Dalbavancin plasma concentrations in 133 patients: a PK/PD observational study.

OBJECTIVES: Limited pharmacokinetics data support dalbavancin long-term use in off-label indications and the optimal dosing regimen is debated. We aimed to describe dalbavancin concentrations in an observational retrospective multicentre study. METHODS: Patients from 13 French hospitals, treated with 1500 mg doses of dalbavancin and for whom therapeutic drug monitoring was performed from June 2018 to March 2021 were included. Dalbavancin plasma concentrations were described at peak and 1, 2, 3, 4, 6 and 8 weeks after the last 1500 mg dose. Concentrations in patients weighing more or less than 75 kg and with a GFR greater or less than 60 mL/min were compared. Microbiological data were collected and dalbavancin MIC was measured when possible. RESULTS: One hundred and thirty-three patients were included (69% treated for bone and joint infections, 16% for endocarditis). Thirty-five patients received a single dose of dalbavancin and 98 received several administrations. Two, 3 and 4 weeks after the last dose, median plasma concentrations were respectively 25.00, 14.80 and 9.24 mg/L for the first doses and 34.55, 22.60 and 19.20 mg/L for the second or subsequent doses. Weight and renal function had an impact on pharmacokinetics. Infection was documented in 105 patients (Staphylococcus spp. in 68% of cases). Staphylococcus aureus was isolated in 32.5% of cases (median MIC: 0.047 mg/L) and Staphylococcus epidermidis in 27% of cases (median MIC of 0.047 mg/L). CONCLUSIONS: Plasma concentrations of dalbavancin were consistent with those described in clinical trials and those sought during the industrial development of the molecule.

Are infection specialists recommending short antibiotic treatment durations? An ESCMID international cross-sectional survey.

Objectives: To evaluate the current practice and the willingness to shorten the duration of antibiotic therapy among infection specialists. Methods: Infection specialists giving at least weekly advice on antibiotic prescriptions were invited to participate in an online cross-sectional survey between September and December 2016. The questionnaire included 15 clinical vignettes corresponding to common clinical cases with favourable outcomes; part A asked about the antibiotic treatment duration they would usually advise to prescribers and part B asked about the shortest duration they were willing to recommend. Results: We included 866 participants, mostly clinical microbiologists (22.8%, 197/863) or infectious diseases specialists (58.7%, 507/863), members of an antibiotic stewardship team in 73% (624/854) of the cases, coming from 58 countries on all continents. Thirty-six percent of participants (271/749) already advised short durations of antibiotic therapy (compared with the literature) to prescribers for more than half of the vignettes and 47% (312/662) chose shorter durations in part B compared with part A for more than half of the vignettes. Twenty-two percent (192/861) of the participants declared that their regional/national guidelines expressed durations of antibiotic therapy for a specific clinical situation as a fixed duration as opposed to a range and in the multivariable analysis this was associated with respondents advising short durations for more than half of the vignettes (adjusted OR 1.5, P = 0.02). Conclusions: The majority of infection specialists currently do not advise the shortest possible duration of antibiotic therapy to prescribers. Promoting short durations among these experts is urgently needed.

Less-drug regimen including atazanavir in maintenance treatment of HIV infection: how, who, when, why?

For many patients living with HIV-1, the efficacy of combined ART (cART) has made the infection turn to a chronic disease. Because cART is associated with a risk of long-term toxicity, switching patients with virological success to another therapy remains a major issue. Studies undertaken and published over recent years have shown that switching patients exhibiting virological suppression to less-drug regimens (LDR) is a possible option of maintenance strategy. The use of ritonavir-boosted PIs (PI/r) as the backbone of LDR-based maintenance therapy is consistent with their virological potency and a high genetic barrier of resistance. Atazanavir is the most documented PI/r regarding maintenance in dual therapy, with favourable results in terms of virological suppression, tolerance improvement and absence of emergence of mutations. Furthermore, atazanavir is the only commonly prescribed PI that can be used after withdrawal of ritonavir, with maintenance of virological suppression whatever the backbone of associated NRTIs. Based on clinical studies, and taking into account the characteristics of the patients included, one may consider that for any patient with a virological suppression on cART for at least 12 months, with the nadir CD4 >100 cells/mm3 and an absence of encephalitis, an LDR-based maintenance therapy including atazanavir can be considered. Cumulative genotypes must be available to make sure that the LDR will not jeopardize future therapeutic options. The final decision regarding the most appropriate LDR must be guided by the objectives shared by the physician and his/her patient.

[Shortened antimicrobial therapy duration]. / Réduction de la durée des antibiothérapies.

SHORTENED ANTIMICROBIAL THERAPY DURATION. Antibiotic treatment durations represent an important field of current clinical research. Indeed, shortening antibiotic duration during bacterial pathologies has several advantages: reducing the emergence of resistance on an individual and collective scale, reducing costs, adverse effects and the environmental impact. However, a rigorous investigation is necessary to properly assess the absence of impact on the individual prognosis. In recent years, several randomized trials have made it possible to validate short durations of antibiotic therapy for frequent bacterial pathologies: 5 days during simple acute pyelonephritis, 7 days for non-febrile urinary tract infections in men, 3 to 5 days during acute bacterial pneumonia, 6 weeks for pyogenic spondylodiscitis. However, some durations seem incompressible and/or require individualization: 14 days for febrile male urinary tract infections, 12 weeks for infections on osteoarticular prostheses. It is necessary to reduce the duration of antibiotic treatment to the minimum necessary and to evaluate personalized durations taking into account, in particular, immunocompromised patients who are often excluded from trials.

RÉDUCTION DE LA DURÉE DES ANTIBIOTHÉRAPIES. Les durées de traitement antibiotique constituent un champ important de la recherche clinique actuelle. En effet, raccourcir ces durées au cours des pathologies bactériennes présente plusieurs avantages : diminuer l'émergence de résistance à une échelle individuelle et collective, réduire les coûts, les effets indésirables et l'impact sur l'environnement. Cependant, une investigation rigoureuse est nécessaire pour bien évaluer l'absence d'impact sur le pronostic individuel du patient. Au cours de ces dernières années, plusieurs essais randomisés ont permis de valider des durées courtes d'antibiothérapie pour des pathologies bactériennes fréquentes : cinq jours au cours de pyélonéphrites aiguës simples, sept jours pour les infections urinaires non fébriles de l'homme, de trois à cinq jours au cours des pneumonies aiguës bactériennes, six semaines pour les spondylodiscites à pyogènes. Néanmoins, certaines durées semblent incompressibles et/ou nécessitent une individualisation : quatorze jours pour les infections urinaires masculines fébriles, douze semaines concernant les infections sur prothèses ostéo-articulaires. Il est nécessaire de réduire les durées de traitement antibiotique au minimum nécessaire et d'évaluer des durées personnalisées prenant notamment en compte les patients immunodéprimés, souvent exclus des essais.

Ceftolozane/Tazobactam for the Treatment of Complicated Infections in Hospital Settings-A French Real-world Study.

Background: This study describes the conditions of use of ceftolozane/tazobactam (C/T) and associated outcomes in French hospital settings. Methods: This was a prospective, multicenter, French observational study. Patients who received at least 1 dose of C/T were included and followed up as per routine clinical practice, until stop of C/T. Results: A total of 260 patients were enrolled between October 2018 and December 2019 in 30 centers across France. Of these, 177 (68.0%) received C/T as per indication of usage following the results of the antibiogram (documented cases). Among documented patients, the mean age was 61.8 years, 73.4% were males, and 93.8% presented with multidrug-resistant (MDR) bacteria at inclusion. C/T was most frequently prescribed for pneumonia (48.6%), bacteremia (14.7%), complicated intra-abdominal infections (13.0%), or complicated urinary tract infections (9.6%). Pseudomonas aeruginosa was the species most frequently isolated with 212 strains from 155 patients, and 96.2% of these strains were susceptible to C/T. The median duration of C/T treatment was 16.1 days (1-115, n = 176). Complete or partial cure was achieved in 71.7% of patients, C/T was discontinued upon adaptation to microbiology results in 11.3% of patients for the following reasons: treatment failure in 2.8%, death in 4.0%, adverse events in 1.7%, and other in 8.5%. Conclusions: This is the first prospective observational study of C/T utilization in a health care setting enrolling many patients in France. C/T demonstrated a high rate of clinical effectiveness in MDR infections, confirming it as an effective treatment option for complicated infections in a high-risk population.

Time to Treatment Initiation and HIV Viral Suppression in People Diagnosed With HIV-1 During COVID-19 Pandemic in Ex-Aquitaine, France (ANRS CO3 AQUIVIH-NA Cohort-QuAliCOV Study).

OBJECTIVES: The COVID-19 pandemic's impact on initiation and effectiveness of antiretroviral therapy (ART) in people diagnosed with HIV remains unclear. We evaluated critical delays in HIV care in people diagnosed before and during the pandemic in ex-Aquitaine, France. METHODS: We considered adults diagnosed with HIV-1 in 2018-2021 and enrolled in the ANRS CO3 AQUIVIH-NA and followed them until October 10, 2022 for those diagnosed during the pandemic (April 01, 2020-December 31, 2021) and until March 31, 2020 for historical controls. We compared their characteristics at inclusion and the median time between diagnosis and ART initiation, ART initiation and viral suppression, and diagnosis and virologic, suppression (effective management). RESULTS: Eighty-three individuals were diagnosed during the pandemic versus 188 during the prepandemic period. Median follow-up was 549 (interquartile range: 329-713) days. Populations were similar in sex, age, HIV acquisition mode, hospital type, and clinical characteristics at diagnosis; however, fewer were foreign-born during the pandemic (15.7% versus 33.5%, P = 0.003). The probability of ART initiation, therapeutic success, and effective management was higher in people living with HIV (PLWH) diagnosed during the pandemic in adjusted analyses (hazard ratio [HR]: 2.0; 95% CI: 1.5 to 2.7; HR: 1.7; 95% CI: 1.2 to 2.3; HR: 1.8; 95% CI: 1.3 to 2.6, respectively). Those diagnosed during the pandemic were 2.3 (95% CI: 1.2 to 4.1) times more likely to be virologically suppressed within six months of diagnosis compared with historical controls. CONCLUSIONS: Pandemic-related reorganizations may have resulted in newly diagnosed PLWH being prioritized; however, the lower proportion of foreign-born PLWH diagnosed during the pandemic period, likely because of reduced migration and potential delays in diagnosis, may contribute to these preliminary findings.

Knowledge of recommended antibiotic treatments for community-acquired infections in general medical practice: a cross-sectional study in Occitanie region, France.

To assess and analyse the knowledge of recommended antibiotic treatments, focusing on the appropriate drugs and treatment durations for the most common community-acquired infections in general medical practice in Occitanie region, France. A web-based survey was conducted over a 3-month period, from October, 2018 to January, 2019. All participants answered directly through the online platform. For the analysis of overtreatment risk, a score based system was adopted and two scores were produced: the duration score and the treatment score. 413 general practitioners completed the survey. The overall rate of concordance with guidelines in terms of both drug choice and treatment length was 2974/4956 (60%) answers. Diseases with at least 70% good answers included cystitis, group A streptococcal pharyngitis, and bacterial superficial skin infections. Diseases with fewer than 50% good answers included pyelonephritis, dog bite wounds, and community-acquired pneumonia in patients aged ≥ 65 years. Factors associated with the risk of overtreatment were age > 40 years, country setting and hospital employment. Knowledge of treatment durations is satisfactory with 60% of recommendations being met. However, varying levels were observed according to different diseases. This study highlighted a very high rate of adherence when recommendations were clear. In contrast, low levels of adherence were observed when recommendations were ambiguous or when conflicting guidelines existed.

Real-world evaluation of ceftolozane/tazobactam therapy and clinical outcomes in France.

OBJECTIVES: To describe the real-world clinical use of ceftolozane/tazobactam (C/T) and associated outcomes in France. PATIENTS AND METHODS: Multicenter, prospective cohort study conducted in 22 hospitals. All adult patients who received at least one dose of C/T were asked to participate (2018-2019). Patients were treated according to standard hospital practice and followed up until C/T stop. RESULTS: At the time of the analysis, 84 patients were evaluated. The median age was 64.8 years, and 67.9% (57/84) of patients were males. Fifty-seven patients (57/82, 69.5%) had one or more risk factors for multidrug-resistant (MDR) infections (missing MDR risk factor data for two patients). Most patients were critically ill and had several comorbidities. A majority (59/84, 70.2%) of patients had nosocomial infections. Half of all patients (n=42) had a diagnosis of pneumonia, of which 69% (29/42) were hospital acquired. Overall, 90.5% (76/84) of patients had MDR bacteria. Pseudomonas aeruginosa was the most frequently isolated bacterium (71/80, 88.8%), including 93% (80/86) of C/T-susceptible strains. C/T was prescribed as the first-line treatment to 29.8% (25/84) of patients. A concomitant antibiotic treatment was prescribed to 48.8% (41/84) of patients, of whom 65.9% (27/41) were prescribed concomitant antibiotics at the same time as C/T initiation. Empirical C/T prescription was microbiologically appropriate in 11/16 patients after susceptibility testing. Most patients (44/72, 61.1%) were cured and four (4/72, 5.6%) deaths were reported. CONCLUSIONS: The results showed that C/T was most frequently prescribed for documented cases of P. aeruginosa infections. Most outcomes were positive, including among pneumonia patients.

Pelvic inflammatory diseases: Updated French guidelines.

Pelvic inflammatory diseases (PID) must be suspected when spontaneous pelvic pain is associated with induced adnexal or uterine pain (grade B). Pelvic ultrasonography is necessary to rule out tubo-ovarian abscess (TOA) (grade C). Microbiological diagnosis requires endocervical and TOA sampling for molecular and bacteriological analysis (grade B). First-line treatment for uncomplicated PID combines ceftriaxone 1 g, once, IM or IV, doxycycline 100 mg ×2/day, and metronidazole 500 mg ×2/day PO for 10 days (grade A). First-line treatment for complicated PID combines IV ceftriaxone 1-2 g/day until clinical improvement, doxycycline 100 mg ×2/day, IV or PO, and metronidazole 500 mg ×3/day, IV or PO for 14 days (grade B). Drainage of TOA is indicated if the pelvic fluid collection measures more than 3 cm (grade B). Follow-up is required in women with sexually transmitted infections (STIs) (grade C). The use of condoms is recommended (grade B). Vaginal sampling for microbiological diagnosis is recommended 3-6 months after PID (grade C), before the insertion of an intrauterine device (grade B), and before elective termination of pregnancy or hysterosalpingography. When specific bacteria are identified, antibiotics targeted at them are preferable to systematic antibiotic prophylaxis.

Mycobacterium marinum infection following contact with reptiles: vivarium granuloma.

A 19-year-old man presented with a 1.5-cm nodule on the first dorsal metacarpal ray. The patient denied having contact with fish tanks or fish, but recalled handling many reptiles without gloves in the vivarium where he worked. A culture of a skin biopsy specimen yielded Mycobacterium marinum. The clinical outcome was favourable after a 2-week course of intramuscular gentamicin (180 mg daily) combined with a 6-week course of oral clarithromycin (500 mg twice a day). Doctors should be aware that vivariums, in addition to fish tanks, can be sources of M. marinum exposure.