RESUMEN
A population pharmacokinetic analysis of dalbavancin was conducted in patients with different infection sites. Non-linear mixed effect modeling was used for pharmacokinetic analysis and covariate evaluation. Monte Carlo simulations assessed the probability of target attainment (PTA) of total dalbavancin concentration ≥ 8.04 mg/L over time (associated with ≥90% probability of optimal pharmacodynamic target attainment of fAUC24h/MIC > 111.1 against S. aureus) associated with a single or double dosage, one week apart, of 1000 or 1500 mg in patients with different classes of renal function. Sixty-nine patients with 289 concentrations were included. Most of them (53/69, 76.8%) had bone and joint infections. A two-compartment model adequately fitted dalbavancin concentration−time data. Creatinine clearance (CLCR) was the only covariate associated with dalbavancin clearance. Monte Carlo simulations showed that, in patients with severe renal dysfunction, the 1000 mg single or double one week apart dosage may ensure optimal PTAs of 2 and 5 weeks, respectively. In patients with preserved renal function, the 1500 mg single or double one-week apart dosage may ensure optimal PTAs of 2 and 4 to 6 weeks, respectively. Therapeutic drug monitoring should be considered mandatory for managing inter-individual variability and for supporting clinicians in long-term treatments of subacute and chronic infections.
RESUMEN
Procalcitonin (PCT) and C-reactive protein (CRP) may be useful to predict complicated forms of malaria. A total of 30 consecutive travelers diagnosed with Plasmodium falciparum malaria over a two-year period were included in the study. Patients with complicated Plasmodium falciparum malaria showed higher levels of parasitemia (P = 0.0001), PCT (P = 0.0018), CRP (P = 0.0005), bilirubinemia (P = 0.004), and a lower platelet count (P<0.0001) compared with patients with uncomplicated forms. PCT levels above 5 ng/mL showed the highest value of specificity (0.86) and positive predictive factor (0.67) among other parameters, and equal sensitivity (0.67) was displayed by CRP levels above 150 mg/dl. None of the patients with complicated malaria showed PCT levels within normal limits (<0.5 ng/ml). Both PCT and CRP correlated with parasitemia (P<0.001) and showed areas under ROC curve of 0.83. At multivariate analysis, only PCT was associated with an increased risk of complicated malaria (OR 8.2, IC 95% 1.2-57.2, P = 0.03). The determination of PCT on admission showed better results compared to CRP, platelet count, and bilirubinemia and can be useful in non-endemic areas for the initial clinical assessment of disease severity in travelers with Plasmodium falciparum malaria.
