[Aminoglycosides therapy in patients with bacteraemia]. / Aminoglykosider og bakteriaemiprognose--sekundaerpublikation.

Metaanalyses have questioned the use of aminoglycosides (AG). We studied the association between AG therapy, mortality and impairment of renal function among patients with bacteraemia who were given appropriate empirical antibiotic therapy with or without AG. Thirty-day mortality was similar in the two groups. AG was associated with decreased mortality in patients with a urinary tract or abdominal focus and with increased mortality in patients with pneumonia. AG therapy modestly increased the risk of rise in serum creatinine. AG therapy appears equivalent to other covering antibiotic regimens.

Aminoglycoside treatment and mortality after bacteraemia in patients given appropriate empirical therapy: a Danish hospital-based cohort study.

OBJECTIVES: The effectiveness and safety of aminoglycoside (AG)/beta-lactam combination therapy has been questioned in several meta-analyses. We examined the association between AG combination therapy and mortality and increase in serum creatinine in adult patients with bacteraemia given appropriate empirical antibiotic therapy. METHODS: Historical cohort study based on prospective registration of bacteraemias in a Danish hospital 1996-2002. AG + beta-lactam was the recommended empirical therapy for severe sepsis. We identified 1,257 patients, of whom 969 received gentamicin or tobramycin (AG cohort); 288 patients not given AGs formed the non-AG cohort. We used Cox regression analysis to compare adjusted mortality rates; the association between AG therapy and increase in serum creatinine was analysed by logistic regression. RESULTS: The cumulative 30 day mortality in the AG cohort was 17.3% versus 18.1% in the non-AG cohort [adjusted mortality rate ratio (MRR) 1.02; 95% CI 0.74-1.39]. The adjusted 31-180 day MRR in the AG cohort was 1.72 (95% CI 1.15-2.55). AG therapy was associated with lower 30 day mortality in patients with an abdominal focus (adjusted 30 day MRR 0.52; 95% CI 0.24-1.10) or a urinary tract focus (adjusted 30 day MRR 0.48; 95% CI 0.22-1.08), but with a worse prognosis in patients with a respiratory tract focus (adjusted 30 day MRR 2.06; 95% CI 0.93-4.53). An increase in serum creatinine of >or=45 micromol/L was observed similarly often in AG- and non-AG-treated patients [14.1% versus 12.4%, adjusted odds ratio 1.06; 95% CI 0.63-1.79]. CONCLUSIONS: Among patients with bacteraemia receiving appropriate empirical coverage, AG combination therapy was not associated with increased 30 day mortality and only a modest risk of raised serum creatinine. The longer-term prognosis should, however, be explored further.

IFN-lambda: novel antiviral cytokines.

The first line of defense against viral infections is mediated by interferons (IFN)s, which are produced rapidly by the infected host. Type I IFNs (IFN-alpha/beta) are known to combat viruses both directly by inhibiting viral replication in the cells and indirectly by stimulating the innate and adaptive immune responses. Recently, a novel class of cytokines was discovered and named IFN-lambda (alternatively type III IFN or interleukin-28/29 [IL- 28/29]), based on IFN-like antiviral activity and induction of typical IFN-inducible genes. Here, we review the literature on IFN-lambda and discuss the current knowledge of the functions and mechanisms of action of IFN-lambda.

Lambda interferon (IFN-lambda), a type III IFN, is induced by viruses and IFNs and displays potent antiviral activity against select virus infections in vivo.

Type III interferons (IFNs) (interleukin-28/29 or lambda interferon [IFN-lambda]) are cytokines with IFN-like activities. Here we show that several classes of viruses induce expression of IFN-lambda1 and -lambda2/3 in similar patterns. The IFN-lambdas were-unlike alpha/beta interferon (IFN-alpha/beta)-induced directly by stimulation with IFN-alpha or -lambda, thus identifying type III IFNs as IFN-stimulated genes. In vitro assays revealed that IFN-lambdas have appreciable antiviral activity against encephalomyocarditis virus (EMCV) but limited activity against herpes simplex virus type 2 (HSV-2), whereas IFN-alpha potently restricted both viruses. Using three murine models for generalized virus infections, we found that while recombinant IFN-alpha reduced the viral load after infection with EMCV, lymphocytic choriomeningitis virus (LCMV), and HSV-2, treatment with recombinant IFN-lambda in vivo did not affect viral load after infection with EMCV or LCMV but did reduce the hepatic viral titer of HSV-2. In a model for a localized HSV-2 infection, we further found that IFN-lambda completely blocked virus replication in the vaginal mucosa and totally prevented development of disease, in contrast to IFN-alpha, which had a more modest antiviral activity. Finally, pretreatment with IFN-lambda enhanced the levels of IFN-gamma in serum after HSV-2 infection. Thus, type III IFNs are expressed in response to most viruses and display potent antiviral activity in vivo against select viruses. The discrepancy between the observed antiviral activity in vitro and in vivo may suggest that IFN-lambda exerts a significant portion of its antiviral activity in vivo via stimulation of the immune system rather than through induction of the antiviral state.