According to 2016 World Health Organization and United Nations Children's Fund country estimates, Eritrea has overall high vaccination coverage with immunization rates for three doses of ...diphtheria/tetanus/pertussis and polio vaccine of 95%, for two doses measles vaccine of 85% and for three doses hepatitis B vaccine of 85%. If confirmed, this could imply that routine basic vaccination of newly arrived Eritreans could be safely omitted.
We used stored serum samples from two cross-sectional studies that screened newly arrived Eritrean refugees for infectious diseases. Consenting refugees aged 16 years and older who registered in one of three neighbouring cantons in northwestern Switzerland were enrolled between January 2016 and December 2017. Antibody titers against the following vaccine-preventable diseases were measured (applied thresholds for seroprotection in brackets): diphtheria (>0.1 IU/ml), tetanus (>0.1 IU/ml), measles (>150 mIU/ml), rubella (only for women, >11 IU/ml), varicella (>50 mIU/ml), hepatitis B hepatitis B surface antigen (HBsAg) Index >0.9, Hepatitis B core antibody (anti-HBc) Index >0.9 and antibodies to HBsAg (anti-HBs) >10 IE/L. Differences between sex and age groups (≤25 and >25 years) were measured by Fisher's exact test.
We analysed samples of 133 study participants (20 women, 15%) with a median age of 25 years (range 16-61). Rates of seropositivity were as follows for women/men, respectively: diphtheria 57.9%/74.8% (difference non-significant), tetanus 94.8%/41.1% (P < 0.001), measles 73.7%/76.6% (non-significant), rubella in women 78.9%, varicella 89.5%/95.3% (non-significant), anti-HBc 15.8%/26.2% (non-significant) and anti-HBs 15.8%/17.8% (non-significant).
Seroprevalence for vaccine-preventable infections did not meet levels required to confer herd immunity in any of the human-to-human transmissible diseases that were studied. In general, the strategy proposed by the Federal Office of Public Health to offer basic immunization to all newly arrived refugees, including newly arriving Eritrean refugees, is justified.
Although most experts recommend empirical antibiotic treatment, covering also atypical bacteria, for patients admitted to an intensive care unit (ICU), the data are not clear for patients admitted to ...a general ward. European guidelines recommend starting empirical treatment with a beta-lactam antibiotic with or without a macrolide, but the with/without is not clarified. We investigated whether the use of antibiotic coverage for atypical pathogens was guided by clinical parameters.
We retrospectively analysed 300 patients hospitalised with community-acquired pneumonia. Four parameters for possible atypical pneumonia (age <55 years, abdominal symptoms, sodium <130 mmol/l, immunosuppression) and three for pneumonia severity (pneumonia severity index PSI, ICU admission, pO2 <8 kPa (60 mm Hg) or O2 saturation <90%) were defined and correlated with the probability of coverage for atypical pathogens. Correlations were calculated using the chi-square test for 2 x 2 tables.
Patients younger than 55 years significantly more likely to receive coverage for atypical pathogens than older patients (odds ratio OR 2.68; 95% confidence interval CI 1.3-5.5, p = 0.009). In patients with a PSI >III the proportion receiving coverage for atypical bacteria was even smaller than in patients with less severe pneumonia (OR 0.77; 95% CI 0.60-0.99, p = 0.03), but no difference was found for PSI >IV compared with PSI ≤IV (OR = 1.03; 95% CI 0.61-1.74, p = 0.9). The other clinical parameters had no effect on antibiotic coverage: ICU admission (OR =1.39; 95% CI 0.87-2.4, p = 0.15); pO2 >8 kPa or O2-Saturation >90% (OR 1.36; 95% CI 0.85-2.17, p = 0.19); abdominal symptoms (OR 1.06; 95% CI 0.51-2.25, p = 0.88); sodium <130 mmol/l (OR 0.63; 95% CI 0.29-1.36, p = 0.2) or immunosuppression (OR 1.007; 95% CI 0.462-44, p = 1). There was also no correlation between the number of clinical parameters present and the coverage of atypical pathogens (r = 0.48). Mortality was no different between patients in whom atypical pathogens were covered compared with those with beta-lactam therapy alone (OR 1.2; 95% CI 0.66-2.25, p = 0.43).
Physicians have difficulties deciding when to cover atypical pathogens in hospitalised patients with community-acquired pneumonia. Guidelines should clarify under what circumstances combination therapy is warranted.
Abstract
Objectives
Dolutegravir is widely prescribed owing to its potent antiviral activity, high genetic barrier and good tolerability. The aim of this study was to characterize dolutegravir’s ...pharmacokinetic profile and variability in a real-life setting and to identify individual factors and co-medications affecting dolutegravir disposition.
Methods
A population pharmacokinetic model was developed using NONMEM®. Relevant demographic factors, clinical factors and co-medications were tested as potential covariates. Simulations based on the final model served to compare expected dolutegravir concentrations under standard and alternative dosage regimens in the case of drug–drug interactions.
Results
A total of 620 dolutegravir plasma concentrations were collected from 521 HIV-infected individuals under steady-state conditions. A one-compartment model with first-order absorption and elimination best characterized dolutegravir pharmacokinetics. Typical dolutegravir apparent clearance (CL/F) was 0.93 L/h with 32% between-subject variability, the apparent volume of distribution was 20.2 L and the absorption rate constant was fixed to 2.24 h−1. Older age, higher body weight and current smoking were associated with higher CL/F. Atazanavir co-administration decreased dolutegravir CL/F by 38%, while darunavir modestly increased CL/F by 14%. Rifampicin co-administration showed the largest impact on CL/F. Simulations suggest that average dolutegravir trough concentrations are 63% lower after 50 mg/12h with rifampicin compared with a standard dosage of 50 mg/24h without rifampicin. Average trough concentrations after 100 mg/24h and 100 mg/12h with rifampicin are 92% and 25% lower than the standard dosage without rifampicin, respectively.
Conclusions
Patients co-treated with dolutegravir and rifampicin might benefit from therapeutic drug monitoring and individualized dosage increase, up to 100 mg/12 h in some cases.
We analyzed the species distribution of Candida blood isolates (CBIs), prospectively collected between 2004 and 2009 within FUNGINOS, and compared their antifungal susceptibility according to ...clinical breakpoints defined by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) in 2013, and the Clinical and Laboratory Standards Institute (CLSI) in 2008 (old CLSI breakpoints) and 2012 (new CLSI breakpoints). CBIs were tested for susceptiblity to fluconazole, voriconazole and caspofungin by microtitre broth dilution (Sensititre® YeastOne™ test panel). Of 1090 CBIs, 675 (61.9%) were C. albicans, 191 (17.5%) C. glabrata, 64 (5.9%) C. tropicalis, 59 (5.4%) C. parapsilosis, 33 (3%) C. dubliniensis, 22 (2%) C. krusei and 46 (4.2%) rare Candida species. Independently of the breakpoints applied, C. albicans was almost uniformly (>98%) susceptible to all three antifungal agents. In contrast, the proportions of fluconazole- and voriconazole-susceptible C. tropicalis and F-susceptible C. parapsilosis were lower according to EUCAST/new CLSI breakpoints than to the old CLSI breakpoints. For caspofungin, non-susceptibility occurred mainly in C. krusei (63.3%) and C. glabrata (9.4%). Nine isolates (five C. tropicalis, three C. albicans and one C. parapsilosis) were cross-resistant to azoles according to EUCAST breakpoints, compared with three isolates (two C. albicans and one C. tropicalis) according to new and two (2 C. albicans) according to old CLSI breakpoints. Four species (C. albicans, C. glabrata, C. tropicalis and C. parapsilosis) represented >90% of all CBIs. In vitro resistance to fluconazole, voriconazole and caspofungin was rare among C. albicans, but an increase of non-susceptibile isolates was observed among C. tropicalis/C. parapsilosis for the azoles and C. glabrata/C. krusei for caspofungin according to EUCAST and new CLSI breakpoints compared with old CLSI breakpoints.
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BFBNIB, DOBA, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UKNU, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The urinary pneumococcal antigen (PnAG) test is widely used in the setting of community acquired pneumonia (CAP). Data regarding the impact of the test on antibiotic prescriptions are lacking.
The ...study population consisted of patients with suspicion of CAP in whom PnAG testing was performed. From November 2007 until August 2008, all patients in whom pneumococcal antigen testing (Binax Now®, PnAG) was performed were evaluated. In a second period, from September 2008 until March 2009, we stopped PnAG testing in our institution. We compared the microbiological verification procedures, antibiotic prescription and the final diagnosis of CAP of the first period (n = 139) against the second period (n = 147).
Only 139/188 patients in whom PnAG was performed had CAP. Of these, 22 (15%) were PnAG positive. In 11/22 patients, the diagnosis of pneumococcal pneumonia was additionally confirmed by positive blood and/or sputum culture. In only 6 of the remaining 11 patients, antibiotic treatment was changed as a consequence of the positive PnAG test. In cases of blood culture positive and in sputum positive pneumococcal pneumonia, only 8/13 (61%) and 3/15 (20%) were PnAG positive, respectively. The costs of the PnAG test were 188 × 42 CHF (in total 7,896 CHF) and no cost savings were observed. Neither with empiric nor with consequently prescribed antibiotic treatment was a difference found between the PnAG and control period.
In our patient population, the routine Binax Now® PnAG testing did not lead to cost savings or narrowing of antibiotic prescriptions. Thus, PnAG testing should be limited to cases of diagnostic uncertainty where blood or sputum cultures are negative or not available.
The efficacy and tolerability of long-acting cabotegravir and rilpivirine were demonstrated in Phase III trials. However, low concentrations combined with other risk factors have been associated with ...an increased risk of virologic failure. This study aims to verify whether drug concentrations measured in a real-world setting are consistent with those previously reported.
SHCS-879 is a nationwide observational study within the Swiss HIV Cohort Study for the monitoring of people with HIV (PWH) on long-acting cabotegravir plus rilpivirine. Samples were collected from March 2022 to March 2023.
Overall, 725 samples were obtained from 186 PWH. Our data show a large inter-individual variability in cabotegravir and rilpivirine concentrations, with some individuals exhibiting repeatedly low concentrations. Rilpivirine trough concentrations were consistent with those from Phase III trials, while cabotegravir concentrations were lower. The first concentrations quartile was only slightly above the target of 664 ng/mL. Exploratory statistical analyses found 35% (p < 0·01) lower cabotegravir trough in males compared to females. Overall, 172 PWH (92%) remained suppressed and three experienced virologic failures (1·6%), of those, two had sub-optimal drug exposure. No association was found between low trough levels and detectable viral load.
Real-world cabotegravir concentrations are substantially lower than previously reported. However, these concentrations appear sufficient to ensure sustained virological suppression in almost every PWH. These reassuring data challenge the rather conservative thresholds adopted to date, which may raise unnecessary concerns. Yet, our study reveals that some PWH have repeatedly very low drug levels, for reasons that remain to be elucidated.
This work was funded by the Swiss National Science Foundation, grant number N
324730_192449. This study received no support from pharmaceutical industries. This study was performed within the framework of the Swiss HIV Cohort Study, supported by the Swiss National Science Foundation (grant #201369), by SHCS project #879, and by the SHCS research foundation. The SHCS data were gathered by the Five Swiss University Hospitals, two Cantonal Hospitals, 15 affiliated hospitals and 36 private physicians (listed in http://www.shcs.ch/180-health-care-providers).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
10.
Die kutane Nocardiose Schröder, Ulrich; Brandenberger, Marcel; Piso, Rein Jan
Forum médical suisse (En ligne),
09/2018
Journal Article
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