Comparative effectiveness of ß-lactams for empirical treatment of methicillin-susceptible Staphylococcus aureus bacteraemia: a prospective cohort study.

OBJECTIVES: Standard once-daily dosing of ceftriaxone may not lead to adequate antibiotic exposure in all cases of Staphylococcus aureus bacteraemia (SAB). Therefore, we compared clinical effectiveness of empirical antibiotic treatment with flucloxacillin, cefuroxime and ceftriaxone in adult patients with MSSA bacteraemia. METHODS: We analysed data from the Improved Diagnostic Strategies in Staphylococcus aureus bacteraemia (IDISA) study, a multicentre prospective cohort study of adult patients with MSSA bacteraemia. Duration of bacteraemia and 30 day SAB-related mortality were compared between the three groups using multivariable mixed-effects Cox regression analyses. RESULTS: In total, 268 patients with MSSA bacteraemia were included in the analyses. Median duration of empirical antibiotic therapy was 3 (IQR 2-3) days in the total study population. Median duration of bacteraemia was 1.0 (IQR 1.0-3.0) day in the flucloxacillin, cefuroxime and ceftriaxone groups. In multivariable analyses, neither ceftriaxone nor cefuroxime was associated with increased duration of bacteraemia compared with flucloxacillin (HR 1.08, 95% CI 0.73-1.60 and HR 1.22, 95% CI 0.88-1.71). In multivariable analysis, neither cefuroxime nor ceftriaxone was associated with higher 30 day SAB-related mortality compared with flucloxacillin [subdistribution HR (sHR) 1.37, 95% CI 0.42-4.52 and sHR 1.93, 95% CI 0.67-5.60]. CONCLUSIONS: In this study, we could not demonstrate a difference in duration of bacteraemia and 30 day SAB-related mortality between patients with SAB empirically treated with flucloxacillin, cefuroxime or ceftriaxone. Since sample size was limited, it is possible the study was underpowered to find a clinically relevant effect.

Implementation of the 2015 European Society of Cardiology guidelines for the management of infective endocarditis in the Netherlands.

Because the occurrence of infective endocarditis (IE) continues to be associated with high mortality, a working group was created by the Dutch Society of Cardiology to examine how the most recent European Society of Cardiology (ESC) guidelines for IE management could be implemented most effectively in the Netherlands. In order to investigate current Dutch IE practices, the working group conducted a country-wide survey. Based on the results obtained, it was concluded that most ESC recommendations could be endorsed, albeit with some adjustments. For instance, the suggested pre-operative screening and treatment of nasal carriers of Staphylococcus aureus as formulated in the ESC guideline was found to be dissimilar to current Dutch practice, and was therefore made less restrictive. The recently adapted ESC diagnostic criteria for IE were endorsed, while the practical employment of the relevant diagnostic techniques was simplified in an adapted flowchart. In addition, the presence of a multidisciplinary, so-called 'endocarditis team' in tertiary centres was proposed as a quality indicator. An adapted flowchart specifically tailored to Dutch practice for microbiological diagnostic purposes was constructed. Lastly, the working group recommended the Stichting Werkgroep Antibioticabeleid (SWAB; Dutch Working Party on Antibiotic Policy) guidelines for IE treatment instead of the antibiotic regimens proposed by the ESC.

[Antibiotic prophylaxis and endocarditis]. / AB-profylaxe en endocarditis.

The use of antibiotics before an invasive dental procedure to prevent endocarditis as a consequence of the procedure is based on experimental research on animals. The efficacy of this measure has, however, not yet been demonstrated in humans. Starting in 2007, therefore, fewer heart diseases have been indicated for endocarditis prophylaxis.

Sofosbuvir plus simeprevir for the treatment of HCV genotype 4 patients with advanced fibrosis or compensated cirrhosis is highly efficacious in real life.

Chronic hepatitis C virus (HCV) infection is a major cause of chronic liver disease and liver-related death. Recently, multiple regimens of different direct-acting antiviral agents (DAAs) have been registered. Although treatment with sofosbuvir (SOF) and simeprevir (SMV) is registered for the treatment of genotype 4 patients in some countries, data on efficacy of this combination are lacking. We aimed to assess the efficacy of SOF and SMV with or without RBV during 12 weeks in a real-life cohort of genotype 4 HCV patients. A retrospective multicentre observational study was conducted in 4 hospitals in Amsterdam, the Netherlands, including patients with advanced liver fibrosis or liver cirrhosis treated with SOF plus SMV with or without RBV during 12 weeks for a genotype 4 chronic HCV infection from 1 January 2015 to 1 August 2015. Sustained viral response (SVR) was established at week 12 after end of treatment. A total of 53 patients with genotype 4 HCV infection, treatment naïve and experienced, were included. SVR was achieved in 49 of 53 patients (92%). The four failures all had a virological relapse and did not receive ribavirin. Three were nonresponder to earlier interferon-based treatment, and one was treatment naive. In this real-life cohort of patients with HCV genotype 4 infection and advanced liver fibrosis/cirrhosis, we show that treatment with SOF and SMV is effective. The addition of RBV could be considered in treatment-experienced patients as recommended in guidelines.

Acute kidney injury in Staphylococcus aureus bacteremia: a recurrent events analysis.

OBJECTIVES: To estimate risk factors for AKI and the effect of AKI on mortality in Staphylococcus aureus bacteremia, while taking into account recurrent AKI episodes, competing risks, time-varying variables and time-varying effects. METHODS: We performed an unplanned analysis using data from a multicenter cohort study of patients with SAB. Primary outcome was cumulative incidence of AKI, according to KDIGO definitions. RESULTS: We included 453 patients in this study of whom 194 (43%) patients experienced one or more AKI episodes. Age (HR 1.013, 95% CI 1.001 - 1.024), Charlson comorbidity index (HR 1.07, 95% CI 1.01 - 1.14), prior chronic kidney disease (HR 1.76, 95% CI 1.28 - 2.42), septic shock (HR 3.28, 95% CI 2.31 - 4.66), persistent bacteremia (HR 1.53, 95% CI 1.08 - 2.17) and vancomycin therapy (HR 1.80, 95% CI 1.05 - 3.09) were independently associated with AKI, but flucloxacillin, cefazolin, rifampicin and aminoglycoside therapy were not. After adjustment for confounders and immortal time bias, AKI was associated with an increased risk of 90-day mortality (HR 4.26, 95% CI 2.91 - 6.23). CONCLUSIONS: Incidence of AKI in SAB is high and a substantial proportion of patients develops recurrent episodes of AKI after recovery. AKI is specifically linked to the use of vancomycin and not to anti-staphylococcal penicillins. Clinical outcome of patients with SAB complicated by AKI is worse than previously estimated.

Effectiveness of highly active antiretroviral therapy administered by general practitioners in rural South Africa.

The purpose of this study was to assess the one-year efficacy of highly active antiretroviral therapy (HAART) administered by general practitioners in a primary care community clinic in rural South Africa. We performed an observational cohort study of 675 treatment-naive human immunodeficiency virus (HIV)-infected patients (including 66 children) who began HAART at least 12 months prior to the data analyses. Throughout treatment, the CD4+ T-cell count (percentage of CD4+ T-cells in children) and plasma HIV-RNA level were determined and the patient's weight was recorded. The primary outcome was mortality. Secondary outcomes were viral suppression, immunological response, and weight gain. One year after the start of HAART, 100 of the 675 (15%) patients were lost to follow-up and 119 patients (18%), including six children, died. Mortality was highest during the first few months of treatment. Based on an on-treatment analysis at one year after the start of therapy, 83% of adults and 71% of children had a viral load <400 copies/ml; the viral load was <50 copies/ml in 70% of adults and 61% of children. At one year, the mean CD4+ T-cell count in adults had increased by 236/mm(3), and the mean body mass index (BMI) had increased by 3.5 kg/m(2). In children, the mean CD4% had increased by 17.6. A low Karnofsky score and a low baseline CD4+ T-cell count were independently associated with death. In addition to these factors, a low baseline BMI and gender were predictive of a poor immunological outcome. Our study shows that adequately monitored HIV/acquired immunodeficiency syndrome (AIDS) care administered by general practitioners and their staff is feasible and leads to good results in a rural, primary care center in sub-Saharan Africa. In order to achieve even better results, early mortality should be reduced and efforts should be made to start HAART earlier.

[Central catheters should be removed immediately if bacteraemia occurs]. / Bij bacteriëmie moet een diepe lijn direct worden verwijderd.

No randomised controlled study has been conducted into the correct treatment of catheter-related bacteraemia infections. This is due to the fact that true bacteraemia is difficult to differentiate from catheter contamination. Experience in the treatment of patients who do not have bacteraemia is therefore often incorrectly extrapolated to patients who do have bacteraemia with a central catheter in situ. Removing the central catheter can reduce the risk of complications of bacteraemia.

Acute hepatitis C in the Netherlands: characteristics of the epidemic in 2014.

Within the Dutch Acute HCV in HIV Study, a surveillance system was initiated to estimate the incidence of hepatitis C virus (HCV) infections in 2014. Following the Dutch HIV treatment guidelines, HIV-positive men having sex with men (MSM) in 19 participating centers were screened. Ninety-nine acute HCV infections were reported, which resulted in a mean incidence of 11 per 1000 patient-years of follow-up. Unfortunately, the HCV epidemic among Dutch HIV-positive MSM is not coming to a halt.

Favourable SVR12 rates with boceprevir or telaprevir triple therapy in HIV/HCV coinfected patients.

BACKGROUND: Recent publications have reported superior efficacy of telaprevir- or boceprevir-based triple therapy over conventional peginterferon-alfa/ribavirin therapy, albeit with varying rates of adverse events and treatment discontinuations in HIV/HCV coinfected patients. Therefore, the aim of this study is to describe the effectiveness of triple therapy in an HIV/HCV coinfection cohort in the Netherlands. METHODS: HIV-infected patients with chronic HCV genotype 1 starting triple therapy including either boceprevir or telaprevir were enrolled, 26% had F3-F4 fibrosis. Data were assessed at Week 4, 8, 12, 24, 48 and SVR12 (i.e. absence of detectable plasma HCV RNA 12 weeks after completion of treatment). Failure was defined as discontinuation of treatment due to virological failure, adverse events or loss to follow-up. RESULTS: A total of 53 HIV/HCV coinfected patients started peginterferon-alfa/ribavirin therapy with either boceprevir (n = 29) or telaprevir (n = 24). SVR12 was achieved in 19 (66%) of the boceprevir-treated and 15 (63%) of the telaprevir-treated patients. Both prior relapse and achievement of a rapid virological response were associated with a higher SVR12 rate. Non- response, breakthrough and relapse occurred in 4, 1 and 5 patients on boceprevir and 3, 2, 2 on telaprevir, respectively. One patient was lost to follow-up and one patient died due to progression of liver failure. Except for these two patients, no treatment discontinuations were observed due to adverse events. CONCLUSION: In HIV/HCV coinfected patients, boceprevir or telaprevir triple therapy was well tolerated and resulted in favourable SVR12 rates comparable with previous publications concerning HCV mono-infected patients.

Risk Factors for Sexual Transmission of Hepatitis C Virus Among Human Immunodeficiency Virus-Infected Men Who Have Sex With Men: A Case-Control Study.

Background. Since 2000, incidence of sexually acquired hepatitis C virus (HCV)-infection has increased among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM). To date, few case-control and cohort studies evaluating HCV transmission risk factors were conducted in this population, and most of these studies were initially designed to study HIV-related risk behavior and characteristics. Methods. From 2009 onwards, HIV-infected MSM with acute HCV infection and controls (HIV-monoinfected MSM) were prospectively included in the MOSAIC (MSM Observational Study of Acute Infection with hepatitis C) study at 5 large HIV outpatient clinics in the Netherlands. Written questionnaires were administered, covering sociodemographics, bloodborne risk factors for HCV infection, sexual behavior, and drug use. Clinical data were acquired through linkage with databases from the Dutch HIV Monitoring Foundation. For this study, determinants of HCV acquisition collected at the inclusion visit were analyzed using logistic regression. Results. Two hundred thirteen HIV-infected MSM (82 MSM with acute HCV infection and 131 MSM without) were included with a median age of 45.7 years (interquartile range [IQR], 41.0-52.2). Receptive unprotected anal intercourse (adjusted odds ratio [aOR], 5.01; 95% confidence interval [CI], 1.63-15.4), sharing sex toys (aOR, 3.62; 95% CI, 1.04-12.5), unprotected fisting (aOR, 2.57; 95% CI, 1.02-6.44), injecting drugs (aOR, 15.62; 95% CI, 1.27-192.6), sharing straws when snorting drugs (aOR, 3.40; 95% CI, 1.39-8.32), lower CD4 cell count (aOR, 1.75 per cubic root; 95% CI, 1.19-2.58), and recent diagnosis of ulcerative sexually transmitted infection (aOR, 4.82; 95% CI, 1.60-14.53) had significant effects on HCV acquisition. Conclusions. In this study, both sexual behavior and biological factors appear to independently increase the risk of HCV acquisition among HIV-infected MSM.

QUOTE-HIV: an instrument for assessing quality of HIV care from the patients' perspective.

BACKGROUND: An HIV-specific version of the QUOTE questionnaire was developed to measure the quality of care of patients infected with HIV from the patients' perspective. The consistency and validity of the questionnaire was assessed. METHODS: Focus group discussions were held to select aspects for inclusion in the questionnaire that are important to patients with HIV. Item and inter-item analysis, factor analysis, and reliability analysis were performed to test the internal consistency and validity of the questionnaire. RESULTS: Twenty seven items (13 generic and 14 HIV specific) were used in the QUOTE-HIV questionnaire. Separate factor analyses of the generic and HIV specific aspects indicated that each loaded onto a single factor. The internal consistency of the total questionnaire was good (Cronbach's alpha >/=0.80). Feasibility of the questionnaire was shown by the diversity of importance and performance scores for general practitioners as well as for HIV specialists and AIDS nursing consultants. CONCLUSION: The QUOTE-HIV questionnaire is a useful instrument for measuring the quality of care from the perspective of HIV infected patients.

Prophylaxis of endocarditis.

For a long time it has been known that bacteraemias caused by medical or dental procedures may cause endocarditis in patients with specific types of congenital or acquired heart disease. In the 1940s it was thought that the administration of antibiotics before such procedures would prevent endocarditis. However, the beneficial effect of this preventive measure on the incidence of endocarditis did not live up to its expectations. Quite soon it became obvious that prophylaxis was not 100% efficacious in man, although it did prevent endocarditis in animals. A controlled study into the protective effect of prophylaxis in humans has never been carried out. In the last decade it has become dear from case-control studies that endocarditis prophylaxis is not a very effective preventive measure but that it reduces an already small risk even further. In this article the theoretical background of endocarditis prophylaxis and possible explanations for its lack of effect are discussed.

Optimisation of the antibiotic guidelines in The Netherlands. VII. SWAB guidelines for antimicrobial therapy in adult patients with infectious endocarditis.

The Working Party on Antibiotic Policy (Dutch acronym is SWAB) is a Dutch organisation that develops guidelines for in-hospital antimicrobial therapy of bacterial infectious diseases. This present guideline describes the antimicrobial treatment for adult patients with infective endocarditis. The choice and duration of antimicrobial therapy is determined by the infecting micro-organism, sensitivity of this micro-organism for antimicrobial therapy, location of the endocarditis, left-sided or right-sided, and presence of intracardial prosthetic material. In this guideline, the empirical therapy for endocarditis is discussed as well as the therapy for the most frequent causative organisms: streptococci, enterococci, staphylococci and HACEK micro-organisms.

[Sexual transmission of hepatitis C in homosexual men]. / Seksuele overdracht van hepatitis C bij homoseksuele mannen.

An acute hepatitis C infection was diagnosed in three HIV-positive gay men, aged 43, 48 and 30 years, respectively. In all three, unprotected sexual intercourse and fisting was a universal risk factor for the infection. They all denied having used drugs intravenously, which is the most common risk factor. The third man had a documented proctitis (lymphogranuloma venereum) at the time when the HCV transmission must have taken place. No serious complications occurred during the acute HCV infection. Because the infection did not resolve spontaneously after a few months, all three men were treated with pegylated interferon and ribavirin. Recently, the number of cases of acute HCV infection has been seen to increase in The Netherlands. This may be due primarily to an increase in unprotected sexual intercourse and fisting. This hypothesis is supported by a documented increased prevalence of sexually transmissible diseases among gay men in The Netherlands. As acute infections may turn into chronic infections, treatment of an acute infection should be considered in order to prevent the chronic disease.

[Guidelines for endocarditis prevention revised by the Netherlands Heart Foundation]. / Richtlijnen van de Nederlandse Hartstichting voor preventie van endocarditis herzien.

The risk of endocarditis developing as the consequence of a bacteremia caused by a health care procedure in a patient with a predisposing heart disease is small. The administration of antibiotics before such a procedure is thought to reduce this risk still further. However, the protective effect of this preventive measure has never been demonstrated in a prospective randomized study. With certainty it can be said though, that it is not 100% efficacious and reports on prophylaxis failure have appeared ever since the introduction of this preventive measure. The revised guidelines are as far as possible based on published data. Where data are lacking, experts opinion was followed. The guidelines are not exhaustive and do not cover each and every circumstance in which prophylaxis could be warrantable. The purpose of the guidelines is to give the clinician something to go by in the most frequently occurring health care procedures. Not everyone will agree with the choices made by the commission in areas where data are lacking. In these areas, local directives may differ from the published directives. For a made to order advice on prophylaxis one should turn to an expert on endocarditis.

Treatment of acute hepatitis C virus infection in HIV+ patients: Dutch recommendations for management.

With a rising incidence of acute hepatitis C virus (HCV) infection in patients coinfected with the human immunodeficiency virus (HIV), there is a need for evidence-based treatment recommendations. There are no randomised trials available and published studies differ with respect to design, patient characteristics and number of patients included, making a comparison between studies difficult. However, it is critical to standardise treatment for this group of patients in order to optimise the outcome of therapy. The Dutch Society for HIV Physicians proposed to write recommendations for the treatment of acute HCV in HIV -coinfected patients. Combination therapy with pegylated interferon-alpha and ribavirin is the preferred regimen initiated preferably within 12 weeks after the diagnosis of acute HCV. A treatment duration of 24 weeks is recommended in case of a favourable virological response (either achievement of a rapid virological response or a > 2 log10 decrease plus undetectable HCV-RNA at week 12). In all other patients prolonging the duration of therapy to 48 weeks should be considered.

Left-sided native valve Staphylococcus aureus endocarditis.

Despite improved diagnostic tools and expanded treatment options, left-sided native valve endocarditis caused by Staphylococcus aureus infection remains a serious and destructive disease. The high morbidity and mortality, however, can be reduced by early recognition, correct diagnosis, and appropriate treatment. In the following article, we discuss the clinical presentation, diagnostic workup and treatment of infective endocarditis, thereby reviewing the current guidelines. Blood cultures and echocardiography are the cornerstones of diagnosis in identifying infective endocarditis but are no substitute for clinical judgement. The modified Duke criteria may facilitate the diagnostic process, but clinical evaluation remains crucial.

Extension of antimicrobial treatment in patients with left-sided native valve endocarditis based on elevated C-reactive protein values.

The aim of this non-randomized study was to investigate whether there is any benefit in the extension of antimicrobial treatment in patients with left-sided native valve endocarditis in whom C-reactive protein levels are still elevated after a standard course of therapy. There was no statistically significant difference in outcome between the group of patients in which treatment was extended in comparison to the group in which treatment was ended at the recommended time. It is unlikely that there is much to gain from extending treatment based on elevated C-reactive protein levels alone.