Effectiveness of protease inhibitor monotherapy versus combination antiretroviral maintenance therapy: a meta-analysis.

BACKGROUND: The unparalleled success of combination antiretroviral therapy (cART) is based on the combination of three drugs from two classes. There is insufficient evidence whether simplification to ritonavir boosted protease inhibitor (PI/r) monotherapy in virologically suppressed HIV-infected patients is effective and safe to reduce cART side effects and costs. METHODS: We systematically searched Medline, Embase, the Cochrane Library, conference proceedings and trial registries to identify all randomised controlled trials comparing PI/r monotherapy to cART in suppressed patients. We calculated in an intention to treat (loss-of follow-up, discontinuation of assigned drugs equals failure) and per-protocol analysis (exclusion of protocol violators following randomisation) and based on three different definitions for virological failure pooled risk ratios for remaining virologically suppressed. FINDINGS: We identified 10 trials comparing 3 different PIs with cART based on a PI/r plus 2 reverse transcriptase inhibitors in 1189 patients. With the most conservative approach (viral load <50 copies/ml on two consecutive measurements), the risk ratios for viral suppression at 48 weeks of PI/r monotherapy compared to cART were in the ITT analysis 0.94 8 (95% CI 0.89 to 1.00) p = 0.06; risk difference -0.06 (95%CI -0.11 to 0) p = 0.05, p for heterogeneity  = 0.08, I(2) = 43.1%) and in the PP analysis 0.93 ((95%CI 0.90 to 0.97) p<0.001; risk difference -0.07 (95%CI -0.10 to -0.03) p<0.001, p for heterogeneity  = 0.44, I(2) = 0%). Reintroduction of cART in 44 patients with virological failure led in 93% to de-novo viral suppression. INTERPRETATION: Virologically well suppressed HIV-infected patients have a lower chance to maintain viral suppression when switching from cART to PI/r monotherapy. Failing patients achieve high rates of de-novo viral suppression following reintroduction of reverse transcriptase inhibitors.

A rifampicin-containing antibiotic treatment improves outcome of staphylococcal deep sternal wound infections.

BACKGROUND: Deep sternal wound infection (DSWI) is a severe complication after cardiac surgery, mostly caused by staphylococci. Little is known about the optimal antibiotic management. METHODS: A 10 year retrospective analysis of 100 patients with staphylococcal DSWI after cardiac surgery in a tertiary hospital. Treatment failure was defined as sternal wound dehiscence or fistula at the end of the prescribed antibiotic therapy, 12 months later, or DSWI-related death. RESULTS: Most patients were male (83%) and the median age was 72 years [interquartile range (IQR) 63-76]. Coronary artery bypass was the most frequent preceding procedure (93%). The median time to diagnosis of DSWI was 13 days (IQR 10-18) after surgery. Clinical presentation consisted of wound discharge in 77% of patients. Coagulase-negative staphylococci were isolated in 54 and Staphylococcus aureus in 46 patients. All patients received antibiotics and 95% underwent surgical debridement. The median duration of antibiotic treatment was 47 days (IQR 41-78). During follow-up, 21 out of 100 patients experienced treatment failure. Of these, 8/21 patients (38%) died from DSWI after a median of 12 days (IQR 8-30). In the multivariate analysis, a rifampicin-containing antibiotic regimen was the only factor associated with lower risk of treatment failure (hazard ratio 0.26, 95% confidence interval 0.10-0.64, P = 0.004). Prolonged treatment (12 weeks instead of 6 weeks) did not alter outcome (P = 0.716) in patients without prosthetic valve endocarditis. CONCLUSIONS: Treatment of rifampicin-susceptible staphylococcal DSWI with a rifampicin-containing antibiotic regimen may improve the outcome. After surgical debridement an antibiotic treatment of 6 weeks may be adequate for staphylococcal DSWI.

Implementation of raltegravir in routine clinical practice: selection criteria for choosing this drug, virologic response rates, and characteristics of failures.

BACKGROUND: Raltegravir (RAL) achieved remarkable virologic suppression rates in randomized-clinical trials, but today efficacy data and factors for treatment failures in a routine clinical care setting are limited. METHODS: First, factors associated with a switch to RAL were identified with a logistic regression including patients from the Swiss HIV Cohort Study with a history of 3 class failure (n = 423). Second, predictors for virologic outcome were identified in an intent-to-treat analysis including all patients who received RAL. Last observation carried forward imputation was used to determine week 24 response rate (HIV-1 RNA >or= 50 copies/mL). RESULTS: The predominant factor associated with a switch to RAL in patients with suppressed baseline RNA was a regimen containing enfuvirtide [odds ratio 41.9 (95% confidence interval: 11.6-151.6)]. Efficacy analysis showed an overall response rate of 80.9% (152/188), whereas 71.8% (84/117) and 95.8% (68/71) showed viral suppression when stratified for detectable and undetectable RNA at baseline, respectively. Overall CD4 cell counts increased significantly by 42 cells/microL (P < 0.001). Characteristics of failures were a genotypic sensitivity score of the background regimen

Less than 28 days of intravenous antibiotic treatment is sufficient for suppurative thrombophlebitis in injection drug users.

Data about the required duration of intravenous therapy for suppurative thrombophlebitis is lacking. Among 36 episodes of proven suppurative thrombophlebitis requiring hospital admission, no relapses occurred when treatment was given for >7 days intravenously and followed by oral therapy. A <4-week course of intravenous antibiotics may be sufficient.

Obituary to analgesic nephropathy--an autopsy study.

BACKGROUND: To determine whether classic analgesic nephropathy with renal papillary and urothelial capillary sclerosis could still be detected at autopsy in the beginning of the 21st century, the present study which is similar to a previous one performed in 1980 was undertaken as suggested by the Ad Hoc Committee of the International Study Group on Analgesics and Nephropathy. METHODS: Consecutive autopsies of 616 adults performed at the Basle Institute of Pathology between November 2000 and February 2002 were analysed. Tissue samples of renal cortex and papilla of 1220 kidneys and of each ureter and main renal artery available were subjected to a very careful and meticulous study using classical histopathological methodology. RESULTS: A number of lesions was found macroscopically but not a single case of papillary necrosis or analgesic nephropathy could be detected preceding histological analysis. Histologically, the most frequent lesions were vascular in 57.8% of kidneys followed by glomerular lesions in 13.1% (mostly diabetic glomerulosclerosis). Tubulo-interstitial lesions, mostly pyelonephritis were detected in 9.3% with only a single case of classic analgesic nephropathy with bilateral complete papillary necrosis and ureteral capillary sclerosis in a female who had received a renal transplant 14 years before her demise at the age of 67. In another five cases, complete papillary necrosis was detected associated with pyelonephritis, hydronephrosis or in completely shrunken kidneys. However, in the absence of capillary sclerosis, a histopathological diagnosis of classic analgesic nephropathy could not be made in any of these five cases. CONCLUSIONS: The Basle autopsy prevalence of analgesic nephropathy decreased continuously from some 3% in 1980 to 0.2% in 2000 as shown by the present study. Similarly, capillary sclerosis of the urinary tract, the initiating event in the pathophysiology of papillary necrosis and analgesic nephropathy and the histological hallmark of the effect of toxic metabolites of phenacetin in analgesic abusers decreased from 4% of autopsy cases between 1978 and 1980 to the single case of the present study observed at the end of 2000. Thus, the classic analgesic nephropathy has disappeared some 20 years after the removal of phenacetin from the analgesic market despite the fact that mixed analgesics containing paracetamol, the main metabolite of phenacetin, have continued to be popular and widely used drugs.