Ceftazidime/avibactam Alone or in Combination with an Aminoglycoside for Treatment of Carbapenem-resistant Enterobacterales Infections: A Retrospective Cohort Study

Overview

Journal Int J Antimicrob Agents

Specialties Infectious Diseases
Pharmacology

Date 2024 Sep 6

PMID 39242050

Authors

Zackery P Bulman

Lishan Cao

Brooke N Curry

Mark Biagi

Amanda Vivo

Katie J Suda

Charlesnika T Evans

Affiliations

Soon will be listed here.

Abstract

Background: Ceftazidime/avibactam is one of the preferred treatment options for carbapenem-resistant Enterobacterales (CRE). However, the benefit of combining ceftazidime/avibactam with another antibiotic remains unclear.

Objectives: To identify variables associated with treatment failure during the use of ceftazidime/avibactam for CRE infections and assess the effect of combining an aminoglycoside with ceftazidime/avibactam.

Methods: This was a retrospective cohort study of patients with a positive CRE culture treated with ceftazidime/avibactam between 2015 and 2021 in 134 Veterans Affairs (VA) facilities. The primary outcome was 30-day mortality and the secondary outcome was in-hospital mortality. A subanalysis in patients who received an aminoglycoside was also performed.

Results: A total of 303 patients were included. The overall 30-day and in-hospital mortality rates were 12.5% and 24.1%, respectively. Age (aOR 1.052, 95% CI 1.013-1.093), presence in the ICU (aOR 2.704, 95% CI 1.071-6.830), and receipt of an aminoglycoside prior to initiation of ceftazidime/avibactam (aOR 4.512, 95% CI 1.797-11.327) were independently associated with 30-day mortality. In the subgroup of patients that received an aminoglycoside (n = 77), their use in combination with ceftazidime/avibactam had a 30-day mortality aOR of 0.321 (95% CI, 0.089-1.155).

Conclusion: In veterans treated with ceftazidime/avibactam for CRE infections, increased age, receipt of an empiric aminoglycoside, and presence in the ICU at the time of index culture were associated with higher 30-day mortality. Among patients who received an aminoglycoside, their use in combination with ceftazidime/avibactam trended toward protectiveness of 30-day mortality, suggesting a potential role for this combination to treat CRE infections in patients who are more severely ill.

References

Huang Y, Sokolowski K, Rana A, Singh N, Wang J, Chen K . Generating Genotype-Specific Aminoglycoside Combinations with Ceftazidime/Avibactam for KPC-Producing . Antimicrob Agents Chemother. 2021; 65(9):e0069221. PMC: 8370209. DOI: 10.1128/AAC.00692-21. View

AlQahtani H, AlGhamdi A, Alobaidallah N, Alfayez A, Almousa R, Albagli R . Evaluation of ceftazidime/avibactam for treatment of carbapenemase-producing carbapenem-resistant Enterobacterales with OXA-48 and/or NDM genes with or without combination therapy. JAC Antimicrob Resist. 2022; 4(5):dlac104. PMC: 9552550. DOI: 10.1093/jacamr/dlac104. View

Tamma P, Aitken S, Bonomo R, Mathers A, van Duin D, Clancy C . Infectious Diseases Society of America 2022 Guidance on the Treatment of Extended-Spectrum β-lactamase Producing Enterobacterales (ESBL-E), Carbapenem-Resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with Difficult-to-Treat Resistance.... Clin Infect Dis. 2022; 75(2):187-212. PMC: 9890506. DOI: 10.1093/cid/ciac268. View

Jorgensen S, Trinh T, Zasowski E, Lagnf A, Bhatia S, Melvin S . Real-World Experience With Ceftazidime-Avibactam for Multidrug-Resistant Gram-Negative Bacterial Infections. Open Forum Infect Dis. 2020; 6(12):ofz522. PMC: 6934163. DOI: 10.1093/ofid/ofz522. View

Wilson G, Fitzpatrick M, Suda K, Smith B, Gonzalez B, Jones M . Comparative effectiveness of antibiotic therapy for carbapenem-resistant Enterobacterales (CRE) bloodstream infections in hospitalized US veterans. JAC Antimicrob Resist. 2022; 4(5):dlac106. PMC: 9596539. DOI: 10.1093/jacamr/dlac106. View

Bulman Z, Wicha S, Nielsen E, Lenhard J, Nation R, Theuretzbacher U . Research priorities towards precision antibiotic therapy to improve patient care. Lancet Microbe. 2022; 3(10):e795-e802. DOI: 10.1016/S2666-5247(22)00121-5. View

Scudeller L, Righi E, Chiamenti M, Bragantini D, Menchinelli G, Cattaneo P . Systematic review and meta-analysis of in vitro efficacy of antibiotic combination therapy against carbapenem-resistant Gram-negative bacilli. Int J Antimicrob Agents. 2021; 57(5):106344. DOI: 10.1016/j.ijantimicag.2021.106344. View

Tsolaki V, Mantzarlis K, Mpakalis A, Malli E, Tsimpoukas F, Tsirogianni A . Ceftazidime-Avibactam To Treat Life-Threatening Infections by Carbapenem-Resistant Pathogens in Critically Ill Mechanically Ventilated Patients. Antimicrob Agents Chemother. 2019; 64(3). PMC: 7038311. DOI: 10.1128/AAC.02320-19. View

Smith N, Boissonneault K, Chen L, Petraitis V, Petraitiene R, Tao X . Mechanistic Insights to Combating NDM- and CTX-M-Coproducing Klebsiella pneumoniae by Targeting Cell Wall Synthesis and Outer Membrane Integrity. Antimicrob Agents Chemother. 2022; 66(9):e0052722. PMC: 9487485. DOI: 10.1128/aac.00527-22. View

10.

Angus D, Lidicker J, Clermont G, Carcillo J, Pinsky M . Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001; 29(7):1303-10. DOI: 10.1097/00003246-200107000-00002. View

11.

Vivo A, Fitzpatrick M, Suda K, Jones M, Perencevich E, Rubin M . Epidemiology and outcomes associated with carbapenem-resistant Acinetobacter baumannii and carbapenem-resistant Pseudomonas aeruginosa: a retrospective cohort study. BMC Infect Dis. 2022; 22(1):491. PMC: 9128216. DOI: 10.1186/s12879-022-07436-w. View

12.

Fitzpatrick M, Suda K, Ramanathan S, Wilson G, Poggensee L, Evans M . Increased carbapenemase testing following implementation of national VA guidelines for carbapenem-resistant Enterobacterales (CRE). Antimicrob Steward Healthc Epidemiol. 2022; 2(1):e88. PMC: 9726513. DOI: 10.1017/ash.2021.220. View

13.

Dat V, Linh B, Kim G . Causes of admissions and in-hospital mortality among patients admitted to critical care units in primary and secondary hospitals in Vietnam in 2018: a multicentre retrospective study. BMJ Open. 2022; 12(6):e061638. PMC: 9196179. DOI: 10.1136/bmjopen-2022-061638. View

14.

Giuliano C, Patel C, Kale-Pradhan P . A Guide to Bacterial Culture Identification And Results Interpretation. P T. 2019; 44(4):192-200. PMC: 6428495. View

15.

Tumbarello M, Raffaelli F, Giannella M, Mantengoli E, Mularoni A, Venditti M . Ceftazidime-Avibactam Use for Klebsiella pneumoniae Carbapenemase-Producing K. pneumoniae Infections: A Retrospective Observational Multicenter Study. Clin Infect Dis. 2021; 73(9):1664-1676. DOI: 10.1093/cid/ciab176. View

16.

Ramirez J, Wiemken T, Peyrani P, Arnold F, Kelley R, Mattingly W . Adults Hospitalized With Pneumonia in the United States: Incidence, Epidemiology, and Mortality. Clin Infect Dis. 2017; 65(11):1806-1812. DOI: 10.1093/cid/cix647. View

17.

Iwashyna T, Odden A, Rohde J, Bonham C, Kuhn L, Malani P . Identifying patients with severe sepsis using administrative claims: patient-level validation of the angus implementation of the international consensus conference definition of severe sepsis. Med Care. 2012; 52(6):e39-43. PMC: 3568444. DOI: 10.1097/MLR.0b013e318268ac86. View

18.

van Duin D, Arias C, Komarow L, Chen L, Hanson B, Weston G . Molecular and clinical epidemiology of carbapenem-resistant Enterobacterales in the USA (CRACKLE-2): a prospective cohort study. Lancet Infect Dis. 2020; 20(6):731-741. PMC: 7473597. DOI: 10.1016/S1473-3099(19)30755-8. View

19.

Mataraci Kara E, Yilmaz M, Tosun A, Ozbek Celik B . Evaluation of the synergy of ceftazidime/avibactam in combination with colistin, doripenem, levofloxacin, tigecycline, and tobramycin against OXA-48 producing Enterobacterales. J Chemother. 2020; 32(4):171-178. DOI: 10.1080/1120009X.2020.1761172. View

20.

Shropshire W, Konovalova A, McDaneld P, Gohel M, Strope B, Sahasrabhojane P . Systematic Analysis of Mobile Genetic Elements Mediating β-Lactamase Gene Amplification in Noncarbapenemase-Producing Carbapenem-Resistant Bloodstream Infections. mSystems. 2022; 7(5):e0047622. PMC: 9601100. DOI: 10.1128/msystems.00476-22. View