Clinical And Molecular Characteristics Of Klebsiella Pneumoniae Pneumonia Among Diabetics

Part one: Antimicrobial resistance,outcome and risk factors for mortality of Klebsiella pneumoniae pneumonia among diabeticsObjectives: This study aimed to investigate antimicrobial resistance,prognosis,and risk factors for mortality of Klebsiella pneumoniae(KP)pneumonia in diabetics and nondiabetics.Methods: A retrospective study was conducted among inpatients of KP pneumonia via electronic medical records in a territory hospital between January 2016 and June 2018.Antimicrobial resistance and prognosis in KP pneumonia were compared between diabetics and nondiabetics.Independent risk factors for mortality in KP pneumonia were identified by univariate and multivariate logistic regression among diabetics and nondiabetics separately.Results: In this study,456 patients with KP pneumonia were included.There were 156 cases with diabetes and 300 without diabetes.KP showed a lower antimicrobial resistance to a multitude of antimicrobials in pneumonia among diabetics than nondiabetics,namely aztreonam,cefotetan,sulperazone,meropenem,amikacin,tobramycin,sulfamethoxazole,and fosfomycin.Carbapenem-resistant Klebsiella pneumoniae(CRKP)was more prevalent among nondiabetics than diabetics who were admitted to intensive care unit(ICU)(63.0% vs 45.1%,P=0.038).The disease severity and mortality of KP pneumonia were higher in diabetic patients,while diabetes was not independently associated with mortality of KP pneumonia.Multivariable analysis showed that independent risk factors for in-hospital mortality in KP pneumonia among diabetics differed from that among nondiabetics as well. Independent predictors for in-hospital mortality of KP pneumonia among diabetics were male(OR: 5.89,95% CI: 1.34-25.93,P=0.019),albumin<35 g/L(OR: 7.00,95% CI: 2.02-24.28,P=0.002),bloodstream infection(BSI)(OR: 21.14,95% CI: 3.18-140.72,P=0.002),and invasive ventilation during hospitalization(OR: 8.00,95% CI: 2.99-21.42,P<0.001).In nondiabetics,independent predictors were higher CURB-65 score(OR: 1.92,95% CI: 1.29-2.86,P=0.001),CRKP(OR: 2.72,95% CI: 1.07-6.90,P=0.035),BSI(OR: 4.98,95% CI: 1.34-18.50,P=0.017),and ICU admission(OR: 4.06,95% CI: 1.57-10.47,P=0.004).Conclusion: In KP pneumonia,diabetics showed lower antimicrobial resistance,higher severity and mortality,and different independent risk factors for mortality compared with nondiabetics.Importantly,further attention should be paid on rational and effective antibiotic and supportive treatments in order to reduce mortality without aggravating antimicrobial resistance and metabolic damage among diabetics.Part two: Carbapenem resistance and virulence characteristics of Klebsiella pneumoniae pneumonia among diabeticsObjectives: This study aimed to explore the distribution of carbapenem resistance genes,virulence genes,virulence associated capsular serotypes and hypermucoviscous phenotype;and clinical characteristics,prognosis and antibiotic resistance of CRKP pneumonia and hypervirulent Klebsiella pneumoniae(Hv KP)pneumonia among diabetics and nondiabetics.Methods: KP strains were prospectively collected from lower respiratory tract samples of KP pneumonia patients in a territory hospital from December 2018 to June 2019.Clinical information of patients was extracted from electronic medical record system.Common carbapenem resistance genes(KPC,IMP,NDM-1,VIM and OXA-48),virulence genes(rmp A,aerobactin,all S and wca G)and virulence related serotype(K1 and K2)genes were detected by Polymerase Chain Reaction.Antimicrobial resistance of KP was explored by drug sensitivity test,and hypermucoviscous phenotype by string test.Results: 191 KP strains causing pneumonia were collected in this study,including 65 strains in diabetics and 126 in nondiabetics.In ICU,KPC gene(70.0% vs 40.7%,P=0.012)and CRKP strain(74.0% vs 48.1%,P =0.023)were more frequently isolated among nondiabetics than diabetics.In non-ICU,Hv KP strain(aerobactin gene positive)was more frequently isolated among diabetics than nondiabetics(78.9% vs 59.2%,P =0.036).Isolation rate of hypermucoviscous Klebsiella pneumoniae was comparable among diabetics and nondiabetics.Besides,4 carbapenem-resistant and hypervirulent Klebsiella pneumoniae(CR-Hv-KP)strains were isolated.In diabetics,there were more male patients(100% vs 80%,P=0.044)and higher fasting blood glucose level(11.3 vs 8.6 mmol/L,P=0.038)in CRKP pneumonia than in Hv KP pneumonia.In nondiabetics,patients with Hv KP pneumonia had a higher proportion of malignant tumors(57.7% vs 21.3%,P<0.001).In addition,in both diabetics and nondiabetics,patients with CRKP pneumonia had higher rates of carbapenem exposure within 30 days,multisystem detection,ICU admission,and death/automatic discharge,higher CURB-65 score,and longer length of hospital stay.With regard to antimicrobial resistance,resistance of KP to commonly used drugs was higher in CRKP than non-carbapenem-resistant-non-hypervirulent Klebsiella pneumoniae(non-CRnon-Hv-KP),and that of Hv KP was lower than non-CR-non-Hv-KP.No significant differences in antimicrobial resistance were found in CRKP strain among diabetics and nondiabetics,nor in Hv KP strain.Conclusion: In KP pneumonia,diabetics were more prone to Hv KP infection in non-ICU,and nondiabetics were more prone to CRKP in ICU.CR-Hv-KP had also appeared.Diabetes and blood glucose level could affect characteristics of CRKP and Hv KP pneumonia.CRKP pneumonia was of higher antibiotic resistance,higher severity and worse prognosis than Hv KP pneumonia.Accordingly,it is necessary to strengthen the effective monitoring of KP in clinical practice,and carry out reasonable treatment according to the virulence and drug resistance characteristics of KP strains.