2435. Clinical Outcomes With Ceftolozane–Tazobactam in Patients With Multidrug-Resistant (MDR) Pseudomonas aeruginosa Bloodstream Infections: A Multi-Center Study

Abstract

BackgroundCeftolozane-tazobactam (TOL-TAZ) is a novel cephalosporin combination that is beneficial for the treatment of multidrug-resistant (MDR) Pseudomonas infections. However, little data are available on the utility of TOL-TAZ for patients with bloodstream infections (BSIs) caused by this organism.MethodsA retrospective, multicenter chart review was conducted at 11 hospitals to evaluate the utility of TOL-TAZ for MDR Pseudomonas BSIs from June 2016 to February 2018. Patients were included if they were over 18 years old with positive blood cultures for Pseudomonas aeruginosa and received TOL-TAZ for at least 24 hours. Patients were evaluated for in-hospital and 30-day mortality, as well as microbiologic and clinical cure.ResultsCharacteristic Results (N = 25)Male gender, n (%)15 (60)Age, median (range)60 (52–66)Charlson comorbidity index, median (IQR)5 (4–7)APACHE II score, median (IQR)19 (16.25–25.5)ICU, n (%)15 (60)Organ transplant, n (%)8 (32)Concomitant antibiotics used, n (%)14 (56)Aminoglycoside, n/N (%)8/14 (57)Fluoroquinolone, n/N (%)5/14 (35)Polymyxin, n/N (%)2/14 (14)β-Lactam, n/N (%)1/14 (7)Duration of TOL-TAZ, days (median, IQR)13 (8-14)Susceptibility to TOL-TAZ, n/N tested (%)19/20 (95)High dose (3g every 8 hours), n (%)6 (24)Renal dose adjustment, n (%)8 (32)Adverse events, n (%)1 (4)Primary infection30 day mortality, n/N (%)In-hospital mortality, n/N (%)Microbiologic success, n/N (%)Clinical Success, n/N (%)Primary bacteremia1/7 (14.3)0/7 (0)7/7 (100)6/7 (85.7)Pneumonia5/8 (62.5)5/8 (62.53/8 (37.5)3/8 (37.5)UTI1/6 (16.7)1/6 (16.7)6/6 (100)6/6 (100)Intra-abdominal0/4 (0)0/4 (0)4/4 (100)4/4 (100)30 day mortality, n (%)7 (28)In hospital mortality, n (%)6 (24)Microbiologic cure, n (%)20 (80)Clinical success, n (%)19 (76)ConclusionIn this multi-center evaluation of 25 patients from 11 health centers, mortality was seen at 30 days and at the end of stay in 28% and 24% of patients, respectively. Clinical and microbiologic success occurred in over 70% of patients. One patient developed C. difficile infection. The 7 patients with primary bacteremia had microbiologic success and survived their hospital stay. Two of 3 patients with pneumonia who survived received high dose TOL-TAZ. TOL-TAZ is an option for patients with MDR Pseudomonas bloodstream infections.Disclosures J. Gallagher, Achaogen: Consultant, Consulting fee. Merck: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee and Research grant. Allergan: Consultant and Speaker’s Bureau, Consulting fee. Astellas: Consultant and Speaker’s Bureau, Consulting fee. Cempra: Consultant, Consulting fee. Cidara: Consultant, Consulting fee. CutisPharma: Consultant, Consulting fee. Paratek: Consultant, Consulting fee. Shionogi: Consultant, Consulting fee. Tetraphase: Consultant, Consulting fee. Theravance: Consultant, Consulting fee. The Medicines Company: Consultant, Consulting fee. Melinta: Speaker’s Bureau, Consulting fee.

Ceftolozane/tazobactam for the treatment of bacteremia: a systematic literature review (SLR)

“…Cohort studies were the most commonly utilized study type (k = 13 retrospective cohort studies, [ 10 – 22 ] one prospective cohort study [ 23 ]), followed by case reports/series (k = 2 case reports [ 24 , 25 ], three case series [ 26 – 28 ], one case–control study [ 29 ]), and clinical trials (k = 2 randomized controlled trials [RCTs], [ 30 , 31 ] one single-arm trial [ 32 ]). Most studies were conducted in the US (k = 10) [ 10 , 11 , 17 – 20 , 26 – 28 , 33 ] and Spain (k = 6 15,18,21,25–27 ); three were conducted internationally [ 21 , 30 , 31 ], two in Italy [ 12 , 24 ], one in Japan [ 32 ], and one in Saudi Arabia [ 13 ]. The studies also varied with respect to clinical setting; with seven conducted in medical centers [ 15 , 18 , 20 , 22 , 26 – 28 ], thirteen conducted in hospitals [ 10 – 14 , 16 , 19 , 21 , 23 – 25 , 29 , 30 ], one conducted in multicenter health systems [ 17 ], and two conducted at unspecified clinical sites [ 31 , 32 ].…”

“…Sample size of overall populations evaluated in the included studies ranged from one [ 13 , 14 , 19 , 22 , 24 , 25 ] to 398 [ 31 ] patients. However, six studies reported on patients with mixed infections [ 11 , 12 , 14 , 17 , 18 , 21 ]. Therefore, the sample size specific to patients with primary (n = 1 to 7 patients), secondary (n = 1 to 25 patients), and mixed or unspecified (n = 1 to 31 patients) bacteremia tended to be smaller and a subset of the overall population.…”

“…The causative pathogen was described in the majority of studies (k = 20/23) [ 10 – 27 , 29 , 30 , 33 ]. Pseudomonas aeruginosa was the most frequently reported pathogen (k = 13/23) [ 11 – 15 , 18 – 21 , 23 , 26 , 29 ]. Six studies evaluated patients with mixed/polymicrobial infections [ 10 , 16 , 24 , 25 , 27 , 30 ], five [ 10 , 16 , 25 , 27 , 30 ] Pseudomonas aeruginosa in combination with other pathogens [ 10 , 16 , 25 , 27 , 30 ], and one joint E. coli and K. pneumonia infection [ 24 ].…”

“…Of the 13 [ 11 , 13 , 14 , 17 – 21 , 25 , 26 , 30 – 32 ] studies reporting on a secondary bacteremia population there was variability in the underlying infection source(s). Six (k = 6/13) studies evaluated patients with mixed underlying infections including a combination of biliary, bone/joint, central-line, intra-abdominal, left-ventricular assist device, otitis and mastoiditis, perianal abscesses, pyelonephritis, respiratory, submandibular fasciitis, surgical site, urinary tract infection (UTI), and/or wound.…”

“…Administered dose of C/T was reported in all the publications and ranged from 0.375 g [ 13 , 18 ] to 3 g [ 26 ]; the most frequently administered doses were 1.5 g (k = 14) [ 10 , 12 – 16 , 18 , 19 , 21 , 24 , 25 , 28 , 31 , 32 ] and 3.0 g IV 8qh (k = 9) [ 10 , 11 , 14 – 16 , 18 – 20 , 30 ]. Actual treatment duration ranged from a minimum of 3 days [ 14 ] to a maximum 48 days [ 18 ] and frequency of administration was reported to be every 8 h in all but two studies, which reported a single daily bolus of C/T [ 27 , 31 ].…”