Clinical Outcomes in Carbapenem-Resistant Enterobacteriaceae Infections Treated With Ceftazidime-Avibactam: A Single-Center Observational Study

Abstract

IntroductionAmong the several newer beta lactam+beta lactase inhibitors (BL/BLI), ceftazidime-avibactam is the only drug showing activity against OXA-48-like producers. Hence, it is being increasingly used in India to treat infections caused by carbapenem-resistant Enterobacteriaceae (CRE), especially as a colistin-sparing agent. We have used ceftazidime-avibactam in patients suspected and confirmed to have CRE infections in our center, and present a retrospective analysis of our experience. MethodsWe conducted a single-center, retrospective study involving all patients who were treated with ceftazidimeavibactam for suspected and proven CRE infections during a one-year period at our 500-bedded hospital. Our primary objective for this study was taken as all-cause mortality. The secondary objectives were to determine the clinical cure, defined as the end of the treatment regimen with a resolution of primary infection and resistance to ceftazidime-avibactam in patients who underwent the Epsilometer test (E-test). ResultsA total of 103 patients who received ceftazidime-avibactam were identified. The all-cause mortality was 27% while a clinical cure was achieved in 73%. Fifty-two patients received empirical therapy and 51 patients received ceftazidime-avibactam for confirmed CRE infection. Forty-eight patients had an E-test done, out of which 79% of patients had CREs sensitive to ceftazidime-avibactam, and 21% of patients had ceftazidimeavibactam resistant CREs. A higher Sequential Organ Failure Assessment (SOFA) score, Charlson comorbidity index (CCI) score, intensive care unit (ICU) admission, inotrope requirement, and lower days of therapy (DOT) with ceftazidime-avibactam were found to be associated with increased mortality. ConclusionColistin has been considered to be the last-line agent in CRE infections, but there are concerns about its adverse effects and the emergence of resistance. Given our relatively low mortality of 27% in CRE infections treated with ceftazidime-avibactam, coupled with the high susceptibility of the tested isolates, there may be a role for the empirical use of this drug in infections caused by CRE, especially in a setting where colistin may not be ideal.

Ceftazidime-Avibactam Therapy Versus Ceftazidime-Avibactam-Based Combination Therapy in Patients With Carbapenem-Resistant Gram-Negative Pathogens: A Meta-Analysis

“…The database search described in Database Search generated 17 eligible articles ( Sousa et al, 2018 ; Kuang et al, 2020 ; Guimarães et al, 2019 ; Rathish et al, 2021 ; Shields et al, 2018 ; Tumbarello et al, 2019 ; Ackley et al, 2020 ; Iannaccone et al, 2020 ; Castón et al, 2020 ; Tumbarello et al, 2021 ; Zhu et al, 2021 ; King et al, 2017 ; Temkin et al, 2017 ; De la Calle et al, 2019 ; Chen et al, 2020 ; Jiang et al, 2020 ; Jorgensen et al, 2020 ). Specifically, 1,106 references were found by searching for the keywords: “ceftazidime avibactam” and “carbapenem resistant.” After removing the duplicates, 667 potentially relevant articles were left.…”

“…The studies were published between 2017 and 2021. Four studies were from the USA ( King et al, 2017 ; Shields et al, 2018 ; Ackley et al, 2020 ; Jorgensen et al, 2020 ), three were from Spain ( Sousa et al, 2018 ; De la Calle et al, 2019 ; Castón et al, 2020 ), four were from China ( Chen et al, 2020 ; Jiang et al, 2020 ; Kuang et al, 2020 ; Zhu et al, 2021 ), three were from Italy ( Tumbarello et al, 2019 ; Iannaccone et al, 2020 ; Tumbarello et al, 2021 ), one was from Brazil ( Guimarães et al, 2019 ), one was from India ( Rathish et al, 2021 ), and one was from Europe and Australia ( Temkin et al, 2017 ). In terms of the pathogens, most of the studies reported carbapenem-resistant Enterobacteriaceae (CRE) with carbapenem-resistant Klebsiella pneumoniae (CKP) as the most frequent, while one study included both CKP and carbapenem-resistant Pseudomonas aeruginosa (CRPA) ( Temkin et al, 2017 ) and one study reported CRE, CRPA, and Acinetobacter baumannii (AB) ( Kuang et al, 2020 ).…”

“…Reagents that have been combined with CAZ-AVI therapy include aminoglycosides (AMG), polymyxin (PM), tigecycline (TGC), colistin (COL), amikacin (AMK), imipenem (IMP), gentamicin (GEN), ciprofloxacin (CIP), meropenem (MEM), fosfomycin (FOS), carbapenems (CAP), fluoroquinolone (FLU), minocycline (MIN), and sulfamethoxazole-trimethoprim (SUL-TRI). Patients were treated by CAZ-AVI and observed for at least 72 h in 12 studies ( Temkin et al, 2017 ; Shields et al, 2018 ; De la Calle et al, 2019 ; Tumbarello et al, 2019 ; Ackley et al, 2020 ; Castón et al, 2020 ; Chen et al, 2020 ; Jiang et al, 2020 ; Jorgensen et al, 2020 ; Kuang et al, 2020 ; Tumbarello et al, 2021 ; Zhu et al, 2021 ), for at least 48 h in three studies ( Sousa et al, 2018 ; Guimarães et al, 2019 ; Rathish et al, 2021 ), and for at least 24 h in one study ( King et al, 2017 ). There is only one study in which the treatment time was not reported ( Iannaccone et al, 2020 ).…”

“…The risk-of-bias assessment results for each study ( Figure 2A ) and each domain ( Figure 2B ) are displayed. Ten studies ( King et al, 2017 ; Shields et al, 2018 ; De la Calle et al, 2019 ; Tumbarello et al, 2019 ; Ackley et al, 2020 ; Castón et al, 2020 ; Chen et al, 2020 ; Jorgensen et al, 2020 ; Kuang et al, 2020 ; Rathish et al, 2021 ) have a critical overall risk of bias (judged by one study was at critical risk of bias in at least one domain ( Sterne et al, 2016b )) and two moderates ( Sousa et al, 2018 ; Tumbarello et al, 2021 ). The quality of the other five studies assessed by the AHRQ tool is all poor quality ( Table 2 ).…”

Therapeutic Options for the Treatment of Carbapenem-resistant Enterobacteriaceae Infections: Hope in the Times of Hype and Despair

“… 17 – 19 Although CZA salvage therapy for severe KPC ( Klebsiella pneumoniae carbapenemase) infections including bacteremia has been well established, its utility would be of limited import for our CRE infections. 20 …”