Co-existence of OXA-48 and NDM-1 in colistin resistant Pseudomonas aeruginosa ST235

Abstract

Here, we presented 11 cases with colistin-resistant Pseudomonas aeruginosa infection and co-existence of OXA-48 and NDM-1 in the ST235 high-risk clone. The molecular analyses were performed by Sanger sequencing and RT-PCR. The eight patients (72.7%) had an invasive infection and three (27.3%) had colonization. The 30-day mortality rate was 87.5% (7/8). Three patients (37.5%, 3/8) received colistin therapy before isolation of P. aeruginosa. In the Multilocus sequence typing (MLST) analysis of 11 isolates, eight (72.7%) isolates belonged to P. aeruginosa ST235 clone. All isolates were NDM-1 positive, and nine isolates (81.8%) were found to be positive for both OXA-48 and NDM-1. Sequences of pmrAB and phoPQ revealed numerous insertions and deletions in all isolates. In 10 isolates pmrAB and phoPQ were found to be upregulated. In conclusion, the co-existence of OXA-48 and NDM-1 genes in colistin-resistant P. aeruginosa ST235 high-risk clone indicates the spread of carbapenemases in clinical isolates and highlights need of continuous surveillance for high-risk clones of P. aeruginosa.

Novel Molecular Markers Linked to Pseudomonas aeruginosa Epidemic High-Risk Clones

“…pmr ALeu71Arg appeared to be highly conserved in some high-risk clones including ST308 (12/14 sequences), ST233 (12/13 sequences), ST253 (11/13 sequences), ST179 (10/10 sequences), and ST175 (8/8 sequences). These findings are supported by findings from a recent study showing upregulation of pmr AB and pho PQ in relation to high-risk clones and colistin resistance [ 39 ]. In addition, some mutations in the two-component sensor-regulator system pmr AB have been linked to a changed aminoglycoside resistance phenotype.…”

Activity of imipenem/relebactam against Pseudomonas aeruginosa producing ESBLs and carbapenemases

“…5,8 Among carbapenemases, MBLs (class B), dominate in most countries, 9 but KPC enzymes (class A) are prevalent in Colombia and Caribbean, 6,10 with reports of OXA-48-like (class D) enzymes from India and Turkey. 11,12 GES enzymes (Class A) occur too: some are ESBLs but others are carbapenemases. 13 Because P. aeruginosa readily mutates resistant to carbapenems (via inactivation of its OprD porin) 1 ESBL producers frequently are as broadly resistant as carbapenemase producers.…”

Phenotypic and Genomic Comparison of the Two Most Common ExoU-Positive Pseudomonas aeruginosa Clones, PA14 and ST235

“…Most ST235 strains were collected between 1998 and 2007. They are susceptible to the common antipseudomonal agents in contrast to the ST235 isolates reported from the last decade that were typically either multidrug or extensively drug resistant ( 21 , 22 , 37 – 49 ). Thus, our strains may be of interest for the research community to study the unusual features of ST235 in a normal antibiotic-sensitive background.…”

“…This work now introduces the high-risk clone ST235 to be the third most common clone in the P. aeruginosa population. So far, almost all publications have dealt with the infection epidemiology and antimicrobial resistance of the ExoU-positive ST235 clone (subject of 88% of publications, PubMed, search term Pseudomonas aeruginosa ST235, assessed 6 March 2020) ( 37 – 49 ). Antibiotic resistance determinants of MDR and extensively drug-resistant (XDR) ST235 strains have been characterized in detail ( 40 – 43 , 45 – 47 , 49 ); otherwise, our current knowledge about the lifestyle, physiology, and metabolism of the pandemic ST235 clone is scarce ( 50 ).…”