The COVID-19 pandemic has led to an increase in the co-production of carbapenemases, primarily attributed to the misuse of antibiotics and the upsurge in hospitalizations. Pascale et al. (2022), reported a statistically significant escalation compared to pre-pandemic infections rates. Our study similarly delineates the previously infrequent carbapenemase strains within the studied microorganism at the specific hospital, thereby highlighting the elevated prevalence of PRCR and carbapenemase NDM.
Coinfections are patients previously hospitalizes with COVID-19 who acquire healthcare infections (HAI). In our study, co-infections represent half of the patient’s cases, and the mortality rate was notable high, surpassing 60%. Pintado et al. (2022) underscore the substantial impact of COVID-19 and Enterobacterial Infections (CRE) on patient outcomes.
The primary invasive device scrutinized by the study groups was mechanical ventilation for respiratory support, which emerged as the predominant risk factor with a p- value < 0.05, and an Odds ratio 20 times higher in the PRCR group than the PRS group. Furthermore, the highest prevalence of the microorganism was observed in tracheal aspirate (33%) (Table 1). This analysis underscore mechanical ventilation as a significant factor in infection among individuals, consistent with the findings of Musuuza et al. (2021).
While KPC remains Brazil’s most reported and disseminated enzyme the global dissemination of NDM occurs at a swifter pace than other carbapenemases (Sampaio; Gales, 2016). A study on Enterobacteriaceae infections by Steweardson et al. (2019) also identified NDM as the most prevalent enzyme. In our study, all isolates exhibited the production of carbapenemase NDM.
Although P. rettgeri is primarily described as an opportunistic pathogen causing bloodstream infections in neonates (Sharma et al. 2017), our study exclusively involved adult patients. P. rettgeri is frequently associated with outbreaks, due to its intrinsic resistance to several classes of antimicrobials, making it a typical selection in hospital environments. Tshisevhe et al. (2017) documented an outbreak in a tertiary hospital for PRCR with carbapenemase NDM. Similarly, in our study, the presence of the carbapenemase enzyme and intrinsic resistance rendered the treatment of those infections exceedingly challenging. Regrettably, our study witnessed a significant mortality rate of 3/5 of the individuals (p-value < 0.05), indicating an unfavorable prognosis for patients with bacterial infections caused by PRCR.
The prescription of appropriate antimicrobial therapy implies the most effective treatment and the reduction of long-term resistance, as evidenced by De Melo et al. (2020). We report a high and significant rate of prior usage of carbapenems (83%~; p-value = 0.003) and polymyxins (77%; p-value 0.007). Similar results were report Yamakawa; Tanaka (2023), wherein approximately 77%of patients admitted to various hospitals in Japan, were administered carbapenems, with different infections and microorganisms.
Bacterial isolates showed resistance against representatives of all antimicrobial classes tested, except monobactams. Resistance to several classes of antimicrobials was one of the main results (Fig. 1). In line with our findings, an outbreak in Korea also showed eight P. rettgeri resistant to all classes of antimicrobials, with resistance genes encompassed carbapenemases, ESBL, and plasmids harboring aminoglycoside resistance genes (Shin et al., 2018). Moreover, both studies shared the co-production of two β-lactam resistance genes, NDM, and genes responsible for producing the enzymes OXA-1 in our study and PER-1 by Shin et al. (2018), both conferring ESBL profile. This further underscores the global dissemination of MBL NDM.
Our study also identified the presence of the gene aac(6’)-1b-cr in a subset of isolates (n = 3). Primary described by Silva et al. (2021) in P. stuartii in Recife, the aac(6’)-1b-cr gene encodes, enzymes that inactivate aminoglycosides and some quinolones. In addition, the authors evaluate four molecular profiles through the ERIC-PCR of 28 isolates with low genetic similarity. Our study found only two molecular profiles, with at least 90% genetic similarity, indicating the clonal origin of the outbreak at the University Hospital of Londrina.
Furthermore, resistance to quinolones in our study was attributed to the presence of qnrB1 and qnrA2genes. Conversely, a Tunisian Hospital detected the qnrA6 gene in Providencia spp., which also inhibits quinolones (Mahrouki et al., 2015).
An outbreak in Rome published this year described fourP. stuartii NDM harboring resistance genes againsttetracyclines (tet(B)), sulfamethoxazole-trimethroprim (sul1), and chloramphenicol (catA3), mirroring our, study’s finding of tetracycline resistance genes tet(A) and tet(B), as well as sul1, sul2, and dfrA1. The catB3 gene in our study conferred resistance to choloramphenicol. The plasmid virulence genes identified in Italy paralleled those presented in our study. In the secretion system, some of its genes are ysaC, hcp-2, and genes associated with flagellum composition, including cheA, flgG, and flgE. Similarly, our study revealed the presence of flhC, cheY, and hcp1 genes, all within the same group and targeting similar targets (Capitani et al., 2023).
This study characterizes NDM-1 metallo-β-lactamase in P. rettgeri isolates among patients at the University Hospital of Londrina, during the COVID-19 pandemic. Identifying novel resistance mechanism within P. rettgeri isolates limits our hospital’s therapeutic options for these infections.