Objective: Analysis and investigation of pathogenic characteristics of polymyxin-and carbapenem-resistant Klebsiella pneumoniae (PR-CRKP). Methods: A total of 23 PR-CRKP strains isolated from clinical specimens from the General Hospital of Southern Theater Command from March 2019 to July 2021 were retrospectively collected, Whole-genome sequencing was performed on 23 PR-CRKP strains, resistance genes were identified by comparison of the CARD and the ResFinder database, high-resolution typing of PR-CRKP strains was analyzed by core genomic multilocus sequencing (cgMLST) and single nucleotide polymorphism (SNP); polymyxin resistance genes were determined by PCR and sequencing. Results: All PR-CRKP strains were KPC-2 producing ST11 types. cgMLST results showed that the evolutionary distance between the PR-CRKP strains and Klebsiella pneumoniae in mainland China was 66.44 on average, which is more closely related than foreign strains; the 23 PR-CRKP strains were divided into 3 main subclusters based on SNP phylogenetic trees, with some aggregation among Clade 2-1 in the isolation department and date. The two-component negative regulatory gene mgrB has seven mutation types including point mutations, different insertion fragments and different insertion positions. Conclusion: The close affinity of PR-CRKP strains indicate the possibility of nosocomial clonal transmission and the need to strengthen surveillance of PR-CRKP strains to prevent epidemic transmission of PR-CRKP.
Humans ; Carbapenems/pharmacology* ; Anti-Bacterial Agents/therapeutic use* ; Klebsiella pneumoniae/genetics* ; Polymyxins/pharmacology* ; beta-Lactamases ; Phylogeny ; Retrospective Studies ; Multilocus Sequence Typing ; Microbial Sensitivity Tests

INTRODUCTIONPolymyxins have become the drug of choice for treatment of multidrug-resistant gram-negative bacilli infections in Singapore, simply because these pathogens are only susceptible to either aminoglycosides and polymyxins, or polymyxins only. Furthermore, there is no new antibiotic in the pipeline that targets these difficult-to-treat infections.

MATERIALS AND METHODSAll published literatures (up to end of February 2008) regarding polymyxins are included for review.

RESULTSThis review serves to give a summary of polymyxins from the current available literature, highlighting relevant clinical studies and information that help to guide informed prescription of polymyxins, should the need arise.

CONCLUSIONSHowever, there are substantial information gaps that needed to be filled urgently, to preserve the clinical utility of this very last line of antibiotic.

Anti-Bacterial Agents ; pharmacology ; therapeutic use ; Drug Resistance, Multiple, Bacterial ; Gram-Negative Bacteria ; drug effects ; Gram-Negative Bacterial Infections ; drug therapy ; microbiology ; Humans ; Microbial Sensitivity Tests ; Polymyxins ; pharmacology ; therapeutic use ; Singapore