| Background and ObjectiveHematological malignancies included acute and chronic leukemia,lymphoma,multiple myeloma,myelodysplastic syndrome,myeloproliferative neoplasms.Due to the disease itself,bone marrow suppression after chemotherapy,neutropenia,mucosal injury(especially respiratory and digestive tract injury)and the use of corticosteroids/immunosuppressive therapy,patients with hematological malignancies showed hypoimmunity and were particularly prone to infection.Bloodstream infection(BSI),one of the most common types of infection in patients with hematologic malignancies,remains a major cause of death.The proportion of gram-negative organisams were highest among all pathogens,and enterobacteriaceae emerged as the most common gram-negative organism.Since the initial description of extended-spectrum ?-lactamases(ESBLs)-producing Klebsiella pneumoniae in 1983,ESBLs-positive organisms have spread worldwide,meanwhile,the increased incidence of antibiotic resistance has became particularly serious.Studies found that the overall 30-day mortality rates were higher for patients with ESBLs-positive Enterobacteriaceae BSI when compared to ESBLs-negetive cases,conversely,no significant difference was found between the two groups in other studies.Currently,researches on clinical features and risk factors for motality of bloodstream infections caused by Escherichia coli and K.pneumoniae in patients with hematological malignancies were relatively few in China.Therefore,in this study,we collected clinical data of patients with hematologic malignancies with E coli and K.pneumoniae bacteremia,analyzed the antimicrobial sensitivity as well as antimicrobial co-resistance rates of E coli,compared the clinical characteristics and investigated the risk factors for infection with ESBLs-positive strains and death of E coli K.pneumoniae bacteremia patients,in order to guide the clinical recognition,and implement effective treatment decisions.Material and methodsA total of 254 episodes E.coli and K.pneumoniae BSI occurring in patients with hematological malignancies in hematologic department of the First Affiliate Hospital of Zhengzhou University were enrolled,including 178 episodes of E.coli BSI and 76 episodes of K.pneumoniae BSI.ESBLs were dectcted in 188 episodes among the whole enrolled cases,and ESBLs-positive(82 episodes)and ESBLs-negetive groups(106 episodes)were divided according to ESBLs expression.All episodes were devided into survival group(66 episodes)and non survival group(188 episodes)according to 30-day matality.The clinical features and antibiotics resistance between ESBLs-positive and ESBLs-negetive groups were compared.Logistic regression was used to identify variables independently associated with 30-day mortality and infection with ESBLs-positive strains.All statistical analyses were performed with the SPSS 22.0 software.All patients were followed up to 30 days after bacteria onset or the date of death with 30 days.Results1.The positive rate of blood culture in Hematologic Department was 10.7%?Gram negative BSI accounted for 75.9%,Gram positive for 20.2%,fungus for 3.9%?Of the total pathogens causing bloodstream infection,E.coli accounted for 31.6% and K.pneumoniae for 13.6%.Of the gram-negative pathogens,E.coli accounted for 41.7% and K.pneumoniae account for 17.9%.2.The positive rate of ESBLs was 43.6%.Acute lymphocytic leukemia(ALL)(40.2% vs.21.7%,P=0.006),E.coli(87.8% vs.57.5%,P<0.001),multidrug-resistant(MDR)organisams(97.6% vs.48.1%,P<0.001)and antibiotic exposure within 30 days before bacteremia onset especially exposed to levofloxacin(35.4 vs.16.0%,P=0.002)and the 3/4 generation cephalosporins(14.6% vs.3.8%,P=0.008)accounted for higher proportion in ESBLs-positive group when compared with ESBLs-negetive group.The proportion of K.pneumoniae(42.5% vs.12.2%,P<0.001)and carbapenem resistant strains(13.2% vs.3.7%,P=0.024)in ESBLs-negetive group were more than the ESBLs-positive group.Other features included age,sex,other diseases,chemotherapy stage,use of corticosteroids or immune agents within 30 days,neutropenia,inappropriate initial antibiotic therapy and 30-day mortality rate were found no significant differences between the two groups(P>0.05).Multiple logistic regression analysis showed ALL(OR,3.339;95%CI,1.355-8.223;P=0.009)and antibiotic exposure within 30 days before bacteremia onset(OR,2.632;95%CI,1.168-5.929;P=0.020)were independent risk factors for bloodstream infection caused by ESBLs-positive E.coli and K.pneumoniae.3.The overall 30-day mortality rate was 26.0%.The univariate analysis showed male(59.1% vs.42.6%,P=0.021),age >55 years(28.8% vs.16.0%,P=0.023),induction chemotherapy(51.5%vs.34.6%,P=0.015),infection with carbapenems-resistant strains(16.7%vs.4.8%,P=0.002),septic shock(50.0% vs.6.4%,P<0.001)and inappropriate initial antibiotics treatment(27.3%vs.12.2%,P= 0.004)accounted for higher proportion in the non survival group than the survival group.Multiple logistic regression analysis showed septic shock(OR,20.114;95%CI,8.806-45.940;P<0.001),male(OR,2.659;95%CI,1.309-5.400;P=0.007)and infection with carbapenemsresistant strains(OR,6.043;95%CI,2.137-17.090;P=0.001)were independent risks factor for death.4.A total of 181 episodes of MDR were detected,including 28 cases of K.pneumoniae and E.coli in 153 cases.6 cases of extensively drug-resistant(XDR)strains were identified,including 2 of K.pneumoniae and 4 of E.coli,no PDR strains were found in the present study.The carbapenem resistant rates of E.coli and K.pneumoniae were 7.3% and 9.2%,respectively.The carbapenem resistant rate of MDR strains was 7.7%.For ESBLs-positive strains,the percentages of in vitro resistance to major antimicrobial classes were the following: Penicillins and the first/second generation cephalosporins 98.6%-100%,the third/fourth generation cephalosporins 30.0%-95.8%,quinolones 50.0%-86.1%,aztreonam 69.4%-70.0%,?-lactamase inhibitors 20.0%-35.7%,cephamycins 0-19.4%,amikacin 9.7-10.0%,carbapenems 0-4.2%.For ESBLs-negetive strains,the percentages of in vitro resistance to major antimicrobial classes were the following: Penicillins and the first/second generation cephalosporins 23.8%-100%,the third/fourth generation cephalosporins 11.1%-24.6%,quinolones 11.1%-50.8%,aztreonam 13.3%-23.3%,?-lactamase inhibitors 15.6%-46.7%,cephamycins 13.3%-23.3%,amikacin 4.4%-8.2%,carbapenems 2.4-13.1%.5.For E.coli,imipenem showed the lowest co-resistance rates to other antibiotics(5.2%-33.3%),followed by ertapenem(7.6%-55.6%)and amikacin(10.4%-50.0%).For K.pneumonia,amikacin showed the lowest co-resistance rates to other antibiotics(0-42.8%),followed by ertapenem(0-50%)and imipenem(9.6%-87.5%)?For ESBLs-positive strains,the co-resistance rates of antibiotics in bacterial sensitivity test were consistent with the rates for the whole E.coli and K.pneumoniae.While for ESBLs-negetive strains,the co-resistance rates of antibiotics were higher than those for ESBLs-positive strains.6.Bloodstream infection of carbapenem resistant strains were identified in 20 patients,the overall mortality rate was 55.0%.ESBLs-negetive strains resistant to carbapenem had a higher proportion than ESBLs-positive cases(82.4% vs.17.6%).All the 20 strains were 100% resistant to cephalosporins and ampicillin/sulbactam,90% to piperacillin/ tazobactam and quinolone,40% to amikacin.However,the higher sensitivity to tigecycline and polymyxin B remains 93.3%(14/15)and 100%(13/13).Conclusion1.E.coli and K.pneumoniae were the most common Gram negative pathogens responsible for bloodstream infection in patients with hematological malignancies.2.ALL patients and prior exposure to antibiotics were identified as independent predictors for bloodstream infection by ESBLs-positive E.coli and K.pneumoniae.3.Male,spetic shock and infection with carbapenems-resistant strains were independent risk factors for 30-day mortality.4.The resistance rates of carbapenems and amikacin for E.coli and K.pneumoniae were lower.Compared with ESBLs-negetive E.coli and K.pneumoniae,high resistance rates of penicillins,cephalosporins,levofloxacin and aztreonam were found in ESBLs-positive strains.5.For E.coli and K.pneumoniae,carbapenems,amikacin and tigecycline had lower co-resistance rates to other antibiotics.6.Most of carbapenem resistant strains were ESBLs-positive pathogens,the 30-day mortality of paitients with carbapenems-resistant pathogens bloodstream infection was high.As an effective treatment,tigecycline could be used as soon as possible. |
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