Secondary infections in mechanically ventilated patients with COVID-19: An overlooked matter?

OBJECTIVE: The susceptibility to infection probably increases in COVID-19 patients due to a combination of virusand drug-induced immunosuppression. The reported rate of secondary infections was quite low in previous studies. The objectives of our study were to investigate the rate of secondary infections, risk factors for secondary infections and risk factors for mortality in COVID-19 critically ill patients. METHODS: We performed a single-center retrospective study in mechanically ventilated critically ill COVID-19 patients admitted to our Critical Care Unit (CCU). We recorded the patients' demographic data; clinical data; microbiology data and incidence of secondary infection during CCU stay, including ventilator-associated pneumonia (VAP) and nosocomial bacteremia (primary and secondary). RESULTS: A total of 107 patients with a mean age 62.2 ± 10.6 years were included. Incidence of secondary infection during CCU stay was 43.0% (46 patients), including nosocomial bacteremia (34 patients) and VAP (35 patients). Age was related to development of secondary infection (65.2 ± 7.3 vs. 59.9 ± 12.2 years, p=0.007). Age ≥ 65 years and secondary infection were independent predictors of mortality (OR=2.692, 95% CI 1.068-6.782, p<0.036; and OR=3.658, 95% CI 1.385- 9.660, p=0.009, respectively). The hazard ratio for death within 90 days in the ≥ 65 years group and in patients infected by antimicrobial resistant pathogens was 1.901 (95% CI 1.198- 3.018; p= 0.005 by log-rank test) and 1.787 (95% CI 1.023-3.122; p= 0.036 by log-rank test), respectively. CONCLUSIONS: Our data suggest that the incidence of secondary infection and infection by antimicrobial resistant pathogens is very high in critically ill patients with COVID-19 with a significant impact on prognosis.

[MDR efflux pumps and antimicrobial resistance]. / Sistemas MDR y resistencia a los antimicrobianos.

The term MDR (Multi Drug Resistance) system refers to a group of transporters which are able to expulse a wide range of quite different substrates. While this type of system was first described in eukaryotic cells in the late 1980s, the presence of MDR efflux-pumps in bacteria showing resistance to several drugs has been increasingly reported in the literature. Under laboratory conditions the expression of these MDR systems is usually down-regulated. On occasion, basal expression of these efflux pumps is allowed in wild type strains, thus suggesting a role of these MDR systems in the intrinsic of these microorganisms resistance to antibiotics. On the other hand, overexpression of these MDR efflux pumps, after induction or because of the emergence of mutations in their regulatory elements, is also important in acquired resistance to antibiotics. This review summarizes the most relevant features of the MDR systems described in bacteria, as well as the mechanisms that regulate their expression.

Sistemas MDR y resistencia a los antimicrobianos / MDR efflux pumps and antimicrobial resistance

Se denominan sistemas MDR (Multi Drug Resistance) a una serie de transportadores que son capaces de expulsar un amplio número de sustratos no relacionados estructuralmente entre sí. Este tipo de sistemas se describieron inicialmente en eucariotas a finales de los años 1980, pero cada vez se dispone de más ejemplos de sistemas MDR bacterianos implicados en la resistencia a los antimicrobianos. La expresión de estos sistemas MDR, al menos en condiciones de laboratorio, suele estar reprimida, aunque en ocasiones se permite una expresión inicial del sistema, causante en parte de la elevada resistencia intrínseca a los antimicrobianos de ciertos microorganismos. Además, la sobreexpresión de estos sistemas MDR, bien por la inducción de su expresión, bien como consecuencia de la aparición de mutaciones en sus elementos reguladores, también es importante en la resistencia adquirida. En esta revisión se han intentado resumir las características más importantes de los sistemas MDR descritos en bacterias gramnegativas, así como los mecanismos que regulan su expresión (AU)