Abstract
The progressive increase in antimicrobial resistance represents a major concern among critically ill patients, leading to prolonged length of hospital stay and increased mortality [1]. In this setting, prescription of adequate antibiotic treatment, which is of outstanding importance to reduce mortality rates and improve clinical outcomes, is frequently delayed, and the most commonly employed empiric antibiotic regimens are often inappropriate [2]. To confront the problem of antimicrobial resistance, many new antibiotics with activity against multidrug resistant (MDR) pathogens have recently been approved, and other agents are currently under investigation. Here we review the characteristics of the new therapeutic options for the treatment of serious infections caused by MDR pathogens, with a specific focus on the potential advantages of these drugs for the management of critically ill patients in everyday clinical practice.
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References
Tabah A, Koulenti D, Laupland K, et al. Characteristics and determinants of outcome of hospital-acquired bloodstream infections in intensive care units: the EUROBACT International Cohort Study. Intensive Care Med. 2012;38:1930ā45.
Zilberberg MD, Shorr AF, Micek ST, Vazquez-Guillamet C, Kollef MH. Multi-drug resistance, inappropriate initial antibiotic therapy and mortality in Gram-negative severe sepsis and septic shock: a retrospective cohort study. Crit Care. 2014;18:596.
Sader HS, Flamm RK, Streit JM, Jones RN. Activity of novel antimicrobial ceftolozane/tazobactam tested against contemporary clinical strains from USA hospitals. Presented at the 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy. 2011 (abst).
Wagenlehner FM, Umeh O, Steenbergen J, Yuan G, Darouiche RO. Ceftolozane/tazobactam compared with levofloxacin in the treatment of complicated urinary-tract infections, including pyelonephritis: a randomised, double-blind, phase 3 trial (ASPECT-cUTI). Lancet. 2015;385:1949ā56.
Popejoy MW, Paterson DL, Cloutier D, et al. Efficacy of ceftolozane/tazobactam against urinary tract and intra-abdominal infections caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae: a pooled analysis of Phase 3 clinical trials. J Antimicrob Chemother. 2017;72:268ā72.
Chandorkar G, Huntington JA, Gotfried MH, Rodvold KA, Umeh O. Intrapulmonary penetration of ceftolozane/tazobactam and piperacillin/tazobactam in healthy adult subjects. J Antimicrob Chemother. 2012;67:2463ā9.
Xiao AJ, Miller BW, Huntington JA, Nicolau DP. Ceftolozane/tazobactam pharmacokinetic/pharmacodynamic-derived dose justification for phase 3 studies in patients with nosocomial pneumonia. J Clin Pharmacol. 2016;56:56ā66.
CastĆ³n JJ, De la Torre Ć, Ruiz-Camps I, SorlĆ ML, Torres V, Torre-Cisneros J. Salvage therapy with ceftolozane-tazobactam for multidrug-resistant Pseudomonas aeruginosa infections. Antimicrob Agents Chemother. 2017;61:e02136ā16.
Monogue ML, Stainton SM, Baummer-Carr A, et al. Pharmacokinetics and tissue penetration of ceftolozane-tazobactam in diabetic patients with lower limb infections and healthy adult volunteers. Antimicrob Agents Chemother. 2017;61:e01449ā17.
Keepers TR, Gomez M, Celeri C, Nichols WW, Krause KM. Bactericidal activity, absence of serum effect, and time-kill kinetics of ceftazidime-avibactam against b-lactamase-producing Enterobacteriaceae and Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2014;58:5297ā305.
Kazmierczak KM, de Jonge BLM, Stone GG, Sahm DF. In vitro activity of ceftazidime/avibactam against isolates of Enterobacteriaceae collected in European countries: INFORM global surveillance 2012ā15. J Antimicrob Chemother. 2018;73:2782ā8.
Zhong H, Zhao XY, Zhang ZL, et al. Evaluation of efficacy and safety of ceftazidime-avibactam in the treatment of Gram-negative bacterial infections: a systematic review and meta-analysis. Int J Antimicrob Agents. 2018;52:443ā50.
Tumbarello M, Trecarichi EM, Corona A, et al. Efficacy of ceftazidime-avibactam salvage therapy in patients with infections caused by KPC-producing Klebsiella pneumoniae. Clin Infect Dis. 2018 (in press).
Gaibani P, Campoli C, Lewis RE, et al. In vivo evolution of resistant subpopulations of KPC-producing Klebsiella pneumoniaeduring ceftazidime/avibactam treatment. J Antimicrob Chemother. 2018;73:1525ā9.
Gaibani P, Lewis RE, Volpe SL, et al. In vitro interaction of ceftazidime-avibactam in combination with different antimicrobials against KPC-producing Klebsiella pneumoniae clinical isolates. Int J Infect Dis. 2017;65:1ā3.
Vazquez JA, GonzĆ”lez PatzĆ”n LD, Stricklin D, et al. Efficacy and safety of ceftazidime-avibactam versus imipenem-cilastatin in the treatment of complicated urinary tract infections, including acute pyelonephritis, in hospitalized adults: results of a prospective, investigator-blinded, randomized study. Curr Med Res Opin. 2012;28:1921ā31.
Lahiri SD, Mangani S, Durand-Reville T, et al. Structural insight into potent broad-spectrum inhibition with reversible recyclization mechanism: avibactam in complex with CTX-M-15 and Pseudomonas aeruginosa AmpC b-lactamases. Antimicrob Agents Chemother. 2013;57:2496ā505.
Karlowsky JA, Kazmierczak KM, de Jonge BLM, Hackel MA, Sahm DF, Bradford PA. In vitro activity of aztreonam-avibactam against Enterobacteriaceae and Pseudomonas aeruginosa isolated by clinical laboratories in 40 countries from 2012 to 2015. Antimicrob Agents Chemother. 2017;61:e00472-17.
Saravolatz LD, Stein GE, Johnson LB. Ceftaroline: a novel cephalosporin with activity against methicillin-resistant Staphylococcus aureus. Clin Infect Dis. 2011;52:1156ā63.
Biedenbach DJ, Iaconis JP, Sahm DF. Comparative in vitro activities of ceftaroline and ceftriaxone against bacterial pathogens associated with respiratory tract infections: results from the AWARE surveillance study. J Antimicrob Chemother. 2016;71:3459ā64.
Taboada M, Melnick D, Iaconis JP, et al. Ceftaroline fosamil versus ceftriaxone for the treatment of community-acquired pneumonia: individual patient data meta-analysis of randomized controlled trials. J Antimicrob Chemother. 2016;71:1748ā9.
Canut A, Isla A, RodrĆguez-GascĆ³n A. Pharmacokinetic/pharmacodynamic analysis to evaluate ceftaroline fosamil dosing regimens for the treatment of community-acquired bacterial pneumonia and complicated skin and skin-structure infections in patients with normal and impaired renal function. Int J Antimicrob Agents. 2015;45:399ā405.
Cosimi RA, Beik N, Kubiak DW, Johnson JA. Ceftaroline for severe methicillin-resistant Staphylococcus aureus infections: a systematic review. Open Forum Infect Dis. 2017;4:ofx084.
Lewis PO, Heil EL, Covert KL, Cluck DB. Treatment strategies for persistent methicillin-resistant Staphylococcus aureus bacteraemia. J Clin Pharm Ther. 2018;43:614ā25.
Walkty A, Adam HJ, LaverdiĆØre M, et al. In vitro activity of ceftobiprole against frequently encountered aerobic and facultative Gram-positive and Gram-negative bacterial pathogens: results of the CANWARD 2007-2009 study. Diagn Microbiol Infect Dis. 2011;69:348ā55.
Nicholson SC, Welte T, File TM Jr, et al. A randomised, double-blind trial comparing ceftobiprole medocaril with ceftriaxone with or without linezolid for the treatment of patients with community-acquired pneumonia requiring hospitalisation. Int J Antimicrob Agents. 2012;39:240ā6.
Awad SS, Rodriguez AH, Chuang YC, et al. A phase 3 randomized double-blind comparison of ceftobiprole medocaril versus ceftazidime plus linezolid for the treatment of hospital-acquired pneumonia. Clin Infect Dis. 2014;59:51ā61.
Castanheira M, Sader HS, Farrell DJ, Mendes RE, Jones RN. Activity of ceftaroline-avibactam tested against Gram-negative organism populations, including strains expressing one or more Ī²-lactamases and methicillin-resistant Staphylococcus aureus carrying various staphylococcal cassette chromosome mec types. Antimicrob Agents Chemother. 2012;56:4779ā85.
Riccobene TA, Su SF, Rank D. Single- and multiple-dose study to determine the safety, tolerability, and pharmacokinetics of ceftaroline fosamil in combination with avibactam in healthy subjects. Antimicrob Agents Chemother. 2013;57:1496ā504.
Li S, Guo Y, Zhao C, et al. In vitro activities of tedizolid compared with other antibiotics against Gram-positive pathogens associated with hospital-acquired pneumonia, skin and soft tissue infection and bloodstream infection collected from 26 hospitals in China. J Med Microbiol. 2016;65:1215ā24.
Lodise TP, Fang E, Minassian SL, Prokocimer PG. Platelet profile in patients with acute bacterial skin and skin structure infections receiving tedizolid or linezolid: findings from the phase 3 ESTABLISH clinical trials. Antimicrob Agents Chemother. 2014;58:7198ā204.
Shaw KJ, Barbachyn MR. The oxazolidinones: past, present, and future. Ann N Y Acad Sci. 2011;1241:48ā70.
Flanagan S, Passarell J, Lu Q. Tedizolid population pharmacokinetics, exposure response, and target attainment. Antimicrob Agents Chemother. 2014;58:6462ā70.
Lodise TP, Drusano GL. Use of pharmacokinetic/pharmacodynamic systems analyses to inform dose selection of tedizolid phosphate. Clin Infect Dis. 2014;58(Suppl 1):S28ā34.
Tessier PR, Keel RA, Hagihara M, Crandon JL, Nicolau DP. Comparative in vivo efficacies of epithelial lining fluid exposures of tedizolid, linezolid, and vancomycin for methicillin-resistant Staphylococcus aureus in a mouse pneumonia model. Antimicrob Agents Chemother. 2012;56:2342ā6.
Livermore DM, Warner M, Mushtaq S. Activity of MK-7655 combined with imipenem against Enterobacteriaceae and Pseudomonas aeruginosa. J Antimicrob Chemother. 2013;68:2286ā90.
Lucasti C, Vasile L, Sandesc D, et al. Phase 2, dose-ranging study of relebactam with imipenem-cilastatin in subjects with complicated intra-abdominal infection. Antimicrob Agents Chemother. 2016;60:6234ā43.
Hackel MA, Lomovskaya O, Dudley MN, Karlowsky JA, Saham DF. In vitro activity of meropenem-vaborbactam against clinical isolates of KPC-positive Enterobacteriaceae. Antimicrob Agents Chemother. 2017;62:e01904-17.
Griffith DC, Loutit JS, Morgan EE, Durso S, Dudley MN. Phase 1 study of the safety, tolerability, and pharmacokinetics of the Ī²-lactamase inhibitor vaborbactam (RPX7009) in healthy adult subjects. Antimicrob Agents Chemother. 2016;60:6326ā32.
Kaye KS, Bhowmick T, Metallidis S, et al. Effect of meropenem-vaborbactam vs piperacillin-tazobactam on clinical cure or improvement and microbial eradication in complicated urinary tract infection: the TANGO I randomized clinical trial. JAMA. 2018;319:788ā99.
Wunderink RG, Giamarellos-Bourboulis EJ, Rahav G, et al. Effect and safety of meropenem-vaborbactam versus best-available therapy in patients with carbapenem-resistant enterobacteriaceae infections: the TANGO II randomized clinical trial. Infect Dis Ther. 2018;7:439ā55.
Hackel MA, Tsuji M, Yamano Y, Echols R, Karlowsky JA, Sahm DF. In vitro activity of the siderophore cephalosporin, cefiderocol, against carbapenem-nonsusceptible and multidrug-resistant isolates of Gram-negative bacilli collected worldwide in 2014 to 2016. Antimicrob Agents Chemother. 2018;62:e01968-17.
Kawaguchi N, Katsube T, Echols R, Wajima T. Population pharmacokinetic analysis of cefiderocol, a parenteral siderophore cephalosporin, in healthy subjects, subjects with various degrees of renal function, and patients with complicated urinary tract infection or acute uncomplicated pyelonephritis. Antimicrob Agents Chemother. 2018;62:e01391-17.
Abdallah M, Olafisoye O, Cortes C, Urban C, Landman D, Quale J. Activity of eravacycline against Enterobacteriaceae and Acinetobacter baumannii, including multidrug-resistant isolates, from New York City. Antimicrob Agents Chemother. 2015;59:1802ā5.
Seifert H, Stefanik D, Sutcliffe JA, Higgins PG. In-vitro activity of the novel fluorocycline eravacycline against carbapenem non-susceptible Acinetobacte baumannii. Int J Antimicrob Agents. 2018;51:62ā4.
Snydman DR, McDermott LA, Jacobus NV, Kerstein K, Grossman TH, Sutcliffe JA. Evaluation of the in vitro activity of eravacycline against a broad spectrum of recent clinical anaerobic isolates. Antimicrob Agents Chemother. 2018;62:e02206-17.
Solomkin J, Evans D, Slepavicius A, Lee P, et al. Assessing the efficacy and safety of eravacycline vs ertapenem in complicated intra-abdominal infections in the Investigating Gram-Negative Infections Treated with Eravacycline (IGNITE 1) trial: a randomized clinical trial. JAMA Surg. 2017;152:224ā32.
Connors KP, Housman ST, Pope JS, et al. Phase I, open-label, safety and & pharmacokinetic study to assess bronchopulmonary disposition of intravenous eravacycline in healthy men and women. Antimicrob Agents Chemother. 2014;58:2113ā8.
Grossman TH, Murphy TM, Slee AM, Lofland D, Sutcliffe JA. Eravacycline (TP-434) is efficacious in animal models of infection. Antimicrob Agents Chemother. 2015;59:2567ā71.
Pfaller MA, Huband MD, Shortridge D, Flamm RK. Surveillance of omadacycline activity tested against clinical isolates from the United States and Europe as part of the 2016 SENTRY Antimicrobial Surveillance Program. Antimicrob Agents Chemother. 2018;62:e02327-17.
Sun H, Ting L, Machineni S, et al. Randomized, open-label study of the pharmacokinetics and safety of oral and intravenous administration of omadacycline to healthy subjects. Antimicrob Agents Chemother. 2016;60:7431ā5.
Noel GJ, Draper MP, Hait H, Tanaka SK, Arbeit RD. A randomized, evaluator-blind, phase 2 study comparing the safety and efficacy of omadacycline to those of linezolid for treatment of complicated skin and skin structure infections. Antimicrob Agents Chemother. 2012;56:5650ā4.
Gotfried MH, Horn K, Garrity-Ryan L, et al. Comparison of omadacycline and tigecycline pharmacokinetics in the plasma, epithelial lining fluid, and alveolar cells of healthy adult subjects. Antimicrob Agents Chemother. 2017;61:e01135-17.
Castanheira M, Davis AP, Mendes RE, Serio AW, Krause KM, Flamm RK. In vitro activity of plazomicin against gram-negative and gram-positive isolates collected from U.S. hospitals and comparative activities of aminoglycosides against carbapenem-resistant Enterobacteriaceae and isolates carrying carbapenemase genes. Antimicrob Agents Chemother. 2018;62:e00313-18.
Thwaites M, Hall D, Stoneburner A, et al. Activity of plazomicin in combination with other antibiotics against multidrug-resistant Enterobacteriaceae. Diagn Microbiol Infect Dis. 2018;92:338ā45.
GarcĆa-Salguero C, RodrĆguez-Avial I, Picazo JJ, Culebras E. Can plazomicin alone or in combination be a therapeutic option against carbapenem-resistant Acinetobacter baumannii? Antimicrob Agents Chemother. 2015;59:5959ā66.
Connolly LE, Riddle V, Cebrik D, Armstrong ES, Miller LG. A multicenter, randomized, double-blind, phase 2 study of the efficacy and safety of plazomicin compared with levofloxacin in the treatment of complicated urinary tract infection and acute pyelonephritis. Antimicrob Agents Chemother. 2018;62:e01989-17.
Veve MP, Wagner JL. Lefamulin: review of a promising novel pleuromutilin antibiotic. Pharmacotherapy. 2018;38:935ā46.
Martin-Loeches I, Dale GE, Torres A. Murepavadin: a new antibiotic class in the pipeline. Expert Rev Anti Infect Ther. 2018;16:259ā68.
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Bassetti, M., Righi, E., Carnelutti, A. (2019). Light and Shade of Antibiotics Recently Approved and inĀ Advanced Development for Critically Ill Patients. In: Vincent, JL. (eds) Annual Update in Intensive Care and Emergency Medicine 2019. Annual Update in Intensive Care and Emergency Medicine. Springer, Cham. https://doi.org/10.1007/978-3-030-06067-1_37
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DOI: https://doi.org/10.1007/978-3-030-06067-1_37
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