Risk Factors and Outcomes of Endocarditis Due to Non-HACEK Gram-Negative Bacilli: Data from the Prospective Multicenter Italian Endocarditis Study Cohort.

The objective of this study was to investigate predisposing factors and outcomes of infective endocarditis (IE) caused by non-HACEK Gram-negative bacilli (GNB) in a contemporary multicenter cohort. Patients with IE due to GNB, prospectively observed in 26 Italian centers from 2004 to 2011, were analyzed. Using a case-control design, each case was compared to three age- and sex-matched controls with IE due to other etiologies. Logistic regression was performed to identify risk factors for IE due to GNB. Factors associated with early and late mortality were assessed by Cox regression analysis. The study group comprised 58 patients with IE due to GNB. We found that Escherichia coli was the most common pathogen, followed by Pseudomonas aeruginosa and Klebsiella pneumoniae The genitourinary tract as a source of infection (odds ratio [OR], 13.59; 95% confidence interval [CI], 4.63 to 39.93; P < 0.001), immunosuppression (OR, 5.16; 95% CI, 1.60 to 16.24; P = 0.006), and the presence of a cardiac implantable electronic device (CIED) (OR, 3.57; 95% CI, 1.55 to 8.20; P = 0.003) were factors independently associated with IE due to GNB. In-hospital mortality was 13.8%, and mortality rose to 30.6% at 1 year. A multidrug-resistant (MDR) etiology was associated with in-hospital mortality (hazard ratio [HR], 21.849; 95% CI, 2.672 to 178.683; P = 0.004) and 1-year mortality (HR, 4.408; 95% CI, 1.581 to 12.287; P = 0.005). We conclude that the presence of a genitourinary focus, immunosuppressive therapy, and an indwelling CIED are factors associated with IE due to GNB. MDR etiology is the major determinant of in-hospital and long-term mortality.

Current features of infective endocarditis in persons on hemodialysis: a prevalence study with case control design from the prospective multicenter SEI cohort.

PURPOSE: Persons on hemodialysis (HD) are at high risk of infective endocarditis (IE). In non-comparative retrospective studies, a higher rate of mortality was reported in IE on HD. We assessed risk factors, clinical characteristics, and outcomes of IE in HD. METHODS: This was a prevalence study with a case control methodology on a set of data from the prospectively followed cohort of the Studio Endocarditi Italiano (SEI), conducted between 2004 and 2011. Included were 42 consecutive cases of IE HD subjects and 126 controls not on HD, matched for age, sex, type of IE, and heart side involved. Clinical, echocardiographic, microbiological features, and disease complications and therapeutic modalities were assessed. RESULTS: HD patients were more often diabetics (42.9 vs 18.2 % in no-HD; p = 0.007) and immune-suppressed (16.7 vs 3.2 %; p = 0.02), and had a higher rate of predisposing cardiac conditions (45 vs 25 %; p = 0.031). A higher prevalence of health care-related acquisition and a shorter diagnostic delay was observed in IE on HD, that was more likely to be caused by staphylococci and less by streptococci (p < 0.002). Cardiac surgery was performed in 38 % of HD patients and 36.5 % of no-HD patients (p = 0.856). Complications were similar and in-hospital mortality did not differ significantly (26.2 % in HD vs 15.9 % in no-HD; p = 0.168). CONCLUSIONS: IE in persons on HD is characterized by distinctive clinical features, including a higher prevalence of some important comorbidities. Inconsistent with prior studies, we could not confirm a higher rate of complications and mortality in HD patients with IE.

OPERA: responses to peginterferon and ribavirin therapy in a subgroup of interferon-naïve patients with HIV/HCV genotype 2/3 co-infection in Italy.

BACKGROUND & AIMS: Hepatitis C virus (HCV) genotype 3 (G3) is common among HIV/HCV co-infected individuals and associated with moderate sustained virological response (SVR) rates with pegylated interferon (PEG-IFN) plus ribavirin (RBV) therapy, while G2 is less frequent and associated with higher SVR. To determine SVR and other response rates, identify SVR predictors and analyse differences between G2 and G3 with PEG-IFN/RBV in a large HIV/HCV G2/3 patient population. METHODS: This subgroup analysis of the prospective, observational OPERA (Optimized Pegylated interferon Efficacy and anti-Retroviral Approach) study was conducted between 2005 and 2011 in Italy in PEG-IFN/RBV-naïve HIV/HCV patients. The primary efficacy endpoint was SVR rate (HCV RNA <50 IU/ml or undetectable 24 weeks after end-of-treatment). RESULTS: Five hundred and fifty-six HCV G2/3 patients (G2 n = 60; G3 n = 496) were treated with PEG-IFN alfa-2a 180 µg/week or PEG-IFN alfa-2b 1.5 µg/kg, + RBV 13.6 ± 2.3 (mean ± SD) mg/kg/day for median 47 (26-54) weeks. SVR rates were 57.7%, 68.3% and 56.5% for G2/3, G2 and G3 respectively) and RVR rates were 53.2%, 57.1% and 45.8% respectively. Independent SVR predictors were undetectable baseline HIV RNA [adjusted odds ratio (AOR), 2.64; 95% CI: 1.523-4.565, P = 0.0005], age (AOR 0.95 per year; 95% CI: 0.908-0.994, P = 0.0258) and anti-HCV treatment duration (AOR 1.034 per week; 95% CI: 1.013-1.057, P = 0.0019). CONCLUSIONS: Undetectable HIV RNA, longer anti-HCV treatment adherence and younger age were independent SVR predictors in treatment-naïve HIV/HCV G2/3 patients receiving PEG-IFN/RBV. Suppressing HIV RNA replication before anti-HCV therapy and increasing adherence to PEG-IFN/RBV treatment SVR rates may improve SVR.

Predicting the occurrence of embolic events: an analysis of 1456 episodes of infective endocarditis from the Italian Study on Endocarditis (SEI).

BACKGROUND: Embolic events are a major cause of morbidity and mortality in patients with infective endocarditis. We analyzed the database of the prospective cohort study SEI in order to identify factors associated with the occurrence of embolic events and to develop a scoring system for the assessment of the risk of embolism. METHODS: We retrospectively analyzed 1456 episodes of infective endocarditis from the multicenter study SEI. Predictors of embolism were identified. Risk factors identified at multivariate analysis as predictive of embolism in left-sided endocarditis, were used for the development of a risk score: 1 point was assigned to each risk factor (total risk score range: minimum 0 points; maximum 2 points). Three categories were defined by the score: low (0 points), intermediate (1 point), or high risk (2 points); the probability of embolic events per risk category was calculated for each day on treatment (day 0 through day 30). RESULTS: There were 499 episodes of infective endocarditis (34%) that were complicated by ≥ 1 embolic event. Most embolic events occurred early in the clinical course (first week of therapy: 15.5 episodes per 1000 patient days; second week: 3.7 episodes per 1000 patient days). In the total cohort, the factors associated with the occurrence of embolism at multivariate analysis were prosthetic valve localization (odds ratio, 1.84), right-sided endocarditis (odds ratio, 3.93), Staphylococcus aureus etiology (odds ratio, 2.23) and vegetation size ≥ 13 mm (odds ratio, 1.86). In left-sided endocarditis, Staphylococcus aureus etiology (odds ratio, 2.1) and vegetation size ≥ 13 mm (odds ratio, 2.1) were independently associated with embolic events; the 30-day cumulative incidence of embolism varied with risk score category (low risk, 12%; intermediate risk, 25%; high risk, 38%; p < 0.001). CONCLUSIONS: Staphylococcus aureus etiology and vegetation size are associated with an increased risk of embolism. In left-sided endocarditis, a simple scoring system, which combines etiology and vegetation size with time on antimicrobials, might contribute to a better assessment of the risk of embolism, and to a more individualized analysis of indications and contraindications for early surgery.

Bactericidal activity of oxacillin and glycopeptides against Staphylococcus aureus in patients with endocarditis: looking for a relationship between tolerance and outcome.

BACKGROUND: There is no clear relationship between in vitro bactericidal activity tests and clinical outcome. We studied bactericidal activity of oxacillin, vancomycin and teicoplanin against Staphylococcus aureus isolates in patients with endocarditis and then we sought to determine if there was a relationship between in vitro bactericidal activity and clinical outcome. METHODS: Minimal bacteriostatic and minimal bactericidal concentrations were determined for Staphylococcus aureus strains isolated from patients with endocarditis following standardized methods. Medical records were reviewed retrospectively to collect data on antimicrobial susceptibility at admission, antimicrobial therapy, need for surgery, embolic events and outcome. RESULTS AND DISCUSSION: Sixty-two Staphylococcus aureus strains were studied in 62 patients with endocarditis. Overall, 91.9% definite, 21% methicillin resistant and 72.6% cured. Surgery was performed in 32.3% and embolic events were documented in 64.5%. Tolerance to oxacillin and teicoplanin was more common than vancomycin tolerance among methicillin susceptible Staphylococcus aureus. Among methicillin resistant Staphylococcus aureus teicoplanin was shown to have a higher rate of tolerance than vancomycin. No statistically significant differences on clinical outcome between oxacillin tolerant and oxacillin non tolerant Staphylococcus aureus infections were observed. Tolerance to oxacillin did not adversely affect clinical outcomes of patients with methicillin susceptible Staphylococcus aureus endocarditis treated with a combination of antimicrobials including oxacillin. The cure rate was significantly lower among patients with methicillin resistant Staphylococcus aureus endocarditis. CONCLUSIONS: In vitro bactericidal test results were not valid predictors of clinical outcome. Physicians need to use additional parameters when treating patients with staphylococcal endocarditis.

Resistance costs and future drug options of antiretroviral therapies: analysis of the role of NRTIs, NNRTIs, and PIs in a large clinical cohort.

OBJECTIVE: To investigate future drug options (FDOs), resistance cost (RCVF), and virologic response to genotypic-driven rescue highly active antiretroviral therapy (HAART), according to type of therapy. METHOD: This was a retrospective analysis in naïve or antiretroviral-experienced patients. Virologic response was defined as HIV RNA <50 copies. RESULTS: There were 108 patients failing first-line HAART; there were 328 experienced patients. FDOs were reduced in subjects failing a thymidine-analogue (TA) regimen (median 3.65, IQR 1.29 ) compared to patients without TA (median 3.82, IQR 1.12) (p = .011). FDOs after first failure were higher for patients with non-nucleoside reverse transcriptase inhibitor (NNRTI; median 3.82; IQR 1.24) than with protease inhibitor (PI; median 3.64, IQR 1.15) (p = .027). In experienced patients, FDOs were much higher for TA (p = .005). Patients responding to genotypic-modified regimens had higher FDOs (median 3.9 4, IQR 2.53) than patients not responding (median 2.18, IQR 3.65) (p > .0001). Switching from an NNRTI-based HAART to a boosted PI had a higher chance (48.1%) of achieving a full virologic suppression, compared to switching from PI to NNRTI (21.4%, p < .0001). CONCLUSION: FDOs and RCVF are parameters that can quantify the therapeutic choices at virologic failure. Different drugs induce different FDOs and RCVF. In successive-line regimens, the higher antiviral effect and genetic barrier of boosted PIs may overcome the limits of using nucleoside reverse transcriptase backbones, with only partial effectiveness.

Effect of adherence to HAART on virologic outcome and on the selection of resistance-conferring mutations in NNRTI- or PI-treated patients.

BACKGROUND: The effect of adherence on the risk of virologic failure and mutations selection was verified in a prospective study. METHOD: At baseline, all patients had a viral load (VL) <50 copies/mL and completed a self-reported questionnaire. Patients were followed for the subsequent 4 months to document virologic rebound (VL > 50 copies/mL). RESULTS: 1,133 patients completed 2,240 questionnaires/follow-up (non-nucleoside reverse transcriptase inhibitor [NNRTI] = 1,479; single protease inhibitor [PI] = 200; boosted PI = 561). Only the type of treatment and the baseline adherence rate were significantly associated with the virologic endpoint. A viral rebound rate >10% was observed in patients treated with single PI (14.7%) or boosted PI (11.7%) up to an adherence rate of 95%, whereas a similar (17.6%) rebound rate was observed only in NNRTI-treated patients with very low adherence (<55%). After adjustment for other baseline predictors of adherence, patients on NNRTIs showed a higher adherence rate than those on PIs but not higher than those on boosted PIs. The same adherence rate did not have the same result, in terms of virologic rebound, in patients on the same HAART for shorter or longer periods of time. Overall, the risk of virologic rebound for patients with >95% adherence rate was 6.2% in the first 6 months of therapy, lowered to 5.0% in the following 6 months, and was 3.2% thereafter. The risk of selecting for resistance-inducing viral mutation for NNRTI-treated patients was higher (4.9%) at very low adherence rates (<75%); the opposite was true for single PI-treated patients (4.2% for adherence >95%). Boosted PI-treated patients showed an intermediate pattern, even if at a much lower level of risk. CONCLUSION: Low adherence is a major determinant of virologic failure, however different therapies have different adherence cutoffs determining a significant increment of risk.

Candida endocarditis: systematic literature review from 1997 to 2014 and analysis of 29 cases from the Italian Study of Endocarditis.

INTRODUCTION: Candida Endocarditis (CE) is a deadly disease. It is of paramount importance to assess risk factors for acquisition of both Candida native (NVE) and prosthetic (PVE) valve endocarditis and relate clinical features and treatment strategies with the outcome of the disease. Areas covered: We searched the literature using the Pubmed database. Cases of CE from the Italian Study on Endocarditis (SEI) were also included. Overall, 140 cases of CE were analyzed. Patients with a history of abdominal surgery and antibiotic exposure had higher probability of developing NVE than PVE. In the PVE group, time to onset of CE was significantly lower for biological prosthesis compared to mechanical prosthesis. In the whole population, greater age and longer time to diagnosis were associated with increased likelihood of death. Patients with effective anti-biofilm treatment, patients who underwent cardiac surgery and patients who were administered chronic suppressive antifungal treatment showed increased survival. For PVE, moderate active anti-biofilm and highly active anti-biofilm treatment were associated with lower mortality. Expert commentary: Both NVE and PVE could be considered biofilm-related diseases, pathogenetically characterized by Candida intestinal translocation and initial transient candidemia. Cardiac surgery, EAB treatment and chronic suppressive therapy might be crucial in increasing patient survival.

Which antibiotic prophylaxis to use for urologic procedures in patients at risk for infective endocarditis: a report on two cases.

In urologic surgery, antibiotic prophylaxis is generally recommended for transrectal prostate biopsies and transurethral prostate resection. While a fluoroquinolone (such as ciprofloxacin or levofloxacin) may be appropriate in most instances, patients at risk for infectious endocarditis (IE) may require a different regimen, effective also against Enterococcus species. We describe and comment on the cases of two patients who, following urologic procedures and antibiotic prophylaxis, developed Enterococcus faecalis endocarditis. We also propose an antibiotic prophylactic regimen for urologic procedures suitable for patients at risk for infectious endocarditis (IE).

OPERA: use of pegylated interferon plus ribavirin for treating HCV-HIV coinfection in interferon-naive patients.

BACKGROUND: The Optimized Pegylated interferons Efficacy and anti-Retroviral Approach (OPERA) study aimed to assess the efficacy and safety profile of treatment with pegylated interferons (PEG-IFNs) in interferon-naive patients with chronic HCV and HIV infection in routine clinical practice. METHODS: This was a multicentre, prospective observational cohort study conducted at 98 Italian referral centres for the treatment of chronic HCV and HIV coinfection. Adult subjects (n=1,523) with a confirmed diagnosis of HCV and stable HIV coinfection were followed between April 2005 and March 2011; of these, 1,284 were interferon-naive and were the focus of this analysis. Patients received PEG-IFN-α2a or -α2b plus ribavirin combination therapy. The choice of treatment and dose was at the investigator's discretion, according to the summary of product characteristics and current guidelines. The primary efficacy end point was sustained virological response (SVR). Secondary end points included rates of rapid viral response, early viral response and response at end of treatment. RESULTS: SVR was achieved by 40.0% of patients; the highest SVR rate was observed in patients with HCV genotypes 2 and 3. More genotype 2 and 3 than genotype 1 and 4 patients achieved rapid and early viral responses, and end of treatment responses. Higher SVR rates were also associated with ≥80% anti-HCV treatment compliance and lower baseline HCV levels. CONCLUSIONS: The OPERA study results show that PEG-IFN plus ribavirin is an effective treatment for HCV-HIV coinfection in interferon-naive patients. Independent predictors of SVR include HCV genotype, undetectable baseline HIV RNA and baseline HCV RNA<500,000 IU/ml.

In-hospital and 1-year mortality in patients undergoing early surgery for prosthetic valve endocarditis.

IMPORTANCE: There are limited prospective, controlled data evaluating survival in patients receiving early surgery vs medical therapy for prosthetic valve endocarditis (PVE). OBJECTIVE: To determine the in-hospital and 1-year mortality in patients with PVE who undergo valve replacement during index hospitalization compared with patients who receive medical therapy alone, after controlling for survival and treatment selection bias. DESIGN, SETTING, AND PARTICIPANTS: Participants were enrolled between June 2000 and December 2006 in the International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS), a prospective, multinational, observational cohort of patients with infective endocarditis. Patients hospitalized with definite right- or left-sided PVE were included in the analysis. We evaluated the effect of treatment assignment on mortality, after adjusting for biases using a Cox proportional hazards model that included inverse probability of treatment weighting and surgery as a time-dependent covariate. The cohort was stratified by probability (propensity) for surgery, and outcomes were compared between the treatment groups within each stratum. INTERVENTIONS: Valve replacement during index hospitalization (early surgery) vs medical therapy. MAIN OUTCOMES AND MEASURES: In-hospital and 1-year mortality. RESULTS: Of the 1025 patients with PVE, 490 patients (47.8%) underwent early surgery and 535 individuals (52.2%) received medical therapy alone. Compared with medical therapy, early surgery was associated with lower in-hospital mortality in the unadjusted analysis and after controlling for treatment selection bias (in-hospital mortality: hazard ratio [HR], 0.44 [95% CI, 0.38-0.52] and lower 1-year mortality: HR, 0.57 [95% CI, 0.49-0.67]). The lower mortality associated with surgery did not persist after adjustment for survivor bias (in-hospital mortality: HR, 0.90 [95% CI, 0.76-1.07] and 1-year mortality: HR, 1.04 [95% CI, 0.89-1.23]). Subgroup analysis indicated a lower in-hospital mortality with early surgery in the highest surgical propensity quintile (21.2% vs 37.5%; P = .03). At 1-year follow-up, the reduced mortality with surgery was observed in the fourth (24.8% vs 42.9%; P = .007) and fifth (27.9% vs 50.0%; P = .007) quintiles of surgical propensity. CONCLUSIONS AND RELEVANCE: Prosthetic valve endocarditis remains associated with a high 1-year mortality rate. After adjustment for differences in clinical characteristics and survival bias, early valve replacement was not associated with lower mortality compared with medical therapy in the overall cohort. Further studies are needed to define the effect and timing of surgery in patients with PVE who have indications for surgery.

Mitochondrial changes during D-drug-containing once-daily therapy in HIV-positive treatment-naive patients.

BACKGROUND: Antiviral drugs of the category of nucleoside reverse transcriptase inhibitors (NRTIs), largely used for the treatment of HIV infection, can have toxic effects on mitochondria. We performed a cross-sectional study on mitochondrial toxicity in a randomized group of patients belonging to a larger randomized study on different NRTI-based once-daily regimens by quantifying mitochondrial DNA (mtDNA), three different mitochondrial RNAs (mtRNAs) and functional parameters in highly purified peripheral CD4+ and CD8+ T-cells. METHODS: A total of 49 previously treatment-naive patients treated for a mean of 15 months with efavirenz plus didanosine plus lamivudine (group 1), or tenofovir disoproxil fumarate plus lamivudine (group 2), or didanosine plus abacavir (group 3) were considered. The groups were matched for sex, age, CDC classification, risk factor for HIV, nadir CD4+ T-cell count and baseline viral load. mtDNA and mtRNA were quantified by using real-time PCR assays. RESULTS: No patient showed any clinical symptom; however, the amount of mtDNA in CD4+ and CD8+ T-cells was significantly lower in groups 1 and 3; similarly, the expression of different mtRNAs in both CD4+ and CD8+ T-cells showed significant differences that were dependent upon the drug used. No differences were found in mitochondrial membrane potential and mitochondrial mass in peripheral lymphocytes. The amount of total HIV DNA in CD4+ T-cells did not differ among the groups, who displayed a similar immune reconstitution and control of the virus. CONCLUSIONS: An efficient didanosine-containing once-daily therapy can have more mitochondrial toxicity than regimens devoid of this drug.

CD4 cell-guided scheduled treatment interruptions in HIV-infected patients with sustained immunologic response to HAART.

OBJECTIVE: To compare continuous HAART with a CD4 cell-driven scheduled treatment interruption (STI) strategy. METHODS: LOng Term Treatment Interruption study is a randomized, controlled, prospective trial. Patients with CD4 cell counts more than 700 cells/microl were eligible, and the immunologic threshold to resume HAART was 350 cells/microl. The primary end point was the development of an opportunistic disease, death from any cause or the occurrence of diseases, other than opportunistic, requiring hospital admission. Secondary end points were major adverse effects, virologic failures and therapeutic costs. RESULTS: Three hundred and twenty-nine patients were randomized 1: 1. Total follow-up was 1388 person-years (mean 4.2 years). Patients in the STI group stopped therapy for a total of 241 STI cycles, their mean off-therapy period was 65.3% of the follow-up. The primary end point occurred in 12.1% of patients on STI and in 11.6% of controls [odds ratio 1.05; 95% confidence interval 0.54-2.05]. A higher proportion of patients in the STI arm were diagnosed with pneumonia (P = 0.037), whereas clinical events influencing the cardiovascular risk of patients were significantly (P < 0.0001) more frequent among controls. Eight patients (4.8%) in the STI group and 11 (6.7%) controls developed viral resistance [odds ratio 0.79, 95% confidence interval 0.27-1.81]. The mean daily therapeutic cost was 20.29 euro for controls and dropped to 9.07 euro in the STI arm (P < 0.0001). CONCLUSION: The two strategies may be considered clinically equivalent. CD4 cell-guided STIs seem a possible alternative for chronically infected individuals responding to HAART provided that CD4 cell decrements would be steadily maintained above a safe threshold.

Candida infective endocarditis: report of 15 cases from a prospective multicenter study.

Candida species are an uncommon cause of infective endocarditis (IE). Given the rarity of this infection, the epidemiology, prognosis, and optimal therapy of Candida IE are poorly defined. We conducted a prospective, observational study at 18 medical centers in Italy, including all consecutive patients with a definite diagnosis of IE admitted from January 2004 through December 2007.A Candida species was the causative organism in 8 cases of prosthetic valve endocarditis (PVE), 5 cases of native valve endocarditis (NVE), 1 case of pacemaker endocarditis, and 1 case of left ventricular patch infection. Candida species accounted for 1.8% of total cases, and for 3.4% of PVE cases. Most patients (86.6%) had a health care-associated infection. PVE associated with a health care contact occurred after a median of 225 days from valve implantation. Ten patients (66.6%) were treated with caspofungin alone or in combination with other antifungal drugs. The overall mortality rate was 46.6%. Mortality was higher in patients with PVE (5 of 8 cases, 62.5%) than in patients with NVE (2 of 5 patients, 40%). A better outcome was observed in patients treated with a combined medical and surgical therapy.Candida IE should be classified as an emerging infectious disease, usually involving patients with intravascular prosthetic devices, and associated with substantial related morbidity and mortality. Candida PVE usually is a late-onset disease, which becomes clinically evident even several months after an initial episode of transient candidemia.

Reduced valve replacement surgery and complication rate in Staphylococcus aureus endocarditis patients receiving acetyl-salicylic acid.

OBJECTIVES: To assess the influence of acetyl-salicylic acid (ASA) on clinical outcomes in Staphylococcus aureus infective endocarditis (SA-IE). METHODS: The International Collaboration on Endocarditis - Prospective Cohort Study database was used in this observational study. Multivariable analysis of the SA-IE cohort compared outcomes in patients with and without ASA use, adjusting for other predictive variables, including: age, diabetes, hemodialysis, cancer, pacemaker, intracardiac defibrillator and methicillin resistance. RESULTS: Data were analysed from 670 patients, 132 of whom were taking ASA at the time of SA-IE diagnosis. On multivariable analysis, ASA usage was associated with a significantly decreased overall rate of acute valve replacement surgery (OR 0.58 [95% CI 0.35-0.97]; p<0.04), particularly where valvular regurgitation, congestive heart failure or periannular abscess was the indication for such surgery (OR 0.46 [0.25-0.86]; p<0.02). There was no reduction in the overall rates of clinically apparent embolism with prior ASA usage, and no increase in hemorrhagic strokes in ASA-treated patients. CONCLUSIONS: In this multinational prospective observational cohort, recent ASA usage was associated with a reduced occurrence of acute valve replacement surgery in SA-IE patients. Future investigations should focus on ASA's prophylactic and therapeutic use in high-risk and newly diagnosed patients with SA bacteremia and SA-IE, respectively.

Prediction of Virologic Outcome of Salvage Antiretroviral Treatment by Different Systems for Interpreting Genotypic HIV Drug Resistance.

The authors assessed the predictive capacity of 3 rule-based algorithms (Bergamo, Stanford University, Rega Institute) for HIV genotypic interpretation. A total of 1132 postgenotypic regimens in 533 patients were considered. The genotypic sensitivity score (GSS) was strongly associated (P < .0001) with the virologic outcome (1 log HIV-RNA reduction). The 3 algorithms had a highly significant prediction efficiency. The Bergamo algorithm receiver-operating characteristic curve area under the curve (AUC) for the prediction of >/=1 log HIV-RNA reduction was 0.753 (95% confidence interval, 0.725-0.781), testifying that the prediction was significantly different (P < .0001) from simple chance. The AUCs obtained by the 2 other systems were similar (0.752 Stanford; 0.741 Rega). The predictive capacity of the algorithms was not influenced by the type of antiviral drugs used. The 3 considered rule-based algorithms for the interpretation of HIV genotypic resistance yield congruent results and may effectively predict the virologic outcome of rescue therapy. Their use may help clinicians in interpreting mutational patterns and in making therapeutic choices.

Reasons for discontinuation of nevirapine-containing HAART: results from an unselected population of a large clinical cohort.

OBJECTIVES: To evaluate the frequency of and predictive factors for nevirapine-based highly active antiretroviral therapy (HAART) discontinuation. METHODS: All patients receiving nevirapine as a component of HAART at our centre were retrospectively evaluated for efficacy and tolerability. Logistic regression was used to evaluate the influence of baseline characteristics on the outcome and Kaplan-Meier (KM) estimates to evaluate time-dependent variables. RESULTS: Between January 1999 and June 2006, 582 patients (72% males) received 744 nevirapine-based HAART regimens. Naive patients counted for 83 of these regimens; of the remaining 661 regimens administered to experienced patients, 306 were failing virologically and 355 were undergoing simplification strategies. A once-a-day schedule was used in 136 patients. The likelihood of maintaining the nevirapine-based regimen was statistically (P < 0.0001 in both cases) influenced by the patient's status (mean KM estimate of 812 days for virological failures, 1294 for naive patients and 1657 for treatment simplifications) and by the dosing schedule (once-daily 1315 days; twice-daily 1198 days). The most frequent reason for treatment discontinuation was resistance (17.5%) followed by reduced tolerability (16.3%), patient's decision (14%) and treatment strategies such as structured treatment interruptions (13.8%). During 10.2% of treatments, a grade 3 or greater increase in aminotransferase levels was observed, reflecting an overall incidence rate equal to 5.3 cases per 100 person-years. This lead to treatment discontinuation in 3.9% of cases. CONCLUSIONS: Nevirapine, especially when used in simplification strategies, enables doctors to extend the use of HAART over a long period of time. The risk of drug-induced hepatotoxicity is low, but nevirapine should be used with caution in patients co-infected with hepatitis C virus or with elevated liver function tests. As with any decision to prescribe a drug, a careful evaluation of the potential risks and benefits of using nevirapine must be made for each individual.