Carbapenem-resistant Enterobacteriaceae: a review of treatment and outcomes.

The emergence of carbapenem resistance in Enterobacteriaceae is an important threat to global health. Reported outcomes of infections with carbapenem-resistant Enterobacteriaceae (CRE) are poor. Very few options remain for the treatment of these virulent organisms. Antibiotics which are currently in use to treat CRE infections include aminoglycosides, polymyxins, tigecycline, fosfomycin, and temocillin. In addition, the role of combination therapy, including carbapenem containing regimens, remains to be defined. There are several important concerns regarding all of these treatment options such as limited efficacy, increasing reports of resistance, and specific toxicities. Data from retrospective studies favor combination therapy over single-agent therapy for the treatment of CRE bloodstream infections. In summary, new antibiotics are greatly needed, as is additional prospective research.

[1]  D. L. Cooper,et al.  Temocillin Concentrations in Human Tissues , 2012, Drugs.

[2]  K. Peck,et al.  Predictors of acute kidney injury associated with intravenous colistin treatment. , 2010, International journal of antimicrobial agents.

[3]  A. Kumar Incidence of and Risk Factors for Colistin-Associated Nephrotoxicity in a Large Academic Health System , 2012 .

[4]  P. J. van Duijn,et al.  Recent trends in antibiotic resistance in European ICUs , 2011, Current opinion in critical care.

[5]  L. Leibovici,et al.  Efficacy and safety of tigecycline: a systematic review and meta-analysis. , 2011, The Journal of antimicrobial chemotherapy.

[6]  C. Natanson,et al.  Excess deaths associated with tigecycline after approval based on noninferiority trials. , 2012, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[7]  S. Pournaras,et al.  Predictors of mortality in patients with bloodstream infections caused by KPC-producing Klebsiella pneumoniae and impact of appropriate antimicrobial treatment. , 2011, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[8]  J. Turnidge,et al.  Simple Method for Assaying Colistin Methanesulfonate in Plasma and Urine Using High-Performance Liquid Chromatography , 2002, Antimicrobial Agents and Chemotherapy.

[9]  A. Michalopoulos,et al.  The revival of fosfomycin. , 2011, International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases.

[10]  D. Paterson,et al.  Use of parenteral colistin for the treatment of serious infection due to antimicrobial-resistant Pseudomonas aeruginosa. , 2003, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[11]  You-ning Liu,et al.  Systematic Review and Meta-Analysis of the Effectiveness and Safety of Tigecycline for Treatment of Infectious Disease , 2010, Antimicrobial Agents and Chemotherapy.

[12]  Steve Millam Potato (Solanum tuberosum L.). , 2006, Methods in molecular biology.

[13]  R. Edson,et al.  The aminoglycosides. , 1999, Mayo Clinic proceedings.

[14]  John Quale,et al.  Rapid spread of carbapenem-resistant Klebsiella pneumoniae in New York City: a new threat to our antibiotic armamentarium. , 2005, Archives of internal medicine.

[15]  A. Haidich,et al.  Efficacy and safety of tigecycline for the treatment of infectious diseases: a meta-analysis. , 2011, The Lancet. Infectious diseases.

[16]  J. Li,et al.  Ascorbic acid protects against the nephrotoxicity and apoptosis caused by colistin and affects its pharmacokinetics. , 2012, The Journal of antimicrobial chemotherapy.

[17]  Adi Gundlapalli,et al.  Drugs of Last Resort? The Use of Polymyxins and Tigecycline at US Veterans Affairs Medical Centers, 2005–2010 , 2012, PloS one.

[18]  W. Couet,et al.  Colistin pharmacokinetics: the fog is lifting. , 2012, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[19]  G. Rahav,et al.  Outcome of carbapenem resistant Klebsiella pneumoniae bloodstream infections. , 2012, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[20]  J. Korth-Bradley,et al.  Serum, tissue and body fluid concentrations of tigecycline after a single 100 mg dose. , 2006, The Journal of antimicrobial chemotherapy.

[21]  D. Nix,et al.  Should tigecycline be considered for urinary tract infections? A pharmacokinetic re-evaluation. , 2010, The Journal of antimicrobial chemotherapy.

[22]  E. Hyle,et al.  Ertapenem-Resistant Enterobacteriaceae Risk Factors for Acquisition and Outcomes , 2010, Infection Control & Hospital Epidemiology.

[23]  J. Turnidge,et al.  Pharmacokinetics of colistin methanesulphonate and colistin in rats following an intravenous dose of colistin methanesulphonate. , 2004, The Journal of antimicrobial chemotherapy.

[24]  V. Yu,et al.  Combination antibiotic therapy versus monotherapy for gram-negative bacteraemia: a commentary. , 1999, International Journal of Antimicrobial Agents.

[25]  Doris Wisher,et al.  Martindale: The Complete Drug Reference. 37th ed , 2012 .

[26]  Brad Spellberg,et al.  Combating antimicrobial resistance: policy recommendations to save lives. , 2011, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[27]  R. Weinstein,et al.  Emergence and rapid regional spread of Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae. , 2011, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[28]  Vincent H Tam,et al.  Detection and treatment options for Klebsiella pneumoniae carbapenemases (KPCs): an emerging cause of multidrug-resistant infection. , 2010, The Journal of antimicrobial chemotherapy.

[29]  K. Hahm,et al.  Potato (Solanum tuberosum L. cv. Gogu valley) protein as a novel antimicrobial agent in weanling pigs. , 2008, Journal of animal science.

[30]  N. Rouphael,et al.  Polymyxin B and Doxycycline Use in Patients with Multidrug-Resistant Acinetobacter baumannii Infections in the Intensive Care Unit , 2006, The Annals of pharmacotherapy.

[31]  R. Weinstein,et al.  Trends in antimicrobial resistance in intensive care units in the United States , 2011, Current opinion in critical care.

[32]  M. Adams,et al.  Carbapenem-resistant Acinetobacter baumannii and Klebsiella pneumoniae across a hospital system: impact of post-acute care facilities on dissemination. , 2010, The Journal of antimicrobial chemotherapy.

[33]  M. Falagas,et al.  Outcome of infections due to pandrug-resistant (PDR) Gram-negative bacteria , 2005, BMC infectious diseases.

[34]  Joshua D. Hartzell,et al.  Nephrotoxicity associated with intravenous colistin (colistimethate sodium) treatment at a tertiary care medical center. , 2009, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[35]  D. Nicolau,et al.  Double-Carbapenem Therapy for Carbapenemase-Producing Klebsiella pneumoniae , 2011, Antimicrobial Agents and Chemotherapy.

[36]  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.

[37]  C. Joukhadar,et al.  Extracellular concentrations of fosfomycin in lung tissue of septic patients. , 2010, The Journal of antimicrobial chemotherapy.

[38]  F. Puntillo,et al.  High-Dose, Extended-Interval Colistin Administration in Critically Ill Patients: Is This the Right Dosing Strategy? A Preliminary Study , 2012, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[39]  R. Bonomo,et al.  Treatment and outcomes in carbapenem-resistant Klebsiella pneumoniae bloodstream infections. , 2011, Diagnostic microbiology and infectious disease.

[40]  G. Turett,et al.  Polymyxin B Nephrotoxicity and Efficacy against Nosocomial Infections Caused by Multiresistant Gram-Negative Bacteria , 2003, Antimicrobial Agents and Chemotherapy.

[41]  G. Tarchini Tigecycline and bacteremia--the dangers of post hoc analysis of pooled data. , 2010, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[42]  K. Kaye,et al.  Retrospective evaluation of colistin versus tigecycline for the treatment of Acinetobacter baumannii and/or carbapenem-resistant Enterobacteriaceae infections. , 2012, American journal of infection control.

[43]  K. Riesenberg,et al.  Attributable Mortality Rate for Carbapenem-Resistant Klebsiella pneumoniae Bacteremia , 2009, Infection Control & Hospital Epidemiology.

[44]  R. Bonomo,et al.  ACHN-490, a Neoglycoside with Potent In Vitro Activity against Multidrug-Resistant Klebsiella pneumoniae Isolates , 2009, Antimicrobial Agents and Chemotherapy.

[45]  C. Kelly,et al.  Health care costs and mortality associated with nosocomial diarrhea due to Clostridium difficile. , 2002, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[46]  Matthew E Falagas,et al.  Colistin: the revival of polymyxins for the management of multidrug-resistant gram-negative bacterial infections. , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[47]  M. Schurgers,et al.  The pharmacokinetics of temocillin in patients with normal and impaired renal function. , 1983, The Journal of antimicrobial chemotherapy.

[48]  D. Paterson,et al.  Treatment Outcome of Bacteremia Due to KPC-Producing Klebsiella pneumoniae: Superiority of Combination Antimicrobial Regimens , 2012, Antimicrobial Agents and Chemotherapy.

[49]  P. Ambrose,et al.  Pharmacokinetic/pharmacodynamic profile for tigecycline—a new glycylcycline antimicrobial agent , 2005 .

[50]  C. Bamia,et al.  Prospective Observational Study of the Impact of VIM-1 Metallo-β-Lactamase on the Outcome of Patients with Klebsiella pneumoniae Bloodstream Infections , 2009, Antimicrobial Agents and Chemotherapy.

[51]  M. Bassetti,et al.  Predictors of mortality in bloodstream infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae: importance of combination therapy. , 2012, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[52]  J. Turnidge,et al.  A simple method for the assay of colistin in human plasma, using pre-column derivatization with 9-fluorenylmethyl chloroformate in solid-phase extraction cartridges and reversed-phase high-performance liquid chromatography. , 2001, Journal of chromatography. B, Biomedical sciences and applications.

[53]  A. Armaganidis,et al.  An outbreak of infection due to beta-Lactamase Klebsiella pneumoniae Carbapenemase 2-producing K. pneumoniae in a Greek University Hospital: molecular characterization, epidemiology, and outcomes. , 2010, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[54]  E. Roilides,et al.  Bloodstream Infections Caused by Metallo-β-Lactamase/Klebsiella pneumoniae Carbapenemase–Producing K. pneumoniae among Intensive Care Unit Patients in Greece: Risk Factors for Infection and Impact of Type of Resistance on Outcomes , 2010, Infection Control & Hospital Epidemiology.

[55]  A Forrest,et al.  Population Pharmacokinetics of Colistin Methanesulfonate and Formed Colistin in Critically Ill Patients from a Multicenter Study Provide Dosing Suggestions for Various Categories of Patients , 2011, Antimicrobial Agents and Chemotherapy.

[56]  W. Bilker,et al.  Colonization with Extended-Spectrum β-Lactamase-Producing Escherichia coli and Klebsiella Species in Long-Term Care Facility Residents , 2012, Infection Control & Hospital Epidemiology.

[57]  M. Schintler,et al.  High fosfomycin concentrations in bone and peripheral soft tissue in diabetic patients presenting with bacterial foot infection. , 2009, The Journal of antimicrobial chemotherapy.

[58]  Ronald N. Jones,et al.  Summary trends for the Meropenem Yearly Susceptibility Test Information Collection Program: a 10-year experience in the United States (1999-2008). , 2009, Diagnostic microbiology and infectious disease.

[59]  J. Fillastre,et al.  Comparative pharmacokinetics of tromethamine fosfomycin and calcium fosfomycin in young and elderly adults , 1988, Antimicrobial Agents and Chemotherapy.

[60]  J. Marschall,et al.  Treatment and clinical outcomes of urinary tract infections caused by KPC-producing Enterobacteriaceae in a retrospective cohort. , 2012, Clinical therapeutics.

[61]  D. Calfee,et al.  Comparative Effectiveness of Aminoglycosides, Polymyxin B, and Tigecycline for Clearance of Carbapenem-Resistant Klebsiella pneumoniae from Urine , 2011, Antimicrobial Agents and Chemotherapy.

[62]  J. Salomon,et al.  Fosfomycin: Efficacy against infections caused by multidrug-resistant bacteria , 2012, Scandinavian journal of infectious diseases.

[63]  R. Bonomo,et al.  Outcomes and Genetic Relatedness of Carbapenem-Resistant Enterobacteriaceae at Detroit Medical Center , 2011, Infection Control & Hospital Epidemiology.

[64]  Neil Woodford,et al.  What remains against carbapenem-resistant Enterobacteriaceae? Evaluation of chloramphenicol, ciprofloxacin, colistin, fosfomycin, minocycline, nitrofurantoin, temocillin and tigecycline. , 2011, International journal of antimicrobial agents.

[65]  G. Daikos,et al.  Carbapenemase-producing Klebsiella pneumoniae: (when) might we still consider treating with carbapenems? , 2011, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[66]  E. Gillespie,et al.  Prevalence of antimicrobial‐resistant organisms in residential aged care facilities , 2011, The Medical journal of Australia.

[67]  Jian Li,et al.  Melatonin Attenuates Colistin-Induced Nephrotoxicity in Rats , 2011, Antimicrobial Agents and Chemotherapy.

[68]  J. Turnidge,et al.  Elucidation of the Pharmacokinetic/Pharmacodynamic Determinant of Colistin Activity against Pseudomonas aeruginosa in Murine Thigh and Lung Infection Models , 2009, Antimicrobial Agents and Chemotherapy.

[69]  Russell E. Lewis,et al.  Pharmacodynamics of Polymyxin B against Pseudomonas aeruginosa , 2005, Antimicrobial Agents and Chemotherapy.

[70]  E. Kühnen,et al.  Penetration of fosfomycin into cerebrospinal fluid across non-inflamed and inflamed meninges , 1987, Infection.

[71]  L. Mody,et al.  Infection rate and colonization with antibiotic-resistant organisms in skilled nursing facility residents with indwelling devices , 2012, European Journal of Clinical Microbiology & Infectious Diseases.

[72]  M. Falagas,et al.  Fosfomycin: evaluation of the published evidence on the emergence of antimicrobial resistance in Gram-negative pathogens. , 2012, The Journal of antimicrobial chemotherapy.

[73]  R. Moore,et al.  Clinical response to aminoglycoside therapy: importance of the ratio of peak concentration to minimal inhibitory concentration. , 1987, The Journal of infectious diseases.

[74]  M. Falagas,et al.  Clinical significance of the pharmacokinetic and pharmacodynamic characteristics of fosfomycin for the treatment of patients with systemic infections. , 2009, International journal of antimicrobial agents.