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Background The preferred antibiotic salvage regimen for persistent methicillin-resistant Staphylococcus aureus bacteremia (pMRSAB) is unclear. Vancomycin plus ceftaroline (V/C) has demonstrated potent in vitro synergistic activity against MRSA; however, clinical data is limited. Thus, we sought to evaluate V/C salvage therapy for pMRSAB. Methods This was a single-center, retrospective cohort study of patients with MRSAB who received V/C salvage therapy between 1/1/2016-3/10/2021. Adult patients were included if blood cultures (BC) were positive for MRSA for ≥ 72 hours, received anti-MRSA monotherapy initially, and subsequently received V/C ≥ 24 hours. Patients were excluded if they received other anti-MRSA antibiotics within 72 hours of V/C initiation. The primary outcome was time to BC clearance following V/C initiation. Secondary outcomes included 90-day all-cause mortality, microbiological cure, 90-day MRSAB recurrence, and length of stay (LOS). Microbiological cure was defined as BC clearance. Results Of 178 patients identified, 20 were evaluated after inclusion and exclusion criteria were applied. Mean (SD) age and Pitt Bacteremia score were 38.5 (14.5) years and 4.2 (3.1), respectively. Most patients were male (70%), intravenous drug users (65%), and admitted to the intensive care unit (65%). The most common source was intravenous drug use (55%) and the majority had infective endocarditis (70%). All patients received infectious disease consultation and median (IQR) vancomycin AUC:MIC was 527 (454, 611). Source control, if possible, was obtained in most patients (55%). Median (IQR) time to bloodstream clearance from first positive BC and from when ceftaroline was initiated was 9.7 (8.4, 10.2) and 2.4 (1.5, 3.1) days, respectively. 90-day all-cause mortality, microbiological cure, and 90-day MRSAB recurrence occurred in 35%, 95%, and 5% of patients, respectively. Median (IQR) LOS was 25 (14.5, 32.0) days. Conclusion To our knowledge, this is the largest cohort to evaluate V/C for pMRSAB. Patients were medically complex; however, median time to MRSAB clearance following ceftaroline initiation was < 2.5 days and microbiological cure was obtained in nearly all patients. V/C may represent a potential salvage regimen for pMRSAB. Disclosures Wesley D. Kufel, PharmD, Melinta (Research Grant or Support)Merck (Research Grant or Support)Theratechnologies, Inc. (Advisor or Review Panel member) Jeffrey Steele, Pharm.D., Paratek Pharmaceuticals (Advisor or Review Panel member)

Background Prevention interventions for coronavirus disease (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), are currently limited to non-pharmaceutical strategies. Observational and laboratory data suggested that hydroxychloroquine (HCQ) had biologic activity against SARS-CoV-2. A blinded trial of HCQ in persons with confirmed exposure and virologic and clinical endpoints is needed. Methods We conducted a national, householdrandomized, double-blind, controlled trial of HCQ post-exposure prophylaxis, with entirely remote study procedures. We enrolled close contacts exposed to persons with SARS-CoV-2 infection in the past 96 hours. Participants were randomized to either HCQ (400 mg daily for three days followed by 200 mg daily for eleven days) or ascorbic acid (500 mg followed by 250 mg daily), as a placebo-equivalent control. Participants self-collected mid-turbinate swabs daily (days 1–14) for SARS-CoV-2 PCR testing. The primary outcome was PCR-confirmed, incident SARS-CoV-2 infection among persons SARS-CoV-2 negative at enrollment. Symptoms were assessed using criteria from the US CDC. Results From March-August 2020, 623 households were randomized; 311 households (381 participants) to the HCQ group and 312 households (400 participants) to the control group. Ninety- one percent of participants were retained up to day 14 and 9,595 of 10,588 (91%) of swabs were tested. Among participants who were SARS-CoV-2 negative at baseline (n=626/781, 80%), the cumulative incidence of SARS-CoV-2 was 14.5% (95% CI: 11.6–17.4) and the cumulative incidence of COVID-19 symptoms was 11.6% (95% CI: 8.9–14.2) at day 14. By day 14, there was no difference between the HCQ group and control group in SARS-CoV-2 acquisition (46 vs. 43 events, aHR= 0.99, 95% CI 0.64–1.52, p=0.95) or symptomatic disease (40 vs. 32 events, aHR= 1.23, 95% CI: 0.76–1.99, p=0.40). The adverse event frequency was similar between groups (59 [15.5%] participants in the HCQ and 45 [11.3%] in the control group, p=0.092). Cumulative incidence of RT-PCR-confirmed SARS-CoV-2 infection among close contacts of diagnosed cases, by study group Conclusion This randomized, double-blind, controlled trial among persons with recent exposure and high incidence of SAR-CoV2 provides strong evidence that HCQ post-exposure prophylaxis did not prevent SARS-CoV-2 infection or modify clinical disease. Disclosures Anna Bershteyn, PhD, Bill and Melinda Gates Foundation (Grant/Research Support)Gates Ventures (Consultant)National Institutes of Health (Grant/Research Support) Kristopher M. Paolino, MD, MTM&H, Nothing to disclose Raphael J. Landovitz, MD, MSc, Gilead (Advisor or Review Panel member)Merck (Advisor or Review Panel member)Roche (Other Financial or Material Support, Speaker Honoraria) Anna Wald, MD, MPH, Aicuris (Individual(s) Involved: Self): Consultant; Gilead (Individual(s) Involved: Self): Consultant; GlaxoSmithKline (Individual(s) Involved: Self): Scientific Research Study Investigator; Merck (Individual(s) Involved: Self): DSMB participation; provision of vaccine for a study, Other Financial or Material Support; Sanofi (Individual(s) Involved: Self): Scientific Research Study Investigator; X-Vax (Individual(s) Involved: Self): Consultant Helen Y. Chu, MD MPH, Cepheid (Grant/Research Support)Ellume (Grant/Research Support)Glaxo Smith Kline (Consultant)Merck (Consultant)Sanofi-Pasteur (Grant/Research Support)

Popular probiotics contain Lactobacillus, Bifidobacterium, and Streptococcus. Lactobacillus is a gram-positive rod-shaped bacterium that colonizes human oropharyngeal, gastrointestinal, and female urogenital tracts. Although lactobacilli are generally nonpathogenic, they have been implicated in uncommon cases of infection and have the potential to cause bacteremia, endocarditis, endometritis, pulmonary abscesses, and orogastrointestinal abscesses, especially in the immunocompromised. We report a case of Lactobacillus infection in a diabetic patient that occurred 2 weeks after wisdom tooth extraction. The only bacterium found was Lactobacillus, possibly related to her diet of yogurt and smoothies after the tooth extraction.

Hantaan virus (HTNV) and Puumala virus (PUUV) are pathogenic hantaviruses found in Asia and Europe, respectively. DNA vaccines targeting the envelope glycoproteins of these viruses have been constructed and found to elicit neutralizing antibodies when delivered to humans by various technologies including intramuscular electroporation. Here, we report findings from a Phase 2a clinical trial of a combined HTNV/PUUV DNA vaccine delivered at varying doses and administration schedules using the Ichor Medical Systems TriGrid intramuscular electroporation delivery technology. The study was designed to characterize the effects of DNA vaccine dose and number of administrations on the frequency and magnitude of immunological response. Subjects (n = 120) were divided into four cohorts. Cohorts 1 and 2 received a dose of 2 mg of DNA (1 mg per plasmid), and cohorts 3 and 4 received a dose of 1 mg of DNA (0.5 mg per plasmid) each vaccination. Each of the four cohorts received a series of four administrations (days 0, 28, 56 and 168). For cohorts 1 and 3, the DNA vaccine candidate was delivered at each of the four administrations. For cohorts 2 and 4, in order to maintain blinding, subjects received the DNA vaccine on days 0, 56 and 168, but on day 28 received only the phosphate buffered saline vehicle rather the DNA vaccine. Sera were collected on days 0, 28, 56, 84, 140, 168, 196, 252 and 365 and evaluated for the presence of neutralizing antibodies by PUUV and HTNV pseudovirion neutralization assays (PsVNAs). Day 84 was also evaluated by a plaque reduction neutralization test (PRNT). Overall the PsVNA50 geometric mean titers (GMTs) and seropositivity rates among cohorts were similar. Cohort 3 exhibited the highest frequency of subjects that became seropositive to both PUUV and HTNV after vaccination, the highest peak GMT against both viruses, and the highest median titers against both viruses.

Background Ceftriaxone and azithromycin are common empiric antibiotics for community-acquired pneumonia (CAP). Despite low suspicion for atypical infection, azithromycin is often continued for a full course. Negative laboratory data for atypical bacteria may assist with azithromycin de-escalation. Thus, a pharmacist-driven azithromycin de-escalation protocol was implemented for immunocompetent, non-intensive care unit (ICU) patients treated for CAP. The primary outcome was to compare azithromycin duration before and after protocol implementation. Secondary outcomes included hospital length of stay (LOS) and all-cause 30-day readmission. Methods This was a single-center, quasi-experimental study of hospitalized, non-ICU patients treated with azithromycin and a beta-lactam for CAP. The pre- and post-intervention cohorts were from 07/01/2018–04/30/2019 and 07/01/2019–04/30/2020, respectively. Patients were included if they were ≥18 years old, diagnosed with CAP, and had a negative Legionella pneumophila urinary antigen and negative nasopharyngeal swab PCR for Mycoplasma pneumoniae and Chlamydia pneumoniae. Patients were excluded if they were immunocompromised, admitted to an ICU, prescribed azithromycin for an alternative indication, or had evidence of atypical bacteria. Results After exclusion criteria were applied, 90 and 100 patients were included in the pre- and post-intervention cohorts, respectively. Demographic and clinical characteristics were mostly similar between cohorts. This initiative was associated with a statistically significant decrease in azithromycin duration (2 days (IQR 1–2.75) vs. 5 days (IQR 3–6), p < 0.001) and hospital LOS (3 days (IQR 2–5) vs. 5 days (IQR 3–8.25), p < 0.001). No statistically significant difference was observed for all-cause 30-day readmission (14 days (15.6%) vs 13 days (13.0%), p=0.614). Conclusion Implementation of a pharmacist-driven azithromycin de-escalation protocol for CAP was associated with reduced azithromycin duration and hospital LOS, but not all-cause 30-day readmission. Disclosures Jeffrey Steele, PharMD, Paratek Pharmaceuticals (Advisor or Review Panel member) Wesley D. Kufel, PharmD, Melinta (Research Grant or Support)Merck (Research Grant or Support)Theratechnologies, Inc. (Advisor or Review Panel member)

Background One of the goals of the Affordable Care Act is to decrease readmission rates, which lead to wasting of resources and are associated with worse patient outcomes. While widely adhered to, there is no published research to support the practice of delaying discharge if the patient exhibits fever or hypothermia in the previous 24 hours. Our study quantifies the effect of abnormal body temperature before discharge on the readmission rate. Methods Retrospective analysis of the minimal (Tmin) and maximal (Tmax) body temperatures during the last 24 hrs before discharge of all patients over 1 year period from our tertiary medical center were analyzed with T-test, ANOVA, uni-and multivariate logistic regression. Fever was defined as Tmax > 100.2F(2SDs from mean Tmax), hypothermia as Tmin < 96.7F(2SDs from mean Tmin). Results Descriptive analysis of the data from 19,038 inpatients are featured in Table 1 and Figure 1. The overall readmission rate was 10.2% (highest for General Medicine and Pediatrics); 4.7% of patients had an abnormal temperature 24 hrs before discharge; body temperature declined with age. ANOVA showed that 1st, the average number of days to readmission was not different between those with fever, hypothermia, and normothermia (mean+/-SD: 10.6+/-8.6; 12.1+/-8.6; 12.5+/-8.1, respectively); 2nd that the rate of readmission was not different between these groups, although there was trend for higher readmission among normothermic patients (2.9%; 0.3%; 7%, respectively). Table 2 features regression analyses that model readmission. Univariate analysis revealed that higher Tmax and age are associated with lower readmission probability. Both uni- and multivariate analysis showed that the presence of fever is associated with lower readmission probability and that compared with General Medicine, the other major primary services have lower readmission probability, when correcting for all the other listed variables. Figure 1 Conclusion Our data clearly showed that abnormal body temperature measured within 24 hrs before discharge is not useful for predicting the chance for readmission. Therefore, delaying patients’ discharge based on Tmax or Tmin alone, taken outside the specific clinical context, may lead to wasting of hospital resources. Disclosures All Authors: No reported disclosures

Plasmodium vivax malaria requires a 2-week course of primaquine (PQ) for radical cure. Evidence suggests that the hepatic isoenzyme cytochrome P450 2D6 (CYP2D6) is the key enzyme required to convert PQ into its active metabolite.CYP2D6 genotypes and phenotypes of 550 service personnel were determined, and the pharmacokinetics (PK) of a 30-mg oral dose of PQ was measured in 45 volunteers. Blood and urine samples were collected, with PQ and metabolites were measured using ultraperformance liquid chromatography with mass spectrometry.Seventy-six CYP2D6 genotypes were characterized for 530 service personnel. Of the 515 personnel for whom a single phenotype was predicted, 58% had a normal metabolizer (NM) phenotype, 35% had an intermediate metabolizer (IM) phenotype, 5% had a poor metabolizer (PM) phenotype, and 2% had an ultrametabolizer phenotype. The median PQ area under the concentration time curve from 0 to ∞ was lower for the NM phenotype as compared to the IM or PM phenotypes. The novel 5,6-ortho-quinone was detected in urine but not plasma from all personnel with the NM phenotype.The plasma PK profile suggests PQ metabolism is decreased in personnel with the IM or PM phenotypes as compared to those with the NM phenotype. The finding of 5,6-ortho-quinone, the stable surrogate for the unstable 5-hydroxyprimaquine metabolite, almost exclusively in personnel with the NM phenotype, compared with sporadic or no production in those with the IM or PM phenotypes, provides further evidence for the role of CYP2D6 in radical cure.NCT02960568.

Haemorrhagic fever with renal syndrome (HFRS) is endemic in Asia, Europe and Scandinavia, and is caused by infection with the hantaviruses Hantaan (HTNV), Seoul (SEOV), Puumala (PUUV), or Dobrava (DOBV) viruses. We developed candidate DNA vaccines for HFRS expressing the Gn and Gc genes of HTNV or PUUV and evaluated them in an open-label, single-centre Phase 1 study. Three groups of nine participants each were vaccinated on days 0, 28 and 56 with the DNA vaccines for HTNV, PUUV, or a mixture of both vaccines using the Ichor Medical Systems TriGrid™ Intramuscular Delivery System. All vaccinations consisted of a total dose of 2.0 mg DNA in an injected volume of 1 mL saline. For the combined vaccine, the mixture contained equal amounts (1.0 mg) of each DNA vaccine. There were no study-related serious adverse events. Neutralizing antibody responses were measured by a plaque reduction neutralization test. Neutralizing antibody responses were detected in five of nine and seven of nine individuals who completed all three vaccinations with the HTNV or PUUV DNA vaccines, respectively. In the combined vaccine group, seven of the nine volunteers receiving all three vaccinations developed neutralizing antibodies to PUUV. The three strongest responders to the PUUV vaccine also had strong neutralizing antibody responses to HTNV. These results demonstrate that the HTNV and PUUV DNA vaccines delivered by electroporation separately or as a mixture are safe. In addition, both vaccines were immunogenic, although when mixed together, more participants responded to the PUUV than to the HTNV DNA vaccine.