Phenotypic antimicrobial susceptibilities are particularly valuable for P. aeruginosa due to the complexity of resistance mechanisms this organism can harbor.…

Identification (ID) and antimicrobial susceptibility testing (AST) of respiratory pathogens are critical to the management of patients with pneumonia to facilitate optimal antibiotic therapy selection. Few studies have examined the time to results (TTR) for this critical specimen, and such data can be valuable for benchmarking the current paradigm of diagnostic approaches. TTR for bronchoalveolar lavage (BAL) and endotracheal aspirate (ETA) specimens from hospitalized patients was evaluated using the Premier Healthcare Database, a comprehensive database of 194 U.S. hospitals. Time from specimen collection to reporting of organism ID/AST were evaluated and compared by specimen types and characteristics. A total of 79,662 (43,129 BAL; 36,533 ETA) specimens were included, of which 19.3% harbored no growth, 47.1% contained normal respiratory flora alone (including yeast), and 0.6% contained mycobacteria/moulds. Potential bacterial pathogens (PBP) were recovered from 33.0%. ETAs had a higher proportion of specimens with isolation of PBP (39.2% vs 27.7%), normal respiratory flora (52.0% vs 43.0%), and were less likely to be negative (8.2% vs 28.6%) than BALs (all P < 0.0001). Staphylococcus aureus and Pseudomonas aeruginosa were isolated in 10.5% and 6.4% of specimens, respectively, and were the most common organisms identified. Median (interquartile range) TTR were 37.0 (21.8-51.7) and 60.5 (46.6-72.4) hours for ID and AST, respectively. Median TTR for major respiratory pathogens by organism ranged from 29.2-43.9 hours for ID and from 47.9-73.9 hours for AST. Organism type, specimen collection time, and hospital teaching status influenced TTR. Mechanically vented patients and ETA specimens were more likely to recover PBP.

Antimicrobial susceptibility testing for Pseudomonas aeruginosa is critical to determine suitable treatment options. Commercial susceptibility tests are typically calibrated against the reference method, broth microdilution (BMD). Imprecision of minimum inhibitory concentrations (MICs) obtained by BMD for the same isolate on repeat testing is known to exist. Factors that impact the extent of variability include concentration of the inoculum, operator effects, contents of the media, inherent strain properties, and the testing process or materials. We evaluated the variability of BMD for anti-pseudomonal beta-lactams (aztreonam, cefepime, ceftazidime, meropenem, piperacillin-tazobactam, ceftazidime-avibactam, ceftolozane-tazobactam) tested against a collection of P. aeruginosa isolates. Multiple replicate BMD tests were performed and MICs were compared to assess reproducibility, including the impact of the inoculum and operator. Overall, essential agreement (EA) was ≥ 90% for all beta-lactams tested. Absolute agreement (AA) was as low as 70% for some beta-lactams. Variability from the inoculum and operators impacted the reproducibility of MICs. Piperacillin-tazobactam exhibited the highest degree of variability with 74% AA and 94%% EA. The implications of MIC variability are extensive as the MIC is essential for multiple facets of microbiology, such as the development of new compounds and susceptibility tests, dose optimization and pharmacokinetic/pharmacodynamic (PK/PD) targets for individual patients.

BackgroundThe Clinical and Laboratory Standards Institute (CLSI) updated fluoroquinolone breakpoints in 2019 in response to evolving resistance and new outcome data. The performance of updated antimicrobial susceptibility testing (AST) algorithms for ciprofloxacin with the 2019 breakpoints for Enterobacteriaceae and Pseudomonas aeruginosa was evaluated using the Accelerate Pheno™ system with contrived positive blood culture samples compared with broth microdilution (BMD).MethodsA total of 294 clinical isolates (100 P. aeruginosa, 82 Klebsiella spp., 56 E. coli, 24 Citrobacter spp., 14 Enterobacter spp., 15 Proteus spp., and 3 S. marcescens) were tested with ciprofloxacin. Aliquots of BD BACTEC™ Standard Aerobic media containing healthy donor blood were seeded with 10–100 bacterial cells and incubated until positivity. Aliquots of the positive blood cultures were run using the Accelerate PhenoTest™ BC kit on the Accelerate Pheno™ system according to the manufacturer instructions for use. Results were obtained using an updated ciprofloxacin algorithm and compared with CLSI standard reference BMD. Only samples with valid results with both the Accelerate Pheno™ system and reference BMD were included in analysis. Essential agreement (EA), categorical agreement (CA), very major error (VME), major error (ME) and minor error (mE) rates were calculated using 2019 CLSI breakpoints.ResultsEA and CA for all antimicrobial/organism combinations were >94%. There were 2 MEs (1 K. pneumoniae, 1 C. freundii) and no VMEs.ConclusionResults with the new research use only (RUO) algorithms are very good and meet FDA acceptance criteria for AST performance. These data will be submitted to the FDA for clearance, once FDA recognizes the CLSI breakpoints. Disclosures All authors: No reported disclosures.

BackgroundDefinitive therapy with piperacillin–tazobactam (TZP) for ceftriaxone (CRO)-resistant E. coli or K. pneumoniae bloodstream infections (BSI) has been shown to be inferior to carbapenem therapy in a randomized trial.MethodsThe Premier US database was queried for hospitalized patients with monomicrobial E. coli or Klebsiella spp BSI that were not susceptible (NS) to CRO between June 2015 and May 2018. Adults with index positive blood culture(s) drawn within the first 2 hospital days who were treated with active antibiotic therapy that continued for ≥3 consecutive days were included. We defined antibiotics administered on or prior to Day 3 as empirical therapy and all subsequent days as definitive therapy. Outcomes among patients who received definitive therapy with a carbapenem vs. TZP were evaluated.ResultsThere were 954 patients (mean age, 67.6 years; 52.4% women) who met selection criteria and received active empirical therapy. 729/954 received carbapenem definitive therapy and 38/954 received TZP definitive therapy. Median Charlson Comorbidity Index scores were similar between carbapenem and TZP definitive therapy groups (6 vs. 5, P = 0.78). Crude 14-day in-hospital mortality for CRO-NS BSI due to E. coli or Klebsiella spp. was 4.4%. Definitive therapy with TZP (6/38; 15.8%) was associated with an increased likelihood of 14-day mortality relative to that of a carbapenem (22/729; 3.0%; P < 0.0001). The increased 14-day mortality observation was consistent in a multivariate cox proportional hazards model (adjusted hazard ratio, 5.70; 95% CI, 2.09 to 13.23; P = 0.002). Of patients who received carbapenem definitive therapy, 14-day mortality was 2.7% (19/693) if a carbapenem was part of empirical therapy and 8.3% (3/36; P = 0.06) if empirical therapy did not include a carbapenem. Median post-blood culture length of stay (7 vs. 6 days, P = 0.65) and hospital costs ($13,886 vs. $13,559, P = 0.62) were similar between carbapenem and TZP definitive therapy groups<./p>ConclusionIn this large US database, definitive therapy with TZP was associated with an increased likelihood of 14-day mortality relative to that of definitive carbapenem therapy in patients with CRO-NS BSI due to E. coli or Klebsiella spp. These findings support recent clinical evidence in favor of definitive carbapenem therapy for CRO-NS BSI due to E. coli or Klebsiella spp.Disclosures All authors: No reported disclosures.