Pharmacokinetics of dolutegravir in a premature neonate after HIV treatment intensification during pregnancy.

We describe the pharmacokinetics of dolutegravir (DTG) in a premature neonate after maternal intensification of an antiretroviral (ARV) regimen by adding DTG. During the last 2 weeks of pregnancy, the ARV was tenofovir-emtricitabine, atazanavir-ritonavir, and DTG (50 mg once daily). From the interaction between atazanavir and DTG via CYP3A4 and UGT1A1 and placental efflux transporter inhibition and considering the infant's probable enzymatic immaturity, the DTG elimination half-life was estimated to be 4-fold longer in neonates than in adults.

Quinolones versus macrolides in the treatment of legionellosis: a systematic review and meta-analysis.

BACKGROUND: Legionellosis is a life-threatening disease. The clinical superiority of quinolones or macrolides for treating patients with legionellosis has not been established. METHODS: We performed a systematic review and meta-analysis of studies reporting data that allowed the comparison of quinolones versus macrolides in the treatment of proven legionellosis published from 1 January 1985 to 31 January 2013. We collected baseline aggregate patient characteristics. Studied outcomes included mortality, clinical cure, time to apyrexia, length of hospital stay and occurrence of complications in each treatment group. Treatment effect was assessed using a Mantel-Haenszel random effects model. RESULTS: Among 1005 abstracts reviewed, 12 studies were selected (n=879 patients). No randomized controlled trial was performed directly comparing quinolone and macrolide efficacy in legionellosis. Mean age was 58.3 years, 27.7% were women and Fine score was ≥ 4 in 35.8%. Among 253 patients who received quinolone monotherapy, 10 died (4.0%). Among 211 patients who received macrolide monotherapy, 23 died (10.9%). The pooled OR of death for treatment with a quinolone versus a macrolide was 0.5 (95% CI 0.2-1.3, n=8 studies, 464 patients). Length of stay was significantly shorter in the quinolone monotherapy group. The difference was 3.0 days (95% CI 0.7-5.3, P=0.001, n=3 studies, 263 patients). Neither of two tests for heterogeneity was significant (I (2)=0% for both, P=1). Other studied outcomes were not significantly different among treatment groups. CONCLUSIONS: Few clinical data on legionellosis treatment are available. This first meta-analysis showed a trend toward a lower mortality rate and a significant decrease in length of hospital stay among patients receiving quinolones. These results must be confirmed by a randomized controlled trial.

Salvage strategy for long-term central venous catheter-associated Staphylococcus aureus infections in children: a multi-centre retrospective study in France.

OBJECTIVES: Catheter removal is recommended in adults with Staphylococcus aureus central-line-associated bloodstream infection (CLABSI) but is controversial in children with long-term central venous catheters (LTCVC). We evaluated the occurrence of catheter salvage strategy (CSS) in children with S. aureus LTCVC-associated CLABSI and assessed determinants of CSS failure. METHODS: We retrospectively included children (<18 years) with an LTCVC and hospitalized with S. aureus CLABSI in eight French tertiary-care hospitals (2010-2018). CSS was defined as an LTCVC left in place ≥72 h after initiating empiric antibiotic treatment for suspected bacteraemia. Characteristics of patients were reviewed, and multi-variable logistic regression was performed to identify factors associated with CSS failure (i.e., persistence, recurrence or complications of bacteraemia). RESULTS: We included 273 episodes of S. aureus LTCVC-associated CLABSI. CSS was chosen in 194 out of 273 (71%) cases and failed in 74 of them (38%). The main type of CSS failure was the persistence of bacteraemia (39 of 74 cases, 53%). Factors independently associated with CSS failure were: history of catheter infection (adjusted odds ratio (aOR) 3.18, 95% confidence interval (CI) 1.38-7.36), CLABSI occurring on an implantable venous access device (aOR 7.61, 95% CI 1.98-29.20) when compared with tunnelled-cuffed CVC, polymicrobial CLABSI (aOR 3.45, 95% CI 1.25-9.50), and severe sepsis at the initial stage of infection (aOR 4.46, 95% CI 1.18-16.82). CONCLUSIONS: CSS was frequently chosen in children with S. aureus LTCVC-associated CLABSI, and failure occurred in one-third of cases. The identified risk factors may help clinicians identify children at risk for CSS failure.

Medical check-up of newly arrived unaccompanied minors: A dedicated pediatric consultation service in a hospital.

BACKGROUND AND AIMS: Healthcare for the increasing number of migrants in Europe, and particularly of unaccompanied minors (UMs) seeking asylum, has become a major challenge. We aimed to describe the health issues of UMs managed in a dedicated pediatric consultation service in a care center in Paris. METHODS: All UMs attending a dedicated migrant medical consultation service in Robert Debré Hospital, Paris, France, were included in a single-center retrospective observational study from September 1, 2017, to September 30, 2018. RESULTS: Out of the 107 UMs who were included, 87% had a health problem (n=93) and 52% had an infectious disease (n=56). The main infectious diagnoses were schistosomiasis (22%), latent tuberculosis (22%), intestinal parasitosis (16%), and chronic hepatitis B (8%). Posttraumatic stress disorder (PTSD) and overweight were common (35% and 20%, respectively). The median age was 15 years old (IQR, 14-16), the male/female ratio was 95/12. Most of the children were from sub-Saharan Africa (n=67), 46% had crossed Libya (n=49) and, when compared to the other migration routes, faced an increasing risk of violence (69%, p=0.04), imprisonment (53%, p=0.03), and forced labor (48%, p=0.02). The median duration of the trip before reaching France was 6 months (IQR, 2-13), the median time to consultation was 2 months (0-5) and was not associated with an increased risk of health problems. A total of 43 UMs were lost to follow-up. CONCLUSION: Health problems, particularly infectious diseases and PTSD, are common among UMs and should prompt an early medical consultation with psychiatric evaluation. Follow-up is problematic and could be improved by an on-line health book.

Management of oral antiretroviral administration in patients with swallowing disorders or with an enteral feeding tube.

HIV infection has evolved into a chronic disease with comorbidities since the combination antiretroviral therapy era. Complications still occur and patients may need to be admitted to an intensive care unit. Acute respiratory failure is the first cause of these admissions, questioning the administration of solid oral dosage formulations. This issue is also observed in geriatric units where the prevalence of dysphagia is high and underestimated. The problem of antiretroviral administration is critical: altered solid oral dosage formulations and/or administration via enteral feeding tubes are sometimes the only option. The aim is to help manage antiretroviral treatment in unconscious or intubated patients and those with swallowing disorders who are hospitalized in intensive care units or geriatric units. This review provides information on the main antiretroviral regimens and on practical and legal aspects of manipulating solid oral dosage formulations and administration via enteral feeding tubes. Alternatives to the solid formulation are available for most of the 27 oral antiretrovirals available, or manufacturers provide recommendations for patients who are unable to swallow. Manipulation of solid oral dosage formulations such as crushing tablets or opening capsules and administration via feeding tubes are frequently reported but should be the last option for safety and liability issues. Before any off-label administration of a drug, physicians should consider alternatives to the solid oral dosage formulation and check whether the drug can be altered. Therapeutic monitoring is important in this particular setting as the pharmacokinetic profile of drugs is difficult to predict.

[An update on measles]. / Actualité de la rougeole.

Measles is a highly contagious infectious disease, which needs more than 95% worldwide vaccination coverage of 2 doses to be eradicated. Despite an important involvement of the WHO for massive immunization, goals have not bean reached, and outbreaks can occur at any time in many countries, including Western Europe. In France, 22,000 cases were identified between 2009 and 2011, mainly in infants and young adults, which are not or not enough vaccinated (one dose). In 2012, even though the number of cases has drastically decreased, the outbreak is still going on, especially in South of France. That is why every clinician needs to be concerned about the clinical manifestations of the disease, and its complications. Besides a febrile rash, measles is often responsible of pneumonia and biologic hepatitis in adults. Hepatitis does not seem frequent in children. Clinicians need to be aware of specific complications, like encephalitis in case of cellular immunodepression, high risk of pneumonia in pregnant women. In patients previously vaccinated, incidence of complications is the same but patients are not contagious. Even if measles diagnosis is clinical, blood confirmation by serology is recommended in France when possible. Outcome is mainly favourable, but measles is not well-tolerated with high levels of hospitalisation even without any complication. Vaccination is the only way to protect against it.

French 2010-2011 measles outbreak in adults: report from a Parisian teaching hospital.

We reviewed 80 adult cases of measles seen in a Parisian hospital during the French 2010-2011 outbreak. Fifty per cent had at least one complication: pneumonia and hepatitis were the most frequent. Forty per cent of hospitalized cases did not have any complications, suggesting clinically poor tolerance of measles in adults. The outcome was always favourable. Subjects were younger, were more often French nationals and had a higher socio-economic status than the overall population. This report suggests that immunity resulting from natural disease in patients from an area where the disease is endemic is protective in the long term.