Objective: To investigate the clinical characteristics and molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infection at a medical center in northeast China, especially after coronavirus disease (COVID-19) pandemic. Methods: Fifty-one patients were diagnosed with CRKP bloodstream infection between January 2015 and December 2020, among which 42 isolates were available for further study. Species identification and antibiotic susceptibilities were tested with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and VITEK 2 systems. Carbapenemase genes, virulence genes and MLST genes were detected by polymerase chain reaction. Moreover, the string test and serum killing assay were performed to evaluate the virulence of the CRKP isolates. Results: During the six-year period, the detection rate of CRKP in bloodstream infection showed an increasing trend, with the intensive care unit, hematology and respiratory medicine wards mainly affected. Molecular epidemiology analyses showed that KPC-2 was the dominant carbapenemase gene. In addition, the dominant sequence type (ST) of CRKP shifted from ST11 to ST15 strains, which were all sensitive to amikacin in contrast to the ST11 stains. Furthermore, ST15 CRKP strains were positive for the KfuB virulence gene and more resistant to serum killing compared to the ST11 CRKP strains. Nonetheless, the mortality rate of patients infected with ST11 and ST15 CRKP did not show any significant differences.
Conclusion:A shift in the dominant sequence type of CRKP bloodstream infections from ST11 to ST15 was observed during the years 2015-2020. Compared to ST11, the ST15 CRKP strains showed amikacin sensitivity, positivity for KfuB gene, and serum resistance, which may indicate stronger virulence.
The activity of clarithromycin and five other antimicrobial agents, namely amikacin, rifampicin, rifabutin, clofazimine and ciprofloxacin, was assessed both by an agar dilution and a radiometric method in broth on 11 Mycobacterium avium-intracellulare complex (MAC) strains, recently isolated from AIDS patients. Minimum inhibitory concentrations (MICs) radiometrically determined were, in general, several times lower than MICs assessed in agar, probably because of a partial degradation of antimicrobials during the long incubation period needed for tests in solid medium. When tested in broth, rifabutin and clofazimine showed very low MICs 90 (0.24 and 0.78 microgram/ml, respectively). Ciprofloxacin and clarithromycin also had MICs90 in the range of peak serum levels (1.93 and 3.76 micrograms/ml, respectively). Moreover, all these antimicrobials are known to concentrate several times in macrophages. MICs90 were higher for amikacin (11 micrograms/ml) and for rifampicin (8 micrograms/ml). When clarithromycin was tested against three MAC strains in combination with another drug, it showed a synergistic effect only when combined with rifampicin. Some synergistic effect was observed also when combining clarithromycin with rifampicin and amikacin, whereas in combination with rifabutin and clofazimine there was only an additive effect.
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