Triazole antifungals (i.e., fluconazole, itraconazole, voriconazole, posaconazole, and isavuconazole) are commonly used in clinical practice to prevent or treat invasive fungal infections. Most triazole antifungals require therapeutic drug monitoring (TDM) due to highly variable pharmacokinetics, known drug interactions, and established relationships between exposure and response. On behalf of the Society of Infectious Diseases Pharmacists (SIDP), this insight describes the pharmacokinetic principles and pharmacodynamic targets of commonly used triazole antifungals and provides the rationale for utility of TDM within each agent.

Objective: We examined the impact of microbiological results from respiratory samples on choice of antibiotic therapy in patients treated for hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP). Design: Four-year retrospective study. Setting: Veterans’ Health Administration (VHA). Patients: VHA patients hospitalized with HAP or VAP and with respiratory cultures between October 1, 2014, and September 30, 2018. Interventions: We compared patients with positive and negative respiratory culture results, assessing changes in antibiotic class and Antibiotic Spectrum Index (ASI) from the day of sample collection (day 0) through day 7. Results: Between October 1, 2014, and September 30, 2018, we identified 5,086 patients with HAP/VAP: 2,952 with positive culture results and 2,134 with negative culture results. All-cause 30-day mortality was 21% for both groups. The mean time from respiratory sample receipt in the laboratory to final respiratory culture result was longer for those with positive (2.9 ± 1.3 days) compared to negative results (2.5 ± 1.3 days; P < .001). The most common pathogens were Staphylococcus aureus and Pseudomonas aeruginosa. Vancomycin and β-lactam/β-lactamase inhibitors were the most commonly prescribed agents. The decrease in the median ASI from 13 to 8 between days 0 and 6 was similar among patients with positive and negative respiratory cultures. Patients with negative cultures were more likely to be off antibiotics from day 3 onward. Conclusions: The results of respiratory cultures had only a small influence on antibiotics used during the treatment of HAP/VAP. The decrease in ASI for both groups suggests the integration of antibiotic stewardship principles, including de-escalation, into the care of patients with HAP/VAP.

Background: The survival of patients with hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) is largely determined by the timely administration of effective antibiotic therapy. Guidelines for the treatment HAP and VAP recommend empiric treatment with broad-spectrum antibiotics and tailoring of antibiotic therapy once results of microbiological testing are available. Objective: We examined the influence of bacterial identification and antibiotic susceptibility testing on antibiotic therapy for patients with HAP or VAP. Methods: We used the US Veterans’ Health Administration (VHA) database to identify a retrospective cohort of patients diagnosed with HAP or VAP between fiscal year 2015 and 2018. We further analyzed patients who were started on empiric antibiotic therapy, for whom microbiological test results from a respiratory sample were available within 7 days and who were alive within 48 hours of sample collection. We used the antibiotic spectrum index (ASI) to compare antibiotics prescribed the day before and the day after availability of bacterial identification and antibiotic susceptibility testing results. Results: We identified 4,669 cases of HAP and VAP in 4,555 VHA patients. The median time from respiratory sample receipt in the laboratory to final result of bacterial identification and antibiotic susceptibility testing was 2.22 days (IQR, 1.31–3.38 days). The most common pathogen was Staphylococcus aureus (n = 994), with methicillin resistance in 58% of those isolates tested. The next most common pathogen was Pseudomonas spp (n = 946 isolates). The susceptibility of antipseudomonal antibiotics, when tested, was as follows: 64% to carbapenems, 74% to cephalosporins, 75% to β-lactam/β-lactamase inhibitors, 69% to fluoroquinolones, and 95% to amikacin. Lactose-fermenting gram-negative bacteria (296 Escherichia coli and 360 Klebsiella pneumoniae) were also common. Among the 3,094 cases who received empiric antibiotic therapy, 607 (20%) had antibiotics stopped the day after antibiotic susceptibility results became available, 920 (30%) had a decrease in ASI, 1,075 (35%) had no change in ASI, and 492 (16%) had an increase in ASI (Fig. 1). Among the 1,098 patients who were not started on empiric antibiotic therapy, only 154 (14%) were started on antibiotic therapy the day after antibiotic susceptibility results became available. Conclusions: Changes in antibiotic therapy occurred in at least two-thirds of cases the day after bacterial identification and antibiotic susceptibility results became available. These results highlight how respiratory cultures can inform the treatment and improve antibiotic stewardship for patients with HAP/VAP.Funding: This study was supported by Accelerate Diagnostics.Disclosures: None

BackgroundPatients with suspected urinary tract infection (UTI) are often prescribed an empiric antibiotic treatment due to delays in obtaining results of urine cultures. The BacterioScan System measures the turbidity of incubating urine specimens to provide a qualitative determination of bacteriuria at a density of >5 × 104 colony-forming units (CFU)/mL within approximately 3 hours. We examined the utility of the BacterioScan assay in predicting bacteriuria and assessed the potential impact of this test to reduce the number of urine cultures processed.MethodsUrine samples received for culture in the microbiology laboratory of the Cleveland VA Medical Center were collected daily between September 2018 and December 2018. For each specimen, we performed a bacterioscan diagnostic test and compared it with the result of the traditional culture and urinalysis if available. Urinary cultures were categorized into 4 groups as defined in Figure 1. We compared the sensitivity and specificity of the bacterioscan vs. urinalysis (leukocyte esterase and/or pyuria) results.Results120 urine samples were tested. As shown in Table 1, the BacterioScan had better sensitivity and specificity than the urinalysis for detection of positive urine cultures. The use of the BacterioScan to rule out UTI could have accurately spared 69 of 120 (57.5%) samples from traditional culture and prevented 26 of 120 (21.6%) from possible misinterpretation as infection due to reporting of growth. BacterioScan resulted in 4 of 31 (12.9%) false negatives, but all occurred when positive cultures were due to viridans streptococci or uropathogens in numbers below 100,000 CFU.ml.ConclusionThe BacterioScan system is a rapid diagnostic test that provides early information on urine culture results that could help to avoid overuse of empirical antimicrobials in patients with suspected UTI and decrease the workload of the Microbiology Laboratory. Disclosures All authors: No reported disclosures.

BackgroundRespiratory specimens help inform the treatment of hospital-acquired pneumonia (HAP), permitting clinicians to ensure effective and, ideally, narrow-spectrum antibiotic therapy. Here, we examine changes in antibiotic regimens to treat HAP based on the antibiotic susceptibility of pathogens recovered from respiratory samples.MethodsAt a single Veterans Affairs (VA) Medical Center, we identified veterans hospitalized between October 2014 and September 2018 with HAP, defined as a clinical respiratory sample obtained >48 hours after admission and corresponding clinical signs and symptoms. Exclusion criteria were death, transfer to hospice care or discharge within 48 hours of sample collection or admission from an outside hospital. For each specimen, we assessed timestamps for collection, Gram stain, identification of organisms and results of susceptibility testing. We used the antibiotic spectrum index (ASI) to assess changes in antibiotics given to patients during hospitalization and at discharge.ResultsBetween October 2014 and September 2018, 70 veterans met our inclusion criteria and experienced 73 episodes of HAP. Their mean age was 66.2 years (±9 years) and 47 (67%) had chronic pulmonary disease. All-cause mortality at 30-days after specimen collection was 14%. The median time from specimen collection to Gram stain result was 0.8 days (interquartile range (IQR) 0.1–1.9) and to antibiotic susceptibility results was 2.4 days (IQR 1.5–3.3). The most common bacteria recovered were Enterobacteriaceae (20 isolates), Pseudomonas aeruginosa (11 isolates), Streptococcus spp. and Staphylococcus aureus (8 isolates each); colonization with Candida spp. was frequent (26 isolates). Vancomycin and piperacillin–tazobactam were the most common antibiotics on day 0 (24%, 22%, respectively) and day 3 (21%, 13%, respectively). Compared with the day of sample collection (day 0), the ASI score was lower at day 3 in 23 (32%) and higher in 21 (29%) cases.ConclusionThe high proportion of escalation and de-escalation of antibiotics suggests that results of bacteria identification and susceptibility testing influence therapeutic decisions, emphasizing the importance of obtaining respiratory samples to inform treatment of HAP and improve antibiotic stewardship.Disclosures All authors: No reported disclosures.