Iatrogenic Cushing syndrome due to drug interaction between inhaled fluticasone and cobicistat.

In this paper we report a case of iatrogenic Cushing syndrome due to a pharmacological interaction between fluticasone and cobicistat. Inhaled corticosteroids were previously thought to be safe, but increasing numbers of cases of iatrogenic Cushing syndrome are being reported, especially in patients taking cytochrome P450 inhibitors, including cobicistat. Although the drug interaction between cobicistat and fluticasone has been described elsewhere, to our knowledge we present one of the first descriptions of iatrogenic Cushing syndrome due to this pharmacological interaction.

International prevalence and risk factors evaluation for drug-resistant Streptococcus pneumoniae pneumonia.

OBJECTIVE: Streptococcus pneumoniae is the most frequent bacterial pathogen isolated in subjects with Community-acquired pneumonia (CAP) worldwide. Limited data are available regarding the current global burden and risk factors associated with drug-resistant Streptococcus pneumoniae (DRSP) in CAP subjects. We assessed the multinational prevalence and risk factors for DRSP-CAP in a multinational point-prevalence study. DESIGN: The prevalence of DRSP-CAP was assessed by identification of DRSP in blood or respiratory samples among adults hospitalized with CAP in 54 countries. Prevalence and risk factors were compared among subjects that had microbiological testing and antibiotic susceptibility data. Multivariate logistic regressions were used to identify risk factors independently associated with DRSP-CAP. RESULTS: 3,193 subjects were included in the study. The global prevalence of DRSP-CAP was 1.3% and continental prevalence rates were 7.0% in Africa, 1.2% in Asia, and 1.0% in South America, Europe, and North America, respectively. Macrolide resistance was most frequently identified in subjects with DRSP-CAP (0.6%) followed by penicillin resistance (0.5%). Subjects in Africa were more likely to have DRSP-CAP (OR: 7.6; 95%CI: 3.34-15.35, p<0.001) when compared to centres representing other continents. CONCLUSIONS: This multinational point-prevalence study found a low global prevalence of DRSP-CAP that may impact guideline development and antimicrobial policies.

Lung ultrasound in the management of pneumocystis pneumonia: A case series.

Despite the decline in HIV mortality and morbidity, Pneumocystis jirovecii pneumonia (PJP) is still frequently seen, particularly in patients with a low CD4+ cell count. We present a case series where we analyzed the possible role of lung ultrasound (LUS) in the management of PJP in a real-life clinical setting. We describe the ultrasound findings from a consecutive series of six HIV patients hospitalized for PJP, all with a favorable outcome, and evaluated with LUS at admission in our ward and then repeated this once during the hospitalization. Multiple B lines indicating interstitial syndrome were detected at admission in all cases, with a bilateral asymmetric pattern mostly localized in middle and upper lobes. In the follow-up LUS, we noted a substantially improved pattern in all patients, observing a reduction of B lines which correlated with clinical amelioration. One patient at admission and three patients during the follow-up showed lung consolidations with hyperechoic spots inside, that might be typical of the disease. In conclusion, LUS could be a practical and noninvasive imaging tool for supporting diagnosis and treatment response of PJP.

Clinical and genetic determinants of nevirapine plasma trough concentration.

BACKGROUND: Only few data are available on the influence of CYP2B6 and CYP3A4/A5 polymorphisms on nevirapine plasma concentrations in the Caucasian population. Our aim was to assess the impact of CYP2B6 and CYP3A4/A5 polymorphisms on nevirapine plasma concentrations consecutively collected. METHODS: We retrospectively analyzed clinical data of all HIV-positive patients who were followed at the Infectious Diseases Unit, DIBIC Luigi Sacco, University of Milan between January 2000 and December 2015. All patients with at least one nevirapine plasma trough concentration (NVP Cmin) determination were tested for CYP2B6 c.516 G>T, CYP3A4*22C>T and CYP3A5*3 A>G polymorphisms. Univariate and multivariate regression analyses were carried out considering NVP Cmin as the dependent variable and genetic polymorphisms and clinical characteristics as independent variables. RESULTS: A total of 143 patients were evaluated. Most of them were males (61.5%) and Caucasian (92.3%). Overall, NVP Cmin varied from 1571 to 14,189 ng/mL (median = 5063 ng/mL, interquartile range = 3915-6854). The median NVP Cmin significantly differed in patients with different CYP2B6 genotypes, but did not vary in those with different CYP3A phenotypes. In the final general linear model, factors significantly associated with a higher NVP Cmin were each extra unit of T alleles of CYP2B6 rs3745274 (ß = 0.328, 95% confidence interval = 0.172-0.484; p < 0.0001), older age (ß = 0.362, 95% confidence interval = 0.193-0.532; p < 0.0001) and hepatitis C virus coinfection (ß = 0.161, 95% confidence interval = 0.006-0.315; p < 0.041). CONCLUSION: Our study, conducted in a prevalent Caucasian population, highlighted the importance of CYP2B6 genetic variants in influencing nevirapine plasma trough concentration. Furthermore, older age and hepatitis C virus coinfection significantly increase exposure to nevirapine.

Primary HIV infection in patients with acute hepatitis B: a report of two cases.

We describe two patients admitted to our institution with a diagnosis of sexually acquired acute hepatitis B who also had underlying hyper acute HIV infection. Both individuals reported high rates of condomless sex. Antiviral therapy active against HBV and HIV was started within days after diagnosis. Treatment was well tolerated and led to a rapid control of both infections and hepatitis B surface antibody seroconversion. The efficacy and safety of contemporary antiretroviral drug combinations suggest that treatment of acute HIV infection is feasible in patients with acute hepatitis B.

Exogenous reinfection of tuberculosis in a low-burden area.

PURPOSE: Recurrence of tuberculosis (TB) can be the consequence of relapse or exogenous reinfection. The study aimed to assess the factors associated with exogenous TB reinfection. METHODS: Prospective cohort study based on the TB database, maintained at the Division of Infectious Diseases, Luigi Sacco Hospital (Milan, Italy). Time period: 1995-2010. INCLUSION CRITERIA: (1) ≥2 episodes of culture-confirmed TB; (2) cure of the first episode of TB; (3) availability of one Mycobacterium tuberculosis isolate for each episode. Genotyping of the M. tuberculosis strains to differentiate relapse and exogenous reinfection. Logistic regression analysis was used to assess the influence of risk factors on exogenous reinfections. RESULT: Of the 4682 patients with TB, 83 were included. Of these, exogenous reinfection was diagnosed in 19 (23 %). It was independently associated with absence of multidrug resistance at the first episode [0, 10 (0.01-0.95), p = 0.045] and with prolonged interval between the first TB episode and its recurrence [7.38 (1.92-28.32) p = 0.004]. However, TB relapses occurred until 4 years after the first episode. The risk associated with being foreign born, extrapulmonary site of TB, and HIV infection was not statistically significant. In the relapse and re-infection cohort, one-third of the patients showed a worsened drug resistance profile during the recurrent TB episode. CONCLUSIONS: Exogenous TB reinfections have been documented in low endemic areas, such as Italy. A causal association with HIV infection could not be confirmed. Relapses and exogenous reinfections shared an augmented risk of multidrug resistance development, frequently requiring the use of second-line anti-TB regimens.