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PubMed1998

Antibiotic-induced release of endotoxin: in-vitro comparison of meropenem and other antibiotics.

The influence of meropenem, a new carbapenem antibiotic, on cell morphology and in-vitro lipopolysaccharide (LPS) release from Escherichia coli was compared with that of imipenem, ceftazidime, tobramycin and ciprofloxacin. Free and cell-associated LPS was quantified by means of a capture ELISA method based on the recognition of E. coli LPS by monoclonal antibodies. Microscopically, meropenem was found to induce spheroplast formation similar to that seen with imipenem, while ceftazidime and ciprofloxacin induced filament formation. Free and cell-associated LPS levels were low in the presence of meropenem, imipenem, ciprofloxacin and tobramycin, but high in the presence of ceftazidime. Reduced endotoxin release appears to be a common property of carbapenem antibiotics. Morphological changes in bacteria in the presence of antibiotics do not predict their LPS-liberating effect since ciprofloxacin induced low levels of LPS despite causing filament formation.

Anti-Bacterial Agents↗

PubMed2000

Concentrations of single-dose meropenem (1 g iv) in bronchoalveolar lavage and epithelial lining fluid.

The concentrations of meropenem were measured in plasma, bronchoalveolar lavage (BAL) and epithelial lining fluid (ELF) 0.5-8 h after the administration of a single 1 g iv dose of meropenem. Thirty-five patients undergoing bronchoscopy were studied. Mean concentrations in plasma, BAL and ELF, respectively, measured by high performance liquid chromatography, were as follows: 0.5 h: 25. 96, 0.14, 5.04 mg/L; 1 h: 14.98, 0.09, 7.07 mg/L; 2 h: 12.01, 0.06, 3.86 mg/L; 4 h: 2.51, 0.04, 2.20 mg/L; 6 h: 0.57, 0, 0.59 mg/L; 8 h: 0.29, 0, 0 mg/L. Throughout the 2 h following infusion, concentrations in ELF exceeded the MIC90 for all nosocomial and community-acquired respiratory pathogens, including Pseudomonas aeruginosa (3.05 mg/L), Haemophilus influenzae (0.16 mg/L) and penicillin-resistant Streptococcus pneumoniae (0.86 mg/L). These results support the clinical efficacy of meropenem in the treatment of a wide range of pulmonary infections.

Adult↗

PubMed2000

Combined effects of meropenem and aminoglycosides on Pseudomonas aeruginosa in vitro.

To investigate combinations of antibiotics against Pseudomonas aeruginosa, the in vitro effects of combinations of meropenem with each of three aminoglycosides, arbekacin, amikacin and netilmicin, were evaluated using an agar dilution chequerboard technique. The combinations of meropenem and aminoglycosides were effective against almost all P. aeruginosa strains tested, which included meropenem-resistant strains. Increased synergic effects were observed in combinations that included arbekacin or amikacin. None of the combinations had an antagonistic effect. Most of the synergic and additive effects were achieved at clinically relevant concentrations.

Aminoglycosides↗

PubMed2002

Bactericidal activity of levofloxacin, gatifloxacin, penicillin, meropenem and rokitamycin against Bacillus anthracis clinical isolates.

This study aimed to evaluate the bactericidal rates of levofloxacin, gatifloxacin, penicillin, meropenem and rokitamycin against seven isolates of Bacillus anthracis clinically isolated between 1960 and 1970. After determination of MIC and MBC, time-kill experiments were carried out. Antimicrobial activity was evaluated at concentrations equal to 1 x, 2 x, 4 x and 8 x MIC after 0, 3, 6, 12 and 24 h of incubation with the drugs. Bactericidal activity was defined as a decrease in bacterial count of at least 3 log10. All the isolates were susceptible to all the antibiotics, by considering the antistaphylococcal breakpoints. Levofloxacin was bactericidal at 1 x MIC after 24 h and at 4 x MIC after 12 h, and gatifloxacin was bactericidal at 2 x MIC after 24 h and at 8 x MIC after 12 h. Meropenem, rokitamycin and penicillin also showed bactericidal activity at concentrations of 4 x and 8 x MIC, respectively, but only after 24 h incubation; after the same time, meropenem and rokitamycin showed a more marked killing than penicillin at 2 x MIC.

Anthrax↗

PubMed2026

Evaluation of sequential phage-antibiotic therapy reveals enhanced biofilm control with meropenem and colistin in clinical MDR hypervirulent Klebsiella pneumoniae strain.

AIMS: The convergence of multidrug resistance and hypervirulence in Klebsiella pneumoniae (MDR-HvKp) has narrowed treatment options. Despite growing interest in phage-antibiotic synergy, this study evaluates the underexplored combinatorial effects of phage and antibiotics, including drug-specific interactions and sequence dependency, against the biofilm-forming MDR-HvKp clinical strain. METHODS AND RESULTS: A T5-like Klebsiella bacteriophage, Round, within the genus Webervirus, was therapeutically and genomically characterized. A biofilm-forming clinical strain, Kleb_134, was used to evaluate in vitro phage-antibiotic interactions with meropenem, colistin, and tigecycline in planktonic and biofilm models.In planktonic assays, phage combinations with meropenem and colistin resulted in a multi-log CFU reduction compared to monotherapies, whereas reduced efficacy was observed with tigecycline. In biofilm assays, pre-phage treatment followed by antibiotic exposure demonstrated the strongest biofilm reduction. Drug-specific and sequence-dependent effects were evident. Meropenem-phage combinations reduced biofilm biomass by 2.85-fold (high phage titre) and 3.8-fold (low phage titre), while colistin-phage combinations achieved reductions of 8.4-fold (high phage titre) and 2.8-fold (low phage titre). CONCLUSIONS: Sequential phage-antibiotic treatment was effective against MDR-HvKp biofilms, with pre-phage exposure enhancing antibiotic access through biofilm disruption. The bacteriostatic nature of tigecycline reduced efficacy by affecting phage replication. These findings highlight the importance of treatment sequence and antibiotic selection, and extend existing knowledge in optimizing therapeutic outcomes in MDR-HvKp infections.

Biofilms↗

PubMed2006

Effectiveness and nephrotoxicity of colistin monotherapy vs. colistin-meropenem combination therapy for multidrug-resistant Gram-negative bacterial infections.

A retrospective cohort study evaluated the effectiveness and nephrotoxicity of intravenous colistin monotherapy vs. colistin-meropenem combination therapy for patients with multidrug-resistant Gram-negative bacterial infections. Fourteen patients received intravenous colistin monotherapy and 57 received colistin-meropenem. No significant differences were found concerning clinical response of the infection (12/14 (85.7%) vs. 39/57 (68.4%), p 0.32) and development of nephrotoxicity (0/14 (0%) vs. 4/57 (7%), p 0.58). A favourable association was revealed between survival and treatment with colistin monotherapy compared to colistin-meropenem (0/14 (0%) vs. 21/57 (36.8%) deaths, p 0.007), even after adjusting for the variables for which significant differences were found.

Acute Kidney Injury↗

PubMed1990

Meropenem pharmacokinetics and penetration into an inflammatory exudate.

The pharmacokinetics and penetration into a cantharidine-induced inflammatory exudate of meropenem was studied in six volunteers following a single 1-g intravenous dose. Concentrations in plasma, urine, and the inflammatory exudate were determined by a microbiological assay. The mean elimination half-life of meropenem in plasma was 1.1 h, with the concentration in plasma declining from a mean of 23.6 micrograms/ml at 1 h to 0.7 micrograms/ml at 6 h. The inflammatory fluid penetration was rapid (time to maximum concentration of drug in serum, 0.75 h), and the penetration was 111%. The recovery of meropenem in urine at 24 h was 65.4% of the administered dose.

Adult↗

PubMed1991

Activity of a new carbapenem antibiotic, meropenem, against Haemophilus influenzae strains with beta-lactamase- and non-enzyme-mediated resistance to ampicillin.

Meropenem was 8- to 32-fold more active (MIC for 90% of strains = 0.125 micrograms/ml) than imipenem against a collection of Haemophilus influenzae strains characterized as either susceptible to ampicillin or resistant to that agent by virtue of beta-lactamase or nonenzymatic mechanisms. MBCs and kinetic kill curve tests showed that meropenem (as well as imipenem, several cephalosporins, and amoxicillin-clavulanate) was bactericidal against all strains at or within four times the respective MICs. Thus, meropenem demonstrated greater inhibitory activity than imipenem and activity comparable to that of cefotaxime against these selected strains.

Ampicillin Resistance↗

PubMed1994

Postantibiotic effect of meropenem on members of the family Enterobacteriaceae determined by five methods.

The postantibiotic effect (PAE) of meropenem was determined for 11 strains, both clinical isolates and reference strains of members of the family Enterobacteriaceae. The study compares PAE results obtained by five methods used to monitor bacterial regrowth, including viable counting, alone and in combination with impedance; bioluminescence, alone and in combination with impedance; and a morphological technique. After exposure of the test organisms to meropenem (0.1 x to 100 x MIC) for 2 h, concentration-dependent differences in counts by bioluminescence and viable counts were observed, the latter always being lower. The differences varied with the test organism. For example, after exposure of Providentia stuartii NCTC 10318 to 0.1 x MIC, the counts were 5.5 x 10(5) and 2.0 x 10(5) whereas after exposure of Citrobacter freundii MR76 to 0.1 x MIC of meropenem the counts were 2.3 x 10(6) and 6.8 x 10(3) by bioluminescence and viable counting, respectively. The discrepancies were probably due to the relative inability of the viable counting procedure to detect fragile aberrant morphologies and resulted in differences in the calculated PAE values. With methods which do not detect fragile morphologies, the PAE may be underestimated. A general trend was observed for the order of magnitude of the PAEs by the following methods (in order of decreasing magnitude of PAE): (i) morphological technique, (ii) bioluminescence technique alone, (iii) bioluminescence in combination with impedance, (iv) viable counting in combination with impedance, and (v) viable counting alone. It is our opinion that of the methods examined in this study, bioluminescence in combination with impedance best reflects the true values for PAEs, and these results were examined more closely.

Bacteriological Techniques↗

PubMed1995

Sequential, single-dose pharmacokinetic evaluation of meropenem in hospitalized infants and children.

Meropenem is a new carbapenem antibiotic which possesses a broad spectrum of antibacterial activity against many of the pathogens responsible for pediatric bacterial infections. In order to define meropenem dosing guidelines for children, an escalating, single-dose, pharmacokinetic study at 10, 20, and 40 mg/kg of body weight was performed. A total of 73 infants and children in four age groups were enrolled in the study: 2 to 5 months, 6 to 23 months, 2 to 5 years, and 6 to 12 years. The first patients enrolled were those in the oldest age group, who received the lowest dose. Subsequent enrollment was determined by decreasing age and increasing dose. Complete studies were performed on 63 patients. No age- or dose-dependent effects on pharmacokinetic parameter estimates were noted. Mean pharmacokinetic parameter estimates were as follows: half-life, 1.13 +/- 0.15 h; volume of distribution at steady state, 0.43 +/- 0.06 liters/kg; mean residence time, 1.57 +/- 0.11 h; clearance, 5.63 +/- 0.75 ml/min/kg; and renal clearance, 2.53 +/- 0.50 ml/min/liters kg. Approximately 55% of the administered dose was recovered as unchanged drug in the urine during the 12 h after dosing. No significant side effects were reported in any patients. By using the derived pharmacokinetic parameter estimates, a dose of 20 mg/kg given every 8 h will maintain plasma meropenem concentrations above the MIC that inhibits 90% of strains tested for virtually all potentially susceptible bacterial pathogens.

Aging↗

PubMed1996

Monotherapy with meropenem versus combination therapy with ceftazidime plus amikacin as empiric therapy for fever in granulocytopenic patients with cancer. The International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer and the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto Infection Program.

Combinations of beta-lactams plus aminoglycosides have been standard therapy for suspected infections in granulocytopenic cancer patients, especially those with profound long-lasting granulocytopenia. With the advent of new broad-spectrum bactericidal antibiotics such as extended-spectrum cephalosporins or carbapenems, the need to combine beta-lactams with aminoglycosides became more controversial. The objective of this prospective randomized multicenter study was to compare the efficacy, safety, and tolerance of meropenem monotherapy with those of the combination of ceftazidime plus amikacin for the empirical treatment of fever in granulocytopenic cancer patients. Of 1,034 randomized patients, 958 were assessable in the intent-to-treat analysis for response to antibacterial therapy, including 483 in the meropenem group and 475 in the ceftazidime-plus-amikacin group. The median durations of neutropenia were 16 and 17 days, respectively. A successful outcome was reported in 270 of 483 (56%) patients treated with monotherapy compared with 245 of 475 (52%) patients treated with the combination group (P = 0.20). The success rates in the monotherapy group and the combination group were similar by type of infection (single gram-negative bacteremia, single gram-positive bacteremia, clinically documented infection, and possible infection). The occurrence of further infections assessed in patients for whom the allocated regimen was not modified did not differ between the two groups (12% in both groups). Mortality due to the presenting infection or further infection was relatively low (8 patients treated with the monotherapy compared with 13 patients treated with the combination). A total of 1,027 patients were evaluable for adverse events; the proportion of those who developed adverse effects was similar between the two groups (29% in both groups), and only 19 (4%) patients in the monotherapy group and 31 (6%) in the combination group experienced an adverse event related or probably related to the study drug. Allergic reactions were the only reason for stopping the protocol antibiotic(s) (3 and 5 patients, respectively). This study confirms that monotherapy with meropenem is as effective as the combination of ceftazidime plus amikacin for the empiric treatment of fever in persistently granulocytopenic cancer patients, and both regimens were well tolerated.

Adolescent↗

PubMed1997

Relationships between antimicrobial effect and area under the concentration-time curve as a basis for comparison of modes of antibiotic administration: meropenem bolus injections versus continuous infusions.

In comparative studies of different modes of administration (MAs) simulated in in vitro dynamic models, only one dose of antibiotic is usually mimicked. Such an experimental design can provide a prediction of the antimicrobial effect (AME) of a given combination of drug, clinical isolate, and infection site, but may be inappropriate for accurate comparison of MAs. An alternative design providing comparison of different MAs with various antibiotic doses in a wide range and with evaluation of the respective relationships between AME and the AUC was proposed and examined. Two series of meropenem pharmacokinetic profiles, i.e., monoexponentially decreasing concentrations (bolus doses) and constant concentrations (6-h continuous infusion), were in vitro simulated. The simulated initial concentrations (Co[from 0.62 to 48 micrograms/ml]) and steady-state concentrations (Css[from 0.016 to 8 micrograms/ml]) were chosen to provide similar AUC for 0 to 6 h (AUC0-6) ranges for both MAs (from 0.070 to 50.0 micrograms.h/ml and from 0.09 to 48.0 micrograms.h/ml, respectively). The AME of meropenem on Staphylococcus aureus ATCC 25923 (MIC, 0.06 micrograms/ml) was determined at each time (t) point as a difference (E) between the logarithms of viable counts (N) in the control cultures without antibiotic (NC) and in cultures exposed to antibiotics (NA). Time courses of E observed at different Co of Css levels were compared in terms of the areas under the E-t curves (ABBCt). The finite values of the ABBCt observed by the end of the 6 -h observation period, which are equivalent to the area between bacterial count-time curves observed in the absence and presence of antibiotic (ABBC), were plotted versus the respective AUCs produced by each of the MAs. The ABBC versus AUC curves had a similar pattern: a plateau achieved at high AUCs followed by a steep rise in ABBC at relatively low AUCs was inherent in both of the MAs. The superiority of bolus dosing over the infusions could be documented only for meropenem concentrations below the MIC. At higher Co or Css (i.e., at an AUC of > or = 0.4 micrograms.h/ml), the ABBC versus AUC curves plotted for each of the MAs could practically be superimposed. On the whole, both MAs appeared to be equiefficient in terms of the ABBC. These results suggest that AUC analysis of the AME may be a useful tool for comparing different MAs. Such comparative studies should be designed in a manner that provides the use of similar AUC ranges, since the AUC may be considered as a common pharmacokinetic denominator in comparing one MA or dosing regimen to another.

Area Under Curve↗

PubMed2001

In vitro activities of linezolid, meropenem, and quinupristin-dalfopristin against group C and G streptococci, including vancomycin-tolerant isolates.

The in vitro activities of meropenem, linezolid, quinupristin-dalfopristin, vancomycin, and penicillin against 130 clinical isolates of group C and G streptococci, including vancomycin-tolerant isolates, were evaluated. Meropenem, linezolid, quinupristin-dalfopristin, vancomycin, and penicillin MICs at which 90% of the isolates were inhibited were 0.06, 2.0, 0.25, 0.5, and < or = 0.016 microg/ml, respectively. Meropenem, linezolid, quinupristin-dalfopristin, and penicillin were active against group C and G streptococci, including vancomycin-resistant strains.

Acetamides↗

PubMed2006

Susceptibilities of Propionibacterium acnes ophthalmic isolates to ertapenem, meropenem, and cefepime.

We investigated the in vitro susceptibilities of 23 Propionibacterium acnes ophthalmic isolates to ertapenem, meropenem, and cefepime by utilizing the Etest. The MICs ranged from 0.094 microg/ml to 0.75 microg/ml, 0.094 microg/ml to 1.5 microg/ml, and 1 microg/ml to 12 microg/ml for ertapenem, meropenem, and cefepime, respectively. Based on our excellent in vitro carbapenem susceptibility results, in vivo studies using ertapenem and meropenem in a rabbit model of P. acnes endophthalmitis are warranted.

Animals↗

PubMedDate not supplied

Time-kill studies of antimicrobial combinations including cefotaxime, ceftriaxone, vancomycin and meropenem against cephalosporin-resistant Streptococcus pneumoniae.

BACKGROUND: Resistance of Streptococcus pneumoniae to penicillin is now widespread and rapidly increasing all over the world. This has led to the critical need for alternative antimicrobial therapy. METHODS: To assess the activities of antimicrobial combinations, including cefotaxime, ceftriaxone, vancomycin and meropenem, time-kill studies were conducted against five strains of penicillin- and cephalosporin-resistant S. pneumoniae at clinically achievable antimicrobial concentrations in cerebrospinal fluid. RESULTS: Combinations of an extended-spectrum cephalosporin with vancomycin were not synergistic. Meropenem had a comparable bactericidal activity to those combinations, and its killing activity was not affected by the addition of cefotaxime, ceftriaxone or vancomycin. CONCLUSIONS: It is suggested that meropenem could be an effective alternative for the treatment of penicillin- and cephalosporin-resistant pneumococcal meningitis. However, more clinical data are required before it can be recommended as an effective antimicrobial agent for such cases.

Anti-Bacterial Agents↗

PubMedDate not supplied

Pharmacokinetics of high-dose meropenem in adult cystic fibrosis patients.

Because patients with cystic fibrosis (CF) have pulmonary exacerbations secondary to multi-antibiotic-resistant Gram-negative bacilli, antibiotics, like meropenem, are often utilized. We studied the pharmacokinetics of meropenem (2 g i.v. administered every 8 h in clinically stable CF patients to determine if the recommended maximum doses could sustain adequate concentrations during the dosing interval. These pharmacokinetic data were similar to those obtained in non-CF populations. Using this regimen, concentrations of meropenem exceed the susceptibility breakpoint (4 microg/ml) for 50% of the dosing interval, and therefore provide optimization of the pharmacodynamic profile of the compound.

Adolescent↗

PubMed2003

In vitro activity of combination therapy with cefepime, piperacillin-tazobactam, or meropenem with ciprofloxacin against multidrug-resistant Pseudomonas aeruginosa strains.

The prevalence of multidrug-resistant Pseudomonas aeruginosa strains has been increasing every year, and treatment with various antimicrobial combinations has been offered alternatively in the clinical practice. The aim of this study was to evaluate the in vitro effects of combinations of meropenem, cefepime, or piperacillin-tazobactam with ciprofloxacin against multidrug-resistant P. aeruginosa strains by the time-kill method. The results show that both the combination of two beta lactams with ciprofloxacin and three beta lactams with ciprofloxacin against 4 of 5 multidrug-resistant P. aeruginosa strains has no effect in vitro. The combination of one beta lactam (meropenem, cefepime, piperacillin-tazobactam) with ciprofloxacin has a synergistic effect against one strain of multidrug-resistant P. aeruginosa that is ciprofloxacin susceptible and resistant to meropenem, cefepime, and piperacillin-tazobactam. None of the combinations had an antagonistic effect against these multidrug-resistant strains.

Anti-Bacterial Agents↗

PubMed2005

In vitro susceptibility to meropenem and other antimicrobial agents among gram-negative bacilli isolated from hospitalized patients in central India.

BACKGROUND: Growing multiple drug resistance among gram-negative bacilli among hospitalized patients is a serious therapeutic problem, and the aim of the study was to assess the situation in our hospital. METHODS: Antimicrobial susceptibility testing with the disk method was carried out on 1,533 isolates of gram-negative bacilli from urine, pus, body fluid and blood from hospitalized patients. RESULTS: Seventeen percent of isolates were susceptible only to meropenem and either to piperacillin + tazobactam, to cefoperazone + sulbactam or to both. Eleven percent of isolates were susceptible only to meropenem and 6% were resistant to all antimicrobial agents including meropenem. CONCLUSION: Growing multiple drug resistance among gram-negative bacilli in hospital practice demands a rigid antibiotic policy and strict infection control measures.

Anti-Bacterial Agents↗