Comparison of antiviral activity of regimens containing nucleos(t)ide (NUC) Pairs in HIV-Infected Patients Initiating REScue therapy (The NUCREST Study).

BACKGROUND: recycling nucleos(t)ides (NUCs) is useful in regions where new antiretrovirals are not available. This study compares the effectiveness of NUC-containing regimens as rescue therapy in routine care. METHODS: retrospective, multicentre cohort study (January 2001 to June 2006) of patients with ≥ 1 virological failure who started therapy with 2 NUCs and 1 non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI). The primary endpoint was the rate of treatment response at 6 months (intention-to-treat [ITT] analysis). RESULTS: we included 719 patients (average of 4 prior regimens over a median 6.1 years). The most frequent NUC pairs were tenofovir plus lamivudine (TDF+3TC; 25%), tenofovir plus stavudine (TDF+d4T; 23%), and stavudine plus didanosine (d4T+ddI; 15%). A boosted PI was used in 68% of total cases. Resistance to both NUCs was more frequent in zidovudine plus lamivudine (AZT+3TC; 22.0%), abacavir plus lamivudine (ABC+3TC; 35.5%), and stavudine plus lamivudine (d4T+3TC; 31.2%). No significant differences were observed in treatment response (overall 65%, P = .67); ddI+3TC (71%) and d4T+3TC (53%) had the highest and lowest response rates, respectively. Median time to failure was shorter with d4T+3TC, d4T+ddI, and ABC+3TC (48, 51, and 58 weeks, respectively; P = .0012). Lower response rates associated with an increasing number of thymidine analog mutations (TAMs) were observed for ABC+3TC (P = .027). CONCLUSION: the clinical utility of NUCs for rescue therapy is limited and selection should be individualized. Specific combinations (d4T+3TC and d4T+ddI) might be less efficacious.

Staphylococcus lugdunensis infective endocarditis: description of 10 cases and analysis of native valve, prosthetic valve, and pacemaker lead endocarditis clinical profiles.

OBJECTIVE: To evaluate the incidence and the clinical and echocardiographic features of infective endocarditis (IE) caused by Staphylococcus lugdunensis and to identify the prognostic factors of surgery and mortality in this disease. DESIGN: Prospective cohort study. SETTING: Study at two centres (a tertiary care centre and a community hospital). PATIENTS: 10 patients with IE caused by S lugdunensis in 912 consecutive patients with IE between 1990 and 2003. METHODS: Prospective study of consecutive patients carried out by the multidisciplinary team for diagnosis and treatment of IE from the study institutions. English, French, and Spanish literature was searched by computer under the terms "endocarditis" and "Staphylococcus lugdunensis" published between 1989 and December 2003. MAIN OUTCOME MEASURES: Patient characteristics, echocardiographic findings, required surgery, and prognostic factors of mortality in left sided cases of IE. RESULTS: 10 cases of IE caused by S lugdunensis were identified at our institutions, representing 0.8% (four of 467), 1.5% (two of 135), and 7.8% (four of 51) of cases of native valve, prosthetic valve, and pacemaker lead endocarditis in the non-drug misusers. Native valve IE was present in four patients (two aortic, one mitral, and one pulmonary), prosthetic valve aortic IE in two patients, and pacemaker lead IE in the other four patients. All patients with left sided IE had serious complications (heart failure, periannular abscess formation, or shock) requiring surgery in 60% (three of five patients) of cases with an overall mortality rate of 80% (four of five patients). All patients with pacemaker IE underwent combined medical treatment and surgery, and mortality was 25% (one patient). In total 59 cases of IE caused by S lugdunensis were identified in a review of the literature. The combined analysis of these 69 cases showed that native valve IE (53 patients, 77%) is characterised by mitral valve involvement and frequent complications such as heart failure, abscess formation, and embolism. Surgery was needed in 51% of cases and mortality was 42%. Prosthetic valve endocarditis (nine of 60, 13%) predominated in the aortic position and was associated with abscess formation, required surgery, and high mortality (78%). Pacemaker lead IE (seven of 69, 10%) is associated with a better prognosis when antibiotic treatment is combined with surgery. CONCLUSIONS: S lugdunensis IE is an uncommon cause of IE, involving mainly native left sided valves, and it is characterised by an aggressive clinical course. Mortality in left sided native valve IE is high but the prognosis has improved in recent years. Surgery has improved survival in left sided IE and, therefore, early surgery should always be considered. Prosthetic valve S lugdunensis IE carries an ominous prognosis.

Native valve endocarditis due to Candida glabrata treated without valvular replacement: a potential role for caspofungin in the induction and maintenance treatment.

Conventional antifungal therapy for fungal endocarditis has been associated with a poor cure rate. Therefore, combined medical and surgical therapy has been recommended. However, new potent antifungal agents, such as echinocandins, could increase the medical options and, in some cases, avoid the need for surgery. We report a case of Candida endocarditis treated successfully without valve replacement with intravenous liposomal amphotericin B (total dose, 4 g) and intravenous caspofungin (a 100-mg loading dose followed by 50 mg per day for 8 weeks) as induction therapy and intravenous caspofungin (100 mg 3 times per week for 12 weeks) as maintenance therapy.

Cytokine-driven inflammatory response is associated with the hypermetabolism of AIDS patients with opportunistic infections.

BACKGROUND: To assess a possible role of systemic inflammation in the resting metabolic response in AIDS patients with active secondary infections. METHODS: Fifty-two patients with AIDS-defined criteria and concomitant active infections and 19 healthy subjects were studied. Measurements were as follows: body composition assessed by bioelectrical impedance; resting energy expenditure (REE) by 30-minute indirect calorimetry; cytokine concentrations (IL-6, IFNalpha, TNFalpha, sTNF-R1) by ELISA; C-reactive protein (CRP), erythrocyte sedimentation rate, fibrinogen, and nutritional parameters by standard techniques. RESULTS: REE adjusted for fat-free mass (REEFFM) was significantly increased in AIDS patients despite 39% of them not being hypermetabolic. The patients were undernourished and were found to have increased levels of acute-phase proteins and increased concentrations of IL-6 and sTNF-R1 relative to controls. REE parameters were positively related to CRP, ESR, ferritin, IL-6, and sTNF-R1 and negatively related to albumin, prealbumin, and transferrin. CRP was an independent predictor of REEFFM in AIDS patients and explained 25% of its variability. Patients with severe inflammation (CRP > or = 37 mg/dL) were significantly hypermetabolic with respect to patients without inflammation (CRP < 6 mg/dL) and had higher levels of IL-6 and sTNF-R1 and lower levels of albumin and prealbumin. Although no significant differences were observed with respect to the infection type, patients with tuberculosis and Pneumocystis carinii infections had higher resting metabolic and inflammatory responses, whereas patients with recurrent bacterial pneumonia were normometabolic and had lower levels of inflammatory markers. CONCLUSIONS: Resting hypermetabolism observed in AIDS patients with concurrent active infections is related to the presence and severity of systemic cytokine-driven inflammatory response, which could reflect the type of secondary infection.

Effect of malabsorption on nutritional status and resting energy expenditure in HIV-infected patients.

OBJECTIVE: To assess the influence of malabsorption on nutritional status and energy expenditure in patients at different stages of HIV infection. DESIGN AND METHODS: Fifty HIV patients were classified into three groups: Group 1, HIV asymptomatic patients (n=17); Group 2, AIDS without opportunistic infection (n=16); Group 3, AIDS patients with active infection (n=17). Clinically-healthy subjects (n=19) were used as controls. Parameters measured were: anthropometry, body composition by tetrapolar bioelectrical impedance; resting energy expenditure (REE) by open-circuit indirect calorimetry; malabsoption by D-xylose absorption and triolein breath tests. RESULTS: Malabsorption (defined as abnormality of xylose and/or fat absorption test) was found in 34 (68%) of patients: 9 (53%) Group 1; 11 (69%) Group 2; 14 (82%) Group 3. Twenty-seven (54%) had sugar malabsorption and 21 (42%) fat malabsorption. A significant relationship was observed between malabsorption and weight loss. REE measured was significantly lower in malabsorptive patients than in non-malabsorptive patients and controls (6006.3+/-846.5 versus 6443.4 + 985.5 versus 6802.1+/-862.7 kJ/day, respectively; P < 0.05). The REE adjusted for fat-free mass was lower in malabsorptive than in non-malabsorptive patients and slightly higher than in controls, although the differences were not statistically significant. CONCLUSIONS: The results suggest that malabsorption is a frequent feature in HIV infection and is related to the HIV-related weight loss. Hypermetabolism is not a constant phenomenon in HIV infection since, in the presence of malabsorption, our patients show an appropriate metabolic response with a compensatory decrease in REE.