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129. Antimicrobial Activity of Ceftazidime–avibactam and Comparator Agents Tested against Gram-Negative Organisms Isolated from Patients with Bloodstream Infections in United States Medical Centers (2017–2018)

Abstract Background We evaluated the antimicrobial susceptibility of Enterobacterales (ENT) and P. aeruginosa (PSA) causing bloodstream infections (BSIs) in the United States (US) hospitals. Methods A total of 3,317 ENT and 331 PSA isolates were consecutively collected (1/patient) from patients with BSI in 68 US medical centers in 2017–2018 and tested for susceptibility (S) by reference broth microdilution methods in a central laboratory as part of the International Network for Optimal Resistance Monitoring (INFORM) Program. β-Lactamase screening was performed by whole-genome sequencing on ENT with decreased S to broad-spectrum cephalosporins (ESBL phenotype). Results The most common ENT species isolated from BSI were E. coli (EC; 41.9% of ENT), K. pneumoniae (KPN; 24.4%), and E. cloacae (ECL; 8.7%), and the most active agents against ENT were ceftazidime–avibactam (CAZ-AVI; 99.9%S), amikacin (AMK; 99.6%S) and meropenem (MEM; 99.3%S). CAZ-AVI was active against all EC and KPN isolates (100.0%S). Only 2 ENT isolates (0.06%) were CAZ-AVI resistant, 2 NDM-1-producing ECL isolated in the New York City area. Ceftolozane–tazobactam (C-T) and piperacillin–tazobactam (PIP-TAZ) showed good activity against EC and KPN (92.2–98.9%S; Table), with limited activity against ECL (81.9–83.7%S). The most common ESBLs were CTX-M-type, which was observed in 93% of ESBL producers (mainly CTX-M-15 [64% of ESBL producers] and CTX-M-27 [13%]), and OXA-1/OXA-30 (42%); 42% of ESBL producers (n = 333, excluding carbapenemase producers) displayed ≥2 ESBL genes, mainly CTX-M-15 and OXA-1/OXA-30 (40% of ESBL producers). The most active agents against ESBL producers were CAZ-AVI (100.0%S), imipenem (99.4%S), and colistin (COL; 99.1%S). Only CAZ-AVI (99.4%S), AMK (96.2%S) and MEM (92.8%S) were active against >90% of multidrug-resistant (MDR) ENT. Among 19 carbapenem-resistant ENT (CRE; 0.6% of ENT), 9 produced a KPC-like, 2 an NDM-1, and 2 an NMC-A; carbapenemase genes were not found in 6 CRE isolates. COL (100.0%S), CAZ-AVI (98.5%S), AMK (98.5%S), C-T (98.1%S), and tobramycin (97.0%S) were very active against PSA. Conclusion CAZ-AVI exhibited potent in vitro activity and great spectrum against ENT (99.9%S) and PSA (98.5%) isolated from patients with BSI from US hospitals. Disclosures All authors: No reported disclosures.

Background. Inadequate empiric antimicrobial therapy for Gram-negative bacteremia is associated with adverse clinical outcomes. The purpose of this study was to evaluate the proportion of Gram-negative bacterial isolates recovered from the bloodstream of patients attending Canadian emergency rooms (ERs) that remain susceptible to commonly prescribed antimicrobials.
Methods. Annually from 2007 to 2018, sentinel hospitals across Canada collected bloodstream isolates from patients attending ERs as part of the CANWARD study. Susceptibility testing was performed using broth microdilution as described by CLSI (data analysis limited to Gram-negative bacteria in the top 10 pathogens), with current CLSI breakpoints applied. Extended-spectrum β-lactamase (ESBL)-producing isolates were confirmed using the CLSI disk diffusion method.
Conclusion. The most consistently active antimicrobials for empiric treatment of patients at Canadian ERs with Gram-negative bacteremia are meropenem and piperacillin-tazobactam. Ceftriaxone susceptibility among E. coli has declined over the last 12 years, mostly related to an increase in ESBL-producing isolates.
Disclosures. All authors: No reported disclosures. Methods. A total of 3,317 ENT and 331 PSA isolates were consecutively collected (1/patient) from patients with BSI in 68 US medical centers in 2017-2018 and tested for susceptibility (S) by reference broth microdilution methods in a central laboratory as part of the International Network for Optimal Resistance Monitoring (INFORM) Program. β-Lactamase screening was performed by whole-genome sequencing on ENT with decreased S to broad-spectrum cephalosporins (ESBL phenotype).
Disclosures. All authors: No reported disclosures. Background. Streptococcus agalactiae (GBS), a leading cause of neonatal infections, also occurs as an invasive infection in elderly people. The aim of this study was to evaluate the clinical aspect of invasive infections and the phenotypic and genetic diversity of GBS isolates to develop better antibiotics treatment and curb the increasing rate of antibiotic resistance in Nara, Japan.

Clinical Presentation and Molecular Epidemiology Characterization of
Methods. GBS strains sequentially collected from blood and cerebrospinal fluid cultures between 2007 and 2016 were identified and evaluated for capsular types, multilocus sequence typing (MLST), antibiotic susceptibility, resistant gene, and pulsed-field gel electrophoresis (PFGE). Clinical characteristics were retrospectively collected.
Results. A total of 42 GBS isolates (12 from children and 30 from adults) were collected. In adults, common underlying conditions were malignancy and diabetes, and primary bacteremia was the most common source of infection. In children, 6 were early-onset diseases, 4 were late-onset diseases, and 2 were school children. Overall, the mortality rate was 0% in children and 17% in adults. The serotypes and main clonal complex are summarized in Table 1. Minimum inhibitory concentrations of the antibiotics were also determined ( Table 2). The serotypes and resistant genes are shown in Table 3. PFGE revealed serotypes V and VI belonging to ST1, and serotype III belonging to ST335 were highly identical.
Conclusion. In clinical aspects, neonates with early-onset diseases experienced certain disorders during the perinatal period. In adults, serotype Ib, which tends to exhibit levofloxacin resistance, was the most common, followed by serotypes V and VI belonging to ST1; however, they were not observed in children. Contrastingly, serotype III belonging to ST335, which tends to exhibit macrolide resistance, was mainly observed in children. Quinolone among adults and macrolide among the younger generation are widely used as oral antibiotics in Japan. A tendency to use antibiotics affects bacterial flora and induces selectivity of specific clones, thereby causing diseases in the local community. Continuous surveillance is warranted in local areas for appropriate antibiotics treatment and prevent increasing antibiotic-resistant isolates.
Disclosures. All authors: No reported disclosures.