Medium-grade proteinuria is a risk factor for incident markers of chronic kidney disease.

OBJECTIVE: Medium-grade proteinuria (100-500 mg/g creatinine) is common among people living with HIV/AIDS (PLWHA) but is often undetected or ignored. This prospective, observational cohort study examined medium-grade proteinuria as a risk factor for markers of chronic kidney disease (CKD). METHODS: Quantitative urine samples were collected from 241 PLWHA without known renal disease at baseline between January 2009 and February 2011 and at follow-up 240 weeks later. Multivariate analysis was performed to assess medium-grade proteinuria as a risk factor for incident markers of CKD (estimated glomerular filtration rate < 60 mL/min/1.73 m2 , albuminuria, phosphaturia). RESULTS: Incident markers of CKD were identified in 33 patients (14%), of whom 24 (74%) had medium-grade proteinuria at baseline. Of these, 22 even had proteinuria of < 200 mg/g creatinine. Multivariate analysis showed an adjusted relative risk (aRR) of 2.4 for patients with baseline medium-grade proteinuria to develop signs of CKD. Age was identified as an additional independent predictor. By testing for interaction, tenofovir disoproxil fumarate (TDF)-independent proteinuria was strongly associated with incident CKD markers (aRR = 12.1). CONCLUSION: Medium-grade proteinuria of 100-500 mg/g creatinine is both frequent in PLWHA and a significant risk factor for developing markers of CKD, especially in the absence of TDF. Relevant risk seems to be associated with proteinuria levels as low as 100-200 mg/g creatinine. Current guidelines recommend specific action for proteinuria exceeding 135-200 mg/g but still will miss a relevant number of PLWHA potentially at risk for CKD. An even lower cut-off to trigger nephrological work-up and potentially renoprotective interventions appears to be indicated.

Measles, mumps, rubella and VZV: importance of serological testing of vaccine-preventable diseases in young adults living with HIV in Germany.

Measles, mumps, rubella (MMR) and varicella zoster virus (VZV) infection can cause serious diseases and complications in the HIV-positive population. Due to successful vaccination programmes measles, mumps and congenital rubella syndrome has become neglected in Germany. However, recent outbreaks of measles have occurred from import-associated cases. In this cross-sectional study the serostatus for MMR and VZV in 2013 HIV-positive adults from three different university outpatient clinics in Bonn (n = 544), Cologne (n = 995) and Munich (n = 474) was analysed. Sera were tested for MMR- and VZV-specific immunglobulin G antibodies using commercial immunoassays. Seronegativity was found in 3% for measles, 26% for mumps, 11% for rubella and 2% for VZV. Regarding MMR, 35% of patients lacked seropositivity against at least one infectious agent. In multivariable analysis younger age was strongly associated with seronegativity against all four viruses, measles, mumps, rubella (P < 0·001, P < 0·001 and P = 0·001, respectively) and VZV (P = 0·001). In conclusion, there is high need for MMR and VZV vaccination in people living with HIV in Germany born in 1970 or later. Thus, systematic MMR and VZV antibody screening and vaccination should be implemented in the HIV-positive population to prevent serious disease and complications of vaccine-preventable diseases.

Medium-grade tubular proteinuria is common in HIV-positive patients and specifically associated with exposure to tenofovir disoproxil Fumarate.

OBJECTIVES: The aim of this cross-sectional study was to evaluate the prevalence and risk factors of medium-grade proteinuria (100-500 mg/g creatinine) among HIV-positive adults. METHODS: Spot urine samples of HIV-positive adults without known renal disease were analyzed quantitatively between January 2009 and February 2011. Demographic and medical data were collected. Multivariate regression models for different patterns of proteinuria were constructed. RESULTS: Among 411 patients, 18 (4.4 %) presented albuminuria >300 mg/g creatinine and/or proteinuria >500 mg/g creatinine and were excluded from further analyses. Among the study population of 393 patients, 181 (46.1 %) had no significant proteinuria or albuminuria (<100 and <30 mg/g creatinine, respectively), 60 (15.3 %) had moderate albuminuria, while 152 (38.7 %) had proteinuria without albuminuria, suggesting tubular proteinuria. Independent predictors for medium-grade tubular proteinuria in multivariate analysis were exposure to tenofovir (DF), a CD4 nadir <500/µl, older age, and anti-HCV-antibodies. There was no association with classic renal risk factors like diabetes mellitus and arterial hypertension, or with estimated glomerular filtration rate (eGFR). CONCLUSIONS: We detected significant proteinuria in 230 (56.0 %) of 411 HIV-positive patients. Among this group, 152 (66.1 %) had medium-grade proteinuria without albuminuria, which was significantly associated with exposure to tenofovir, older age, a lower CD4 nadir and Hepatitis C. Nephrologic or HIV treatment guidelines fail to detect most of these patients but rather identify patients with high cardiovascular risk. In the absence of an association with eGFR the role of medium-grade tubular proteinuria as a potential early marker of chronic kidney disease remains unclear. Prospective studies are needed.

Novel antibiotics: are we still in the pre-post-antibiotic era?

PURPOSE: Therapeutic efficacy and safety in infections due to multidrug-resistant bacteria can be improved by the clinical development of new compounds and devising new derivatives of already useful antibiotics. Due to a striking global increase in multidrug-resistant Gram-positive but even more Gram-negative organisms, new antibiotics are urgently needed. METHODS: This paper provides a review of novel antibiotic compounds which are already in clinical development, mainly in phase III clinical trials. CONCLUSION: Each of these new trials increases the possibility of new antibiotics receiving approval.

[MRSA - hygiene management, diagnostics and treatment]. / MRSA - Hygiene-Management, Diagnostik und Therapie.

Methicillin-resistant Staphyococcus aureus strains remain a challenge to both patient care and infection control efforts. In addition to the defining resistance to beta-lactams several other antibiotic classes may be ineffective. Some resistance phenotypes exhibit a characteristic distribution pattern between healthcare-associated, community-associated, and livestock-associated MRSA strains. For patients with defined risk factors a search-, destroy-, follow-up-strategy is recommended in order to identify and eliminate MRSA colonization. Mupirocin nasal ointment and extensive hygiene measures are the mainstays of decolonization efforts. Besides vancomycin several other antimicrobials such as rifampin, trimethoprim-sulfamethoxazol, clindamycin, linezolid, and daptomycin are used to treat specific MRSA infections.

Sexual and reproductive health services for people living with HIV/AIDS in Germany: are we up to the challenge?

PURPOSE: Germany is witnessing an increase in the number of new infections with human immunodeficiency virus (HIV). Enabling persons living with HIV (PLHIV) to adopt safer sex practices might contribute towards reducing the incidence of HIV infections. The aim of this study was to identify gaps in the sexual and reproductive health (SRH) services provided to PLHIV in Germany. METHODS: Within the framework of the European public health project Eurosupport 5, self-reported questionnaires were distributed to PLHIV and a survey of SRH-service providers was carried out. The completed questionnaires and survey results were analysed. RESULTS: Of the questionnaires distributed, 218 PLHIV (90 % men, 10 % women) returned a completed questionnaire. Of these, 74 % self-identified as men having sex with men (MSM) and 13 % as heterosexual men. MSM reported a median number of ten casual partners in the previous 6 months and unprotected sex in one-third of anal intercourses with casual partners, demonstrating that this group adopted more risky sexual behaviours than heterosexual PLHIV. Even though all PLHIV stated they would appreciate more support and service providers indicated that they provided a wide range of SRH services, SRH-relevant topics were rarely discussed between PLHIV and service providers. According to the patients' perception, shortage of time, lack of initiative by service providers and their own difficulty to address SRH-related topics were the most relevant obstacles to receiving satisfactory support. CONCLUSION: Many PLHIV consult their HIV-physician regularly for medical follow-up and also indicate that HIV-physicians should be the source of information concerning SRH counselling. HIV-physicians should take advantage of their key role in HIV care and strengthen their efforts to integrate SRH services in routine HIV care.

Staphylococcus aureus infection following nasal colonization: an approach to rapid risk stratification in a university healthcare system.

Staphylococcus aureus carriage increases the risk of infection. Demographic and microbiological data from adult patients with nasal S. aureus carriage were analysed in order to define effect modifiers of this association. Predictors for growth of S. aureus from clinical cultures were identified in a case-control study using bivariate and multi-variate logistic regression analysis. Between 1 January 2005 and 1 April 2009, 645 patients with nasal S. aureus colonization and documented follow-up of ≥90 days were identified; 159 (25%) patients were found to carry meticillin-resistant S. aureus (MRSA). The median age of patients was 58 years, and 421 (65%) were male. During the subsequent 90 days, one or more clinical cultures were positive for S. aureus in 131 patients (20%). Multi-variate analysis identified a prior history of any S. aureus positive culture [adjusted odds ratio (aOR) 2.4, 95% confidence interval (CI) 1.5-3.8; P=0.0005) as an independent predictor of subsequent S. aureus infection. MRSA colonization was a predictor of infection in patients aged >40 years (aOR 2.5, 95% CI 1.4-4.1; P=0.0004), and even more so in patients aged ≤40 years (aOR 12.4, 95% CI 3.0-51; P=0.0005). Age >40 years was an additional independent risk factor for meticillin-susceptible S. aureus carriers (aOR 3.0, 95% CI 1.2-7.8; P=0.02) but not for MRSA carriers. Preferential screening of patients at high risk for MRSA carriage and subsequent infection, as well as the absence of a universal policy for the use of decolonization regimens, may partly explain the relatively high risk of S. aureus infection in the patient population. MRSA carriers and older patients with recurrent S. aureus positive cultures may gain the greatest benefit from routine decolonization measures.

Changes in lipid profiles after switching to a protease inhibitor-containing cART--unfavourable effect of fosamprenavir in obese patients.

OBJECTIVE: One focus in the medical care of HIV-infected patients today is cardiovascular risk reduction. Metabolic disturbances occur frequently in patients taking protease inhibitors (PI) and are a major risk factor for atherosclerosis. With few published head-to-head studies substance-specific differences concerning metabolic effects are insufficiently defined. Therefore this cohort study directly compared the metabolic profiles of boosted atazanavir (ATV/r), fosamprenavir (FPV/r) and saquinavir (SQV/r). METHODS: Data from a cohort of 124 HIV patients initiating a boosted regimen with one of the PIs at the University of Munich (LMU) infectious diseases outpatient clinic were retrospectively analyzed. The main outcome measures were median absolute total cholesterol levels and median relative change of total cholesterol levels after six months of PI-therapy. A multivariate linear regression model was built to identify and control for potential confounders of the association between PI-therapy and serum cholesterol level. RESULTS: 84 patients were treated with ATV/r, 23 patients received FPV/r and 17 patients SQV/r. Demographically the cohort constituted a representative sample of HIV-infected patients in Germany. There were no statistically significant differences between the comparison groups at baseline. - After six months of therapy median serum cholesterol in the ATV/r group dropped significantly from 204 mg/dl to 186 mg/dl, while in the FPV/r and SQV/r groups a rise in serum cholesterol levels was observed from 179 mg/dl to 204 mg/dl and from 173 mg/dl to 209 mg/dl respectively. The multivariate linear regression model identified a significant interaction between BMI at baseline and treatment with FPV/r: patients with higher BMI showed more prominent increases in serum cholesterol while taking FPV/r compared to patients with lower BMI. CONCLUSION: This cohort study demonstrated the most favourable impact on serum cholesterol levels and thus cardiovascular risk for ATV/r compared to FPV/r and SQV/r under real-life conditions. Given the statistical interaction detected between FPV/r and BMI further studies assessing metabolic profiles of different antiretroviral drugs in specific patient populations are urgently needed.

[Long-term efficacy of second-line treatment of HIV infection after class change following virological failure on protease inhibitor-based therapy]. / Langfristig wirksame Zweit-Therapie der HIV-Infektion bei Klassenwechsel nach virologischem Versagen unter Protease-Inhibitoren.

BACKGROUND AND OBJECTIVE: While there are evidence-based recommendations for the initial combination antiretroviral treatment (cART) of HIV infection, there are no comparative studies on long-term efficacy of different second-line strategies after initial virological failure. The aim of this study was to compare different second-line strategies after virological failure of an initial protease inhibitor (PI) based regimen, specifically the comparison between change to a different PI and class change to a non-nucleoside reverse transcriptase inhibitor (NNRTI). PATIENTS AND METHODS: This cohort study retrospectively analyzed patient data documented for the Clinical Surveillance of HIV Disease project (ClinSurv) between 1999 and 2008, run by the Robert Koch Institute in Berlin, Germany. Follow-up data for at least three months of a treatment switch after virological failure of the first-line regimen were available for 157 patients out of the 14,377 patients in the ClinSurv cohort. Eighty-four (54%) of these had a PI-based first-line regimen and were therefore included into the analysis. Fifty-one (61%) of the 84 patients were switched to a different PI (group 1), 33 (39%) to a NNRTI (group 2). Primary end points were the probability of virological failure of the second-line regimen, the duration of a successful second-line regimen and the time to suppression of viral load below the level of detectability. RESULTS: There was no significant difference in the median time to virological suppression with 88 days in group 1 and 57 days in group 2 (p = 0.16). After > 3,000 days more than 50% of patients in group 2 (class switch to NNRTI) were still on an effective regimen, their risk of virologic failure thus was significantly lower than in group 1 (switch to a different PI), where the median duration of second-line therapy was only 581 days. Multivariate Cox regression analysis did not identify any of the available covariates as significant predictors of duration of the second-line treatment or as confounders. For group 1, with patients switching within the PI class, there was a more than two-fold risk of virological failure during the time of observation (HR = 2.3; 95%CI 1.1 - 4.9; p = 0.03). CONCLUSION: Class switch to a NNRTI as opposed to changing to a different PI following virological failure of a PI-based first-line regimen is associated with significantly better durability of the second-line regimen.

Stenotrophomonas maltophilia induced post-cataract-surgery endophthalmitis: Outbreak investigation and clinical courses of 26 patients.

BACKGROUND: Stenotrophomonas maltophilia, a microorganism which colonizes plastic material, is a rare causative agent of iatrogenic endophthalmitis. PATIENTS AND METHODS: A cluster of 26 cases of acute post-cataract-surgery endophthalmitis (PE) was identified. An outbreak investigation was performed. Information was abstracted from patients' charts and questionnaires sent to patients and their general practitioners. Vision was examined before, during, as well as one and six months after acute PE. Bacterial isolates were subjected to molecular typing. RESULTS: All patients initially received empiric systemic antibiotic treatment. The source of the infections was identified to be the rinsing solution used during cataract surgery, which was contaminated with two strains of S. maltophilia. Antibiotic therapy was subsequently changed to trimethoprim/sulfamethoxazol and ciprofloxacin for 30 days, complemented with iv fluocortolone and topical treatment with prednisolone, ciprofloxacin, and chloramphenicol. Twenty-one patients (81%) received pars plana vitrectomy and were additionally treated with intravitreal injections of vancomycin, amikacin and dexamethasone, or imipenem and dexamethasone, respectively. In addition, oxacillin, mezlocillin, and prednisolone were applied subconjunctivally after vitrectomy. Six months after acute infection, a final visual acuity of > or = 0.2 was achieved by 21/26 patients (80%), a visual acuity of > or = 0.5 by 14/26 patients (54%). Twenty of 26 patients (77%, 17 of whom had undergone vitrectomy) achieved a higher visual acuity than before surgery. Patients from the vitrectomy group had a median final visual acuity of 0.5 compared to 0.4 in the 5 patients without vitrectomy. There was 1 retinal ablation, 2 intra-retinal bleedings, and relapse of infection in 2/26 patients (8%), with isolation of S. maltophilia in one of the relapsing infection cases. CONCLUSIONS: Empiric antibiotic treatment of PE may not adequately treat rare pathogens such as S. maltophilia. Administration of an effective systemic or intravitreal antibiotic treatment after identification of S. maltophilia may have contributed to the favorable clinical course and relatively low relapse frequency in our patients. Despite the known problem of persistence of S. maltophilia, visual acuity outcome after treatment is comparable to PE induced by other Gram-positive or Gram-negative bacteria.

Clonal diversity in episodes with multiple coagulase-negative Staphylococcus bloodstream isolates suggesting frequent contamination.

BACKGROUND: Coagulase-negative Staphylococci (CoNS) are frequently recovered from blood cultures, which may indicate contamination or true bacteremia. PATIENTS AND METHODS: CoNS isolates recovered from patients with episodes of two or more blood cultures positive for CoNS within 24 h were typed by both pulsed-field gel electrophoresis (PFGE) and speciation. RESULTS: PFGE typing of 94 CoNS isolates recovered from episodes with two or more positive blood cultures for CoNS within 24 h discriminated 35 strain clusters. The CoNS isolates were unrelated in 15 (39%) of 38 episodes, suggesting contamination. Sensitivity and specificity of CoNS speciation compared to PFGE was 96% and 67%, respectively. Clonal and species diversity differed between hospital areas. CONCLUSION: Contamination may frequently be present even in the setting of the recovery of CoNS from two or more blood culture sets within 24 h. Speciation of CoNS bloodstream isolates is rapid and may improve patient care as well as reduce unnecessary antibiotic use.