What do beta-lactams add to vancomycin or daptomycin in the treatment of patients with methicillin-resistant Staphylococcus aureus bacteraemia? A review.

Several studies have documented the synergy between vancomycin/daptomycin and various beta-lactams, and clinical studies have studied this combination therapy in humans. We review the published literature on this topic to know the utility of the combined treatment with beta-lactams in treating bacteraemia methicillin-resistant Staphylococcus aureus (MRSA) infections. Fifteen observational studies, three randomised clinical trials and three systematics reviews are analysed in this article. Observational studies used ceftaroline, cefazolin, piperacillin/tazobactam or cefepime among the beta-lactams. Clinical trials used cloxacillin or flucloxacillin as the most used beta-lactam in two trials and ceftaroline in one. Three systematic reviews are published. One of them only includes studies with vancomycin and included six studies. The other two systematic reviews include patients with daptomycin or vancomycin and included 15 and 9 studies, respectively. Adding a beta-lactam to vancomycin or daptomycin may help shorten bacteraemia and avoid recurrences in patients with MRSA bacteraemia. There is no evidence that combined therapy improves mortality. Nephrotoxicity in clinical trials precludes the use of combination therapy mainly with cloxacillin or flucloxacillin, but systematic reviews have not found a significant difference in this point in observational studies with other beta-lactams. The role of other beta-lactams such as ceftaroline should be thoroughly studied in these patients.

Effectiveness of direct-acting antiviral therapy in patients with a HCV/HIV coinfection. A multicenter cohort study.

INTRODUCTION: The effectiveness of direct-acting antiviral (DAA) agents has been demonstrated in clinical trials both in patients with mono and coinfections. The goal of the study was to analyze the effectiveness and toxicity of this therapy in real-life patients with a HIV/HCV coinfection and to identify variables that are associated with an unfavorable outcome. METHODS: This was a multicenter ambispective study in a cohort of coinfected patients. Data were collected from eight centers in Castilla-La Mancha from 2014 to 2016. An intent-to-treat analysis was performed and any loss to follow-up, treatment withdrawal or toxicity was considered as a failure. RESULTS: A total of 229 patients were included with a median age of 49.6 years and the majority were male (83%). Fewer than 10% had a detectable HIV-related viral load (VL). The most prevalent HCV genotype was 1 (65.1%). Fifty percent had cirrhotic liver disease and 65% had over 800,000 copies/ml of HCV VL. The global sustained viral response (SVR) was reached by 91.7% of cases. The most commonly used DAA regimen was sofosbuvir/ledipasvir. Ribavirin was included in 52% of regimens, 65.9% of cases completed 12-week regimens and 30% completed 24-week schemes. There were 19 therapy failures. No differences were observed between the various DAA strategies used. No independent predictor was found for SVR. CONCLUSIONS: HCV treatment in coinfected patients is highly successful in terms of SVR rate in the real-life setting and toxicity is exceptional. We identified no specific predictors of an unfavorable outcome.

Current Evidence on the Antimicrobial Treatment and Chemoprophylaxis of Human Leptospirosis: A Meta-Analysis.

BACKGROUND: Leptospirosis is a worldwide zoonotic infection, and its management needs to be refined. This study aims to discern which antibiotic would be the best option to treat leptospirosis disease and analyze the efficacy of chemoprophylaxis regimens to prevent this illness. METHODS: systematic review and meta-analysis on the efficacy of antibiotic treatment and chemoprophylaxis of leptospirosis in humans. RESULTS: Ten clinical trials compared an antibiotic treatment with placebo or other antibiotic treatments in leptospirosis (the most recent one was published in 2007). The meta-analysis shows no effect of penicillin treatment on mortality compared to placebo (OR 1.65; 95% CI 0.76-3.57; p = 0.21). There are no differences between penicillin and cephalosporins or doxycycline. Penicillin does not reduce the time of defervescence (MD-0.16; 95% CI (-1.4) -1.08; p = 0.80) nor hospital stay (MD 0.15; 95% CI (-0.75)-1.06; p = 0.74). Besides, the data did not demonstrate any effectiveness of the use of penicillin in terms of the incidence of oliguria/anuria, the need for dialysis treatment, time to creatinine normalization, incidence of jaundice, or the liver function normalization time. Eight trials have assessed prophylactic treatment against leptospirosis with different strategies. A weekly dose of 200 mg of doxycycline does not show benefit versus placebo regarding the number of new cases of symptomatic leptospirosis (OR 0.20; 95% CI 0.02-1.87; p = 0.16). A single dose of doxycycline at exposure to flood water could have a beneficial effect (OR 0.23; 95% CI 0.07-0.77; p = 0.02). None of the other chemoprophylaxis regimens tested have shown a statistically significant effect on the number of new symptomatic cases. CONCLUSION: There is no evidence that antibiotics are a better treatment than placebo regarding mortality, shortening of fever, liver and kidney function, or reduction in the hospital stay. On the other hand, neither doxycycline nor penicillin, nor azithromycin have shown statistically significant differences in preventing symptomatic infection. Well-designed clinical trials, including other antibiotics such as quinolones or aminoglycosides, are urgently needed to improve our understanding of the treatment for this infection, which continues to be a neglected disease.

[Clinical usefulness of biochemical markers of bone turnover in early postmenopausal women: two years longitudinal study]. / Utilidad clínica de los marcadores bioquímicos de remodelado óseo en la mujer posmenopáusica reciente: estudio longitudinal a 2 años.

BACKGROUND AND OBJECTIVE: Many studies have been performed on the ability of bone turnover markers (BTM) for the prediction of bone loss and to assess the correlation of BTM with bone mineral density (BMD). However, the results from these studies have been mixed. The aim of this study was to assess the usefulness of BTM to predict bone loss and to analize the correlation of BTM with BMD in early postmenopausal women. SUBJECTS AND METHOD: 183 healthy women, aged 50 to 55 years, with natural menopause of 6 to 36 months were randomly selected. We measured bone alkaline phosphatase (BALP), intact osteocalcine (OC) and C-telopeptide (sCTx) in serum, and calcium, deoxipiridinoline (DPD) and N-telopeptide (NTx) in urine. Bone densitometry of the spine (L(2)-L(4)) was performed at the start of the study and two years later. Student t test, ANOVA, chi2 test and ROC curves were used for the statistical analysis. RESULTS: Bone markers, mainly OC and CTx, correlated with BMD and discriminated osteoporosis, osteopenia and normal bone mass (p < 0.001). According to the ROC curves, OC had a sensitivity of 77.8% and specificity of 80.6% for the diagnosis of osteoporosis and sCTx, 83.3% and 74.5%, respectively. Regarding the relation to bone loss, only sCTx showed difference between the lowest and the highest quartile (p = 0.042), but we did not find an association between high turnover and fast bone losers. CONCLUSIONS: Bone markers, mainly OC and sCTx, are useful for identification of osteoporotic and osteopenic early postmenopausal women. However, regarding the bone loss, only CTx has a weak predictive value.