Early hydroxychloroquine but not chloroquine use reduces ICU admission in COVID-19 patients.

BACKGROUND: The global push for the use of hydroxychloroquine (HCQ) and chloroquine (CQ) against COVID-19 has resulted in an ongoing discussion about the effectivity and toxicity of these drugs. Recent studies report no effect of (H)CQ on 28-day mortality. We investigated the effect of HCQ and CQ in hospitalized patients on the non-ICU COVID-ward. METHODS: A nationwide, observational cohort study was performed in The Netherlands. Hospitals were given the opportunity to decide independently on the use of three different COVID-19 treatment strategies: HCQ, CQ, or no treatment. We compared the outcomes between these groups. The primary outcomes were 1) death on the COVID-19 ward, and 2) transfer to the intensive care unit (ICU). RESULTS: The analysis included 1064 patients from 14 hospitals: 566 patients received treatment with either HCQ (n = 189) or CQ (n = 377), and 498 patients received no treatment. In a multivariate propensity-matched weighted competing regression analysis, there was no significant effect of (H)CQ on mortality on the COVID ward. However, HCQ was associated with a significantly decreased risk of transfer to the ICU (hazard ratio (HR) = 0.47, 95% CI = 0.27-0.82, p = 0.008) when compared with controls. This effect was not found in the CQ group (HR = 0.80, 95% CI = 0.55-1.15, p = 0.207), and remained significant after competing risk analysis. CONCLUSION: The results of this observational study demonstrate a lack of effect of (H)CQ on non-ICU mortality. However, we show that the use of HCQ - but not CQ - is associated with a 53% reduction in risk of transfer of COVID-19 patients from the regular ward to the ICU. Recent prospective studies have reported on 28-day, all-cause mortality only; therefore, additional prospective data on the early effects of HCQ in preventing transfer to the ICU are still needed.

The effect of antimicrobial drug use on the composition of the genitourinary microbiota in an elderly population.

BACKGROUND: The urinary tract is inhabited by a diversity of microorganisms, known as the genitourinary microbiota. Here, we investigated the association between the use of antimicrobial drugs and the composition of the genitourinary microbiota. RESULTS: Clean-catch urinary samples were collected from 27 participants of the Rotterdam Study. Bacterial DNA was extracted and the 16S ribosomal RNA gene variable regions V3 and V4 were analyzed using Illumina sequencing. 23 of the 27 participants were included in the analysis. The population consisted of 10 men and 13 women with a mean age of 75 ± 3 years. The time between the last prescription of an antimicrobial drug and sampling was determined and categorized. The use of antimicrobial drugs prior to urine sampling was associated with statistically significant differences in the beta-diversity of the genitourinary microbiota. No association was found between antimicrobial drug use and the alpha-diversity of the genitourinary microbiota. Operational Taxonomic Units (OTUs) that were lowest in participants who used antimicrobial drug belonged to Lactobacillus and Finegoldia. In contrast, an OTU belonging to the genus Parabacteroides had higher abundances. Also, an OTU belonging to the species E.coli was higher in the participants who used antimicrobial drugs. CONCLUSION: Prior use of antimicrobial drugs is associated with a different composition of the genitourinary microbiota. Our results might indicate a persisting effect of antimicrobial drugs on the composition of the microbiota, but reverse causality cannot be ruled out. Future studies are needed to differentiate between two possibilities. Genitourinary dysbiosis could be the result of antimicrobial drug use or genitourinary dysbiosis could be a risk factor for urinary tract infections resulting in increased use of antimicrobial drugs. This may have important implications for treatment and prevention of (recurrent) UTIs.

[ASalmonellainfection in a pregnant traveller]. / EenSalmonella-infectie bij een zwangere reiziger.

BACKGROUND: Infectious diseases are a common problem in people who travel to countries with poor hygiene standards. Pregnant travellers are subjected to increased risk because of the higher probability of complications in case of certain infectious diseases and the variability of prenatal care quality in these countries. CASE DESCRIPTION: A pregnant patient presented herself at the emergency department with recurring fever and chills, a month after she had been to Indonesia. This was associated with a Salmonella infection; the placenta was the infection reservoir. CONCLUSION: Travelling while pregnant is not without risk. Quick diagnosis and treatment of infections, which may sometimes have an atypical presentation during pregnancy, can be of crucial importance. It is extra important for pregnant people to get travel advice before the trip, so that risks, alarming symptoms and additional hygiene measures can be discussed.

Hepatitis E prevalence among HIV infected patients with elevated liver enzymes in the Netherlands.

BACKGROUND: In recent years chronic hepatitis E virus (HEV) infections have been reported in immunosuppressed patients, including HIV-positive patients with low CD4 cell counts. Because of delayed anti-HEV seroconversion in patients with CD4 cell count<200 cells/ml it is difficult to draw firm conclusions on HEV-seroprevalence in a population of HIV positive patients. OBJECTIVES: To determine the HEV seroprevalence in a population of HIV infected patients. STUDY DESIGN: We retrospectively analysed the HEV prevalence in a population of 256 HIV infected patients with liver enzyme elevations (LEEs), using HEV specific antibody testing and HEV-RNA detection. RESULTS: Within this cohort we observed a HEV-seroprevalence of 11.7%, without any anti-HEV IgM positive or HEV-RNA positive cases. HEV seropositivity was equally prevalent among different CD4(+) cell count groups. CONCLUSION: Although HIV infected patients in the Netherlands are at risk of acquiring HEV, the number of acute infections is low and no chronic cases were found.

Decreased ciprofloxacin susceptibility in Salmonella Typhi and Paratyphi infections in ill-returned travellers: the impact on clinical outcome and future treatment options.

The emergence of decreased ciprofloxacin susceptibility (DCS) in Salmonella enterica serovar Typhi and serovar Paratyphi A, B or C limits treatment options. We studied the impact of DCS isolates on the fate of travellers returning with enteric fever and possible alternative treatment options. We evaluated the clinical features, susceptibility data and efficacy of empirical treatment in patients with positive blood cultures of a DCS isolate compared to patients infected with a ciprofloxacin-susceptible (CS) isolate in the period from January 2002 to August 2008. In addition, the pharmacokinetic and pharmacodynamic parameters of ciprofloxacin, levofloxacin and gatifloxacin were determined to assess if increasing the dose would result in adequate unbound fraction of the drug 24-h area under the concentration-time curve/minimum inhibitory concentration (ƒAUC(0-24)/MIC) ratio. Patients with DCS more often returned from the Indian subcontinent and had a longer fever clearance time and length of hospital stay compared to patients in whom the initial empirical therapy was adequate. The mean ƒAUC(0-24)/MIC was 41.3 ± 18.8 in the patients with DCS and 585.4 ± 219 in patients with a CS isolate. For DCS isolates, the mean ƒAUC0-24/MIC for levofloxacin was 60.5 ± 28.7 and for gatifloxacin, it was 97.9 ± 28.0. Increasing the dose to an adequate ƒAUC(0-24)/MIC ratio will lead to conceivably toxic drug levels in 50% of the patients treated with ciprofloxacin. Emerging DCS isolates has led to the failure of empirical treatment in ill-returned travellers. We demonstrated that, in some cases, an adequate ƒAUC(0-24)/MIC ratio could be achieved by increasing the dose of ciprofloxacin or by the use of alternative fluoroquinolones.

[First case of chikungunya diagnosed in the Netherlands]. / Chikungunya voor het eerst gediagnosticeerd in Nederland.

A 52-year-old man was seen in the Diagnostic Centre for Tropical Diseases of the Havenziekenhuis, Rotterdam, presenting with arthralgia, fever and exanthema following a stay in Mauritius. Infection with the Dengue virus infection is a common diagnosis for this combination of complaints, but nowadays chikungunya should also be considered. This is particularly the case when a patient has visited a country in or around the Indian Ocean. Risk areas are La Réunion and Mauritius, where, in February 2005 and April 2005 respectively, epidemics broke out. Chikungunya is a viral infection. The causative virus is an Alpha virus, transmitted by mosquitoes. The symptoms include arthralgia, myalgia, diffuse maculopapular rash, fever and headache. In contrast to dengue, chikungunya is not associated with haemorrhagic diathesis. Treatment takes place in response to the symptoms, since there is no targeted therapy available. The main preventive measure is to prevent mosquito bites. The disease is not deadly and healing is spontaneous. To our knowledge this is the first case of chikungunya diagnosed in the Netherlands during this epidemic. The disease has recently been reported in Italy, where native mosquitoes transmit it.