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Optimizing Antibiotic Dosing Strategies for the Treatment of Gram-negative Infections in the Era of Resistance

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Pages 459-476 | Received 22 Oct 2015, Accepted 14 Dec 2015, Published online: 16 Jan 2016

References

  • Gaynes R, Edwards JR. Overview of nosocomial infections caused by gram-negative bacilli. Clin Infect Dis. 2005;41(6):848–854.
  • Cosgrove SE, Kaye KS, Eliopoulous GM, et al. Health and economic outcomes of the emergence of third-generation cephalosporin resistance in Enterobacter species. Arch Intern Med. 2002;162:185–190.
  • McGowan JE Jr. Economic impact of antimicrobial resistance. Emerg Infect Dis. 2001;7:286–292.
  • Correa L, Martino MD, Siqueira I, et al. A hospital-based matched case-control study to identify clinical outcome and risk factors associated with carbapenem-resistant Klebsiella pneumoniae infection. BMC Infect Dis. 2013;13:80.
  • Centers for Disease Control and Prevention (CDC). Antibiotic resistance threats in the United States, 2013. Atlanta: CDC; 2013 [Last accessed 29 September 2015] Available at: http://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf
  • Livermore DM. Bacterial resistance: origins, epidemiology, and impact. Clin Infect Dis. 2003;36(Suppl 1):S11–23.
  • Pitout JD, Laupland KB. Extended-spectrum β-lactamase–producing Enterobacteriaceae: an emerging public-health concern. Lancet Infect Dis. 2008;8:159–166.
  • Rhomberg PR, Jones RN. Summary trends for the meropenem yearly susceptibility test information collection program: a 10-year experience in the United States (1999-2008). Diagn Microbiol Infect Dis. 2009;65:414–426.
  • Nordmann P, Picazo JJ, Mutters R, et al. COMPACT study group. Comparative activity of carbapenem testing: the COMPACT study. J Antimicrob Chemother. 2011;66(5):1070–1078.
  • Arnold RS, Thom KA, Sharma S, et al. Emergence of Klebsiella pneumoniae carbapenemase-producing bacteria. South Med J. 2011;104(1):40–45.
  • 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;53:3365–3370.
  • Hersh AL, Newland JG, Beekmann SE, et al. Unmet medical need in infectious diseases. Clin Infect Dis. 2012;54:1677–1678.
  • Rice LB. Federal funding for the study of antimicrobial resistance in nosocomial pathogens: no ESKAPE. J Infect Dis. 2008;197:1079–1081.
  • Spellberg B, Bartlett J, Wunderink R, et al. Novel approaches are needed to develop tomorrow’s antibacterial therapies. Am J Respir Crit Care Med. 2015;191(2):135–40.
  • Shlaes DM, Sahm D, Opiela C, et al. The FDA reboot of antibiotic development. Antimicrob Agents Chemother. 2013;57:4605–4607.
  • Cooper M, Shlaes DM. Fix the antibiotic pipeline. Nature. 2011;472:32.
  • Spellberg B, Powers JH, Brass EP, et al. Trends in antimicrobial drug development: implications for the future. Clin Infect Dis. 2004;38:1279–1286.
  • Defife R, Scheetz MH, Feinglass JM, et al. Effect of differences in MIC values on clinical outcomes in patients with bloodstream infections caused by gram-negative organisms treated with levofloxacin. Antimicrob Agents Chemother. 2009;53(3):1074–1079.
  • 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.
  • Bhat SV, Peleg AY, Lodise TP, et al. Failure of current cefepime breakpoints to predict clinical outcomes of bacteremia caused by gram-negative organisms. Antimicrob Agents Chemother. 2007;51(12):4390–4395.
  • Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing;twenty-fifth informational supplement.CLSI document M100-S25. Wayne, PA: Clinical and Laboratory Standards Institute; 2015.
  • 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.
  • Kim A, Sutherland CA, Kuti JL, et al. Optimal dosing of piperacillin-tazobactam for the treatment of Pseudomonas aeruginosa infections: prolonged or continuous infusion? Pharmacotherapy. 2007;27(11):1490–1497.
  • Nightingale CH, Ambrose PG, Drusano GL, et al. Antimicrobial pharmacodynamics in theory and clinical practice. 2nd ed. Vol. 2, New York, NY: CRC Press; 2007. p. 1–21.
  • Connors KP, Kuti JL, Nicolau DP. Optimizing antibiotic pharmacodynamics for clinical practice. Pharmaceut Anal Acta. 2013;4:214.
  • Craig WA. Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men. Clin Infect Dis. 1998;26(1):1–2.
  • Macvane SH, Crandon JL, Nicolau DP. Characterizing in vivo pharmacodynamics of carbapenems against Acinetobacter baumannii in a murine thigh infection model to support breakpoint determinations. Antimicrob Agents Chemother. 2014;58(1):599–601.
  • Moore RD, Lietman PS, Smith CR. Clinical response to aminoglycoside therapy: importance of the ratio of peak concentration to minimal inhibitory concentration. J Infect Dis. 1987;155(1):93–99.
  • Drusano GL, Ambrose PG, Bhavnani SM, et al. Back to the future: using aminoglycosides again and how to dose them optimally. Clin Infect Dis. 2007;45(6):753–760.
  • Nicolau DP, Freeman CD, Belliveau PP, et al. Experience with a once-daily aminoglycoside program administered to 2,184 adult patients. Antimicrob Agents Chemother. 1995;39:650–655.
  • Dudhani RV, Turnidge JD, Coulthard K, et al. Elucidation of the pharmacokinetic/pharmacodynamic determinant of colistin activity against Pseudomonas aeruginosa in murine thigh and lung infection models. Antimicrob Agents Chemother. 2010;54(3):1117–1124.
  • Dudhani RV, Turnidge JD, Nation RL, et al. fAUC/MIC is the most predictive pharmacokinetic/pharmacodynamic index of colistin against Acinetobacter baumannii in murine thigh and lung infection models. J Antimicrob Chemother. 2010;65(9):1984–1990.
  • Tigecycline—EUCAST Rationale Document 2006. Rationale for the EUCAST Clinical Breakpoints. Available from http://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Rationale_documents/Tigecyclinerationale1.0.pdf [Last accessed 13 October 2015].
  • Bhavnani SM, Rubino CM, Ambrose PG, et al. Impact of different factors on the probability of clinical response in tigecycline-treated patients with intra-abdominal infections. Antimicrob Agents Chemother. 2010;54:1207–1212.
  • Kim A, Kuti JL, Nicolau DP. Probability of pharmacodynamic target attainment with standard and prolonged-infusion antibiotic regimens for empiric therapy in adults with hospital-acquired pneumonia. Clin Ther. 2009;31(11):2765–2778.
  • Lodise TP Jr, Lomaestro B, Drusano GL. Piperacillin-tazobactam for Pseudomonas aeruginosa infection: clinical implications of an extended-infusion dosing strategy. Clin Infect Dis. 2007;44:357–363.
  • Bhalodi AA, Keel RA, Quintiliani R, et al. Pharmacokinetics of doripenem in infected patients treated within and outside the intensive care unit. Ann Pharmacother. 2013;47(5):617–627.
  • Roos JF, Bulitta J, Lipman J, et al. Pharmacokinetic-pharmacodynamic rationale for cefepime dosing regimens in intensive care units. J Antimicrob Chemother. 2006;58(5):987–993.
  • Nicasio AM, Ariano RE, Zelenitsky SA, et al. Population pharmacokinetics of high-dose, prolonged-infusion cefepime in adult critically ill patients with ventilator-associated pneumonia. Antimicrob Agents Chemother. 2009;53(4):1476–1481.
  • Mouton JW, Punt N, Vinks AA. A retrospective analysis using Monte Carlo simulation to evaluate recommended ceftazidime dosing regimens in healthy volunteers, patients with cystic fibrosis, and patients in the intensive care unit. Clin Ther. 2005;27(6):762–772.
  • Bulitta JB, Landersdorfer CB, Hüttner SJ, et al. Population pharmacokinetic comparison and pharmacodynamic breakpoints of ceftazidime in cystic fibrosis patients and healthy volunteers. Antimicrob Agents Chemother. 2010;54(3):1275–1282.
  • Koomanachai P, Crandon JL, Kuti JL, et al. Comparative pharmacodynamics for intravenous antibiotics against Gram-negative bacteria in Europe between 2002 and 2006: a report from the OPTAMA program. Int J Antimicrob Agents. 2009;33(4):348–353.
  • Crandon JL, Schuck VJ, Banevicius MA, et al. Comparative in vitro and in vivo efficacies of human simulated doses of ceftazidime and ceftazidime-avibactam against Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2012;56(12):6137–6146.
  • Bulik CC, Tessier PR, Keel RA, et al. In vivo comparison of CXA-101 (FR264205) with and without tazobactam versus piperacillin-tazobactam using human simulated exposures against phenotypically diverse gram-negative organisms. Antimicrob Agents Chemother. 2012;56(1):544–549.
  • Xiao AJ, Miller BW, Huntington JA, et al. Ceftolozane/tazobactam pharmacokinetic/pharmacodynamic-derived dose justification for phase 3 studies in patients with nosocomial pneumonia. J Clin Pharmacol. 2015. doi:10.1002/jcph.566.
  • Jaruratanasirikul S, Aeinlang N, Jullangkoon M, et al. Pharmacodynamics of imipenem in critically ill patients with ventilator-associated pneumonia. J Med Assoc Thai. 2013;96(5):551–557.
  • 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.
  • Roberts JA, Kirkpatrick CM, Lipman J. Monte Carlo simulations: maximizing antibiotic pharmacokinetic data to optimize clinical practice for critically ill patients. J Antimicrob Chemother. 2011;66(2):227–231.
  • Shea KM, Cheatham SC, Smith DW, et al. Comparative pharmacodynamics of intermittent and prolonged infusions of piperacillin/tazobactam using Monte Carlo simulations and steady-state pharmacokinetic data from hospitalized patients. Ann Pharmacother. 2009;43(11):1747–1754.
  • Lorente L, Jiménez A, Martín MM, et al. Clinical cure of ventilator-associated pneumonia treated with piperacillin/tazobactam administered by continuous or intermittent infusion. Int J Antimicrob Agents. 2009;33(5):464–468.
  • Xamplas RC, Itokazu GS, Glowacki RC, et al. Implementation of an extended-infusion piperacillin-tazobactam program at an urban teaching hospital. Am J Health Syst Pharm. 2010;67(8):622–628.
  • Wang D. Experience with extended-infusion meropenem in the management of ventilator-associated pneumonia due to multidrug-resistant Acinetobacter baumannii. Int J Antimicrob Agents. 2009;33:290–291.
  • Capitano B, Nicolau DP, Potoski BA, et al. Meropenem administered as a prolonged infusion to treat serious gram-negative central nervous system infections. Pharmacotherapy. 2004;24:803–807.
  • Cheatham SC, Shea KM, Healy DP, et al. Steady-state pharmacokinetics and pharmacodynamics of cefepime administered by prolonged infusion in hospitalised patients. Int J Antimicrob Agents. 2011;37:46–50.
  • Maglio D, Ong C, Banevicius MA, et al. Determination of the in vivo pharmacodynamic profile of cefepime against extended-spectrum-beta-lactamase-producing Escherichia coli at various inocula. Antimicrob Agents Chemother. 2004;48(6):1941–1947.
  • Crandon JL, Bulik CC, Kuti JL, et al. Clinical pharmacodynamics of cefepime in patients infected with Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2010;54(3):1111–1116.
  • Macvane SH, Kuti JL, Nicolau DP. Clinical pharmacodynamics of antipseudomonal cephalosporins in patients with ventilator-associated pneumonia. Antimicrob Agents Chemother. 2014;58(3):1359–1364.
  • Zelenitsky SA, Rubinstein E, Ariano RE, et al. Integrating pharmacokinetics, pharmacodynamics and MIC distributions to assess changing antimicrobial activity against clinical isolates of Pseudomonas aeruginosa causing infections in Canadian hospitals (CANWARD). J Antimicrob Chemother. 2013;68(Suppl 1):i67–72.
  • Nicasio AM, Eagye KJ, Nicolau DP, et al. Pharmacodynamic-based clinical pathway for empiric antibiotic choice in patients with ventilator-associated pneumonia. J Crit Care. 2010;25(1):69–77.
  • Bauer KA, West JE, O’brien JM, et al. Extended-infusion cefepime reduces mortality in patients with Pseudomonas aeruginosa infections. Antimicrob Agents Chemother. 2013;57(7):2907–2912.
  • Navas D, Caillon J, Batard E, et al. Trough serum concentrations of beta-lactam antibiotics in cancer patients: inappropriateness of conventional schedules to pharmacokinetic/ pharmacodynamic properties of beta-lactams. Int J Antimicrob Agents. 2006;27:102–107.
  • Sime FB, Roberts MS, Tiong IS, et al. Adequacy of high-dose cefepime regimen in febrile neutropenic patients with hematological malignancies. Antimicrob Agents Chemother. 2015;59(9):5463–5469.
  • Georges B, Conil JM, Ruiz S, et al. Ceftazidime dosage regimen in intensive care unit patients: from a population pharmacokinetic approach to clinical practice via Monte Carlo simulations. Br J Clin Pharmacol. 2012;73(4):588–596.
  • Moriyama B, Henning SA, Childs R, et al. High-dose continuous infusion beta-lactam antibiotics for the treatment of resistant Pseudomonas aeruginosa infections in immunocompromised patients. Ann Pharmacother. 2010;44(5):929–935.
  • Lorente L, Jiménez A, Palmero S, et al. Comparison of clinical cure rates in adults with ventilator-associated pneumonia treated with intravenous ceftazidime administered by continuous or intermittent infusion: a retrospective, nonrandomized, open-label, historical chart review. Clin Ther. 2007;29(11):2433–2439.
  • Nicolau DP, Mcnabb J, Lacy MK, et al. Continuous versus intermittent administration of ceftazidime in intensive care unit patients with nosocomial pneumonia. Int J Antimicrob Agents. 2001;17(6):497–504.
  • Turner RB, Slain D, Petros K, et al. Clinical outcomes following hospital-wide implementation of prolonged-infusion cefepime and ceftazidime. Int J Antimicrob Agents. 2015;46(1):129–130.
  • Zhanel GG, Lawson CD, Adam H, et al. Ceftazidime-avibactam: a novel cephalosporin/β-lactamase inhibitor combination. Drugs. 2013;73(2):159–177.
  • Macvane SH, Crandon JL, Nichols WW, et al. In vivo efficacy of humanized exposures of Ceftazidime-Avibactam in comparison with Ceftazidime against contemporary Enterobacteriaceae isolates. Antimicrob Agents Chemother. 2014;58(11):6913–6919.
  • Camerago JF, Simkins J, Beduschi T, et al. Successful treatment of carbapenemase-producing pandrug-resistant klebsiella pneumoniae Bacteremia. Antimicrob Agents Chemother. 2015;59(10):5903–5908.
  • Singh R, Kim A, Tanudra MA, et al. Pharmacokinetics/pharmacodynamics of a β-lactam and β-lactamase inhibitor combination: a novel approach for aztreonam/avibactam. J Antimicrob Chemother. 2015;70(9):2618–2626.
  • ZERBAXA® (ceftolozane and tazobactam for injection) package insert. Whitehouse Station, NJ: Merck & Co., Inc.; 2015.
  • Hong M-C, Hsu DI, Bounthavong M. Ceftolozane/tazobactam: a novel antipseudomonal cephalosporin and β-lactamase-inhibitor combination. Infect Drug Resist. 2013;6:215–223.
  • Shlaes DM, New β-lactam-β-lactamase inhibitor combinations in clinical development. Ann N Y Acad Sci. 2013;1277:105–114.
  • Craig WA, Andes DR. In vivo activities of ceftolozane, a new cephalosporin, with and without tazobactam against Pseudomonas aeruginosa and Enterobacteriaceae, including strains with extended-spectrum β-lactamases, in the thighs of neutropenic mice. Antimicrob Agents Chemother. 2013;57(4):1577–1582.
  • Fantin B, Leggett J, Ebert S, et al. Correlation between in vitro and in vivo activity of antimicrobial agents against gram-negative bacilli in a murine infection model. Antimicrob Agents Chemother. 1991;35(7):1413–1422.
  • DeRyke CA, Banevicius MA, Fan HW, et al. Evaluation of the bactericidal activity of meropenem and ertapenem against extended-spectrum beta-lactamase producing Escherichia coli and Klebsiella pneumoniae in a neutropenic mouse thigh model. Antimicrob Agents Chemother. 2007;51:1481–1486.
  • 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 a monte carlo simulation to design an optimized pharmacodynamic dosing strategy for meropenem. J Clin Pharmacol. 2003;43:1116–1123.
  • Bulik CC, Christensen H, Li P, et al. Comparison of the activity of a human simulated, high-dose, prolonged infusion of meropenem against Klebsiella pneumoniae producing the KPC carbapenemase versus that against Pseudomonas aeruginosa in an in vitro pharmacodynamic model. Antimicrob Agents Chemother. 2010;54:804–810.
  • Kiratisin P, Keel RA, Nicolau DP. Pharmacodynamic profiling of doripenem, imipenem and meropenem against prevalent Gram-negative organisms in the Asia-Pacific region. Int J Antimicrob Agents. 2013;41(1):47–51.
  • Eagye KJ, Banevicius MA, Nicolau DP. Pseudomonas aeruginosa is not just in the intensive care unit any more: implications for empirical therapy. Crit Care Med. 2012;40(4):1329–1332.
  • Fehér C, Rovira M, Soriano A, et al. Effect of meropenem administration in extended infusion on the clinical outcome of febrile neutropenia: a retrospective observational study. J Antimicrob Chemother. 2014;69(9):2556–2562.
  • Hsaiky L, Murray KP, Kokoska L, et al. Standard versus prolonged doripenem infusion for treatment of gram-negative infections. Ann Pharmacother. 2013;47(7–8):999–1006.
  • Chastre J, Wunderink R, Prokocimer P, et al. Efficacy and safety of intravenous infusion of doripenem versus imipenem in ventilator-associated pneumonia: a multicenter, randomized study. Crit Care Med. 2008;36(4):1089–1096.
  • 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.
  • Dulhunty JM, Roberts JA, Davis JS, et al. Continuous infusion of beta-lactam antibiotics in severe sepsis: a multicenter double-blind, randomized controlled trial. Clin Infect Dis. 2013;56(2):236–244.
  • Dulhunty JM, Roberts JA, Davis JS, et al. A multicenter randomized trial of continuous versus Intermittent β-Lactam infusion in severe sepsis. Am J Respir Crit Care Med. 2015;192:1298–1305. DOI:10.1164/rccm.201505-0857OC.
  • Teo J, Liew Y, Lee W, et al. Prolonged infusion versus intermittent boluses of β-lactam antibiotics for treatment of acute infections: a meta-analysis. Int J Antimicrob Agents. 2014;43(5):403–411.
  • 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):223–30.
  • Maglio D, Ong C, Banevicius MM, et al. Determination of the in vivo pharmacodynamic profile of cefepime against extended-spectrum-beta-lactamase-producing Escherichia coli at various inocula. Antimicrob Agents Chemother. 2004;48:1941–1947.
  • Bulik CC, Nicolau DP. In vivo efficacy of simulated human dosing regimens of prolonged-infusion doripenem against carbapenemase- producing Klebsiella pneumoniae. Antimicrob Agents Chemother. 2010;54(10):4112–4115.
  • Wiskirchen DE, Nordmann P, Crandon JL, et al. Efficacy of humanized carbapenem and ceftazidime regimens against Enterobacteriaceae producing OXA-48 carbapenemase in a murine infection model. Antimicrob Agents Chemother. 2014;58(3):1678–1683.
  • Wiskirchen DE, Nordmann P, Crandon JL, et al. Efficacy of humanized carbapenem exposures against New Delhi metallo-beta-lactamase (NDM-1) producing enterobacteriaceae in a murine infection model. Antimicrob Agents Chemother. 2013;57:3936–3940.
  • Daikos GL, Tsaousi S, Tzouvelekis LS, et al. Carbapenemase-producing klebsiella pneumoniae bloodstream infections: lowering mortality by antibiotic combination schemes and the role of carbapenems. Antimicrob Agents Chemother. 2014;58(4):2322–2328.
  • Taccone FS, Cotton F, Roisin S, et al. Optimal meropenem concentrations to treat multidrug-resistant pseudomonas aeruginosa septic shock. Antimicrob Agents Chemother. 2012;56(4):2129–2131.
  • Saçar S, Turqut H, Cenger DH, et al. Successful treatment of multidrug resistant Acinetobacter baumannii meningitis. J Infect Dev Ctries. 2007;1(3):342–344.
  • Drusano GL, Louie A. Optimization of aminoglycoside therapy. Antimicrob Agents Chemother. 2011;55(6):2528–2531.
  • Chuck SK, Raber SR, Rodvold KA, et al. National survey of extended-interval aminoglycoside dosing. Clin Infect Dis. 2000;30(3):433–439.
  • Smyth AR, Campbell EL. Prescribing practices for intravenous aminoglycosides in UK cystic fibrosis clinics: a questionnaire survey. J Cyst Fibros. 2014;13(4):424–427.
  • Prescott WA. A survey of extended-interval aminoglycoside dosing practices in United States adult cystic fibrosis programs. Respir Care. 2014;59(9):1353–1359.
  • Lee GC, Burgess DS. Treatment of Klebsiella pneumoniae carbapenemase (KPC) infections: a review of published case series and case reports. Ann Clin Microbiol Antimicrob. 2012;11:32.
  • Lee GC, Burgess DS. Polymyxins and Doripenem Combination Against KPC-Producing Klebsiella pneumoniae. J Clin Med Res. 2013;5(2):97–100.
  • Owen RJ, Li J, Nation RL, et al. In vitro pharmacodynamics of colistin against Acinetobacter baumannii clinical isolates. J Antimicrob Chemother. 2007;59(3):473–477.
  • Poudyal A, Howden BP, Bell JM, et al. In vitro pharmacodynamics of colistin against multidrug-resistant Klebsiella pneumoniae. J Antimicrob Chemother. 2008;62(6):1311–1318.
  • Ortwine JK, Sutton JD, Kaye KS, et al. Strategies for the safe use of colistin. Expert Rev Anti Infect Ther. 2015;13(10):1237–1247.
  • Ortwine JK, Kaye KS, Li J, et al. Colistin: understanding and applying recent pharmacokinetic advances. Pharmacotherapy. 2015;35(1):11–16.
  • Lim LM, Ly N, Anderson D, et al. Resurgence of colistin: a review of resistance, toxicity, pharmacodynamics, and dosing. Pharmacotherapy. 2010;30(12):1279–1291.
  • Li J, Turnidge J, Milne R, et al. In vitro pharmacodynamic properties of colistin and colistin methanesulfonate against Pseudomonas aeruginosa isolates from patients with cystic fibrosis. Antimicrob Agents Chemother. 2001;45:781.
  • Bergen PJ, Li J, Nation RL, et al. Comparison of once-, twice- and thrice daily dosing of colistin on antibacterial effect and emergence of resistance: studies with Pseudomonas aeruginosa in an in vitro pharmacodynamic model. J Antimicrob Chemother. 2008;61:636–642.
  • Dudhani RV, Turnidge JD, Coulthard K, et al. Elucidation of the pharmacokinetic/pharmacodynamic determinant of colistin activity against Pseudomonas aeruginosa in murine thigh and lung infection models. Antimicrob Agents Chemother. 2010;54:1117–1124.
  • Dudhani RV, Turnidge JD, Nation RL, et al. fAUC/MIC is the most predictive pharmacokinetic/pharmacodynamic index of colistin against Acinetobacter baumannii in murine thigh and lung infection models. J Antimicrob Chemother. 2010;65(9):1984–1990.
  • Coly-Mycin® M Parenteral (Colistimethate for Injection, USP) Package Insert. Rochester, MI: Parkedale Pharmaceuticals, Inc.; 2006.
  • Markou N, Markantonis SL, Dimitrakis E, et al. Colistin serum concentrations after intravenous administration in critically ill patients with serious multidrug-resistant, gram-negative bacilli infections: a prospective, open-label, uncontrolled study. Clin Ther. 2008;30(1):143–151.
  • Imberti R, Cusato M, Villani P, et al. Steady-state pharmacokinetics and BAL concentration of colistin in critically ill patients after IV colistin methanesulfonate administration. Chest. 2010;138(6):1333–1339.
  • Plachouras D, Karvanen M, Friberg LE, et al. Population pharmacokinetic analysis of colistin methanesulfonate and colistin after intravenous administration in critically ill patients with infections caused by Gram-negative bacteria. Antimicrob Agents Chemother. 2009;53(8):3430–3436.
  • Grégoire N, Mimoz O, Mégarbane B, et al. New colistin population pharmacokinetic data in critically ill patients suggesting an alternative loading dose rationale. Antimicrob Agents Chemother. 2014;58(12):7324–30.
  • Garonzik SM, Li J, Thamlikitkul V, 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. Antimicrob Agents Chemother. 2011;55(7):3284–3294.
  • Dalfino L, Puntillo F, Mosca A, et al. High-dose, extended-interval colistin administration in critically ill patients: is this the right dosing strategy? A preliminary study. Clin Infect Dis. 2012;54(12):1720–1726.
  • Michalopoulos AS, Tsiodras S, Rellos K, et al. Colistin treatment in patients with ICU-acquired infections caused by multiresistant Gram-negative bacteria: the renaissance of an old antibiotic. Clin Microbiol Infect. 2005;11(2):115–121.
  • Reina R, Estenssoro E, Sáenz G, et al. Safety and efficacy of colistin in Acinetobacter and Pseudomonas infections: a prospective cohort study. Intensive Care Med. 2005;31(8):1058–1065.
  • Cheng C-Y, Sheng W-H, Wang J-T, et al. Safety and efficacy of intravenous colistin (colistin methanesulphonate) for severe multidrug-resistant Gram-negative bacterial infections. Int J Antimicrob Agents. 2010;35(3):297–300.
  • Kasiakou SK, Michalopoulos A, Soteriades ES, et al. Combination therapy with intravenous colistin for management of infections due to multidrug-resistant Gram-negative bacteria in patients without cystic fibrosis. Antimicrob Agents Chemother. 2005;49(8):3136–3146.
  • Sandri AM, Landersdorfer CB, Jacob J, et al. Population pharmacokinetics of intravenous polymyxin B in critically ill patients: implications for selection of dosage regimens. Clin Infect Dis. 2013;57(4):524–531.
  • Nelson BC, Eiras DP, Gomez-simmonds A, et al. Clinical outcomes associated with Polymyxin B Dose in patients with bloodstream infections due to carbapenem-resistant gram-negative rods. Antimicrob Agents Chemother. 2015;59:7000–7006. DOI:10.1128/AAC.00844-15.
  • Van Duin D, Kaye KS, Neuner EA, et al. Carbapenem-resistant Enterobacteriaceae: a review of treatment and outcomes. Diagn Microbiol Infect Dis. 2013;75(2):115–120.
  • De Rosa FG, Corcione S, Di Perri G, et al. Scaglione F2. Re-defining tigecycline therapy. New Microbiol. 2015;38(2):121–136.
  • Yahav D, Lador A, Paul M, et al. Efficacy and safety of tigecycline: a systematic review and meta-analysis. J Antimicrob Chemother. 2011;66(9):1963–1971.
  • Prasad P, Sun J, Danner RL, et al. Excess deaths associated with tigecycline after approval based on noninferiority trials. Clin Infect Dis. 2012;54(12):1699–1709.
  • Burkhardt O, Rauch K, Kaever V, et al. Tigecycline possibly underdosed for the treatment of pneumonia: a pharmacokinetic viewpoint. Int J Antimicrob Agents. 2009;34(1):101–102.
  • Freire AT, Melnyk V, Kim MJ, et al. Comparison of tigecycline with imipenem/cilastatin for the treatment of hospital-acquired pneumonia. Diagn Microbiol Infect Dis. 2010;68(2):140–151.
  • Meagher AK1, Ambrose PG, Grasela TH, et al. Pharmacokinetic/pharmacodynamic profile for tigecycline-a new glycylcycline antimicrobial agent. Diagn Microbiol Infect Dis. 2005;52(3):165–171.
  • Koomanachai P1, Kim A, Nicolau DP. Pharmacodynamic evaluation of tigecycline against Acinetobacter baumannii in a murine pneumonia model. J Antimicrob Chemother. 2009;63(5):982–987.
  • Ramirez J, Dartois N, Gandjini H, et al. Randomized phase 2 trial to evaluate the clinical efficacy of two high-dosage tigecycline regimens versus imipenem-cilastatin for treatment of hospital-acquired pneumonia. Antimicrob Agents Chemother. 2013;57(4):1756–1762.
  • Tumbarello M, Viale P, Viscoli C, et al. Predictors of mortality in bloodstream infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae: importance of combination therapy. Clin Infect Dis. 2012;55(7):943–950.
  • Kiem S, Schentag J. Interpretation of antibiotic concentration ratios measured in epithelial lining fluid. Antimicrob Agents Chemother. 2008;52(1):24–36.
  • Kollef M, Hamilton C, Montgomery B. Aerosolized antibiotics: do they add to the treatment of pneumonia? Curr Opin Infect Dis. 2013;26:538–544.
  • Crozier DN, Khan SR. Tobramycin in treatment of infections due to Pseudomonas aeruginosa in patients with cystic fibrosis. J Infect Dis. 1976;134 Suppl:S187–90.
  • Michalopoulos AS, Falagas ME. Inhaled antibiotics in mechanically ventilated patients. Minerva Anestesiol. 2014;80(2):236–244.
  • Miller DD, Amin MM, Palmer LB, et al. Aerosol delivery and modern mechanical ventilation: in vitro/in vivo evaluation. Am J Respir Crit Care Med. 2003;168:1205–1209.
  • Harvey CJ, O’doherty MJ, Page CJ, et al. Comparison of jet and ultrasonic nebulizer pulmonary aerosol deposition during mechanical ventilation. Eur Respir J. 1997;10(4):905–909.
  • Dhand R, Aerosol delivery during mechanical ventilation: from basic techniques to new devices. J Aerosol Med Pulm Drug Deliv. 2008;21:45–60.
  • Luyt CE, Clavel M, Guntupalli K, et al. Pharmacokinetics and lung delivery of PDDS-aerosolized amikacin (NKTR-061) in intubated and mechanically ventilated patients with nosocomial pneumonia. Crit Care. 2009;13(6):R200.
  • Waldrep JC, Berlinski A, Dhand R. Comparative analysis of methods to measure aerosols generated by a vibrating mesh nebulizer. J Aerosol Med. 2007;20(3):310–319.
  • Waldrep JC, Dhand R. Advanced nebulizer designs employing vibrating mesh/aperture plate technologies for aerosol generation. Curr Drug Deliv. 2008;5(2):114–119.
  • Fink JB, Schmidt D. In vitro comparison of nebulizers for aerosol delivery during mechanical ventilation. Am J Respir Crit Care Med. 2002;165:A375.
  • Ferrari F, Liu ZH, Lu Q, et al. Comparison of lung tissue concentrations of nebulized ceftazidime in ventilated piglets: ultrasonic versus vibrating plate nebulizers. Intensive Care Med. 2008;34:1718–1723.
  • Rau JL. The inhalation of drugs: advantages and problems. Respir Care. 2005;50(3):367–382.
  • Dhand R. Nebulizers that use a vibrating mesh or plate with multiple apertures to generate aerosol. Respir Care. 2002;47(12):1406–1408.
  • Montgomery AB, Vallance S, Abuan T, et al. A randomized double-blind placebo-controlled dose-escalation phase 1 study of aerosolized amikacin and fosfomycin delivered via the PARI investigational eFlow® inline nebulizer system in mechanically ventilated patients. J Aerosol Med Pulm Drug Deliv. 2014;27(6):441–448.
  • Niederman MS, Chastre J, Corkery K, et al. BAY41-6551 achieves bactericidal tracheal aspirate amikacin concentrations in mechanically ventilated patients with Gram-negative pneumonia. Intensive Care Med. 2012;38(2):263–271.
  • So W, Crandon JL, Hamada Y, et al. In vitro Pharmacodynamics (PD) of Amikacin Inhale (AMK‐I) as Monotherapy and as an Adjunct to Meropenem (MER) Against K. pneumoniae (KP) and P. aeruginosa (PA). ICAAC; 2015. Abstract A-503.
  • Falagas ME, Kastoris AC, Karageorgopoulos DE, et al. Fosfomycin for the treatment of infections caused by multidrug-resistant non-fermenting Gram-negative bacilli: a systematic review of microbiological, animal and clinical studies. Int J Antimicrob Agents. 2009;34(2):111–120.
  • Montgomery AB, Vallance S, Abuan T, et al. A randomized double-blind placebo-controlled dose-escalation phase 1 study of aerosolized amikacin and fosfomycin delivered via the PARI investigational eFlow® inline nebulizer system in mechanically ventilated patients. J Aerosol Med Pulm Drug Deliv. 2014;27(6):441–448.
  • Meiji Initiates Phase 1 Clinical Trial of Arbekacin Inhalation Solution (ME1100) in the U.S. and Enters into a Licensing Agreement with PARI Pharma for a Customized eFlow® Technology Inhalation Device [Press release]. Meiji Seika Pharma Co. 2013. Available from http://www.meiji-seika pharma.co.jp/english/pressrelease/2013/detail/130726_01.html [Last accessed 27 September 2015].
  • Lu Q, Girardi C, Zhang M, et al. Nebulized and intravenous colistin in experimental pneumonia caused by Pseudomonas aeruginosa. Intensive Care Med. 2010;36:1147–1155.
  • Gontijo AV, Grégoire N, Lamarche I, et al. Biopharmaceutical characterization of nebulized antimicrobial agents in rats: 2. Colistin. Antimicrob Agents Chemother. 2014;58(7):3950–3956.
  • Valachis A, Samonis G, Kofteridis DP. The role of aerosolized colistin in the treatment of ventilator-associated pneumonia: a systematic review and metaanalysis. Crit Care Med. 2015;43(3):527–533.
  • Rattanaumpawan P, Lorsutthitham J, Ungprasert P, et al. Randomized controlled trial of nebulized colistimethate sodium as adjunctive therapy of ventilator-associated pneumonia caused by Gram-negative bacteria. J Antimicrob Chemother. 2010;65:2645–2649.
  • Lu Q, R L, Bodin L, et al Efficacy of high-dose nebulized colistin in ventilator-associated pneumonia caused by multidrug-resistant pseudomonas aeruginosa and acinetobacter baumannii. Anesthesiology. 2012;117(6):1335–1347.
  • Claridge JA, Edwards NM, Swanson J, et al. Aerosolized ceftazidime prophylaxis against ventilator-associated pneumonia in high-risk trauma patients: results of a double-blind randomized study. Surg Infect (Larchmt). 2007;8(1):83–90.
  • Wood GC, Boucher BA, Croce MA, et al. Aerosolized ceftazidime for prevention of ventilator-associated pneumonia and drug effects on the proinflammatory response in critically ill trauma patients. Pharmacotherapy. 2002;22(8):972–982.
  • Lu Q, Yang J, Liu Z, et al. Nebulized ceftazidime and amikacin in ventilator-associated pneumonia caused by Pseudomonas aeruginosa. Am J Respir Crit Care Med. 2011;184(1):106–115.
  • Dellit TH, Owens RC, Mcgowan JE, et al. Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Clin Infect Dis. 2007;44(2):159–177.
  • Roberts JA, Abdul-aziz MH, Lipman J, et al. Individualised antibiotic dosing for patients who are critically ill: challenges and potential solutions. Lancet Infect Dis. 2014;14(6):498–509.
  • Infectious Diseases Society of America. The 10 x ‘20 Initiative: pursuing a global commitment to develop 10 new antibacterial drugs by 2020. Clin Infect Dis. 2010;50(8):1081–1083.
  • Lapuebla A, Abdallah M, Olafisoye O, et al. Activity of Meropenem Combined with RPX7009, a Novel β-Lactamase Inhibitor, against gram-negative clinical isolates in New York City. Antimicrob Agents Chemother. 2015;59(8):4856–4860.
  • Cass RT, Brooks CD, Havrilla NA, et al. Pharmacokinetics and safety of single and multiple doses of ACHN-490 injection administered intravenously in healthy subjects. Antimicrob Agents Chemother. 2011;55:5874–5880.

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