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Carbapenem-resistant Serratia marcescens isolates producing Bush group 2f beta-lactamase (SME-1) in the United States: results from the MYSTIC Programme.

Two carbapenem (imipenem, meropenem)-resistant Serratia marcescens strains were isolated in the United States (Chicago, IL) through the 1999 MYSTIC (Meropenem Yearly Susceptibility Test Information Collection) Programme. The S. marcescens antimicrobial susceptible patterns were: susceptible to ceftriaxone, ceftazidime, and cefepime (MICs, < or = 0.25 microg/ml), and resistance to the carbapenems (imipenem and meropenem; MIC, > 32 microg/ml) and aztreonam (MIC, > = 16 microg/ml). Each S. marcescens isolate shared an identical epidemiologic type (ribotype and PFGE) and the outer membrane protein profile was also identical to those of the wild type susceptible strains from the same medical center. The PCR utilizing bla(sme-1) primers amplified a gene product that was identified as consistent with SME-1 after DNA sequencing. Imipenem and meropenem resistance due to production of carbapenem-hydrolyzing enzymes among clinical isolates is still very rare, but microbiology laboratories should be aware of these chromosomally encoded enzymes among class C beta-lactamases producing enteric bacilli such as S. marcescens and Enterobacter cloacae.

Drug Resistance, Microbial↗

Unit differences in pathogen occurrence arising from the MYSTIC program European database (1997-2000).

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program is a longitudinal global antimicrobial surveillance study that compares the activity of meropenem and comparator antimicrobial agents against pathogens isolated from intensive care, neutropenic or cystic fibrosis patients, and general wards. Data from the different European MYSTIC Program units (1997-2000) showed that the most prevalent isolates tested overall were methicillin-susceptible Staphylococcus aureus (MSSA; in accordance with study design methicillin-resistant S. aureus was not tested), Pseudomonas aeruginosa and Escherichia coli. In all the unit types, E. coli (approximately 20% having an extended spectrum beta-lactamase phenotype) and MSSA were highly susceptible to meropenem (97-99% susceptibility). Isolates of MSSA showed lower levels of susceptibility to ciprofloxacin (61-77% susceptibility) in both cystic fibrosis and neutropenia patients, and particularly high levels of resistance to ceftazidime (38% susceptibility) in cystic fibrosis units. Ciprofloxacin (54% susceptibility) and gentamicin (46% susceptibility) demonstrated low levels of activity against P. aeruginosa (frequently encountered in cystic fibrosis units). Meropenem and piperacillin/tazobactam were the most active agents against P. aeruginosa in all the unit types. Carbapenems and piperacillin/tazobactam have sustained > 90% susceptibility rates overall against the most frequently isolated pathogens. The analysis of specific units that house patients with a high-risk of contracting antimicrobial-resistant pathogens remains very important for the optimal selection of empiric regimens.

Burkholderia cepacia↗

Use of Etests with carbapenems for Gram-negative rods producing beta-lactamases.

The in vitro activity of imipenem and meropenem on strains of Gram-negative rods producing extended-spectrum beta-lactamase (ESBL) and inducible beta-lactamase (IBL) was studied using the Etest. In all, 185 strains from the surgical intensive care units of four different hospitals were looked at over 2 years. Of these, 94 were ESBL producers and 91 were IBL positive. The in vitro sensitivities of imipenem and meropenem were 89.7 and 95.1%, respectively, against all strains. The imipenem and meropenem sensitivities of Klebsiella spp. were 98.4 and 100%, respectively, but imipenem resistance (21.6%) in Pseudomonas aeruginosa strains was higher than that of meropenem (10.8%).

Drug Resistance, Multiple, Bacterial↗

In vitro activities of three carbapenems against recent bacterial isolates from severely ill patients at Swedish hospitals.

To study the in vitro activity of imipenem, meropenem and ertapenem against common pathogens isolated from patients in intensive care, haematology and dialysis/nephrology units at 7 Swedish university hospitals, a total of 788 isolates were collected during 2002-2003. The distribution of the isolates was as follows: Escherichia coli (n = 140), Klebsiella spp. (n = 132), Proteus spp. (n = 97), Enterobacter spp. (n = 113), Pseudomonas aeruginosa (n = 126), Acinetobacter spp. (n = 53) and Enterococcus faecalis (n = 127). The susceptibility to the 3 carbapenems was determined by E-test, and the MICs were interpreted according to SRGA criteria. All 3 carbapenems were highly active against Enterobacteriaceae. The overall susceptibility to imipenem, meropenem and ertapenem was 90%, 98% and 93%, respectively. Against Enterobacteriaceae, Enterobacter spp. excluded, ertapenem had an equal or lower MIC(90) than meropenem. Apart from being the most active carbapenem against Enterobacteriaceae, meropenem was also the most active carbapenem against P. aeruginosa, whereas imipenem was the most active drug against Acinetobacter spp. The carbapenems are still potent antibiotics. With the introduction of ertapenem, and an expected increase in the carbapenem consumption due to an increased prevalence of strains with extended-spectrum beta-lactamases, continuous surveillance of carbapenem resistance appears to be warranted, with special attention to P. aeruginosa, Enterobacter and Proteus spp.

Acinetobacter↗

Pharmacodynamic modeling of beta-lactam antibiotics for the empiric treatment of secondary peritonitis: a report from the OPTAMA program.

BACKGROUND: In this report of the OPTAMA (Optimizing Pharmacodynamic Target Attainment using the MYSTIC Antibiogram) program, we utilized Monte Carlo simulation to compare the probabilities of achieving bactericidal time above the minimum inhibitory concentration (MIC) (%T > MIC) exposures for imipenem-cilastatin 500 mg q6h and 1000 mg q8h, meropenem 500 mg q6h and 1000 mg q8h and piperacillin/tazobactam 3.375 g q6h and 4.5 g q8h in the empiric treatment of secondary peritonitis. METHODS: The prevalence of pathogens causing secondary peritonitis was identified from the primary surgical and infectious diseases literature. Data for these pathogens with respect to MIC were obtained from the 2003 MYSTIC surveillance study and weighted by the prevalence of each pathogen. A sensitivity analysis varying the prevalence of P. aeruginosa was performed with two additional models to determine the robustness of the data. Pharmacokinetic parameters, obtained from previously published studies in healthy volunteers were used to simulate the %T > MIC for 10,000 patients receiving imipenem-cilastatin, meropenem, and piperacillin/tazobactam. The likelihood of obtaining bactericidal exposure is reported. RESULTS: Empiric utilization of imipenem-cilastatin and meropenem 500 mg q6h and 1000 mg q8h regimens achieved 99.6%-99.7% likelihood of bactericidal exposure. Piperacillin/ tazobactam 3.375 g q6h and 4.5 g q8h produced bactericidal target attainments of 92.9% and 85.2%, respectively. Models simulating higher prevalence of P. aeruginosa reduced the likelihood of bactericidal exposure for piperacillin/tazobactam regimens significantly and had little effect on the carbapenems. CONCLUSION: All of the beta-lactams used in the current analysis were predicted to achieve high target attainment consistently for the empiric treatment of secondary peritonitis. However, imipenem-cilastatin 500 mg q6h and 1000 mg q8h, meropenem 1000 mg q8h and 500 mg q6h, and piperacillin/tazobactam 3.375 g q6h achieved the highest likelihood. These, in particular, would be effective choices for the empiric treatment of secondary peritonitis.

Anti-Bacterial Agents↗

Is it safe to use carbapenems in patients with a history of allergy to penicillin?

OBJECTIVES: The purpose of this retrospective study was to ascertain the clinical safety of administering carbapenems, namely imipenem/cilastatin and meropenem, in patients with a history of penicillin allergy compared with administering carbapenems in patients with no reported penicillin allergy. Carbapenems are similar in chemical structure to the penicillins and therefore are associated with a risk for allergic cross-hypersensitivity. Carbapenems are commonly avoided in patients with a reported penicillin allergy on the basis of a potential cross-hypersensitivity with penicillin, however, very few studies have been conducted describing the incidence of cross-hypersensitivity between penicillin and carbapenems. METHODS: A retrospective review was conducted in a total of 266 patients who were administered either imipenem/cilastatin or meropenem. The patients were admitted to the Cleveland Clinic Health System--Eastern Region Hospitals during the years 2001 and 2002. RESULTS: Fifteen of the 163 patients (9.2%) with reported penicillin allergy developed a hypersensitivity reaction to meropenem or imipenem/cilastatin whereas 3.9% of the 103 patients without penicillin allergy developed a hypersensitivity reaction to meropenem or imipenem/cilastatin. These results are not statistically significant. CONCLUSIONS: Based on this study and other similar studies, the true incidence of cross-hypersensitivity reactions between penicillin and carbapenems may be lower than previously reported. Carbapenem use may be reasonable for penicillin allergic patients if caution is exercised.

Adult↗

Carbapenem resistance mechanisms in Pseudomonas aeruginosa: alterations of porin OprD and efflux proteins do not fully explain resistance patterns observed in clinical isolates.

Imipenem resistance in Pseudomonas aeruginosa is considered to be associated with loss of the porin OprD combined with activity of chromosomal beta-lactamase (AmpC), while overexpression of multidrug efflux pumps is considered to confer meropenem resistance. Carbapenem resistance can also result from production of metallo-beta-lactamases. Transcription of oprD and efflux pump genes mexB, mexY and mexF was analysed in 23 clinical isolates of P. aeruginosa by quantitative RT-PCR. oprD was sequenced in all, and mexR, regulator of efflux pump MexAB-OprM, in selected isolates. Four isolates that were imipenem susceptible had significant reduction of oprD mRNA and presence of oprD mutations causing frameshift or translational stop. In strains only resistant to imipenem no significant difference in transcription of oprD was observed between low-level and high-level resistant isolates. The differences could not be explained by either pattern of oprD mutations. Increased transcription of mexB generally correlated well with meropenem resistance. One high-level meropenem-resistant isolate showed no significant change in mexB mRNA, but sequencing confirmed presence of a nalB mutation. Furthermore, one meropenem-susceptible isolate showed significant increase in mexB transcription, but no mexR mutations. In summary, our findings indicate that the resistance patterns observed cannot be fully explained by the currently described carbapenem resistance mechanisms.

Amino Acid Sequence↗

Comparative convulsant potencies of two carbapenem derivatives in C57 and DBA/2 mice.

The behavioural and convulsant effects of imipenem and meropenem were studied after intraperitoneal administration in DBA/2 mice, a strain genetically susceptible to sound-induced seizure, and in C57 mice, a strain not prone to seizure. DBA/2 mice were more susceptible than C57 mice to seizures induced by imipenem-cilastatin or meropenem. Imipenem was also 1.9 times more potent than meropenem in inducing clonus in DBA/2 mice. To investigate the possibility that the seizure-inducing activity of imipenem might be due to a probenecid-like effect of cilastatin, animals were treated with imipenem alone. No significant differences were observed between imipenem-cilastatin and imipenem-treated animals. Thus, it is reasonable to exclude a probenecid-like effect of cilastatin. Although the main mechanism for seizure-like activity of imipenem cannot be easily determined, we believe that several mechanisms may be involved. An increased excitation of the central nervous system (CNS) by inhibition of GABA binding to receptors and a slow clearance of imipenem from the CNS may be postulated. Cilastatin did not induce seizures. In addition, meropenem, a compound structurally related to imipenem, showed weak or no convulsant effects.

Animals↗

Antimicrobial effects of continuous versus intermittent administration of carbapenem antibiotics in an in vitro dynamic model.

In an in vitro dynamic model we compared the antimicrobial effects of two carbapenems, imipenem (MIC, 1 microg/ml) and meropenem (MIC, 0.25 microg/ml) on Pseudomonas aeruginosa. The antibiotics were administered either as short-time infusions once or three times a day or as continuous infusions with steady-state levels ranging from 0.5 to 20 microg/ml. From the resulting kill curves the period of time until the onset of bacterial death (dt), the rate constant of bacterial death (ka), the maximal reduction of CFU (mr), and the period of time until bacterial regrowth occurred (tr) were determined. Additionally, the occurrence of bacterial resistance during the simulations (rq) and the postantibiotic effect (PAE) were recorded. For both investigated carbapenems no significant difference in dt, ka, mr, and PAE values between the short-time infusions and continuous infusions with steady-state levels above 2 microg/ml could be detected. The tr was longest with continuous infusions of over approximately 24 h, corresponding to steady-state levels of 3 microg/ml for imipenem and 2.5 microg/ml for meropenem. An increase in MIC was observed only during continuous infusions with steady-state levels below 2 microg/ml. Independent of the chosen method of application and despite the lower MIC of meropenem, imipenem was slightly more effective than meropenem.

Bacteremia↗

Novel carbapenem-hydrolyzing beta-lactamase, KPC-1, from a carbapenem-resistant strain of Klebsiella pneumoniae.

A Klebsiella pneumoniae isolate showing moderate to high-level imipenem and meropenem resistance was investigated. The MICs of both drugs were 16 microg/ml. The beta-lactamase activity against imipenem and meropenem was inhibited in the presence of clavulanic acid. The strain was also resistant to extended-spectrum cephalosporins and aztreonam. Isoelectric focusing studies demonstrated three beta-lactamases, with pIs of 7.2 (SHV-29), 6.7 (KPC-1), and 5.4 (TEM-1). The presence of bla(SHV) and bla(TEM) genes was confirmed by specific PCRs and DNA sequence analysis. Transformation and conjugation studies with Escherichia coli showed that the beta-lactamase with a pI of 6.7, KPC-1 (K. pneumoniae carbapenemase-1), was encoded on an approximately 50-kb nonconjugative plasmid. The gene, bla(KPC-1), was cloned in E. coli and shown to confer resistance to imipenem, meropenem, extended-spectrum cephalosporins, and aztreonam. The amino acid sequence of the novel carbapenem-hydrolyzing beta-lactamase, KPC-1, showed 45% identity to the pI 9.7 carbapenem-hydrolyzing beta-lactamase, Sme-1, from Serratia marcescens S6. Hydrolysis studies showed that purified KPC-1 hydrolyzed not only carbapenems but also penicillins, cephalosporins, and monobactams. KPC-1 had the highest affinity for meropenem. The kinetic studies also revealed that clavulanic acid and tazobactam inhibited KPC-1. An examination of the outer membrane proteins of the parent K. pneumoniae strain demonstrated that the strain does not express detectable levels of OmpK35 and OmpK37, although OmpK36 is present. We concluded that carbapenem resistance in K. pneumoniae strain 1534 is mainly due to production of a novel Bush group 2f, class A, carbapenem-hydrolyzing beta-lactamase, KPC-1, although alterations in porin expression may also play a role.

Amino Acid Sequence↗

Novel approach to characterization of combined pharmacodynamic effects of antimicrobial agents.

There is considerable need for new modeling approaches in the study of combined antimicrobial effects. Current methods based on the Loewe additivity and Bliss independence models are associated with implicit assumptions about the interacting system. To circumvent these limitations, we propose an alternative approach to the quantification of pharmacodynamic drug interaction (PDI). Pilot time-kill studies were performed with 10(8) CFU of Pseudomonas aeruginosa/ml at baseline with meropenem or tobramycin alone. The studies were repeated with 25 concentration combinations of meropenem (0 to 64 mg/liter) and tobramycin (0 to 32 mg/liter) in a five-by-five array. The data were modeled with a three-dimensional response surface using effect summation as the basis of null interaction. The interaction index (Ii) is defined as the ratio of the volumes under the planes (VUP) of the observed and expected surfaces: VUP(observed)/VUP(expected). Synergy and antagonism are defined as Ii values of <1 and >1, respectively. In all combinations, an enhanced killing effect was seen compared to that of either drug at the same concentration. The most significant synergism was observed between 1 and 5 mg/liter of meropenem and between 1 and 4 mg/liter of tobramycin; seven out of nine combinations had a >2-log drop compared to the more potent agent. The Ii was found to be 0.76 (95% confidence interval, 0.65 to 0.91) for the concentration ranges of the agents. The results corroborate previous data indicating that meropenem is synergistic with an aminoglycoside when used in combination against P. aeruginosa. Our parametric approach to quantifying PDI appears robust and warrants further investigations.

Algorithms↗

A cluster of nosocomial cross-infection due to multiple antibiotic-resistant Acinetobacter baumannii: Characterization of the strain and antibiotic susceptibility studies.

A multiple antibiotic-resistant (MAR) strain of Acinetobacter baumannii caused nosocomial cross-infection among 3 patients of a surgical intensive care unit. The isolates were of identical biochemical profile (77776 S-U-) and serotype (serovar 36) and identical in terms of pulsed-field gel electrophoresis macrorestriction (SmaI, ApaI) analysis. This MAR strain was susceptible only to netilmicin, tobramycin, imipenem, meropenem, polymyxin B, and trovafloxacin. The minimal bactericidal concentrations of imipenem and meropenem were markedly higher than the corresponding minimal inhibitory concentrations against this strain. Combined fresh defibrinated human blood (65 vol%) and antimicrobial drug assays yielded the following results: polymyxin was the most rapidly bactericidally effective antibiotic in the presence of blood and in broth. Tobramycin and netilmicin were efficacious in 65 vol% blood. Imipenem was slightly more effective than meropenem in broth, whereas both carbapenems sterilized blood-containing assay tube contents. Trovafloxacin failed to achieve bactericidal activity (to 99.9% kill) in the presence of blood, presumably because this strain was resistant to ciprofloxacin and borderline susceptible to ofloxacin. Trovafloxacin combined with either imipenem or meropenem yielded an indifferent effect. However, the combination of trovafloxacin (2 microg/ml) plus tobramycin (1 microg/ml) achieved sterilization of tube contents in the presence of blood within 4 h after exposure and in broth following extended (overnight) incubation. This MAR strain of A. baumannii was high-level resistant to rifampin; thus the combination of polymyxin B plus rifampin proved indifferent.

Acinetobacter↗

Is late antibiotic prophylaxis effective in the prevention of secondary pancreatic infection?

BACKGROUND: Secondary infection of the inflamed pancreas is the principal cause of death after severe acute pancreatitis (AP). Although patients are not always managed early in the course of AP in clinical practice, prophylactic antibiotics that were used in experimental studies in rats were always initiated early after induction of pancreatitis. The effectiveness of antibiotics initiated later is unknown. AIM: The aim of this study was to compare the effectiveness of ciprofloxacin and meropenem initiated early versus later in the course of acute necrotizing pancreatitis (ANP) in rats. METHODS: 100 Sprague-Dawley rats were studied. ANP was induced in rats by intraductal injection of 3% taurocholate. Rats were divided randomly into five groups: group I rats received normal saline as a placebo, group II and IV rats received three times daily meropenem 60 mg/kg i.p. at 2 and 24 h, respectively and group III and V rats received twice daily ciprofloxacin 50 mg/kg i.p. at 2 and 24 h, respectively, after induction. At 96 h, all rats were killed for quantitative bacteriologic study. A point-scoring system of histological features was used to evaluate the severity of pancreatitis. RESULTS: Meropenem and ciprofloxacin initiated 2 h after induction of pancreatitis significantly reduced the prevalence of pancreatic infection (p < 0.001 and p < 0.04, respectively) as compared to controls. Neither of the antibiotics initiated later during the course of AP caused a significant decrease in pancreatic infection in rats (p > 0.05). Although the rats treated early infected less frequently than the rats treated later, the comparison reached statistical significance only in the meropenem group (p < 0.02). CONCLUSION: Early antibiotic treatment reduces pancreatic infection more efficiently than late antibiotic treatment in ANP in rats.

Animals↗

Structure-activity relationships of carbapenem compounds to anti-Haemophilus influenzae activity and affinity for penicillin-binding proteins. Effect of 1 beta-methyl group and C-2 side chain.

The anti-H. influenzae activity of meropenem (1a) was much higher than those of imipenem (4). panipenem (2b) and biapenem (7). To clarify the major structural features responsible for the anti-H. influenzae activity of carbapenem compounds, the structure-activity relationship to the anti-H. influenzae activity was investigated. The anti-H. influenzae activities of meropenem (1a) and 1 beta-methyl-panipenem (2a) were much higher than those of desmethyl-meropenem (1b) and panipenem (2b). respectively. Two carbapenems (5, 6) and imipenem (4), that have a strong basic C-2 side chain, showed lower anti-H. influenzae activity than meropenem (1a) having a weakly basic C-2 side chain and N-acetyl thienamycin (3) having a neutral C-2 side chain, respectively. As a result, we found that the introduction of the 1 beta-methyl group or the reduction of the basicity (cationic character) of the C-2 side chain increased the antimicrobial activity and bactericidal activity of carbapenems against H. influenzae due to their increased affinity for PBP-4 and PBP-5.

Anti-Bacterial Agents↗

[Evaluation of disk diffusion test for carbapenem sensitivity in Acinetobacter baumannii and Pseudomonas aeruginosa strains].

This study was conducted upon the detection of discordant results obtained for Acinetobacter species against meropenem by disk diffusion susceptibility and E-test method. The aim of this study was to investigate the reliability of disk diffusion method for the determination of carbapenem susceptibility in non-fermentative bacilli. Carbapenem (imipenem and meropenem) sensitivites of 157 Acinetobacter baumanii and 157 Pseudomonas aeruginosa strains were performed by disk diffusion test and E-test in our laboratory where quality control of antibiotic susceptibility tests are performed weekly. For meropenem, discordance of the two tests were 10.8% and 4.5% for A. baumannii and P. aeruginosa, respectively. MIC values and disk diffusion zone diameters were significantly different from each other. There was no difference in terms of imipenem in A. baumannii strains but 5.1% of P. aeruginosa isolates showed discordance. Since, for the P. aeruginosa isolates with discordant imipenem susceptibility results, the imipenem disk diffusion zones were close to the lower level and their MIC values were within the intermediate resistance range, it was assumed that this technical discordance had low risk of reproducibility. In routine laboratories, meropenem resistance detected by disk diffusion method, should be verified by another technique. This is not only important for patient results but for epidemiological data as well. Routine quality control studies for antibiotic susceptibility tests and close observation of suspicious results, is mandatory for each laboratory, in order to achieve good quality performance.

Acinetobacter baumannii↗

Emerging resistance to carbapenems in a tertiary care hospital in north India.

BACKGROUND AND OBJECTIVES: Carbapenems are beta-lactam antibiotics, presently considered as most potent agents for treating multi-drug resistant Gram-negative bacilli infections. In India carbapenems available for use are meropenem and imipenem, introduced recently. Resistance to these has been reported in a few bacteria especially Pseudomonas spp. We therefore retrospectively evaluated the antibiotic susceptibility pattern to these agents amongst various clinical isolates in a tertiary care hospital in north India. METHODS: In this study Gram-negative bacterial pathogens isolated from clinical samples were tested for extended spectrum beta lactamase (ESBL) production. All ESBL positive bacteria were tested for meropenem and imipenem activity pattern using NCCLS guidelines. A total of 2626 consecutively isolated Gram-negative bacteria, which tested positive for ESBL production by the double disk diffusion method, were included. RESULTS: The different bacteria isolated were Pseudomonas spp. 759, Acinetobacter spp. 676, Escherichia coli 569, Klebsiella spp. 343, Enterobacter spp. 150, Citrobacter spp. 57 and Proteus spp. 72. Overall resistance to meropenem was more (22.16%) than imipenem (17.32%). Maximum resistance was seen in Pseudomonas spp. M(R) 37.6 per cent, I(R) 30 per cent. In isolates from intensive care units (ICU) resistance to carbapenems was significantly higher than non-ICU patients. INTERPRETATION AND CONCLUSION: Resistance to meropenem and imipenem was seen in various clinical isolates of Gram-negative ESBL-positive bacteria. There is a need to alarm our clinicians for judicious use of antibiotics.

Anti-Bacterial Agents↗

Changing role of carbapenems in the treatment of lower respiratory tract infections.

The acquisition of antibiotic-resistance genes by virtually all major bacterial pathogens is currently a world-wide phenomenon. This problem is especially evident in nosocomial lower respiratory tract infections (LRTI). Carbapenems like imipenem and meropenem offer interesting antibacterial activities and beta-lactamase-stability, as well as adequate pharmacokinetic characteristics, to cover most of the pathogens involved in moderate to severe community-acquired and nosocomial LRTI. In contrast to imipenem, meropenem is not nephrotoxic and offers the advantage of greater stability against renal dehydropeptidase-I, so no concomitant application of an enzyme inhibitor is necessary. Meropenem can also be given by intravenous infusion or injection without the nausea and vomiting often associated with the administration of imipenem/cilastatin. Preliminary results with meropenem in LRTI show excellent cure rates and good tolerance for this new carbapenem.

Adolescent↗

Immune response in patients with intra-abdominal infections treated with carbapenems.

The immune responses against isolated microorganisms in patients with intraabdominal infections treated with meropenem or imipenem/cilastatin were investigated. Fifty-nine patients received meropenem 500 mg t.i.d. intravenously for 3-21 days (mean 5.4 days) and 50 patients imipenem/cilastatin 500 mg/500 mg t.i.d. intravenously for 3-17 days (mean 5.1 days). Three serum samples were taken from each patient, the first sample at admission, the second sample between three and seven days after start of antibiotic treatment, and the third sample between 14 and 28 days later. Ninety-eight per cent of the patients in the meropenem group and 95% of the patients in the imipenem/cilastatin group were cured. There was no difference in the clinical outcome between the two treatment groups. Escherichia coli, Bacteroides fragilis group, anaerobic cocci, Staphylococcus epidermidis, and Klebsiella spp. predominated among the isolated microorganisms. Thirty-nine patients in the meropenem group had significant immune responses against one or more of the isolated microorganisms while 31 patients in the imipenem/group had significant responses. E. coli and B. fragilis gave rise in antibody titres in most patients indicating that these species are the most important pathogens in intraabdominal infections.

Abdominal Abscess↗