BackgroundMultidrug-resistant Pseudomonas aeruginosa infections remain common in hospitals worldwide. We investigated the outcomes associated with the use of ceftolozane-tazobactam for the treatment of these infections.MethodsData were collected retrospectively from 20 hospitals across the United States about adults who received ceftolozane-tazobactam for the treatment of multidrug-resistant P aeruginosa infections of any source for at least 24 hours. The primary outcome was a composite of 30-day and inpatient mortality, and secondary outcomes were clinical success and microbiological cure. Multivariable regression analysis was conducted to determine factors associated with outcomes.ResultsTwo-hundred five patients were included in the study. Severe illness and high degrees of comorbidity were common, with median Acute Physiology and Chronic Health Evaluation (APACHE) II scores of 19 (interquartile range [IQR], 11–24) and median Charlson Comorbidity Indexes of 4 (IQR, 3–6). Delayed initiation of ceftolozane-tazobactam was common with therapy started a median of 9 days after culture collection. Fifty-nine percent of patients had pneumonia. On susceptibility testing, 125 of 139 (89.9%) isolates were susceptible to ceftolozane-tazobactam. Mortality occurred in 39 patients (19%); clinical success and microbiological cure were 151 (73.7%) and 145 (70.7%), respectively. On multivariable regression analysis, starting ceftolozane-tazobactam within 4 days of culture collection was associated with survival (adjusted odds ratio [OR], 5.55; 95% confidence interval [CI], 2.14–14.40), clinical success (adjusted OR, 2.93; 95% CI, 1.40–6.10), and microbiological cure (adjusted OR, 2.59; 95% CI, 1.24–5.38).ConclusionsCeftolozane-tazobactam appeared to be effective in the treatment of multidrug-resistant P aeruginosa infections, particularly when initiated early after the onset of infection.

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.

Background:The impact of donor colonization or infection with multidrug-resistant organisms (MDROs) on solid organ transplant (SOT) recipient outcomes remains uncertain. We thus evaluated the association between donor MDROs and risk of posttransplant infection, graft failure, and mortality.Methods: A multicenter retrospective cohort study was performed. All SOT recipients with a local deceased donor were included. The cohort was divided into three exposure groups: recipients whose donors had (1) an MDRO, (2) a non-MDRO bacterial or candidal organism, or (3) no growth on cultures. The primary outcomes were (1) bacterial or invasive candidal infection within 3 months and (2) graft failure or death within 12 months posttransplant. Mixed effect multivariable frailty models were developed to evaluate each association.Results: Of 658 total SOT recipients, 93 (14%) had a donor with an MDRO, 477 (73%) had a donor with a non-MDRO organism, and 88 (13%) had a donor with no organisms on culture. On multivariable analyses, donor MDROs were associated with a significantly increased hazard of infection compared to those with negative donor cultures (adjust hazard ratio [aHR] 1.63, 95% CI 1.01-2.62, p = .04) but were not associated with graft failure or death (aHR 0.45, 95% CI 0.15-1.36, p = .16).

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BackgroundCeftolozane/tazobactam (TOL-TAZ) is a novel cephalosporin antibiotic combined with a known β-lactamase inhibitor. It has activity against some extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae and multidrug-resistant Pseudomonas aeruginosa (MDRPA). To date, little experience has been published on outcomes with TOL-TAZ for MDRPA infections in immunocompromised patients.MethodsThis was a retrospective study of adult patients (≥18 years) with an immunocompromising condition (solid-organ transplant; hematologic malignancy; solid tumors; metastatic cancer) at 20 academic medical centers who had microbiologically confirmed MDRPA isolated in culture and received TOL-TAZ for at least 24 hours. 30-day survival, in-hospital mortality, and the rates of microbiologic and clinical cure were assessed.ResultsCharacteristic Result (N = 65)Immunocompromising condition:Solid-organ transplantSolid tumorLeukemiaLymphoma/multiple myelomaMetastatic cancer n(%)35 (53.8)20 (30.7)4 (6.1)3 (4.6)3 (4.6)Male, n(%)38 (58.4)Age (median, IQR)64 (20–87)Charlson Comorbidity Index (median, IQR)6 (1–12)APACHE II score (median, IQR)20 (4–41)ICU, n(%)37(56.9)Hospital day index infection diagnosed (median, IQR)17 (0–265)Hospital day TOL-TAZ started (median, IQR)19 (0–284)3grs q8hrs, n(%)1.5grs q8hrs, n(%)23 (35.3)23 (35.3)Concomitant IV antibiotics, n(%)Aminoglycoside, n/N(%)Fluoroquinolone, n/N(%)Polymyxin, n/N(%)Β-lactam, n/N(%)15 (23.0)7/15 (46.7)4/15 (26.7)3/15 (20)1/15 (6.6)TOL-TAZ susceptible isolates, n/N (%)35/37 (94.6) Outcomes by primary infection Primary infectionn (%)30-day survival n/N(%)Microbiologic cure n/N(%)Clinical cure n/N(%)Pneumonia33 (50.7)30/33 (90.9)24/33 (72.7)28/33 (84.8)Wound/Bone/Joint12 (18.4)8/12 (66.6)7/12 (58.3)7/12 (58.3)UTI9 (13.8)7/9 (77.7)7/9 (77.7)8/9 (88.8)Intra-abdominal7 (10.7)7/7 (100)7/7 (100)4/7 (57.1)Bloodstream4 (6.1)4/4 (100)4/4 (100)4/4 (100) Overall outcomes, n(%)30-day survival56 (86.1)In-hospital mortality17 (26.1)Microbiologic cure49 (75.3)Clinical cure51(78.4)ConclusionIn this study of 65 critically-ill immunocompromised patients, the 30-day survival was 86.1%; clinical cure was78.4% and microbiologic cure 75.3%. TOL-TAZ is a viable option for immunocompromised patients with MDRPA 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.