Rainer Weber

University of Zurich, Zürich, Zurich, Switzerland

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Publications (194)1461.92 Total impact

  • Clinical Infectious Diseases 05/2015; DOI:10.1093/cid/civ398 · 9.42 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate the clinical value of positron emission tomography/computed tomography with (18)F-fluorodeoxyglucose (FDG-PET/CT) for therapy control in patients with prosthetic vascular graft infections (PVGI). In this single-centre, observational, prospective cohort study, 25 patients with a median age of 66 years (range: 48-81) were included who had a proven PVGI. Follow-up FDG-PET/CT was performed at a median time interval of 170 days (range: 89-249) after baseline examination. Two independent and blinded readers measured maximum standardized uptake values (SUV max.) to quantify metabolic activity and analysed whole body datasets for secondary diagnosis (i.e., infectious foci not within graft vicinity). The metabolic activity of the graft was correlated with clinical information and two laboratory markers (C-reactive protein (CRP) and white blood cell count (WBC)). FDG-PET/CT had an impact on management in all patients. In 19 of 25 patients (76%) antibiotic treatment was continued due to the results of follow-up FDG-PET/CT. Antibiotic treatment was stopped or changed in 8% and 16% of patients, respectively. In eight patients (32%) additional incidental findings were detected on follow-up FDG-PET/CT which had further impact on patient management. Only in a subgroup of patients with PVGI and no other sites of infection, a significant correlation between the difference in CRP at the time of baseline and follow-up FDG-PET/CT and the difference in SUV max. was found (n = 11; r = 0.84; P = 0.001). FDG-PET/CT represents a useful tool in therapy monitoring of PVGI and impacts on patient management. By providing quantitative data on the course of the graft infection and whole body imaging data, PET/CT differentiates between response of therapy to PVGI and other infectious foci. Copyright © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
    Journal of Nuclear Medicine 05/2015; DOI:10.2967/jnumed.115.156265 · 5.56 Impact Factor
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    ABSTRACT: The landscape of HCV treatments is changing dramatically. At the beginning of this new era, we highlight the challenges for HCV-therapy by assessing the long-term epidemiological trends in treatment uptake, efficacy and mortality among HIV/HCV-coinfected people since the availability of HCV therapy. We included all SHCS participants with detectable HCV RNA between 2001 and 2013. To identify predictors for treatment uptake uni- and multivariable Poisson regression models were applied. We further used survival analyses with Kaplan-Meier curves and Cox regression with drop-out as competing risk. Of 12,401 participants 2107 (17%) were HCV RNA positive. Of those, 636 (30%) started treatment with an incidence of 5.8/100 person years (PY) (95% CI 5.3-6.2). Sustained virological response (SVR) with pegylated interferon/ribavirin was achieved in 50% of treated patients, representing 15% of all participants with replicating HCV infection. 344 of 2107 (16%) HCV RNA positive persons died, 59% from extrahepatic causes. Mortality/100 PY was 2.9 (95% CI 2.6-3.2) in untreated patients, 1.3 (1.0-1.8) in those treated with failure, and 0.6 (0.4-1.0) in patients with SVR. In 2013, 869/2107 (41%) participants remained HCV RNA positive. Over the last 13 years HCV treatment uptake was low and by the end of 2013, a large number of persons remain to be treated. Mortality was high, particularly in untreated patients, and mainly due to non-liver related causes. Accordingly, in HIV/HCV-coinfected patients, integrative care including the diagnosis and therapy of somatic and psychiatric disorders is important to achieve mortality rates similar to HIV-monoinfected patients. Copyright © 2015. Published by Elsevier B.V.
    Journal of Hepatology 04/2015; DOI:10.1016/j.jhep.2015.04.019 · 10.40 Impact Factor
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    ABSTRACT: Patients with HIV exposed to the antiretroviral drug abacavir may have an increased risk of cardiovascular disease (CVD). There is concern that this association arises because of a channelling bias. Even if exposure is a risk, it is not clear how that risk changes as exposure cumulates. We assess the effect of exposure to abacavir on the risk of CVD events in the Swiss HIV Cohort Study. We use a new marginal structural Cox model to estimate the effect of abacavir as a flexible function of past exposures while accounting for risk factors that potentially lie on a causal pathway between exposure to abacavir and CVD. 11,856 patients were followed for a median of 6.6 years; 365 patients had a CVD event (4.6 events per 1000 patient years). In a conventional Cox model, recent - but not cumulative - exposure to abacavir increased the risk of a CVD event. In the new marginal structural Cox model, continued exposure to abacavir during the past four years increased the risk of a CVD event (hazard ratio 2.06, 95% confidence interval 1.43-2.98). The estimated function for the effect of past exposures suggests that exposure during the past 6 to 36 months caused the greatest increase in risk. Abacavir increases the risk of a CVD event: the effect of exposure is not immediate, rather the risk increases as exposure cumulates over the past few years. This gradual increase in risk is not consistent with a rapidly acting mechanism, such as acute inflammation.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 04/2015; DOI:10.1097/QAI.0000000000000662 · 4.39 Impact Factor
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    ABSTRACT: With the aging of the population living with HIV, the absolute risk of cardiovascular disease (CVD) is increasing. There is a need to further facilitate the identification of persons at elevated risk in routine practice. Prospective information was collected on 32,663 HIV-positive persons from 20 countries in Europe and Australia, who were free of CVD at entry into the Data-collection on Adverse Effects of Anti-HIV Drugs (D:A:D) study. Cox regression models (full and reduced) were developed that predict the risk of a global CVD endpoint. The predictive performance of the D:A:D models were compared with a recent CVD prediction model from the Framingham study, which was assessed recalibrated to the D:A:D dataset. A total of 1010 CVD events occurred during 186,364.5 person-years. The full D:A:D CVD prediction model included age, gender, systolic blood pressure, smoking status, family history of CVD, diabetes, total cholesterol, high-density lipoprotein, CD4 lymphocyte count, cumulative exposure to protease- and nucleoside reverse transcriptase-inhibitors, and current use of abacavir. A reduced model omitted antiretroviral therapies. The D:A:D models statistically significantly predicted risk more accurately than the recalibrated Framingham model (Harrell's c-statistic of 0.791, 0.783 and 0.766 for the D:A:D full, D:A:D reduced, and Framingham models respectively; p < 0.001). The D:A:D models also more accurately predicted five-year CVD-risk for key prognostic subgroups. An updated, easily recalibrated, global CVD-risk equation tailored to HIV-positive persons was developed using routinely collected CVD risk parameters and incorporating markers on immune function (CD4 lymphocyte count), and exposure to antiretroviral therapies. The estimated CVD risk can be used to quantify risk and to guide preventive care. © The European Society of Cardiology 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
    04/2015; DOI:10.1177/2047487315579291
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    ABSTRACT: Background. Invasive Mycobacterium chimaera infections were diagnosed in 2012 in two heart surgery patients on extracorporeal circulation. We launched an outbreak investigation to identify the source and extent of the potential outbreak, and to implement preventive measures. Methods. We collected water samples from operating theatres, intensive care units, and wards, including air samples from operating theatres. M. chimaera strains were characterised by randomly amplified polymorphic DNA polymerase chain reaction (RAPD-PCR). Case detection was performed based on archived histopathology samples and M. chimaera isolates since 2006, and the patient population at risk was prospectively surveyed. Results. We identified six male patients aged between 49−64 years with prosthetic valve endocarditis or vascular graft infection due to M. chimaera, which became clinically manifest with a latency of between 1.5 and 3.6 years after surgery. M. chimaera was isolated from cardiac tissue specimens, blood cultures, or other biopsy specimens. We were able also to culture M. chimaera from water circuits of heater-cooler units connected to the cardiopulmonary bypass, and air samples collected when the units were in use. RAPD-PCR demonstrated identical patterns among M. chimaera strains from heater-cooler unit water circuits and air samples, and strains in two patient clusters. Conclusions. The epidemiological and microbiological features of this prolonged outbreak provided evidence for the airborne transmission of M. chimaera from contaminated heater-cooler unit water tanks to patients during open-heart surgery.
    Clinical Infectious Diseases 03/2015; DOI:10.1093/cid/civ198 · 9.42 Impact Factor
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    ABSTRACT: infection Published online December 2, 2014 hhttp://dx.doi.org/10.1016/S1473-3099(14)71000-X 1 Articles Travel-associated infection presenting in Europe (2008–12): an analysis of EuroTravNet longitudinal, surveillance data, and evaluation of the eff ect of the pre- Summary Background Travel is important in the acquisition and dissemination of infection. We aimed to assess European surveillance data for travel-related illness to profi le imported infections, track trends, identify risk groups, and assess the usefulness of pre-travel advice.
    The Lancet Infectious Diseases 12/2014; DOI:10.1016/S1473-3099(14)71000-X · 19.45 Impact Factor
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    ABSTRACT: Introduction A recent meta-analysis of 4 RCTs showed an increased rate of suicidality events (suicidal ideation or attempted/completed suicide) associated with efavirenz (EFV) compared to other regimens, but only a trend towards a higher rate of completed/attempted suicides, as only 17 events occurred. We investigated the association between EFV use and completed suicide. Materials and Methods All D:A:D participants were followed from study entry to the first of death, last study visit or 1 February 2013. Deaths are centrally validated using cause of death methodology, which assigns underlying, immediate and up to four contributing causes of death. Two endpoints were considered: 1) suicide or psychiatric disease as the underlying cause, and 2) suicide or psychiatric disease mentioned as an underlying, immediate or contributing cause of death (anywhere). Adjusted rate ratios were calculated using Poisson regression. Results A total of 4420 deaths occurred in 49,717 people over 371,333 person-years (PY) (rate 11.9 per 1000 PY; 95% CI 11.6–12.3). A total of 193 deaths (rate 0.52; 0.45–0.59) had an underlying cause of suicide or psychiatric disease, and 482 deaths (1.30; 1.18–1.41) had suicide or psychiatric disease mentioned anywhere. A strong association with current CD4 count was seen: for suicide or psychiatric disease mentioned anywhere, rates were: 3.18 (2.55–3.80) for <200 cells/uL, 1.60 (1.29–1.90) for 201–350 cells/uL, 1.07 (0.86–1.29) for 351–500 cells/uL, 0.95 (0.80–1.09) for >500 cells/uL and 1.30 (1.18–1.41) for unknown. Highest rate of suicide or psychiatric deaths were seen in ART-experienced people currently off ART, but no differences were seen according to current ART regimen, which remained after adjustment (Table 1). Consistent results were obtained when considering additional endpoints of suicide alone as the underlying cause and death from suicide or any possibly related cause (psychiatric disease, drug overdose, alcohol related, accidental or violent), as well as considering recent EFV use in the previous 3 and 6 months. Conclusions The finding of no higher death rates from suicide amongst those receiving EFV is reassuring. However, there is likely confounding by indication in our observational study. In light of conflicting results from RCTs, this potentially could suggest that in clinical practice EFV may be less frequently prescribed in those with underlying psychiatric conditions.
    Journal of the International AIDS Society 11/2014; 17(4 Suppl 3):19512. DOI:10.7448/IAS.17.4.19512 · 4.21 Impact Factor
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    ABSTRACT: Introduction According to reports from observational databases, classic AIDS-defining opportunistic infections (ADOIs) occur in patients with CD4 counts above 500/µL on and off cART. Adjudication of these events is usually not performed. However, ADOIs are often used as endpoints, for example, in analyses on when to start cART. Materials and Methods In the database, Swiss HIV Cohort Study (SHCS) database, we identified 91 cases of ADOIs that occurred from 1996 onwards in patients with the nearest CD4 count >500/µL. Cases of tuberculosis and recurrent bacterial pneumonia were excluded as they also occur in non-immunocompromised patients. Chart review was performed in 82 cases, and in 50 cases we identified CD4 counts within six months before until one month after ADOI and had chart review material to allow an in-depth review. In these 50 cases, we assessed whether (1) the ADOI fulfilled the SHCS diagnostic criteria (www.shcs.ch), and (2) HIV infection with CD4 >500/µL was the main immune-compromising condition to cause the ADOI. Adjudication of cases was done by two experienced clinicians who had to agree on the interpretation. Results More than 13,000 participants were followed in SHCS in the period of interest. Twenty-four (48%) of the chart-reviewed 50 patients with ADOI and CD4 >500/µL had an HIV RNA <400 copies/mL at the time of ADOI. In the 50 cases, candida oesophagitis was the most frequent ADOI in 30 patients (60%) followed by pneumocystis pneumonia and chronic ulcerative HSV disease (Table 1). Overall chronic HIV infection with a CD4 count >500/µL was the likely explanation for the ADOI in only seven cases (14%). Other reasons (Table 1) were ADOIs occurring during primary HIV infection in 5 (10%) cases, unmasking IRIS in 1 (2%) case, chronic HIV infection with CD4 counts <500/µL near the ADOI in 13 (26%) cases, diagnosis not according to SHCS diagnostic criteria in 7 (14%) cases and most importantly other additional immune-compromising conditions such as immunosuppressive drugs in 14 (34%). Conclusions In patients with CD4 counts >500/ µL, chronic HIV infection is the cause of ADOIs in only a minority of cases. Other immuno-compromising conditions are more likely explanations in one-third of the patients, especially in cases of candida oesophagitis. ADOIs in HIV patients with high CD4 counts should be used as endpoints only with much caution in studies based on observational databases.
    Journal of the International AIDS Society 11/2014; 17(4 Suppl 3):19621. DOI:10.7448/IAS.17.4.19621 · 4.21 Impact Factor
  • Therapeutische Umschau 08/2014; 71(8):461-468. DOI:10.1024/0040-5930/a000538
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    ABSTRACT: Incidence as well as morbidity and mortality of opportunistic infections (OI) have declined remarkably since the availability of antiretroviral treatment (ART). Nearly half of all persons infected with HIV however do not know their HIV-status, and the diagnosis of an OI may be the first manifestation of their HIV infection. Therefore, knowledge of the presentation of OIs as well as their management should remain an essential part of clinicians' expertise. After starting ART the immune system will improve; in this context OI may be unmasked or the clinical presentation of known OI may worsen. Before starting ART therefore, it is essential to rule out any asymptomatic or latent OI. For the same reason, in the case of a known OI, the start of ART must often be deferred for some weeks after the start of OI treatment. Treatment of OIs is complex and often results in a large pill-burden for the patient with the potential for multiple drug-drug-interactions, particularly once ART has to be started. Many of the OI treatments are also associated with frequent drug side-effects and allergies. OIs can be prevented with specific antimicrobial agents once the CD4 have decreased below a defined threshold. However, the main prevention of OI is the timely recognition of HIV infection and an early start of ART before complications of OI appear.
    Therapeutische Umschau 08/2014; 71(8):475-82. DOI:10.1024/0040-5930/a000540
  • Rainer Weber, Huldrych F. Günthard
    Therapeutische Umschau 08/2014; 71(8):433-435. DOI:10.1024/0040-5930/a000534
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    ABSTRACT: Background With the advent of effective antiretroviral treatment, the life expectancy for people with HIV is now approaching that seen in the general population. Consequently, the relative importance of other traditionally non-AIDS-related morbidities has increased. We investigated trends over time in all-cause mortality and for specific causes of death in people with HIV from 1999 to 2011. Methods Individuals from the Data collection on Adverse events of anti-HIV Drugs (D:A:D) study were followed up from March, 1999, until death, loss to follow-up, or Feb 1, 2011, whichever occurred first. The D:A:D study is a collaboration of 11 cohort studies following HIV-1-positive individuals receiving care at 212 clinics in Europe, USA, and Australia. All fatal events were centrally validated at the D:A:D coordinating centre using coding causes of death in HIV (CoDe) methodology. We calculated relative rates using Poisson regression. Findings 3909 of the 49 731 D:A:D study participants died during the 308 719 person-years of follow-up (crude incidence mortality rate, 12·7 per 1000 person-years [95% CI 12·3–13·1]). Leading underlying causes were: AIDS-related (1123 [29%] deaths), non-AIDS-defining cancers (590 [15%] deaths), liver disease (515 [13%] deaths), and cardiovascular disease (436 [11%] deaths). Rates of all-cause death per 1000 person-years decreased from 17·5 in 1999–2000 to 9·1 in 2009–11; we saw similar decreases in death rates per 1000 person-years over the same period for AIDS-related deaths (5·9 to 2·0), deaths from liver disease (2·7 to 0·9), and cardiovascular disease deaths (1·8 to 0·9). However, non-AIDS cancers increased slightly from 1·6 per 1000 person-years in 1999–2000 to 2·1 in 2009–11 (p=0·58). After adjustment for factors that changed over time, including CD4 cell count, we detected no decreases in AIDS-related death rates (relative rate for 2009–11 vs 1999–2000: 0·92 [0·70–1·22]). However, all-cause (0·72 [0·61–0·83]), liver disease (0·48 [0·32–0·74]), and cardiovascular disease (0·33 [0·20–0·53) death rates still decreased over time. The percentage of all deaths that were AIDS-related (87/256 [34%] in 1999–2000 and 141/627 [22%] in 2009–11) and liver-related (40/256 [16%] in 1999–2000 and 64/627 [10%] in 2009–11) decreased over time, whereas non-AIDS cancers increased (24/256 [9%] in 1999–2000 to 142/627 [23%] in 2009–11). Interpretation Recent reductions in rates of AIDS-related deaths are linked with continued improvement in CD4 cell count. We hypothesise that the substantially reduced rates of liver disease and cardiovascular disease deaths over time could be explained by improved use of non-HIV-specific preventive interventions. Non-AIDS cancer is now the leading non-AIDS cause and without any evidence of improvement. Funding Oversight Committee for the Evaluation of Metabolic Complications of HAART, with representatives from academia, patient community, US Food and Drug Administration, European Medicines Agency and consortium of AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, ViiV Healthcare, Merck, Pfizer, F Hoffmann-La Roche, and Janssen Pharmaceuticals.
    The Lancet 07/2014; 384(9939):241–248. DOI:10.1016/S0140-6736(14)60604-8 · 39.21 Impact Factor
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    ABSTRACT: Objective:The presence of minority nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV-1 variants prior to antiretroviral therapy (ART) has been linked to virologic failure in treatment-naive patients.Design:We performed a large retrospective study to determine the number of treatment failures that could have been prevented by implementing minority drug-resistant HIV-1 variant analyses in ART-naive patients in whom no NNRTI resistance mutations were detected by routine resistance testing.Methods:Of 1608 patients in the Swiss HIV Cohort Study, who have initiated first-line ART with two nucleoside reverse transcriptase inhibitors (NRTIs) and one NNRTI before July 2008, 519 patients were eligible by means of HIV-1 subtype, viral load and sample availability. Key NNRTI drug resistance mutations K103N and Y181C were measured by allele-specific PCR in 208 of 519 randomly chosen patients.Results:Minority K103N and Y181C drug resistance mutations were detected in five out of 190 (2.6%) and 10 out of 201 (5%) patients, respectively. Focusing on 183 patients for whom virologic success or failure could be examined, virologic failure occurred in seven out of 183 (3.8%) patients; minority K103N and/or Y181C variants were present prior to ART initiation in only two of those patients. The NNRTI-containing, first-line ART was effective in 10 patients with preexisting minority NNRTI-resistant HIV-1 variant.Conclusion:As revealed in settings of case-control studies, minority NNRTI-resistant HIV-1 variants can have an impact on ART. However, the implementation of minority NNRTI-resistant HIV-1 variant analysis in addition to genotypic resistance testing (GRT) cannot be recommended in routine clinical settings. Additional associated risk factors need to be discovered.
    AIDS (London, England) 07/2014; 28(15). DOI:10.1097/QAD.0000000000000397 · 6.56 Impact Factor
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    ABSTRACT: The association between antiretroviral treatment and cardiovascular disease (CVD) risk in HIV-positive persons has been the subject of much debate since the Data collection on Adverse events of Anti-HIV Drugs (D:A:D) study reported that recent use of two antiretroviral drugs, abacavir (ABC) and didanosine (DDI), was associated with increased risk. We focus on the potential impact of DDI use, as this drug has not been as studied intensively as ABC. We propose a flexible marginal structural Cox model with weighted cumulative exposure modeling (Cox WCE MSM) to address two key challenges encountered when using observational longitudinal data to assess the adverse effects of medication: (1) the need to model the cumulative effect of a time-dependent treatment and (2) the need to control for time-dependent confounders that also act as mediators of the effect of past treatment. Simulations confirm that the Cox WCE MSM yields accurate estimates of the causal treatment effect given complex exposure effects and time-dependent confounding. We then use the new flexible Cox WCE MSM to assess the association between DDI use and CVD risk in the Swiss HIV Cohort Study. In contrast to the nonsignificant results obtained with conventional parametric Cox MSMs, our new Cox WCE MSM identifies a significant short-term risk increase due to DDI use in the previous year. Supplementary materials for this article are available online.
    Journal of the American Statistical Association 06/2014; 109(506). DOI:10.1080/01621459.2013.872650 · 2.11 Impact Factor
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    ABSTRACT: Treponema pallidum, herpes simplex virus types 1 or 2 (HSV-1/2) and Haemophilus ducreyi are sexually transmitted pathogens that can cause genital, anal and oropharyngeal ulcers. Laboratory evaluation of these pathogens in ulcers requires different types of specimens and tests, increasing the risk for improper specimen handling and time lapse until analysis. We sought to develop a new real-time PCR to facilitate the detection of T. pallidum, HSV-1/2 and H. ducreyi in ulcers. The new real-time PCR was tested (1) in a retrospective study on 193 specimens of various clinical origin; (2) in a prospective study on 36 patients with genital, anal or oropharyngeal ulcers (ClinicalTrials.gov # NCT01688258). The results of the new real-time PCR were compared with standard diagnostic methods (T. pallidum: serology, dark field microscopy; HSV-1/2: PCR; H. ducreyi: cultivation). Sensitivity and specificity of the new real-time PCR for T. pallidum were both 100%, for HSV-1 100% and 98%, and for HSV-2 100% and 98%, respectively. T. pallidum and HSV-1/2 were detected in 53% and 22% of patients in the prospective study, H. ducreyi was not detected. In the prospective study, 5/19 (26%) specimens were true positive for T. pallidum in the new real-time PCR but non-reactive in the VDRL. The new real-time PCR is sensitive and specific in the detection of T. pallidum and HSV-1/2 in clinical routine and it appears superior to serology in early T. pallidum infections. This article is protected by copyright. All rights reserved.
    Clinical Microbiology and Infection 06/2014; DOI:10.1111/1469-0691.12710 · 5.20 Impact Factor
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    ABSTRACT: A 34-year-old man from Ethiopia had been suffering from inflammatory lower backpain for five months. The imaging showed multiple osteolytic lesions histologically corresponding to a granulomatous inflammation. Detection of multiresistant Mycobacteria Tuberculosis (MDR-TB) was delayed because of initially negative microbiological findings. During the therapy of MDR-TB, the patient developed different side effects. In this article we focus on the challenge to diagnose and treat MDR-TB also in a resource-rich setting as it is the case for Switzerland.
    Praxis 03/2014; 103(6):337-40.
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    ABSTRACT: Cotrimoxazole reduces mortality in HIV-infected adults with tuberculosis (TB), and in vitro data suggest potential anti-mycobacterial activity of cotrimoxazole. We aimed to evaluate whether prophylaxis with cotrimoxazole is associated with a decreased risk of incident TB in SHCS participants. We determined the incidence of TB per 1000 person-years from January 1992 to December 2012. Rates were analyzed separately in participants with current or no previous antiretroviral treatment (ART) using Poisson regression adjusted for CD4 cell count, sex, region of origin, injecting drug use, and age. 13,431 cohort participants contributed 107,549 person-years follow-up; 182 patients had incident TB; 132 (73%) before and 50 (27%) after ART initiation. The multivariable incidence rate ratios for cumulative cotrimoxazole exposure per year for persons with no previous and current ART were 0.70 (95% CI 0.55-0.89) and 0.87 (0.74-1.0) respectively. Cotrimoxazole may prevent the development of TB among HIV-positive persons, especially among those with no previous ART.
    Antimicrobial Agents and Chemotherapy 02/2014; 58(4). DOI:10.1128/AAC.01868-13 · 4.45 Impact Factor
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    ABSTRACT: Neisseria gonorrhoeae can rapidly develop resistance to antimicrobial agents. Over the last years, decreased gonococcal susceptibility to third-generation cephalosporins, especially cefixime, emerged worldwide. Therefore, current international guidelines recommend dual therapy for gonorrhoea with ceftriaxone plus either azithromycin or doxycycline. Gonococcal susceptibility data in Switzerland are sparse. We investigated the prevalence of antibiotic susceptibility of N. gonorrhoeae in specimens collected between 1990 and 2012 at the University of Zurich, Switzerland. Minimum inhibitory concentrations (MICs) for cefixime, ceftriaxone, ciprofloxacin, and penicillin were determined by Etests. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints were used to define reduced susceptibility. A total of 320 isolates were tested. Between 1990 and 2006 all tested samples were susceptible to both cephalosporins. Subsequently, the prevalence of elevated MICs for cefixime increased to 10.4% (2007/2008), 11.5% (2009/2010), and 11.4% (2011/2012); and for ceftriaxone to 2.4% (2007/2008), 4.7% (2009/2010), and 0% (2011/2012), respectively. The prevalence of resistance to ciprofloxacin (72.7%) and penicillin (22.7%) was high in 2011/2012. Decreasing susceptibility of N. gonorrhoeae to third-generation cephalosporins in Switzerland supports treatment recommendations with ceftriaxone plus azithromycin or doxycycline. Health-care providers need to be aware of possible treatment failures with cephalosporins. Continued surveillance of gonococcal antimicrobial resistance is essential.
    BMC Infectious Diseases 12/2013; 13(1):603. DOI:10.1186/1471-2334-13-603 · 2.56 Impact Factor
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    ABSTRACT: We studied whether the change in antibiotic susceptibility testing (AST) guidelines from CLSI to EUCAST influenced cumulative antibiograms in a tertiary care hospital in Switzerland. Antibiotic susceptibilities of non-duplicate isolates collected within a one-year period before (period A) and after (period B) changing AST interpretation from CLSI 2009 to EUCAST 1.3 (2011) guidelines were analysed. In addition, period B isolates were reinterpreted according to the CLSI 2009, CLSI 2013 and EUCAST 3.1 (2013) guidelines. The majority of species/drug combinations showed no differences in susceptibility rates comparing periods A and B. However, in some gram-negative bacilli, decreased susceptibility rates were observed when comparing CLSI 2009 with EUCAST 1.3 within period B: Escherichia coli / cefepime, 95.8% (CLSI 2009) vs. 93.1% (EUCAST 1.3), P=0.005; Enterobacter cloacae / cefepime, 97.0 (CLSI 2009) vs. 90.5% (EUCAST 1.3), P=0.012; Pseudomonas aeruginosa / meropenem, 88.1% (CLSI 2009) vs. 78.3% (EUCAST 1.3), P=0.002. These differences were still evident when comparing susceptibility rates according to the CLSI 2013 guideline with EUCAST 3.1 guideline. For P. aeruginosa and imipenem, a trend towards a lower antibiotic susceptibility rate in ICUs compared to general wards turned into a significant difference after the change to EUCAST: 87.9% vs. 79.8%, P=0.08 (CLSI 2009) and 86.3% vs. 76.8%, P=0.048 (EUCAST 1.3). The change of AST guidelines from CLSI to EUCAST led to a clinically relevant decrease of susceptibility rates in cumulative antibiograms for defined species/drug combinations, particularly in those with considerable differences in clinical susceptibility breakpoints between the two guidelines.
    PLoS ONE 11/2013; 8(11):e79130. DOI:10.1371/journal.pone.0079130 · 3.53 Impact Factor

Publication Stats

10k Citations
1,461.92 Total Impact Points

Institutions

  • 1996–2015
    • University of Zurich
      • Division of Infectuous Dieseases
      Zürich, Zurich, Switzerland
  • 2003–2010
    • Universitätsspital Basel
      • Institute for Clinical Epidemiology and Biostatistics (CEB)
      Bâle, Basel-City, Switzerland
    • Copenhagen University Hospital Hvidovre
      Hvidovre, Capital Region, Denmark
  • 1996–2009
    • University Hospital Zürich
      Zürich, Zurich, Switzerland
  • 2008
    • Hospital for Tropical Diseases, Ho Chi Minh City
      Thành phố Hồ Chí Minh, Ho Chi Minh City, Vietnam
    • Azienda Ospedaliera San Paolo - Polo Universitario
      Milano, Lombardy, Italy
  • 2007
    • University College London
      • Department of Infection and Population Health
      Londinium, England, United Kingdom
  • 1999–2007
    • University of Lausanne
      • Institute of Microbiology
      Lausanne, Vaud, Switzerland
    • University of Bristol
      • School of Social and Community Medicine
      Bristol, England, United Kingdom
  • 2002–2005
    • University Hospital of Lausanne
      • Institute of Microbiology (IMUL)
      Lausanne, Vaud, Switzerland
    • University of Colorado
      Denver, Colorado, United States
    • Universität Basel
      Bâle, Basel-City, Switzerland
  • 2004
    • University of California, San Diego
      San Diego, California, United States
    • ETH Zurich
      • Institute of Microbiology
      Zürich, ZH, Switzerland
    • University of Geneva
      • Division of Infectious Diseases
      Genève, Geneva, Switzerland