Bloodstream Infections caused by Klebsiella pneumoniae and Serratia marcescens isolates co-harboring NDM-1 and KPC-2

Abstract

Carbapenem-resistant Enterobacteriaceae are a worldwide health problem and isolates carrying both blaKPC-2 and blaNDM-1 are unusual. Here we describe the microbiological and clinical characteristics of five cases of bloodstream infections (BSI) caused by carbapenem-resistant Klebsiella pneumoniae and Serratia marcescens having both blaKPC-2 and blaNDM-1. Of the five blood samples, three are from hematopoietic stem cell transplantation patients, one from a renal transplant patient, and one from a surgical patient. All patients lived in low-income neighbourhoods and had no travel history. Despite antibiotic treatment, four out of five patients died. The phenotypic susceptibility assays showed that meropenem with the addition of either EDTA, phenylboronic acid (PBA), or both, increased the zone of inhibition in comparison to meropenem alone. Molecular tests showed the presence of blaKPC-2 and blaNDM-1 genes. K. pneumoniae isolates were assigned to ST258 or ST340 by whole genome sequencing. This case-series showed a high mortality among patients with BSI caused by Enterobacteriae harbouring both carbapenemases. The detection of carbapenemase-producing isolates carrying both blaKPC-2 and blaNDM-1 remains a challenge when using only phenotypic assays. Microbiology laboratories must be alert for K. pneumoniae isolates producing both KPC-2 and NDM-1.

Detecting KPC-2 and NDM-1 Coexpression in Klebsiella pneumoniae Complex from Human and Animal Hosts in South America

“…In recent years, several studies have reported the emergence of pathogens coproducing multiple carbapenemases. In this regard, while coproduction of OXA-48 and NDM-1 has been previously reported ( 46 , 47 ), coproduction of KPC-2 and NDM-1 among K. pneumoniae isolates increased during the COVID-19 pandemic as a major challenge for clinical laboratories ( 3 , 4 , 19 , 43 – 45 ). CZA has demonstrated both excellent in vitro and in vivo activities against class A carbapenemase producers.…”

“… a MICs were determined by broth microdilution method according to CLSL and EUCAST guidelines ( 18 , 19 ). The MIC reduction of ATM (aztreonam), CAZ (ceftazidime), and CZA (ceftazidime-avibactam) was evaluated in the presence of avibactam (AVI; 4 µg/mL), dipicolinic acid (DPA; 500 µg/mL), and EDTA (320 µg/mL).…”

“…On the other hand, combinations of ATM plus meropenem-vaborbactam or plus CZA have demonstrated synergy against MβL and ATM-resistant NDM-producing Enterobacterales . Thus, the combination of aztreonam plus avibactam appears to be a promising option against Enterobacterales isolates coproducing class A and class B β-lactamases while awaiting development of new antimicrobials ( 19 – 24 ).…”

Occurrence of Serratia marcescens Carrying blaIMP-26 and mcr-9 in Southern China: New Insights in the Evolution of Megaplasmid IMP-26

“…Even though this organism exhibits a wide range of virulence factors and is relatively weak in virulence, it can infect critically ill or immunocompromised patients, as well as infants and newborns [ 4 , 5 , 6 ]. Researchers have pointed out that this microorganism could cause multiple infections, including meningitis, pneumonia, septicemia, and urinary tract infections, associated with poor clinical outcomes [ 7 , 8 , 9 , 10 ]. Due to their capability of adherence to invasive hospital equipment and forming biofilm, nosocomial infections caused by S. marcescens were difficult to treat [ 11 , 12 ].…”

Genetic Factors of Klebsiella Pneumoniae Antibiotic Resistance

“…Анализ нуклеотидных последовательностей паттернов устойчивости позволил установить, что присутствие bla NDM с высокой частотой ассоциировано с наличием в геноме микроорганизма детерминант устойчивости к другим антибактериальным ЛС (AmpC, другие типы карбапенемаз -OXA-48, VIM и KPC), что значительно сужает спектр ЛС для лечения пациентов, инфицированных микроорганизмами -продуцентами NDM-1. Как правило, NDM-продуцирующие микроорганизмы устойчивы к действию всех групп антибактериальных ЛС и чувствительны лишь к полимиксинам (колистину) и тигециклину [31,[47][48][49][50].…”