University of São Paulo: Difficulties in controlling the pandemic increased transmission of resistant bacteria in hospitals

The high number of serious cases at the peak of the covid-19 pandemic caused a collapse in the health system. Among the main difficulties faced were the overcrowding of Intensive Care Units (ICUs), high workload for health professionals, lack of experienced professionals in ICU care, increased use of antimicrobials and lack of resources (drugs and supplies) . This scenario, according to a study carried out by researchers at USP, contributed to the increase in the number of patients with disease caused by Klebsiella pneumoniae, bacteria extensively resistant to the use of antibiotics. This conclusion was obtained from the analysis of blood samples, tracheal secretions, urine and other fluids collected from 26 patients positive for the bacterium and who were hospitalized at the Hospital das Clínicas of the Faculty of Medicine of Ribeirão Preto (HCFMRP) at USP between September and November 2020, which corresponds to the first peak of covid-19 cases in Brazil.

Cases were confirmed in covid-19 ICUs, in the ICU of patients without covid-19 or in clinical and surgical wards. “We observed a significant increase in cases of extensively resistant Klebsiella pneumoniae in the ICUs that were dedicated to the care of covid-19. When analyzing samples from other places, such as wards, for example, the cases decrease”, says the infectious disease doctor and head of the Hospital Infection Control Commission of the HCFMRP and one of the study coordinators, Gilberto Gambero Gaspar.

The research analyzed three important aspects, according to Gaspar, the epidemiological issue based on clinical cases and the transmission chain, microbiological and drug susceptibility studies, and molecular analyzes through the complete sequencing of the bacterial genome; “everything to try to understand a little more about the transmission”, explains the infectologist.

Cross-transmission and mortality
The researchers point out that they are possibly the result of cross-transmission, contamination between people, on the surface and between objects and people, during the pandemic. And, among the possible causes, the high overload of patients with mechanical ventilation in the ICU, the need for the health team to perform maneuvers to avoid low blood oxygen (pronation, which means lying the patient on his stomach), high workload of health professionals and patients in extremely critical condition.

Another highlight of the study pointed out by the researchers is the mortality rate of 30.7% among the infected analyzed in the study, and the fact that 80% of the patients who died had at least one comorbidity. “This drew a lot of attention, as it shows the difficulty of treatment, that is, we have little therapeutic arsenal with efficacy considered good for these cases, which leads the patient to an empirical treatment, which is the initial use of antimicrobials based on bacteria more likely before the microbial diagnosis is finalized”, says the doctor.

Also according to Gilberto, the results reinforce the importance of hand hygiene practices, environmental cleaning programs and the rational use of antimicrobials. “In the context of the pandemic, we observe the abusive use of antimicrobials, often due to the difficulty of diagnostic differentiation between severe covid-19 and a picture of associated bacterial pneumonia”, he concludes.

Genetic sequencing and bacterial resistance
To expand the understanding of transmission, the researchers performed the sequencing of the complete genome of the Klebsiella pneumoniae found in 26 patients and compared it with the genomic profile of the same bacterium that had been isolated two years earlier, in 2018, in a previous work also done at the HCFMRP by researchers from FMRP and Faculty of Philosophy, Sciences and Letters of Ribeirão Preto (FFCLRP) from USP.

“There was a predominance of a particular type of bacteria that has been present in the hospital since 2018. We observed that this type is responsible for 75% of the cases of patients who presented infection with this bacterium in our study and that the type carries DNA molecules , called plasmids, which allow the microorganism to spread very quickly”, explains María Eugenia Guazzaroni, professor at the FFCLRP, microbiologist and co-author of the study.

Research into the mechanisms of resistance in Klebsiella pneumoniae also involved testing to identify which antibiotics the bacterium showed resistance to and which genes were associated with this mechanism. Among the drugs under study were polymyxin B and carbapenems, which are part of the group of the most potent drugs in the treatment of bacterial infections.

“It is important to know the bacteria as in a war or a sport game, because only when we know them in depth is it possible to create strategies to win the battle. For that, we have to know how they survive antibiotic treatment, mechanisms and genes that make them resistant, how these genes are transferred from one bacterium to another and how they can be compared in other parts of the world. Only in this way can we get to know it better and look for treatment alternatives that are more effective in combating it and overcoming this major public health problem,” says Leonardo Andrade, professor at FCFRP at USP, biomedical doctor, microbiologist and co-author of the study.