In:
Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 6, No. Supplement_2 ( 2019-10-23), p. S768-S769
Abstract:
Ceftolozane/tazobactam (C/T) is a novel cephalosporin/β-lactamase inhibitor combination for treating Gram-negative infections, particularly Pseudomonas aeruginosa (PA). C/T has been FDA-approved for complicated intra-abdominal and urinary tract infections and has just completed a trial in ventilator nosocomial pneumonia, but real-world outcome data are still emerging. Methods Demographic, microbiologic, treatment and outcome data of patients who received C/T for ≥48 hours from January 2016 to August 2018 at multiple centers within a single hospital system were retrospectively collected. Available isolates were analyzed for C/T susceptibility (by Etest) and whole-genome sequencing (WGS). Spades v.3.11.1 was used for assembly, multi-locus sequence typing v2.10 performed for in silico MLST with the PubMLST database and Abricate v0.7 was used for resistance gene screening with the CARD database. Results Among 45 patients, 58% were non-white, 53% were female and 13% were immunocompromised. The median age was 64 years (IQR, 50 to 69). At the time of the index event, a high proportion of patients required ICU care (42%) and pressor support (13%) as well as had invasive devices in place (64%). A minority (2.4%) had prior exposure to C/T. Respiratory infections were most common (38%) followed by urinary tract (20%). Concomitant Gram-negative agents were used in 18%. 69% achieved clinical success (i.e., recovery from infection-related signs and symptoms). The in-hospital mortality rate was 16% of which 5 out of 7 were attributed to infection. Microbiology was available for 91% of patients; 84% had PA isolates resistant to at least 3 antipseudomonal classes (Figures 1 and 2). Ten PA isolates were analyzed with WGS (Table 1). C/T resistance arose during therapy in one patient (MIC increase from 1 to 128 µg/mL). WGS showed a substitution in AmpC β-lactamase (A46D) and presence of blaCARB-2. Conclusion Although C/T was used in a critically ill population with highly resistant organisms, cure rates were high and mortality was low. Acquired β-lactamases were not frequently seen among the PA isolates. C/T is a vital therapeutic option, particularly on MDR isolates for which options are limited. Disclosures Samuel L. Aitken, PharmD, Melinta Therapeutoics: Grant/Research Support, Research Grant; Merck, Sharpe, and Dohme: Advisory Board; Shionogi: Advisory Board.
Type of Medium:
Online Resource
ISSN:
2328-8957
DOI:
10.1093/ofid/ofz360.1926
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2019
detail.hit.zdb_id:
2757767-3
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