| Objective: To study the clinical characteristics and risk factors of carbapenem-resistant klebsiella pneumoniae bloodstream infection,and analyze its drug resistance and the possible drug resistance mechanism.Methods: A retrospective analysis was performed on 29 cases of non-repetitive carbapenem-resistant Klebsiella pneumoniae bloodstream infection in our hospital from January 2018 to December 2020.Relevant clinical data and drug sensitivity results were collected.The in vitro drug sensitivity tests of ceftazidime-avibactam and tigecycline were performed using broth dilution method,and the bacterial genome was sequenced.By relying on the databases such as Res Finder and Virulence Factor Database,and using the Kleborate Tool,the risk factors and drug resistance mechanisms of carbapenem-resistant Klebsiella pneumoniae bloodstream infection were analyzed.Result:1.CRKP in bloodstream infection showed high resistance to commonly used clinical antibiotics,especially β-lactams and the lowest resistance rate to amikacin.Compared with CSKP,the resistance rates of CRKP to the remaining 19 antibiotics except ampicillin and nitrofurantoin were significantly different(P<0.001).2.ICU admission,nosocomial infection,cerebrovascular disease,central venous catheter,tracheal intubation,use of vasoactive drugs,progression to septic shock,pitt’s bacteremia score(>5),APACHE II score(>20)and Chalson comorbidity index(>4)were the risk factors associated with CRKP bloodstream infection(P < 0.005)and no independent risk factor was found.3.26 CRKP strains were sensitive to CAZ-AVI(89.65%)while 27 CRKP strains were sensitive to tigecycline,with the sensitivity rate of 93.10%.4.Genome sequencing showed that ST11-K64 and ST11-K21 CRKP were the dominant strains,accounting for 41.38% and 20.69%,respectively.A variety of virulence genes were detected,including fimbrial synthesis and adhesion genes(types I,III,and IV),iron uptake(Aerobactin,Salmochelin,Yersiniabactin,ent B,and kfu ABC),urea nitrogen acquisition related genes(all S),mucus phenotyping regulatory gene(rmp A/rmp A2),and type VI secretion system synthetic gene.A total of 17 CRKP strains harboring both Aerobactin and rmp A/rmp A2 genes.As for drug-resistant genes,multiple drug resistance genotypes and mutants were detected,including beta-lactams,carbapenems,Fosfomycin(fos A,fos A3),fluoroquinolones(qnr S1),macrolides [mph(A)、 mph(E)],Tetracyclines [tet(A)] and trimethoprim-sulfamethoxazole(sul1,sul2)and other related drug resistance genes,with the beta-lactams being the most detected.Six carbapenemase genotypes(bla KPC-2,bla NDM-1,bla NDM-9,bla OXA-1,bla OXA-10,and bla IMP-4)were detected,and bla KPC-2 and bla NDM-1 was the main genotypes,with the detection rates of 65.52% and 27.59%,respectively.No carbapenem genotype was detected in the 4 CRKP strains,but there were omp K36/37 porin mutations,mainly missense mutations and amino acid insertions.Conclusion:1.CRKP in bloodstream infection is highly resistant and multi-resistant to commonly used antibiotics and the resistance rate to amikacin is low.2.Admission to ICU,nosocomial infection,cerebrovascular disease,central venous catheterization,tracheal intubation,use of vasoactive drugs,progression to septic shock,pitt bacteremia score(>5),APACHE II score(>20)and Chalson comorbidity index(>4)are associated with CRKP bloodstream infection(<0.005).No independent risk factors of CRKP bloodstream infection were found.3.Drug-resistant genes related to-lactams,carbapenems,fosfomycin,fluoroquinolones,sulfamethoxazole,tetracyclines and macrolides were detected.Carbapenemase like bla KPC-2,bla NDM-1,bla NDM-9,bla OXA-1,bla OXA-10 and bla IMP-4 were also detected.omp K36/37 porin mutations,like missense mutations and amino acid insertions,may lead to the drug resistance to carbapenems.4.CR-Hv KP has been prevalent in our hospital,so we should strengthen monitoring and formulate effective hospital infection control measures to reduce its spread and prevalence. |
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