysis of total genomic DNA by pulse-field gel electrophoresis. The first eight strains were sensitive to meropenem and imipenem (MICs < 1 g/l). The MIC of the last one, which had been recovered after 32 days during two courses of treatment with meropenem, increased to > 32 g/l for meropenem, while with imipenem the increase was minimal (MIC = 1.5 g/l). The microorganism persisted in the central nervous system despite the administration of different antimicrobials, including intraventricular aminoglycosides and six changes in the external ventricular system. The patient died 68 days after admission to the intensive care unit from bilateral cerebral ischemic lesions, intraventricular hemorrhage and cerebral edema with endocraneal hypertension, the Acinetobacter ventriculitis also contributing to this state.

Acinetobacter↗

PubMedDate not supplied

Experience with cefepime versus meropenem as empiric monotherapy for neutropenia and fever in pediatric patients with solid tumors.

A prospective, open-label, randomized, comparative study in pediatric cancer patients was conducted to evaluate the efficacy and safety of cefepime and meropenem in the empiric therapy of febrile neutropenic patients. Febrile episodes were classified as microbiologically documented infection, clinical documented infection, or fever of unknown origin. Clinical response to therapy was classified as success or failure. In this period 37 children with solid tumors including lymphoma, 25 males, 12 females, had neutropenia on 65 occasions. Microbiologically documented infections occurred in 21 episodes (32.31%). Frequency of positive bacteria isolated was higher than gram-negative bacteria. There was no infection-related death. There were no statistical differences between the cefepime and meropenem groups for duration of fever or neutropenia, response rate, and necessity for modification. Cefepime appears to be as effective and safe as meropenem for empiric treatment of febrile episodes in neutropenic pediatric cancer patients.

Adolescent↗

PubMed2006

Mechanical effects of the use of vancomycin and meropenem in acrylic bone cement.

BACKGROUND: The increasing resistance of certain bacteria to antibiotics commonly used in bone cements has led to a demand for alternative antibacterial agents. The antibiotics added to bone cements may, however, have detrimental effects on the mechanical properties of the cement. MATERIAL AND METHODS: We evaluated the mechanical effects of adding vancomycin and meropenem to bone cement by compression, bending and fatigue tests. RESULTS: Addition of vancomycin at a concentration of up to 2.5% (w/w) had no effect on the compressive strength. Bending and fatigue strength were negatively affected by vancomycin but not by meropenem. INTERPRETATION: A cement containing 1.25% vancomycin and 1.25% meropenem might be an interesting compromise between the introduction of antibacterial properties and preservation of the mechanical properties. With this concentration of additives the compressive strength and the fatigue strength remain unchanged, while the bending strength (-14%) and the bending modulus (-9%) are only slightly reduced and remain above the limits set by the ISO5833 standard.

Anti-Bacterial Agents↗

PubMed2005

Pharmacodynamic modeling of imipenem-cilastatin, meropenem, and piperacillin-tazobactam for empiric therapy of skin and soft tissue infections: a report from the OPTAMA Program.

BACKGROUND: The bactericidal exposures necessary for positive clinical outcomes among skin and soft tissue infections are largely dependent on interpatient pharmacokinetic variability and pathogen drug susceptibility. By simulating the probability of achieving target bactericidal exposures, the pharmacodynamics of three beta-lactam agents were compared against a range of pathogens implicated commonly in complicated skin and soft tissue infections. METHODS: Using Monte Carlo simulation, pharmacodynamic target attainment expressed as the percentage of the time interval during which the antibiotic concentration exceeded the minimal inhibitory concentration (%T > MIC) in serum and blister fluid was calculated for 5,000 simulated patients receiving imipenem-cilastatin 0.5 g q8h, meropenem 0.5 g q8h, piperacillin-tazobactam 3.375 g q6h, and piperacillin-tazobactam 4.5 g q8h. The pharmacokinetics for each antibiotic were derived from previously published healthy volunteer studies. The MICs for Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Enterobacter sp., Klebsiella sp., coagulase-negative staphylococci, Proteus sp., beta-hemolytic streptococci, and Serratia sp. were taken from the MYSTIC 2003 surveillance study and weighted by the prevalence of each pathogen among 1,404 isolates collected from skin and soft tissue infections during the 2000 SENTRY study. The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) was added into the model at increasing resistance rates. RESULTS: Imipenem-cilastatin, meropenem, and piperacillin-tazobactam 3.375 g q6h achieved greater than 90% likelihood of achieving bactericidal exposure in serum and blister fluid until the prevalence of MRSA increased beyond 10%. Piperacillin-tazobactam 4.5 g q8h achieved a lower probability of achieving bactericidal exposure than the other regimens (88.7%, p < 0.001). CONCLUSIONS: When the incidence of MRSA is low, imipenem-cilastatin, meropenem and piperacillin-tazobactam 3.375 g q6h would be optimal choices for the empiric treatment of complicated skin and soft tissue infections among the regimens studied. When MRSA is suspected, a drug that retains activity against this pathogen should be considered.

Anti-Bacterial Agents↗

PubMed2005

Determination of meropenem by capillary electrophoresis using direct injection of serum.

Concentration determination of meropenem, a carbapenem antibiotic, using a capillary electrophoresis method by direct injection of serum samples without any pretreatment is described herein. Sodium tetraborate (25 mM)-sodium hydroxide (0.1 M) containing sodium dodecyl sulfate (90 mM) is used as a run buffer (pH 10.0). Meropenem is detected at its absorption maximum at 297 nm. Migration time of meropenem is approximately 7.2 min, and the detection limit of the assay is 2.0 mg/L at a signal-to-noise ratio of 3.0. The relative standard deviations of intra- and interassay accuracies are 3.43-8.87% and 4.28-8.54%, respectively, at a nominal concentration of 6.3-100.0 mg/L, and their recovery rates are 94-111% and 92-105%, respectively.

Electrophoresis, Capillary↗

PubMed1995

Meropenem versus tobramycin plus clindamycin for treatment of intraabdominal infections: results of a prospective, randomized, double-blind clinical trial.

The efficacy of meropenem was compared to that of the combination of tobramycin plus clindamycin (T/C) in a multiinstitutional clinical trial of treatment for patients suffering intraabdominal infection. Among the 177 patients enrolled and randomized, 127 were clinically evaluable and 86 were microbiologically evaluable. Analysis of data on an intent-to-treat basis for all randomized patients and on the basis of a successful outcome (absence of any infection) for clinically evaluable patients failed to detect any difference in efficacy between the two treatments. Infection was cleared in 92% of meropenem- and 89% of T/C-treated clinically evaluable patients. Eradication of pathogens also was similar in the two treatment groups. Overall, adverse drug experiences were comparable between the two treatment groups, with the exception of an increase in serum creatinine level (which occurred more frequently in patients receiving T/C). Meropenem appears to be efficacious for the treatment of intraabdominal infections.

Abdomen↗

PubMed1997

Pharmacokinetics of meropenem in patients with liver disease.

Eight subjects with chronic stable alcoholic cirrhosis and eight matched controls with normal liver function were given an initial 30-minute intravenous infusion of 1 g of meropenem; beginning 24 hours later, they received five additional 1-g doses at 6-hour intervals. No statistically significant differences were found between the first dose and steady state or between groups for any plasma pharmacokinetic parameters-including the highest observed plasma concentrations, plasma concentrations at 6 hours after dosing (C6h), terminal half-life, area under the plasma concentration-time curve (AUC), area under the first moment of the curve, plasma clearance, steady-state volume of distribution, and accumulation ratios-on the basis of either AUC or C6h. There were also no statistically significant differences in any of the measured or calculated pharmacokinetic parameters of the microbiologically inactive metabolite of meropenem (ICI 213,689). A total of 11 adverse experiences (one moderate and 10 mild) were reported by four patients; nine of these experiences, including two in controls, were rated by the investigator as "possibly" drug related. It is concluded that meropenem is well tolerated with repeated intravenous dosing and that dosage adjustments are not necessary for patients with hepatic disease.

Adolescent↗

PubMed1997

Use of meropenem in the treatment of serious infections in children: review of the current literature.

Meropenem is a new beta-lactam carbapenem antibiotic that appears to be promising in the treatment of hospitalized infants and children with serious infections. It has broad-spectrum activity against microorganisms, including most of the major aerobic (gram-negative and gram-positive) and anaerobic pathogens that cause serious bacterial infections in neonates and children. In addition, its pharmacokinetic profile makes possible parenteral administration every 8 hours. Several studies have demonstrated that meropenem is an effective and safe treatment for infants and children with serious pediatric infections (e.g., urinary tract infections, pneumonia, sepsis, intraabdominal infections, and skin and soft-tissue infections), bacterial meningitis, and cystic fibrosis. The results of further studies of the use of meropenem in the treatment of high-risk seriously ill infants and children are awaited with interest.

Anti-Bacterial Agents↗

PubMed1989

Susceptibility of anaerobic bacteria to meropenem.

The activity of meropenem was determined against 350 strains of anaerobic bacteria by an agar dilution method. It was compared with those of piperacillin, cefoxitin, imipenem, clindamycin, metronidazole and chloramphenicol. Meropenem and imipenem were the most active agents tested. On the basis of these results, meropenem appears to be a promising antimicrobial agent for anaerobic infections and warrants further clinical investigation.

Anti-Bacterial Agents↗

PubMed1989

Interactions of meropenem with class I chromosomal beta-lactamases.

Most newer penicillins and cephalosporins are labile to the Class I beta-lactamases that are inducible in Pseudomonas aeruginosa. Enterobacter spp., Citrobacter spp., Serratia spp. and indole-positive Proteeae, but fail to induce enzyme synthesis below the MIC. They remain active against the inducible strains but not against mutants (termed 'stably depressed') that manufacture beta-lactamase copiously without induction. Such mutants are segregated at high frequency and may be selected during therapy, sometimes causing clinical failure. Meropenem induced Class I enzymes weakly below the MIC in Ps. aeruginosa, Ent. cloacae, C. freundii, Ser. marcescens, Morganella morganii and Pr. vulgaris. Nonetheless it remained equally active against inducible strains and their derepressed mutants, and was no more active against laboratory-derived beta-lactamase basal mutants. It did not select derepressed mutants from beta-lactamase-inducible populations. These data suggested great stability to Class I beta-lactamases, and this deduction was confirmed by direct assays with purified beta-lactamases. Initial hydrolysis rates ranged from 0.9-10.0 drug molecules hydrolysed/enzyme molecule/minute but these values declined by 80-90% before 5% of the antibiotic had been hydrolysed, indicating that the carbapenem could deactivate the enzymes. Deactivation was reversible, full activity being restored once the meropenem was removed. These results suggest that meropenem, like imipenem and various experimental penems, may overcome the resistance problems presented by Class I beta-lactamases.

Bacteria↗

PubMed1989

Interactions of meropenem, with beta-lactamases, including enzymes with extended-spectrum activity against third-generation cephalosporins.

The interactions of a meropenem were studied with a set of beta-lactamases including the new TEM- and SHV-related plasmid-mediated enzymes that have extended-spectrum activity against third-generation cephalosporins ('cefotaximases' and 'ceftazidimases'). Meropenem and imipenem were highly resistant to the hydrolytic activity of all the TEM and SHV related beta-lactamases, and to the OXA enzymes, as were the cephamycins: cefoxitin and cefotetan. The two carbapenems were also highly stable to Class C beta-lactamases (chromosomal cephalosporinases) whereas third-generation cephalosporins and cephamycins were slowly hydrolyzed. Both carbapenems demonstrated quite similar affinities for all the enzymes studied. In some instances, and particularly with Class A (TEM- and SHV-derived) enzymes, meropenem inactivated the beta-lactamase activity. Imipenem appeared less reactive in this respect.

Acylation↗

PubMed1989

Bacteriostatic and bactericidal in-vitro activity of meropenem against clinical isolates, including Mycobacterium avium complex.

For clinical isolates the MICs of meropenem were significantly lower than the MICs of imipenem, especially against Pseudomonas aeruginosa. Furthermore, meropenem was bactericidal for Pseudomonas spp., including Ps. (Xanthomonas) maltophilia, and staphylococci, with MBCs on average only two-fold above the respective MICs. The bactericidal activity was confirmed by killing curve assays. Strains with high meropenem MICs (greater than or equal to 8 mg/l) were killed by a combination of the carbapenem and amikacin, with kinetics that indicated synergism between the two antimicrobial agents.

Amikacin↗

PubMed1993

Comparative susceptibility of the Bacteroides fragilis group species and other anaerobic bacteria to meropenem, imipenem, piperacillin, cefoxitin, ampicillin/sulbactam, clindamycin and metronidazole.

The in-vitro activity of meropenem, imipenem, piperacillin, cefoxitin, ampicillin/sulbactam, clindamycin and metronidazole was determined against 395 strains of strict and facultative anaerobes, including Gardnerella vaginalis, Lactobacillus spp. and Mobiluncus spp. The activities of meropenem and imipenem were within one dilution of their MIC50 and MIC90 values. One isolate of Bacteroides fragilis, two of Bacteroides distasonis, and two of Bacteroides ovatus showed resistance or diminished susceptibility to meropenem and imipenem. Metronidazole was active against almost all obligate anaerobic isolates. Some non-spore-forming Gram-positive bacilli and lactobacilli were resistant. Ampicillin/sulbactam inhibited almost all isolates at < or = 16/8 mg/L. The activity of clindamycin and cefoxitin was relatively good, but some strains of non-fragilis B. fragilis group species were resistant. Piperacillin was the least active agent tested.

Ampicillin↗

PubMed1993

Studies on the postantibiotic effect and the postantibiotic sub-MIC effect of meropenem.

The postantibiotic effect (PAE), the postantibiotic sub-MIC effect (PA SME) and the sub-MIC effect (SME) of a new carbapenem, meropenem, were determined for different strains of Escherichia coli and Pseudomonas aeruginosa. A PAE was induced by 10 x MIC of meropenem for 2 h. After induction, the antibiotic was eliminated by washing and dilution. The strains in the postantibiotic exposure phase and the controls were then exposed to no antibiotic or to different sub-MICs concentrations (0.1-0.6 x MIC) of meropenem. The growth curves were followed for 24 h with viable counts and/or measured by continuous monitoring of optical density in a BioScreen C apparatus. Zero or very low values for the PAE were seen in the strains studied. However, a long PA SME and SME were seen for P. aeruginosa when determined by both methods, which at 0.3 x MIC gave comparable results. At lower concentrations the PA SMEs measured with BioScreen C were shorter, probably due to differences in the definition between the two methods. The BioScreen C method was less laborious than viable counting. However, one disadvantage of the BioScreen C method was that manual viable counting still had to be used to determine bacterial killing. No PA SME or SME against E. coli was observed, and the increased sensitivity of P. aeruginosa to sub-MICs of carbapenems remains unexplained.

Escherichia coli↗

PubMed1995

Control-related effective regrowth time and post-antibiotic effect of meropenem on gram-negative bacteria studied by bioluminescence and viable counts.

A study was performed to compare viable counts and bioluminescence for determining control related effective regrowth time (CERT) and postantibiotic effect (PAE) on Gram-negative bacteria after two hours of exposure to meropenem. There was a good correlation between bioluminescence and viable counts in determining the cell numbers in growing cultures of Escherichia coli. CERT was defined as the time required for the resumption of logarithmic growth and an increase of 1 log10 to occur over the pre-exposure inoculum in the test culture minus corresponding time for the control culture. PAE and CERT were studied on reference strains of Enterobacter cloacae, E. coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. At 4 x MIC of meropenem the CERTs of these four Gram-negative strains were 4.1, 4.9, 4.2, and 3.6 h, respectively, when assayed by bioluminescence. Corresponding CERTs using viable counts were 4.2, 5.0, 5.1 and 3.8 h, respectively. In contrast to this good agreement between the methods in assessing CERT, the corresponding PAEs were highly method dependent. At 4 x MIC of meropenem the PAEs on E. cloacae, E. coli, K. pneumoniae and P. aeruginosa were 3.9, 4.8, 4.7, and 3.5 h, respectively, when assayed by bioluminescene. However, the corresponding and simultaneously determined viable count PAEs were -0.4, 0.5, -0.1, and 0.7 h, respectively. The poor correlation between these methods in assessing the PAE is caused by greater initial decrease in viability compared with the less prominent initial change in cell density as measured by bioluminescence.(ABSTRACT TRUNCATED AT 250 WORDS)

Colony Count, Microbial↗

PubMed1995

The pharmacokinetics of meropenem in infants and children: a population analysis.

Plasma meropenem concentration versus time data collected during a single dose, pharmacokinetic study in infants and children were analysed using the population pharmacokinetics program NONMEM. A total of 300 meropenem concentrations was obtained from 65 patients ranging from 2 months to 12 years of age; weighing between 3.7 and 46 kg. A two-compartment open pharmacokinetic model with a zero-order infusion over 30 min was fitted to the data. The most important determinant of meropenem clearance was the creatinine clearance but an additional improvement occurred when a nonlinear dependence upon age was included. The most important determinant of the volume of distribution in the central and peripheral compartments was the body weight. The distributional clearance showed a nonlinear dependence on body weight. Demographic factors other than weight and age were not found to be influential in the model. Both clearance and distributional clearance were markedly different in the younger (< 2 years) or lighter (< 10 kg) patients, respectively. Thereafter the parameter values slowly approached those found in adults. In this study, a mean of 4.6 samples per patient was used to provide information on the pharmacokinetics and the determinants of the pharmacokinetic variability in infants and children. The findings in the younger, lighter patients, if generally applicable, might have significance for the dosage recommendations for drugs with narrow therapeutic indices.

Age Factors↗

PubMed1997

Meropenem susceptibility of Neisseria meningitidis and Streptococcus pneumoniae from meningitis patients in The Netherlands.

In-vitro susceptibility of 299 Neisseria meningitidis and 157 Streptococcus pneumoniae strains from meningitis patients in The Netherlands in 1993 and 1994 to meropenem was determined using the Etest. Susceptibility to penicillin, ceftriaxone, and chloramphenicol was also determined. Rifampicin susceptibility was additionally tested for N. meningitidis. Of the meningococci, 4.3% were of intermediate resistance to penicillin and 0.3% were resistant to rifampicin. One pneumococcal isolate (0.6%) was of intermediate resistance to penicillin. All strains were susceptible to meropenem. We conclude that meropenem is in vitro highly active against N. meningitidis and S. pneumoniae.

Anti-Bacterial Agents↗