Forty-eight-week efficacy and safety and early CNS tolerability of doravirine (MK-1439), a novel NNRTI, with TDF/FTC in ART-naive HIV-positive patients

INTRODUCTION: Doravirine (DOR) is an investigational NNRTI (aka MK-1439) that retains activity against common NNRTI-resistant mutants. We have previously reported the Part 1 results from a two-part, randomized, double-blind, Phase IIb study in ART-naïve HIV-1-positive patients (1). At doses of 25, 50, 100 and 200 mg qd, DOR plus open-label tenofovir/emtricitabine (TDF/FTC) demonstrated potent antiretroviral activity comparable to EFV 600 mg qhs plus TDF/FTC and was generally well tolerated at week 24. DOR 100 mg was selected for use in patients continuing in Part 1 and those newly enrolled in Part 2. METHODS: Patients receiving DOR 25, 50 or 200 mg in Part 1 were switched to 100 mg after dose selection. In Part 2, 132 additional patients were randomized 1:1 to DOR 100 mg qd or EFV 600 mg qhs (each with TDF/FTC). We present week 48 efficacy and safety results for all patients in Part 1, and early (week 8) CNS tolerability only for patients randomized to DOR 100 mg or to EFV in Parts 1 and 2 combined. The primary safety endpoint is the % of patients with pre-specified CNS events (all causality) by week 8 for DOR 100 mg qd vs EFV (Parts 1 + 2 combined). RESULTS: Part 1 week 48 efficacy and safety results are shown below. CONCLUSIONS: In ART-naïve, HIV-1-positive patients also receiving TDF/FTC, DOR 100 mg qd demonstrated potent antiretroviral activity and immunological effect at week 48 and was generally safe and well tolerated. Patients who received DOR 100 mg qd had significantly fewer treatment-emergent CNS AEs by week 8 than those who received EFV

Antibiotic susceptibilities of bacteria isolated within the oral flora of Florida blacktip sharks: guidance for empiric antibiotic therapy.

Sharks possess a variety of pathogenic bacteria in their oral cavity that may potentially be transferred into humans during a bite. The aim of the presented study focused on the identification of the bacteria present in the mouths of live blacktip sharks, Carcharhinus limbatus, and the extent that these bacteria possess multi-drug resistance. Swabs were taken from the oral cavity of nineteen live blacktip sharks, which were subsequently released. The average fork length was 146 cm (±11), suggesting the blacktip sharks were mature adults at least 8 years old. All swabs underwent standard microbiological work-up with identification of organisms and reporting of antibiotic susceptibilities using an automated microbiology system. The oral samples revealed an average of 2.72 (±1.4) bacterial isolates per shark. Gram-negative bacteria, making up 61% of all bacterial isolates, were significantly (p<0.001) more common than gram-positive bacteria (39%). The most common organisms were Vibrio spp. (28%), various coagulase-negative Staphylococcus spp. (16%), and Pasteurella spp. (12%). The overall resistance rate was 12% for all antibiotics tested with nearly 43% of bacteria resistant to at least one antibiotic. Multi-drug resistance was seen in 4% of bacteria. No association between shark gender or fork length with bacterial density or antibiotic resistance was observed. Antibiotics with the highest overall susceptibility rates included fluoroquinolones, 3rd generation cephalosporins and sulfamethoxazole/trimethoprim. Recommended empiric antimicrobial therapy for adult blacktip shark bites should encompass either a fluoroquinolone or combination of a 3rd generation cephalosporin plus doxycycline

ANTIBIOTIC SUSCEPTIBILITIES OF BACTERIA ISOLATED WITHIN THE ORAL FLORA OF FLORIDA BLACKTIP SHARKS: GUIDANCE FOR EMPIRIC ANTIBIOTIC THERAPY

Objective. Identify the bacteria present and extent of multi-drug resistance in the oral flora of live blacktip sharks in order to provide definitive microbiologically based guidance for appropriate empiric antimicrobial therapy for severe shark bite victims Background. Several studies have identified pathogenic bacteria in marine animals, including sharks. Of great concern is the level of antibiotic resistance observed in these studies, including resistance to broad-spectrum antibiotic reserved for multi-drug resistant infections. Methods. Blacktip sharks were caught and released from the beach in South Florida after collecting a swab of its oral cavity. All swabs underwent standard microbiological work-up with identification of organisms and reporting of antibiotic susceptibilities was performed using an automated microbiology system. Results. Results from 18 sharks were analyzed and revealed an average of 2.72 bacterial isolates per shark. Gram-negative bacteria were significantly more common than gram-positive (61 vs 39%, P \u3c 0.001) and the most common organisms were Vibrio sp. (28%), various coagulase-negative Staphylococcus sp. (16%), and Pasteurella sp. (12%). The overall resistance rate was 17% for all antibiotics tested with nearly 43% of bacteria resistant to at least one antibiotic. Multi-drug resistance was seen in 4% of bacteria. No isolates of Staphylococcus aureus were methicillin-resistant. The level of antibiotic resistance observed in Florida blacktip sharks is comparable to that of published literature. Antibiotics with the highest susceptibility rates included fluoroquinolones, 3rd generation cephalosporins and sulfamethoxazole/trimethoprim. Conclusion. The level of antibiotic resistance observed in our study is comparable to that of similarly conducted studies. For severe shark bite victims where the suspected species is blacktip, we recommend empiric antimicrobial with either a fluoroquinolone or combination of a 3rd generation cephalosporin plus doxycycline. Grants. The research was supported by Nova Southeastern University\u27s Health Profession Division Research Grant and St. Mary\u27s Medical Center

Comparison bacteriology and antibiotic resistant within the oral flora of multiple shark species using data from previously published literature [15].

a<p>Calculated using susceptibility data for only the antibiotics tested in both current study and Interaminense et al. If antibiotic susceptibility testing indicated an organism was intermediate, it was deemed resistant.</p

Level of antibiotic resistance in the oral flora of blacktip sharks.

<p>Level of antibiotic resistance in the oral flora of blacktip sharks.</p

Bacteria isolated in the oral cavity of blacktip sharks^a.

a<p>Percentages may not add up to 100% due to rounding.</p

Gender comparison of bacteria and antibiotic resistance.

<p>All results presented as mean number per shark±SD (95% CI).</p

Antibiotic susceptibilities (%) for gram-positive bacteria isolated in the oral cavity of blacktip sharks^a.

<p>CoNS: Coagulase-negative Staphylococcus sp.</p>a<p><i>Micrococcus sp</i>., <i>Bacillus sp</i>., and alpha-hemolytic <i>Streptococcus sp</i>. not included due to exclusion of susceptibility testing.</p>b<p>Includes non-speciated coagulase-negative <i>Staphylococcus sp</i>., <i>S. cohnii-urea</i>, <i>S. epidermidis</i>, <i>S. hominis</i>, and <i>S. scuiri.</i></p

Antibiotic susceptibilities (%) for gram-negative bacteria isolated in the oral cavity of blacktip sharks^a.

a<p>Pasteurella spp not included in table due to exclusion of susceptibility testing.</p>b<p>Reported susceptibility is for 2 of the 14 isolates.</p>c<p>Reported susceptibility is for 4 of the 14 isolates.</p