320
Views
9
CrossRef citations to date
0
Altmetric
Review

Carbapenem susceptibility breakpoints, clinical implications with the moving target

, , , , &
Pages 389-401 | Received 04 Dec 2015, Accepted 24 Feb 2016, Published online: 16 Mar 2016

References

  • CDC. Antibiotic resistant threats in the United States. 2013. [cited 2015 Jul 6]. Available from: http://www.Cdc.Gov/drugresistance/threat-report-2013/.
  • American Thoracic S and Infectious Diseases Society of A. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005;171(4):388–416.
  • Freifeld AG, Bow EJ, Sepkowitz KA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis. 2011;52(4):e56–93.
  • Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Clin Infect Dis. 2010;50(2):133–164.
  • Guh AY, Limbago BM, Kallen AJ. Epidemiology and prevention of carbapenem-resistant Enterobacteriaceae in the United States. Expert Rev Anti Infect Ther. 2014;12(5):565–580.
  • Scheetz MH, Qi C, Warren JR, et al. In vitro activities of various antimicrobials alone and in combination with tigecycline against carbapenem-intermediate or -resistant Acinetobacter baumannii. Antimicrob Agents Chemother. 2007;51(5):1621–1626.
  • Esterly JS, Qi C, Malczynski M, et al. Predictability of doripenem susceptibility in Acinetobacter baumannii isolates based on other carbapenem susceptibilities and bla oxa gene status. Pharmacotherapy. 2010;30(4):354–360.
  • Jones RN, Sader HS, Fritsche TR. Comparative activity of doripenem and three other carbapenems tested against Gram-negative bacilli with various beta-lactamase resistance mechanisms. Diagn Microbiol Infect Dis. 2005;52(1):71–74.
  • Davies TA, Marie Queenan A, Morrow BJ, et al. Longitudinal survey of carbapenem resistance and resistance mechanisms in Enterobacteriaceae and non-fermenters from the USA in 2007–09. J Antimicrob Chemother. 2011;66(10):2298–2307.
  • Munoz-Price LS, Poirel L, Bonomo RA, et al. Clinical epidemiology of the global expansion of Klebsiella pneumoniae carbapenemases. Lancet Infect Dis. 2013;13(9):785–796.
  • Deshpande LM, Jones RN, Fritsche TR, et al. Occurrence and characterization of carbapenemase-producing Enterobacteriaceae: report from the SENTRY Antimicrobial Surveillance Program (2000–2004). Microb Drug Resist. 2006;12(4):223–230.
  • Kitchel B, Rasheed JK, Patel JB, et al. Molecular epidemiology of KPC-producing Klebsiella pneumoniae isolates in the United States: clonal expansion of multilocus sequence type 258. Antimicrob Agents Chemother. 2009;53(8):3365–3370.
  • Scheetz MH, Hurt KM, Noskin GA, et al. Applying antimicrobial pharmacodynamics to resistant Gram-negative pathogens. Am J Health Syst Pharm. 2006;63(14):1346–1360.
  • CLSI. Performance standards for antimicrobial susceptibility testing: twenty-fifth informal supplement. CLSI document m100-s25. Wayne (PA): Clinical laboratory and standards institute; 2015.
  • CLSI. Performance standards for antimicrobial susceptibility testing: 20th informal supplement (June 2010, update). CLSI document m100-s20-u. CLSI. Wayne (PA): Clinical laboratory and standards institute; 2010.
  • European committee on antimicrobial susceptibility testing. Breakpoint tables for interpretation of MICs and zone diameters, version 1.1. Vaxjo (Sweden): Eucast; 2010. [cited 2015 Nov 28]. Available from: http://www.Eucast.Org/ast_of_bacteria/previous_versions_of_documents/.
  • European committee on antimicrobial susceptibility testing. Breakpoint tables for interpretation of MICs and zone diameters, version 5.0. Vaxjo (Sweden): Eucast; 2015. [cited 2015 Nov 28]. Available from:: http://www.Eucast.Org/ast_of_bacteria/previous_versions_of_documents/.
  • Grant EM, Kuti JL, Nicolau DP, et al. Clinical efficacy and pharmacoeconomics of a continuous-infusion piperacillin-tazobactam program in a large community teaching hospital. Pharmacotherapy. 2002;22(4):471–483.
  • European committee on antimicrobial susceptibility testing. Eucast definitions of clinical breakpoints and epidemiologic cut off values. Vaxjo (Sweden): Eucast; 2015. [cited 2016 Feb 12]. Available from:: http://www.Eucast.Org/fileadmin/src/media/pdfs/eucast_files/eucast_sops/eucast_definitions_of_clinical_breakpoints_and_ecoffs.Pdf.
  • Dudley MN, Ambrose PG, Bush K, et al. Posting date. CLSI working group. 2010 Jan 25. [cited 2015 Nov 28]. Available from: http://www.Clsi.Org/standards/micro/microbiology-files/.
  • Rennie RP, Jones RN. Effects of breakpoint changes on carbapenem susceptibility rates of Enterobacteriaceae: results from the SENTRY Antimicrobial Surveillance Program, United States, 2008 to 2012. Can J Infect Dis Med Microbiol. 2014;25(5):285–287.
  • Brink AJ, Botha RF, Poswa X, et al. Antimicrobial susceptibility of Gram-negative pathogens isolated from patients with complicated intra-abdominal infections in South African hospitals (SMART study 2004-2009): impact of the new carbapenem breakpoints. Surg Infect (Larchmt). 2012;13(1):43–49.
  • Hombach M, Bloemberg GV, Bottger EC. Effects of clinical breakpoint changes in CLSI guidelines 2010/2011 and EUCAST guidelines 2011 on antibiotic susceptibility test reporting of Gram-negative bacilli. J Antimicrob Chemother. 2012;67(3):622–632.
  • Huang CC, Chen YS, Toh HS, et al. Impact of revised CLSI breakpoints for susceptibility to third-generation cephalosporins and carbapenems among Enterobacteriaceae isolates in the Asia-Pacific region: results from the Study for Monitoring Antimicrobial Resistance Trends (SMART), 2002-2010. Int J Antimicrob Agents. 2012;40(Suppl):S4–S10.
  • Rodríguez-Baño J, Picón E, Navarro MD, et al. Impact of changes in CLSI and EUCAST breakpoints for susceptibility in bloodstream infections due to extended-spectrum beta-lactamase-producing Escherichia coli. Clin Microbiol Infect. 2012;18(9):894–900.
  • Esterly JS, Wagner J, McLaughlin MM, et al. Evaluation of clinical outcomes in patients with bloodstream infections due to Gram-negative bacteria according to carbapenem MIC stratification. Antimicrob Agents Chemother. 2012;56(9):4885–4890.
  • Lee NY, Lee CC, Huang WH, et al. Carbapenem therapy for bacteremia due to extended-spectrum-beta-lactamase-producing Escherichia coli or Klebsiella pneumoniae: implications of ertapenem susceptibility. Antimicrob Agents Chemother. 2012;56(6):2888–2893.
  • Patel TS, Nagel JL. Clinical outcomes of Enterobacteriaceae infections stratified by carbapenem MICs. J Clin Microbiol. 2015;53(1):201–205.
  • Biehle LR, Cottreau JM, Thompson DJ, et al. Outcomes and risk factors for mortality among patients treated with carbapenems for Klebsiella spp. bacteremia. PLoS One. 2015;10(11):e0143845.
  • Falagas ME, Tansarli GS, Rafailidis PI, et al. Impact of antibiotic MIC on infection outcome in patients with susceptible Gram-negative bacteria: a systematic review and meta-analysis. Antimicrob Agents Chemother. 2012;56(8):4214–4222.
  • Torres E, Delgado M, Valiente A, et al. Impact of borderline minimum inhibitory concentration on the outcome of invasive infections caused by Enterobacteriaceae treated with beta-lactams: a systematic review and meta-analysis. Eur J Clin Microbiol Infect Dis. 2015;34(9):1751–1758.
  • Rhodes NJ, O’Donnell JN, Lizza BD, et al. Tree-based models for predicting mortality in Gram-negative bacteremia: avoid putting the cart before the horse. Antimicrob Agents Chemother. 2015;60(2):838–844.
  • Bedikian A, Okamoto MP, Nakahiro RK, et al. Pharmacokinetics of meropenem in patients with intra-abdominal infections. Antimicrob Agents Chemother. 1994;38(1):151–154.
  • Cheatham SC, Kays MB, Smith DW, et al. Steady-state pharmacokinetics and pharmacodynamics of meropenem in hospitalized patients. Pharmacotherapy. 2008;28(6):691–698.
  • Kitzes-Cohen R, Farin D, Piva G, et al. Pharmacokinetics and pharmacodynamics of meropenem in critically ill patients. Int J Antimicrob Agents. 2002;19(2):105–110.
  • Novelli A, Adembri C, Livi P, et al. Pharmacokinetic evaluation of meropenem and imipenem in critically ill patients with sepsis. Clin Pharmacokinet. 2005;44(5):539–549.
  • Ariano RE, Nyhlén A, Donnelly JP, et al. Pharmacokinetics and pharmacodynamics of meropenem in febrile neutropenic patients with bacteremia. Ann Pharmacother. 2005;39(1):32–38.
  • Jaruratanasirikul S, Thengyai S, Wongpoowarak W, et al. Population pharmacokinetics and Monte Carlo dosing simulations of meropenem during the early phase of severe sepsis and septic shock in critically ill patients in intensive care units. Antimicrob Agents Chemother. 2015;59(6):2995–3001.
  • Lomaestro BM, Drusano GL. Pharmacodynamic evaluation of extending the administration time of meropenem using a Monte Carlo simulation. Antimicrob Agents Chemother. 2005;49(1):461–463.
  • Wittau M, Scheele J, Kurlbaum M, et al. Population pharmacokinetics and target attainment of meropenem in plasma and tissue of morbidly obese patients after laparoscopic intraperitoneal surgery. Antimicrob Agents Chemother. 2015;59(10):6241–6247.
  • Lodise TP, Sorgel F, Melnick D, et al. Penetration of meropenem into epithelial lining fluid of patients with ventilator-associated pneumonia. Antimicrob Agents Chemother. 2011;55(4):1606–1610.
  • Scheetz MH, Wunderink RG, Postelnick MJ, et al. Potential impact of vancomycin pulmonary distribution on treatment outcomes in patients with methicillin-resistant Staphylococcus aureus pneumonia. Pharmacotherapy. 2006;26(4):539–550.
  • Belzberg H, Zhu J, Cornwell EE 3rd, et al. Imipenem levels are not predictable in the critically ill patient. J Trauma. 2004;56(1):111–117.
  • Lee LS, Kinzig-Schippers M, Nafziger AN, et al. Comparison of 30-min and 3-h infusion regimens for imipenem/cilastatin and for meropenem evaluated by Monte Carlo simulation. Diagn Microbiol Infect Dis. 2010;68(3):251–258.
  • MacGregor RR, Gibson GA, Bland JA. Imipenem pharmacokinetics and body fluid concentrations in patients receiving high-dose treatment for serious infections. Antimicrob Agents Chemother. 1986;29(2):188–192.
  • McKindley DS, Boucher BA, Hess MM, et al. Pharmacokinetics of aztreonam and imipenem in critically ill patients with pneumonia. Pharmacotherapy. 1996;16(5):924–931.
  • Sakka SG, Glauner AK, Bulitta JB, et al. Population pharmacokinetics and pharmacodynamics of continuous versus short-term infusion of imipenem-cilastatin in critically ill patients in a randomized, controlled trial. Antimicrob Agents Chemother. 2007;51(9):3304–3310.
  • Primaxin I.V. (imipenem and cilastatin for injection). Whitehouse station (NJ): Merck Sharp and Dohme Co.; 2014 Oct. Package insert. Distributed by merck & co., Inc.
  • Invanz I.V. (ertapenem for injection). Whitehouse station (NJ): Merck Sharp and Dohme Co.; 2014 Aug. Package insert. Distributed by Merck & Co., Inc.
  • Brink AJ, Richards GA, Schillack V, et al. Pharmacokinetics of once-daily dosing of ertapenem in critically ill patients with severe sepsis. Int J Antimicrob Agents. 2009;33(5):432–436.
  • Burkhardt O, Kumar V, Katterwe D, et al. Ertapenem in critically ill patients with early-onset ventilator-associated pneumonia: pharmacokinetics with special consideration of free-drug concentration. J Antimicrob Chemother. 2007;59(2):277–284.
  • Pletz MW, Rau M, Bulitta J, et al. Ertapenem pharmacokinetics and impact on intestinal microflora, in comparison to those of ceftriaxone, after multiple dosing in male and female volunteers. Antimicrob Agents Chemother. 2004;48(10):3765–3772.
  • Burkhardt O, Hafer C, Langhoff A, et al. Pharmacokinetics of ertapenem in critically ill patients with acute renal failure undergoing extended daily dialysis. Nephrol Dial Transplant. 2009;24(1):267–271.
  • Cardone KE, Grabe DW, Kulawy RW, et al. Ertapenem pharmacokinetics and pharmacodynamics during continuous ambulatory peritoneal dialysis. Antimicrob Agents Chemother. 2012;56(2):725–730.
  • Boselli E, Breilh D, Saux MC, et al. Pharmacokinetics and lung concentrations of ertapenem in patients with ventilator-associated pneumonia. Intensive Care Med. 2006;32(12):2059–2062.
  • Wittau M, Scheele J, Bulitta JB, et al. Pharmacokinetics of ertapenem in colorectal tissue. Chemotherapy. 2011;57(5):437–448.
  • Bhavnani SM, Hammel JP, Cirincione BB, et al. Use of pharmacokinetic-pharmacodynamic target attainment analyses to support phase 2 and 3 dosing strategies for doripenem. Antimicrob Agents Chemother. 2005;49(9):3944–3947.
  • Ikawa K, Morikawa N, Uehara S, et al. Pharmacokinetic-pharmacodynamic target attainment analysis of doripenem in infected patients. Int J Antimicrob Agents. 2009;33(3):276–279.
  • Van Wart SA, Andes DR, Ambrose PG, et al. Pharmacokinetic-pharmacodynamic modeling to support doripenem dose regimen optimization for critically ill patients. Diagn Microbiol Infect Dis. 2009;63(4):409–414.
  • Justo J, Gotfried MH, Deyo K, et al. Doripenem intrapulmonary pharmacokinetics in healthy adult subjects. Poster session presented at: 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy; 2013 Sep 10-13; Denver, CO.
  • Drusano GL. Prevention of resistance: a goal for dose selection for antimicrobial agents. Clin Infect Dis. 2003;36(Suppl 1):S42–S50.
  • Kuti JL, Dandekar PK, Nightingale CH, et al. Use of Monte Carlo simulation to design an optimized pharmacodynamic dosing strategy for meropenem. J Clin Pharmacol. 2003;43(10):1116–1123.
  • Krueger WA, Bulitta J, Kinzig-Schippers M, et al. Evaluation by Monte Carlo simulation of the pharmacokinetics of two doses of meropenem administered intermittently or as a continuous infusion in healthy volunteers. Antimicrob Agents Chemother. 2005;49(5):1881–1889.
  • Frei CR, Wiederhold NP, Burgess DS. Antimicrobial breakpoints for Gram-negative aerobic bacteria based on pharmacokinetic-pharmacodynamic models with Monte Carlo simulation. J Antimicrob Chemother. 2008;61(3):621–628.
  • DeRyke CA, Kuti JL, Nicolau DP. Reevaluation of current susceptibility breakpoints for Gram-negative rods based on pharmacodynamic assessment. Diagn Microbiol Infect Dis. 2007;58(3):337–344.
  • Kuti JL, Florea NR, Nightingale CH, et al. Pharmacodynamics of meropenem and imipenem against Enterobacteriaceae, Acinetobacter baumannii, and Pseudomonas aeruginosa. Pharmacotherapy. 2004;24(1):8–15.
  • Crandon JL, Ariano RE, Zelenitsky SA, et al. Optimization of meropenem dosage in the critically ill population based on renal function. Intensive Care Med. 2011;37(4):632–638.
  • Roberts JA, Kirkpatrick CM, Roberts MS, et al. Meropenem dosing in critically ill patients with sepsis and without renal dysfunction: intermittent bolus versus continuous administration? Monte Carlo dosing simulations and subcutaneous tissue distribution. J Antimicrob Chemother. 2009;64(1):142–150.
  • Jaruratanasirikul S, Limapichat T, Jullangkoon M, et al. Pharmacodynamics of meropenem in critically ill patients with febrile neutropenia and bacteraemia. Int J Antimicrob Agents. 2011;38(3):231–236.
  • Wiskirchen DE, Housman ST, Quintiliani R, et al. Comparative pharmacokinetics, pharmacodynamics, and tolerability of ertapenem 1 gram/day administered as a rapid 5-minute infusion versus the standard 30-minute infusion in healthy adult volunteers. Pharmacotherapy. 2013;33(3):266–274.
  • Chen M, Nafziger AN, Drusano GL, et al. Comparative pharmacokinetics and pharmacodynamic target attainment of ertapenem in normal-weight, obese, and extremely obese adults. Antimicrob Agents Chemother. 2006;50(4):1222–1227.
  • Burkhardt O, Kumar V, Schmidt S, et al. Underdosing of ertapenem in critically ill patients with pneumonia confirmed by Monte Carlo simulations. Int J Antimicrob Agents. 2010;35(1):96–97.
  • Eyler RF, Vilay AM, Nader AM, et al. Pharmacokinetics of ertapenem in critically ill patients receiving continuous venovenous hemodialysis or hemodiafiltration. Antimicrob Agents Chemother. 2014;58(3):1320–1326.
  • Zhou J, Sulaiman Z, Llorin RM, et al. Pharmacokinetics of ertapenem in outpatients with complicated urinary tract infections. J Antimicrob Chemother. 2014;69(9):2517–2521.
  • Kays MB, Fleming MR, Cheatham SC, et al. Comparative pharmacokinetics and pharmacodynamics of doripenem and meropenem in obese patients. Ann Pharmacother. 2014;48(2):178–186.
  • Jaruratanasirikul S, Wongpoowarak W, Kositpantawong N, et al. Pharmacodynamics of doripenem in critically ill patients with ventilator-associated Gram-negative bacilli pneumonia. Int J Antimicrob Agents. 2012;40(5):434–439.
  • Samtani MN, Flamm R, Kaniga K, et al. Pharmacokinetic-pharmacodynamic-model-guided doripenem dosing in critically ill patients. Antimicrob Agents Chemother. 2010;54(6):2360–2364.
  • Pai H, Kim J, Kim J, et al. Carbapenem resistance mechanisms in Pseudomonas aeruginosa clinical isolates. Antimicrob Agents Chemother. 2001;45(2):480–484.
  • Li C, Kuti JL, Nightingale CH, et al. Population pharmacokinetic analysis and dosing regimen optimization of meropenem in adult patients. J Clin Pharmacol. 2006;46(10):1171–1178.
  • Meropenem for injection. Lake Forest (IL): Hospira, Inc.; 2014 Dec. Package insert. Manufactured by Hospira, Inc.
  • Stein GE, Kulhanek G, Smith CL, et al. Pharmacokinetics and Monte Carlo simulations of doripenem in patients with febrile neutropenia. Ann Pharmacother. 2012;46(10):1281–1286.
  • Guh AY, Bulens SN, Mu Y, et al. Epidemiology of carbapenem-resistant Enterobacteriaceae in 7 US communities, 2012-2013. Jama. 2015;314(14):1479–1487.
  • Queenan AM, Bush K. Carbapenemases: the versatile beta-lactamases. Clin Microbiol Rev. 2007;20(3):440–458. table of contents
  • Bonomo RA, Szabo D. Mechanisms of multidrug resistance in Acinetobacter species and Pseudomonas aeruginosa. Clin Infect Dis. 2006;43(Suppl 2):S49–S56.
  • Esterly JS, Richardson CL, Eltoukhy NS, et al. Genetic mechanisms of antimicrobial resistance of Acinetobacter baumannii. Ann Pharmacother. 2011;45(2):218–228.
  • Poirel L, Nordmann P. Carbapenem resistance in Acinetobacter baumannii: mechanisms and epidemiology. Clin Microbiol Infect. 2006;12(9):826–836.
  • Poole K. Efflux pumps as antimicrobial resistance mechanisms. Ann Med. 2007;39(3):162–176.
  • Quale J, Bratu S, Gupta J, et al. Interplay of efflux system, ampC, and oprD expression in carbapenem resistance of Pseudomonas aeruginosa clinical isolates. Antimicrob Agents Chemother. 2006;50(5):1633–1641.
  • Rodriguez-Martinez JM, Poirel L, Nordmann P. Molecular epidemiology and mechanisms of carbapenem resistance in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2009;53(11):4783–4788.
  • Tam VH, Chang KT, Abdelraouf K, et al. Prevalence, resistance mechanisms, and susceptibility of multidrug-resistant bloodstream isolates of Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2010;54(3):1160–1164.
  • Nordmann P, Naas T, Poirel L. Global spread of carbapenemase-producing Enterobacteriaceae. Emerg Infect Dis. 2011;17(10):1791–1798.
  • Livermore DM. Of pseudomonas, porins, pumps and carbapenems. J Antimicrob Chemother. 2001;47(3):247–250.
  • Walsh TR, Toleman MA, Poirel L, et al. Metallo-beta-lactamases: the quiet before the storm? Clin Microbiol Rev. 2005;18(2):306–325.
  • Walther-Rasmussen J, Hoiby N. Oxa-type carbapenemases. J Antimicrob Chemother. 2006;57(3):373–383.
  • Daikos GL, Markogiannakis A. Carbapenemase-producing Klebsiella pneumoniae: (when) might we still consider treating with carbapenems? Clin Microbiol Infect. 2011;17(8):1135–1141.
  • Daikos GL, Panagiotakopoulou A, Tzelepi E, et al. Activity of imipenem against VIM-1 metallo-beta-lactamase-producing Klebsiella pneumoniae in the murine thigh infection model. Clin Microbiol Infect. 2007;13(2):202–205.
  • Souli M, Konstantinidou E, Tzepi I, et al. Efficacy of carbapenems against a metallo-beta-lactamase-producing Escherichia coli clinical isolate in a rabbit intra-abdominal abscess model. J Antimicrob Chemother. 2011;66(3):611–617.
  • Heritier C, Poirel L, Lambert T, et al. Contribution of acquired carbapenem-hydrolyzing oxacillinases to carbapenem resistance in Acinetobacter baumannii. Antimicrob Agents Chemother. 2005;49(8):3198–3202.
  • Chen TL, Lee YT, Kuo SC, et al. Emergence and distribution of plasmids bearing the blaoxa-51-like gene with an upstream isaba1 in carbapenem-resistant Acinetobacter baumannii isolates in Taiwan. Antimicrob Agents Chemother. 2010;54(11):4575–4581.
  • Turton JF, Ward ME, Woodford N, et al. The role of isaba1 in expression of oxa carbapenemase genes in Acinetobacter baumannii. FEMS Microbiol Lett. 2006;258(1):72–77.
  • Bush K, Jacoby GA. Updated functional classification of beta-lactamases. Antimicrob Agents Chemother. 2010;54(3):969–976.
  • Rasheed JK, Kitchel B, Zhu W, et al. New Delhi metallo-β-lactamase-producing Enterobacteriaceae, United States. Emerg Infect Dis. 2013;19(6):870–878.
  • Poirel L, Nordmann P, Lagrutta E, et al. Emergence of KPC-producing Pseudomonas aeruginosa in the United States. Antimicrob Agents Chemother. 2010;54(7):3072.
  • Cornaglia G, Giamarellou H, Rossolini GM. Metallo-beta-lactamases: a last frontier for beta-lactams? Lancet Infect Dis. 2011;11(5):381–393.
  • Yigit H, Queenan AM, Anderson GJ, et al. Novel carbapenem-hydrolyzing beta-lactamase, KPC-1, from a carbapenem-resistant strain of Klebsiella pneumoniae. Antimicrob Agents Chemother. 2001;45(4):1151–1161.
  • Centers for Disease C and Prevention. Vital signs: carbapenem-resistant Enterobacteriaceae. MMWR Morb Mortal Wkly Rep. 2013;62(9):165–170.
  • Bennett JW, Herrera ML, Lewis JS 2nd, et al. KPC-2-producing Enterobacter cloacae and Pseudomonas putida coinfection in a liver transplant recipient. Antimicrob Agents Chemother. 2009;53(1):292–294.
  • Villegas MV, Lolans K, Correa A, et al. First identification of Pseudomonas aeruginosa isolates producing a KPC-type carbapenem-hydrolyzing beta-lactamase. Antimicrob Agents Chemother. 2007;51(4):1553–1555.
  • Robledo IE, Aquino EE, Sante MI, et al. Detection of KPC in Acinetobacter spp. In puerto rico. Antimicrob Agents Chemother. 2010;54(3):1354–1357.
  • Brown S, Young HK, Amyes SG. Characterisation of OXA-51, a novel class D carbapenemase found in genetically unrelated clinical strains of Acinetobacter baumannii from Argentina. Clin Microbiol Infect. 2005;11(1):15–23.
  • Pfeifer Y, Schlatterer K, Engelmann E, et al. Emergence of oxa-48-type carbapenemase-producing Enterobacteriaceae in German hospitals. Antimicrob Agents Chemother. 2012;56(4):2125–2128.
  • Mathers AJ, Hazen KC, Carroll J, et al. First clinical cases of oxa-48-producing carbapenem-resistant Klebsiella pneumoniae in the United States: the “menace” arrives in the new world. J Clin Microbiol. 2013;51(2):680–683.
  • Poirel L, Potron A, Nordmann P. Oxa-48-like carbapenemases: the phantom menace. J Antimicrob Chemother. 2012;67(7):1597–1606.
  • Tam VH, Chang KT, LaRocco MT, et al. Prevalence, mechanisms, and risk factors of carbapenem resistance in bloodstream isolates of Pseudomonas aeruginosa. Diagn Microbiol Infect Dis. 2007;58(3):309–314.
  • El Amin N, Giske CG, Jalal S, et al. Carbapenem resistance mechanisms in Pseudomonas aeruginosa: alterations of porin oprd and efflux proteins do not fully explain resistance patterns observed in clinical isolates. APMIS. 2005;113(3):187–196.
  • Mena A, Plasencia V, García L, et al. Characterization of a large outbreak by CTX-M-1-producing Klebsiella pneumoniae and mechanisms leading to in vivo carbapenem resistance development. J Clin Microbiol. 2006;44(8):2831–2837.
  • Kaczmarek FM, Dib-Hajj F, Shang W, et al. High-level carbapenem resistance in a Klebsiella pneumoniae clinical isolate is due to the combination of bla(ACT-1) beta-lactamase production, porin ompk35/36 insertional inactivation, and down-regulation of the phosphate transport porin PhoE. Antimicrob Agents Chemother. 2006;50(10):3396–3406.
  • Stapleton PD, Shannon KP, French GL. Carbapenem resistance in Escherichia coli associated with plasmid-determined CMY-4 beta-lactamase production and loss of an outer membrane protein. Antimicrob Agents Chemother. 1999;43(5):1206–1210.
  • Tsai YK, Fung CP, Lin JC, et al. Klebsiella pneumoniae outer membrane porins Ompk35 and Ompk36 play roles in both antimicrobial resistance and virulence. Antimicrob Agents Chemother. 2011;55(4):1485–1493.
  • Masuda N, Sakagawa E, Ohya S, et al. Substrate specificities of mexab-oprm, mexcd-oprj, and mexxy-oprm efflux pumps in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2000;44(12):3322–3327.
  • Okamoto K, Gotoh N, Nishino T. Alterations of susceptibility of Pseudomonas aeruginosa by overproduction of multidrug efflux systems, MexAB-oprM, MexCD-oprJ, and MexXY/oprM to carbapenems: substrate specificities of the efflux systems. J Infect Chemother. 2002;8(4):371–373.
  • Siempos II, Vardakas KZ, Manta KG, et al. Carbapenems for the treatment of immunocompetent adult patients with nosocomial pneumonia. Eur Respir J. 2007;29(3):548–560.
  • Rempex pharmaceuticals. Efficacy, safety, tolerability of carbavance compared to best available therapy in serious infections due to carbapenem resistant Enterobacteriaceae, in adults. In: Clinicaltrials.Gov [internet]. Bethesda (MD): National Library of Medicine (US); 2000. [cited 2015 Nov 28]. Available from: https://clinicaltrials.Gov/ct2/show/nct02168946 nlm identifier: Nct02168946.
  • Kollef MH, Chastre J, Clavel M, et al. A randomized trial of 7-day doripenem versus 10-day imipenem-cilastatin for ventilator-associated pneumonia. Crit Care. 2012;16(6):R218.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.