A total of 904 consecutive nosocomial isolates of Escherichia coli and Klebsiella pneumoniae collected from 28 Russian hospitals were screened for production of extended-spectrum ␤-lactamases (ESBLs). The ESBL phenotype was detected in 78 (15.8%) E. coli and 248 (60.8%) K. pneumoniae isolates. One hundred fifteen isolates carried the genes for CTX-M-type ␤-lactamases, which, as shown by PCR-restriction fragment length polymorphism analysis, were distributed into the two genetic groups of CTX-M-1 (93%)-and CTX-M-2 (7%)-related enzymes. Isolates producing the enzymes of the first group were found in 20 hospitals from geographically distant regions of the country and were characterized by considerable diversity of genetic types, as was demonstrated by enterobacterial repetitive consensus PCR typing. Within this group the CTX-M-3 and the CTX-M-15 ␤-lactamases were identified. In contrast, the enzymes of the CTX-M-2 group (namely, CTX-M-5) were detected only in eight clonally related E. coli isolates from a single hospital. Notably, the levels of resistance to ceftazidime were remarkably variable among the CTX-M producers. This study provides further evidence of the global dissemination of CTX-M type ESBLs and emphasizes the need for their epidemiological monitoring.During the past decade extended-spectrum ␤-lactamases (ESBLs) of the CTX-M type emerged in many countries of the world. The first organisms producing ␤-lactamases of this type were identified both as single and epidemic clinical isolates in very distant geographic regions (Germany and France and Argentina) in the early 1990s (3, 5, 7). More recently, a rapid increase in the proportion of multiple CTX-M variants to the TEM-and SHV-derived ESBLs has been reported in many hospitals in Spain (9,12,15,35) (14), and Korea (28). Furthermore, CTX-M ␤-lactamases, mainly types CTX-M-2 and CTX-M-3, were found to be widespread or even predominant ESBL types in several countries, including Argentina (31, 34; M. Galas, F. Pasteran, R. Melano, A. Petroni, G. Lopez, A. Corso, A. Rossi, et al., Abstr. 38th Intersci. Conf. Antimicrob. Agents Chemother., abstr. E-109, 1998), Japan (41), and Poland (1).Currently the CTX-M family includes more than 20 ␤-lactamases, which may be grouped on the basis of sequence similarity into four distinct clusters (subtypes) epitomized by CTX-M-1, CTX-M-2, CTX-M-8, and CTX-M-9 (26, 37; http: //www.lahey.org/studies/webt.htm). Within each cluster there is a high degree of bla CTX-M gene sequence identity (Ͼ95%), although members of different subtypes share only 70 to 77% similarity at the nucleotide level. The recent finding of Kluyvera ascorbata species-specific ␤-lactamases (KluA) which share 98.6 to 100% identity with CTX-M-2 and CTX-M-5 and analysis of DNA sequences adjacent to the KluA-and CTX-Mcoding genes provide strong evidence of the direct evolution of the CTX-M-2 cluster from the chromosomal enzyme of K. ascorbata (20,36). Likewise, the chromosomal KLUG-1 enzyme of Kluyvera georgiana was found to be the most-probable progenitor of ...

In a randomized, evaluator-blind, multicenter trial, we compared cefepime (2 g three times a day) with imipenem-cilastatin (500 mg four times a day) for the treatment of nosocomial pneumonia in 281 intensive care unit patients from 13 centers in six European countries. Of 209 patients eligible for per-protocol analysis of efficacy, favorable clinical responses were achieved in 76 of 108 (70%) patients treated with cefepime and 75 of 101 (74%) patients treated with imipenem-cilastatin. The 95% confidence interval (CI) for the difference between these response rates (؊16 to 8%) failed to exclude the predefined lower limit for noninferiority of ؊15%. In addition, therapy of pneumonia caused by an organism producing an extendedspectrum ␤-lactamase (ESBL) failed in 4 of 13 patients in the cefepime group but in none of 10 patients in the imipenem group. However, the clinical efficacies of both treatments appeared to be similar in a secondary intent-to-treat analysis (95% CI for difference, ؊9 to 14%) and a multivariate analysis (95% CI for odds ratio, 0.47 to 1.75). Furthermore, the all-cause 30-day mortality rates were 28 of 108 (26%) patients in the cefepime group and 19 of 101 (19%) patients in the imipenem group (P ‫؍‬ 0.25). Rates of documented or presumed microbiological eradication of the causative organism were similar with cefepime (61%) and imipenem-cilastatin (54%) (95% CI, ؊23 to 8%). Primary or secondary resistance of Pseudomonas aeruginosa was detected in 19% of the patients treated with cefepime and 44% of the patients treated with imipenem-cilastatin (P ‫؍‬ 0.05). Adverse events were reported in 71 of 138 (51%) and 62 of 141 (44%) patients eligible for safety analysis in the cefepime and imipenem groups, respectively (P ‫؍‬ 0.23). Although the primary end point for this study does not exclude the possibility that cefepime was inferior to imipenem, some secondary analyses showed that the two regimens had comparable clinical and microbiological efficacies. Cefepime appeared to be less active against organisms producing an ESBL, but primary and secondary resistance to imipenem was more common for P. aeruginosa. Selection of a single agent for therapy of nosocomial pneumonia should be guided by local resistance patterns.

The problem of antimicrobial resistance surveillance in Europe has been debated extensively in many excellent documents issued by national committees that often assume the value of national guidelines. However, a comprehensive document addressing the whole matter from a European perspective, as well as reviewing its present status and drafting future perspectives, has been lacking. The present recommendations have been produced by the ESCMID Study Group for Antimicrobial Resistance Surveillance (ESGARS) through a consensus process involving all members of the Study Group. The recommendations focus on the detection of bacterial resistance and its reporting to clinicians, public health officers and a wider-and ever-increasing-audience. The leading concept is that the basis for resistance monitoring is microbiological diagnostics. The prerequisites for resistance monitoring are findings of adequate quality and quantity, which have been recorded properly and evaluated correctly. Different types of surveillance studies should fulfil different requirements with regard to data collection and reporting, the expected use of data, and the prerequisites for networking such activities. To generate relevant indicators, bacterial resistance data should be reported using adequate denominators and stratification. Reporting of antimicrobial resistance data is necessary for selection of empirical therapy at the local level, for assessing the scale of the resistance problem at the local, national or international levels, for monitoring changes in resistance rates, and for detecting the emergence and spread of new resistances types. Any type of surveillance study should conclude, where appropriate, with a proposal for intervention based on the data obtained.

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The objective of this study was to inventory the stock of antimicrobials in the home medicine cabinets (HMCs) of the general population in Russia and to find out for which indications people report that they would use antibiotics without a physician's recommendation. The research was performed in 9 Russian cities by physicians who visited households. An inventory of antibiotics in HMCs was made, and respondents were asked about instances in which they would choose automedication with antibiotics. We found that 83.6% of families had antibiotics for systemic use in HMCs. The most common antibiotics in HMCs were trimethoprim-sulfamethoxazole (46.3% of HMCs), ampicillin (45.1%), chloramphenicol (32.7%), erythromycin (25.5%), and tetracycline (21.8%). The major indications for automedication with antibiotics were acute viral respiratory tract infections (12.3% of total indications), cough (11.8%), intestinal disorders (11.3%), fever (9%), and sore throat (6.8%). According to this study, antibiotics are widely stocked among the general population in Russia, and people use antibiotics in an uncontrolled and imprudent manner.

The urine antigen test allowed targeted use of a penicillin (amoxicillin) for young immunocompetent individuals with nonsevere, community-acquired pneumonia. Clarithromycin was highly effective against both S. pneumoniae pneumonia and pneumonia due to atypical pathogens.

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Thirty-four cefotaxime-resistant Salmonella enterica serovar Typhimurium isolates representative of the isolates that caused outbreaks of gastroenteritis in 10 hospitals in seven regions of Russia and Belarus from 1994 to 2003 were analyzed. All isolates produced the CTX-M-5-like extended-spectrum ␤-lactamase, which confers high-level resistance to cefotaxime and ceftriaxone and decreased susceptibility to ceftazidime. The bla CTX-M genes were located on small (7.4-to 12-kb) non-self-transferable plasmids approximately 20 bp downstream of the ISEcp1 insertion sequences. Some isolates carried additional conjugative plasmids mediating resistance to penicillin-inhibitor combinations and various non-␤-lactam agents, including tetracycline, chloramphenicol, gentamicin, tobramycin, and co-trimoxazole. Despite the minor differences in susceptibility patterns, all isolates were considered clonally related on the basis of arbitrarily primed PCR and pulsed-field gel electrophoresis analysis. The similarities of the restriction profiles of the CTX-M-coding plasmids further supported the clonal origin of these isolates.