Antibiotics involved in the occurrence of antibiotic-resistant bacteria: a nationwide multilevel study suggests differences within antibiotic classes.

OBJECTIVES To identify the antibiotics potentially the most involved in the occurrence of antibiotic-resistant bacteria from an ecological perspective in French healthcare facilities (HCFs). METHODS This study was based on data from the French antimicrobial surveillance network (ATB-RAISIN, 2007-09). Antibiotics were expressed in defined daily doses per 1000 patient-days. Antibiotic-resistant bacteria were considered as count data adjusted for patient-days. These were third-generation cephalosporin (3GC)- and ciprofloxacin-resistant Escherichia coli, cefotaxime-resistant Enterobacter cloacae, methicillin-resistant Staphylococcus aureus and ceftazidime-, imipenem- and ciprofloxacin-resistant Pseudomonas aeruginosa. Three-level negative binomial regression models were built to take into account the hierarchical structure of data: level 1, repeated measures each year (count outcome, time, antibiotics); level 2, HCFs (type and size); and level 3, regions (geographical area). RESULTS A total of 701 HCFs from 20 French regions and up to 1339 HCF-years were analysed. The use of ceftriaxone, but not of cefotaxime, was positively correlated with incidence rates of 3GC- and ciprofloxacin-resistant E. coli. In contrast, both 3GCs were positively correlated with the incidence rate of cefotaxime-resistant E. cloacae. Higher levels of use of ciprofloxacin and/or ofloxacin, but not of levofloxacin, were associated with higher incidence rates of 3GC- and ciprofloxacin-resistant E. coli, cefotaxime-resistant E. cloacae, methicillin-resistant S. aureus and ceftazidime- and ciprofloxacin-resistant P. aeruginosa. CONCLUSIONS Our study suggests differences within antibiotic classes in promoting antibiotic resistance. We identified ceftriaxone, ciprofloxacin and ofloxacin as priority targets in public health strategies designed to reduce antibiotic use and antibiotic-resistant bacteria in French HCFs.

[1]  B. Amadéo,et al.  Antibiotic usage in south-western French hospitals: trends and association with antibiotic stewardship measures. , 2011, The Journal of antimicrobial chemotherapy.

[2]  J. Schrenzel,et al.  Modelling the impact of antibiotic use on antibiotic-resistant Escherichia coli using population-based data from a large hospital and its surrounding community. , 2011, The Journal of antimicrobial chemotherapy.

[3]  S. Boussat,et al.  Antibiotic use in 530 French hospitals: results from a surveillance network at hospital and ward levels in 2007. , 2010, The Journal of antimicrobial chemotherapy.

[4]  V. Tam,et al.  Surveillance and Correlation of Antibiotic Prescription and Resistance of Gram-Negative Bacteria in Singaporean Hospitals , 2010, Antimicrobial Agents and Chemotherapy.

[5]  M. Falagas,et al.  Extended-spectrum b-lactamase-producing organisms , 2022 .

[6]  Á. Soriano,et al.  Previous ciprofloxacin exposure is associated with resistance to beta-lactam antibiotics in subsequent Pseudomonas aeruginosa bacteremic isolates. , 2009, American journal of infection control.

[7]  Daniel Yordanov,et al.  Pseudomonas aeruginosa - a phenomenon of bacterial resistance. , 2009, Journal of medical microbiology.

[8]  R. Masterton.  The new treatment paradigm and the role of carbapenems. , 2009, International journal of antimicrobial agents.

[9]  K. Laupland,et al.  Extended-spectrum β-lactamase-producing Enterobacteriaceae: an emerging public-health concern , 2008 .

[10]  D. Monnet,et al.  Relationship between Antibiotic Use and Incidence of MexXY-OprM Overproducers among Clinical Isolates of Pseudomonas aeruginosa , 2008, Antimicrobial Agents and Chemotherapy.

[11]  P. Donnan,et al.  Effect of individual- and group-level antibiotic exposure on MRSA isolation: a multilevel analysis. , 2006, The Journal of antimicrobial chemotherapy.

[12]  C. M. Fortaleza,et al.  Risk Factors for Recovery of Imipenem- or Ceftazidime-Resistant Pseudomonas aeruginosa Among Patients Admitted to a Teaching Hospital in Brazil , 2006, Infection Control & Hospital Epidemiology.

[13]  Y. Carmeli,et al.  Differential Effects of Levofloxacin and Ciprofloxacin on the Risk for Isolation of Quinolone-Resistant Pseudomonas aeruginosa , 2006, Antimicrobial Agents and Chemotherapy.

[14]  G. Ray,et al.  Hospital-level rates of fluoroquinolone use and the risk of hospital-acquired infection with ciprofloxacin-nonsusceptible Pseudomonas aeruginosa. , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[15]  Spencer E. Harpe,et al.  Pseudomonas aeruginosa, Staphylococcus aureus, and Fluoroquinolone Use , 2005, Emerging infectious diseases.

[16]  J. Quinn,et al.  Bowel colonization with resistant gram-negative bacilli after antimicrobial therapy of intra-abdominal infections: observations from two randomized comparative clinical trials of ertapenem therapy , 2005, European Journal of Clinical Microbiology and Infectious Diseases.

[17]  Y. Carmeli,et al.  High Levels of Antimicrobial Coresistance among Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae , 2005, Antimicrobial Agents and Chemotherapy.

[18]  Risto Lehtonen,et al.  Multilevel Statistical Models , 2005 .

[19]  H. Goossens,et al.  Outpatient antibiotic use in Europe and association with resistance: a cross-national database study , 2005, The Lancet.

[20]  G. Jacoby,et al.  The new beta-lactamases. , 2005, The New England journal of medicine.

[21]  G. Jacoby,et al.  Mechanisms of disease: The new β-lactamases , 2005 .

[22]  F. Baquero,et al.  Dramatic Increase in Prevalence of Fecal Carriage of Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae during Nonoutbreak Situations in Spain , 2004, Journal of Clinical Microbiology.

[23]  A. Muller,et al.  Relationship between ceftriaxone use and resistance to third-generation cephalosporins among clinical strains of Enterobacter cloacae. , 2004, The Journal of antimicrobial chemotherapy.

[24]  N. Lehn,et al.  Mutant prevention concentration of nalidixic acid, ciprofloxacin, clinafloxacin, levofloxacin, norfloxacin, ofloxacin, sparfloxacin or trovafloxacin for Escherichia coli under different growth conditions. , 2004, The Journal of antimicrobial chemotherapy.

[25]  Y. Carmeli,et al.  Fluoroquinolones and the Risk for Methicillin-resistant Staphylococcus aureus in Hospitalized Patients , 2003, Emerging infectious diseases.

[26]  Jerome J. Schentag,et al.  Effect of fluoroquinolone expenditures on susceptibility of Pseudomonas aeruginosa to ciprofloxacin in U.S. hospitals. , 2003, American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists.

[27]  R. Venezia,et al.  Risk factors associated with nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infection including previous use of antimicrobials. , 2002, The Journal of antimicrobial chemotherapy.

[28]  D. Livermore,et al.  Multiple mechanisms of antimicrobial resistance in Pseudomonas aeruginosa: our worst nightmare? , 2002, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[29]  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.

[30]  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.

[31]  D. Gilbert,et al.  Phenotypic Resistance of Staphylococcus aureus, Selected Enterobacteriaceae, and Pseudomonas aeruginosa after Single and Multiple In Vitro Exposures to Ciprofloxacin, Levofloxacin, and Trovafloxacin , 2001, Antimicrobial Agents and Chemotherapy.

[32]  Y. Carmeli,et al.  Emergence of Antibiotic-Resistant Pseudomonas aeruginosa: Comparison of Risks Associated with Different Antipseudomonal Agents , 1999, Antimicrobial Agents and Chemotherapy.

[33]  D. Monnet.  Methicillin-Resistant Staphylococcus aureus and Its Relationship to Antimicrobial Use: Possible Implications for Control , 1998, Infection Control & Hospital Epidemiology.

[34]  D. Livermore.  Interplay of impermeability and chromosomal beta-lactamase activity in imipenem-resistant Pseudomonas aeruginosa , 1992, Antimicrobial Agents and Chemotherapy.

[35]  J. Mcgowan,et al.  Antimicrobial resistance in hospital organisms and its relation to antibiotic use. , 1983, Reviews of infectious diseases.

[36]  M. Glauser,et al.  Pharmacokinetic and microbial susceptibility studies of ceftriaxone , 1983, European Journal of Clinical Microbiology.

[37]  D. Paterson,et al.  Escherichia coli O25b-ST131: a pandemic, multiresistant, community-associated strain. , 2011, The Journal of antimicrobial chemotherapy.

[38]  J. Bartlett,et al.  Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. , 2009, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[39]  J. Hilbe.  Negative Binomial Regression: Preface , 2007 .

[40]  G. Jacoby,et al.  The New b -Lactamases , 2005 .

[41]  C. Soussy,et al.  Comité de l'Antibiogramme de la Société Française de Microbiologie report 2003. , 2003, International journal of antimicrobial agents.

[42]  Organización Mundial de la Salud.  Guidelines for ATC classification and DDD assignment , 1996 .

[43]  F. Allerberger,et al.  Influence of cephalosporines III generation with varying biliary excretion on fecal flora and emergence of resistant bacteria during and after cessation of therapy. , 1986, Pädiatrie & Pädologie.