Emergence of tigecycline-resistant Klebsiella pneumoniae ST11 clone in patients without exposure to tigecycline

Abstract

Introduction: Tigecycline is a unique class of semi-synthetic glycylcyclines developed to treat infections caused by multidrug-resistant Klebsiella pneumoniae. In the past decades, eight tigecycline-resistant Acinetobacter baumannii isolates have been identified in Tehran and no Klebsiella pneumoniae has been reported.
 Methodology: To elucidate the mechanism of K. pneumoniae efflux pump-mediated resistance, the expression of efflux pump genes (oqxA, oqxB, acrA, acrB, tolC) and regulators (acrR, ramA, marA, soxS, rarA, rob) was investigated by real-time RT-PCR. Multilocus sequence typing (MLST) of tigecycline-resistant strains was also performed.
 Results: Compared to the tigecycline sensitive strain K32 (negative control), all resistant strains showed higher expression levels of efflux genes and regulatory factors. Three tigecycline-resistant strains (K53, K67, K79) showed higher levels of rarA expression (38.1-fold, 41-fold and 24-fold, respectively) and oqxB pump gene (48.2-fold, 60-fold and 58-fold, respectively). The increased expression of acrB was associated with the expression of ramA. However, to the best of our knowledge, studies on the mechanisms of resistance of K. pneumoniae strains to tigecycline are limited, especially in developing countries such as Iran.
 Conclusions: In the present study, we found that both AcrAB-TolC and OqxAB efflux pumps may play an important role in tigecycline resistance in K. pneumoniae isolates. Finally, the emergence of ST11 molecular type of resistant isolates should be monitored in hospitals to identify factors leading to tigecycline resistance.

Predictors of Occurrence and 30-Day Mortality for Co-Infection of Carbapenem-Resistant Klebsiella pneumoniae and Carbapenem-Resistant Acinetobacter baumannii

“…Studies have shown that high doses of tigecycline, such as 100 mg every 12 hours, are more effective in treating multidrug-resistant gram-negative bacteria, and that lower doses may not only be insufficient to treat bacterial infections but also increase antibiotic pressure leading to the growth of dominant flora ( Zhou et al., 2021 ). Of concern is the gradual emergence of tigecycline-resistant K. pneumoniae and A. baumannii due to the widespread use of tigecycline, which undoubtedly increases the challenge of antibiotic therapy, making optimization of tigecycline treatment regimens urgent for clinicians ( Goodarzi et al., 2021 ; Sun et al., 2022 ). We also focused on the differences in blood tests between the three groups, the results of host immune indicators indicate that the co-infection response is mainly countered by neutrophils, which have no effect on T cell proliferation.…”

Molecular mechanisms of tigecycline-resistance among Enterobacterales

“…Kingdom and the United States (Goodarzi et al, 2021). Interestingly, a tigecycline-resistant Acinetobacter baumannii strain was isolated in Iran, but tigecycline was not approved in this country at that time (Goodarzi et al, 2021).…”

“…The incidence of tigecycline resistance has been increasing yearly since 2007 ( Sun et al., 2013 ). In recent decades, many strains of tigecycline-resistant pathogens have been reported in France, Germany, Greece, Saudi Arabia, Spain, Taiwan, the United Kingdom and the United States ( Goodarzi et al., 2021 ). Interestingly, a tigecycline-resistant Acinetobacter baumannii strain was isolated in Iran, but tigecycline was not approved in this country at that time ( Goodarzi et al., 2021 ).…”

“…AcrB is the most well-characterized member of the RND superfamily. High expression of AcrAB-TolC and OqxAB efflux pumps plays a crucial role in tigecycline resistance ( Goodarzi et al., 2021 ).…”

“…Moreover, other studies documented activation of AcrAB-TolC and OqxAB efflux pumps by other regulators, such as marA , soxS , robA , or acrR . This observation indicates that ramA is not always a necessary regulator, as marA can also elicit overexpression of the AcrAB pump, for instance in Klebsiella species ( Goodarzi et al., 2021 ).…”