Perspectives on the use of ceftolozane/tazobactam: a review of clinical trial data and real-world evidence

References

• Antimicrobial Resistance Collaborators. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet 399(10325), 629–655 (2022).
   PubMed Web of Science ®Google Scholar
• Cassini A, Hogberg LD, Plachouras D et al. Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: a population-level modelling analysis. Lancet Infect Dis 19(1), 56–66 (2019).
   PubMed Web of Science ®Google Scholar
• Antibiotic resistance threats in the United States (2019). https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf ( May 9).
   Google Scholar
• Antibiotic resistance. https://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance ( June 9).
   Google Scholar
• Antimicrobial Resistance Collaborators. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet 399(10325), 629–655 (2022).
   PubMed Web of Science ®Google Scholar
• Infectious Diseases Society of America. The 10 × '20 Initiative: pursuing a global commitment to develop 10 new antibacterial drugs by 2020. Clin. Infect. Dis. 50(8), 1081–1083 (2010).
   PubMed Web of Science ®Google Scholar
• Boucher HW, Talbot GH, Bradley JS et al. Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin. Infect. Dis. 48(1), 1–12 (2009).
   PubMed Web of Science ®Google Scholar
• WHO publishes list of bacteria for which new antibiotics are urgently needed. https://www.who.int/news-room/detail/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-needed ( May 11).
   Google Scholar
• Shortridge D, Carvalhaes C, Deshpande L, Castanheira M. Activity of meropenem/vaborbactam and comparators against Gram-negative isolates from Eastern and Western European patients hospitalized with pneumonia including ventilator-associated pneumonia (2014–19). J. Antimicrob. Chemother. 76(10), 2600–2605 (2021).
   PubMed Web of Science ®Google Scholar
• Micek ST, Wunderink RG, Kollef MH et al. An international multicenter retrospective study of Pseudomonas aeruginosa nosocomial pneumonia: impact of multidrug resistance. Crit Care 19(1), 219 (2015).
   PubMedGoogle Scholar
• Magill SS, Edwards JR, Bamberg W et al. Multistate point-prevalence survey of health care-associated infections. N. Engl. J. Med. 370(13), 1198–1208 (2014).
   PubMed Web of Science ®Google Scholar
• Shebl E, Gulick PG. Nosocomial pneumonia. In: StatPearls [Internet]. StatPearls Publishing (2023).
   Google Scholar
• Bart SM, Rubin D, Kim P, Farley JJ, Nambiar S. Trends in Hospital-Acquired and Ventilator-Associated Bacterial Pneumonia Trials. Clin. Infect. Dis. 73(3), e602–e608 (2021).
   PubMed Web of Science ®Google Scholar
• Suetens C, Latour K, Kärki T et al. Prevalence of healthcare-associated infections, estimated incidence and composite antimicrobial resistance index in acute care hospitals and long-term care facilities: results from two European point prevalence surveys, 2016 to 2017. Euro Surveill 23(46), 1800516 (2018).
   PubMedGoogle Scholar
• Karlowsky JA, Lob SH, Young K, Motyl MR, Sahm DF. Activity of ceftolozane/tazobactam against Gram-negative isolates from patients with lower respiratory tract infections - SMART United States 2018–2019. BMC Microbiol 21(1), 74 (2021).
   PubMed Web of Science ®Google Scholar
• Lob S, Hackel M, Siddiqui F et al. Activity of ceftolozane/tazobactam and comparators against clinical MDR and DTR Pseudomonas aeruginosa isolates – SMART United States 2018–2020. Open Forum Infect Dis 9(Suppl. 2), ofac492 (2022).
   Google Scholar
• Lob SH, Depestel DD, Deryke CA et al. Ceftolozane/tazobactam and imipenem/relebactam cross-susceptibility among clinical isolates of Pseudomonas aeruginosa from patients with respiratory tract infections in ICU and Non-ICU wards – SMART United States 2017–2019. Open Forum Infect Dis 8(7), ofab320 (2021).
   PubMed Web of Science ®Google Scholar
• Puzniak L, Depestel DD, Yu K, Ye G, Gupta V. Epidemiology and regional variation of nonsusceptible and multidrug-resistant Pseudomonas aeruginosa isolates from intensive versus non-intensive care units across multiple centers in the United States. Diagn. Microbiol. Infect. Dis. 99(2), 115172 (2021).
   PubMed Web of Science ®Google Scholar
• Lob S, Hackel M, Siddiqui F et al. Trends in antimicrobial susceptibility to ceftolozane/tazobactam and comparators of Pseudomonas aeruginosa from patients with respiratory tract infections in five Latin American countries–SMART 2017–2020. Open Forum Infect Dis 9, ofac492.1304 (2022).
   Google Scholar
• Jernigan JA, Hatfield KM, Wolford H et al. Multidrug-resistant bacterial infections in U.S. hospitalized patients, 2012–2017. N. Engl. J. Med. 382(14), 1309–1319 (2020).
   PubMed Web of Science ®Google Scholar
• Karlowsky JA, Lob SH, Raddatz J et al. In vitro activity of imipenem/relebactam and ceftolozane/tazobactam against clinical isolates of gram-negative bacilli with difficult-to-treat resistance and multidrug-resistant phenotypes-study for monitoring antimicrobial resistance trends, United States 2015–2017. Clin. Infect. Dis. 72(12), 2112–2120 (2021).
   PubMed Web of Science ®Google Scholar
• Juan C, Maciá MD, Gutiérrez O, Vidal C, Pérez JL, Oliver A. Molecular mechanisms of beta-lactam resistance mediated by AmpC hyperproduction in Pseudomonas aeruginosa clinical strains. Antimicrob. Agents Chemother. 49(11), 4733–4738 (2005).
   PubMed Web of Science ®Google Scholar
• Xia J, Gao J, Tang W. Nosocomial infection and its molecular mechanisms of antibiotic resistance. Biosci Trends 10(1), 14–21 (2016).
   PubMed Web of Science ®Google Scholar
• Chevalier S, Bouffartigues E, Bodilis J et al. Structure, function and regulation of Pseudomonas aeruginosa porins. FEMS Microbiol. Rev. 41(5), 698–722 (2017).
   PubMed Web of Science ®Google Scholar
• Olivares Pacheco J, Alvarez-Ortega C, Alcalde Rico M, Martinez JL. Metabolic compensation of fitness costs is a general outcome for antibiotic-resistant Pseudomonas aeruginosa mutants overexpressing efflux pumps. mBio 8(4), e00500–00517 (2017).
   PubMed Web of Science ®Google Scholar
• Verchere A, Dezi M, Adrien V, Broutin I, Picard M. In vitro transport activity of the fully assembled MexAB-OprM efflux pump from Pseudomonas aeruginosa. Nat Commun 6, 6890 (2015).
   PubMed Web of Science ®Google Scholar
• Zilberberg MD, Shorr AF. Prevalence of multidrug-resistant Pseudomonas aeruginosa and carbapenem-resistant Enterobacteriaceae among specimens from hospitalized patients with pneumonia and bloodstream infections in the United States from 2000 to 2009. J. Hosp. Med. 8(10), 559–563 (2013).
   PubMed Web of Science ®Google Scholar
• Carvalhaes CG, Shortridge D, Sader HS, Castanheira M. Activity of meropenem-vaborbactam against bacterial isolates causing pneumonia in patients in U.S. hospitals during 2014 to 2018. Antimicrob. Agents Chemother. 64(3), (2020).
   Web of Science ®Google Scholar
• Albin OR, Henig O, Patel TS et al. Clinical implications of microbiologic treatment failure in the setting of clinical cure of bacterial pneumonia. Clin. Infect. Dis. 71(12), 3033–3041 (2020).
   PubMed Web of Science ®Google Scholar
• Bonine NG, Berger A, Altincatal A et al. Impact of delayed appropriate antibiotic therapy on patient outcomes by antibiotic resistance status from serious Gram-negative bacterial infections. Am. J. Med. Sci. 357(2), 103–110 (2019).
   PubMed Web of Science ®Google Scholar
• 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 18(6), 596 (2014).
   PubMed Web of Science ®Google Scholar
• Drwiega EN, Rodvold KA. Penetration of antibacterial agents into pulmonary epithelial lining fluid: an update. Clin. Pharmacokinet. 61(1), 17–46 (2022).
   PubMed Web of Science ®Google Scholar
• Ruiz-Ramos J, Gras-Martín L, Ramírez P. Antimicrobial pharmacokinetics and pharmacodynamics in critical care: adjusting the dose in extracorporeal circulation and to prevent the genesis of multiresistant bacteria. Antibiotics (Basel) 12(3), (2023).
   Web of Science ®Google Scholar
• Paterson DL, Bassetti M, Motyl M et al. Ceftolozane/tazobactam for hospital-acquired/ventilator-associated bacterial pneumonia due to ESBL-producing Enterobacterales: a subgroup analysis of the ASPECT-NP clinical trial. J. Antimicrob. Chemother. 77(9), 2522–2531 (2022).
   PubMed Web of Science ®Google Scholar
• Lodise TP, Puzniak LA, Chen LH et al. Outcomes of adult patients in the intensive care unit with Pseudomonas aeruginosa pneumonia who received an active anti-pseudomonal beta-lactam: does “S” equal success in the presence of resistance to other anti-pseudomonal beta-lactams? Pharmacotherapy 41(8), 658–667 (2021).
   PubMed Web of Science ®Google Scholar
• Zerbaxa 1 g/0.5 g powder for concentrate for solution for infusion - Summary of Product Characteristics. https://www.ema.europa.eu/en/documents/product-information/zerbaxa-epar-product-information_en.pdf ( March 30).
   Google Scholar
• Gallagher JC, Satlin MJ, Elabor A et al. Ceftolozane-tazobactam for the treatment of multidrug-resistant Pseudomonas aeruginosa infections: a multicenter study. Open Forum Infect Dis 5(11), ofy280 (2018).
   PubMed Web of Science ®Google Scholar
• Castanheira M, Mills JC, Farrell DJ, Jones RN. Mutation-driven beta-lactam resistance mechanisms among contemporary ceftazidime-nonsusceptible Pseudomonas aeruginosa isolates from U.S. hospitals. Antimicrob. Agents Chemother. 58(11), 6844–6850 (2014).
   PubMed Web of Science ®Google Scholar
• Bassetti M, Vena A, Giacobbe DR et al. Ceftolozane/tazobactam for treatment of severe ESBL-producing Enterobacterales infections: a multicenter nationwide clinical experience (CEFTABUSE II Study). Open Forum Infect Dis 7(5), ofaa139 (2020).
   PubMed Web of Science ®Google Scholar
• Caro L, Nicolau DP, De Waele JJ et al. Lung penetration, bronchopulmonary pharmacokinetic/pharmacodynamic profile and safety of 3 g of ceftolozane/tazobactam administered to ventilated, critically ill patients with pneumonia. J. Antimicrob. Chemother. 75(6), 1546–1553 (2020).
   PubMed Web of Science ®Google Scholar
• Rodvold KA, Hope WW, Boyd SE. Considerations for effect site pharmacokinetics to estimate drug exposure: concentrations of antibiotics in the lung. Curr Opin Pharmacol 36, 114–123 (2017).
   PubMed Web of Science ®Google Scholar
• Zhang Z, Patel YT, Fiedler-Kelly J, Feng HP, Bruno CJ, Gao W. Population pharmacokinetic analysis for plasma and epithelial lining fluid ceftolozane/tazobactam concentrations in patients with ventilated nosocomial pneumonia. J. Clin. Pharmacol. 61(2), 254–268 (2021).
   PubMed Web of Science ®Google Scholar
• Gao W, Patel YT, Zhang Z et al. Ceftolozane/tazobactam probability of target attainment in patients with hospital-acquired or ventilator-associated bacterial pneumonia. J. Clin. Pharmacol. 63(3), 352–357 (2023).
   PubMed Web of Science ®Google Scholar
• Kollef MH, Nováček M, Kivistik Ü et al. Ceftolozane-tazobactam versus meropenem for treatment of nosocomial pneumonia (ASPECT-NP): a randomised, controlled, double-blind, phase 3, non-inferiority trial. Lancet Infect Dis 19(12), 1299–1311 (2019).
   PubMed Web of Science ®Google Scholar
• Solomkin J, Hershberger E, Miller B et al. Ceftolozane/tazobactam plus metronidazole for complicated intra-abdominal infections in an era of multidrug resistance: results from a randomized, double-blind, phase 3 trial (ASPECT-cIAI). Clin. Infect. Dis. 60(10), 1462–1471 (2015).
   PubMed Web of Science ®Google Scholar
• 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 385(9981), 1949–1956 (2015).
   PubMed Web of Science ®Google Scholar
• ZERBAXA® Prescribing Information. https://www.merck.com/product/usa/pi_circulars/z/zerbaxa/zerbaxa_pi.pdf ( May 26).
   Google Scholar
• Sun Y, Fan J, Chen G et al. A phase III, multicenter, double-blind, randomized clinical trial to evaluate the efficacy and safety of ceftolozane/tazobactam plus metronidazole versus meropenem in Chinese participants with complicated intra-abdominal infections. Int J Infect Dis 123, 157–165 (2022).
   PubMed Web of Science ®Google Scholar
• Mikamo H, Monden K, Miyasaka Y et al. The efficacy and safety of tazobactam/ceftolozane in combination with metronidazole in Japanese patients with complicated intra-abdominal infections. J. Infect. Chemother. 25(2), 111–116 (2019).
   PubMed Web of Science ®Google Scholar
• Miller B, Popejoy MW, Hershberger E, Steenbergen JN, Alverdy J. Characteristics and outcomes of complicated intra-abdominal infections involving Pseudomonas aeruginosa from a randomized, double-blind, phase 3 ceftolozane-tazobactam study. Antimicrob. Agents Chemother. 60(7), 4387–4390 (2016).
   PubMed Web of Science ®Google Scholar
• Arakawa S, Kawahara K, Kawahara M et al. The efficacy and safety of tazobactam/ceftolozane in Japanese patients with uncomplicated pyelonephritis and complicated urinary tract infection. J. Infect. Chemother. 25(2), 104–110 (2019).
   PubMed Web of Science ®Google Scholar
• Kullar R, Wagenlehner FM, Popejoy MW, Long J, Yu B, Goldstein EJ. Does moderate renal impairment affect clinical outcomes in complicated intra-abdominal and complicated urinary tract infections? Analysis of two randomized controlled trials with ceftolozane/tazobactam. J. Antimicrob. Chemother. 72(3), 900–905 (2017).
   PubMed Web of Science ®Google Scholar
• ZERBAXA® (ceftolozane/tazobactam) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/206829s008lbl.pdf ( June 9).
   Google Scholar
• Safety and efficacy study of ceftolozane/tazobactam to treat ventilated nosocomial pneumonia (MK-7625A-008) (ASPECT-NP). https://clinicaltrials.gov/ct2/show/NCT02070757 ( March 21).
   Google Scholar
• Mahmoud SH, Shen C. Augmented renal clearance in critical illness: an important consideration in drug dosing. Pharmaceutics 9(3), e0617 (2017).
   Web of Science ®Google Scholar
• Shorr AF, Bruno CJ, Zhang Z et al. Ceftolozane/tazobactam probability of target attainment and outcomes in participants with augmented renal clearance from the randomized phase 3 ASPECT-NP trial. Crit Care 25(1), 354 (2021).
   PubMed Web of Science ®Google Scholar
• Huntington JA, Yu B, Li L et al. Outcomes in participants with renal impairment from a phase 3 clinical trial for ceftolozane/tazobactam treatment of nosocomial pneumonia (ASPECT-NP). Antimicrob. Agents Chemother. 64(12), (2020).
   PubMed Web of Science ®Google Scholar
• Motowski H, Ilges D, Hampton N, Kollef MH, Micek ST. Determinants of mortality for ventilated hospital-acquired pneumonia and ventilator-associated pneumonia. Crit Care Explor 5(3), e0867 (2023).
   PubMedGoogle Scholar
• Talbot GH, Das A, Cush S et al. Evidence-based study design for hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. J. Infect. Dis. 219(10), 1536–1544 (2019).
   PubMed Web of Science ®Google Scholar
• Timsit JF, Huntington JA, Wunderink RG et al. Ceftolozane/tazobactam versus meropenem in patients with ventilated hospital-acquired bacterial pneumonia: subset analysis of the ASPECT-NP randomized, controlled phase 3 trial. Crit Care 25(1), 290 (2021).
   PubMed Web of Science ®Google Scholar
• Kollef MH, Timsit JF, Martin-Loeches I et al. Outcomes in participants with failure of initial antibacterial therapy for hospital-acquired/ventilator-associated bacterial pneumonia prior to enrollment in the randomized, controlled phase 3 ASPECT-NP trial of ceftolozane/tazobactam versus meropenem. Crit Care 26(1), 373 (2022).
   PubMed Web of Science ®Google Scholar
• Johnson MG, Bruno C, Castanheira M et al. Evaluating the emergence of nonsusceptibility among Pseudomonas aeruginosa respiratory isolates from a phase-3 clinical trial for treatment of nosocomial pneumonia (ASPECT-NP). Int J Antimicrob Agents 57(3), 106278 (2021).
   PubMed Web of Science ®Google Scholar
• Martin-Loeches I, Timsit JF, Kollef MH et al. Clinical and microbiological outcomes, by causative pathogen, in the ASPECT-NP randomized, controlled, Phase 3 trial comparing ceftolozane/tazobactam and meropenem for treatment of hospital-acquired/ventilator-associated bacterial pneumonia. J. Antimicrob. Chemother. 77(4), 1166–1177 (2022).
   PubMed Web of Science ®Google Scholar
• Harris PNA, Tambyah PA, Lye DC et al. Effect of piperacillin-tazobactam vs meropenem on 30-day mortality for patients with. JAMA 320(10), 984–994 (2018).
   PubMed Web of Science ®Google Scholar
• Pogue JM, Heil EL. Laces out Dan! The role of tazobactam based combinations for invasive ESBL infections in a post-MERINO world. Expert Opin Pharmacother 20(17), 2053–2057 (2019).
   PubMed Web of Science ®Google Scholar
• 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. 72(1), 268–272 (2017).
   PubMed Web of Science ®Google Scholar
• Martin-Loeches I, Shorr AF, Wunderink RG et al. Outcomes in participants with ventilated nosocomial pneumonia and organ failure treated with ceftolozane/tazobactam versus meropenem: a subset analysis of the phase 3, randomized, controlled ASPECT-NP trial. Ann Intensive Care 13(1), 8 (2023).
   PubMed Web of Science ®Google Scholar
• Puzniak L, Dillon R, Palmer T, Collings H, Enstone A. Systematic literature review of real-world evidence of ceftolozane/tazobactam for the treatment of respiratory infections. Infect Dis Ther 10(3), 1227–1252 (2021).
   PubMed Web of Science ®Google Scholar
• Gallagher JC, Satlin MJ, Elabor A et al. Ceftolozane-tazobactam for the treatment of multidrug-resistant. Open Forum Infect Dis 5(11), ofy280 (2018).
   PubMed Web of Science ®Google Scholar
• Puzniak L, Dillon R, Palmer T, Collings H, Enstone A. Real-world use of ceftolozane/tazobactam: a systematic literature review. Antimicrob Resist Infect Control 10(1), 68 (2021).
   PubMed Web of Science ®Google Scholar
• Pogue JM, Kaye KS, Veve MP et al. Ceftolozane/tazobactam vs polymyxin or aminoglycoside-based regimens for the treatment of drug-resistant Pseudomonas aeruginosa. Clin. Infect. Dis. 71(2), 304–310 (2020).
   PubMed Web of Science ®Google Scholar
• Chaftari AM, Hachem R, Malek AE et al. A prospective randomized study comparing ceftolozane/tazobactam to standard of care in the management of neutropenia and fever in patients with hematological malignancies. Open Forum Infect Dis 9(6), ofac079 (2022).
   PubMed Web of Science ®Google Scholar
• Fernández-Cruz A, Alba N, Semiglia-Chong MA et al. A case-control study of real-life experience with ceftolozane-tazobactam in patients with hematologic malignancy and. Antimicrob. Agents Chemother. 63(2), e02340–02318 (2019).
   PubMed Web of Science ®Google Scholar
• Hart DE, Gallagher JC, Puzniak LA, Hirsch EB. A multicenter evaluation of ceftolozane/tazobactam treatment outcomes in immunocompromised patients with multidrug-resistant. Open Forum Infect Dis 8(3), ofab089 (2021).
   PubMed Web of Science ®Google Scholar
• Martin-Loeches I, Reyes LF, Nseir S et al. European Network for ICU-Related Respiratory Infections (ENIRRIs): a multinational, prospective, cohort study of nosocomial LRTI. Intensive Care Med. 49(10), 1212–1222 (2023).
   PubMed Web of Science ®Google Scholar
• Torres A, Niederman MS, Chastre J et al. International ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia: guidelines for the management of hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) of the European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Asociacion Latinoamericana del Torax (ALAT). Eur. Respir. J. 50(3), 1700582 (2017).
   PubMed Web of Science ®Google Scholar
• Kalil AC, Metersky ML, Klompas M et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin. Infect. Dis. 63(5), e61–e111 (2016).
   PubMed Web of Science ®Google Scholar
• Aulin LBS, de Lange DW, Saleh MAA, van der Graaf PH, Völler S, van Hasselt JGC. Biomarker-guided individualization of antibiotic therapy. Clin. Pharmacol. Ther. 110(2), 346–360 (2021).
   PubMed Web of Science ®Google Scholar