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PubMed1998

Disposition and elimination of meropenem in cerebrospinal fluid of hydrocephalic patients with external ventriculostomy.

The broad antibacterial spectrum and the low incidence of seizures in meropenem-treated patients qualifies meropenem for therapy of bacterial meningitis. The present study evaluates concentrations in ventricular cerebrospinal fluid (CSF) in the absence of pronounced meningeal inflammation. Patients with occlusive hydrocephalus caused by cerebrovascular diseases, who had undergone external ventriculostomy (n = 10, age range 48 to 75 years), received 2 g of meropenem intravenously over 30 min. Serum and CSF were drawn repeatedly and analyzed by liquid chromatography-mass spectroscopy. Pharmacokinetics were determined by noncompartmental analysis. Maximum concentrations in serum were 84.7 +/- 23.7 microg/ml. A CSF maximum (CmaxCSF) of 0.63 +/- 0.50 microg/ml (mean +/- standard deviation) was observed 4.1 +/- 2.6 h after the end of the infusion. CmaxCSF and the area under the curve for CSF (AUCCSF) depended on the AUC for serum (AUCS), the CSF-to-serum albumin ratio, and the CSF leukocyte count. Elimination from CSF was considerably slower than from serum (half-life at beta phase [t1/2beta] of 7.36 +/- 2.89 h in CSF versus t1/2beta of 1.69 +/- 0.60 h in serum). The AUCCSF/AUCS ratio for meropenem, as a measure of overall CSF penetration, was 0.047 +/- 0.022. The AUCCSF/AUCS ratio for meropenem was similar to that for other beta-lactam antibiotics with a low binding to serum proteins. The concentration maxima of meropenem in ventricular CSF observed in this study are high enough to kill fully susceptible pathogens. They may not be sufficient to kill bacteria with a reduced sensitivity to carbapenems, although clinical success has been reported for patients with meningitis caused by penicillin-resistant pneumococci and Pseudomonas aeruginosa.

Aged↗

PubMed1998

Single-dose pharmacokinetics of meropenem during continuous venovenous hemofiltration.

The pharmacokinetic properties of meropenem were investigated in nine critically ill patients treated by continuous venovenous hemofiltration (CVVH). All patients received one dose of 1 g of meropenem intravenously. High-flux polysulfone membranes were used as dialyzers. Meropenem levels were measured in plasma and ultrafiltrate by high-performance liquid chromatography. The total body clearance and elimination half-life were 143.7 +/- 18.6 ml/min and 2.46 +/- 0.41 h, respectively. The post- to prehemofiltration ratio of meropenem was 0.24 +/- 0.06. Peak plasma drug concentrations measured 60 min postinfusion were 28.1 +/- 2.7 microgram/ml, and trough levels after 6 h of CVVH were 6.6 +/- 1.5 microgram/ml. The calculated total daily meropenem requirement in these patients with acute renal failure and undergoing CVVH was 2,482 +/- 321 mg. Based on these data, we conclude that patients with severe infections who are undergoing CVVH can be treated effectively with 1 g of meropenem every 8 h.

Aged↗

PubMed2001

C-terminal region of Pseudomonas aeruginosa outer membrane porin OprD modulates susceptibility to meropenem.

We investigated the unusual susceptibility to meropenem observed for seven imipenem-resistant clinical isolates of Pseudomonas aeruginosa. These strains were genetically closely related, expressed OprD, as determined by Western blot analyses, and were resistant to imipenem (>5 microg/ml) but susceptible to meropenem (<1 microg/ml). The oprD genes from two isolates were entirely sequenced, and their deduced protein sequences showed 93% identity with that of OprD of strain PAO1. The major alteration consisted of the replacement of a stretch of 12 amino acids, located in putative external loop L7 of OprD, by a divergent sequence of 10 amino acid residues. The oprD gene variants and the wild-type oprD gene were cloned and expressed in a defined oprD mutant. The meropenem MICs for strains carrying the oprD genes from clinical isolates were four times lower than that for the strain carrying the wild-type oprD gene. Imipenem activities, however, were comparable for all strains. Furthermore, meropenem hypersusceptibility was obtained with a hybrid OprD porin that consisted of the PAO1 oprD gene containing loop L7 from a clinical isolate. These results show that the C-terminal portion of OprD, in particular, loop L7, was responsible for the unusual meropenem hypersusceptibility. Competition experiments suggested that the observed OprD modifications in the clinical isolates did not affect antagonism between imipenem and the basic amino acid L-lysine. We further propose that shortening of putative loop L7 of the OprD porin by 2 amino acid residues sufficiently opens the porin channel to allow optimal penetration of meropenem and increase its activity. In contrast, this alteration would not affect susceptibility to a smaller carbapenem molecule, such as imipenem.

Amino Acid Sequence↗

PubMed2004

Outcomes of patients with melioidosis treated with meropenem.

Melioidosis, an infection due to Burkholderia pseudomallei, is endemic in southeast Asia and northern Australia. We reviewed our experience with meropenem in the treatment of severe melioidosis in 63 patients over a 6-year period. Outcomes were similar to those of ceftazidime-treated patients (n = 153) despite a deliberate selection bias to more-unwell patients receiving meropenem. The mortality among meropenem-treated patients was 19%. One patient had a possible drug fever associated with the use of meropenem. We conclude that meropenem (1 g or 25 mg/kg every 8 h intravenously for >/=14 days) is an alternative to ceftazidime and imipenem in the treatment of melioidosis. The use of meropenem may be associated with improved outcomes in patients with severe sepsis associated with melioidosis.

Adolescent↗

PubMed2004

Penetration of meropenem into pneumonic human lung tissue as measured by in vivo microdialysis.

Until recently, information on antibiotic pharmacokinetic properties in infected human lung tissue was limited. We therefore studied a microdialysis-based approach for measurement of the penetration of meropenem into the extracellular space fluid of human pneumonic lung parenchyma. The lung penetration of meropenem was determined for seven patients with pneumonia and metapneumonic pleural empyema treated by decortication. Intraoperatively, two microdialysis probes were inserted into pneumonic lung tissue and one was inserted into healthy skeletal muscle for reference values. Serum and microdialysis samples were collected at 20-min intervals for at least 8 h following a single intravenous dose of 1 g of meropenem. The maximum free interstitial concentration (mean and standard deviation) of meropenem in infected lung tissue was 11.4 +/- 10.9 mg/liter, and that in serum was 47.3 +/- 21.0 mg/liter. The areas under the curve for infected lung tissue (36.2 +/- 17.9 mg. h/liter) and serum (95.4 +/- 46.6 mg. h/liter) revealed a significant difference. This technique enabled quasi-continuous tissue pharmacokinetic measurements of free, unbound antibiotic in pneumonic lung tissue of patients with pneumonia. The present data corroborate the use of meropenem in the treatment of lung infections caused by extracellular bacteria, demonstrating the excellent distribution profile for meropenem in the interstitial space of human pneumonic lung tissue.

Adult↗

PubMedDate not supplied

Meropenem resistance in Pseudomonas aeruginosa.

Two genetically distinct classes of meropenem-low-susceptibility Pseudomonas aeruginosa PAO2152 mutants, which arose spontaneously, were isolated. Two meropenem resistance genes, mpmA and mpmB, were mapped near ilvB/C and proC, respectively, on the P. aeruginosa PAO chromosome. The mpmA was thought to be identical to oprD2 because of the cross-resistance to carbapenems and the association with the loss of the outer membrane protein D2 (OprD2). The mpmB mutation conferred a 4-fold increase in resistance to meropenem, and cross-resistance to various types of antimicrobial agents, e.g. carbenicillin, norfloxacin and chloramphenicol. However, the mpmB mutant was susceptible to imipenem. This mutant still possessed OprD2 and showed increased expression of a 48-kD outer membrane protein, although its profiles of beta-lactamase activity and affinities of penicillin-binding proteins for beta-lactams were indistinguishable from those of the parent strain. The resistance gene mpmB was considered to be an allele of nalB (or cfxB or oprK) from the results of the transductional analysis. The mutation frequency of mpmA:mpmB was in the ratio of 4:1. The same results were obtained in another clinically isolated P. aeruginosa strain. Meropenem resistance caused by both mpmA and mpmB mutations seemed to be due to the reduction in permeability of antibiotics through the outer membrane. These findings suggest a new pathway for the translocation of meropenem other than that mediated by OprD2 across the outer membrane. Thus, meropenem showed about 4- to 8-fold higher activity than imipenem against OprD2-deficient P. aeruginosa.

Bacterial Outer Membrane Proteins↗

PubMed2002

Antimicrobial resistance in gram-negative isolates from European intensive care units: data from the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) programme.

Susceptibility data were collected for 6243 gram-negative isolates from 29 European ICUs participating in the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Programme (1997-2000). The most commonly isolated bacteria were Pseudomonas aeruginosa (22.5%), Escherichia coli (19.8%), Klebsiella pneumoniae (10.4%), and Enterobacter cloacae (7.7%). The incidence of extended-spectrum beta-lactamase-producers was higher in Turkish, Russian and Italian ICUs (27.9-39.6%) than in other countries (2.5-10.8%). The frequency of AmpC-cephalosporin hyper-producers was 16.8-55.4%. Meropenem was more active against Proteus mirabilis than imipenem (99.0% versus 88.8% susceptibility, respectively). Against Acinetobacter baumannii, meropenem (79.6% susceptible) and imipenem (82.2%) were more active than comparators (34.3-51.6%). Meropenem and imipenem exhibited good activity against P. aeruginosa (76.1% and 68.2%, respectively; but with inter-country variation). Ciprofloxacin resistance in E. coli and K. pneumoniae increased and needs close monitoring. Meropenem (98.2-99.8% susceptibility) and imipenem (88.8-99.4%) remained potent against important species of gram-negative bacteria from European ICUs actively using meropenem.

Drug Resistance, Bacterial↗

PubMed2003

Successful meropenem desensitization in a patient with cystic fibrosis.

OBJECTIVE: To report a case of successful meropenem desensitization in a patient with cystic fibrosis (CF) with documented hypersensitivity to multiple antibiotics including carbapenems. CASE SUMMARY: A 20-year-old white man with CF was admitted to the hospital for treatment of an acute pulmonary exacerbation caused by multidrug-resistant Burkholderia cepacia complex and methicillin-resistant Staphylococcus aureus (MRSA). Past treatments of his CF exacerbations were complicated by urticarial eruptions following administration of beta-lactams, including meropenem, and ototoxicity from aminoglycosides. Skin testing revealed hypersensitivity reactions to beta-lactam antibiotics including penicillin, piperacillin/tazobactam, ceftazidime, and imipenem. A literature review (MEDLINE, January 3, 2002) and communication with the manufacturer of meropenem revealed no specific information on desensitizing patients to this agent. Because of meropenem's activity against B. cepacia complex alone and in combination with other antimicrobials, a desensitization protocol was adapted and applied to meropenem in an effort to provide the most beneficial treatment available. A 12-dose escalation protocol was successfully employed without incident. DISCUSSION: Antimicrobial therapy is limited in CF patients by susceptibility profiles of common infecting organisms (e.g., Pseudomonas spp., B. cepacia complex, MRSA). Unfortunately, host responses may further reduce the utility of many effective antibiotic classes due to hypersensitivity and/or adverse reactions. Desensitization is a useful alternative that allows the administration of beneficial medications to patients with documented allergy histories. CONCLUSIONS: Meropenem is an important treatment option in the CF population, particularly due to its activity against B. cepacia complex. Successful desensitization using a dose-escalation protocol in patients with a documented carbapenem allergy will allow the most beneficial therapy to continue.

Adult↗

PubMed2005

Acute seizures due to a probable interaction between valproic acid and meropenem.

OBJECTIVE: To report a probable interaction between meropenem and valproic acid that resulted in the development of epileptic seizures. CASE SUMMARY: A 21-year-old woman presented to our emergency department because of a new-onset, generalized tonic-clonic seizure and was admitted to the intensive care unit. Treatment with valproic acid 1000 mg as a continuous intravenous infusion over 24 hours was initiated. On day 6, the serum concentration of valproic acid was 52.5 microg/mL. On day 13, treatment with intravenous meropenem 1 g 3 times daily was started. On day 15, when the patient was afebrile, numerous myoclonic episodes occurred involving her arms and face; the serum concentration of valproic acid at that time was 42 mug/mL. The valproic acid dose was increased to 2880 mg. Two days later, a generalized tonic-clonic seizure occurred despite the increased dosage, and the plasma concentration of valproic acid fell to 7 microg/mL. The valproic acid dose was increased the following day to 3600 mg; however, the serum concentrations remained <10 microg/mL. On day 19, based on the results of a blood culture and the suspicion of an interaction between meropenem and valproic acid, meropenem therapy was suspended. The serum concentration of valproic acid was 52.4 microg/mL on day 27. Three days later, the patient was asymptomatic and was discharged. DISCUSSION: Coadministration of valproic acid and other drugs that are metabolized by the hepatic cytochrome P450 isoenzyme system can lead to clinically relevant interactions by induction or inhibition of enzymes in shared metabolic pathways. In view of studies in experimental models, the interaction between carbapenem antibiotics and valproic acid is at least possible. Use of the Naranjo probability scale indicated a probable relationship between acute seizures and a meropenem-valproic acid interaction in this patient. CONCLUSIONS: This case report provides strong evidence for an interaction between valproic acid and meropenem. Clinicians should be aware of this potential interaction that may be associated with a serious adverse effect as the result of the decrease of the valproic acid serum concentrations.

Acute Disease↗

PubMed2007

Meropenem -valproic acid interaction in patients with cefepime-associated status epilepticus.

PURPOSE: Two case reports of rapid decreases in valproic acid levels after initiation of meropenem in patients who developed new-onset seizure activity during treatment with cefepime are presented. SUMMARY: A 60-year-old Caucasian woman with myelodysplasia was transferred to the medical intensive care unit (MICU) on day 11 of her hospitalization. Cefepime was given as empiric therapy for febrile neutropenia. Pulmonary invasive aspergillosis was diagnosed. On day 16 of hospitalization, epileptic activity was confirmed. Valproic acid was initiated. Cefepime was discontinued and meropenem was initiated for treatment of cefepime-resistant pneumonia. Serum valproic acid levels decreased to subtherapeutic levels within 24 hours. Meropenem was discontinued and ceftazidime was started on day 22; serum valproic acid levels gradually increased but never reached therapeutic levels again. The patient died of intractable invasive aspergillosis on day 33. A 54-year-old Caucasian man with myelodysplasia was admitted to the MICU for nonconvulsive status epilepticus. Ten days before admission, cefepime had been started empirically for the treatment of neutropenic fever. One day before MICU admission, valproic acid was initiated as treatment for status epilepticus. The next day, serum valproic acid levels were therapeutic; cefepime was switched to meropenem. Serum valproic acid levels decreased within 24 hours and phenytoin was added. On day 4, the patient's serum valproic acid levels decreased further and meropenem was discontinued. Although the valproic acid dosage was increased, valproic acid levels did not return to the therapeutic range. The patient died on day 11. CONCLUSION: Following cefepime therapy, a clinically important interaction between meropenem and valproic acid occurred in two critically ill patients with new-onset status epilepticus.

Anti-Bacterial Agents↗

PubMed1995

Meropenem clinical pharmacokinetics.

Meropenem is a recently developed carbapenem antibiotic, similar to imipenem, with a wide spectrum of activity against Gram-positive and Gram-negative bacteria. In comparison with imipenem, meropenem is relatively stable to hydrolysis by the enzyme dehydropeptidase I (DHP-I), thus precluding the need for coadministration with an inhibitor of DHP-I, such as cilastatin. Furthermore, meropenem may be less nephrotoxic and neurotoxic than imipenem. Plasma meropenem concentrations reach a peak (Cmax) of approximately 30 mg/L after administration of a standard dose of 1 g intravenously. The elimination half-life (t1/2) is approximately 1 hour, and the area under the plasma concentration-time curve increases linearly in a dose-related manner. The volume of distribution is 21L, indicating predominantly extracellular distribution. Meropenem distributes partly into cerebrospinal fluid. The drug is eliminated both by metabolism and excretion. In normal volunteers, up to 70% is recovered in urine, and the remainder is accounted for by a beta-lactam ring-opened form of the compound, ICI 213689. The t1/2 of meropenem is prolonged in patients with renal insufficiency and correlates well with creatinine clearance. Dosage adjustments in people with decreased creatinine clearance can, thus, be made on the basis of creatinine clearance.

Aged↗

PubMed1995

Meropenem. A review of its antibacterial activity, pharmacokinetic properties and clinical efficacy.

The parenteral carbapenem meropenem is relatively stable to inactivation by human renal dehydropeptidase (DHP-1) and does not require concomitant administration of a DHP-1 inhibitor such as cilastatin. It has a broad spectrum of antibacterial activity in vitro, the majority of Gram-negative, Gram-positive and anaerobic pathogens being highly susceptible to the drug. Meropenem has shown clinical and bacteriological efficacy in the treatment of a wide range of serious infections in adults and children which is at least comparable with that of currently available treatment options. Its clinical and bacteriological efficacy is similar to that of imipenem/cilastatin, clindamycin plus tobramycin and cefotaxime plus metronidazole in the treatment of intraabdominal infections; cefotaxime or ceftriaxone in the treatment of meningitis; imipenem/cilastatin, and ceftazidime with or without an aminoglycoside, in lower respiratory tract infections; and imipenem/cilastatin or ceftazidime in the treatment of urinary tract infections. Satisfactory clinical and bacteriological response rates have also been achieved in patients with skin and skin structure infections, obstetric and gynaecological infections or septicaemia, and in immunocompromised patients with febrile episodes. Preliminary findings also indicate efficacy in the treatment of respiratory tract infections in patients with cystic fibrosis. The tolerability profile of meropenem is generally similar to that of comparator agents, although it is associated with a lower incidence of adverse gastrointestinal effects (nausea and vomiting) than imipenem/cilastatin. Importantly, the incidence of seizures in patients with meningitis is not increased following administration of meropenem. Thus, meropenem is an effective broad spectrum antibacterial drug for the treatment of a wide range of infections including polymicrobial infections in both adults and children, with comparable efficacy to imipenem/cilastatin and various other treatment regimens. Meropenem is likely to be of greatest value as empiric monotherapy in the treatment of serious infections for those caused by multiply-resistant pathogens. Further clinical experience is necessary, however, to ultimately define its place in therapy.

Absorption↗

PubMed1997

Imipenem/cilastatin (1.5 g daily) versus meropenem (3.0 g daily) in patients with intra-abdominal infections: results of a prospective, randomized, multicentre trial.

An open-label prospective, randomized, parallel multicentre study was undertaken to compare the efficacy and tolerability of 1.5 g/day intravenous imipenem/cilastatin with 3 g/day intravenous meropenem in the treatment of intra-abdominal infections. A total of 287 patients were enrolled: 201 patients, divided between the 2 treatment groups, were evaluable. Clinical outcome, bacteriological outcome, untoward microbiological effects, and clinical and laboratory adverse experiences were evaluated. 98% of patients receiving imipenem/cilastatin therapy were cured, with 96% showing eradication of infection. 95% of those on meropenem were cured, with 98% showing eradication. These differences in clinical and bacteriological outcome between the 2 treatments were not statistically significant. Two patients receiving imipenem/cilastatin and 5 receiving meropenem had untoward microbiological effects. There was a 0.7% frequency (1/139 patients) of possibly or probably drug-related clinical or laboratory adverse experiences with imipenem/cilastatin and a 2.7% frequency (4/148) with meropenem. The mean time to defervescence was significantly less for patients in the imipenem/cilastatin treatment group than for those receiving meropenem. This study shows that 1.5 g/day of imipenem/cilastatin is equivalent to 3.0 g/day meropenem in clinical and bacteriological outcome, as well as in incidence of side effects.

APACHE↗

PubMed1999

In-vitro disk diffusion sensitivity of meropenem against bacterial pathogens in Harare.

OBJECTIVE: To compare the in-vitro sensitivity of meropenem with imipenem and other antibiotics against clinically significant bacteria. DESIGN: A longitudinal survey. SETTING: Department of Medical Microbiology, in a tertiary care university hospital. SUBJECTS: Specimens obtained from patients attending various clinics at tertiary care and teaching hospital in Harare. Those submitted to the Public Health Bacteriology Laboratory were analysed. MAIN OUTCOME MEASURES: Rates of resistance or susceptibility of the various bacteria to the antibiotics employed in the study. RESULTS: There was excellent in-vitro bacterial activity of meropenem against virtually all clinically significant Gram positive and Gram negative isolates when compared with other antibiotics such as imipenem, ciprofloxacin, gentamicin, penicillin, ampicillin, fusidic acid, tetracyclines, erythromycin and clindamycin (p < 0.5). All isolates of Streptococcus pyogenes, Pseudomonas aeruginosa, Enterobacteriaceae, Neisseria meningitidis were susceptible to meropenem. Meropenem showed 99% overall in-vitro sensitivity against Gram positive and Gram negative bacteria. About 80% of staphylococci were resistant to penicillin whereas at least 20-25% of S. aureus, coagulase negative staphylococci, S. pyogenes showed resistance to ampicillin, erythromycin, gentamicin, tetracycline and clindamycin. CONCLUSION: Meropenem is not included in the list of routinely tested antibiotics in our laboratory, a major tertiary laboratory in the country. As a result of the ultra-broad spectrum of activity, we recommend its inclusion in our routine antibiotic sensitivity testing and observe that there is a great potential for meropenem in the treatment of infections caused by several genera of bacteria in our environment.

Drug Resistance, Microbial↗

PubMed2001

Empirical monotherapy with meropenem in serious bacterial infections in children.

The efficacy and safety profile of meropenem were analyzed according to data collected from hospitalized pediatric patients aged 4 days to 20 years who had serious bacterial infections and were treated in a major teaching hospital in Taipei. Of the 53 patients enrolled, 47 were analyzed for clinical efficacy and 53 for safety. The satisfactory clinical response rate was 57% in lower respiratory tract infection, 58% in septicemia, 100% in complicated urinary tract infection, osteomyelitis, and central nervous system infection, 83% in skin and soft tissue infection, and 93% in intra-abdominal infection. Eleven (21%) patients experienced adverse events related to meropenem. The most commonly observed adverse reactions were elevated hepatic enzymes (7.5%), increased alkaline phosphatase (3.8%), and thrombocytosis (3.8%). There was no meropenem-related seizure, withdrawal, or death. The results of this study suggested that meropenem is well tolerated even in young infants, and is effective in treating serious childhood bacterial infection. However, this study also identified a proportion of hospitalized pediatric patients with isolates that were resistant to meropenem. The trends in meropenem resistance among nosocomially acquired bacteria should be monitored closely.

Adult↗

PubMed2002

A randomized, controlled clinical trial on meropenem versus imipenem/cilastatin for the treatment of bacterial infections.

OBJECTIVE: To evaluate the efficacy and safety of meropenem in Chinese patients, we conducted a study for the treatment of patients with lower respiratory tract infections, urinary tract infections and other infections. METHODS: A total of 182 hospitalized patients were enrolled in the study. 90 patients received 500 mg meropenem every 12 hours (or 1 g every 12 hours if necessary) and 92 patients received imipenem/cilastatin 500 mg/500 mg every 12 hours (or 1 g every 12 hours if necessary) by intravenous infusion. The duration of treatment was 7 - 14 days for both groups. RESULTS: Seventy of 90 cases receiving meropenem and 70 of 92 cases receiving imipenem/cilastatin were assessable for clinical efficacy. The overall efficacy rates were 90% for the meropenem group and 87% for the imipenem/cilastatin group, and the bacterial eradication rates were 86% in both groups. 93 (76%) of 123 strains isolated from patients produced beta-lactamases. Adverse drug reactions were evaluated in 72 cases in the meropenem group and 70 cases in the imipenem/cilastatin group. The adverse drug reaction rates were 9.7% and 8.6%, respectively. The results showed that there were no statistical differences between these two groups (P > 0.05). CONCLUSION: Meropenem is effective and safe for the treatment of bacterial infections caused mainly by beta-lactamase-producing strains.

Adult↗

PubMed2003

Resistance emergence among P. aenrginosa in a rat thigh-abscess model. Comparison of imipenem and meropenem treatment.

Resistance emergence to carbapenem antibiotics was studied in a rat-thigh abscess model. Abscesses were developed in three groups with a total of 15 P. aeruginosa strains (three rats per strain). Groups were assigned to imipenem or meropenem treatment while one was left antibiotic-free. Test strains were fully susceptible to these antibiotics and the "Mutant Preventing Concentrations" of imipenem and meropenem over these strains were comparable. Antibiotic serum levels, assessed by serum bioassay test, were similar among therats. After four days, rats (n=45) were sacrificed and carbapenem resistant mutants were selected on imipenem (4 mg/L) and meropenem (4 mg/L) supplemented agar plates. Resistant variants of three strains, from four abscesses, were detected; one in the meropenem group, two in the imipenem and one in the untreated group. The MICs of imipenem and meropenem for the mutants were increased fourfold times or even higher of their counterparts. Resistance emergence under antibiotic pressure in P. aeruginosa has been shown in various conditions. To our knowledge, however, resistance emergence in abscess and also the comparison of imipenem and meropenem in this regard has not been studied before.

Abscess↗

PubMed2003

[Meropenem therapy in children with febrile neutropenia].

OBJECTIVES: Infectious complications are the major causes of morbidity and mortality in children receiving chemotherapy for malignant diseases. Granulocytopenia carries the risk of bacterial infection, and also, if prolonged, of fungal infection. The aim of this study was to evaluate the clinical effectiveness of meropenem in immunocompromised children in association with isolated bacteria from blood cultures and clinical background. METHODS: Retrospective study of all febrile episodes when meropenem was used in neutropenic children between January 1998 and December 2002 in the haemato-oncological units of the authors hospital. During the study period meropenem was used in 87 febrile events diagnosed in 55 patients (mean age 10 years 5 months), and 328 bacterial cultures were performed. Blood samples were taken from each patient with granulocytopenia (< 0.5 G/l) and fever (> or = 38 degrees C), prior to the start of any antibiotic therapy. For the microbiological process Bactec 9050 (Becton Dickinson) blood culture systems were used. RESULTS: Microorganisms were detected and identified in 64 (19.5%) from the 328 hemocultures. There was a predominance of Gram-positive strains, 67% (43/64)--the most common bacteria being coagulase negative Staphylococcus (cnS). From the 87 periods in 43 cases (49.4%) the infection was documented microbiologically. In 16 additional cases the infection was proven clinically (based on the clinical course, laboratory and radiologic results) and 32.2% (28/87) of the febrile neutropenic episodes were considered to be fever of unknown origin. Meropenem was used in a mean dose of 60.8 (30-120) mg/kg/die, for 9.3 (2-24) days. The success rate of the meropenem therapy -excluding the proven fungal (n = 13) or cnS (n = 15) infections-was 72.9%. No severe side effects occurred in any regimens. CONCLUSION: The results demonstrate that meropenem is effective and well-tolerated when used for the treatment of feverish neutropenic cancer children.

Adolescent↗