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Objective:Lack of judicious testing can result in the incorrect diagnosis of Clostridioides difficile infection (CDI), unnecessary CDI treatment, increased costs and falsely augmented hospital-acquired infection (HAI) rates. We evaluated facility-wide interventions used at the VA San Diego Healthcare System (VASDHS) to reduce healthcare-onset, healthcare-facility–associated CDI (HO-HCFA CDI), including the use of diagnostic stewardship with test ordering criteria.Design:We conducted a retrospective study to assess the effectiveness of measures implemented to reduce the rate of HO-HCFA CDI at the VASDHS from fiscal year (FY)2015 to FY2018.Interventions:Measures executed in a stepwise fashion included a hand hygiene initiative, prompt isolation of CDI patients, enhanced terminal room cleaning, reduction of fluoroquinolone and proton-pump inhibitor use, laboratory rejection of solid stool samples, and lastly diagnostic stewardship with C. difficile toxin B gene nucleic acid amplification testing (NAAT) criteria instituted in FY2018.Results:From FY2015 to FY2018, 127 cases of HO-HCFA CDI were identified. All rate-reducing initiatives resulted in decreased HO-HCFA cases (from 44 to 13; P ≤ .05). However, the number of HO-HCFA cases (34 to 13; P ≤ .05), potential false-positive testing associated with colonization and laxative use (from 11 to 4), hospital days (from 596 to 332), CDI-related hospitalization costs (from $2,780,681 to $1,534,190) and treatment cost (from $7,158 vs $1,476) decreased substantially following the introduction of diagnostic stewardship with test criteria from FY2017 to FY2018.Conclusions:Initiatives to decrease risk for CDI and diagnostic stewardship of C. difficile stool NAAT significantly reduced HO-HCFA CDI rates, detection of potential false-positives associated with laxative use, and lowered healthcare costs. Diagnostic stewardship itself had the most dramatic impact on outcomes observed and served as an effective tool in reducing HO-HCFA CDI rates.

Background Antibiotic dosing optimization is a key principle of antimicrobial stewardship. This study evaluated the impact of an extended infusion piperacillin/tazobactam dosing protocol on clinical outcomes in acutely ill veterans treated for infections at VA San Diego. Methods This retrospective cohort study looked at veterans admitted to the medical-surgical unit who were treated with piperacillin/tazobactam for at least 48 hours. The control group included patients who received treatment between 12/14/2017 to 7/22/2018, and the “protocol” or after protocol implementation group included patients who received treatment between 7/23/2018 to 2/28/2019. Excluded from the study were veterans with microbiological cultures showing intermediate sensitivity or resistance to piperacillin/tazobactam, those who experienced interruption in therapy, or those who required dialysis. Primary clinical outcomes included in-hospital mortality rate, 30-day mortality rate, hospital length of stay (LOS), and 30-day readmission rates. Rates of adverse effects such as elevated liver enzymes, thrombocytopenia, acute kidney impairment (AKI), and Clostridium difficile infection were also collected. χ 2, Fisher’s exact, and Mann-Whitney U tests were used for statistical analysis. Results 260 veterans were included in the final analysis: 96% male, mean age 65 years, mean BMI 29, 84 met SIRS criteria for sepsis, and 55% received at least 48 hours of concomitant vancomycin. Groups had similar outcomes for median LOS, in-hospital mortality, and 30-day mortality. The incidence of AKI was significantly lower in the protocol group (39.2% vs. 56.9%, p=0.004), in veterans on concomitant vancomycin (42.3% vs. 63.2%, p=0.011), and in veterans with obesity (36.4% vs. 70.8%, p=0.001). Rates of liver enzyme elevation, thrombocytopenia, and C. difficile infection were lower in the protocol group though these were not significant. Conclusion There was a significantly lower rate of AKI with EI dosing which supports enhanced patient safety. This may be the preferred method of administration for obese patients and/or those receiving vancomycin concurrently. This is the first study to demonstrate that EI piperacillin/tazobactam dosing significantly reduces rates of AKI in patients on concomitant vancomycin. Disclosures All Authors: No reported disclosures

Encephalopathy complicates beta-lactam therapy, particularly with impaired renal function, though no studies have reported ceftaroline-associated encephalopathy. Among 28 patients with estimated glomerular filtration rates

Background Bacterial prostatitis (BP) is notoriously difficult to treat. Few antibiotics penetrate the prostate well, and antibiotic resistance can further restrict options. A small body of recent literature suggests fosfomycin, a bactericidal antibiotic that can treat multidrug resistant (MDR) organisms and has little cross-resistance, may both effectively penetrate the prostate and treat BP. This study sought to add to the limited literature on the efficacy and safety of fosfomycin for BP. Methods Patients treated for BP with fosfomycin between November 2009 and May 2019 at the San Diego VAMC were retrospectively examined. Patients were excluded if they died within 6 months of completion of fosfomycin or if fosfomycin was used for less than half of the treatment course. If fosfomycin was used to treat a urinary tract infection (UTI), an infectious disease physician determined if the UTI may have been undiagnosed BP. Outcomes were clinical and microbiological cure at 6 months and adverse events to fosfomycin reported during the trial period. Results The study included 29 patient cases. All but one had chronic BP. Most initially presented outpatient (66%). Almost all had prior occurrences of BP treated with antibiotics (90%). The most common pathogen was E. coli (73%), and 87% of all pathogens were MDR. The most common fosfomycin dosing regimen was 3g PO q48h (66%), with 3g PO q24h as the next most common (21%). Less than half of patient cases received fosfomycin courses > 28 days (38%), while the remaining received courses < 14 days (62%). At 6 months, 48% achieved clinical cure and 44% achieved microbiological cure. When comparing those who received courses > 28 days vs. courses < 14 days, clinical cure was achieved in 55% vs. 44% and microbiological cure in 56% vs. 39%, respectively. Adverse events were reported in 6 unique patients (27%), mostly diarrhea with one instance of nausea. Conclusion Fosfomycin may be a safe and effective alternative for the treatment of chronic BP. Treatment courses longer than 4 weeks may be more effective than courses shorter than 2 weeks with a similar rate of adverse events. This study also highlights inpatients as a relevant BP population and a need for provider education on identifying BP and prescribing optimal durations of therapy. Disclosures All Authors: No reported disclosures

Background The vancomycin AUC/MIC target ratio of 400 to 600 mg*h/L that is recommended (level IA+) in the 2020 IDSA/ASHP vancomycin TDM guidelines is appropriate for patients with complicated MRSA infections; using lower targets for less complicated infections may reduce the risk for nephrotoxicity without compromising efficacy. The current methodology surrounding vancomycin AUC/MIC targets is unrefined, with no source specific targets identified, especially for relatively lower risk MRSA infections such as skin and soft tissue infections (SSTIs). Methods This was a retrospective observational study of hospitalized patients at the Veterans Affairs Health Care System in San Diego, CA with a SSTI and prescribed intravenous vancomycin between January 1, 2016 and December 31, 2019. Patients included were adults, 18 years of age and older, treated with IV vancomycin with ≥1 measured concentration for at least one of the ICD-10 CM codes for SSTI. Patients were excluded if they had any of the following SSTIs: (1) osteomyelitis; (2) infection related to chronic ulcers or wounds; (3) head SSTI; (4) peri-rectal SSTI; (5) human or animal bite SSTI; (6) SSTI related to retained foreign body; (7) necrotizing SSTI; (8) surgical site infection. Patients were also excluded if they were undergoing dialysis or had severe immunosuppression. Results A total of 722 patients on vancomycin for a SSTI were identified from the database query for screening, and 243 (34%) met inclusion criteria for the study. Classification and Regression Tree (CART) modeling identified a calculated AUC of >253 as having the highest correlation with clinical success. Clinical cure was significantly different between the AUC ≤253 (6/9 [67%]) and AUC >253 (214/234 [91%]) cohorts (p=0.043). There were no differences in hospital length of stay or duration of vancomycin therapy. Nephrotoxicity occurred in seven patients, all of who had AUC >253. Conclusion Overall treatment success in patients with SSTIs was associated with a vancomycin AUC >253, which is lower than the guideline recommended range of 400–600. Identification of vancomycin AUC targets for other low risk sources of infection, such as UTIs, is needed to prevent vancomycin overexposure. Disclosures All Authors: No reported disclosures

Background Recent studies have given rise to the concern that some integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy may lead to weight gain in PLWH. The objectives of this study were to compare the incidence of weight gain following initiation of bictegravir (BIC) compared to other INSTIs, and to assess whether any differences were associated with changes in metabolic indices. Methods Patients from the VA San Diego Healthcare System (VASDHS) were included in this retrospective cohort study if they were at least 18 years old and being treated for HIV with an INSTI that was started exclusively with FTC/TAF for at least 6 months. INSTI-containing regimens were excluded if initiated with non-FTC/TAF antiretroviral agents or if the patient was pregnant, using prescription weight loss drugs, or did not have weights recorded after the start of the studied regimen. The primary outcome was weight gain at 12 and 18 months after the start of the studied regimen. Secondary outcomes included changes in parameters used to define metabolic syndrome. Statistical analysis was performed using Mann-Whitney U, Chi-square, and Spearman’s Rho tests. Results 560 patients with 809 instances of new INSTI prescriptions from VASDHS during November 2015 to October 2019 were reviewed for inclusion. Raltegravir-based regimens were excluded from analysis due to the limited number of eligible regimens. Study groups included group 1 (BIC, n=265), group 2 (elvitegravir/cobicistat, n=123), and group 3 (dolutegravir, n=35). There were no significant differences in baseline weight between groups. Median weight change at 12 months was 2.8 lbs. in group 1, 4.4 lbs. in group 2 (p=0.328 vs. group 1), and 5.3 lbs. in group 3 (p=0.133 vs. group 1). At 18 months, median weight change was 4.5 lbs. in group 1, 3.4 lbs. in group 2 (p=0.597 vs. group 1), and 7.7 lbs. in group 3 (p=0.585 vs. group 1). Within group 1, there was a significant increase in weight at 3, 6, 12, and 18 months compared to index date. Conclusion These results support the growing body of evidence associating INSTI use with weight gain, which was persistent over 18 months in all groups and in the context of a consistent FTC/TAF backbone in this study. No significant differences in magnitude of weight gain were observed between INSTIs. Disclosures All Authors: No reported disclosures

Herpes zoster (HZ) occurs at a higher age-specific rate in people living with HIV (PLWH) than in the general population. We implemented a quality improvement study to assess herpes zoster vaccine (HZV) usage among PLWH, assess HZV usage after additional reminders/prompts, and identify barriers to HZV among older PLWH. HZV rates in PLWH were determined in six institutions with varying payment structures. For the intervention, Part 1, PLWH eligible for HZV at the University of Colorado were identified, and providers were notified of patient eligibility. In Part 2, in addition to provider notification, an order for HZV was placed in the patient's chart before a clinic appointment. HZ vaccination rates ranged from 1.5% to 42.4% at six sites. Before the intervention, 21.3% of eligible University of Colorado patients had received HZV. An additional 8.3% received HZV with Part 1 and 17.8% with Part 2 interventions. At completion, a total of 53.2% of eligible patients had received HZV through routine clinical care or the interventions. Insurance coverage concern was cited as a common reason for not receiving HZV. Minor adverse reactions occurred in 26.7% patients and did not require medical care. HZV coverage was low at a majority of sites. Clinical reminders with links to vaccination orders or preplaced vaccination orders led to improved HZV coverage in our clinic, but published guidelines for use of HZV in PLWH and improvement in logistic or insurance barriers to HZV receipt are paramount to improved HZV coverage.

Background VISN 22 is comprised of eight VA hospitals serving Southern California, Arizona, and New Mexico. The VISN 22 Antimicrobial Stewardship Workgroup formed in November 2018 with the purpose of sharing strong practices and program strategies. We compared antibiogram compilation strategies and antimicrobial susceptibilities and correlated antimicrobial susceptibilities for Pseudomonas aeruginosa and Escherichia coli with inpatient and outpatient antibiotic use. Methods 2018 antibiograms were collected from each hospital. Antibiotic utilization rates (antibiotic days per 1000 patient-days present) were extracted from VA Corporate Data Warehouse data. Pearson correlation coefficients were calculated between 2018 utilization of specific agents and P. aeruginosa and E. coli susceptibilities to those agents at each facility. Results Antibiograms varied according to authorship (microbiology and/or infectious diseases), reporting frequency, rules regarding isolate reporting, and location and specimen specificity (Table 1). Facilities reported at least 90% susceptibility to a median of 3 antibiotics (range 1 to 5) for P. aeruginosa and 5 antibiotics (range 1 to 7) for E. coli. The strongest negative correlations between antimicrobial use and susceptibility were observed for meropenem/imipenem (-0.43) and piperacillin–tazobactam (-0.41) with P. aeruginosa and piperacillin–tazobactam (-0.23) and fluoroquinolones (-0.21) with E. coli. A moderate negative correlation was observed between outpatient fluoroquinolone prescriptions per 1000 patients and E. coli susceptibility (-0.24). Conclusion Antibiogram composition is variable across VISN 22; not all reporting is consistent with CLSI recommendations. There was a modest correlation between some categories of antimicrobial use and resistance in P. aeruginosa and E. coli. Sharing antibiogram and antibiotic utilization data are helpful in developing antimicrobial stewardship strategies especially as we examine those hospitals with lower rates of resistance and antibiotic use. Disclosures All authors: No reported disclosures.

Background There are limited prospective data available to guide the management of severe coccidioidomycosis. In particular, the treatment of disseminated coccidioidomycosis often requires extended courses of antifungal therapy, for which there are often intolerable side-effects, toxicities, and failures. In recent years, newer oral triazole antifungals with in vitro activity against Coccidioides have become available, but data are lacking on their efficacy in coccidioidomycosis. Isavuconazole lacks many of the toxicities of older triazole antifungals, such as QT prolongation and certain key drug interactions, making it an appealing option in selected patients. Methods Based on pharmacy prescription history at two federal facilities in southern California, we identified adult patients with coccidioidomycosis who received isavuconazole from 2017 to 2019. Patient records were reviewed to identify age, sex, ethnicity, sites of infection, prior antifungal therapy, indication for switch to isavuconazole, duration of follow-up, and outcomes. Results 12 patients were identified between the ages of 36 and 86 years; 3 were women. 6 were of Pacific Islander descent, 4 were African American, 1 European-American, and 1 Latino. 6 (50%) had significant pre-infection comorbidities. 8 (67%) had evidence of extrapulmonary dissemination, including 1 patient with meningitis. All but one had received prior treatment with other azoles; two had previously been treated with amphotericin B. Six (50%) were switched to isavuconazole due failure or progression of disease on prior therapy; 3 (25%) due to drug toxicity; and 2 (17%) due to drug interactions. Seven (58%) patients improved on isavuconazole; 4/12 (33%) were stable; one developed hepatotoxicity but improved on posaconazole, and one patient deteriorated. Conclusion Isavuconazole appears to be a promising agent for the treatment of coccidioidomycosis. Long-term follow-up will be required to assess the risks of toxicity, disease progression, or relapse. For patients who are clinically stable but with an extensive disease burden or toxicity from older agents, isavuconazole may present an amphotericin-sparing option. Disclosures All authors: No reported disclosures.

Objective The aim was to measure patient satisfaction with the Pharmacy Specialty Immunization Clinic (PSIC), a pharmacist-run vaccination clinic. Methods Patient satisfaction was measured using a non-validated instrument containing 10 items with a five-point Likert scale (strongly agree, agree, not sure, disagree and strongly disagree). Patients who were seen at the PSIC and who received at least one vaccination were eligible to take part in the patient satisfaction survey. Priority index, a method used to identify areas where limited resources can be used to maximize patient satisfaction, was calculated for the different items of the instrument to determine areas for quality improvement. This study was conducted at the Veterans Affairs San Diego Healthcare System (VASDHS). Key findings A total of 188 (55.1%) out of 341 patients who received at least one vaccine in the PSIC completed the survey. Prior to any encounter with the PSIC, patients perceived that the VASDHS was doing a good job providing vaccinations (92.5% answered agree or strongly agree). This perception continued when asked about overall satisfaction after receiving vaccination through the PSIC (86.9% answered agree or strongly agree). When asked about the time the pharmacist spent with the patient, nearly all answered that the pharmacist spent as much time as necessary (97.8% answered agree or strongly agree). Patient satisfaction with pharmacist counselling was equally well received and reflected good communication between patient and pharmacist (97.8% answered agree or strongly agree). In regard to pharmacist competency, 98.9% (n= 184) of patients agreed that pharmacists in the PSIC administered vaccinations appropriately. Priority index identified access to the vaccine as an area where performance-improvement efforts should be committed to improve patient satisfaction. Conclusions Patients perceived good overall satisfaction with the pharmacist-run immunization clinic in terms of professionalism and access to vaccination. Priority index identified access to vaccination as a focus for future quality improvement.

Author(s): Glinka, ER; Smith, DM; Johns, ST | Abstract: ObjectivesPatients with HIV infection vaccinated early in the flu season are more likely to contract influenza or influenza-like illness (ILI) compared with those receiving late vaccination. It is known that antibody titres wane over time, particularly among individuals with HIV infection. It is unclear if the timing of influenza vaccination within the flu season affects the probability of an influenza infection later during the flu season. The aim of this study is to evaluate if there is a relationship between the timing of influenza vaccination and incidence of influenza or ILI in patients with HIV infection.MethodsA retrospective cohort study of HIV-infected patients in care at the Department of Veterans Affairs San Diego Healthcare System was conducted from 1 September 2005 to 31 May 2013. Among these patients, we evaluated whether there was a relationship between the timing of influenza vaccination and the incidence of laboratory-confirmed influenza, influenza diagnosed by a physician, or ILI.ResultsPatients who received influenza vaccine early in the season were more likely to contract influenza or ILI than patients who were vaccinated late (P l 0.01). Vaccinated patients who developed influenza or ILI were more likely to do so later in the season (P l 0.01).ConclusionsHIV-infected patients vaccinated early in the flu season were more likely to contract influenza or ILI than those vaccinated later in the season.

In response to a difference in pricing, the San Diego Veterans Administration Medical Center changed its tuberculin preparation from Tubersol to Aplisol in the fall of 2006. Following the change, an increased number of employee skin test conversions was noted. Employee tuberculin skin test converters from 2006 were screened with the QuantiFERON Gold (QFT-G) gamma interferon release assay. Those employees who tested negative by QFT-G were asked to repeat their skin test with both Tubersol and Aplisol tuberculin preparations. Of the new purified protein derivative converters, 12 of 14 returned for repeat testing with QFT-G, and the assay was negative for 83% (10/12), positive for 8% (1/12), and indeterminate for 8% (1/12) of the individuals. Nine of the individuals who were QFT-G negative agreed to repeat skin testing with both tuberculin preparations, and 7/8 (87.5%) demonstrated reactivity with the Aplisol preparation, while 0/8 (0%) reacted to the Tubersol preparation. A change from Tubersol to Aplisol resulted in elevated tuberculin skin test conversion rates that may be due to false-positive reactions. The differences in skin test reactivity between preparations support CDC guidelines that recommend that institutions should not change tuberculin preparations, as doing so may falsely increase the number of positive reactions.