Smith, Jeannina A.

Abstract Background Small colony variants (SCVs) of Staphylococcus aureus (SA) have significant intracellular persistence. Fluoroquinolones demonstrate intracellular activity and are often utilized to treat SCVs. Delafloxacin is a fluroquinolone with increased potency at a low pH, which could lead to enhanced intracellular activity. This study evaluates delafloxacin activity against intracellular MSSA and MSRA SCV isolates.Figure 1.Illustration of SCV co-culture methods Methods Six clinical SCV-SA isolates were co-cultured with human macrophages for 1 hour, allowing for phagocytosis (Fig 1). The remaining extracellular bacteria were removed and antibiotic treatments of delafloxacin, levofloxacin, gentamicin, cefazolin, or vancomycin were added. After 5-hour and 24-hour incubation periods, supernatants were collected for extracellular colony forming unit (CFU) enumeration. Macrophages were washed, lysed, collected, and plated for intracellular bacterial CFU enumeration. All conditions were repeated in triplicate and compared using a Mann Whitney U test.Figure 2.Intracellular SCV-MSSA CFUs Results Delafloxacin resulted in a 1.9-log reduction in intracellular CFUs (p< 0.001) at 5 hours and a 3.4 log reduction (p< 0.001) at 24 hours compared to antibiotic-free control for MSSA strains (Fig 2). Similarly, levofloxacin resulted in a 1.6-log (p< 0.001) and 1.9-log (p< 0.001) reduction in CFUs after 5 and 24 hours, respectively. Delafloxacin was more effective at clearing intracellular bacteria than levofloxacin at 24 hours (p= 0.004). In MRSA-SCV isolates, delafloxacin demonstrated CFU reduction of 2.4-log (p< 0.001) at 5 hours and 4.7-log (p< 0.001) at 24 hours compared to antibiotic-free control (Fig 3). Levofloxacin demonstrated a 1.6-log (p< 0.001) reduction at 5 hours and 1.5-log (p= 0.034) reduction at 24 hours. In comparison to levofloxacin, delafloxacin led to greater reductions in MRSA CFUs at both 5 hours and 24 hours of incubation, 0.85-log (p= 0.028) and 3.2-log (p< 0.001) respectively.Figure 3.Intracellular SCV-MRSA CFUs Conclusion The results demonstrate delafloxacin having greater intracellular activity than levofloxacin and other comparator antibiotics against both MSSA and MRSA SCVs. These results support using delafloxacin to treat recurrent or chronic infections caused by either MSSA or MRSA SCVs and suggest that the observed efficacy may be a result of enhanced intracellular activity. Disclosures All Authors: No reported disclosures

AbstractBackgroundThe optimal treatment for respiratory syncytial virus (RSV) infection in adult immunocompromised patients is unknown. We assessed the management of RSV and other non‐influenza respiratory viruses in Midwestern transplant centers.MethodsA survey assessing strategies for RSV and other non‐influenza respiratory viral infections was sent to 13 centers.ResultsMultiplex polymerase chain reaction assay was used for diagnosis in 11/12 centers. Eight of 12 centers used inhaled ribavirin (RBV) in some patient populations. Barriers included cost, safety, lack of evidence, and inconvenience. Six of 12 used intravenous immunoglobulin (IVIG), mostly in combination with RBV. Inhaled RBV was used more than oral, and in the post‐stem cell transplant population, patients with lower respiratory tract infection (LRTI), graft‐versus‐host disease, and more recent transplantation were treated at higher rates. Ten centers had experience with lung transplant patients; all used either oral or inhaled RBV for LRTI, 6/10 treated upper respiratory tract infection (URTI). No center treated non‐lung solid organ transplant (SOT) recipients with URTI; 7/11 would use oral or inhaled RBV in the same group with LRTI. Patients with hematologic malignancy without hematopoietic stem cell transplantation were treated with RBV at a similar frequency to non‐lung SOT recipients. Three of 12 centers, in severe cases, treated parainfluenza and metapneumovirus, and 1/12 treated coronavirus.ConclusionsTreatment of RSV in immunocompromised patients varied greatly. While most centers treat LRTI, treatment of URTI was variable. No consensus was found regarding the use of oral versus inhaled RBV, or the use of IVIG. The presence of such heterogeneity demonstrates the need for further studies defining optimal treatment of RSV in immunocompromised hosts.