β-laktam Antibiyotiklere Dirençli Bakteriler ile Gelişen Enfeksiyonlarda Tedavi
Özet
ß-laktam antibiyotiklerin, enfeksiyon hastalıklarının tedavisinde uzun yıllardır temel ilaç gruplarından biri olmasına karşın, artan ß-laktamaz kaynaklı direnç bu ilaçların etkinliğini önemli ölçüde azaltmaktadır. Bu derlemede, karbapenemaz üreten Enterobacterales (KDE), Pseudomonas aeruginosa ve Acinetobacter baumannii gibi dirençli gram negatif bakterilerin neden olduğu enfeksiyonlarda güncel tedavi yaklaşımları özetlenmiştir. Karbapenem direnci başta olmak üzere, OXA-48, NDM ve KPC tipi ß-laktamazların klinik önemi ve bu izolatlara karşı geliştirilen yeni antibiyotikler (seftazidim-avibaktam, meropenem-vaborbaktam, imipenem-silastatin-relebaktam, sefiderokol, durlobaktam-sulbaktam) ele alınmıştır. Ayrıca aminoglikozitler, tigesiklin, fosfomisin ve polimiksinlerin kullanım alanları, kombinasyon tedavilerinin yeri ve sınırlamaları tartışılmıştır. Yeni ß-laktam/ß-laktamaz inhibitör kombinasyonları dirençli gram negatif enfeksiyonların tedavisinde önemli bir ilerleme sağlamıştır. Bununla birlikte, tedavi seçiminde direnç mekanizmasının doğru tanımlanması, yerelepidemiyolojik verilerin dikkate alınması ve antibiyotik duyarlılık testlerinin kılavuzluğunda bireyselleştirilmiş tedavi uygulanması gereklidir. Direnç gelişimini önlemek için antimikrobiyal yönetim programlarının güçlendirilmesi ve hızlı tanı testlerinin rutin klinik uygulamaya sokulması büyük önem taşımaktadır.
Although ß-lactam antibiotics have been the cornerstone of infection therapy for decades, the emergence of ß-lactamase–mediated resistance has markedly reduced their efficacy. This review summarizes current therapeutic strategies for infections caused by resistant Gram-negative bacteria such as carbapenemase-producing Enterobacterales (CPE), Pseudomonas aeruginosa, and Acinetobacter baumannii. The review highlights the clinical relevance of carbapenemase types including OXA-48, NDM, and KPC, and discusses the therapeutic roles of novel agents such as ceftazidime-avibactam, meropenem-vaborbactam, imipenem-silastatin-relebactam, cefiderocol, and sulbactam-durlobactam. The role of aminoglycosides, tigecycline, fosfomycin, and polymyxins, as well as the limited use of combination therapies, are also evaluated. Recently developed ß-lactam/ß-lactamase inhibitor combinations represent a major advance in managing multidrug-resistant Gram-negative infections. However, successful treatment requires precise identification of resistance mechanisms, consideration of local epidemiology, and individualized therapy guided by susceptibility testing. To prevent further resistance, robust antimicrobial stewardship and integration of rapid diagnostic tools into routine clinical practice are essential.
Referanslar
Pande N, Cascella M. ß-Lactam Antibiotics. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan. Erişim tarihi: 18 Ekim 2025.
Ibrahim ME, Abbas M, Al-Shahrai AM, Elamin BK. Phenotypic Characterization and Antibiotic Resistance Patterns of Extended-Spectrum β-Lactamase- and AmpC β-Lactamase-Producing Gram-Negative Bacteria in a Referral Hospital, Saudi Arabia. Can J Infect Dis Med Microbiol. 2019; 2019:6054694.
Shields RK, Clancy CJ, Press EG, Nguyen MH. Aminoglycosides for Treatment of Bacteremia Due to Carbapenem-Resistant Klebsiella pneumoniae. Antimicrob Agents Chemother. 2016; 60:3187
Goodman KE, Lessler J, Cosgrove SE, et al. A Clinical Decision Tree to Predict Whether a Bacteremic Patient Is Infected With an Extended-Spectrum β-Lactamase-Producing Organism. Clin Infect Dis. 2016; 63:896.
Levasseur P, Girard AM, Miossec C, et al. In vitro antibacterial activity of the ceftazidime-avibactam combination against enterobacteriaceae, including strains with well-characterized β-lactamases. Antimicrob Agents Chemother. 2015; 59:1931.
Davido B, Fellous L, Lawrence C, et al. Ceftazidime-Avibactam and Aztreonam, an Interesting Strategy To Overcome β-Lactam Resistance Conferred by Metallo-β-Lactamases in Enterobacteriaceae and Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2017; 61(9):e01008-17. doi: 10.1128/AAC.01008-17.
Kelesidis T, Karageorgopoulos DE, Kelesidis I, Falagas ME. Tigecycline for the treatment of multidrug-resistant Enterobacteriaceae: a systematic review of the evidence from microbiological and clinical studies. J Antimicrob Chemother. 2008; 62:895.
Kaye KS, Rice LB, Dane AL, et al. Fosfomycin for Injection (ZTI-01) Versus Piperacillin-tazobactam for the Treatment of Complicated Urinary Tract Infection Including Acute Pyelonephritis: ZEUS, A Phase 2/3 Randomized Trial. Clin Infect Dis. 2019; 69:2045.
Adelman MW, Bower CW, Grass JE, et al. Distinctive Features of Ertapenem-Mono-Resistant Carbapenem-Resistant Enterobacterales in the United States: A Cohort Study. Open Forum Infect Dis 2022; 9:ofab643. Erişim tarihi: 18 Ekim 2025.
Tamma PD, Goodman KE, Harris AD, et al. Comparing the Outcomes of Patients With Carbapenemase-Producing and Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae Bacteremia. Clin Infect Dis. 2017; 64:257.
Zhao Z, Lan F, Liu M, et al. Evaluation of automated systems for aminoglycosides and fluoroquinolones susceptibility testing for Carbapenem-resistant Enterobacteriaceae. Antimicrob Resist Infect Control. 2017; 6:77
Luterbach CL, Boshe A, Henderson HI, et al. The Role of Trimethoprim/Sulfamethoxazole in the Treatment of Infections Caused by Carbapenem-Resistant Enterobacteriaceae. Open Forum Infect Di.s 2019; 6:ofy351.
Satlin MJ, Kubin CJ, Blumenthal JS, et al. Comparative effectiveness of aminoglycosides, polymyxin B, and tigecycline for clearance of carbapenem-resistant Klebsiella pneumoniae from urine. Antimicrob Agents Chemother. 2011; 55:5893
McKinnell JA, Dwyer JP, Talbot GH, et al. Plazomicin for Infections Caused by Carbapenem-Resistant Enterobacteriaceae. N Engl J Med. 2019; 380:791.
Amladi AU, Abirami B, Devi SM, et al. Susceptibility profile, resistance mechanisms & efficacy ratios of fosfomycin, nitrofurantoin & colistin for carbapenem-resistant Enterobacteriaceae causing urinary tract infections. Indian J Med Res. 2019; 149:185
Falagas ME, Kastoris AC, Kapaskelis AM, Karageorgopoulos DE. Fosfomycin for the treatment of multidrug-resistant, including extended-spectrum ß-lactamase producing, Enterobacteriaceae infections: a systematic review. Lancet Infect Dis. 2010; 10:43.
Elliott ZS, Barry KE, Cox HL, et al. The Role of fosA in Challenges with Fosfomycin Susceptibility Testing of Multispecies Klebsiella pneumoniae Carbapenemase-Producing Clinical Isolates. J Clin Microbiol 2019; 57(10):e00634-19. doi: 10.1128/JCM.00634-19
Ito R, Mustapha MM, Tomich AD, et al. Widespread Fosfomycin Resistance in Gram-Negative Bacteria Attributable to the Chromosomal fosA Gene. mBio 2017; 8(4):e00749-17. doi: 10.1128/mBio.00749-17.
Sabour S, Huang JY, Bhatnagar A, et al. Detection and Characterization of Targeted Carbapenem-Resistant Health Care-Associated Threats: Findings from the Antibiotic Resistance Laboratory Network, 2017 to 2019. Antimicrob Agents Chemother. 2021; 65:e0110521
Boyd SE, Livermore DM, Hooper DC, Hope WW. Metallo-β-Lactamases: Structure, Function, Epidemiology, Treatment Options, and the Development Pipeline. Antimicrob Agents Chemother. 2020; 64(10):e00397-20
van Duin D, Lok JJ, Earley M, et al. Colistin Versus Ceftazidime-Avibactam in the Treatment of Infections Due to Carbapenem-Resistant Enterobacteriaceae. Clin Infect Dis. 2018; 66:163.
Tumbarello M, Trecarichi EM, Corona A, et al. Efficacy of Ceftazidime-Avibactam Salvage Therapy in Patients With Infections Caused by Klebsiella pneumoniae Carbapenemase-producing K. pneumoniae. Clin Infect Dis. 2019; 68:355
Motsch J, Murta de Oliveira C, Stus V,Koksal I, et al. RESTORE-IMI 1: A Multicenter, Randomized, Double-blind Trial Comparing Efficacy and Safety of Imipenem/Relebactam vs Colistin Plus Imipenem in Patients With Imipenem-nonsusceptible Bacterial Infections. Clin Infect Dis. 2020; 70:1799.
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; 7:439.
Castanheira M, Doyle TB, Kantro V, et al. Meropenem-Vaborbactam Activity against Carbapenem-Resistant Enterobacterales Isolates Collected in U.S. Hospitals during 2016 to 2018. Antimicrob Agents Chemother. 2020; 64(2):e01951-19. doi: 10.1128/AAC.01951-19.
Yang TY, Hsieh YJ, Kao LT, et al. Activities of imipenem-relebactam combination against carbapenem-nonsusceptible Enterobacteriaceae in Taiwan. J Microbiol Immunol Infect. 2022; 55:86,
Johnston BD, Thuras P, Porter SB, et al. Activity of Imipenem-Relebactam against Carbapenem-Resistant Escherichia coli Isolates from the United States in Relation to Clonal Background, Resistance Genes, Coresistance, and Region. Antimicrob Agents Chemother 2020; 64
Kazmierczak KM, Tsuji M, Wise MG, et al. In vitro activity of cefiderocol, a siderophore cephalosporin, against a recent collection of clinically relevant carbapenem-non-susceptible Gram-negative bacilli, including serine carbapenemase- and metallo-β-lactamase-producing isolates (SIDERO-WT-2014 Study). Int J Antimicrob Agents 2019; 53:177.
Morrissey I, Olesky M, Hawser S, et al. In Vitro Activity of Eravacycline against Gram-Negative Bacilli Isolated in Clinical Laboratories Worldwide from 2013 to 2017. Antimicrob Agents Chemother 2020; 64(3):e01699-19. doi: 10.1128/AAC.01699-19.
Castanheira M, Doyle TB, Collingsworth TD, et al. InKDEasing frequency of OXA-48-producing Enterobacterales worldwide and activity of ceftazidime/avibactam, meropenem/vaborbactam and comparators against these isolates. J Antimicrob Chemother 2021; 76:3125.,
Johnston BD, Thuras P, Porter SB, et al. Activity of Cefiderocol, Ceftazidime-Avibactam, and Eravacycline against Carbapenem-Resistant Escherichia coli Isolates from the United States and International Sites in Relation to Clonal Background, Resistance Genes, Coresistance, and Region. Antimicrob Agents Chemother 2020; 64: (10):e00797-20. doi: 10.1128/AAC.00797-20.
Lob SH, Karlowsky JA, Young K, et al. In vitro activity of imipenem-relebactam against resistant phenotypes of Enterobacteriaceae and Pseudomonas aeruginosa isolated from intraabdominal and urinary tract infection samples - SMART Surveillance Europe 2015-2017. J Med Microbiol 2020; 69:207.
Lutgring JD, Balbuena R, Reese N, et al. Antibiotic Susceptibility of NDM-Producing Enterobacterales Collected in the United States in 2017 and 2018. Antimicrob Agents Chemother. 2020; 64: (9):e00499-20. doi: 10.1128/AAC.00499-20.
Alraddadi BM, Saeedi M, Qutub M, et al. Efficacy of ceftazidime-avibactam in the treatment of infections due to Carbapenem-resistant Enterobacteriaceae. BMC Infect Dis. 2019; 19:772.,
Kulengowski B, Burgess DS. Imipenem/relebactam activity compared to other antimicrobials against non-MBL-producing carbapenem-resistant Enterobacteriaceae from an academic medical center. Pathog Dis. 2019; 77(4):ftz040. doi: 10.1093/femspd/ftz040.
Kadri SS, Adjemian J, Lai YL, et al. Difficult-to-Treat Resistance in Gram-negative Bacteremia at 173 US Hospitals: Retrospective Cohort Analysis of Prevalence, Predictors, and Outcome of Resistance to All First-line Agents. Clin Infect Dis. 2018; 67:1803.
Rosenthal VD, Yin R, Nercelles P, et al. International Nosocomial Infection Control Consortium (INICC) report of health care associated infections, data summary of 45 countries for 2015 to 2020, adult and pediatric units, device-associated module. Am J Infect Control. 2024; 52:1002
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.
Falagas ME, Tansarli GS, Ikawa K, Vardakas KZ. Clinical outcomes with extended or continuous versus short-term intravenous infusion of carbapenems and piperacillin/tazobactam: a systematic review and meta-analysis. Clin Infect Dis. 2013; 56:272.
Phe K, Bowers DR, Babic JT, Tam VH. Outcomes of empiric aminoglycoside monotherapy for Pseudomonas aeruginosa bacteremia. Diagn Microbiol Infect Dis. 2019; 93:346.
Wagenlehner FM, Umeh O, Steenbergen J, et al. 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; 385:1949
Torres A, Zhong N, Pachl J, et al. Ceftazidime-avibactam versus meropenem in nosocomial pneumonia, including ventilator-associated pneumonia (REPROVE): a randomised, double-blind, phase 3 non-inferiority trial. Lancet Infect Dis. 2018; 18:285.
Portsmouth S, van Veenhuyzen D, Echols R, et al. Cefiderocol versus imipenem-cilastatin for the treatment of complicated urinary tract infections caused by Gram-negative uropathogens: a phase 2, randomised, double-blind, non-inferiority trial. Lancet Infect Dis 2018; 18:1319.
Craddock VD, Steere EL, Harman H, Britt NS. Activity of Delafloxacin and Comparator Fluoroquinolones against Multidrug-Resistant Pseudomonas aeruginosa in an In Vitro Cystic Fibrosis Sputum Model. Antibiotics (Basel) 2023; 12(6):1078. doi: 10.3390/antibiotics12061078.
UpToDate. Pseudomonal infections. Erişim tarihi: 30 Ekim 2025.
De Rosa FG, Corcione S, Pagani N, Di Perri G. From ESKAPE to ESCAPE, from KPC to CCC. Clin Infect Dis. 2015; 60:1289
Higgins PG, Dammhayn C, Hackel M, Seifert H. Global spread of carbapenem-resistant Acinetobacter baumannii. J Antimicrob Chemother 2010; 65:233.
Seifert H, Blondeau J, Lucaßen K, Utt EA. Global update on the in vitro activity of tigecycline and comparators against isolates of Acinetobacter baumannii and rates of resistant phenotypes (2016-2018). J Glob Antimicrob Resist 2022; 31:82.
Fishbain J, Peleg AY. Treatment of Acinetobacter infections. Clin Infect Dis 2010; 51:79.
Makris D, Petinaki E, Tsolaki V, et al. Colistin versus Colistin Combined with Ampicillin-Sulbactam for Multiresistant Acinetobacter baumannii Ventilator-associated Pneumonia Treatment: An Open-label Prospective Study. Indian J Crit Care Med 2018; 22:67.
Liu J, Shu Y, Zhu F, et al. Comparative efficacy and safety of combination therapy with high-dose sulbactam or colistin with additional antibacterial agents for multiple drug-resistant and extensively drug-resistant Acinetobacter baumannii infections: A systematic review and network meta-analysis. J Glob Antimicrob Resist. 2021; 24:136.
Karlowsky JA, Hackel MA, McLeod SM, Miller AA. In Vitro Activity of Sulbactam-Durlobactam against Global Isolates of Acinetobacter baumannii-calcoaceticus Complex Collected from 2016 to 2021. Antimicrob Agents Chemother. 2022; 66:e0078122.
Referanslar
Pande N, Cascella M. ß-Lactam Antibiotics. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan. Erişim tarihi: 18 Ekim 2025.
Ibrahim ME, Abbas M, Al-Shahrai AM, Elamin BK. Phenotypic Characterization and Antibiotic Resistance Patterns of Extended-Spectrum β-Lactamase- and AmpC β-Lactamase-Producing Gram-Negative Bacteria in a Referral Hospital, Saudi Arabia. Can J Infect Dis Med Microbiol. 2019; 2019:6054694.
Shields RK, Clancy CJ, Press EG, Nguyen MH. Aminoglycosides for Treatment of Bacteremia Due to Carbapenem-Resistant Klebsiella pneumoniae. Antimicrob Agents Chemother. 2016; 60:3187
Goodman KE, Lessler J, Cosgrove SE, et al. A Clinical Decision Tree to Predict Whether a Bacteremic Patient Is Infected With an Extended-Spectrum β-Lactamase-Producing Organism. Clin Infect Dis. 2016; 63:896.
Levasseur P, Girard AM, Miossec C, et al. In vitro antibacterial activity of the ceftazidime-avibactam combination against enterobacteriaceae, including strains with well-characterized β-lactamases. Antimicrob Agents Chemother. 2015; 59:1931.
Davido B, Fellous L, Lawrence C, et al. Ceftazidime-Avibactam and Aztreonam, an Interesting Strategy To Overcome β-Lactam Resistance Conferred by Metallo-β-Lactamases in Enterobacteriaceae and Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2017; 61(9):e01008-17. doi: 10.1128/AAC.01008-17.
Kelesidis T, Karageorgopoulos DE, Kelesidis I, Falagas ME. Tigecycline for the treatment of multidrug-resistant Enterobacteriaceae: a systematic review of the evidence from microbiological and clinical studies. J Antimicrob Chemother. 2008; 62:895.
Kaye KS, Rice LB, Dane AL, et al. Fosfomycin for Injection (ZTI-01) Versus Piperacillin-tazobactam for the Treatment of Complicated Urinary Tract Infection Including Acute Pyelonephritis: ZEUS, A Phase 2/3 Randomized Trial. Clin Infect Dis. 2019; 69:2045.
Adelman MW, Bower CW, Grass JE, et al. Distinctive Features of Ertapenem-Mono-Resistant Carbapenem-Resistant Enterobacterales in the United States: A Cohort Study. Open Forum Infect Dis 2022; 9:ofab643. Erişim tarihi: 18 Ekim 2025.
Tamma PD, Goodman KE, Harris AD, et al. Comparing the Outcomes of Patients With Carbapenemase-Producing and Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae Bacteremia. Clin Infect Dis. 2017; 64:257.
Zhao Z, Lan F, Liu M, et al. Evaluation of automated systems for aminoglycosides and fluoroquinolones susceptibility testing for Carbapenem-resistant Enterobacteriaceae. Antimicrob Resist Infect Control. 2017; 6:77
Luterbach CL, Boshe A, Henderson HI, et al. The Role of Trimethoprim/Sulfamethoxazole in the Treatment of Infections Caused by Carbapenem-Resistant Enterobacteriaceae. Open Forum Infect Di.s 2019; 6:ofy351.
Satlin MJ, Kubin CJ, Blumenthal JS, et al. Comparative effectiveness of aminoglycosides, polymyxin B, and tigecycline for clearance of carbapenem-resistant Klebsiella pneumoniae from urine. Antimicrob Agents Chemother. 2011; 55:5893
McKinnell JA, Dwyer JP, Talbot GH, et al. Plazomicin for Infections Caused by Carbapenem-Resistant Enterobacteriaceae. N Engl J Med. 2019; 380:791.
Amladi AU, Abirami B, Devi SM, et al. Susceptibility profile, resistance mechanisms & efficacy ratios of fosfomycin, nitrofurantoin & colistin for carbapenem-resistant Enterobacteriaceae causing urinary tract infections. Indian J Med Res. 2019; 149:185
Falagas ME, Kastoris AC, Kapaskelis AM, Karageorgopoulos DE. Fosfomycin for the treatment of multidrug-resistant, including extended-spectrum ß-lactamase producing, Enterobacteriaceae infections: a systematic review. Lancet Infect Dis. 2010; 10:43.
Elliott ZS, Barry KE, Cox HL, et al. The Role of fosA in Challenges with Fosfomycin Susceptibility Testing of Multispecies Klebsiella pneumoniae Carbapenemase-Producing Clinical Isolates. J Clin Microbiol 2019; 57(10):e00634-19. doi: 10.1128/JCM.00634-19
Ito R, Mustapha MM, Tomich AD, et al. Widespread Fosfomycin Resistance in Gram-Negative Bacteria Attributable to the Chromosomal fosA Gene. mBio 2017; 8(4):e00749-17. doi: 10.1128/mBio.00749-17.
Sabour S, Huang JY, Bhatnagar A, et al. Detection and Characterization of Targeted Carbapenem-Resistant Health Care-Associated Threats: Findings from the Antibiotic Resistance Laboratory Network, 2017 to 2019. Antimicrob Agents Chemother. 2021; 65:e0110521
Boyd SE, Livermore DM, Hooper DC, Hope WW. Metallo-β-Lactamases: Structure, Function, Epidemiology, Treatment Options, and the Development Pipeline. Antimicrob Agents Chemother. 2020; 64(10):e00397-20
van Duin D, Lok JJ, Earley M, et al. Colistin Versus Ceftazidime-Avibactam in the Treatment of Infections Due to Carbapenem-Resistant Enterobacteriaceae. Clin Infect Dis. 2018; 66:163.
Tumbarello M, Trecarichi EM, Corona A, et al. Efficacy of Ceftazidime-Avibactam Salvage Therapy in Patients With Infections Caused by Klebsiella pneumoniae Carbapenemase-producing K. pneumoniae. Clin Infect Dis. 2019; 68:355
Motsch J, Murta de Oliveira C, Stus V,Koksal I, et al. RESTORE-IMI 1: A Multicenter, Randomized, Double-blind Trial Comparing Efficacy and Safety of Imipenem/Relebactam vs Colistin Plus Imipenem in Patients With Imipenem-nonsusceptible Bacterial Infections. Clin Infect Dis. 2020; 70:1799.
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; 7:439.
Castanheira M, Doyle TB, Kantro V, et al. Meropenem-Vaborbactam Activity against Carbapenem-Resistant Enterobacterales Isolates Collected in U.S. Hospitals during 2016 to 2018. Antimicrob Agents Chemother. 2020; 64(2):e01951-19. doi: 10.1128/AAC.01951-19.
Yang TY, Hsieh YJ, Kao LT, et al. Activities of imipenem-relebactam combination against carbapenem-nonsusceptible Enterobacteriaceae in Taiwan. J Microbiol Immunol Infect. 2022; 55:86,
Johnston BD, Thuras P, Porter SB, et al. Activity of Imipenem-Relebactam against Carbapenem-Resistant Escherichia coli Isolates from the United States in Relation to Clonal Background, Resistance Genes, Coresistance, and Region. Antimicrob Agents Chemother 2020; 64
Kazmierczak KM, Tsuji M, Wise MG, et al. In vitro activity of cefiderocol, a siderophore cephalosporin, against a recent collection of clinically relevant carbapenem-non-susceptible Gram-negative bacilli, including serine carbapenemase- and metallo-β-lactamase-producing isolates (SIDERO-WT-2014 Study). Int J Antimicrob Agents 2019; 53:177.
Morrissey I, Olesky M, Hawser S, et al. In Vitro Activity of Eravacycline against Gram-Negative Bacilli Isolated in Clinical Laboratories Worldwide from 2013 to 2017. Antimicrob Agents Chemother 2020; 64(3):e01699-19. doi: 10.1128/AAC.01699-19.
Castanheira M, Doyle TB, Collingsworth TD, et al. InKDEasing frequency of OXA-48-producing Enterobacterales worldwide and activity of ceftazidime/avibactam, meropenem/vaborbactam and comparators against these isolates. J Antimicrob Chemother 2021; 76:3125.,
Johnston BD, Thuras P, Porter SB, et al. Activity of Cefiderocol, Ceftazidime-Avibactam, and Eravacycline against Carbapenem-Resistant Escherichia coli Isolates from the United States and International Sites in Relation to Clonal Background, Resistance Genes, Coresistance, and Region. Antimicrob Agents Chemother 2020; 64: (10):e00797-20. doi: 10.1128/AAC.00797-20.
Lob SH, Karlowsky JA, Young K, et al. In vitro activity of imipenem-relebactam against resistant phenotypes of Enterobacteriaceae and Pseudomonas aeruginosa isolated from intraabdominal and urinary tract infection samples - SMART Surveillance Europe 2015-2017. J Med Microbiol 2020; 69:207.
Lutgring JD, Balbuena R, Reese N, et al. Antibiotic Susceptibility of NDM-Producing Enterobacterales Collected in the United States in 2017 and 2018. Antimicrob Agents Chemother. 2020; 64: (9):e00499-20. doi: 10.1128/AAC.00499-20.
Alraddadi BM, Saeedi M, Qutub M, et al. Efficacy of ceftazidime-avibactam in the treatment of infections due to Carbapenem-resistant Enterobacteriaceae. BMC Infect Dis. 2019; 19:772.,
Kulengowski B, Burgess DS. Imipenem/relebactam activity compared to other antimicrobials against non-MBL-producing carbapenem-resistant Enterobacteriaceae from an academic medical center. Pathog Dis. 2019; 77(4):ftz040. doi: 10.1093/femspd/ftz040.
Kadri SS, Adjemian J, Lai YL, et al. Difficult-to-Treat Resistance in Gram-negative Bacteremia at 173 US Hospitals: Retrospective Cohort Analysis of Prevalence, Predictors, and Outcome of Resistance to All First-line Agents. Clin Infect Dis. 2018; 67:1803.
Rosenthal VD, Yin R, Nercelles P, et al. International Nosocomial Infection Control Consortium (INICC) report of health care associated infections, data summary of 45 countries for 2015 to 2020, adult and pediatric units, device-associated module. Am J Infect Control. 2024; 52:1002
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.
Falagas ME, Tansarli GS, Ikawa K, Vardakas KZ. Clinical outcomes with extended or continuous versus short-term intravenous infusion of carbapenems and piperacillin/tazobactam: a systematic review and meta-analysis. Clin Infect Dis. 2013; 56:272.
Phe K, Bowers DR, Babic JT, Tam VH. Outcomes of empiric aminoglycoside monotherapy for Pseudomonas aeruginosa bacteremia. Diagn Microbiol Infect Dis. 2019; 93:346.
Wagenlehner FM, Umeh O, Steenbergen J, et al. 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; 385:1949
Torres A, Zhong N, Pachl J, et al. Ceftazidime-avibactam versus meropenem in nosocomial pneumonia, including ventilator-associated pneumonia (REPROVE): a randomised, double-blind, phase 3 non-inferiority trial. Lancet Infect Dis. 2018; 18:285.
Portsmouth S, van Veenhuyzen D, Echols R, et al. Cefiderocol versus imipenem-cilastatin for the treatment of complicated urinary tract infections caused by Gram-negative uropathogens: a phase 2, randomised, double-blind, non-inferiority trial. Lancet Infect Dis 2018; 18:1319.
Craddock VD, Steere EL, Harman H, Britt NS. Activity of Delafloxacin and Comparator Fluoroquinolones against Multidrug-Resistant Pseudomonas aeruginosa in an In Vitro Cystic Fibrosis Sputum Model. Antibiotics (Basel) 2023; 12(6):1078. doi: 10.3390/antibiotics12061078.
UpToDate. Pseudomonal infections. Erişim tarihi: 30 Ekim 2025.
De Rosa FG, Corcione S, Pagani N, Di Perri G. From ESKAPE to ESCAPE, from KPC to CCC. Clin Infect Dis. 2015; 60:1289
Higgins PG, Dammhayn C, Hackel M, Seifert H. Global spread of carbapenem-resistant Acinetobacter baumannii. J Antimicrob Chemother 2010; 65:233.
Seifert H, Blondeau J, Lucaßen K, Utt EA. Global update on the in vitro activity of tigecycline and comparators against isolates of Acinetobacter baumannii and rates of resistant phenotypes (2016-2018). J Glob Antimicrob Resist 2022; 31:82.
Fishbain J, Peleg AY. Treatment of Acinetobacter infections. Clin Infect Dis 2010; 51:79.
Makris D, Petinaki E, Tsolaki V, et al. Colistin versus Colistin Combined with Ampicillin-Sulbactam for Multiresistant Acinetobacter baumannii Ventilator-associated Pneumonia Treatment: An Open-label Prospective Study. Indian J Crit Care Med 2018; 22:67.
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