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Clinical Relevance Of Beta Lactamase

Clinical relevance of gram-negative bacteria having inducible chromosomic beta-lactamase at an intensive care unit:
The aim of the study was to determine the frequency of third-generation cephalosporins and aztreonam resistance in gram-negative bacteria with inducible chromosomal beta-lactamase (beta Lac-ind) after beta-lactam therapy in the medical-surgical intensive care unit (ICU) at a university-affiliated hospital. PATIENTS AND METHODS: studied 34 infections in 29 patients admitted to the ICU. All were infected by strains with beta Lac-ind and all were treated with beta-lactam antibiotics. Susceptibility was determined by disc-diffusion. The beta-lactamase activity of those strains showing constitutive beta-lactamase overproduction were characterized by isoelectrofocusing. When this derepression occurred during the therapy, the strains were compared by genomic macrorestriction (PGFE). RESULTS: In 29 out of 34 infections the initial strains was susceptible. In 11 cases, the culture were not negativized in spite of their susceptible pattern. In 4 cases there was derepression during therapy. In 5 cases the initial strains were derepressed. The microorganisms isolated more frequently were Pseudomonas aeruginosa (22 cases) and Enterobacter cloacae (5 cases). The beta-lactamase activity detected correspond well with a betaLac-ind. In those cases with derepression during therapy, the initial susceptible strain and the resistant strain were identical by PGFE.

Extended-spectrum beta-lactamases: implications for the clinical microbiology laboratory, therapy, and infection control.
Extended-spectrum beta-lactamase (ESBL) producing gram-negative bacilli are a growing concern in human medicine today. When producing these enzymes, organisms (mostly K. pneumoniae and E. coli) become highly efficient at inactivating the newer third-generation cephaloporins (such as cefotaxime, ceftazidime, and ceftriaxone). In addition, ESBL-producing bacteria are frequently resistant to many classes of non-beta-lactam antibiotics, resulting in difficult-to-treat infections. This review gives an introduction into the topic and is focused on various aspects of ESBLs; it covers the current epidemiology, the problems of ESBL detection and the clinical relevance of infections caused by ESBL-producing organisms. Therapeutic options and potential strategies for dealing with this growing problem are also discussed in this article.

Beta-Lactamase producing bacteria in adult periodontitis:
In 23 untreated adult periodontitis patients, the occurrence of beta-lactamase producing periodontal bacteria was determined. In addition to non-selective isolation media, selective isolation and growth of beta-lactamase positive subgingival bacterial species was carried out on blood agar plates supplemented with amoxicillin and plates with amoxicillin+clavulanic acid. Porphyromonas gingivalis, Prevotella intermedia, Actinobacillus actinomycetemcomitans, Peptostreptococcus micros, Fusobacterium nucleatum, Bacteroides forsythus and Campylobacter rectus isolates from the non-selective medium were tested for beta-lactamase activity by a nitrocefin disk method (DrySlide) and by a laboratory chromogenic nitrocefin-based test. Isolates from the amoxicillin plates that were absent on the amoxicillin/clavulanic acid plates were identified and tested for beta-lactamase production. Based on the non-selective plates, six of 23 P. intermedia isolates, 2 of 19 B. forsythus isolates and 3 of 23 F. nucleatum isolates were beta-lactamase positive. The beta-lactamase positive species Prevotella loescheii, Prevotella buccae, Prevotella buccalis and Actinomyces spp were recovered from the selective amoxicillin plates. beta-Lactamase positive subgingival species were recovered from 17 of 23 patients (74%) but usually comprised low proportions of the subgingival microbiota (range < 0.01-15%). Comparison of the DrySlide test and the nitrocefin-based laboratory test revealed full agreement of test results. beta-Lactamase activity in whole subgingival plaque was detected in 12 patient samples (52%). It was concluded that beta-lactamase activity in subgingival bacteria in adult periodontitis is a common feature. However, since the majority of the samples showed only low-level enzymatic activity, the clinical relevance of this observation with regard to therapy with unprotected enzyme-susceptible beta-lactams is uncertain, though failure on the other hand, is difficult to rule out when a mechanism of resistance is present. The majority of beta-lactamase positive strains was found among species of the Prevotella genus.

Postantibiotic and Post-Beta-Lactamase Inhibitor Effect of Carbapenems Combined with EDTA against Pseudomonas aeruginosa Strains Producing VIM-Metallo Beta-Lactamases:
Postantibiotic effect (PAE) is a delay of bacterial growth after short exposure to antibiotics. The phenomenon of continuing suppression of bacterial growth after removal of Beta-lactamase inhibitors is termed post-beta-lactamase inhibitor effect (PLIE). Recently, Pseudomonas aeruginosa strains producing metallo-beta-lactamases were described in many countries of the world. The aim of the study was to investigate the PLIE of carbapenems in combinations with EDTA against VIM-MBL-positive strains of P. aeruginosa. Methods: The experiments were performed on two Pseudomonas aeruginosa isolates, one producing VIM-1 and the other producing VIM-2 metallo-beta-lactamase. Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBC) of imipenem and meropenem alone and combined with EDTA, time-kill curves, PAE and PLIE were performed as described previously. Results: The duration of PAE with meropenem combined with EDTA at 8 MIC was longer against both VIM-1 and VIM-2 producer than that of imipenem with EDTA on VIM-1- and VIM-2-positive strains. The duration of PLIE was similar on both strains of P. aeruginosa regardless of the sort of carbapenem. At lower concentrations, meropenem with EDTA induced slightly longer PAE and PLIE than imipenem with EDTA. Conclusions: This study has shown that EDTA combined with carbapenems produced a significant PLIE on VIM-MBL-positive P. aeruginosa strains. The results do not have any clinical relevance so far since metal chelators such as EDTA are not used as therapeutic agents due to their toxicity.

Clinical relevance of Proteus mirabilis in hospital patients:
A retrospective study was performed on 1072 non-duplicate isolates of Proteus mirabilis, taken in the period April 1996 to March 1998, and on 100 patient charts randomly selected during the same period. P. mirabilis isolates accounted for 7.7% of Enterobacteriaceae. The isolates were predominantly from urine (70.2%); of the total, 38.0% were penicillinase-producing isolates, 6.9% were extended-spectrum beta-lactamase (ESBL)-producing isolates and 3.6% produced inhibitor-resistant beta-lactamase (IRB). ESBL-producing isolates were observed in long-stay and intensive care and IRB-producing isolates in paediatric units. Of the 95 patients whose charts were examined, 69 had a confirmed infection, which in 42 cases was nosocomial.

Bacterial resistance to beta-lactam antibiotic
The historical development of antibiotic resistance, mechanisms of resistance, classification schemes for beta-lactamases, the clinical relevance of resistance, and approaches to overcoming resistance are reviewed. The promise of eradication of infectious diseases has not been fulfilled, in great part owing to the emergence of antibiotic-resistant organisms. Although genes for bacterial resistance may have existed before the clinical use of antibiotics, selection of new resistant strains is driven by the widespread use of antimicrobials in humans and animals. The most commonly prescribed antimicrobials in the United States are the beta-lactam antibiotics, and the most common mechanism of bacterial resistance to these agents is inactivation by beta-lactamase. The clinical and economic consequences of therapeutic failure and relapse--extended hospital stays, increased morbidity and mortality, and the use of potentially more toxic and costly antimicrobial agents--require new strategies to prevent the spread of resistant organisms and to limit future resistance.

Ability of newer beta-lactam antibiotics to induce beta-lactamase production in Enterobacter cloacae:
The beta-lactamase inducing properties of various new beta-lactam antibiotics in two isogenic strains of Enterobacter cloacae were investigated. Beta-lactamase activity was measured two hours after addition of inducer to cells in the late logarithmic growth-phase. Beta-lactamase expression was highly dependent on the growth medium used, highest levels being obtained after induction with cefoxitin in Tryptic Soy broth, Mueller-Hinton broth and Nutrient broth. Upon induction the mutant 908 Ssi produced tenfold higher beta-lactamase levels than its parent wild type 908 Swi. Among the new antibiotics investigated, sulfoxides of several oxyimino-cephalosporins, HR 810, cefetamet, cefteram, carumonam and BRL 36650 were moderate or poor inducers. The penem FCE 22101 resembled imipenem in its strong inducing properties.