FDA Public Workshop Summary: Advancing Animal Models for Antibacterial Drug Development.

The U.S. Food and Drug Administration (FDA) hosted a public workshop entitled "Advancing Animal Models for Antibacterial Drug Development" on 5 March 2020. The workshop mainly focused on models of pneumonia caused by Pseudomonas aeruginosa and Acinetobacter baumannii The program included discussions from academic investigators, industry, and U.S. government scientists. The potential use of mouse, rabbit, and pig models for antibacterial drug development was presented and discussed.

Community-associated methicillin-resistant Staphylococcus aureus bacteremia and endocarditis among HIV patients: a cohort study.

BACKGROUND: HIV patients are at increased risk of development of infections and infection-associated poor health outcomes. We aimed to 1) assess the prevalence of USA300 community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) among HIV-infected patients with S. aureus bloodstream infections and. 2) determine risk factors for infective endocarditis and in-hospital mortality among patients in this population. METHODS: All adult HIV-infected patients with documented S. aureus bacteremia admitted to the University of Maryland Medical Center between January 1, 2003 and December 31, 2005 were included. CA-MRSA was defined as a USA 300 MRSA isolate with the MBQBLO spa-type motif and positive for both the arginine catabolic mobile element and Panton-Valentin Leukocidin. Risk factors for S. aureus-associated infective endocarditis and mortality were determined using logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI). Potential risk factors included demographic variables, comorbid illnesses, and intravenous drug use. RESULTS: Among 131 episodes of S. aureus bacteremia, 85 (66%) were MRSA of which 47 (54%) were CA-MRSA. Sixty-three patients (48%) developed endocarditis and 10 patients (8%) died in the hospital on the index admission Patients with CA-MRSA were significantly more likely to develop endocarditis (OR = 2.73, 95% CI = 1.30, 5.71). No other variables including comorbid conditions, current receipt of antiretroviral therapy, pre-culture severity of illness, or CD4 count were significantly associated with endocarditis and none were associated with in-hospital mortality. CONCLUSIONS: CA-MRSA was significantly associated with an increased incidence of endocarditis in this cohort of HIV patients with MRSA bacteremia. In populations such as these, in which the prevalence of intravenous drug use and probability of endocarditis are both high, efforts must be made for early detection, which may improve treatment outcomes.

Comparison of the methicillin-resistant Staphylococcus aureus acquisition among rehabilitation and nursing home residents.

OBJECTIVE: To assess risk factors for methicillin-resistant Staphylococcus aureus (MRSA) acquisition among extended care residents focusing on level of care (residential vs rehabilitation) and room placement with an MRSA-positive resident. DESIGN: Prospective cohort study. SETTING: Extended care units at 2 healthcare systems in Maryland. PARTICIPANTS: Four hundred forty-three residents with no history of MRSA and negative MRSA surveillance cultures of the anterior nares and areas of skin breakdown at enrollment. METHODS: Follow-up cultures were collected every 4 weeks and/or at discharge for a period of 12 weeks. Study data were collected by a research nurse from the medical staff and the electronic medical records. Cox proportional hazards modeling was used to calculate adjusted hazards ratios (aHRs) and 95% confidence intervals (CIs). RESULTS: Residents in rehabilitation care had 4-fold higher risk of MRSA acquisition compared with residents in residential care (hazard ratio [HR], 4. [95% CI, 2.2-8.8]). Being bedbound was significantly associated with MRSA acquisition in both populations (residential care, aHR, 4.3 [95% CI, 1.5-12.2]; rehabilitation care, aHR, 4.8 [95% CI, 1.2-18.7]). Having an MRSA-positive roommate was not significantly associated with acquisition in either population (residential care, aHR, 1.4 [95% CI, 0.5-3.9]; rehabilitation care, aHR, 0.5 [95% CI, 0.1-2.2]); based on concordant spa typing, only 2 of 8 residents who acquired MRSA and had room placement with an MRSA-positive resident acquired their MRSA isolate from their roommate. CONCLUSION: Residents in rehabilitation care appear at higher risk and have different risk factors for MRSA acquisition compared to those in residential care.

Prolonged colonization with the methicillin-resistant Staphylococcus aureus strain USA300 among residents of extended care facilities.

We performed a retrospective cohort study (n=129) to assess whether residents of extended care facilities who were initially colonized or infected with the methicillin-resistant Staphylococcus aureus (MRSA) strain USA300 were less likely to have prolonged colonization than were residents colonized or infected with other MRSA strains. We found no difference in prolonged colonization (adjusted odds ratio, 1.1 [95% confidence interval, 0.5-2.4]).

Colonization sites of USA300 methicillin-resistant Staphylococcus aureus in residents of extended care facilities.

BACKGROUND: The anterior nares are the most sensitive single site for detecting methicillin-resistant Staphylococcus aureus (MRSA) colonization. Colonization patterns of USA300 MRSA colonization are unknown. OBJECTIVES: To assess whether residents of extended care facilities who are colonized with USA300 MRSA have different nares or skin colonization findings, compared with residents who are colonized with non-USA300 MRSA strains. METHODS: The study population included residents of 5 extended care units in 3 separate facilities who had a recent history of MRSA colonization. Specimens were obtained weekly for surveillance cultures from the anterior nares, perineum, axilla, and skin breakdown (if present) for 3 weeks. MRSA isolates were categorized as USA300 MRSA or non-USA300 MRSA. RESULTS: Of the 193 residents who tested positive for MRSA, 165 were colonized in the anterior nares, and 119 were colonized on their skin. Eighty-four percent of USA300 MRSA-colonized residents had anterior nares colonization, compared with 86% of residents colonized with non-USA300 MRSA (P= .80). Sixty-six percent of USA300 MRSA-colonized residents were colonized on the skin, compared with 59% of residents colonized with non-USA300 MRSA (P= .30). CONCLUSIONS: Colonization patterns of USA300 MRSA and non-USA300 MRSA are similar in residents of extended care facilities. Anterior nares cultures will detect most--but not all--people who are colonized with MRSA, regardless of whether it is USA300 or non-USA300 MRSA.