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PubMed2003

Deferoxamine and meropenem combination therapy in experimental acute pancreatitis.

INTRODUCTION: Recent data from the experimental clinical studies suggest that antibiotics having good penetration to pancreas may reduce mortality by preventing pancreatic infection, which is the most important prognostic factor in acute pancreatitis (AP). Deferoxamine is an active free oxygen radical scavenger, which has been shown to have a protective role in development of acute pancreatitis. AIM: To determine the effects of combination of deferoxamine and meropenem in acute necrotizing pancreatitis. METHODOLOGY: One hundred male Sprague-Dawley rats were randomly divided into 5 groups. All rats underwent laparotomy with cannulation of biliopancreatic duct. Group 1 received intraductal saline injection. Acute necrotizing pancreatitis was induced in group 2, 3, 4, and 5 by intraductal injection of 3% taurocholate. Group 1 (sham operated) and group 2 were injected with saline of 0.3 mL/kg intraperitoneally (i.p). Group 3 was injected with meropenem 60 mg/kg/d i.p, group 4 with deferoxamine 80 mg/kg/d s.c and group 5 with combination of these 2 agents at the same doses. While meropenem was started 2 hours later, all treatments were started immediately after the induction of pancreatitis. All rats were killed at the 48th hour of the treatment and blood and tissue samples were collected for amylase determinations, pathologic examinations, and culture. RESULTS: There was no difference in serum amylase levels between AP induced groups (P > 0.05). Pancreatic histology scores were significantly low in rats treated with deferoxamine (group 4), and combination regimen (group 5) (P < 0.001). Meropenem significantly reduced the incidence of pancreatic infection. Although combination of deferoxamine with meropenem showed better effects than meropenem alone in terms of pancreatic infection, the difference did not reach to statistical significance. CONCLUSIONS: Meropenem treatment reduces secondary pancreatic infections in acute pancreatitis. Treatment with deferoxamine and meropenem combination may be more beneficial than single therapies in reducing the severity of pancreatitis. Further studies investigating the effects of this combination on survival are needed.

Acute Disease↗

PubMed1995

Meropenem versus imipenem/cilastatin in the treatment of hospitalized patients with skin and soft tissue infections.

Meropenem is a new carbapenem antibiotic shown to resist degradation by renal dehydropeptidase I. In a multicenter, open-label, prospective trial, we compared the efficacy and safety of meropenem with imipenem/cilastatin in patients with skin and soft tissue infections. Patients received either 500 mg of meropenem every 8 hours (n = 184) or 500 mg of imipenem/cilastatin every 6 hours (n = 193), by intravenous infusion for an average of 6 to 7 days. Satisfactory clinical responses were achieved in 120 (98%) of 123 assessable meropenem-treated patients and in 120 (95%) of 126 assessable imipenem/cilastatin-treated patients. Satisfactory bacteriologic responses were achieved in 120 (98%) of 123 assessable meropenem-treated patients and in 120 (95%) of 126 assessable imipenem/cilastatin-treated patients. Satisfactory bacteriologic response rates were high as well: 94% with meropenem and 91% with imipenem/cilastatin. Between-group differences in satisfactory response rates were not significant (95% confidence interval, -2.29 to 6.93 [clinical]; -2.73 to 10.39 [bacteriologic]). Overall pathogen eradication rates (for aerobes and anaerobes) were slightly higher for meropenem. Elevated liver enzymes were the most frequent adverse events in each treatment group. Meropenem was well tolerated and as effective as imipenem/cilastatin in treatment of hospitalized patients with skin and soft tissue infections.

Abscess↗

PubMed1996

Serum bactericidal activities and comparative pharmacokinetics of meropenem and imipenem-cilastatin.

The pharmacokinetics and serum bactericidal activities (SBAs) of imipenem and meropenem were investigated in a randomized crossover study. Twelve healthy male volunteers received a constant 30-min infusion of either 1 g of imipenem plus 1 g of cilastatin or 1 g of meropenem. The concentrations of the drugs in serum and urine were determined by bioassay and high-pressure liquid chromatography. Pharmacokinetic parameters were based on an open two-compartment model and a noncompartmental technique. At the end of infusion, the mean concentrations of imipenem and meropenem measured in serum were 61.2 +/- 9.8 and 51.6 +/- 6.5 mg/liter, respectively; urinary recoveries were 48.6% +/- 8.2% and 60.0% +/- 6.5% of the dose in 12 h, respectively; and the areas under the concentration-time curve from time zero to infinity were 96.1 +/- 14.4 and 70.5 +/- 10.3 mg.h/liter, respectively (P < or = 0.02). Imipenem had a mean half-life of 66.7 +/- 10.4 min; that of meropenem was 64.4 +/- 6.9 min. The volumes of distribution at steady state of imipenem and meropenem were 15.3 +/- 3.3 and 18.6 +/- 3.0 liters/70 kg, respectively, and the mean renal clearances per 1.73 m2 were 85.6 +/- 17.6 and 144.6 +/- 26.0 ml/min, respectively. Both antibiotics were well tolerated in this single-dose administration study. The SBAs were measured by the microdilution method of Reller and Stratton (L. B. Reller and C. W. Stratton, J. Infect. Dis. 136:196-204, 1977) against 40 clinically isolated strains. Mean reciprocal bactericidal titers were measured 1 and 6 h after administration. After 1 and 6 h the median SBAs for imipenem and meropenem, were 409 and 34.9 and 97.9 and 5.8, respectively, against Staphylococcus aureus, 19.9 and 4.4 and 19.4 and 4.8, respectively, against Pseudomonas aeruginosa, 34.3 and 2.2 and 232 and 15.5, respectively, against Enterobacter cloacae, and 13.4 and 2.25 and 90.7 and 7.9, respectively, against Proteus mirabilis. Both drugs had rather short biological elimination half-lives and a predominantly renal route of elimination. Both carbapenems revealed high SBAs against clinically important pathogens at 1 h; meropenem had a higher SBA against E. cloacae and P. mirabilis, and the SBA of imipenem against S. aureus was greater than the SBA of meropenem.

Adult↗

PubMed2005

Optimization of meropenem minimum concentration/MIC ratio to suppress in vitro resistance of Pseudomonas aeruginosa.

Suppression of resistance in a dense Pseudomonas aeruginosa population has previously been shown with optimized quinolone exposures. However, the relevance to beta-lactams is unknown. We investigated the bactericidal activity of meropenem and its propensity to suppress P. aeruginosa resistance in an in vitro hollow-fiber infection model (HFIM). Two isogenic strains of P. aeruginosa (wild type and an AmpC stably derepressed mutant [MIC = 1 mg/liter]) were used. An HFIM inoculated with approximately 1 x 10(8) CFU/ml of bacteria was subjected to various meropenem exposures. Maintenance doses were given every 8 h to simulate the maximum concentration achieved after a 1-g dose in all regimens, but escalating unbound minimum concentrations (C(min)s) were simulated with different clearances. Serial samples were obtained over 5 days to quantify the meropenem concentrations, the total bacterial population, and subpopulations with reduced susceptibilities to meropenem (>3x the MIC). For both strains, a significant bacterial burden reduction was seen with all regimens at 24 h. Regrowth was apparent after 3 days, with the C(min)/MIC ratio being < or = 1.7 (time above the MIC, 100%). Selective amplification of subpopulations with reduced susceptibilities to meropenem was suppressed with a C(min)/MIC of > or = 6.2 or by adding tobramycin to meropenem (C(min)/MIC = 1.7). Investigations that were longer than 24 h and that used high inocula may be necessary to fully evaluate the relationship between drug exposures and the likelihood of resistance suppression. These results suggest that the C(min)/MIC of meropenem can be optimized to suppress the emergence of non-plasmid-mediated P. aeruginosa resistance. Our in vitro data support the use of an extended duration of meropenem infusion for the treatment of severe nosocomial infections in combination with an aminoglycoside.

Drug Resistance, Bacterial↗

PubMed1994

Comparison of sensititre broth microdilution and agar dilution susceptibility testing techniques for meropenem to determine accuracy, reproducibility, and predictive values.

The stability, accuracy, reproducibility, and predictive value of Sensititre MIC panels containing meropenem (Merrem) were evaluated by using National Committee for Clinical Laboratory Standards (NCCLS)-recommended American Type Culture Collection (ATCC) strains and 110 selected strains of rapidly growing and fastidious aerobes and anaerobes with various degrees of susceptibility to meropenem. The NCCLS-recommended agar dilution method was used as a standard reference method. Meropenem-containing Sensititre MIC panels were monitored for their stabilities at room temperature and reproducibilities over 24 months by using six ATCC strains. Ninety-nine percent of the MICs of both meropenem and imipenem obtained for NCCLS-recommended ATCC strains were within the established ranges after 2 years. The overall agreement (+/- 1 twofold dilution) between the Sensititre and the agar dilution meropenem MICs was greater than 93%. The predictive value of meropenem MICs for indicating suspeptibility or resistance obtained by the Sensititre method was greater than 90%. No major or very major interpretive errors were observed, and only 5% of meropenem MICs were associated with minor interpretive errors. Problematic organisms were not observed. The Sensititre MIC panels containing meropenem offer a convenient and valid alternative to the NCCLS reference method for the susceptibility testing of potential pathogens likely to be recovered from mixed infections.

Agar↗

PubMed2005

Pharmacokinetic evaluation of meropenem and imipenem in critically ill patients with sepsis.

OBJECTIVE: To evaluate and compare the pharmacokinetic profiles of imipenem and meropenem in a population of critically ill patients with sepsis to find possible differences that may help in selecting the most appropriate drug and/or dosage in order to optimise empiric antimicrobial therapy. PATIENTS AND METHODS: This was a single-centre, randomised, nonblind study of the pharmacokinetics of both intravenous imipenem 1g and meropenem 1g in 20 patients admitted to an intensive care unit with sepsis in whom antimicrobial therapy was indicated on clinical grounds. Patients were divided into two groups: group I received intravenous imipenem 1g plus cilastatin 1g, and group II received intravenous meropenem 1g over 30 minutes. Peripheral blood samples were collected at 0, 0.5 (end of infusion), 0.75, 1, 1.5, 2, 3, 4, 6 and 8 hours after the first dose and were centrifuged for 10 minutes at 4 masculineC. Urine samples were collected during the 8 hours after antimicrobial administration at 2-hour intervals: 0-2, 2-4, 4-6 and 6-8 hours. The total volume of urine was recorded; the serum and urine samples were immediately frozen and stored at -80 masculineC until assayed. Pharmacokinetic analysis was carried out through computerised programs using the least-square regression method and a two-compartment open model. Statistical differences were evaluated by means of one-way ANOVA. RESULTS: The following pharmacokinetic differences between the two drugs were observed: the imipenem mean peak serum concentration was significantly higher than for meropenem (90.1 +/- 50.9 vs 46.6 +/- 14.6 mg/L, p < 0.01); the area under the serum concentration-time curve was significantly higher for imipenem than for meropenem (216.5 +/- 86.3 vs 99.5 +/- 23.9 mg . h/L, p < 0.01), while the mean volume of distribution and mean total clearance were significantly higher for meropenem than for imipenem (25 +/- 4.1 vs 17.4 +/- 4.5L, p < 0.01 and 191 +/- 52.2 vs 116.4 +/- 42.3 mL/min, p < 0.01, respectively). CONCLUSION: The more favourable pharmacokinetic profile of imipenem compared with meropenem in critically ill patients with sepsis might balance the possibly greater potency demonstrated in vitro for meropenem against Gram-negative strains. Hence, the clinical efficacy of the two carbapenems depends mostly on their correct dosage.

Adult↗

PubMed2000

Meropenem: an updated review of its use in the management of intra-abdominal infections.

UNLABELLED: Meropenem is a carbapenem antibacterial agent with a broad spectrum of activity which encompasses gram-negative, gram-positive and anaerobic bacteria. Like other carbapenems, meropenem is stable against chromosomal and extended-spectrum beta-lactamases. In patients with moderate to severe intra-abdominal infections, empirical monotherapy with meropenem achieved clinical response rates ranging from 91 to 100% in 7 randomised comparative trials. Efficacy rates were similar to those of imipenem/cilastatin (94 to 97%), clindamycin plus tobramycin (93%) and, overall, to cefotaxime plus metronidazole (75 to 100%), although there were differences between trials versus this combination regimen. According to limited data, meropenem also achieved clinical response rates of over 80% in patients with severe intra-abdominal infections. Meropenem is well tolerated, the most common adverse events being diarrhoea, rash, nausea/vomiting and inflammation at the injection site which are reported in <2.5% of patients each. Meropenem also has an improved CNS tolerability profile compared with imipenem/cilastatin. CONCLUSIONS: Extensive comparative clinical data demonstrate that meropenem can be used effectively as empirical monotherapy in moderate to severe intra-abdominal infections. It also shows potential in the most severe forms of infection, although experience in this infection type remains limited. Compared with standard combination regimens, meropenem offers the benefits of ease of administration without the need for monitoring. It also offers improved CNS tolerability compared with imipenem/cilastatin with the option of a higher maximum dosage, which may be a particular advantage in patients with severe intra-abdominal infections.

Abdomen↗

PubMed1998

Meropenem. A pharmacoeconomic review of its use in serious infections.

Meropenem is a carbapenem antibiotic which is active against the majority of aerobic and anaerobic bacteria implicated in serious infections. Its therapeutic efficacy in a wide range of serious infections is similar to that of imipenem/cilastatin and standard combination drug regimens. Hence, meropenem is suitable for use as monotherapy. Although the acquisition cost of meropenem is likely to be higher than that of aminoglycoside- and metronidazole-containing combination regimens, the latter incur additional drug administration costs and potentially higher costs for treatment of adverse effects. In addition, aminoglycoside-containing regimens also incur assay and toxicity monitoring costs. Economic analyses are required to compare overall treatment costs with combination therapy and meropenem. Cost analyses indicate that the ability to give meropenem, but not imipenem/cilastatin, by rapid intravenous bolus injection results in lower drug administration costs than with the standard infusion method. More comprehensive pharmacoeconomic data on meropenem are required. However, assuming that meropenem and imipenem/cilastatin have similar acquisition costs, the option of administering meropenem by bolus injection and its lower epileptogenic potential at high dosages (thus permitting its use in meningitis) should be considered potentially important attributes when choosing a carbapenem antibiotic for inclusion in a hospital formulary.

Bacterial Infections↗

PubMed1999

Multicenter randomized trial comparing meropenem (1.5 g daily) and imipenem/cilastatin (2 g daily) in the hospital treatment of community-acquired pneumonia.

An open, multicenter study with 144 patients, aged between 18 and 94 years, was performed to compare the efficacy and safety of meropenem with imipenem/cilastatin in the hospital treatment of community-acquired pneumonia. Patients were randomized to receive either intravenous meropenem (500 mg every 8 h) or intravenous imipenem/cilastatin (1,000 mg every 12 h). The primary end point was considered to be clinical efficacy and the secondary end points were bacteriological response and safety assessment. At the end of therapy, cure or improvement in signs and symptoms as a satisfactory clinical response was observed in 57 of 64 (89.1%) meropenem-treated patients and in 60 of 66 (90.9%) imipenem/cilastatin patients. The mean duration of treatment was 10 days for meropenem and 9.7 days for imipenem/cilastatin. In patients who were followed up for weeks 2-4, the response was satisfactory (100%) for both treatments. A satisfactory bacteriological response, defined as either presumed or confirmed eradication of all pathogens, was found in eight patients who had received meropenem and in 14 patients who had received imipenem/cilastatin. Response was considered satisfactory in 100% of the meropenem group and in 92.9% of the imipenem/cilastatin group and at follow-up, it was 100% for both treatments. Drug-related adverse events were reported in three (4.2%) meropenem-treated patients and in eight (11.0%) imipenem/cilastatin-treated patients. None of these events was classified as serious. The results of this study show that the clinical and bacteriological efficacy and tolerability of meropenem (500 mg every 8 h) are similar to that of imipenem/cilastatin (1,000 mg every 12 h) in the hospital treatment of community-acquired pneumonia.

Adolescent↗

PubMed2002

Pneumococcal susceptibility to meropenem in a mid-south children's hospital.

BACKGROUND: We investigated pneumococcal susceptibility to meropenem in isolates from a tertiary children's hospital where pneumococci are commonly resistant to penicillin and cefotaxime. METHODS: From July 1998 to August 1999, meropenem susceptibilities were determined by E-test for all Streptococcus pneumoniae isolates from blood or cerebrospinal fluid and for penicillin-nonsusceptible pneumococcal isolates from other sites. RESULTS: Isolates that were penicillin-susceptible or penicillin-intermediate were all susceptible to meropenem. Of 29 penicillin-resistant isolates, 27 were nonsusceptible to meropenem (13 intermediate, 14 resistant). Cefotaxime-susceptible isolates were all susceptible to meropenem. Of 11 cefotaxime-intermediate isolates, 10 were nonsusceptible to meropenem (9 intermediate, 1 resistant). Of 20 cefotaxime-resistant isolates, 17 were nonsusceptible to meropenem (4 intermediate, 13 resistant). CONCLUSIONS: Meropenem resistance is common among pneumococci with decreased susceptibility to penicillin or cefotaxime. The role of this agent in the treatment of invasive infections caused by pneumococci that are resistant to penicillin and cefotaxime may be limited.

Child↗

PubMed1997

Comparative in vitro Activity of Meropenem Versus Other Extended-Spectrum Antimicrobial Agents Against 2,085 Clinical Isolates Tested in 13 Brazilian Centers.

Meropenem is a parenteral carbapenem antibacterial agent with a very broad spectrum of antibacterial activity. It is the second agent of its class to become available in Brazil. The in vitro antibacterial activity of meropenem was compared with imipenem and four other antimicrobial agents in a multicenter study. This study involved 13 clinical microbiology laboratories, 10 of which came from 8 Brazilian states. A total of 2,085 clinical isolates consecutively collected between December 1995 and March 1996 were susceptibility tested using the Etest and following the NCCLS procedures. Meropenem inhibited more than 90% of isolates of Enterobacteriaceae at 0.5 µg/mL, except for Citrobacter sp. (1 µg/ml). Generally, meropenem was slightly more active than imipenem against Gram-negative organisms and its spectrum of antimicrobial activity was broader than those of all other drugs tested. Against Pseudomonas aeruginosa, meropenem (MIC50, 0.38 µg/ml) was approximately 8-fold more active than imipenem (MIC 50,3 µg/mL). Imipenem was two-to eight-fold more active than meropenem against some Gram-positive specees oxacillin, including Enterococcus faecalis (MIC 50 of 0.75 µg/mL and 2 µg/mL respectively), oxacillin-susceptible Staphylococcus aureus (MIC 50 of 0.47 &mul;g/mL and 0.094 µg/mL), oxacillin-susceptible Staphylococcus epidermidis (MIC 50 of 0.064 µg/mL and 0.5mg/mL). Against Streptococcus sp. meropenem was slightly more active than imipenem (MIC 50, 0.016 µg/mL). The results of this study may be used to guide empiric therapy in Brazil and indicates that meropenem may have an important role in the treatment of infections caused by multiresistant strains of bacteria.

Journal Article↗

PubMed1991

In vitro synergistic activity between meropenem and other beta-lactams against methicillin-resistant Staphylococcus aureus.

The in vitro activity of meropenem, a carbapenem antibiotic, combined with eight other beta-lactams against methicillin-resistant Staphylococcus aureus (MRSA) was tested. The MICs of these antibiotics alone ranged from 12.5 to 1,600 micrograms/ml for the 25 clinical isolates of MRSA studied. All combinations with meropenem exhibited marked synergy as determined by the checkerboard method. The MICs in combinations of meropenem with other beta-lactams were reduced to 1/4-1/64 those of the antibiotics alone. No antagonism was observed for any of the combinations of meropenem with other beta-lactams. Synergism between meropenem and cefpiramide was the highest among the combinations tested, the geometric mean of the fractional inhibitory concentration index for this combination being 0.237. This combination also demonstrated strong bactericidal activity, the MBCs decreasing to 1/16-1/64 of those for the agents alone. In terms of the fractional inhibitory concentration index, this was the most effective combination against MRSA highly resistant to meropenem alone with synergism for 85% (81/95) of the strains. In addition, synergism of imipenem with cephalosporins against MRSA was demonstrated. The affinity of meropenem and cefpiramide for MRSA penicillin-binding protein (PBP) 2' was very low, and the combination of both antibiotics showed an additive increase in affinity for this protein, but not a synergistic increase. Thus, the mechanism of synergism did not seem to be related to affinity for PBP2'. It is possible that there is another factor besides PBP2' which increases the resistance that the combinations inhibit the unknown factor.

Anti-Bacterial Agents↗

PubMed2001

Meropenem pharmacokinetics in children and adolescents receiving hemodialysis.

The emergence of multi-drug-resistant bacteria is of great concern to the care of pediatric end-stage renal disease (ESRD) patients who receive either hemodialysis or peritoneal dialysis via a catheter. Infections with gram-negative organisms, especially Pseudomonas aeruginosa, are difficult to eradicate and often necessitate catheter removal. Meropenem, a broad-spectrum antibiotic of the carbapenem class of beta-lactams, is effective against most gram-positive and gram-negative bacteria and has enhanced activity against P. aeruginosa. We studied the pharmacokinetics of meropenem during and between hemodialysis treatments in seven pediatric patients. Meropenem was given as a single dose of 20 mg/kg (maximum 500 mg) before and after two separate hemodialysis treatments. Meropenem administration was tolerated without any adverse effects. Hemodialysis effectively cleared meropenem in a manner that correlated with percent urea reduction. Median drug half-life was 7.3 h off dialysis (range 4.9-11.7 h). The dose of 20 mg/kg was not sufficient to produce an acceptable interdialytic pharmacodynamic profile of 70% duration with a meropenem concentration >4 microg/ml, the MIC90 of meropenem for P. aeruginosa. Dosing simulations revealed that a daily dose of 25 mg/kg or an alternate day dose of 40 mg/kg would result in an acceptable pharmacodynamic profile. Both simulated doses achieved acceptable peak concentrations.

Adolescent↗

PubMed1998

Antibacterial activity of meropenem against Pseudomonas aeruginosa, including antibiotic-induced morphological changes and endotoxin-liberating effects.

The in vitro effects of meropenem on Pseudomonas aeruginosa were examined by studying (i) the inhibitory and bactericidal concentrations of meropenem versus those of imipenem for clinical isolates; (ii) changes in bacterial morphology during in vitro culture; and (iii) release of endotoxin induced by meropenem compared with that induced by other antipseudomonal compounds. Meropenem MIC90 and MBC90 values for 108 clinical isolates were 2 and 4.8 mg/l compared to 4.5 and 9.6 mg/l for imipenem. Morphological studies using phase-contrast and scanning electron microscopy showed that meropenem induced the formation of indeterminate bacterial cell forms at drug concentrations of 1-2.5 mg/l (0.5- to 1.25-fold the MIC), while spheroplasts predominated at drug levels exceeding 5 mg/l (2.5-fold the MIC). Determination of free and EDTA-releasable endotoxin activity by means of the Limulus lysate test showed that both meropenem and imipenem liberated significantly less endotoxin than did ceftazidime. Therefore, although meropenem binds to penicillin-binding proteins (PBPs) 2 and 3 (in contrast to imipenem, which binds to PBP2 only), endotoxin release should not be a cause of concern when treating systemic gram-negative infections with this drug.

Anti-Infective Agents↗

PubMed2000

In vitro activity of meropenem and four other antibiotics against 554 clinical strains obtained from Beijing in 1999.

In 1999, a surveillance study was initiated in a hospital in Beijing to monitor the potency and spectrum of five extended-spectrum beta-lactam antimicrobial agents (meropenem, imipenem, cefepime, ceftazidime, and cefoperazone/sulbactam) tested against 554 strains of bacteria. Five groups of organisms were tested by the E-test method, with results validated by concurrent quality control strain analysis. Results were tabulated, and 100% of quality assurance tests (16/16 tests) were within ranges recommended by the National Committee for Clinical Laboratory Standards. Of the five beta-lactam drugs tested, meropenem and imipenem were the most active against all isolates tested. Overall, the rank order of activity of the five agents was: meropenem (94.6% susceptible) > imipenem (90.1%) > cefepime (77.6%), cefoperazone/sulbactam (77.5%), ceftazidime (76.6%). Ninety-five percent of Enterobacter were to meropenem, while 82% were susceptible to imipenem. Meropenem was more active than imipenem against Pseudomonas aeruginosa. The minimum inhibitory concentration (MIC) of meropenem was eightfold lower than that of imipenem. Meropenem had excellent activity against Haemophilus influenzae, Streptococcus pneumoniae, and oxacillin-susceptible staphylococci.

Anti-Bacterial Agents↗

PubMedDate not supplied

In vitro activity of three carbapenem antibiotics. Comparative studies with biapenem (L-627), imipenem, and meropenem against aerobic pathogens isolated worldwide.

The in vitro activity of biapenem (formerly L-627 or LJC10, 627), a new carbapenem, was compared with that of imipenem and meropenem against > 6000 clinically significant pathogens isolated in six countries worldwide. Biapenem was active against members of the family Enterobacteriaceae with a 90% minimum inhibitory concentration (MIC90) ranging from < or = 0.06 to 2 micrograms/ml. Only Serratia spp. and Providencia spp. were less susceptible (MIC90, 8 micrograms/ml). Pseudomonas aeruginosa and Xanthomonas maltophilia displayed an MIC90 of > or = 8 micrograms/ml biapenem/ml whereas Acinetobacter spp. were susceptible at < or = 1 micrograms/ml. Oxacillin-resistant staphylococci were resistant to biapenem at > 8 micrograms/ml whereas oxacillin-sensitive staphylococci were susceptible at < or = 1 micrograms/ml. Biapenem, imipenem, and meropenem displayed poor activity against Ent. faecium (MIC90, > or = 8 micrograms/ml), and only imipenem displayed slightly better activity against Ent. faecalis (MIC90, 4 micrograms/ml). The rank order of activity against groups of isolates was Enterobacteriaceae (meropenem > biapenem > or = imipenem), Ps. aeruginosa (biapenem = meropenem = imipenem), oxacillin-sensitive staphylococci (imipenem > or = biapenem = meropenem), oxacillin-resistant staphylococci (biapenem = meropenem = imipenem), and Enterococcus spp. (biapenem = meropenem = imipenem). These in vitro suggest that further developmental work on biapenem is warranted.

Enterobacteriaceae↗

PubMed2005

An overview of the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program: 1997-2004.

This overview provides a summary of the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program over an 8-year period from 1997 to 2004. The evolution of the MYSTIC Program is described, as well as its design compared with other surveillance programs. In addition, the global MYSTIC Program data, published to date, are summarized, and the empiric use of carbapenems, their current indications, and meropenem usage versus resistance was discussed. From 1997 to 2004, 120 medical centers that were actively prescribing meropenem in 32 countries worldwide participated in the program. The MYSTIC Program results demonstrate the sustained potency and continued effectiveness of meropenem globally against clinically relevant Gram-negative and Gram-positive pathogens including extended spectrum beta-lactamase- and AmpC beta-lactamase-producing organisms, which may also display resistance to the fluoroquinolones and/or aminoglycosides. Furthermore, in centers actively prescribing meropenem, resistance to meropenem is not increasing despite greater resistance among the comparator antimicrobial agents. Thus, antipseudomonal carbapenems such as meropenem and imipenem remain an effective treatment option.

Anti-Bacterial Agents↗

PubMed2004

Optimizing antimicrobial pharmacodynamics: dosage strategies for meropenem.

INTRODUCTION: Carbapenems are broad-spectrum antibiotics that are often employed as the last line of therapy for patients with nonresponsive nosocomial infections. Consideration of pharmacodynamic principles in dosage regimens for these agents can maximize their antibacterial effectiveness and reduce the number of bacterial strains that survive to mutate or continue infection. OBJECTIVE: The objectives of this review were to highlight examples of the application of pharmacodynamics to the carbapenems (particularly meropenem) and to comment on clinical utility of these dosage regimens. METHODS: Relevant information was identified through a MEDLINE search of the literature (1980-present) using the terms carbapenem, pharmacodynamic, pharmacokinetic, pharmacoeconomic, meropenem, imipenem, ertapenem, biapenem, and panipenem. Additionally, meeting posters were identified from the International Conference of Antimicrobial Agents and Chemotherapy (years 2001-2003) and the International Conference of the American Thoracic Society (years 2002-2003). All studies demonstrating the pharmacodynamics of the carbapenems by incorporating changes in dosage strategies were included. RESULTS: Only relevant data for meropenem were identified in our literature search. The dosage scheme for meropenem may be modified to maximize the percentage of the dosage interval that drug concentrations remain above the minimum inhibitory concentration, an important parameter related to the bacterial kill rate. Only relevant data for meropenem were identified in our literature search. Human volunteer and Monte Carlo simulation studies suggested that in the treatment of susceptible pathogens, higher meropenem doses, increased frequency of administration, or prolonged duration of infusion resulted in improved pharmacodynamics. CONCLUSION: When proper pharmacodynamic principles are applied to dosage strategies for meropenem, clinical and microbiological outcomes can be optimized.

Anti-Bacterial Agents↗