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- W1554620281 abstract "Extended-spectrum β-lactamases (ESBL) confer resistance to aztreonam, cefotaxime, ceftazidime and related oxyimino-β-lactams, but are unable to hydrolyze cephamycins or carba-penems. Each ESBL may confer universal resistance to these oxyimino-compounds or selective resistance for particular β-lactams. In most instances, ESBL enzymes are inhibitable by clavulanate or other inhibitors such as tazobactam or sulbactam. ESBLs have rapidly established a global presence and, once established in a region, often become a prominent resistance mechanism. Within 5 years of detection of the first ESBL in France, the overall prevalence of ESBL-producing Klebsiella pneumoniae increased to 14% and in certain hospitals the prevalence surpassed 35% [1Sirot DL Goldstein FW Soussy CJ et al.Resistance to cefotaxime and seven other beta-lactams in members of the family Enterobacteriaceae: a 3-year survey in France.Antimicrob Agents Chemother. 1992; 36: 1677-1681Crossref PubMed Scopus (128) Google Scholar]. Today, hospital outbreaks of ESBL-producing K. pneumoniae have been described from many countries and, in particular regions, the prevalence of these organisms has exceeded 40-50% [2Burwen DR Banerjee SN Gaynes RP Ceftazidime resistance among selected nosocomial gram-negative bacilli in the United States. National Nosocomial Infections Surveillance System.J Infect Dis. 1994; 170: 1622-1625Crossref PubMed Scopus (214) Google Scholar, 3Monnet DL Biddle JW Edwards JR et al.Evidence of interhospital transmission of extended-spectrum beta-lactam-resistant Klebsiella pneumoniae in the United States. 1986-93.Infect Control Hosp Epidemiol. 1997; 18: 492-498Crossref PubMed Google Scholar]. Epidemiologic studies including molecular typing methods have revealed clonal spread within hospitals as well as interhospital transmission of extended-spectrum β-lactam-resistant K. pneumoniae [3Monnet DL Biddle JW Edwards JR et al.Evidence of interhospital transmission of extended-spectrum beta-lactam-resistant Klebsiella pneumoniae in the United States. 1986-93.Infect Control Hosp Epidemiol. 1997; 18: 492-498Crossref PubMed Google Scholar, 4Neuwirth C Siebor E Lopez J Pechinot A Kazmierczak A Outbreak of TEM-24-producing Enterobacter aerogenes in an intensive care unit and dissemination of the extended-spectrum beta-lactamase to other members of the family enterobacteriaceae.J Clin Microbiol. 1996; 34: 76-79PubMed Google Scholar]. In addition, plasmids carrying ESBL genes have been spread between bacterial species and to genetically unrelated Klebsiella isolates [5Sirot J Chanal C Petit A Sirot D Labia R Gerbaud G Klebsiella pneumoniae and other Enterobacteriaceae producing novel plasmid-mediated beta-lactamases markedly active against third-generation cephalosporins: epidemiologic studies.Rev Infect Dis. 1988; 10: 850-859Crossref PubMed Scopus (122) Google Scholar]. More recently, K. pneumoniae and Escherichia coli isolates have acquired plasmid-mediated AmpC β-lactamases [6Papanicolaou GA Medeiros AA Jacoby GA Novel plasmid-mediated beta-lactamase (MIR-1) conferring resistance to oxyimino- and alpha-methoxy beta-lactams in clinical isolates of Klebsiella pneumoniae.Antimicrob Agents Chemother. 1990; 34: 2200-2209Crossref PubMed Scopus (236) Google Scholar, 7Payne DJ Woodford N Amyes SG Characterization of the plasmid mediated beta-lactamase BIL-1.J Antimicrob Chemother. 1992; 30: 119-127Crossref PubMed Scopus (47) Google Scholar, 8Gonzalez Leiza M Perez-Diaz JC Ayala J et al.Gene sequence and biochemical characterization of FOX-1 from Klebsiella pneumoniae, a new AmpC-type plasmid-mediated beta-lactamase with two molecular variants.Antimicrob Agents Chemother. 1994; 38: 2150-2157Crossref PubMed Google Scholar]. These enzymes are constitutively expressed at high levels and confer resistance to the cephamycins as well as the extended-spectrum cephalosporins. In this study, we have characterized the antimicrobial phenotypes, molecular epidemiology and the general patterns of β-lactamases expressed by a series of ESBL-producing K. pneumoniae isolates obtained from six Russian medical centres. Thirty-one K. pneumoniae isolates were collected from six Russian medical centres during 1994-96. The organisms were isolated from blood, cerebrospinal fluid, urine, sputum and wounds. Isolates were selected on the basis of intermediate or resistant minimum inhibitory concentrations (MICs) to third generation cephalosporins. Seventeen strains came from one medical centre (Medical Center 1,Table 1). Strains labelled ‘A’ were isolated between September and October, 1994; ‘B’ isolates from September, 1995 to January 1996; and the single ‘C’ strain was isolated in late March 1996. Other medical centres (Medical Centers 2-6) were located in cities ranging from Western Russia to Siberia.Table 1Comprehensive evaluation of 31 Klebsiella pneumoniae strains isolated from patients in six medical centers in Russia. Epidemiologic, molecular, and phenotypic studies were focused on strains consistent with the production of extended spectrum beta-lactamasesMIC (mg/L)bCTAZ, ceftazidime; CROX, cefuroxime; CTAX, cefotaxime; CTRI, ceftriaxone; CFOX, cefoxitin; IMIP, imipenem.ESBL test resultsdESBL tests were substrate MICs measured in an Etest format with a fixed concentration of clavuIanic acid (CA; 2 μg/ml). A > 2 log2 dilution step reduction in the MIC with CA compared to the substrate cephalosporin alone was defined as a positive test.OrganismPFGEaMolecular typing by pulsed field gel electrophoresis (PFGE).Medical centerCTAZCROXCTAXCTRICPIMCFOXIMIPplCo-resistancescCo-resistance defined as an MIC in the resistant range by NCCLS criteria (1998). F, fluoroquinolones (using ciprofloxacin as an index drug); G, gentamicin; To, tobramycin; Tc, tetracyclines; S, trimethoprim-sulfamethoxazole.CTAZCROXCTAXCTRICPIM1G1IA1.561.520.3830.55,4,7.6G To Tc S+−+++2G3IA81244180.255.4,7.6G To Tc S+–+++3G2IA64>256>256>256128160.257.6F G To Tc S+++++4G2IA96>25696>256241617.6G To Tc S+++++5G4IA96>256>256>25648160.257.6G To Tc S+++++6G5IB4328162425.4,7.6G To Tc S+++++7G5IB63232164845.4,7.6G To Tc S+++++8G5IB316431425.4,7.6G To Tc S+++++9G5IB261.520.38415.4,7.6G To Tc S+−+++10G5IB8321216260.55.4,7.6Tc+++++11G2IB161282464830.55.4,7.6GToTc+++++12G6IB241284896880.55.4,7.6G To Tc S+++++13G2IB282120.5815.4,7.6GToTc+−+++14MIB316241120.125.4,7.6G To Tc S+−+++15KIB6>256>256>2563230.55.4, 7.6, 7.9eThese β(-lactamases were inhibited by cefoxitin (5 mg/ml)., 8.5eThese β(-lactamases were inhibited by cefoxitin (5 mg/ml).G To Tc S+++++16KIB12>256>256>25612425.4, 7.6,7.9eThese β(-lactamases were inhibited by cefoxitin (5 mg/ml)., 8.5eThese β(-lactamases were inhibited by cefoxitin (5 mg/ml).G To Tc S+++++17LIC616382325.4,7.5,7.6GToS+++++18I23162432130.127.6G To Tc S+++++19I283212241.540.125.4,7.6G To Tc S+++++20D13>256>256>256>2563230.127.2,8.2GToS+++++21D13>256>25648>256430.57.2,8.2GToS+++++22D23326424256120.57.2,8.2GToS+++++23A432>256>256>256840.55.4, 8.8eThese β(-lactamases were inhibited by cefoxitin (5 mg/ml).GToS+++++24A432>256>256>2563260.255.4, 7.6, 8.8eGToS+++++25B49632481120.257.6,8.2GToS+−+++26C52>25664256460.256.1,7.6, 8.5eThese β(-lactamases were inhibited by cefoxitin (5 mg/ml).GToS−++++27C5>256>25648>2561280.126.1, 7.6, 8.2, 8.5eThese β(-lactamases were inhibited by cefoxitin (5 mg/ml).GTo+++++28C596>256>256>256640.256.1,7.6,8.2,8.5eGTo+++++29E6>256>256>256>256128320.125.4,7.6,8.2GToTc+++++30E6>256>256>256>25648640.255.4,7.6,8.2GToTc+++++31F6>256>256>256>2561680.255.4,7.6,8.2GToTc+++++a Molecular typing by pulsed field gel electrophoresis (PFGE).b CTAZ, ceftazidime; CROX, cefuroxime; CTAX, cefotaxime; CTRI, ceftriaxone; CFOX, cefoxitin; IMIP, imipenem.c Co-resistance defined as an MIC in the resistant range by NCCLS criteria (1998). F, fluoroquinolones (using ciprofloxacin as an index drug); G, gentamicin; To, tobramycin; Tc, tetracyclines; S, trimethoprim-sulfamethoxazole.d ESBL tests were substrate MICs measured in an Etest format with a fixed concentration of clavuIanic acid (CA; 2 μg/ml). A > 2 log2 dilution step reduction in the MIC with CA compared to the substrate cephalosporin alone was defined as a positive test.e These β(-lactamases were inhibited by cefoxitin (5 mg/ml). Open table in a new tab The MICs were determined by broth microdilution and E-test methodologies (AB Biodisk, Solna, Sweden) as per the 1998 National Committee for Clinical Laboratory Standards (NCCLS) recommendations. All isolates demonstrated an ESBL phenotype using double-disk synergy [9Jarlier V Nicolas MH Fournier G Philippon A Extended broad-spectrum beta-lactamases conferring transferable resistance to newer beta-lactam agents in Enterobacteriaceae: hospital prevalence and susceptibility patterns.Rev Infect Dis. 1988; 10: 867-878Crossref PubMed Scopus (1285) Google Scholar]. Additionally, ESBL phenotypes were characterized with ESBL E-test strips containing 0.016 to 256 mg/L of ceftazidime, cefuroxime, cefotaxime, ceftriaxone or cefepime in the presence of a fixed concentration of clavulanic acid (2 mg/L, generously provided by AB Biodisk) (seeTable 1). Each isolate was evaluated for evidence of a eight-fold or greater decrease in MIC to one or more oxyimino-cephalosporins [10Cormican MG Marshall SA Jones RN Detection of extended-spectrum beta-lactamase (ESBL)-producing strains by the Etest ESBL screen.J Clin Microbiol. 1996; 34: 1880-1884PubMed Google Scholar]. Cefotaxime, ceftriaxone and cefepime detected 100% of the ESBLs whereas ceftazidime detected 97% and cefuroxime detected only 81% of ESBL phenotypes. The currently marketed ceftazidime E-test strip would have missed only one isolate (organism 26;Table 1). This organism had a ceftazidime MIC of 2mg/L that dropped to 1 mg/L in the presence of clavulanic acid. Typically, the genes for ESBLs reside on large plasmids which also carry resistance genes for other classes of antimicrobials [11Jacoby GA Sutton L Properties of plasmids responsible for production of extended-spectrum beta-lactamases.Antimicrob Agents Chemother. 1991; 35: 164-169Crossref PubMed Scopus (175) Google Scholar, 12Vatopoulos AC Philippon A Tzouvelekis LS Komninou Z Legakis NJ Prevalence of a transferable SHV-5 type beta-lactamase in clinical isolates of Klebsiella pneumoniae and Escherichia coli in Greece.J Antimicrob Chemother. 1990; 26: 635-648Crossref PubMed Scopus (79) Google Scholar]. Indeed, it has been suggested that multidrug resistance in enteric Gram-negative isolates should instigate further testing for ESBLs [11Jacoby GA Sutton L Properties of plasmids responsible for production of extended-spectrum beta-lactamases.Antimicrob Agents Chemother. 1991; 35: 164-169Crossref PubMed Scopus (175) Google Scholar, 13Philippon A Labia R Jacoby G Extended-spectrum beta-lactamases.Antimicrob Agents Chemother. 1989; 33: 1131-1136Crossref PubMed Scopus (487) Google Scholar]. The Russian isolates demonstrated co-resistances to tobramycin or gentamicin (97%), trimethoprim-sulfa-methoxazale (84%) and tetracycline (68%) (Table 1). Fluoroquinolone resistance among the Russian isolates was rare (3%), probably reflecting the fact that quinolone resistance is most commonly acquired through chromosomal mutations rather than plasmid exchange. In most cases, high level fluoroquinolone resistance results from chromosomal mutations in the gyr A and par C genes or changes in permeability or efflux which reflect selective pressure in the clinical environment [14Rice LB Bonomo RA Genetic and biochemical mechanisms of bacterial resistance to antimicrobial agents.in: Lorian V Antibiotics in Laboratory Medicine. Williams & Wilkins, Baltimore, MD1996: 453-501Google Scholar]. Only one study has demonstrated low-level quinolone resistance transmitted on plasmid DNA [15Martinez-Martinez L Pascual A Jacoby GA Quinolone resistance from a transferable plasmid.Lancet. 1998; 351: 797-799Abstract Full Text Full Text PDF PubMed Scopus (887) Google Scholar]. To determine whether clonal spread of organisms carrying an ESBL was common in Russia, genotype analysis was performed using pulsed-field gel electrophoresis (PFGE) of SpeI-digested chromosomal DNA (Table 1 and Figure 1). Genomic DNA was isolated and digested with Spe1 (New England Biolabs, Beverly, MA, USA) as previously described [16Pfaller MA Hollis RJ Sader HS Chromosomal restriction fragment analysis by pulsed-field gel electrophoresis.in: Isenberg HD Clinical Microbiology Procedures Handbook. Volume. American Society for Microbiology, Washington, DC1994: 10.5c.1-12Google Scholar]. Electrophoresis was performed on the CHEF-DRII (Bio-Rad Laboratories, Richmond, CA, USA) with the following conditions: 0.5 × TBE, 1% Agarose, 13°C, 200V, 23h with the switch interval at 5 to 60 s. Gels were stained with ethidium bromide. Strains that contained restriction fragment patterns that differed by more than three bands were considered unique and were assigned a letter designation. If banding patterns differed by three bands or less, an alpha numeric designation was assigned to each minor subtype (e.g. A1, A2, etc.) [17Tenover FC Arbeit RD Goering RV et al.Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterial strain typing.J Clin Microbiol. 1995; 33: 2233-2239PubMed Google Scholar]. Thirteen of 17 isolates that came from Medical Center 1 were highly related by PFGE. Although there were six PFGE subtypes (G1-G6) among these 13 isolates, none of the patterns differed by more than three bands. Of the remaining four organisms isolated at Medical Center 1, two were identical by PFGE analysis and the remaining organisms represented single molecular types. Similarly, organisms isolated from each of the five remaining medical centres showed a high degree of molecular relatedness (Table 1). With the exception of Medical Center 4, all isolates within each medical centre showed highly related PFGE patterns whereas Medical Center 4 contributed three organisms, two of which demonstrated identical PFGE. These results suggest that there was significant clonal transmission within each institution. However, there was no evidence for clonal spread between medical centers. Medical Center 1 continued to identify clonal isolates over 18 months. Unfortunately, this experience is not uncommon. A number of hospitals have identified the prolonged endemic or epidemic presence of K. pneumoniae isolates carrying ESBLs [18Meyer KS Urban C Eagan JA Berger BJ Rahal JJ Nosocomial outbreak of Klebsiella infection resistant to late-generation cephalosporins [see comments].Ann Intern Med. 1993; 119: 353-358Crossref PubMed Scopus (524) Google Scholar]. The ISO-electric focussing (IEF) analysis of β-lactamases carried by organisms can provide indications that help place enzymes into the Bush-Jacoby-Medeiros functional group 2be enzyme class or other enzyme classes such as, the plasmid-mediated Amp-C-like enzymes Bush-Jacoby-Medeiros functional group 1 [19Bush K Jacoby GA Medeiros AA A functional classification scheme for beta-lactamases and its correlation with molecular structure.Antimicrob Agents Chemother. 1995; 39: 1211-1233Crossref PubMed Scopus (2039) Google Scholar]. Although IEF alone cannot differentiate specific β-lactamases, it does provide a rapid method to assess the relative nature of β-lactamases present in a particular organism and a means for comparison of β-lactamases present in different organisms. Crude β-lactamase extracts were prepared by freeze-thaw lysis of bacterial cultures grown exponentially in tryptic soy broth, as previously described [20Bradford PA Cherubin CE Idemyor V Rasmussen BA Bush K Multiply resistant Klebsiella pneumoniae strains from two Chicago hospitals: identification of the extended-spectrum TEM-12 and TEM-10 ceftazidime-hydrolyzing beta-lactamases in a single isolate.Antimicrob Agents Chemother. 1994; 38: 761-766Crossref PubMed Scopus (116) Google Scholar]. Analytical isoelectric focusing was performed using a Multiphore II electrophoresis system and prepared ampholine-polyacrylamide plates, pI 3.5-9.5 and pI 5.5-8.5 (Amersham Pharmacia Biotech, Piscataway, NJ, USA) with limits of 1500 V, 30mA, 30W for 1.5h or 1600 V, 50 mA, 25 W for 2.5 h, respectively. The β-lactamase activity was detected with nitrocephin 500 mg/L (Beckton Dickinson Microbiology Systems, Cockeysville, MD, USA). TEM 1, TEM 4, SHV 1, SHV 3, and SHV 5 β-lactamases expressed in E. coli C600 (generously provided by G. Jacoby) were used as pI standards [21Jacoby GA Carreras I Activities of beta-lactam antibiotics against Escherichia coli strains producing extended-spectrum beta-lactamases.Antimicrob Agents Chemother. 1990; 34: 858-862Crossref PubMed Scopus (185) Google Scholar]. Known pI values of each standard were plotted against the distance from the cathode and a regression analysis was performed (Microsoft, Redmond, WA, USA, Excel 98). Unknown β-lactamase pIs were calculated using the regression curve generated from each gel. Crude lysates were also analyzed for cefoxitin-inhibitable β-lactamases typical of the AmpC or Bush-Jacoby-Medeiros functional Class 1 enzymes [20Bradford PA Cherubin CE Idemyor V Rasmussen BA Bush K Multiply resistant Klebsiella pneumoniae strains from two Chicago hospitals: identification of the extended-spectrum TEM-12 and TEM-10 ceftazidime-hydrolyzing beta-lactamases in a single isolate.Antimicrob Agents Chemother. 1994; 38: 761-766Crossref PubMed Scopus (116) Google Scholar]. These gels were developed with a mixture of nitrocephin (500 mg/L) and cefoxitin (5000 mg/L) [6Papanicolaou GA Medeiros AA Jacoby GA Novel plasmid-mediated beta-lactamase (MIR-1) conferring resistance to oxyimino- and alpha-methoxy beta-lactams in clinical isolates of Klebsiella pneumoniae.Antimicrob Agents Chemother. 1990; 34: 2200-2209Crossref PubMed Scopus (236) Google Scholar]. The IEF analysis of the β-lactamases provided some explanation for the complexity of antimicrobial resistance in these Russian isolates. Most isolates contained two or more β-lactamases (Table 1 and Figure 2) with a range between one and four β-lactamases per isolate. The β-lactam susceptibilities probably reflect additivity among these multiple enzymes. Twenty isolates (65%) expressed a β-lactamase that comigrated with TEM1 at pI 5.4. This number closely resembles French studies where 66% of ESBL-expressing K. pneumoniae isolates carried TEM1 [22Soilleux MJ Morand AM Arlet GJ Scavizzi MR Labia R Survey of Klebsiella pneumoniae producing extended-spectrum beta-lactamases: prevalence of TEM-3 and first identification of TEM-26 in France.Antimicrob Agents Chemother. 1996; 40: 1027-1029PubMed Google Scholar]. This coexpression of TEM1 and an ESBL can significantly compromise the effects of β-lactamase inhibitors potentially resulting in significant therapeutic consequences [23Jacoby GA Genetics of extended-spectrum beta-lactamases.Eur J Clin Microbiol Infect Dis. 1994; 13: S2-11Crossref PubMed Scopus (107) Google Scholar]. Isolates from a single medical centre typically displayed β-lactamases with shared pIs. Some of these enzymes appeared to be unique for a particular medical centre. For example, Medical Center 3 contained a β-lactamase, pI 7.2, which was seen only within this medical centre and was shared by all isolates analyzed from this hospital. Medical Center 6 demonstrated three organisms with identical IEF profiles yet, two different PFGE patterns suggesting plasmid dissemination within this hospital as well as clonal transmission. Twenty-seven strains expressed one or more ESBLs that comigrated at a pI of 7.6. Since several SHV ESBL variants (SHV 2,2a, 6, 7, 8) and the Klebsiella pneumoniae chromosomal SHV1 enzyme cluster at this pI, it is difficult to determine whether these isolates contain identical β-lactamases or whether they express one or more SHV enzymes [24Jacoby GA Bush K Amino acid sequences for TEM, SHV and OXA extended-spectrum beta-lactamases. 1998; http://www.lahey.org/studies/webt.htmGoogle Scholar]. In Medical Center 1, the 13 isolates that shared PFGE patterns also shared β-lactamases with similar pIs (5.4 and 7.6). Interestingly, three isolates from this group contained only a single β-lactamase of pI 7.6. The antibiograms from these three organisms differed markedly from other related strains from the same medical centre, showing significantly higher MICs for all oxyimino-cephalosporins and related compounds, as well as cefoxitin. These three organisms may express an SHV variant better able to hydrolyze extended-spectrum cephalosporins. Alternatively, differences in antimicrobial susceptibilities may reflect differences in promoter strength, plasmid number or permeability differences among these isolates [25Nuesch-Inderbinen MT Hachler H Kayser FH New system based on site-directed mutagenesis for highly accurate comparison of resistance levels conferred by SHV beta-lactamases.Antimicrob Agents Chemother. 1995; 39: 1726-1730Crossref PubMed Scopus (32) Google Scholar, 26Livermore DM Beta-lactamases in laboratory and clinical resistance.Clin Microbiol Rev. 1995; 8: 557-584Crossref PubMed Google Scholar]. Sequence analysis and further molecular studies will be required to determine the exact nature of antimicrobial resistances in these isolates. Seven isolates from three different medical centres expressed β-lactamases with highly basic pIs of 8.5-8.8. This pI range often includes enzymes from the Amp-C or functional class 1 family [20Bradford PA Cherubin CE Idemyor V Rasmussen BA Bush K Multiply resistant Klebsiella pneumoniae strains from two Chicago hospitals: identification of the extended-spectrum TEM-12 and TEM-10 ceftazidime-hydrolyzing beta-lactamases in a single isolate.Antimicrob Agents Chemother. 1994; 38: 761-766Crossref PubMed Scopus (116) Google Scholar]. To determine whether these highly basic enzymes were inhibited by cefoxitin, IEF gels were developed with nitrocephin 500 mg/L or nitrocephin plus cefoxitin (5000 mg/L). All enzymes comigrating at 8.5 and 8.8 were inhibited by cefoxitin. However, only two of these isolates expressed intermediate MICs (16 mg/L) to cefoxitin. Although derepressed AmpC enzymes typically confer high-level cefoxitin resistance, low levels of expression of these enzymes can lead to lower cefoxitin MICs. The Russian isolates containing these highly basic, cefoxitin-inhibitable β-lactamases may express only low levels of an AmpC enzyme. Alternatively, these enzymes may represent another class of β-lactamase that hydrolzes cefoxitin at low levels. Conjugation and sequence analysis experiments will be required to further identify these enzymes. This study was not designed to address prevalence or to identify all organisms carrying ESBLs. However, in 1996, 33% of 168 isolated nosocomial strains of K. pneumoniae from Russian intensive care units (ICU) demonstrated an elevated MIC for third-generation cephalosporins and an ESBL phenotype. Within each ICU the percentages of K. pneumoniae expressing an ESBL phenotype ranged from 29 to 83% (L. Stratcounski and O. Stetsiouk, unpublished data). These numbers are high, but not unprecedented. The literature demonstrates many cases where hospitals have noted rapid increases in the numbers of organisms carrying ESBLs, interunit spread through each hospital and interhospital spread to neighbouring hospitals and nursing care facilities [3Monnet DL Biddle JW Edwards JR et al.Evidence of interhospital transmission of extended-spectrum beta-lactam-resistant Klebsiella pneumoniae in the United States. 1986-93.Infect Control Hosp Epidemiol. 1997; 18: 492-498Crossref PubMed Google Scholar, 4Neuwirth C Siebor E Lopez J Pechinot A Kazmierczak A Outbreak of TEM-24-producing Enterobacter aerogenes in an intensive care unit and dissemination of the extended-spectrum beta-lactamase to other members of the family enterobacteriaceae.J Clin Microbiol. 1996; 34: 76-79PubMed Google Scholar, 9Jarlier V Nicolas MH Fournier G Philippon A Extended broad-spectrum beta-lactamases conferring transferable resistance to newer beta-lactam agents in Enterobacteriaceae: hospital prevalence and susceptibility patterns.Rev Infect Dis. 1988; 10: 867-878Crossref PubMed Scopus (1285) Google Scholar, 18Meyer KS Urban C Eagan JA Berger BJ Rahal JJ Nosocomial outbreak of Klebsiella infection resistant to late-generation cephalosporins [see comments].Ann Intern Med. 1993; 119: 353-358Crossref PubMed Scopus (524) Google Scholar, 27Rice RJ Knapp JS Antimicrobial susceptibilities of Neisseria gonorrhoeae strains representing five distinct resistance phenotypes.Antimicrob Agents Chemother. 1994; 38: 155-158Crossref PubMed Scopus (33) Google Scholar, 28Rice LB Willey SH Papanicolaou GA et al.Outbreak of ceftazidime resistance caused by extended-spectrum beta-lactamases at a Massachusetts chronic-care facility.Antimicrob Agents Chemother. 1990; 34: 2193-2199Crossref PubMed Scopus (319) Google Scholar, 29Schiappa DA Hayden MK Matushek MG et al.Ceftazidime-resistant Klebsiella pneumoniae and Escherichia coli bloodstream infection: a case-control and molecular epidemiologic investigation.J Inf Dis. 1996; 174: 529-536Crossref PubMed Scopus (223) Google Scholar]. It is clear that identification of a single isolate containing an ESBL requires rapid epidemiologic response including strict infection control measures and review of antimicrobial use policies. P. L.W. was supported in part by a Merit Review Award from the Veterans Administration. J. B. was supported in part by the Fogarty International Center International Training and Research Program in Environmental and Occupational Health (National Institutes of Health) and Pioneer Hi-bred International, Inc. We also thank the following microbiology laboratories and directors for submitting nosocomial K. pneumoniae isolates: V. K. Taraban and N. P. Melnikova, Regional Clinical Hospital of Krasnodar; D. E. Zdzitovetski and T. B. Skazka, Clinical Emergency Hospital of Krasnojarsk; N. E. Marusina, Republic Child Clinical Hospital of Kazan; V. E. Iljina, Regional Clinical Hospital of Novosibirsk, V. V. Tetz and N. V. Zsaslavskaya, Medical Academy, St. Petersburg." @default.
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- W1554620281 title "Russian Klebsiella pneumoniae isolates that express extended-spectrum β-lactamases" @default.
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