Longitudinal increase in the detection rate of Mycobacterium chimaera in heater-cooler device-derived water samples.

BACKGROUND: Colonization with Mycobacterium chimaera and other non-tuberculous mycobacteria (NTM) has been reported for heater-cooler devices (HCDs) produced by several manufacturers. Up until now, exclusively LivaNova (London, UK) HCDs have been associated with M. chimaera infections after cardiac surgery. The vast majority of studies on HCD colonization were cross-sectional. AIM: We were interested in longitudinal dynamics of mycobacterial growth in HCD water samples and analysed data of a prospective mycobacterial surveillance of five LivaNova 3T HCDs. METHODS: Five LivaNova HCDs were subjected to prospective mycobacterial surveillance. For each HCD and the total of HCDs, results of mycobacterial detection were analyzed. Logistic regression was applied to model the association between growth of any NTM or M. chimaera and duration of HCD use. RESULTS: Non-tuberculous mycobacteria were isolated in 319 (48.0%, 21 water samples grew more than one mycobacterial species) of a total of 665 water samples. The most frequently detected species were M. chimaera (N = 247/319, 77.4%), Mycobacterium gordonae (46/319, 14.4%) and Mycobacterium paragordonae (34/319, 10.7%). Detection rates increased prospectively for any NTM (odds ratio (OR) per year in use: 1.60, 95% confidence interval (CI) 1.17-2.24, P<0.001) and for M. chimaera (OR per year in use: 1.67, 95% CI 1.11-2.57, P<0.01). CONCLUSION: Longer duration of HCD use was associated with higher detection rates for any NTM and M. chimaera, respectively.

Diversity of nontuberculous mycobacteria in Heater-Cooler Devices - results from prospective surveillance.

OBJECTIVE: The international outbreak of cardiac surgery-associated Mycobacterium chimaera infections was traced back to infectious aerosols originating from contaminated water reservoirs of heater-cooler devices (HCD). In general, nontuberculous mycobacteria (NTM) frequently colonize water systems and can contaminate medical devices. Data on detection of NTM other than M. chimaera in samples gathered from HCDs are scarce. The present study summarizes prospective mycobacterial surveillance of five HCDs over more than four years. METHODS: A cohort of five, in 2014 factory-new acquired, LivaNova 3T (London, UK) HCDs were prospectively followed. Until mid-April 2014 HCDs were maintained according to the manufacturer's recommendations, subsequently according to an intensified in-house protocol including exhaust air evacuation. Mycobacterial surveillance cultures consisted of monthly water samples gathered from patient and cardioplegia circuits, as well as airflow samples. RESULTS: Out of 441 water samples, 170 (38.6%) revealed NTM growth. The most frequently detected NTM were Mycobacterium chimaera (n=120 (67.4%)), Mycobacterium gordonae (n=35 (19.7 %)), and Mycobacterium paragordonae (n=17 (9.6%)). Growth of NTM, M. chimaera and M. paragordonae was significantly more common in water samples derived from the patient than the cardioplegia circuit of the HCD. Three (2.0%) out of 150 air samples grew NTM. CONCLUSION: Growth of NTM in HCD water samples was frequent. Diverse NTM species were detected, with M. chimaera being most common. The majority of air samples remained negative. The relevance of NTM other than M. chimaera contaminating HCDs is poorly defined, but a recent report on a HCD-associated outbreak with Mycobacterium abscessus confirms a potential threat.

International Society of Cardiovascular Infectious Diseases Guidelines for the Diagnosis, Treatment and Prevention of Disseminated Mycobacterium chimaera Infection Following Cardiac Surgery with Cardiopulmonary Bypass.

Mycobacterial infection-related morbidity and mortality in patients following cardiopulmonary bypass surgery is high and there is a growing need for a consensus-based expert opinion to provide international guidance for diagnosing, preventing and treating in these patients. In this document the International Society for Cardiovascular Infectious Diseases (ISCVID) covers aspects of prevention (field of hospital epidemiology), clinical management (infectious disease specialists, cardiac surgeons, ophthalmologists, others), laboratory diagnostics (microbiologists, molecular diagnostics), device management (perfusionists, cardiac surgeons) and public health aspects.

Detection limit of Mycobacterium chimaera in water samples for monitoring medical device safety: insights from a pilot experimental series.

BACKGROUND: A growing number of Mycobacterium chimaera infections after cardiosurgery have been reported by several countries. These potentially fatal infections were traced back to contaminated heater-cooler devices (HCDs), which use water as a heat transfer medium. Aerosolization of water contaminated with M. chimaera from HCDs enables airborne transmission to patients undergoing open chest surgery. Infection control teams test HCD water samples for mycobacterial growth to guide preventive measures. The detection limit of M. chimaera in water samples, however, has not previously been investigated. AIM: To determine the detection limit of M. chimaera in water samples using laboratory-based serial dilution tests. METHODS: An M. chimaera strain representative of the international cardiosurgery-associated M. chimaera outbreak was used to generate a logarithmic dilution series. Two different water volumes, 50 and 1000mL, were inoculated, and, after identical processing (centrifugation, decantation, and decontamination), seeded on mycobacteria growth indicator tube (MGIT) and Middlebrook 7H11 solid media. FINDINGS: MGIT consistently showed a lower detection limit than 7H11 solid media, corresponding to a detection limit of ≥1.44 × 104cfu/mL for 50mL and ≥2.4cfu/mL for 1000mL water samples. Solid media failed to detect M. chimaera in 50mL water samples. CONCLUSION: Depending on water volume and culture method, major differences exist in the detection limit of M. chimaera. In terms of sensitivity, 1000mL water samples in MGIT media performed best. Our results have important implications for infection prevention and control strategies in mitigation of the M. chimaera outbreak and healthcare water safety in general.

Emergence of Acquired HIV-1 Drug Resistance Almost Stopped in Switzerland: A 15-Year Prospective Cohort Analysis.

BACKGROUND: Drug resistance is a major barrier to successful antiretroviral treatment (ART). Therefore, it is important to monitor time trends at a population level. METHODS: We included 11 084 ART-experienced patients from the Swiss HIV Cohort Study (SHCS) between 1999 and 2013. The SHCS is highly representative and includes 72% of patients receiving ART in Switzerland. Drug resistance was defined as the presence of ≥1 major mutation in a genotypic resistance test. To estimate the prevalence of drug resistance, data for patients with no resistance test was imputed based on the patient's risk of harboring drug-resistant viruses. RESULTS: The emergence of new drug resistance mutations declined dramatically from 401 to 23 patients between 1999 and 2013. The upper estimated prevalence limit of drug resistance among ART-experienced patients decreased from 57.0% in 1999 to 37.1% in 2013. The prevalence of 3-class resistance decreased from 9.0% to 4.4% and was always <0.4% for patients who initiated ART after 2006. Most patients actively participating in the SHCS in 2013 with drug-resistant viruses initiated ART before 1999 (59.8%). Nevertheless, in 2013, 94.5% of patients who initiated ART before 1999 had good remaining treatment options based on Stanford algorithm. CONCLUSIONS: Human immunodeficiency virus type 1 drug resistance among ART-experienced patients in Switzerland is a well-controlled relic from the era before combination ART. Emergence of drug resistance can be virtually stopped with new potent therapies and close monitoring.

HIV-1 Transmission During Recent Infection and During Treatment Interruptions as Major Drivers of New Infections in the Swiss HIV Cohort Study.

BACKGROUND: Reducing the fraction of transmissions during recent human immunodeficiency virus (HIV) infection is essential for the population-level success of "treatment as prevention". METHODS: A phylogenetic tree was constructed with 19 604 Swiss sequences and 90 994 non-Swiss background sequences. Swiss transmission pairs were identified using 104 combinations of genetic distance (1%-2.5%) and bootstrap (50%-100%) thresholds, to examine the effect of those criteria. Monophyletic pairs were classified as recent or chronic transmission based on the time interval between estimated seroconversion dates. Logistic regression with adjustment for clinical and demographic characteristics was used to identify risk factors associated with transmission during recent or chronic infection. FINDINGS: Seroconversion dates were estimated for 4079 patients on the phylogeny, and comprised between 71 (distance, 1%; bootstrap, 100%) to 378 transmission pairs (distance, 2.5%; bootstrap, 50%). We found that 43.7% (range, 41%-56%) of the transmissions occurred during the first year of infection. Stricter phylogenetic definition of transmission pairs was associated with higher recent-phase transmission fraction. Chronic-phase viral load area under the curve (adjusted odds ratio, 3; 95% confidence interval, 1.64-5.48) and time to antiretroviral therapy (ART) start (adjusted odds ratio 1.4/y; 1.11-1.77) were associated with chronic-phase transmission as opposed to recent transmission. Importantly, at least 14% of the chronic-phase transmission events occurred after the transmitter had interrupted ART. CONCLUSIONS: We demonstrate a high fraction of transmission during recent HIV infection but also chronic transmissions after interruption of ART in Switzerland. Both represent key issues for treatment as prevention and underline the importance of early diagnosis and of early and continuous treatment.

Strong Impact of Smoking on Multimorbidity and Cardiovascular Risk Among Human Immunodeficiency Virus-Infected Individuals in Comparison With the General Population.

Background. Although acquired immune deficiency syndrome-associated morbidity has diminished due to excellent viral control, multimorbidity may be increasing among human immunodeficiency virus (HIV)-infected persons compared with the general population. Methods. We assessed the prevalence of comorbidities and multimorbidity in participants of the Swiss HIV Cohort Study (SHCS) compared with the population-based CoLaus study and the primary care-based FIRE (Family Medicine ICPC-Research using Electronic Medical Records) records. The incidence of the respective endpoints were assessed among SHCS and CoLaus participants. Poisson regression models were adjusted for age, sex, body mass index, and smoking. Results. Overall, 74 291 participants contributed data to prevalence analyses (3230 HIV-infected; 71 061 controls). In CoLaus, FIRE, and SHCS, multimorbidity was present among 26%, 13%, and 27% of participants. Compared with nonsmoking individuals from CoLaus, the incidence of cardiovascular disease was elevated among smoking individuals but independent of HIV status (HIV-negative smoking: incidence rate ratio [IRR] = 1.7, 95% confidence interval [CI] = 1.2-2.5; HIV-positive smoking: IRR = 1.7, 95% CI = 1.1-2.6; HIV-positive nonsmoking: IRR = 0.79, 95% CI = 0.44-1.4). Compared with nonsmoking HIV-negative persons, multivariable Poisson regression identified associations of HIV infection with hypertension (nonsmoking: IRR = 1.9, 95% CI = 1.5-2.4; smoking: IRR = 2.0, 95% CI = 1.6-2.4), kidney (nonsmoking: IRR = 2.7, 95% CI = 1.9-3.8; smoking: IRR = 2.6, 95% CI = 1.9-3.6), and liver disease (nonsmoking: IRR = 1.8, 95% CI = 1.4-2.4; smoking: IRR = 1.7, 95% CI = 1.4-2.2). No evidence was found for an association of HIV-infection or smoking with diabetes mellitus. Conclusions. Multimorbidity is more prevalent and incident in HIV-positive compared with HIV-negative individuals. Smoking, but not HIV status, has a strong impact on cardiovascular risk and multimorbidity.

Increases in Condomless Sex in the Swiss HIV Cohort Study.

Condomless sex is a key driver of sexually transmitted diseases. In this study, we assess the long-term changes (2000-2013) of the occurrence of condomless sex among human immunodeficiency virus (HIV)-infected individuals enrolled in the Swiss HIV Cohort study. The frequencies with which HIV-infected individuals reported condomless sex were either stable or only weakly increasing for 2000-2008. For 2008-2013, these rates increased significantly for stable relationships among heterosexuals and men who have sex with men (MSM) and for occasional relationships among MSM. Our results highlight the increasing public health challenge posed by condomless sex and show that condomless sex has been increasing even in the most recent years.

Incident Hepatitis C Virus Infections in the Swiss HIV Cohort Study: Changes in Treatment Uptake and Outcomes Between 1991 and 2013.

Background. The hepatitis C virus (HCV) epidemic is evolving rapidly in patients infected with human immunodeficiency virus (HIV). We aimed to describe changes in treatment uptake and outcomes of incident HCV infections before and after 2006, the time-point at which major changes in HCV epidemic became apparent. Methods. We included all adults with an incident HCV infection before June 2012 in the Swiss HIV Cohort Study, a prospective nationwide representative cohort of individuals infected with HIV. We assessed the following outcomes by time period: the proportion of patients starting an HCV therapy, the proportion of treated patients achieving a sustained virological response (SVR), and the proportion of patients with persistent HCV infection during follow-up. Results. Of 193 patients with an HCV seroconversion, 106 were diagnosed before and 87 after January 2006. The proportion of men who have sex with men increased from 24% before to 85% after 2006 (P < .001). Hepatitis C virus treatment uptake increased from 33% before 2006 to 77% after 2006 (P < .001). Treatment was started during early infection in 22% of patients before and 91% after 2006 (P < .001). An SVR was achieved in 78% and 29% (P = .01) of patients treated during early and chronic HCV infection. The probability of having a detectable viral load 5 years after diagnosis was 0.67 (95% confidence interval [CI], 0.58-0.77) in the group diagnosed before 2006 and 0.24 (95% CI, 0.16-0.35) in the other group (P < .001). Conclusions. In recent years, increased uptake and earlier initiation of HCV therapy among patients with incident infections significantly reduced the proportion of patients with replicating HCV.

Diagnostic performance of 18F-FDG-PET/CT in vascular graft infections.

OBJECTIVE: The aim of this study was to evaluate the diagnostic accuracy of positron emission tomography/computed tomography with (18)F-fludeoxyglucose (FDG-PET/CT) in a population with suspected graft infection and to validate a new diagnostic imaging score for FDG-PET/CT. METHODS: This was a prospective cohort study. FDG-PET/CT was performed prospectively in 34 patients with suspected graft infection, in 12 of them before the start of antimicrobial treatment. Diagnostic accuracy was assessed using a new five point visual grading score and by using a binary score. Maximum standardized uptake values (SUVmax) were calculated for quantitative measurements of metabolic activity, and cut off points were calculated using the receiver operator curve (ROC). The standard of reference was a microbiological culture, obtained after open biopsy or graft explantation. RESULTS: Using the new scale, FDG-PET/CT correctly recognized 27 patients with graft infection, one patient was diagnosed as false positive, six patients were correctly classified as true negative, and no patients were rated false negative. Hence, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of FDG-PET/CT for the diagnosis of graft infections were 100%, 86%, 96%, 100%, and 97%, respectively. Using a previously established binary score, sensitivity, specificity, PPV, NPV, and accuracy were 96%, 86%, 96%, 86%, and 94% respectively. ROC analysis suggested an SUVmax cut off value of ≥3.8 to differentiate between infected and non-infected grafts (p < .001). Additionally, FDG-PET/CT provided a conclusive clinical diagnosis in six of seven patients without graft infection (i.e., other sites of infections). CONCLUSIONS: The diagnostic accuracy of FDG-PET/CT in the detection of aortic graft infection is high. A newly introduced five point visual grading score and early imaging prior to antimicrobial treatment may further improve the diagnostic accuracy.

Obesity Trends and Body Mass Index Changes After Starting Antiretroviral Treatment: The Swiss HIV Cohort Study.

BACKGROUND: The factors that contribute to increasing obesity rates in human immunodeficiency virus (HIV)-positive persons and to body mass index (BMI) increase that typically occurs after starting antiretroviral therapy (ART) are incompletely characterized. METHODS: We describe BMI trends in the entire Swiss HIV Cohort Study (SHCS) population and investigate the effects of demographics, HIV-related factors, and ART on BMI change in participants with data available before and 4 years after first starting ART. RESULTS: In the SHCS, overweight/obesity prevalence increased from 13% in 1990 (n = 1641) to 38% in 2012 (n = 8150). In the participants starting ART (n = 1601), mean BMI increase was 0.92 kg/m(2) per year (95% confidence interval, .83-1.0) during year 0-1 and 0.31 kg/m(2) per year (0.29-0.34) during years 1-4. In multivariable analyses, annualized BMI change during year 0-1 was associated with older age (0.15 [0.06-0.24] kg/m(2)) and CD4 nadir <199 cells/µL compared to nadir >350 (P < .001). Annualized BMI change during years 1-4 was associated with CD4 nadir <100 cells/µL compared to nadir >350 (P = .001) and black compared to white ethnicity (0.28 [0.16-0.37] kg/m(2)). Individual ART combinations differed little in their contribution to BMI change. CONCLUSIONS: Increasing obesity rates in the SHCS over time occurred at the same time as aging of the SHCS population, demographic changes, earlier ART start, and increasingly widespread ART coverage. Body mass index increase after ART start was typically biphasic, the BMI increase in year 0-1 being as large as the increase in years 1-4 combined. The effect of ART regimen on BMI change was limited.

Novel inhibitory activity of the Staphylococcus aureus NorA efflux pump by a kaempferol rhamnoside isolated from Persea lingue Nees.

OBJECTIVES: To isolate a plant-derived compound with efflux inhibitory activity towards the NorA transporter of Staphylococcus aureus. METHODS: Bioassay-guided isolation was used, with inhibition of ethidium bromide efflux via NorA as a guide. Characterization of activity was carried out using MIC determination and potentiation studies of a fluoroquinolone antibiotic in combination with the isolated compound. Everted membrane vesicles of Escherichia coli cells enriched with NorA were prepared to study efflux inhibitory activity in an isolated manner. RESULTS: The ethanolic extract of Persea lingue was subjected to bioassay-guided fractionation and led to the isolation of the known compound kaempferol-3-O-α-L-(2,4-bis-E-p-coumaroyl)rhamnoside (compound 1). Evaluation of the dose-response relationship of compound 1 showed that ethidium bromide efflux was inhibited, with an IC(50) value of 2 µM. The positive control, reserpine, was found to have an IC(50) value of 9 µM. Compound 1 also inhibited NorA in enriched everted membrane vesicles of E. coli. Potentiation studies revealed that compound 1 at 1.56 mg/L synergistically increased the antimicrobial activity of ciprofloxacin 8-fold against a NorA overexpresser, and the synergistic activity was exerted at a fourth of the concentration necessary for reserpine. Compound 1 was not found to exert a synergistic effect on ciprofloxacin against a norA deletion mutant. The 2,3-coumaroyl isomer of compound 1 has been shown previously not to cause acute toxicity in mice at 20 mg/kg/day. CONCLUSIONS: Our results show that compound 1 acts through inhibition of the NorA efflux pump. Combination of compound 1 with subinhibitory concentrations of ciprofloxacin renders a wild-type more susceptible and a NorA overexpresser S. aureus susceptible.

High specificity of line-immunoassay based algorithms for recent HIV-1 infection independent of viral subtype and stage of disease.

BACKGROUND: Serologic testing algorithms for recent HIV seroconversion (STARHS) provide important information for HIV surveillance. We have shown that a patient's antibody reaction in a confirmatory line immunoassay (INNO-LIA HIV I/II Score, Innogenetics) provides information on the duration of infection. Here, we sought to further investigate the diagnostic specificity of various Inno-Lia algorithms and to identify factors affecting it. METHODS: Plasma samples of 714 selected patients of the Swiss HIV Cohort Study infected for longer than 12 months and representing all viral clades and stages of chronic HIV-1 infection were tested blindly by Inno-Lia and classified as either incident (up to 12 m) or older infection by 24 different algorithms. Of the total, 524 patients received HAART, 308 had HIV-1 RNA below 50 copies/mL, and 620 were infected by a HIV-1 non-B clade. Using logistic regression analysis we evaluated factors that might affect the specificity of these algorithms. RESULTS: HIV-1 RNA < 50 copies/mL was associated with significantly lower reactivity to all five HIV-1 antigens of the Inno-Lia and impaired specificity of most algorithms. Among 412 patients either untreated or with HIV-1 RNA ≥ 50 copies/mL despite HAART, the median specificity of the algorithms was 96.5% (range 92.0-100%). The only factor that significantly promoted false-incident results in this group was age, with false-incident results increasing by a few percent per additional year. HIV-1 clade, HIV-1 RNA, CD4 percentage, sex, disease stage, and testing modalities exhibited no significance. Results were similar among 190 untreated patients. CONCLUSIONS: The specificity of most Inno-Lia algorithms was high and not affected by HIV-1 variability, advanced disease and other factors promoting false-recent results in other STARHS. Specificity should be good in any group of untreated HIV-1 patients.

Extended-spectrum ß-lactamase-producing Gram-negative pathogens in community-acquired urinary tract infections: an increasing challenge for antimicrobial therapy.

BACKGROUND: Extended-spectrum ß-lactamases (ESBLs) are an increasing challenge in the treatment of urinary tract infections (UTIs), and also in the community. We aimed to investigate the characteristics of patients with UTIs due to ESBL-producing Escherichia coli and to assess the risk factors for ESBLs in community-acquired isolates. METHODS: We performed a retrospective study from January 1, 2007 to December 31, 2009 at a tertiary care teaching hospital in Switzerland, comparing patients with community-acquired versus healthcare-associated UTIs due to ESBL-producing E. coli. Additionally, we investigated the antimicrobial susceptibility of these isolates. RESULTS: A total of 123 patients were studied, of whom 79 (64%) had community-acquired and 44 (36%) had healthcare-associated UTIs. Community-acquired isolates were associated with acute uncomplicated UTIs (odds ratio [OR] 6.62, 95% confidence interval [CI] 1.83-36.5, P < 0.001). Risk factors were recurrent UTI (OR 3.04, 95% CI 1.14-9.14, P = 0.022) and female sex (OR 2.46, 95% CI 1.01-6.08). Community-acquired ESBL-producing E. coli urinary isolates showed high resistance rates to most of the currently used oral antimicrobial agents, including ß-lactam antibiotics (amoxicillin-clavulanic acid, 69.6% resistance), quinolones (ciprofloxacin, 84.8% resistance; norfloxacin, 83.9% resistance), and trimethoprim-sulfamethoxazole (75.9% resistance), except for nitrofurantoin (15% resistance) and fosfomycin (0% resistance). CONCLUSION: UTI due to ESBL-producing E. coli are emerging, and also in a country with low antibiotic use. Because of increasing antibiotic resistance rates of E. coli to current standard therapy and because of the resistance patterns of ESBL-producing E. coli, guidelines for the management of UTIs must be revised. Fosfomycin or nitrofurantoin are recommended for the first-line empirical oral treatment of community-acquired uncomplicated UTIs.

Clinical relevance of cytomegalovirus viraemia(*,†).

BACKGROUND: Using new sensitive quantitative polymerase chain reaction (PCR) assays, cytomegalovirus (CMV) DNA is often detectable in the plasma of immunosuppressed patients. We investigated the prognostic value of a positive CMV DNA test for the development of CMV end-organ disease, other AIDS-defining events and mortality. METHODS: A survival analysis was performed, using the Kaplan-Meier method and Cox proportional hazards models, for patients prospectively followed in the Swiss HIV Cohort Study, from January 1996 to December 2007, who were CMV-seropositive, had a CD4 count of ≤ 100 cells/µL, and had a plasma sample available for the measurement of baseline CMV DNA with an ultrasensitive PCR. The outcome analysed was an AIDS-defining event, including CMV end-organ disease, or death. Variables analysed at the time of CMV measurement were demographic variables, CD4 cell counts, HIV-1 RNA loads, and use and type of highly active antiretroviral therapy (HAART). RESULTS: Of 1128 patients, 208 (18%) presented an AIDS-defining event and 246 (22%) died. A total of 368 patients (34% of samples) had detectable CMV DNA at baseline, with DNA concentrations of up to 38 800 copies/mL. In the multivariate analysis, CMV DNA predicted evolution not only towards CMV end-organ disease [hazard ratio (HR) 12.6; 95% confidence interval (CI) 4.27-37.41], but also towards other AIDS-defining events (HR 2.6; 95% CI 1.60-4.33) and death (HR 1.9; 95% CI 1.10-3.34). CONCLUSION: Quantitative CMV DNA detected in the plasma of HIV-infected patients with CD4 counts ≤ 100 cells/µL is a predictor for HIV disease progression, CMV disease and death. A single low value of 80 copies/mL identifies patients at low but significantly increased risk during the following months, after the measurement.

Lipid and lipoprotein profile in HIV-infected patients treated with lopinavir/ritonavir as a component of the first combination antiretroviral therapy.

We characterized lipid and lipoprotein changes associated with a lopinavir/ritonavir-containing regimen. We enrolled previously antiretroviral-naive patients participating in the Swiss HIV Cohort Study. Fasting blood samples (baseline) were retrieved retrospectively from stored frozen plasma and posttreatment (follow-up) samples were collected prospectively at two separate visits. Lipids and lipoproteins were analyzed at a single reference laboratory. Sixty-five patients had two posttreatment lipid profile measurements and nine had only one. Most of the measured lipids and lipoprotein plasma concentrations increased on lopinavir/ritonavir-based treatment. The percentage of patients with hypertriglyceridemia (TG >150 mg/dl) increased from 28/74 (38%) at baseline to 37/65 (57%) at the second follow-up. We did not find any correlation between lopinavir plasma levels and the concentration of triglycerides. There was weak evidence of an increase in small dense LDL-apoB during the first year of treatment but not beyond 1 year (odds ratio 4.5, 90% CI 0.7 to 29 and 0.9, 90% CI 0.5 to 1.5, respectively). However, 69% of our patients still had undetectable small dense LDL-apoB levels while on treatment. LDL-cholesterol increased by a mean of 17 mg/dl (90% CI -3 to 37) during the first year of treatment, but mean values remained below the cut-off for therapeutic intervention. Despite an increase in the majority of measured lipids and lipoproteins particularly in the first year after initiation, we could not detect an obvious increase of cardiovascular risk resulting from the observed lipid changes.

Risks factors for infections with extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae at a tertiary care university hospital in Switzerland.

BACKGROUND: There are considerable geographical differences in the occurrence of extended-spectrum beta-lactamase(ESBL)-producing bacteria, both in the community and in the hospital setting. Our aim was to assess risk factors for blood stream, urinary tract, and vascular catheter-associated infections with ESBL-producing Escherichia coli and Klebsiella pneumoniae at a tertiary care hospital in a low-prevalence country. METHODS: We performed a case-control study comparing 58 patients with infections due to ESBL-producing E. coli orK. pneumoniae vs 116 controls with infections due to non-ESBL producing organisms at the University Hospital Zurich, Switzerland, between 1 July 2005 and 30 June 2007. RESULTS: Cases included 15 outpatients and 43 inpatients. Multivariable analyses found three risk factors for ESBL-producing isolates: begin of symptoms or recent antibiotic pre-treatment in a foreign country (odds ratio [OR] 27.01,95% confidence interval [CI] 2.38-1,733.28], p = 0.042),antibiotic therapy within the year preceding the isolation of the ESBL-producing strain (OR 2.88, 95% CI 1.13-8.49,p = 0.025), and mechanical ventilation (OR 10.56, 95% CI 1.06-579.10, p = 0.042). CONCLUSIONS: The major risk factors for infections due to ESBL-producing bacteria were travel in high-prevalence countries, prior antibiotic use, and mechanical ventilation during a stay in the intensive care unit. Community-acquired infections were documented in 17% of the patients.An early identification of risk factors is crucial to providing the patients an optimal empiric antibiotic therapy and to keep the use of carbapenems to a minimum.

Prevalence of etravirine mutations and impact on response to treatment in routine clinical care: the Swiss HIV Cohort Study (SHCS).

OBJECTIVES: Etravirine (ETV) is a novel nonnucleoside reverse transcriptase inhibitor (NNRTI) with reduced cross-resistance to first-generation NNRTIs, which has been primarily studied in randomized clinical trials and not in routine clinical settings. METHODS: ETV resistance-associated mutations (RAMs) were investigated by analysing 6072 genotypic tests. The antiviral activity of ETV was predicted using different interpretation systems: International AIDS Society-USA (IAS-USA), Stanford, Rega and Agence Nationale de Recherches sur le Sida et les hépatites virales (ANRS). RESULTS: The prevalence of ETV RAMs was higher in NNRTI-exposed patients [44.9%, 95% confidence interval (CI) 41.0-48.9%] than in treatment-naïve patients (9.6%, 95% CI 8.5-10.7%). ETV RAMs in treatment-naïve patients mainly represent polymorphism, as prevalence estimates in genotypic tests for treatment-naïve patients with documented recent (<1 year) infection, who had acquired HIV before the introduction of NNRTIs, were almost identical (9.8%, 95% CI 3.3-21.4). Discontinuation of NNRTI treatment led to a marked drop in the detection of ETV RAMs, from 51.7% (95% CI 40.8-62.6%) to 34.5% (95% CI 24.6-45.4%, P=0.032). Differences in prevalence among subtypes were found for V90I and V179T (P<0.001). Estimates of restricted virological response to ETV varied among algorithms in patients with exposure to efavirenz (EFV)/nevirapine (NVP), ranging from 3.8% (95% CI 2.5-5.6%) for ANRS to 56.2% (95% CI 52.2-60.1%) for Stanford. The predicted activity of ETV decreased as the sensitivity of potential optimized background regimens decreased. The presence of major IAS-USA mutations (L100I, K101E/H/P and Y181C/I/V) reduced the treatment response at week 24. CONCLUSIONS: Most ETV RAMs in drug-naïve patients are polymorphisms rather than transmitted RAMs. Uncertainty regarding predictions of antiviral activity for ETV in NNRTI-treated patients remains high. The lowest activity was predicted for patients harbouring extensive multidrug-resistant viruses, thus limiting ETV use in those who are most in need.