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PubMed2003

Monotherapy with meropenem versus combination therapy with ceftazidime plus amikacin as empirical therapy for neutropenic fever in children with malignancy.

Fifty-four pediatric cancer patients with a total of 100 febrile neutropenic episodes treated at China Medical College Hospital were randomized to receive meropenem or ceftazidime plus amikacin from January 2001 to April 2002. The characteristics of 76 assessable febrile episodes (39 with meropenem and 37 with ceftazidime plus amikacin) were compared between the 2 groups. The success rate with unmodified therapy was not significantly different between the meropenem group (72%) and the ceftazidime-plus-amikacin group (57%). The incidence of side effects was similar between the 2 groups and these side effects were reversible. Microbiologically documented infection, clinically documented infection, and unexplained fever accounted for 35%, 37%, and 28% of episodes, respectively. The clinical response rates in subgroups of documented infection and unexplained fever did not significantly differ between the 2 treatment groups. Meropenem was significantly more effective than ceftazidime plus amikacin in children at high risks of developing severe infection who had profound neutropenia (absolute neutrophil count [ANC] < 100/mm3), prolonged neutropenia (ANC < 500/mm3 lasting for > 10 days), or clinically deteriorating shock (p=0.045). As an empirical treatment, meropenem seems to be as effective and safe as ceftazidime plus amikacin for febrile episodes in children with cancer and neutropenia. Meropenem is more effective for pediatric cancer patients at the high risk of severe infection.

Adolescent↗

PubMed1997

[Clinical pharmacology and indications of meropenem in severe pediatric infection].

The choice of an antibiotic for the treatment of a serious paediatric infection is generally a difficult problem. The arrival of Carbapenem resulted an important advance in the field of medicine due to its broad-spectrum, low incidence of resistances and good safety profile. Among Carbapenems, Meropenem introduction represents a progress because of its pharmacokinetics characteristics and blood-brain barrier penetration. Meropenem dosage depends on the patient weight, and the way of administration is potentially easier. Meropenem has been compared with the most used paediatric antimicrobial in controlled and randomised clinical trials, showing a high efficacy in the treatment of several infections (respiratory, urinary, intraabdominal, dermatological, septicemia) and in neutropenic and cystic fibrosis patients aged between one month and twelve years old. Meropenem is specially useful in the bacterial meningitis treatment because it penetrates into the cerebrospinal fluid of patients with inflamed meninges and reaches therapeutic concentrations, and because appearance of seizures is low. Adverse reactions produced by Meropenem show a poor incidence and its severity is usually mild. With regard to this characteristics, it can be concluded that Meropenem is an antimicrobial which efficacy and safety profiles guarantee its use in the treatment of severe paediatric infections.

Bacterial Infections↗

PubMed1997

[The role of meropenem in bacterial meningitis].

Meropenem is a new carbapenem antibiotic of with an antibacterian spectrum similar to that of imipenem, but from which it may mainly be differentiated by the possibility of its administration at high doses and it has no demonstrated proconvulsive effect, properties which make it applicable in the treatment of bacterial meningitis. The clinical and experimental experience in the treatment of bacterial meningitis with this antibiotic is herein reviewed. It has been observed that the efficacy and safety of meropenem in meningitis caused by N. meningitidis, H. influenzae and pneumococci sensitive to penicillin may be similar to that of cefotaxime or ceftriaxone in both the pediatric and adult population. There are very few reports on the treatment of meningitis caused by pneumococci resistant to penicillin. However, given that the activity of meropenem on these pneumococci is similar to that of cefotaxime and that the doses administered are much lower, it does not appear to be recommendable in the treatment of this indication, although it should be tested in all meningeal strain to these characteristics isolated. It may currently be considered that the main indication of meropenem in the infections of the central nervous system is in nosocomial meningitis by multiresistant gram negative bacilli such as those of the Klebsiella-Serratia-Enterobacter and Acinetobacter sp. group. Therefore a limited, albeit favorable, report on the clinical experience with meropenem is herein presented. Meropenem may also be useful in the treatment of meningitis by Pseudomonas aeruginosa in which other treatments have failed.

Adult↗

PubMedDate not supplied

[Bactericidal activity and capacity for selection of mutants resistant to imipenmen and meropenem in strains of Proteus, Morganella and Providencia].

BACKGROUND: To compare the bactericidal activity and frequency of mutation for meropenem and imipenem against Proteus mirabilis, Morganella morganii and Providencia rettgeri. MATERIAL AND METHODS: Minimum inhibitory concentrations (MIC) were determined by agar dilution method. Bactericidal activities were evaluated by killing curves method employing 4 and 16x MIC. One-step resistant mutant selection was performed by spreading more than 5 x 10(8) UFC/ml on cystine-lactose-electrolyte deficient agar containing 4 times the MIC of meropenem or imipenem. RESULTS: MIC were 8 to 16 times lower for meropenem. After 24 h, bactericidal activity was observed for meropenem at 4 and 16 x MIC against 76.7 and 100% of the strains in comparison to 26.7 and 83.3% with imipenem. After 24 h incubation with imipenem, re-growth occurred in 80 and 90% of P. mirabilis and M. morganii strains, respectively. Imipenem resistant mutants were selected from 3 strains of P. mirabilis. One of them was stable and MIC of meropenem and imipenem were 8 to 16-fold higher. CONCLUSIONS: From the laboratory point of view we consider that meropenem is more active against Proteeae because it was more potent in terms of inhibitory and bactericidal activity. In addition the risk to select for resistant mutants was significant with imipenem and P. mirabilis.

Drug Resistance, Microbial↗

PubMed1994

Concentration of meropenem in serum and in bronchial secretions in patients undergoing fibreoptic bronchoscopy.

The objective of the study was to evaluate the ability of meropenem to reach the bronchial lumen. 24 patients undergoing fibreoptic bronchoscopy for exploratory purposes were given a single dose of meropenem 1 g as an (i.v., infusion over 30 min. Plasma (P) sampling times were: 0, 0.5, 1, 2 and 3 h. Bronchial secretions (BS) were collected by fibreoptic bronchoscopy at the same sampling times (except for 0 and 0.5 h) in three groups of 8 patients. Meropenem was measured by bioassay using E. coli ATCC 39118 as the test-organism. The results showed that meropenem had reached a high plasma concentration at the first sampling time (59.8 mg.l-1) and then the plasma level decreased rapidly to 10.6 mg.l-1 and 2.7 mg.l-1 at 2 and 3 h respectively. The highest concentration achieved in bronchial secretion was 0.53 mg.l-1 in the third hour, ie 20% of the serum level. The data indicate significant penetration of meropenem into bronchial secretions and achievement of a local level sufficiently high to eradicate most respiratory pathogens.

Adolescent↗

PubMedDate not supplied

Meropenem monotherapy versus cefotaxime plus metronidazole combination treatment for serious intra-abdominal infections.

In an open, randomised, multicentre trial, the efficacy and tolerability of empirical meropenem monotherapy (1 g intravenously every 8 hours) and cefotaxime (2 g every 8 hours) plus metronidazole (0.5 g intravenously every 8 hours) for 5 to 10 days was compared in 94 patients with serious intra-abdominal infection who required surgery. Eighty-three patients had an evaluable clinical response. Significantly more patients in the meropenem group had a satisfactory clinical response at the end of treatment (41/43 [95.3%] vs 30/40 [75.0%]; p = 0.008). The bacteriological response was also higher in the meropenem group (31/33 vs 26/32). In the bacteriologically evaluable population, a satisfactory clinical response was observed in 31/33 of those who received meropenem compared to 24/32 of the cefotaxime/metronidazole recipients (p = 0.03). Empirical meropenem monotherapy should prove a useful alternative to the currently standard combination treatment for serious intraabdominal infections.

Adult↗

PubMed1993

Meropenem versus imipenem/cilastatin in the treatment of intraabdominal infections requiring surgery.

In a prospective randomized study meropenem was compared with imipenem/cilastatin in the treatment of 62 patients with intraabdominal infections requiring surgery. The patients were suffering from diffuse or local peritonitis of moderate severity complicating in most cases gangrenous appendicitis, stomach perforation or gallbladder disease. There were 30 patients in the meropenem group and 32 patients in the imipenem/cilastatin group. Both antibiotic regimens were given intravenously at a dosage of 1 g every 8 h for a mean duration of 7.7 days in the meropenem group versus 8.6 days in the imipenem/cilastatin group. Fifty-nine aerobic strains and 15 anaerobic strains were isolated from cultures of pus taken intraoperatively, the meropenem MICs ranging from < or = 0.25 to 2 micrograms/ml. At follow-up at least one month after treatment the outcome was considered successful in all of 27 evaluable patients given meropenem and in all of 29 evaluable patients given imipenem/cilastatin. Both antibiotic regimens were well tolerated.

Adult↗

PubMed1995

Pharmacodynamic effects of meropenem on gram-negative bacteria.

The in vitro initial killing and post-antibiotic effect (PAE) of meropenem on five gram-negative reference strains were evaluated by bioluminescence assay of bacterial adenosine triphosphate (ATP) and viable count. Morphology studies were performed in parallel. Meropenem showed concentration-dependent long (2-5 h) PAEs on Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Serratia marcescens when assayed by bioluminescence and induced spheroplasts at almost all concentrations. The bioluminescence PAEs reached a maximum response at 4 x MIC. These PAEs of meropenem on Escherichia coli, Klebsiella pneumoniae and Serratia marcescens were longer than corresponding PAEs of imipenem shown in previous studies. The higher affinity of meropenem than imipenem for PBP 3 might explain the longer PAEs obtained with meropenem. However, there was only a very short PAE, no PAE or even a negative PAE when viable count was used as the initial value for the PAE calculation. A strong initial decrease in viability but a less pronounced change in intracellular ATP was registered. Since this initial change in cell numbers is the initial value for the PAE calculation, the length of PAE was highly method dependent. In summary, a strong initial killing and no PAE were shown using viable count as the initial value for the PAE calculation, but a weak initial killing and long PAEs were shown when bioluminescence was used throughout the experiments.

Gram-Negative Bacteria↗

PubMed2004

Meropenem therapy failure in Listeria monocytogenes infection.

Listeria monocytogenes is highly susceptible to meropenem in vitro, but data on the efficacy of meropenem in clinical cases of listeriosis are scarce. Described here is the case of a child with aplastic anemia who acquired nosocomial listeriosis and failed to respond to initial meropenem therapy. Resolution of fever was not noted after 5 days of therapy with meropenem and, more importantly, clinical worsening was observed during this period. The patient began to improve after ampicillin was introduced to the therapeutic regimen. In total, meropenem was administered for 15 days and ampicillin for 10 days.

Ampicillin↗

PubMedDate not supplied

Release of teichoic and lipoteichoic acids from 30 different strains of Streptococcus pneumoniae during exposure to ceftriaxone, meropenem, quinupristin/dalfopristin, rifampicin and trovafloxacin.

The release of teichoic acids (TA) and lipoteichoic acids (LTA) from 30 different strains of Streptococcus pneumoniae during exposure to ceftriaxone, meropenem, quinupristin/dalfopristin, rifampicin and trovafloxacin at concentrations of 10 micrograms/ml and of the respective MIC was determined by an enzyme immunoassay. At 10 micrograms/ml the most rapid and intense release was detected during treatment with the beta-lactam antibiotics ceftriaxone and meropenem, the lowest release was seen with rifampicin and quinupristin/dalfopristin. Trovafloxacin delayed the release of TA/LTA. The maximum concentrations of TA/LTA, however, during trovafloxacin treatment were almost as high as those during exposure to ceftriaxone and meropenem. During exposure to the MIC, ceftriaxone, meropenem, rifampicin and trovafloxacin released significantly higher amounts of TA/LTA than during exposure to 10 micrograms/ml (p < 0.01). Only quinupristin/dalfopristin released small amounts of TA/LTA at the low and high concentration. In conclusion, at high concentrations antibiotics that do not affect the bacterial cell wall released less pro-inflammatory compounds from S. pneumoniae than ceftriaxone and meropenem. This may be of value in the treatment of meningitis and sepsis.

Animals↗

PubMed2005

In vitro synergy test of meropenem and sulbactam against clinical isolates of Acinetobacter baumannii.

Meropenem and imipenem are often the drugs of choice for the treatment of infections due to multidrug-resistant Acinetobacter baumannii. The present study aimed at evaluating the interaction between meropenem and sulbactam through microdilution and checkerboard methods against 48 clinical isolates of A. baumannii collected from Brazilian hospitals. All the isolates presented elevated minimum inhibitory concentration (>or=2 microg/mL) to either meropenem or sulbactam. The checkerboard method with the combination of meropenem and sulbactam demonstrated 29.2% (14/48) synergism, 47.9% (23/48) partial synergism, 10.5% (5/48) additive, 6.2% (3/48) indifference, and 6.2% (3/48) antagonism (SigmaFIC(min)=0.09 and SigmaFIC(max)=8). Thus, combinations of meropenem and sulbactam may show synergism or partial synergism for most A. baumannii isolates. Further studies may help identify treatment options for patients with infections caused by these organisms, particularly with this combination, where both drugs have time-dependent activities and might be suitable for therapy optimization studies.

Acinetobacter baumannii↗

PubMed2005

Activity of meropenem and comparators against Pseudomonas aeruginosa and Acinetobacter spp. isolated in the MYSTIC Program, 2002-2004.

This study examines the susceptibilities of meropenem and other broad-spectrum antimicrobials tested against bacterial isolates collected from hospitalized patients during 2002-2004 from worldwide medical centers participating in the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program. The in vitro activity of meropenem and 5 comparator antimicrobial agents was assessed against Pseudomonas aeruginosa and Acinetobacter spp. Generally, the susceptibility of Australasian and North American isolates was higher than that of the European and South American isolates. The rank order of activity of the antimicrobial agents tested against a worldwide collection of P. aeruginosa was piperacillin/tazobactam (77.7% susceptible) > meropenem (75.4%) > ceftazidime (70.0%) > imipenem (69.7%) > gentamicin (66.1%) > ciprofloxacin (62.0%). Against a worldwide collection of Acinetobacter spp. meropenem (76.1% susceptible) was the most active compound followed by imipenem (74.7%) > gentamicin (51.9%) > ciprofloxacin (40.5%) > piperacillin/tazobactam (39.8%) > ceftazidime (38.1%). The carbapenems appear to be a valuable option for the treatment of serious nosocomial infections caused by P. aeruginosa or Acinetobacter spp. over a broad geographical region.

Acinetobacter↗

PubMed2004

Results from the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Programme: report of the 2001 data from 15 United States medical centres.

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Programme is an international surveillance network of more than 100 medical centres where meropenem is the primary therapeutic carbapenem. Institutions have been monitored since 1997 (1999 in United States (US)) using National Committee for Clinical Laboratory Standards (NCCLS) reference susceptibility methods to monitor in vitro activity of meropenem and selected other broad-spectrum antimicrobial agents. In 2001, a total of 2874 strains were processed from the 15 US medical centres. Molecular methods were associated with MIC methods as needed for defining epidemic spread of resistant strains. The meropenem MIC(90) values were 0.03 mg/l for Citrobacter spp., Escherichia coli and Klebsiella spp.; 0.06 mg/l for Proteus mirabilis and Serratia spp. and 0.12 mg/l for Enterobacter spp. This potency was 8-16-fold greater than that of imipenem and the meropenem spectrum of activity versus the Enterobacteriaceae was the broadest of all tested antimicrobial agents. Only piperacillin/tazobactam (MIC(9), 64 mg/l) and tobramycin (MIC(90), 4 mg/l) were active against more than 90.0% of Pseudomonas aeruginosa at the NCCLS susceptible breakpoint, and the carbapenems were the most active compounds against Acinetobacter spp. However, Acinetobacter spp. isolates were resistant to all of the antimicrobial agents tested and the molecular typing results suggested that they were epidemiologically related. Only ciprofloxacin and ceftazidime had significantly reduced activity against oxacillin-susceptible staphylococci (87.9-92.6% susceptible. These 2001 US MYSTIC Programme results demonstrated no significant decline in carbapenem activity or susceptibility rates compared with the previously monitored years (1999-2000). Most apparent were the decreasing susceptibility rates for ciprofloxacin and ceftazidime against staphylococci. Continued surveillance in these institutions appears warranted as sites of high potential emerging resistance risk.

Academic Medical Centers↗

PubMed2006

Stability and degradation kinetics of meropenem in powder for injection and reconstituted sample.

The stability of broad-spectrum antibiotic meropenem was studied in order to investigate the kinetics of degradation of this drug in powder for injection and reconstituted sample. Carbapenem was submitted to conditions of accelerated thermal decomposition. Degradation of meropenem was adequately modeled by specific equations for order rate kinetics. The analyses of the degraded samples were performed by high-performance liquid chromatographic (HPLC) method and microbiological assay. At higher temperatures, the decomposition reactions of meropenem in powder for injection could be described by first-order kinetics. The higher rate of degradation was observed in meropenem reconstituted in 0.9% sodium chloride, and the thermal decomposition obeyed also first-order kinetics. The results obtained confirm the reliability of chromatographic method for determining the kinetics run of meropenem in the presence of its degradation products. The present study reveals the thermal lability of the drug, especially as reconstituted sample. Thus, appropriate thermal protection is recommended during the storage and handling.

Anti-Bacterial Agents↗

PubMed2002

Determination and pharmacokinetic study of meropenem in rat bile using on-line microdialysis and liquid chromatography.

Meropenem is a carbapenem antibiotic with a wide spectrum of activity against both Gram-positive and Gram-negative bacteria. Because of its clinical efficacy, meropenem is an excellent choice for the treatment of serious infections in both adults and children. The knowledge of tissue concentrations of antibiotic in an infection site is valuable for the prediction of treatment outcome. To investigate the biliary disposition of meropenem, we utilized a minimally invasive sampling technique with a shunt linear microdialysis probe for continuous sampling in the biliary excretion studies. Analysis of meropenem in the dialysates was achieved using a LiChrosorb RP-18 column (Merck, 250 x 4.6 mm I.D.; particle size 5 microm) maintained at ambient temperature. The mobile phase was 50 mM monosodium phosphoric acid-methanol (80:20, v/v, pH 3.0). The UV detector wavelength was set at 298 nm. The area under the concentration-time curve and elimination half-lives of meropenem were about 6144 +/- 1494 min microg/ml and 61 +/- 17 min, respectively. This study represents a successful application of the microdialysis technique, which is an effective method for pharmacokinetic and biliary drug excretion studies.

Animals↗

PubMed2001

Comparative in vitro pharmacodynamics of imipenem and meropenem against ATCC strains of Escherichia coli, Staphylococcus aureus and Bacteroides fragilis.

We evaluated the pharmacodynamics of imipenem and meropenem, utilizing time-kill studies over a concentration/MIC (C/MIC) range of 0.0625-1024 for E. coli ATCC 35218 (EC) and S. aureus ATCC 29213 (SA) and from 0.125-512 for B. fragilis ATCC 25285 (BF). Area under the time-kill curves were converted to percent response (%R). AUCs were calculated from drug concentrations corrected for degradation and %R vs. C/MIC and AUC/MIC were fit to a sigmoidal Emax model. Emax was similar for both agents for all organisms. Meropenem was 4x more potent than imipenem against EC based on the MIC and required 7 and 13.5-fold lower AUCs to achieve E50 and E90, (50% and 90% of the maximal response, respectively) respectively, whereas imipenem was 8x more potent than meropenem against SA based on the MIC and required 8 and 13-fold lower AUCs to achieve E50 and E90, respectively. The C/MIC and AUC/MIC to achieve E50 and E90 with imipenem were 2- and fourfold higher, respectively than meropenem against EC. There was less than a twofold difference in C/MICs and AUC/MIC between imipenem and meropenem for both E50 and E90 against SA. Against BF, concentrations and AUCs at E50 were similar for both agents; however, imipenem required 4 to 6-fold higher concentrations and AUC to achieve E90. Although there are differences in the potency of these agents as assessed by the MIC or AUC vs. response, when normalized by the MIC and corrected for drug degradation, these agents displayed similar pharmacodynamic parameter-response relationships.

Bacteroides fragilis↗

PubMed2003

Antimicrobial spectrum of activity for meropenem and nine broad spectrum antimicrobials: report from the MYSTIC Program (2002) in North America.

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program provides susceptibility data for participating medical centers where carbapenems are utilized. The activity of meropenem and nine broad-spectrum antimicrobial agents were assessed against 3,047 bacterial isolates collected during 2002 from 16 North American sites. The overall rank order of susceptibility of the 10 antimicrobial agents tested against Gram-negative isolates was: meropenem (98%) > imipenem (97%) > cefepime (95%) > tobramycin (93%) > piperacillin/tazobactam = gentamicin (92%) > ceftazidime (91%) > ciprofloxacin (87%) > aztreonam (86%) > ceftriaxone (74%). These results and those from previous years, demonstrate the continued excellent potency and spectrum of activity for meropenem. The utility of meropenem against Pseudomonas aeruginosa isolates has increased steadily with a rise in percent susceptibility each year from 78.2% in 1999 to a present rate of 93.1% susceptible. Conversely, we showed the susceptibility for ciprofloxacin against these same P. aeruginosa isolates has decreased from 82.9 to 72.3% susceptible over four years. Many medical centers have observed a decreased activity of some aminoglycosides, cephalosporins and fluoroquinolones due to increases in rates of extended-spectrum beta-lactamases, Amp C and other resistance mechanisms. Carbapenem resistance remains rarely documented and these beta-lactamase-stable agents appear to be an alternative treatment option for serious community-acquired or nosocomial infections in high risk patient populations.

Anti-Bacterial Agents↗

PubMed2002

Pharmacokinetics and pharmacodynamics of meropenem in critically ill patients.

The pharmacokinetics and pharmacodynamics of meropenem were investigated in 14 critically ill patients with sepsis. Patients with creatinine clearance (CrCl) higher than 50 ml/min received 1 g meropenem three times daily (Group I) and patients with CrCl lower than 50 ml/min received 1 g meropenem twice daily (Group II). Meropenum concentrations in plasma were determined by high performance liquid chromatography with UV detection. The pharmacokinetic parameters differed between the two groups as follows, Group I, maximal concentration 56.3 +/- 19.1 microg/ml; trough concentration 3.3 +/- 2.5 microg/ml; elimination half life 2.5 +/- 1.2 h; clearance (Cl) 155.8 +/- 40.6 ml/min; MRT 2.2 +/- 0.4 h; steady state volume of distribution (V(ss)) 21.7 +/- 5.7 l, and AUC(-8) 119.4 +/- 32.6 microg/ml h. Group II, maximal concentration 71.1 +/- 5.1 microg/ml; trough concentration 3.4 +/- 1.8 microg/ml; elimination half life 3.9 +/- 1.6 h; Cl 77.7 +/- 15.8 ml/min; MRT 3.5 +/- 0.6 h; V(ss), 17.1 +/- 2.1 l, and AUC(0-12) 230.2 +/- 43.3 microg/ml h. The most frequently isolated bacteria from blood and wound infections were Acinetobacter baumanii, Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia coli; their meropenem minimal inhibitory concentrations (MICs) ranged from 0.064 to 3.0 mg/l. In most cases the pharmacodynamic parameters, measured as T>MIC index, were higher than 75%. In both groups, patients with susceptible pathogens (MIC<1 mg/l) had meropenem plasma levels which exceeded the MIC for the whole dosing interval. When pathogens were highly resistant (A. baumanii or P. aeruginosa) the T>MIC indices were lower.

Aged↗