The MIC determined for novel antimicrobial agents/combinations showed that the most effective drugs were meropenem-vaborbactam (94.8%) and cefiderocol (93.8%), followed by ceftazidime-avibactam (CAZ-AVI) (91.8%), imipenem-relebactam (88.7%), and plazomicin (81.4%). pneumoniae complex isolates, recovered from clinical specimens of patients attending different hospitals in Brazil and characterized by whole-genome sequencing.Īccording to antimicrobial susceptibility testing, isolates were mainly categorized as extensively drug resistant (XDR, n = 53 54.6%) or multidrug resistant (MDR, n = 43 44.3%) one isolate was identified as pandrug resistant (PDR, 1%), per Magiorakus’ criteria 14. Therefore, the aim of this study was to evaluate the in vitro activity of classical and new antimicrobial agents/combinations in a contemporary collection of KPC-producing K. The most promising options rely on novel β-lactam/β-lactamase inhibitors (BLBLIs) (ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-relebactam), new aminoglycosides (plazomicin) and tetracyclines (and their derivatives, such as eravacycline), and siderophore-complexed cephalosporins (cefiderocol) 12.ĭata on the emergence of carbapenem and polymyxin resistance among Gram-negative bacteria are widely available in the literature nevertheless, results on the activity of novel potential therapeutic options for the treatment of CRE infections are limited, especially in low- and medium-income countries 13. For instance, in the largest public hospital of Latin America, located in the city of Sao Paulo, resistance to polymyxin among Enterobacterales increased from 6.6 to 9.4% over a 5-year period (2010–2014) 11, reflecting the urgent need for new therapeutic treatments. Polymyxins (colistin and polymyxin B) have been used for the treatment of CRE in recent years, but increased rates of resistance to these antimicrobial agents have been documented. However, infections due to CRE demand the use of other antimicrobial classes, usually in combined therapy 10. Over the years, KPC-producing organisms have spread in Brazilian hospitals, and currently, KPC is as frequent as 96% among the carbapenemase-producing Enterobacterales (CRE) organisms identified in a multicenter study with ten Brazilian institutions 8.Ĭarbapenems are still used for treatment of Gram-negative infections in Brazil, mainly in intensive care units 9. The KPC enzyme was first described in the United States in 1996 and identified in Brazil 10 years later 7. Although resistance to carbapenems in Gram-negative bacteria may be the result of efflux systems, impermeability and altered transpeptidases, the main mechanism associated with this phenotype is the production of acquired β-lactamase enzymes 3.Ĭarbapenemases are widely spread worldwide, and Klebsiella pneumoniae carbapenemase (KPC) is the leading enzyme in terms of frequency, including in Brazil 4, a continental country with high rates of hospital-acquired infections and antimicrobial resistance 5, 6. pneumoniae, underscoring the urgent need for stringent policies for antimicrobial stewardship to preserve the activity of such drugs.Ĭarbapenem-resistant Klebsiella pneumoniae ranks among the top priority pathogens according to the World Health Organization and the Centers for Disease Control and Prevention 1, 2. Our findings showed limited susceptibility to antimicrobial drugs employed for infection treatment of carbapenem-resistant K. Although high in vitro susceptibility rates were detected for meropenem-vaborbactam and cefiderocol, only ceftazidime-avibactam is currently available in Brazil. The 97 isolates were distributed into 17 different sequence types, with a predominance of ST11 (37.4%). Colistin and polymyxin B were active against 58.6% of the isolates. The most active antimicrobial agents were meropenem-vaborbactam, cefiderocol, and ceftazidime-avibactam, with sensitivities higher than 90% resistance to ceftazidime-avibactam was associated with KPC-33 or KPC-44 variants. The majority of the isolates (54.6%) were classified as extensively drug resistant or multidrug resistant (44.3%) one isolate showed a pandrug resistance phenotype. Clonality, resistance and virulence genes were detected by whole-genome sequencing. We evaluated the in vitro activity of novel antimicrobial drugs/combinations against 97 KPC-producing Klebsiella pneumoniae isolates recovered from different hospitals in Brazil during 2021–2022. Therefore, evaluation of novel antimicrobial drugs is needed to identify potential treatments with better outcomes. Carbapenem-resistant Klebsiella pneumoniae (CRKP) are highly disseminated worldwide, and isolates co-resistant to other antimicrobial agents pose a threat to effective antimicrobial therapy.
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