Gentamicin as Empirical Treatment in Hemodialysis Patients: Safety, Pharmacokinetics, and Pharmacodynamics.

The aim of this study was to describe the safety profile and pharmacokinetic/pharmacodynamic parameters in end-stage renal disease patients who received gentamicin as empirical treatment in catheter-related bacteremia when they showed infection signs, regardless of the timing of the next HD. Patients received gentamicin 3 mg/kg before blood culture extraction when they showed infection signs and regardless of the timing of next hemodialysis session. Serum concentrations were collected after the gentamicin administration (peak level) and before the next HD (trough level). Toxicities and adverse drug events were registered. The main pharmacokinetic/pharmacodynamic goal for Gram-negative infections was peak:minimum inhibitory concentration (MIC) ≥10. Sixteen patients were included. Nephrotoxicity was not assessed in this population, and no ototoxicity was found. According to microbial isolation and gentamicin susceptibility, the value of peak:MIC was 5.4 ± 2.0. The administration of gentamicin in these conditions was safe. Estimated pharmacokinetic values were consistent with previous studies and appropriate according to peak:MIC goal for Gram-negative organisms with MIC ≤1 mg/L.

Impact on hospital mortality of catheter removal and adequate antifungal therapy in Candida spp. bloodstream infections.

OBJECTIVES: We set out to identify the prognostic factors in adult patients with Candida spp. bloodstream infection, assessing the impact on in-hospital mortality of catheter removal and adequacy of antifungal therapy. METHODS: Patients with positive blood culture for Candida spp. and a central venous catheter in place at the time of candidaemia were included. Data collected included demographics, underlying diseases, severity of illness, clinical presentation, catheter withdrawal and adequacy of empirical therapy. RESULTS: We included 188 patients (mortality 36.7%). The mortality rate was 34.9% (23/66) in patients with early adequate antifungal treatment and 18.9% (7/37) in patients with early adequate antifungal therapy and catheter withdrawal in the first 48 h. The APACHE (Acute Physiology and Chronic Health Evaluation) II score on the day of candidaemia [adjusted hazard ratio (aHR) 1.12; 95% CI 1.06-1.17; P < 0.001] was associated with death whereas early adequate therapy (aHR 0.4; 95% CI 0.23-0.83; P = 0.012) and catheter withdrawal (aHR 0.34; 95% CI 0.16-0.70; P = 0.03) were protective factors. In primary candidaemia, mortality was 28% (14/50) in patients with adequate therapy and decreased to 17.7% (6/34) in patients with both interventions in the first 48 h. Catheter removal was a protective factor and adequacy of antifungal therapy in the first 48 h showed a strong tendency to protection against death (aHR 0.46; 95% CI 0.19-1.08; P = 0.07). In secondary non-catheter-related candidaemia, only early adequate therapy was a protective factor for mortality. CONCLUSIONS: Delay in catheter withdrawal and in administration of adequate antifungal therapy was associated with increased mortality in candidaemic patients. Catheter management did not influence the prognosis of secondary non-catheter-related candidaemia.

Determinants of outcome in patients with bacteraemic pneumococcal pneumonia: importance of early adequate treatment.

We set out to determine the factors influencing mortality in 125 adult patients with bacteraemic pneumococcal community-acquired pneumonia (CAP), assessing the impact on outcomes of early adequate therapy in particular. Presumed prognostic factors with p < 0.1 in the unadjusted model were subjected to multivariate Cox regression analysis, with in-hospital and 90-day mortalities as the dependent variables. A time period of >4 h from admission to start of adequate antibiotic treatment (adjusted hazard ratio (aHR) 2.62, 95% confidence interval (CI) 1.06-6.45; p =0.037) and severe sepsis or septic shock (aHR 5.06, 95% CI 1.63-15.71; p = 0.005) were independently associated with in-hospital mortality. Variables associated with 90-day mortality were Charlson comorbidity index (aHR 1.17, 95% CI 1.02-1.34; p = 0.018), severe sepsis or septic shock (aHR 3.03, 95% CI 1.22-7.51; p = 0.016) and delay of adequate antibiotic therapy >4 h (aHR 2.21, 95% CI 1.01-4.86; p = 0.048). The use of combination therapy was not included in these models but was a protective factor for delayed adequate therapy (aHR 0.53, 95% CI 0.29-0.95; p = 0.033). Administration of adequate antimicrobial therapy within 4 h of arrival is a critical determinant of survival in patients with bacteraemic pneumococcal CAP.