Pharmacokinetics and safety of daptomycin administered subcutaneously in healthy volunteers: a single-blinded randomized crossover trial.

BACKGROUND: Daptomycin stands as a key IV antibiotic in treating MRSA infections. However, patients facing challenges with difficult venous access require alternative administration routes. This study aimed to evaluate the pharmacokinetic (PK) profile and safety of subcutaneous (SC) daptomycin. PATIENTS AND METHODS: In a two-period, two-treatment, single-blind crossover Phase I trial (ClinicalTrials.gov NCT04434300), participants with no medical history received daptomycin (10 mg/kg) both IV and SC in a random order, with a minimum 2 week washout period together with matched placebo (NaCl 0.9%). Blood samples collected over 24 h facilitated PK comparison. Monte Carlo simulations assessed the PTA for various dosing regimens. Adverse events were graded according to Common Terminology Criteria for Adverse Events(CTCAE) v5.0. RESULTS: Twelve participants (aged 30.9 ±â€Š24.4 years; 9 male,75%) were included. SC daptomycin exhibited delayed (median Tmax 0.5 h for IV versus 4 h for SC) and lower peak concentration than IV (Cmax = 132.2 ±â€Š16.0 µg/mL for IV versus 57.3 ±â€Š8.6 µg/mL for SC; P < 0.001). SC AUC0-24 (937.3 ±â€Š102.5 µg·h/mL) was significantly lower (P = 0.005) than IV AUC0-24 (1056.3 ±â€Š123.5 µg·h/mL) but was deemed bioequivalent. PTA demonstrated target AUC0-24 attainment for 100% of simulated individuals, for both 8 and 10 mg/kg/24 h SC regimens. Adverse events (AEs) related to SC daptomycin were more frequent than for SC placebo (25 versus 13, P = 0.016). No serious AEs were reported. CONCLUSIONS: Single-dose SC daptomycin infusion proved to be safe, exhibiting a bioequivalent AUC0-24 compared with the IV route. The SC route emerges as a potential and effective alternative when IV administration is not possible.

Bioavailability of dissolved and crushed single tablets of bictegravir, emtricitabine, tenofovir alafenamide in healthy adults: the SOLUBIC randomized crossover study.

BACKGROUND: Crushing or dissolving bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) tablets is not recommended because there are no data supporting this practice. METHODS: A crossover, randomized trial in healthy adults (NCT04244448) investigated the bioavailability of two off-label uses of BIC/TAF/FTC (50/200/25 mg), dissolved in water or crushed in apple compote, compared with the solid tablet. Pharmacokinetic (PK) parameters were estimated from sequential intensive plasma antiretroviral concentrations over a 72 h period post dose. Bioequivalence was met if the 90% CIs of the geometric least-squares means ratios comparing BIC/TAF/FTC exposures (AUC and Cmax) from the experimental phases were within 80%-125% of the reference. RESULTS: Eighteen subjects participated in each of the three phases. Dissolved tablet Cmax geometric mean ratio (90% CI) for BIC/TAF/FTC was 105% (93-119)/97% (87-108)/96% (74-124), respectively. Dissolved tablet AUC geometric mean ratio (90% CI) for BIC/TAF/FTC was 111% (100-122)/100% (94 to 105)/99% (81 to 120), respectively. Crushed tablet Cmax geometric mean ratio (90%) CI for BIC/TAF/FTC was 110% (97 to 124)/70% (63-78)/66% (51-85), respectively. Crushed tablet AUC geometric mean ratio (90%) CI for BIC/TAF/FTC was 107% (96-118)/86% (82-91)/84% (69-103), respectively. CONCLUSIONS: Crushing BIC/TAF/FTC tablets may lead to suboptimal emtricitabine and tenofovir alafenamide drug exposures. Dissolving BIC/TAF/FTC in water may be acceptable if the tablet cannot be swallowed whole.

Enterocytozoon bieneusi Microsporidiosis in Stem Cell Transplant Recipients Treated with Fumagillin

Enterocytozoon bieneusi microsporidiosis is an emerging disease in immunocompromised patients. We report 2 cases of this disease in allogeneic hematopoietic stem cell transplant patients successfully treated with fumagillin. Thrombocytopenia occurred but without major adverse events. Modifications of immunosuppression could be avoided when E. bieneusi is rapidly identified and fumagillin therapy is started promptly.

Mycobacterium genavense Infections in Immunocompromised Patients Without HIV: Case Series of Solid Organ Transplant Patients and Literature Review.

Background: Mycobacterium genavense infection is rare and can occur in immunocompromised patients without human immunodeficiency virus (HIV). Methods: We describe 2 cases of M genavense infection in solid organ transplant (SOT) recipients, and we performed a literature review of immunocompromised patients without HIV. Results: Fifty-two cases are reported. Predisposing factors were receipt of SOT (40.4%) and autoimmune disease (36.5%). Infection was disseminated in 86.5% of cases. Organs involved were lymph nodes (72.3%), gastrointestinal tract (56.5%), lung (35.5%), and bone marrow (28.8%). Most patients were treated with at least 3 antimycobacterial agents (98%), with a clinical cure achieved in 54.9%. In multivariate analysis, lack for cure was associated with age of the time infection (odds ratio [OR], 15.81 [95% confidence interval {CI}, 2.92-152.93]; P = .011) and positive bone marrow culture (OR, 1.05 [95% CI, 1.01-1.12]; P = .042). Conclusions: Mycobacterium genavense infection is a rare and generally disseminated disease with a poor prognosis. Optimal treatment regimen and its duration remain to be defined.

Valvular and infection-associated risk factors as criteria to guide the use of echocardiography in patients with native joint infections.

BACKGROUND: Native joint and bone infections (NJBI) are associated with infective endocarditis (IE) in 15% of cases. There are no studies analyzing the use of cardiac imaging in cases of NJBI. The objective of this study was to identify factors associated with echocardiography suggestive of IE in patients with NJBI. METHODS: This medical records review was conducted in patients hospitalized for NJBI between 2007 and 2017 in Rheumatology and Infectious Diseases departments of 2 university hospitals. Patients included had a microbiologically proven NJBI during their hospitalization. RESULTS: In this cohort of 546 patients, median age 66 years, echocardiography was suggestive of IE in 66 (12%). In multivariate analysis, factors associated with echocardiography suggestive of IE were 2 or more positive blood cultures (OR 11.55 (CI95% 3.24-74.20)), cardiac conditions with a high risk of IE (OR 7.34 (CI95% 2.95-18.61)), unknown heart murmur (OR 4.59 (CI95% 1.79-11.74)), multifocal infection (OR 2.26 (CI95% 1.21-4.23)) and an infection due to S. bovis (OR 3.52 (CI95% 1.26-9.79)). The factor associated with the absence of an echocardiography evocative of IE was infection due to unconventional bacteria for IE (OR 0.13 (CI95% 0.01-0.76)). According to the factors associated with echocardiography evocative of IE, we propose the Normandy score based on three kinds of data: cardiac condition, bacterial strain and NJBI mechanism. Echocardiography should be realized when this score, whose negative predictive value is 100% CI95% (98-100%) for prescription of echocardiography, is more than zero. CONCLUSIONS: A score based on valvular condition, bacterial strain and NJBI mechanism could guide clinicians in prescribing echocardiography during NJBI with an excellent negative predictive value.

Average adherence to boosted protease inhibitor therapy, rather than the pattern of missed doses, as a predictor of HIV RNA replication.

Consecutive missed doses may differentially impact the efficacy of antiretroviral therapy associated with the use of a nonnucleoside reverse-transcriptase inhibitor (NNRTI) and a ritonavir-boosted protease inhibitor (PI). In a cohort of 72 subjects receiving a boosted PI, average adherence to dosage was a better predictor of human immunodeficiency virus (HIV) replication than was the duration or frequency of treatment interruption. In contrast with an NNRTI, consecutive missed doses of a boosted PI did not emerge as a major risk factor for HIV replication.

A Pilot Study of Tobacco Screening and Referral for Smoking Cessation Program among HIV-Infected Patients in France.

BACKGROUND: The prevalence of tobacco smoking is high among patients living with HIV, supporting the need for effective targeted interventions. MATERIALS AND METHODS: All current smokers at our outpatient HIV clinic were invited to participate in a smoking cessation program. RESULTS: Of the 716 patients living with HIV, 280 (39%) reported active smoking and were younger, more recently HIV infected and more frequently infected due to intravenous drug use (IDU). One hundred forty-seven (53%) smokers agreed to participate in the smoking cessation program and had a higher Fagerström score and were less likely IDU. During follow-up, 41 (28%) smokers withdrew from the program. After 6 months, 60 (57%) of the 106 smokers who completed the intervention had stopped tobacco smoking and were more likely to use varenicline, adjusting for a history of depression. CONCLUSION: Our smoking cessation program was feasible. However, strategies to reach and retain in smoking cessation program specific groups such as IDU are needed to improve the smoking cessation cascade.

How to Optimize the Use of Blood Cultures for the Diagnosis of Bloodstream Infections? A State-of-the Art.

Bloodstream infection (BSI) is a major cause of death in developed countries and the detection of microorganisms is essential in managing patients. Despite major progress has been made to improve identification of microorganisms, blood culture (BC) remains the gold standard and the first line tool for detecting BSIs. Consensus guidelines are available to ensure optimal BSI procedures, but BC practices often deviate from the recommendations. This review provides an update on clinical and technical issues related to blood collection and to BC performance, with a special focus on the blood sample strategy to optimize the sensitivity and specificity of BCs.

Are pyogenic liver abscesses still a surgical concern? A Western experience.

Backgrounds. Pyogenic liver abscess is a rare disease whose management has shifted toward greater use of percutaneous drainage. Surgery still plays a role in treatment, but its indications are not clear. Method. We conducted a retrospective study of pyogenic abscess cases admitted to our university hospital between 1999 and 2010 and assessed the factors potentially associated with surgical treatment versus medical treatment alone. Results. In total, 103 liver abscess patients were treated at our center. The mortality was 9%. The main symptoms were fever and abdominal pain. All of the patients had CRP > 6 g/dL. Sixty-nine patients had a unique abscess. Seventeen patients were treated with antibiotics alone and 57 with percutaneous drainage and antibiotics. Twenty-seven patients who were treated with percutaneous techniques required surgery, and 29 patients initially received it. Eventually, 43 patients underwent abscess surgery. The factors associated with failed medical treatment were gas-forming abscess (P = 0.006) and septic shock at the initial presentation (P = 0.008). Conclusion. Medical and percutaneous treatment constitute the standard management of liver abscess cases. Surgery remains necessary after failure of the initial treatment but should also be considered as an early intervention for cases presenting with gas-forming abscesses and septic shock and when treatment of the underlying cause is immediately required.

Enterococcus gallinarum endocarditis occurring on native heart valves.

We report the first case of Enterococcus gallinarum endocarditis developing on normal native heart valves. Using phenotypic and molecular methods, a precise identification of this naturally vancomycin-resistant species allowed an optimal antibiotic therapy and the patient's recovery.