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PubMedDate not supplied

Comparative stability of meropenem against beta-lactamases from Bacteroides spp.

The activity of meropenem was similar to that of imipenem against 88 clinical isolates of Bacteroides spp., including 28 non-fragilis strains. Four of the isolates were able to hydrolyse cephamycins or penems. Investigation of beta-lactamases from these strains and 10 laboratory stock culture Bacteroides showed that meropenem and imipenem were degraded at a similar rate by cell-free preparations of these enzymes. Some of these strains were able to completely hydrolyse the carbapenems within 2 h. Despite this rapid hydrolysis, MICs of meropenem and imipenem for some of the strains remained within the susceptible range as judged by agar dilution titration.

Anti-Bacterial Agents↗

PubMed1992

In vitro activity of meropenem and other agents against oral bacteria.

The susceptibility of 106 oral bacteria to meropenem, a new carbapenem antimicrobial, penicillin V, tetracycline and metronidazole was assessed by an agar dilution method. Meropenem was the most effective of the antimicrobials, with all strains tested being inhibited at < or = 1 mg/l. A number of strains were resistant to penicillin V, particularly Bacteroides gracilis, and tetracycline resistance was widespread amongst the streptococci tested. Metronidazole was extremely effective against obligate anaerobes. The results of this study suggest that meropenem has potential for use in the treatment of serious head and neck infections.

Anti-Bacterial Agents↗

PubMed2005

Meropenem and continuous renal replacement therapy: in vitro permeability of 2 continuous renal replacement therapy membranes and influence of patient renal function on the pharmacokinetics in critically ill patients.

The pharmacokinetics of meropenem were characterized in 20 patients with different degrees of renal function who underwent continuous renal replacement therapy. Previously, no differences were detected in vitro in the removal of meropenem by continuous venovenous hemofiltration or continuous venovenous hemodialysis or when AN69 or polysulfone membranes were compared. In patients, no significant differences in the sieving coefficient or the saturation coefficient with the renal function were found, and the mean sieving coefficient/saturation coefficient value (0.80 +/- 0.12) was similar to the unbound fraction (0.79 +/- 0.08). An increase in total clearance and a decrease in elimination half-life were observed to the extent that the patient's creatinine clearance was higher. Likewise, the contribution of continuous renal replacement therapy to total clearance diminished in patients with less renal impairment. The results suggest that the renal function of the patient may influence meropenem pharmacokinetics during continuous renal replacement therapy. The lower trough plasma levels observed in nonrenal patients would not lead to adequate time during which serum drug concentrations are above the minimum inhibitory concentration values in many infections.

Acrylic Resins↗

PubMed2005

Seizure worsening caused by decreased serum valproate during meropenem therapy.

Serum concentrations of valproate were reduced and seizures were exacerbated by concomitant meropenem therapy in a child with a neurodegenerative disorder and epilepsy. In this patient, a rapid decline of valproate serum concentrations was observed on two occasions with meropenem antibiotic therapy. This event was the most likely cause of observed seizure exacerbation. Meropenem should be used with caution in patients treated with valproate owing to the drastic lowering of serum valproate concentration and the consequent risk of seizure worsening.

Anti-Bacterial Agents↗

PubMed1996

In vitro activity of meropenem against ciprofloxacin-resistant enterobacteriaceae and Pseudomonas aeruginosa.

The in-vitro susceptibilities of a total of 174 ciprofloxacin-resistant Enterobacteriaceae and Pseudomonas aeruginosa were determined. According to the BSAC and NCCLS breakpoints, meropenem, aztreonam, ceftibuten, ceftazidime, imipenem and cefotaxime were the most active (> 90%) antimicrobial agents tested against Enterobacteriaceae. Susceptibility of these strains to piperacillin/tazobactam, cefpodoxime and cefixime (84.96%) was higher than that to tobramycin, gentamicin and fosfomycin (50-75%). More than 90% of P. aeruginosa were susceptible to meropenem when both interpretative susceptibility breakpoint criteria were used. Piperacillin, piperacillin/tazobactam and ceftazidime were active against 50-75% of the same strains. Meropenem was the most active antimicrobial tested against all ciprofloxacin-resistant clinical isolates assayed.

Anti-Bacterial Agents↗

PubMed1998

Successful meropenem therapy of a brain abscess and meningitis arising from acute purulent otomastoiditis: case report.

We describe a case of a 25-year-old female with an acute left otomastoiditis, accompanied by a left temporal extradural abscess with moderate perifocal edema and meningitis. Intravenous meropenem (2 g 8-hourly) and intravenous methylprednisolone (40 mg once daily) were commenced empirically. Teicoplanin (400 mg once daily intravenously) was added after 5 days when culture results were available. Teicoplanin was discontinued on day 25 but meropenem and methylprednisolone were continued for a further 15 days, after which the abscess completely resolved without sequelae. No treatment-induced adverse effects or seizures were observed. Thus, in selected patients, antibacterials (in conjunction with a corticosteroid) may be successfully used without surgery to treat brain abscesses and in such circumstances meropenem is a useful option for empiric therapy.

Adult↗

PubMed2004

Meropenem monotherapy for the treatment of hospital-acquired pneumonia: results of a multicenter trial.

The efficacy and tolerability of meropenem as empirical treatment in patients with hospital-acquired pneumonia was determined in a prospective, open-label, non-randomized trial. Patients from 28 centers in the USA received meropenem 1 g every 8 h intravenously. Of 255 patients enrolled, 111 were evaluable for efficacy, including 60 patients with ventilator-associated pneumonia. At end of treatment 74% of patients had a satisfactory clinical response and 64% had this response at follow-up, which could last up to 28 days after treatment. In patients with ventilator-associated pneumonia, a satisfactory clinical response was observed in 68% at the end of treatment and 63% at follow-up. The overall satisfactory response rate for individual pretreatment pathogens ranged from 65% to 100%. This study demonstrates that meropenem monotherapy is effective and well tolerated for patients with hospital-acquired pneumonia, including a subgroup of patients with ventilator-associated pneumonia.

Adolescent↗

PubMed2000

Comparative cerebrospinal fluid diffusion of imipenem and meropenem in rats.

The main objective of this study was to compare the cerebrospinal fluid (CSF) diffusion of imipenem and meropenem at steady state, following intravenous infusions at various rates in rats. A preliminary experiment was conducted to estimate the elimination half-lives of these two carbapenem antibiotics, and then to evaluate the infusion duration necessary to reach steady state. CSF diffusion of imipenem was essentially linear over the wide range of infusion rates (66-1,320microg min(-1)) and corresponding steady-state plasma concentrations (11.7-443.0 microg mL(-1)). Conversely the CSF diffusion of meropenem was saturable, with a predicted maximum CSF concentration equal to 1.3 microg mL(-1). Extrapolation of these data to the clinical situation may not be possible since the rats had normal blood-brain and blood-CSF barriers whereas patients with diseases such as meningitis may not. However, it is suggested that the observed differences in the diffusion characteristics of imipenem and meropenem may be partly responsible for their differences in toxicity and efficacy at the central level.

Animals↗

PubMed1995

In vivo and in vitro study of several pharmacodynamic effects of meropenem.

Several pharmacodynamic parameters are being studied and applied to the design of dosage regimens. The thigh infection model in neutropenic mice has been used in this study to investigate the in vivo postantibiotic effect (PAE) of meropenem against S. aureus, E. coli and P. aeruginosa. The sub-minimum inhibitory concentration (sub-MIC) postantibiotic effect (PA SME) of 1/2, 1/4 and 1/8 x MIC was also determined in vitro on S. aureus and E. coli after pre-exposure of these microorganisms to 10 x MIC of meropenem. The in vitro PAE was also determined. In vivo killing curves using 2 different short dosage regimens were also studied to relate the lethal effect to the time that serum levels were above the MIC. No significant in vivo and in vitro PAEs were observed. The PA SMEs were higher for S. aureus than for E. coli. The 2 short dosage regimens, in vivo, were equally effective in killing S. aureus, but not E. coli. These results suggest that the pharmacodynamics of meropenem on Gram-negative strains may need further study to elucidate the mechanisms and characteristics of these parameters. On the other hand, we need to standardize a reliable in vitro method to monitor regrowth with a good correlation with the in vivo conditions.

Animals↗

PubMed1993

Studies on the structures of meropenem(SM-7338) and it's primary metabolite.

The structure and solution conformation of meropenem was examined by using 1H and 13C NMR spectroscopy and nuclear Overhauser enhancement experiments. Similar to the X-ray crystal structure, the close spacing of 1 beta-methyl substituent to the beta-lactam ring and the accessible conformation of C-2 side chain in relation to the carbapenem skeleton was confirmed. The structure of the primary metabolite of meropenem by dehydropeptidase-I was shown to be the beta-lactam ring-opened product by comparing the spectroscopic data with those of meropenem, and confirmed by the preparation and structural analysis of its crystalline derivative. This metabolite existed as a mixture of 1-pyrroline and 2-pyrroline isomers, and the coexistence of two isomers at equilibrium in aqueous solution was observed by NMR.

Animals↗

PubMed1999

[Efficacy of meropenem in the treatment of severe complicated urinary tract infections].

The clinical and bacteriological efficacies of meropenem in the treatment of 12 patients with urinary tract infection were studied. In 8 patients the drug was administered intravenously in a dose of 1 g every 8 hours and in 4 patients with the creatinine clearance below 50 ml/min it was administered in a dose of 1 g every 12 hours (the treatment course of 7 to 10 days). Meropenem was used in the monotherapy. Severe complicated urinary tract infections were mainly observed in the patients with long-term urolithiasis, subjected to repeated surgical interventions and isolating as a rule polyresistant strains of Pseudomonas aeruginosa and E.agglomerans as the pyelonephritis pathogens at a titre of 5 x 10(5)-5 x 10(8) microbial cells per 1 ml of the urine susceptible to meropenem in 80 to 96 per cent of the cases. The clinical efficacy of the drug was stated in all the patients while the bacteriological efficacy amounted to 88.9 per cent.

Adult↗

PubMed2000

[Activity of imipenem and meropenem against strains of Acinetobacter baumannii isolated from various Chilean hospitals].

The activity of two carbapenem compounds, imipenem and meropenem, against 447 strains of Acinetobacter baumannii isolated between 1990 and 1998 in different Chilean hospitals was determined. MIC ranges, MIC(50) and MIC(90), were determined by an agar dilution method. Similar antibacterial activities were observed for both antibacterials; however, a slight increase in the MIC(50) of imipenem and meropenem, and in the MIC(90) of meropenem was found among strains isolated from 1997-1998. Although A. baumannii remains susceptible to these antibiotics, the MIC(50) and MIC(90) have increased in recent years.

Acinetobacter↗

PubMed2005

[The comparison of optimized pharmacodynamic dosing strategy for meropenem using Monte Carlo simulation].

Monte Carlo simulation was enmloyed to determine pharmacodynamic target attainment rates for several meropenem dosage regimens against E. coli and P. aeruginosa populations. Percent Time above MIC (% T > MIC) exposures for several meropenem dosage regimens were simulated for 10,000 subjects. Variability in pharmacokinetic parameters and MIC distributions were derived from studies in healthy volunteers and the injection antibiotics include of Meropenem susceptibility test surveillance program. The probabilities of attaining bacteriostatic responses (30% T > MIC) and bactericidal responses (50% T > MIC) exposures were high for all dosage regimens against populations of E. coli. Against P. aeruginosa, the 1000 g 3.0 infusion q8 dosage regimen provided the hightest target attainment rates. Further study of these dosage recommendations in clinical trials is suggested.

Adult↗

PubMed2005

[Nationwide surveillance of parenteral antibiotics containing meropenem activities against clinically isolated strains in 2004].

The antibacterial activity of meropenem (MEPM) and other parenteral antibiotics against clinical isolates of 907 strains of Gram-positive bacteria, 1790 strains of Gram-negative bacteria, and 192 strains of anaerobic bacteria obtained from 30 medical institutions during 2004 was measured. The results were as follows; 1. MIC90 of MEPM for almost all of enterobacteriaceae and Haemophilus influenzae were 4-fold to 32-fold lower than those of other carbapenems. MEPM was more active than other carbapenem antibiotics against Gram-negative bacteria, especially against enterobacteriaceae and H. influenzae. MEPM were active against most of the species tested in Gram-positive and anaerobic bacteria, except for multi-drug resistant strains including methicillin-resistant Staphylococcus aureus. 2. As for Pseudomonas aeruginosa, imipenem (IPM) showed high cross-resistant rate againt meropenem-resistant P. aeruginosa (87.9%). MEPM showed low cross-resistant rate both againt IPM-resistant P. aeruginosa (49.2%) and ciprofloxacin-resistant P. aeruginosa (38.0%). 3. The proportion of extended-spectrum beta-lactamase (ESBL) strains was 3.1% (4 strains) in Escherichia coli, 8.0% (2 strains) in Citrobacter koseri, 2.5% (3 strains) in Klebsiella pneumoniae, 2.5% (2 strains) in Enterobacter cloacae, 0.9% (1 strains) in Serratia marcescens, and 2.2% (2 strains) in Proteus mirabilis. The proportion of metallo-beta-lactamase strains was 1.6% (5 strains) in P. aeruginosa. 4. Of all species tested, Peptostreptococcus spp. was the only species, which MIC90 of MEPM was more than 4-fold higher than that in our previous study using clinical isolates during 2002 (0.25 microg/ml --> 1 microg/ml). Therefore, there is almost no siginificant decrease in susceptibility of clinical isolates to meropenem. In conclusion, the results from this surveillance study suggest that MEPM retains its potent and broad antibacterial activity and therefore is a clinically useful carbapenem at present, 9 years after available for commercial use.

Anti-Infective Agents↗

PubMedDate not supplied

[Meropenem activity against staphylococci].

Meropenem is a new carbapenem with excellent activity against different Gram-negative and Gram-positive bacteria. Its good antibacterial activity is closely related to high hydrolysis resistance by bacterial beta-lactamases. The aim of this study was to evaluate antimicrobial activity of meropenem by comparison that of oxacillin, gentamicin, clarithromycin and ciprofloxacin against 458 staphylococci collected during 2004 period from healthy individuals. Minimum inhibitory concentrations were determined by agar dilution technique. Meropenem has an activity clearly superior to the other tested agents. Resistance rate is zero for all investigated strains.

Anti-Bacterial Agents↗

PubMed1995

The pharmacokinetics of meropenem.

Meropenem is a new carbapenem antibiotic which differs chemically from imipenem/cilastatin by having a 1-beta-methyl substitution, providing it with excellent intrinsic stability to human renal dehydropeptidase-I. In addition, an altered 2' side chain enhances its anti-pseudomonal activity. The drug has one identified metabolite, a beta-lactam ring-opened form which is devoid of microbiological activity, as would be expected. The parent compound displays linear pharmacokinetics over a dose range of 250 mg to 2 g. The terminal half-life is approximately 1 hour and the plasma clearance is approximately 15.5 L/h/70 kg. The plasma concentrations after a 1 g dose show a trough concentration (8 hours) of slightly greater than 0.25 mg/L. The renal route is the major clearance pathway for this drug and its metabolite, with renal clearance accounting for approximately 70% of the plasma clearance and there being approximately 70% of an administered dose recovered in the urine as intact parent compound over 12 hours. When combined with metabolite, over 90% of administered radiolabel is recovered in the urine over this 12 hour period. As expected, renal functional impairment alters the clearance of meropenem, but the alteration is predictable. Hepatic functional impairment does not alter drug disposition and no dosing alterations are required here. In summary, meropenem's disposition is similar to that seen for imipenem/cilastatin, except that no renal dehydropeptidase-I inhibitor is required. When evaluated against the background of its excellent profile of in vitro activity, it is clear that this is a drug of great promise which should be extensively evaluated in clinical trials of seriously ill patients with nosocomial infections.

Animals↗

PubMed1994

[In vitro activity of meropenem and seven other beta-lactam antibiotics against K.pneumoniae and enterobacteriaceae producing beta-lactamases with extended spectrum].

Meropenem is a broad antibacterial spectrum carbapenem with a good activity on betalactam resistant Gram-negative bacilli. 120 non repetitive strains isolated from clinical samples from 1989 to 1992 were selected: 60 K. pneumoniae, 7 E. coli, 2 E. aerogenes and 1 S. marcescens with extended spectrum betalactamases (23 CTX-1, 18 SHV-2, 5 SHV-3, 16 SHV-4, 4 SHV-5, 3 CTX-1 + SHV-4, 1 CAZ-1), 10 K. pneumoniae with broad spectrum TEM-1 enzyme, and 40 K. pneumoniae with only SHV-1 chromosomal betalactamase. Determination of Minimal inhibitory concentrations (MIC) was done by agar dilution method for meropenem and 7 other betalactams (amoxicillin + clavulanic acid 2 mg/l, piperacillin + tazobactam 4 mg/l, cefoxitin, cefotetan, cefotaxime, ceftazidime, imipenem). All antibiotics except amoxicillin + clavulanic acid are active against strains with constitutive penicillinase. For strains with TEM-1 penicillinase, cephamycins, third generation cephalosporins and carbapenems are active. For strains with different extended spectrum betalactamases only cephamycins and carbapenems are efficious. There is no difference according to the period of isolation: 1989-90 or 1991-92. Meropenem has the best in vitro activity (MIC50 = 0.03 mg/l) for all strains independently of the nature of betalactamase.

Anti-Bacterial Agents↗

PubMedDate not supplied

Meropenem, a new carbapenem antibiotic.

Meropenem is the second carbapenem antibiotic available in the United States. It has a broad spectrum of activity that includes moderate activity against gram-positive bacteria and excellent gram-negative aerobic and anaerobic activity. Meropenem has enhanced gram-negative activity relative to imipenem-cilastatin and often retains activity against strains resistant to third-generation cephalosporins and imipenem-cilastatin. The drug penetrates well into most body fluids and tissues, including cerebrospinal fluid. It is also stable against renal dehydropeptidase hydrolysis and does not require coadministration of a dehydropeptidase inhibitor. Meropenem showed excellent efficacy in clinical studies involving seriously ill patients with intraabdominal, central nervous system, lower respiratory tract, skin and soft tissue, urinary tract, and febrile neutropenic infections. It appears well tolerated and, relative to imipenem-cilastatin, may have reduced potential for causing seizures and other central nervous system toxicities. Although it has many favorable qualities and some potential advantages relative to other broad-spectrum agents, additional trials and clinical experience are necessary to define its optimal place in clinical practice.

Appendicitis↗