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Background. When hospital-acquired or ventilator-associated bacterial pneumonia (HABP/VABP) is caused by gram-positive and gram-negative pathogens or both (mixed infections), the adequacy of gram-negative coverage (GNC) can confound the assessment of a gram-positive agent under study. This analysis examines the influence of gram-negative infections and the adequacy of GNC on clinical efficacy and all-cause mortality in the telavancin HABP/VABP phase 3 ATTAIN trials (Assessment of Telavancin for Treatment of Hospital-Acquired Pneumonia). Methods. This post hoc analysis evaluated 3 patient groups from ATTAIN: (1) gram-positive-only infections, (2) gram-positive-only and mixed infections-adequate GNC, and (3) gram-negative-only infections and mixed infections with inadequate GNC. For each, clinical efficacy at test of cure and all-cause mortality at day 28 were compared for telavancin and vancomycin. Results/Conclusions. In the ATTAIN safety population therewere 16more deaths in the telavancin arms than in the vancomycin arms. Of these, 13 were in patients with gram-negative-only infections (n = 9) or with mixed infections and inadequate GNC (n = 4) and all had estimated baseline creatinine clearances of <30ml/min. Based on this analysis, clinical response and all-cause mortality could be confounded because there were more patients with gram-negative pathogens at baseline and more patients received inadequate treatment of these gram-negative infections in the telavancin groups. [ABSTRACT FROM AUTHOR]

Pharmacokinetic parameters were calculated from plasma and urine latamoxef (‘Moxalactam’) levels determined by HPLC assay after single and multiple intramuscular (im) and single intravenous (iv) doses of 500 mg given to eight healthy volunteers. After im administration, systemic bio-availability was 92% after both the first and sixth doses. Peak plasma concentration was 18 mg/l (first dose) and 22 mg/l (sixth dose), reached at 1.2 h and 1.3 h respectively. The terminal phase half-lives were 2.5 h and 2.7 h respectively. After iv administration, the initial phase plasma half-life was 0.23 h and the terminal phase half-life, 2.4 h. Plasma clearance was 87.0 ml/min. The steady state distribution volume was 210 ml/kg. After iv administration, 72% of the dose was found in the urine in the first 24 h. Urinary clearance was 66 ml/min (iv dose) and 63 ml/min (sixth im dose). Most systemic infections will permit eight hourly dosing with 500 mg im or iv. Many urinary infections will be best treated with im administration, rather than iv administration. [ABSTRACT FROM PUBLISHER]

Background Patients with serious bacterial infections (SBI), identified as bone and joint infections (BJI), bacteremia/endocarditis, and central nervous system (CNS) infections are frequently discharged on outpatient parenteral antimicrobial therapy (OPAT). They account for 48% of all infections treated in our network of Infectious Disease (ID) physician office infusion centers (POICs). Care for these patients poses risks and challenges to ensure safe and successful outcomes while avoiding hospitalizations. This study examines clinical outcomes and complications of our SBI patients receiving OPAT in ID POICs. Methods All patients were identified with SBI receiving OPAT in 2017 from 14 POICs. A group of 250 patients were randomly selected by incidence of diagnosis and a retrospective chart review performed. Demographics, treatment regimen, clinical outcomes, adverse drug reactions (ADRs) and unplanned hospitalizations during OPAT were collected. Clinical success was defined as clinical cure or improvement at completion of OPAT. Patients were included who were hospitalized for <7 days and subsequently completed OPAT. ADRs leading to hospitalization or discontinuation of OPAT were deemed serious. Descriptive statistics were used for distribution of variables. Results SBI patients included BJI (n = 175), bacteremia/endocarditis (n = 60) and CNS infections (n = 15) as described in Table 1. Successful clinical outcomes were reported in 224 patients (89.6%) after a mean duration of OPAT of 32±20 days. Of these, 15 patients (6.7%) were hospitalized during OPAT and returned to the POIC for a successful clinical outcome. Clinical success rates for BJI, bacteremia/endocarditis and CNS infections were 89.1%, 91.6% and 86.7%, respectively. The primary reason for nonfavorable outcomes was worsening of infection (15/26, 58%). Serious ADRs were reported in 12 patients (4.8%) with 6 (2.4%) leading to hospitalization. Unplanned hospitalizations during OPAT occurred in 33 patients (13.2%) with the majority (21/33, 64%) related to disease. ADRs and hospitalizations compare favorably to data previously reported. (Schmidt et al. OFID 16.4, 2017). Conclusion Patients with serious bacterial infections had high success rates when treated by an ID physician in infusion centers. Adverse events and unplanned hospitalization rates were low. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Ibalizumab-uiyk (IBA) was recently approved for the treatment of multi-drug-resistant HIV-1 infection in patients (pts) failing other antiretroviral regimens. Clinical trial data demonstrated a decrease in HIV-1 viral load in 83% and 43% of patients (n = 40) receiving IBA for 2 and 25 weeks (weeks), respectively. Real-world post marketing data are needed. This pilot study reports the experience of IBA utilization in POICs. Methods Medical records of patients receiving intravenous IBA from approval through April 2019 were reviewed. Data collected include demographics, infection and treatment history, IBA regimen and adverse events. Plasma HIV-1 RNA viral load (log10 copies/mL) and CD4 count (cells/µL) were collected at baseline and as available during therapy. Based on available follow-up (FU) labs, response was assessed at 4–10 weeks (FU 1), 14–22 weeks (FU 2), and 24–37 weeks (FU 3). Results Nine patients (mean age: 48 ± 11 years, 67% male) from 7 POICs received IBA for a median duration of 33 weeks (range 4–43). Median length of HIV-1 diagnosis was 22 years (range 8–25). Resistance to ≥1 drug in at least 3 drug classes was reported in 56%. All patients received at least one concurrent anti-retroviral agent. IBA was initiated at 2000 mg followed by 800 mg every 2 weeks. All patients received infusions as scheduled (151 total infusions) except for one requiring a second loading dose. Baseline mean CD4 count and viral load were 49 cells/µL and 4.9 log10 copies/mL, respectively. Labs obtained at FU 1 indicated a decrease in viral load of at least 0.5 log10 copies/mL in 6/8 patients (75%); a mean reduction of 2.1 ± 1.8 log10 copies/mL (Table 1). Mean HIV-1 titers available for patients at FU 2 (n = 6) and FU 3 (n = 7) were 3.1 ± 2.0 and 3.2 ± 2.6 log10 copies/mL, respectively. Mean CD4 counts were 65 ± 57 cells/µL at FU 1, 96 ± 61 cells/µL at FU 2 and 88 ± 82 cells/µL at FU 3. Adverse events were reported in 8 patients (89%), most common itching/rash, diarrhea and abdominal pain. None resulted in discontinuation of IBA. Conclusion This study confirms the antiviral activity of IBA in patients with advanced HIV-1 infection in the real-world setting. We observed well-tolerated therapy with an early reduction in HIV-1 viral load of 75%, followed by a 43% reduction ≥24 weeks, consistent with the clinical trial. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background The Health-Related Quality of life (HR-QOL) instrument, the Cdiff32, allows studies on QOL changes associated with recurrent CDI. An ongoing real-world study of bezlotoxumab (BEZ) provided a unique opportunity to study anxiety-related HR-QOL in patients at high risk for recurrent CDI using the anxiety sub-domain of Cdiff32. The aims of this study were to assess baseline anxiety-related HR-QOL based on the number of prior episodes of CDI and to evaluate changes in patients with or without recurrence. Methods Patients at high risk for recurrent CDI given BEZ were administered the anxiety sub-domain questions of the Cdiff32 prior to infusion and at approximately 90 days after administration (0 = worst anxiety; 100 = no anxiety). The number of prior episodes of CDI were collected, along with demographics and co-morbid conditions. Patients were followed for 90 days for CDI recurrence, which was defined as new onset of diarrhea requiring CDI-active antibiotics. Results There were 107 patients evaluated, aged 68 ± 14 years (mean ± SD) with multiple co-morbid conditions (mean Charlson: 4 ± 3) and multiple previous CDI episodes (3 ± 1 episodes). Fourteen patients (13%) experienced a further CDI recurrence within 90 days following BEZ. Overall, baseline anxiety HR-QOL was 29 ± 22. Risk factors for lower baseline anxiety-related HR-QOL included immunocompromised conditions (P < 0.046) and receipt of a proton pump inhibitor (P < 0.018). Compared with patients with primary CDI disease (Score: 35 ± 20), baseline anxiety HR-QOL was worse with subsequent prior recurrences (Score: 26 ± 23) for CDI episodes 2–4, and then improved for subsequent episodes (Score: 38 ± 22). Anxiety-related HR-QOL improved by a mean of 32 ± 25 points compared with patients that experienced a further recurrence where HR-QOL declined (P < 0.0001). Results were confirmed in a multivariate model controlling for Charlson score and chronic renal failure. Conclusion Poor anxiety-related HR-QOL was observed at baseline in all patients regardless of number of prior episodes. QOL improved 90 days after BEZ infusion in patients without further recurrences of CDIs and worsened in patients with a subsequent recurrence. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]