The new beta-lactamases.

The β-lactamases are the major bacterial defense of gram-negative bacteria against β-lactam antibiotics. This review details the many types of β-lactamases, explains how they can be detected, and summarizes information on the genetics of this form of resistance. The authors also suggest strategies for clinical management and prevention of this difficult type of antibiotic resistance.

[1]  R. Hedges,et al.  Transposition of ampicillin resistance from RP4 to other replicons , 2004, Molecular and General Genetics MGG.

[2]  Ronald N. Jones,et al.  Global patterns of susceptibility for 21 commonly utilized antimicrobial agents tested against 48,440 Enterobacteriaceae in the SENTRY Antimicrobial Surveillance Program (1997-2001). , 2003, Diagnostic microbiology and infectious disease.

[3]  K. Bush,et al.  Effects of Inoculum and β-Lactamase Activity in AmpC- and Extended-Spectrum β-Lactamase (ESBL)-Producing Escherichia coli and Klebsiella pneumoniae Clinical Isolates Tested by Using NCCLS ESBL Methodology , 2004, Journal of Clinical Microbiology.

[4]  R A Weinstein,et al.  Multiple antibiotic-resistant Klebsiella and Escherichia coli in nursing homes. , 1999, JAMA.

[5]  H. Goossens,et al.  Epidemiology of ciprofloxacin resistance and its relationship to extended-spectrum beta-lactamase production in Klebsiella pneumoniae isolates causing bacteremia. , 2000, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[6]  J. D. Di Conza,et al.  Early Dissemination of CTX-M-Derived Enzymes in South America , 2002, Antimicrobial Agents and Chemotherapy.

[7]  Robert A Bonomo,et al.  Ultrahigh resolution structure of a class A beta-lactamase: on the mechanism and specificity of the extended-spectrum SHV-2 enzyme. , 2003, Journal of molecular biology.

[8]  R. Cantón,et al.  Variations in the prevalence of strains expressing an extended-spectrum beta-lactamase phenotype and characterization of isolates from Europe, the Americas, and the Western Pacific region. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[9]  S. Haeggman,et al.  An allelic variant of the chromosomal gene for class A beta-lactamase K2, specific for Klebsiella pneumoniae, is the ancestor of SHV-1 , 1997, Antimicrobial agents and chemotherapy.

[10]  H. Goossens,et al.  Antibiotic therapy for Klebsiella pneumoniae bacteremia: implications of production of extended-spectrum beta-lactamases. , 2004, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[11]  R. Gaynes,et al.  Ceftazidime resistance among selected nosocomial gram-negative bacilli in the United States. National Nosocomial Infections Surveillance System. , 1994, The Journal of infectious diseases.

[12]  J. Jorgensen,et al.  Clinical and Microbiologic Analysis of a Hospital's Extended‐Spectrum β‐Lactamase‐Producing Isolates Over a 2‐Year Period , 2003, Pharmacotherapy.

[13]  P. Lagrange,et al.  Molecular epidemiology of Klebsiella pneumoniae strains that produce SHV-4 beta-lactamase and which were isolated in 14 French hospitals , 1994, Journal of clinical microbiology.

[14]  J. Karlowsky,et al.  Trends in Antimicrobial Susceptibilities among Enterobacteriaceae Isolated from Hospitalized Patients in the United States from 1998 to 2001 , 2003, Antimicrobial Agents and Chemotherapy.

[15]  C. Segura,et al.  SHV-1 β-Lactamase Is Mainly a Chromosomally Encoded Species-Specific Enzyme in Klebsiella pneumoniae , 2001, Antimicrobial Agents and Chemotherapy.

[16]  J. Ariza,et al.  Epidemiology and Successful Control of a Large Outbreak Due to Klebsiella pneumoniae Producing ExtendedSpectrum β-Lactamases , 1998, Antimicrobial Agents and Chemotherapy.

[17]  L. Rice,et al.  Extended-Spectrum β-Lactamases in Klebsiella pneumoniae Bloodstream Isolates from Seven Countries: Dominance and Widespread Prevalence of SHV- and CTX-M-Type β-Lactamases , 2003, Antimicrobial Agents and Chemotherapy.

[18]  George A. Jacoby,et al.  Plasmid-Determined AmpC-Type β-Lactamases , 2002, Antimicrobial Agents and Chemotherapy.

[19]  G. Papanicolaou,et al.  Outbreak of ceftazidime resistance caused by extended-spectrum beta-lactamases at a Massachusetts chronic-care facility , 1990, Antimicrobial Agents and Chemotherapy.

[20]  Y. Arakawa,et al.  PCR Typing of Genetic Determinants for Metallo-β-Lactamases and Integrases Carried by Gram-Negative Bacteria Isolated in Japan, with Focus on the Class 3 Integron , 2003, Journal of Clinical Microbiology.

[21]  V. Dubois,et al.  Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae in Community and Private Health Care Centers , 2003, Antimicrobial Agents and Chemotherapy.

[22]  G. Jacoby,et al.  Roles of β-Lactamases and Porins in Activities of Carbapenems and Cephalosporins against Klebsiella pneumoniae , 1999, Antimicrobial Agents and Chemotherapy.

[23]  U. Garza-Ramos,et al.  TLA-1: a New Plasmid-Mediated Extended-Spectrum β-Lactamase from Escherichia coli , 2000, Antimicrobial Agents and Chemotherapy.

[24]  H. Hächler,et al.  Contribution of Natural Amino Acid Substitutions in SHV Extended-Spectrum β-Lactamases to Resistance against Various β-Lactams , 2000, Antimicrobial Agents and Chemotherapy.

[25]  P. Fey,et al.  Characterization of Plasmids Carrying CMY-2 from Expanded-Spectrum Cephalosporin-Resistant Salmonella Strains Isolated in the United States between 1996 and 1998 , 2002, Antimicrobial Agents and Chemotherapy.

[26]  R. Venezia,et al.  The SHV-5 extended-spectrum beta-lactamase gene of pACM1 is located on the remnant of a compound transposon. , 2004, Plasmid.

[27]  P. Nordmann,et al.  Emergence of Oxacillinase-Mediated Resistance to Imipenem in Klebsiella pneumoniae , 2004, Antimicrobial Agents and Chemotherapy.

[28]  T. Pitt,et al.  Epidemiological typing of klebsiellae with extended-spectrum beta-lactamases from European intensive care units. , 1998, The Journal of antimicrobial chemotherapy.

[29]  Peter S. Shenkin,et al.  Amino Acid Sequence Determinants of β-Lactamase Structure and Activity , 1996 .

[30]  J. Patel,et al.  Extended-Spectrum β-Lactamase–Producing Escherichia coli and Klebsiella Species: Risk Factors for Colonization and Impact of Antimicrobial Formulary Interventions on Colonization Prevalence , 2002, Infection Control & Hospital Epidemiology.

[31]  G. Cornaglia,et al.  Hospital outbreak of carbapenem-resistant Pseudomonas aeruginosa producing VIM-1, a novel transferable metallo-beta-lactamase. , 2000, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[32]  P. Nordmann,et al.  Ambler Class A Extended-Spectrum β-Lactamases in Pseudomonas aeruginosa: Novel Developments and Clinical Impact , 2003, Antimicrobial Agents and Chemotherapy.

[33]  J. Doise,et al.  Spread of Extended-Spectrum β-Lactamase—Producing Klebsiella pneumoniae: Are β-Lactamase Inhibitors of Therapeutic Value? , 1998 .

[34]  K S Meyer,et al.  Nosocomial Outbreak of Klebsiella Infection Resistant to Late-Generation Cephalosporins , 1993, Annals of Internal Medicine.

[35]  D. Livermore,et al.  OXA-17, a Further Extended-Spectrum Variant of OXA-10 β-Lactamase, Isolated from Pseudomonas aeruginosa , 1999, Antimicrobial Agents and Chemotherapy.

[36]  P. Bradford,et al.  Molecular epidemiology of a citywide outbreak of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae infection. , 2002, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[37]  R. Bonnet,et al.  A Novel Class A Extended-Spectrum β-Lactamase (BES-1) in Serratia marcescens Isolated in Brazil , 2000, Antimicrobial Agents and Chemotherapy.

[38]  B. Shoichet,et al.  An ultrahigh resolution structure of TEM-1 beta-lactamase suggests a role for Glu166 as the general base in acylation. , 2002, Journal of the American Chemical Society.

[39]  D. Maki,et al.  The Commonality of Risk Factors for Nosocomial Colonization and Infection with Antimicrobial-Resistant Staphylococcus aureus, Enterococcus, Gram-Negative Bacilli, Clostridium difficile, and Candida , 2002, Annals of Internal Medicine.

[40]  R. Ambler,et al.  The structure of beta-lactamases. , 1980, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[41]  A. Hossain,et al.  Discovery of CTX-M-Like Extended-Spectrum β-Lactamases in Escherichia coli Isolates from Five U.S. States , 2003, Antimicrobial Agents and Chemotherapy.

[42]  P. Nordmann,et al.  Emergence in Klebsiella pneumoniae of a Chromosome-Encoded SHV β-Lactamase That Compromises the Efficacy of Imipenem , 2003, Antimicrobial Agents and Chemotherapy.

[43]  G. Jacoby,et al.  A functional classification scheme for beta-lactamases and its correlation with molecular structure , 1995, Antimicrobial agents and chemotherapy.

[44]  R. Reichley,et al.  In vitro activities of various beta-lactam antimicrobial agents against clinical isolates of Escherichia coli and Klebsiella spp. resistant to oxyimino cephalosporins , 1995, Antimicrobial agents and chemotherapy.

[45]  A. Medeiros,et al.  Evolution of extended-spectrum beta-lactam resistance (SHV-8) in a strain of Escherichia coli during multiple episodes of bacteremia , 1997, Antimicrobial agents and chemotherapy.

[46]  M. Inoue,et al.  Characterization of SFO-1, a Plasmid-Mediated Inducible Class A β-Lactamase from Enterobacter cloacae , 1999, Antimicrobial Agents and Chemotherapy.

[47]  E. Kim,et al.  Bloodstream Infections by Extended-Spectrum β-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae in Children: Epidemiology and Clinical Outcome , 2002, Antimicrobial Agents and Chemotherapy.

[48]  M. Schaller,et al.  Cefepime versus Imipenem-Cilastatin for Treatment of Nosocomial Pneumonia in Intensive Care Unit Patients: a Multicenter, Evaluator-Blind, Prospective, Randomized Study , 2003, Antimicrobial Agents and Chemotherapy.

[49]  S. Campoy,et al.  Novel Complex sul1-Type Integron in Escherichia coli Carrying blaCTX-M-9 , 2002, Antimicrobial Agents and Chemotherapy.

[50]  R A Weinstein,et al.  Ceftazidime-resistant Klebsiella pneumoniae and Escherichia coli bloodstream infection: a case-control and molecular epidemiologic investigation. , 1996, The Journal of infectious diseases.

[51]  G. Jacoby,et al.  Activities of beta-lactam antibiotics against Escherichia coli strains producing extended-spectrum beta-lactamases , 1990, Antimicrobial Agents and Chemotherapy.

[52]  H. Leblebicioglu,et al.  Widespread detection of PER-1-type extended-spectrum beta-lactamases among nosocomial Acinetobacter and Pseudomonas aeruginosa isolates in Turkey: a nationwide multicenter study , 1997, Antimicrobial agents and chemotherapy.

[53]  P. Bradford,et al.  Emergence of carbapenem-resistant Klebsiella species possessing the class A carbapenem-hydrolyzing KPC-2 and inhibitor-resistant TEM-30 beta-lactamases in New York City. , 2004, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[54]  G. Jacoby,et al.  Comparative in vitro activities of carbapenem L-749,345 and other antimicrobials against multiresistant gram-negative clinical pathogens , 1997, Antimicrobial agents and chemotherapy.

[55]  Victor L. Yu,et al.  Outcome of Cephalosporin Treatment for Serious Infections Due to Apparently Susceptible Organisms Producing Extended-Spectrum β-Lactamases: Implications for the Clinical Microbiology Laboratory , 2001, Journal of Clinical Microbiology.

[56]  Y. Arakawa,et al.  Worldwide proliferation of carbapenem-resistant gram-negative bacteria , 1999, The Lancet.

[57]  J. Heritage,et al.  Transposition of the gene encoding a TEM-12 extended-spectrum beta-lactamase , 1992, Antimicrobial Agents and Chemotherapy.

[58]  W. Bilker,et al.  Epidemiological investigation of fluoroquinolone resistance in infections due to extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[59]  B. Kreiswirth,et al.  Clinical and molecular epidemiology of acinetobacter infections sensitive only to polymyxin B and sulbactam , 1994, The Lancet.

[60]  A. Endimiani,et al.  Bacteremia due to Klebsiella pneumoniae isolates producing the TEM-52 extended-spectrum beta-lactamase: treatment outcome of patients receiving imipenem or ciprofloxacin. , 2004, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[61]  J. Gourgand,et al.  A case-control study of an outbreak of infections caused by Klebsiella pneumoniae strains producing CTX-1 (TEM-3) beta-lactamase. , 1991, The Journal of hospital infection.

[62]  K. Thomson,et al.  Version 2000: the new beta-lactamases of Gram-negative bacteria at the dawn of the new millennium. , 2000, Microbes and infection.

[63]  Annie Wong-Beringer,et al.  Molecular correlation for the treatment outcomes in bloodstream infections caused by Escherichia coli and Klebsiella pneumoniae with reduced susceptibility to ceftazidime. , 2002, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[64]  S. Chevret,et al.  Outbreak of multiply resistant enterobacteriaceae in an intensive care unit: epidemiology and risk factors for acquisition. , 1996, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[65]  F. Tenover,et al.  Detection and Reporting of Organisms Producing Extended-Spectrum β-Lactamases: Survey of Laboratories in Connecticut , 1999, Journal of Clinical Microbiology.

[66]  K. Bush,et al.  Imipenem resistance in Klebsiella pneumoniae is associated with the combination of ACT-1, a plasmid-mediated AmpC beta-lactamase, and the foss of an outer membrane protein , 1997, Antimicrobial agents and chemotherapy.

[67]  J. Ariza,et al.  Risk factors for faecal carriage of Klebsiella pneumoniae producing extended spectrum beta-lactamase (ESBL-KP) in the intensive care unit. , 1997, The Journal of hospital infection.

[68]  J M Ghuysen,et al.  The active-site-serine penicillin-recognizing enzymes as members of the Streptomyces R61 DD-peptidase family. , 1988, The Biochemical journal.

[69]  Carine Bebrone,et al.  Update of the Standard Numbering Scheme for Class B β-Lactamases , 2004, Antimicrobial Agents and Chemotherapy.

[70]  Dechang Chen,et al.  Extended-spectrum beta-lactamase-producing Escherichiacoli and Klebsiellapneumoniae bloodstream infection: risk factors and clinical outcome , 2002, Intensive Care Medicine.

[71]  N. Woodford,et al.  Outbreak of Carbapenem-Resistant Acinetobacter baumannii Producing the OXA-23 Enzyme in Curitiba, Brazil , 2003, Journal of Clinical Microbiology.

[72]  K. Bush,et al.  Clinical Characteristics and Molecular Epidemiology Associated with Imipenem-Resistant Klebsiella pneumoniae , 1999 .

[73]  N. Woodford,et al.  Outbreak of Infections Caused by Pseudomonas aeruginosa Producing VIM-1 Carbapenemase in Greece , 2000, Journal of Clinical Microbiology.

[74]  M. Oh,et al.  Epidemiology and Clinical Features of Bloodstream Infections Caused by AmpC-Type-β-Lactamase-Producing Klebsiella pneumoniae , 2004, Antimicrobial Agents and Chemotherapy.

[75]  Samson S. Y. Wong,et al.  Bacteremia Caused by Escherichia coli producing Extended-spectrum Beta-lactamase: a Case-control Study of Risk Factors and Outcomes , 2002, Scandinavian journal of infectious diseases.

[76]  P. Nordmann,et al.  OXA-type beta-lactamases. , 1999, Current pharmaceutical design.

[77]  A. Medeiros,et al.  Evolution and dissemination of β-lactamases accelerated by generations of β-lactam antibiotics , 1997 .

[78]  A. Tsakris,et al.  IBC-1, a Novel Integron-Associated Class A β-Lactamase with Extended-Spectrum Properties Produced by anEnterobacter cloacae Clinical Strain , 2000, Antimicrobial Agents and Chemotherapy.

[79]  D. Livermore,et al.  Are SHV β-Lactamases Universal in Klebsiella pneumoniae? , 2000, Antimicrobial Agents and Chemotherapy.

[80]  G. Paul,et al.  A 5‐year epidemiological study of extended‐spectrum ββ‐lactamase‐producing Klebsiella pneumoniae isolates in a medium‐ and long‐stay neurological unit , 2000, Journal of applied microbiology.

[81]  S. Queener,et al.  Beta-lactam antibiotics for clinical use , 1986 .

[82]  J. Knox,et al.  Extended-spectrum and inhibitor-resistant TEM-type beta-lactamases: mutations, specificity, and three-dimensional structure , 1995, Antimicrobial agents and chemotherapy.

[83]  F. Tenover,et al.  Ability of Laboratories To Detect Emerging Antimicrobial Resistance: Proficiency Testing and Quality Control Results from the World Health Organization's External Quality Assurance System for Antimicrobial Susceptibility Testing , 2001, Journal of Clinical Microbiology.

[84]  C. Recule,et al.  A complex mutant of TEM-1 beta-lactamase with mutations encountered in both IRT-4 and extended-spectrum TEM-15, produced by an Escherichia coli clinical isolate , 1997, Antimicrobial agents and chemotherapy.

[85]  P. Bradford Extended-Spectrum β-Lactamases in the 21st Century: Characterization, Epidemiology, and Detection of This Important Resistance Threat , 2001, Clinical Microbiology Reviews.

[86]  F. Heffron,et al.  DNA sequence analysis of the transposon Tn3: Three genes and three sites involved in transposition of Tn3 , 1979, Cell.

[87]  V L Yu,et al.  Enterobacter bacteremia: clinical features and emergence of antibiotic resistance during therapy. , 1991, Annals of internal medicine.

[88]  Yasuaki Yamada,et al.  Clinical and bacteriological characteristics of IMP-type metallo-beta-lactamase-producing Pseudomonas aeruginosa. , 2003, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[89]  H. Goossens,et al.  International Prospective Study of Klebsiella pneumoniae Bacteremia: Implications of Extended-Spectrum -Lactamase Production in Nosocomial Infections , 2004, Annals of Internal Medicine.

[90]  P. Nordmann,et al.  Emerging carbapenemases in Gram-negative aerobes. , 2002, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[91]  Ronald N. Jones,et al.  bla VIM-7, an Evolutionarily Distinct Metallo-β-Lactamase Gene in a Pseudomonas aeruginosa Isolate from the United States , 2004, Antimicrobial Agents and Chemotherapy.

[92]  J. Lucet,et al.  Control of a prolonged outbreak of extended-spectrum beta-lactamase-producing enterobacteriaceae in a university hospital. , 1999, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[93]  D. Yong,et al.  High Prevalence of PER-1 Extended-Spectrum β-Lactamase-Producing Acinetobacter spp. in Korea , 2003, Antimicrobial Agents and Chemotherapy.

[94]  M. Samore,et al.  The molecular and clinical epidemiology of enterobacteriaceae-producing extended-spectrum β-lactamase in a tertiary care hospital* , 1998 .

[95]  R. Bonomo,et al.  Structure of the SHV-1 beta-lactamase. , 1999, Biochemistry.

[96]  K. Riesenberg,et al.  Clinical significance and impact on mortality of extended-spectrum beta lactamase-producing Enterobacteriaceae isolates in nosocomial bacteremia. , 2001, Scandinavian journal of infectious diseases.

[97]  R. Bonnet Growing Group of Extended-Spectrum β-Lactamases: the CTX-M Enzymes , 2004, Antimicrobial Agents and Chemotherapy.

[98]  K. Umezawa,et al.  Isolation of a novel cyclic hexadepsipeptide pipalamycin from Streptomyces as an apoptosis-inducing agent. , 2002, The Journal of antibiotics.

[99]  C. Bizet,et al.  In vivo selection of a cephamycin-resistant, porin-deficient mutant of Klebsiella pneumoniae producing a TEM-3 beta-lactamase. , 1989, The Journal of infectious diseases.

[100]  M. Kaufmann,et al.  Community and hospital spread of Escherichia coli producing CTX-M extended-spectrum beta-lactamases in the UK. , 2004, The Journal of antimicrobial chemotherapy.

[101]  W. Bilker,et al.  Extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae: risk factors for infection and impact of resistance on outcomes. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[102]  H. Goossens,et al.  Comparison of screening methods for detection of extended-spectrum beta-lactamases and their prevalence among blood isolates of Escherichia coli and Klebsiella spp. in a Belgian teaching hospital , 1997, Journal of clinical microbiology.

[103]  Kenneth S. Thomson,et al.  Cefepime, Piperacillin-Tazobactam, and the Inoculum Effect in Tests with Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae , 2001, Antimicrobial Agents and Chemotherapy.

[104]  Barry G. Hall,et al.  Evolution of the serine β-lactamases: past, present and future , 2004 .

[105]  G. Jacoby,et al.  In vivo selection of porin-deficient mutants of Klebsiella pneumoniae with increased resistance to cefoxitin and expanded-spectrum-cephalosporins , 1996, Antimicrobial agents and chemotherapy.

[106]  H. Goossens,et al.  Decreasing antibiotic resistance of Enterobacteriaceae by introducing a new antibiotic combination therapy for neutropenic fever patients , 1998, Leukemia.

[107]  L. Rice,et al.  Ceftazidime-resistant Klebsiella pneumoniae isolates recovered at the Cleveland Department of Veterans Affairs Medical Center. , 1996, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[108]  S. B. Singer,et al.  Biochemical characteristics of extended broad spectrum β-lactamases , 1989, Infection.

[109]  F. Mostashari,et al.  Emergence of domestically acquired ceftriaxone-resistant Salmonella infections associated with AmpC beta-lactamase. , 2000, JAMA.

[110]  J. Gerberding,et al.  Detection of antimicrobial resistance by small rural hospital microbiology laboratories: comparison of survey responses with current NCCLS laboratory standards. , 2003, Diagnostic microbiology and infectious disease.

[111]  S. Joshi,et al.  Plasmid-borne extended-spectrum beta-lactamase in a clinical isolate of Acinetobacter baumannii. , 2003, Journal of medical microbiology.

[112]  M.-L. Huang,et al.  Risk factors in the acquisition of extended-spectrum beta-lactamase Klebsiella pneumoniae: a case-control study in a district teaching hospital in Taiwan. , 2003, The Journal of hospital infection.

[113]  A. Wong-Beringer Therapeutic Challenges Associated with Extended‐Spectrum, β‐Lactamase‐Producing Escherichia coli and Klebsiella pneumoniae , 2001, Pharmacotherapy.