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The risk of liver toxicity during antiretroviral drug use in human immunodeficiency virus (HIV)-positive patients increases in the presence of chronic hepatitis C virus (HCV) infection. It is unknown whether sustained HCV clearance after interferon (IFN)-based therapy might reduce this complication. The incidence of severe elevations in liver enzyme levels during antiretroviral therapy was retrospectively analyzed in a group of HIV/HCV-coinfected patients after completion of a full course of IFN-based therapy. Hepatic events were recorded according to the achievement of a sustained virological response (SVR) and the presence of advanced liver fibrosis was assessed by transient elastometry. A total of 132 HIV/HCV-coinfected patients were analyzed (66% men; mean age 38 years). Overall 33% achieved an SVR and 40% had advanced liver fibrosis after IFN therapy. A total of 49 episodes of liver toxicity occurred during a mean of 35 months of follow-up (9.7% per year) after IFN therapy. The yearly incidence of hepatic events was greater in patients who did not achieve an SVR than in those who did (12.9% vs. 3.1%; P < .001) and in patients with advanced liver fibrosis than in those without it (14.4% vs. 7.6%; P = .003). Drugs involved in hepatic events were dydeoxynucleoside analogues (namely didanosine and stavudine; 40%) nevirapine (30%) efavirenz (11%) and protease inhibitors (PIs; 8%). In logistic regression analysis lack of an SVR (odds ratio [OR] 6.13 [95% confidence interval {CI} 1.83-37.45]; P = .003) and the use of dydeoxynucleosides (OR 3.59 [95% CI 1.23-10.42]; P = .02) were independent predictors of hepatotoxicity after IFN therapy. Conversely regimens containing PIs (OR 0.07 [95% CI 0.02-0.30]; P < .01) or efavirenz (OR 0.13 [95% CI 0.04-0.44]; P = .001) were associated with a diminished risk of hepatic events. Sustained HCV clearance after IFN-based therapy reduces the risk of liver toxicity during antiretroviral therapy which should further encourage the treatment of chronic hepatitis C in HIV-coinfected patients. In this population prescription of PIs or efavirenz decreases and use of dydeoxynucleoside analogues increases the risk of hepatotoxicity. (authors)

Purpose: The extent and predictors of liver fibrosis were examined in a HIV/HBVcoinfected cohort with extensive exposure to anti-HBV active HAART. Method: Liver fibrosis was measured using transient elastography. Results: Thirty-seven patients of a median age of 43 were included in the study. All but 2 patients had received anti-HBV drugs for a median time of 40 months in the context of HAART. F0-F1 METAVIR fibrosis scores (minimal or no fibrosis) as measured by elastography were found in 21 (57%) patients. AST levels were significantly lower among F0-F1 patients (33 IU/L) compared to F2-F4 patients (48 IU/L) (p = .01). ALT levels were also lower in F0-F1 patients (38 IU/L) than in F2-F4 patients (54 IU/L) (p = .05). Conclusion: In this HIV/HBV-coinfected cohort, with extensive HAART exposure including anti-HBV agents, more than half of the patients had no or minimal liver fibrosis. Higher transaminase levels were recognized in patients with higher degree of fibrosis.

Background Chronic hepatitis C leads to progressive liver fibrosis, which is accelerated in HIV-coinfected patients. Unfortunately, hepatitis C virus (HCV) therapy provides sustained virological response (SVR) to only 40% of coinfected patients. Little is known about the regression of hepatic fibrosis in treated patients. Methods All coinfected patients who had completed a full course of HCV therapy at our institution were identified. Liver fibrosis staging was estimated using non-invasive procedures at the time of initiating HCV therapy and reassessed at the last patient's follow-up using elastometry (FibroScan®). Results A total of 103 coinfected patients were identified. HCV genotype distribution was 1 (63%), 3 (29%) and 4 (8%). SVR had been attained by 34 individuals, while the remaining 69 were non-responders and/or relapsers. The mean lag time between the end of HCV therapy and the current assessment of liver fibrosis was 40 months, without differences between groups. Metavir score estimates were comparable before initiating HCV therapy in SVR and non-SVR patients. By contrast, current Metavir scores were lower in SVR than in non-SVR patients; for instance, F3-F4 estimates were 12% versus 54%, respectively ( PConclusions SVR after HCV therapy is associated with non-progression of liver fibrosis in HCV/HIV-coinfected patients, although this benefit may not be universal and improvement only been recognizable after several years of follow-up.

In a point-prevalence study performed in 145 Spanish hospitals in 2006, we collected 463 isolates of Staphylococcus aureus in a single day. Of these, 135 (29.2%) were methicillin (meticillin)-resistant S. aureus (MRSA) isolates. Susceptibility testing was performed by a microdilution method, and mecA was detected by PCR. The isolates were analyzed by pulsed-field gel electrophoresis (PFGE) after SmaI digestion, staphylococcal chromosomal cassette mec (SCC mec ) typing, agr typing, spa typing with BURP (based-upon-repeat-pattern) analysis, and multilocus sequence typing (MLST). The 135 MRSA isolates showed resistance to ciprofloxacin (93.3%), tobramycin (72.6%), gentamicin (20.0%), erythromycin (66.7%), and clindamycin (39.3%). Among the isolates resistant to erythromycin, 27.4% showed the M phenotype. All of the isolates were susceptible to glycopeptides. Twelve resistance patterns were found, of which four accounted for 65% of the isolates. PFGE revealed 36 different patterns, with 13 major clones (including 2 predominant clones with various antibiotypes that accounted for 52.5% of the MRSA isolates) and 23 sporadic profiles. Two genotypes were observed for the first time in Spain. SCC mec type IV accounted for 6.7% of the isolates (70.1% were type IVa, 23.9% were type IVc, 0.9% were type IVd, and 5.1% were type IVh), and SCC mec type I and SCC mec type II accounted for 7.4% and 5.2% of the isolates, respectively. One isolate was nontypeable. Only one of the isolates produced the Panton-Valentine leukocidin. The isolates presented agr type 2 (82.2%), type 1 (14.8%), and type 3 (3.0%). spa typing revealed 32 different types, the predominant ones being t067 (48.9%) and t002 (14.8%), as well as clonal complex 067 (78%) by BURP analysis. The MRSA clone of sequence type 125 and SCC mec type IV was the most prevalent throughout Spain. In our experience, PFGE, spa typing, SCC mec typing, and MLST presented good correlations for the majority of the MRSA strains; we suggest the use of spa typing and PFGE typing for epidemiological surveillance, since this combination is useful for both long-term and short-term studies.

Streptococcus pneumoniae is an uncommon cause of skin and soft tissue infections, yet the incidence and clinical significance of its isolation in samples of skin or soft tissues in unselected hospital samples is poorly understood. In the present study, a review was conducted of the records of all patients with skin and soft tissue infections due to S. pneumoniae at a university hospital between January 1994 and December 2005. The isolates were identified by standard methods and were serotyped, and susceptibility testing was performed by the broth microdilution method following the guidelines of the Clinical and Laboratory Standards Institute. During the study period, 3,201 isolates of S. pneumoniae were recovered from several sources. Of these, 69 (2.2%) were from skin and soft tissue samples (69 patients). Complete information could not be obtained for 13 patients. Of the 56 patients remaining, 36 (64.3%) were infected and fulfilled the inclusion criteria. The following types of infections were observed: surgical wound infection (n = 11), burn infection (n = 7), pyomyositis (n = 6), cellulitis (n = 4), perineal or scrotal abscess (n = 3), and other (n = 5). Thirty-one (86%) patients had a favorable outcome, and 5 (13.8%) patients died. Mortality was directly attributable to S. pneumoniae infection in three of the five fatal cases. Of the 39 S. pneumoniae isolates obtained (36 from skin and soft tissues, three from blood cultures), 58.9% were penicillin nonsusceptible, 7.7% were cefotaxime nonsusceptible, and 20.5% were erythromycin resistant. The most frequent serotypes were 3, 19, 11, and 23. Of the overall number of isolates of S. pneumoniae recovered in a general institution, 2.2% involved skin and soft tissues (of which 64% were clinically significant). Mortality due to pneumococcal skin and soft tissue infections was low.

A point-prevalence study, performed in 2002 in 143 Spanish hospitals, collected 439 isolates of Staphylococcus aureus. Of these, 134 (30.5%) were resistant to methicillin (i.e., MRSA). Susceptibility testing was performed by a microdilution method, and mecA was detected by PCR. The isolates were characterised by phage typing, pulsed-field gel electrophoresis (PFGE) after SmaI digestion, and SCCmec typing. The 134 MRSA isolates showed resistance to ciprofloxacin (93.3%), tobramycin (88.8%), erythromycin (67.9%), clindamycin (59.7%), gentamicin (42.5%), mupirocin (17.9%), rifampicin (5.2%) and trimethoprim–sulphamethoxazole (5.2%). All of the isolates were susceptible to glycopeptides. Twenty-five resistance patterns were found, of which four accounted for 66% of the isolates. Phage group III was the most frequent (41.1%). PFGE revealed 31 different patterns, with ten major clones (including two predominant clones with variable antibiotypes that accounted for 43.3% of the MRSA isolates) and 21 sporadic patterns. Two isolates belonged to two variants of the Iberian clone (ST247-MRSA-I), one to the Brazilian clone (ST239-MRSA-III), and seven to the EMRSA-16 clone (ST36-MRSA-II). SCCmecIV accounted for 70.2% of the isolates (73.9% were type IVA), while SCCmecI, SCCmecII and SCCmecIII accounted for 22.1%, 6.9% and 0.8% of isolates, respectively, with three non-typeable isolates. Isolates of SCCmecIV and SCCmecIVA were predominantly nosocomial (95.8% and 97.1%, respectively). None of the isolates produced Panton–Valentine leukocidin. Thus, two clones carrying SCCmecIV and SCCmecIVA, respectively, were predominant among nosocomial MRSA isolates throughout Spain.