Bacterial infection in coronavirus disease 2019 patients: co-infection, super-infection and how it impacts on antimicrobial use.

PURPOSE OF REVIEW: Since the beginning of the severe acute respiratory syndrome coronavirus 2 pandemic, there has been a large increase in the consumption of antimicrobials, both as a form of treatment for viral pneumonia, which has been shown to be ineffective, and in the treatment of secondary infections that arise over the course of the severe presentation of coronavirus disease 2019 (COVID-19). This increase in consumption, often empirical, ends up causing an increase in the incidence of colonization and secondary infections by multi and pan-resistant germs. RECENT FINDINGS: The presence of a hyperinflammatory condition induced by the primary infection, associated with the structural damage caused by viral pneumonia and by the greater colonization by bacteria, generally multiresistant, are important risk factors for the acquisition of secondary infections in COVID-19. Consequently, there is an increased prevalence of secondary infections, associated with a higher consumption of antimicrobials and a significant increase in the incidence of infections by multi and pan-resistant bacteria. SUMMARY: Antimicrobial stewardship and improvement in diagnostic techniques, improving the accuracy of bacterial infection diagnosis, may impact the antibiotic consumption and the incidence of infections by resistant pathogens.

Free renal levels of voriconazole determined by microdialysis in healthy and Candida sp.-infected Wistar rats.

The aims of this study were to evaluate free levels of voriconazole (VCZ) in the kidney of healthy and Candida albicans- or Candida krusei-infected Wistar rats using microdialysis and to establish the relationship between free renal and free plasma levels in both conditions. VCZ (40mg/kg or 60mg/kg) was administered orally (n=6 per group) and blood and microdialysate samples were collected at predetermined time points up to 18h. The mean area under the total concentration-time curve (AUC(0-infinity)) in healthy animals increased from 44.2+/-7.3microg/h/mL to 78.8+/-4.0microg/h/mL for plasma and from 15.1+/-2.4microg/h/mL to 27.9+/-2.6microg/h/mL for tissue after 40mg/kg and 60mg/kg VCZ dosing, respectively, showing non-linear pharmacokinetics described by a one-compartment model with Michaelis-Menten elimination. There were no statistical differences between the AUC(0-infinity) of plasma and tissue for either healthy or infected groups for the same dose. The antifungal tissue penetration was similar for both doses and all conditions investigated (0.34+/-0.06). VCZ protein binding was concentration-independent and was on average 66.0+/-4.0%, allowing the prediction of free renal levels using pharmacokinetic parameters obtained from total plasma fitting. The results showed that VCZ free renal and free plasma levels are similar in healthy rats and in rats with disseminated candidiasis caused by C. albicans or C. krusei. Therefore, plasma free levels can be used to optimise dosing regimens for this drug.