Incidence of and risk factors for severe liver toxicity in HIV-infected patients on anti-tuberculosis treatment.

OBJECTIVE: To assess the incidence and risk factors for severe liver toxicity in human immunodeficiency virus (HIV) infected patients on anti-tuberculosis treatment and the impact of patients' characteristics and concomitant medications instituted during the first week of antituberculosis treatment. METHODS: HIV-infected patients referred to six French hospitals between 1 January 1992 and 31 December 2004, with confirmed or 'presumptive' tuberculosis (TB). Liver toxicity was studied during the first 2 months of TB treatment. RESULTS: During the 12 years of the study period, 144 patients were enrolled. Severe liver toxicity developed in 15 (10.7%). The median time to development of liver toxicity was 14 days. In the univariate analysis, high baseline bilirubin levels (P = 0.004), CD4 cell counts between 50 and 100 cells/mm3 (P = 0.022) and the use of fluconazole (P = 0.0005) were associated with liver toxicity. In the multivariate analysis, independent risk factors were abnormal baseline alanine aminotransferase (ALT) (P = 0.028) and bilirubin levels (P = 0.033) and the use of fluconazole (P = 0.008). CONCLUSION: Severe liver toxicity is frequent, and occurs early in the course of anti-tuberculosis treatment. ALT and bilirubin levels should be closely monitored during the first month of treatment, especially in patients with high baseline ALT or bilirubin levels. We suggest caution when prescribing fluconazole and anti-tuberculosis drugs concomitantly, although this needs to be confirmed and further investigated.

Major amputation of lower extremity: prognostic value of positive bone biopsy cultures.

BACKGROUND: To assess the correlation between culture results of section's osseous slice biopsy (SOB) and the distal infected site responsible for the amputation performed concomitantly during major amputation of lower extremity. The influence of a positive culture of SOB on the patients' outcome was also evaluated. MATERIALS AND METHODS: We conducted a retrospective study of medical charts of patients who underwent SOB during major amputation of lower extremity at our institution from 2000 to 2009. RESULTS: Fifty-seven patients (42 males/15 females, mean age 52.16years) who undergone major limb amputation (47 below knee and ten above knee) were included. The initial medical conditions of the investigated patients were: trauma (n=32), infection (n=13), trophic disorders (n=10) and tumor (n=2). The major cause of amputation was an uncontrolled infection, accouting for 64.9% of the cases (37/57) (foot=5, ankle=8, leg=24), the remaining 20 patients had trophic disorders of lower limb. Twenty-one (36.8%) from 57 biopsies were sterile, 12 (21.1%) doubtful and 24 (42.1%) positive. Thirty-one (54.4%) patients had an antibiotic-free interval before limb amputation. Independently of the bacterial species, 69.6% of the microorganisms identified from SOB were found in the distal infected site. Patients with positive SOB had a significantly longer interval between the decision to amputate the patient and the surgical procedure (200.2 vs. 70.1days; P<0.03) and a shorter total duration of antibiotic therapy before amputation than patients with negative SOB (3.68 vs. 6.08months; P<0.03). The delay for complete healing was significantly higher in patients with a positive SOB compared with those with a negative SOB (3.57 vs. 2.48months; P<0.03). CONCLUSION: Our results suggest that the infection may extend from the distal site to the level of amputation in a large proportion of cases and that the delay with which the amputation is performed after the decision has been taken may play a role in this event. LEVEL OF EVIDENCE: Study level IV: retrospective observationnal study.