Real-World Experience with Ceftolozane-Tazobactam for Multidrug-Resistant Gram-Negative Bacterial Infections

Abstract

Our objective was to describe the prescribing practices, clinical characteristics, and outcomes of patients treated with ceftolozane-tazobactam (C/T) for multidrug-resistant (MDR) Gram-negative infections. This was a multicenter, retrospective, cohort study at eight U.S. medical centers (2015 to 2019). Inclusion criteria were age ≥18 years and receipt of C/T (≥72 hours) for suspected or confirmed MDR Gram-negative infection. The primary efficacy outcome, evaluated among patients with MDR Pseudomonas aeruginosa infections, was composite clinical failure, namely, 30-day all-cause mortality, 30-day recurrence, and/or failure to resolve or improve infection signs or symptoms after C/T treatment. In total, 259 patients were included, and P. aeruginosa was isolated in 236 (91.1%). The MDR and extremely drug-resistant phenotypes were detected in 95.8% and 37.7% of P. aeruginosa isolates, respectively. The most common infection source was the respiratory tract (62.9%). High-dose C/T was used in 71.2% of patients with a respiratory tract infection (RTI) overall but in only 39.6% of patients with an RTI who required C/T renal dose adjustment. In the primary efficacy population (n = 226), clinical failure and 30-day mortality occurred in 85 (37.6%) and 39 (17.3%) patients, respectively. New C/T MDR P. aeruginosa resistance was detected in 3 of 31 patients (9.7%) with follow-up cultures. Hospital-acquired infection and Acute Physiological and Chronic Health Evaluation II (APACHE II) score were independently associated with clinical failure (adjusted odds ratio [aOR], 2.472 and 95% confidence interval [CI], 1.322 to 4.625; and aOR, 1.068 and 95% CI, 1.031 to 1.106, respectively). Twenty-five (9.7%) patients experienced ≥1 adverse effect (9 acute kidney injury, 13 Clostridioides difficile infection, 1 hepatotoxicity, 2 encephalopathy, and 2 gastrointestinal intolerance). C/T addresses an unmet medical need in patients with MDR Gram-negative infections.

Real-world use of ceftolozane/tazobactam: a systematic literature review

“…Including studies that recruited patients from multiple countries, the most common study locations were the US (N = 50), [ 21 , 22 , 24 , 27 – 29 , 33 , 34 , 39 – 41 , 43 – 45 , 50 , 51 , 54 , 56 , 57 , 59 , 61 , 62 , 68 – 71 , 73 – 77 , 79 – 85 , 87 – 92 , 94 , 95 , 97 – 100 ] Spain (N = 15) [ 26 , 28 , 30 – 32 , 35 – 37 , 42 , 47 , 49 , 58 , 66 , 79 , 96 ], and Italy (N = 13) [ 18 , 20 , 23 , 25 , 48 , 52 , 53 , 55 , 64 , 67 , 72 , 79 , 86 ]. A variety of study designs were captured: 27 were non-comparative retrospective studies [ 18 , 19 , 22 , 24 , 25 , 28 , 32 , 33 , 40 , 41 ,…”

“…Additional file 1 : Table S2 in the supplementary material summarizes the single-patient case reports identified by the SLR. There were 47 studies (24 multicenter) reporting on more than one patient, as summarized in Table 2 [ 18 , 22 , 23 , 25 , 27 , 28 , 33 , 37 , 38 , 40 , 79 – 81 , 83 – 85 , 87 – 91 , 94 , 97 , 99 ].…”

“…(range): 14 (14) days 100.0 (4/4) - 0 Jones et al 2020 [ 21 ] Retrospective single center, case series US 7 PsA (57.1% non-MDR; 42.9% MDR) infections (one patient also had an E. coli infection), including pneumonia (42.9%), cUTI (28.6%), and bacteremia (14.3%) – Dose C/T: 4.5 g qd (CI; 85.7%), 9 g qd (CI; 14.3%) Duration: med. (range): 14 (6–42) days 85.7 (6/7) 100.0 (3/3) 0 a Jorgensen et al 2020 [ 22 ] Retrospective, multicenter US 259 MDR gram-negative infections (91.1% PsA; 23.2% Enterobacterales) including, RTIs (62.9%), SSTIs (10.8%), and UTIs (10.0%). Patients with MDR PsA infections (N = 226) were used as the primary analysis set ICU N = 131 IMC N = 23 APACHE II med.…”

Real-world Use of Ceftolozane/tazobactam: a Systematic Literature Review

“…Including studies that recruited patients from multiple countries, the most common study locations were the US (N = 50), (21, 22, 24, 27-29, 33, 34, 39-41, 43-45, 50, 51, 54, 56, 57, 59, 61, 62, 68-71, 73-77, 79-85, 87-92, 94, 95, 97-100) Spain (N = 15), (26, 28, 30-32, 35-37, 42, 47, 49, 58, 66, 79, 96) and Italy (N = 13). (18,20,23,25,48,52,53,55,64,67,72,79,86) A variety of study designs were captured: 27 were non-comparative retrospective studies, (18,19,22,24,25,28,32,33,40,41,79,81,(84)(85)(86)(87)(88)(89)(90)(91)(92)(94)(95)(96)(97)(98)(99) 14 were case series, (20, 21, 29, 31, 34-39, 42, 43, 82, 100) ve were comparative (including two cohort studies, (80,83) and three case-control studies, (23,…”

“…Nine publications, comprising 794 patients treated with C/T, reported APACHE scores ranging from 13-40, with larger studies (> 50 patients) ranging from 18-40 (22,24,33,36,80,84,90,97,100). Six publications, comprising 472 patients treated with C/T, reported SOFA scores ranging from 3-8 (22,26,27,30,38,39). The CC index quanti es the comorbidity burden of included patients by predicting the mortality of patients with multiple comorbidities.…”