Keith S. Kaye

Ceftazidime–avibactam (caz-avi) is a new treatment option for carbapenem-resistant Enterobacteriaceae (CRE). The Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE-2) is a multi-center, prospective, observational study of 60 hospitals in all five regions of the USA. Hospitalized patients with CRE isolated from clinical cultures are enrolled in CRACKLE-2. CRE was defined per CDC guidelines. Pitt Bacteremia score (PBS) and Charlson comorbidity score (CMS) were calculated. caz–avi susceptibility was tested as clinically indicated in participating clinical laboratories. From June 1, 2016–April 4, 2017, 568 unique patients with 591 admissions and 681 culture episodes (42% infection, 58% colonization) were included. The distribution of 252 first CRE infections per unique patient was 78 (31%) blood, 67 (27%) urine, 37 (15%) respiratory, 34 (13%) intra-abdominal, 30 (12%) wound, and 6 (2%) other. Patients with CRE infections were chronically ill (CMS median [IQR] 3 [1,5]) and acutely ill (PBS median [IQR] 3 [2,6]). Outcomes were available for 198 patients with infections; all-cause mortality was 29/198 (15%) at 14 days, and 55/198 (28%) at 90 days. K. pneumoniae (62%), E. cloacae (17%), and E. coli (13%) were the top three CRE species. A total of 124 isolates were tested for carbapenemase genes; 62/124 (50%), and 29/124 (23%) were positive for blaKPC-2, and blaKPC-3, respectively. Within 96 tested CR K. pneumoniae (CRKP) isolates, 22/96 (23%), 36/96 (38%), 38/96 (40%) were ST258-1, ST258-2, and non-ST258 clades, respectively. Antibiotic data were available for 224 patients with infections. In various combinations, 37/224 (16%) patients received polymyxins, 74/224 (33%) aminoglycosides, 111/224 (49%) carbapenems, 47/224 (21%) ceftazidime/avibactam, and 26/224 (12%) tigecycline. A total of 111 CRE were tested for caz–avi susceptibility; 32/111 (29%) were non-susceptible. All-cause mortality by caz–avi susceptibility did not differ among 62 patients with outcomes (P = 0.74). In this national sample of hospitalized patients with CRE, 29% of tested isolates were caz–avi non-susceptible. Results need to be confirmed by central laboratory testing. D. Van Duin, Astellas: Scientific Advisor, Consulting fee. Achaogen: Scientific Advisor, Consulting fee. Allergan: Scientific Advisor, Consulting fee. MedImmune: Scientific Advisor, Consulting fee. Shionogi: Scientific Advisor, Consulting fee. S. S. Richter, bioMerieux: Investigator, Research support. BD Diagnostics: Investigator, Research support. Roche: Investigator, Research support. BioFire: Investigator, Research support. OpGen: Investigator, Research support. K. S. Kaye, Xellia: Consultant, Consulting fee. Merck: Consultant and Grant Investigator, Consulting fee and Research support. The Medicines Company: Consultant and Grant Investigator, Consulting fee and Research support. C. Arias, Bayer Global: Consultant and Speaker’s Bureau, Consulting fee...

OBJECTIVES: To determine the effect of surgical site infection (SSI) on mortality, duration of hospitalization, and hospital cost in older operative patients. DESIGN: Retrospective matched‐outcomes study. SETTING: Eight hospitals, including Duke University Medical Center, and seven community hospitals. PARTICIPANTS: Patients aged 65 and older undergoing surgery from 1991 to 2003. Cases were defined as patients who developed deep incisional or organ or space SSI; controls were operative patients who did not develop SSI. Controls were frequency matched to cases according to type and year of operative procedure and to hospital in a 1:1 ratio. MEASUREMENTS: Mortality, duration of hospitalization (including re‐admissions), and hospital charges for the 90 days after surgery. RESULTS: One thousand three hundred thirty‐seven patients were enrolled in the study: 561 cases with SSI and 576 controls without SSI. In cases, the most common SSI pathogen was Staphylococcus aureus (n=275, 51.6%). Of S. aureus isolates, 58.2% were methicillin resistant. One hundred sixteen subjects died within 90 days of surgery (8.6%). In multivariable analysis, SSI was associated with greater mortality risk (odds ratio (OR)=3.51, 95% confidence interval (CI)=2.20–5.59), 2.9 times longer postoperative hospitalization (95% CI=2.61–3.13), and 1.9 times greater hospital charges (95% CI=1.78–2.10). CONCLUSION: In elderly operative patients, SSI was associated with almost 4 times greater mortality, a mean attributable duration of hospitalization after surgery of 15.7 days (95% CI=13.9–17.6) and mean attributable hospital charges of $43,970 (95% CI=$31,881–56,060).