AECOPD病人痰中病原菌分布及耐药情况分析
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摘要
目的:了解我院呼吸内科慢性阻塞性肺病急性发作期(AECOPD)住院病人下呼吸道感染的病原菌分布及细菌耐药情况,以指导临床用药。
     方法:系统回顾分析(2005年1月至2007年10月)我院呼吸内科住院的725例慢性阻塞性肺疾病急性发作期(AECOPD)病人的痰细菌培养及药敏结果,其中女性356例,男性369例,年龄20-93岁,平均年龄69.12岁,明确各种病原菌的构成比及细菌的耐药情况。
     结果:
     1.725例AECOPD病人中211例病人进行了痰细菌培养检查,送检率仅为29.10%;共送检痰标本258份,其中痰培养阳性141份,阳性率54.65%。
     2.共分离培养出致病菌138株。革兰氏阴性菌67株,占48.55%,其中假单胞菌属分离率最高,其次为克雷伯菌属和不动杆菌属;真菌58株,以白色念珠菌为主;革兰氏阳性菌13株。
     3.研究结果显示,AECOPD病人感染的革兰氏阴性菌对二代头孢耐药率较高,对头孢呋辛的耐药率达64.10%;对三代头孢类抗生素的耐药率也较高,其对头孢哌酮的耐药率为45.45%,但对头孢他啶的耐药率较低,为19.48%;对喹诺酮类抗生素的耐药率也相对较高,环丙沙星35.21%、氧氟沙星43.14%;对四代头孢类、氨基糖苷类抗生素较敏感,其耐药率≤23.0%;对阿莫西林/棒酸、氨苄西林/舒巴坦的耐药率较高,≥57.63%,但其对替卡西林/棒酸、哌拉西林/他唑巴坦的耐药率较低,≤24.62%;对碳青酶烯类抗生素高度敏感,耐药率≤12.99%。
     4.研究结果显示,AECOPD病人感染的革兰氏阳性菌对青霉素类、青霉素与酶抑制剂的复合制剂、头孢类、喹诺酮类、复方新诺明及红霉素的耐药性也相对较高,≥70.83%;但其对阿米卡星、氯霉素、米诺环素的敏感性较好,耐药率≤20.00%;对万古霉素100%敏感。
     结论:
     1.目前临床痰细菌培养送检率、检出率较低。
     2.AECOPD病人感染的病原菌以革兰氏阴性菌及真菌感染为主。
     3.AECOPD病人感染的革兰氏阴性菌对二代头孢、三代头孢及喹诺酮类抗生素耐药率较高,但其对四代头孢类、氨基糖苷类抗生素较敏感,对部分青霉素类抗生素和酶抑制剂的复合制剂敏感性较好;对碳青酶烯类抗生素高度敏感。
     4.AECOPD病人感染的革兰氏阳性菌对青霉素类、头孢类及喹诺酮类抗生素的耐药性也相对较高,但其对氨基糖苷类抗生素、氯霉素敏感性较好,对万古霉素高度敏感。
     5.对于重症AECOPD病人,经验治疗上应选用四代头孢类、四代喹诺酮、碳青酶烯类抗生素及青霉素与酶抑制剂的复合制剂。
     6.应动态监测临床病原菌变迁情况及细菌耐药情况,指导临床抗感染治疗,并为经验用药提供依据。
Chronic obstructive pulmonary disease is characterized by poorlyreversible airflow limitation, while the airflow limitation wil l become more andmore severe. During the progressive deterioration up to end -stage COPD, acuteexacerbations of chronic obstructive pulmonary disease (AECOPD) usuallyoccur. When the complications take place, such as respiratory failure,pulmonary encephalopathy, disseminated introvascular coagulation and shock,the life quality of the patients with AECOPD will be greatly affected. Also theacute exacerbation of COPD is a common cause of mortality. And therespritory infection is the important reason for t he AECOPD. Threrfore, usingthe antibiotic to control the infection is an important meas of AECOPD. Butbecause of the abuse of the antibiotics now and the lower immunity of the mostpatients who are hospital -acquired infective, the growing bacteria resist ancehas become a very difficult issue. And this difficult issue has brought an newchallenge to the doctor. So detecting the pathogen and acknowle dging thebacteria resistance is very important for the treatment and the prognosis ofAECOPD.
     The objects are the 725 patients with AECOPD, who had hospitalized inthe respiratory department of our hospital from January 2005 to October 2007.There are 369men and 356 women. Th eir age ranges from 20 to 93, and theiraverage age is 69.12. The internist collects th e patients’phlegm and send thecollecting phlegm to the microbial laboratory in one hour. The doctors in themicrobial lab cultivate the phlegm, choose the suspicious bacteria and perform the aitibiotic sensitivity test. Then account pathogens and calculat e the drugresistant rate of Gram-negative bacteria and Gram-positive bacteria.
     The research shows that there are 211 patients whose phlegm was sendedto the lab in 725 patients, the check rate is 29.10%. The phlegm cultivationamount is 258, but the phlegm cultivation positive amout is 141, the positiverate is 53. 24%. we bred and separate 138 bacteria. There are 58 fungi, whichhave a rate of 46.38% in all pathogen, the main pathogen is Candida albicans;and 67 Gram-negative bacteria, which have a rate of 48.55%, the main bacteriawas Pseudomonas, Acinetobacter and Klebsiella; and 13 Gram -positivebacteria. Gram-negative bacteria have high rate of drug resistance to the secondgeneration cephalosporins. The rate of the resistance to cefuroxime is 64.10%.Gram-negative bacteria also have high rate of drug resistance to the thirdgeneration cephalosporins. The rate of the resistance to cefoperazone is 45.45%.But ceftazidime is sensitive to the Gram- negative bacteria, the resistance rateis only 19.48%. The fourth generation cephalosporins, quinolones andaminoglycosides are sensitive to the Gram -negative bacteria, the resistance rateis below 23.0%. Amoxicillin/clavulanic acid and ampicillin/sulbactam havehigh resistant rate to the Gram-negative bacteria, and the resistant rate is above57.63%. But ticarcillin/clavulanic acid and piperacillin/tazobactam aresensitive to Gram-negative bacteria, and the resistant rate is below 24.62%.Imipenem is highly sensitive to the Gram -negative bacteria, the resistant rate isbelow 12.99%. Gram-positive bacteria are resistant to penicillin, thecompliance of penicillin and the enzyme inhibitor, cephalosporins, quinolonesantibiotic, cotrimoxazole and erythromycin. The resistant rate is above 70.83%.But Gram-positive bacteria are sensitive to amikacin, chloramphenicol, minocycline and furans. The resistant rate is below 20.00%. Gram-positivebacteria are 100% sensitive to vancomycin.
     The research shows that the check rate and the detection rate of phelgmcultivation in clinic was low at present. The clinician should actively improvethe patient’s assistant check. Every patient with AECOPD in the hospitalshould do the sputum cultivation. And we need to notice the quality of thephlegm. The phlegm should be the second phleg m which is morning phlegmafter gargling and should be checked in 1 hour. And also we shluld improve theseparate method and construct the advanced microorganism lab. After thisresearch we know that the composing proportion of the pathogens in clinicchanged. The main pathogen are Gram-negative bacteria and fungi. Theresistance of Gram-negative bacteria which the clinicians should pay moreattention to become severe. The clinicians should choose the fourth generationcephalosporins, fourth generation quinolone, Imipenem, ticarcillin/clavulanicacid and piperacillin/tazobactam for treating the severe AECOPD. Theclinicians should reasonably use the antibiotic in order to avoid superinfectionand reduce the formation of resistance.
     In abstracto every patient with AECOPD in the hospital should do thesputum cultivation , and doctor should choose the antibiotics basing on thecultivation result. But in clinic the antibiotic is used based on the experiencebefore the result of sputum cultivation and the antibiot ic sensitivity test. Thesuccessful experience of medication is usually built on the prevalence ofpathogens investigation, monitoring, as well as durg resistance and treatmentgoals established on the basis of the programme. Strictly speaking, empiricaltreatment can not only rely on the clinicians’ideas, it should base on the actual situation. The doctors choose the antibiotics and strictly control the dose andtreatment time of antibiotics in order to prevent the abuse of antibiotics toreduce the emergence of drug resistance. The monitoring of the bacteriaresistance is the important methed to acknowledge the change of bacteriadistribution and resistance. Understanding of the bacterial resistance is in favorof the reasonable choice of antibiotic, and t his will reduce and delay theformation of the durg resistance and improve the quality of the treatment forthe infectious diseases.
     The conclusion: at present the check rate and the detection rate of sputumcultivation in clinic was low. The main pathogen s of the patients withAECOPD are Gram-negative bacteria and fungi. The resistance ofGram-negative bacteria is very severe. Gram-negative bacteria are resistant tothe second and third generation cephalosporin, but are sensitive to the fourthgeneration cephalosporin, Quinolones and Animoglycoside antibiotics. Alsothey are sensitive to the complex of the penicillins and lactanase inhibitor,imipenem. Gram-positive bacteria are resistant to the penicillins,Cephalosporin, Quinolones, but they are sensitiv e to the anmioglycosidantibiotic and chloramphenicol, and are 100% sensitive to the vancocin. T heclinicians should choose the fourth generation cephalosporins, fourthgeneration quinolone, Imipenem, ticarcillin/clavulanic acid andpiperacillin/tazobactam for treating the severe AECOPD. The doctor shoulddynamicly surveil the chang of pathogen and antibiotic resistance to providethe basis for clinical treatment with experiecce.
引文
1.Chain E,Florey HW, Adelaide MB,et al. Penicillin as a chemotherapeuticagent. Clin Orthop Relat Res,1993,10(295):3-7.
    2.周贵民,张军民.我国细菌耐药性监测应注意的几个问题.中华检验医学杂志,2004,27(1):5.
    3.张永标,张扣兴,唐英春,等.产质粒介导的AmpC 酶和ESBLs 细菌的耐药性及β-内酰胺酶基因型研究.中华微生物和免疫学杂志,2004,24(7):577-562.
    4.Fuso L,Incalzi RA,Pistrelli R,et al. Predicting mortality of patients hospitalized foracutely exacerbated chronic obstructive pulmonary disease[J].Am J Med, 1995,98:272-277.
    5.邵海枫.Ampc 酶的研究进展.临床检验杂志,2002,20(特刊):61-62.
    6.李显志,凌保东.2006 年细菌对抗菌药物耐药机制研究进展回顾.中国抗生素杂志,2007,4,32(4):193-203.
    7.Ambler RP, Coulson AF, Frere JM, et al. A standard numbering scheme forthe class A beta-lactamases. Biochem J, 1991, 276(Pt 1):269 –270.
    8.Bush K, Jacoby GA, Medeiros AA. A functional classification scheme forbeta-lactamases and its correlation with molecular str ucture. AntimicrobAgents Chemother 1995,39(6):1211–1233.
    9.Perez F, Endimiani A, Hujer KM,et al. The continuing challenge of ESBLs.Curr Opin Pharmacol. 2007,10,7(5):459-469.
    10.逄淑华,秦丽梅.超广谱β-内酰胺酶的研究进展.中华实用医药杂志, 2004,4(4):12-13.
    11.黄支密,陈榆,毛培华,等.鲍曼不动杆菌耐药性及β-内酰胺酶基因型研究.中华检验医学杂志, 2003, 26: 683-685.
    12.糜祖煌,陆亚华,丁云芳,等. β-内酰胺酶TEM、SHV 全长基因检测与应用.中华医院感染学杂志, 2004, 14: 1201-1203.
    13.Girlich D, Poirel L, Leelaporn A, et al. Molecular epidemiology of theintegron-located VEB-1 extended-spectrum bata-lactamase in nosocomialenterobacterial isolates in Bangkok, Thainland. J Clin Microbiol, 2001,39(1):175-182.
    14.David L Paterson, Robert A Bonomo. Extended Spectrum β- Lactamases: aClinical Update. Clin Microbiol Rev. 2005,10, 18(4): 657–686.
    15.Datta N, Kontomichalou P. Penicillinase synthesis controlled by infectiousR factors in Enterobacteriaceae. Nature, 1965, 16, 208(5007): 239–241.
    16.Jhhn heritage, Fatima H.M’Zali, Deborah Gascoyne -Binzi, Peter M.Hawkey.Evolution and spread of SHV extended-spectrum β-lactamases in Gramnegativebacteria. Journal of Antimicrobial Chemotherapy, 1999, (44): 309-319.
    17.Tzouvelekis LS, Tzelepi E, Tassios PT,et al. CTX-M-type beta- lactamases:an emerging group of extended -spectrum enzymes. Int J AntimicrobAgents,2000,14(2):137-142.
    18.Jacoby GA. Genetics of extended-spectrum beta-lactamases. Eur J ClinMicrobiol Infect Dis,1994,13(Suppl 1):2–11.
    19.Jacoby GA,Medeiros AA. More extended-spectrum beta lactamases.Antimicrob Agents Chemothe,1991,35(9):1697–1704.
    20.Philippon A,Labia R, Jacoby G. Extended-spectrum beta-lactamases.Antimicrob Agents Chemother ,1989,33(8):1131–1136.
    21.陆玮新,章自强.质粒介导的AmpC 酶分子生物学研究进展.中华现代内科学杂志,2006,3(3):40-42.
    22.Stapleton P,Shannon K, Phillips I. DNA sequence differences of ampDmutants of Citrobatter freundii[J]. Antimicrob Agents Chemother , 1995, 39(11):2494-2498.
    23. 徐修礼, 刘晓宇, 孙怡群.AmpC 酶的监测方法及研究进展.医学综述,2004,10(10):593-596.
    24.Korfmann G, Sanders CC, Moland ES. Altered Phenotypes associated withampD mutations in Enterobacter cloacae[J].Antimicrob Agents Chemother ,1991,35(2):358-364.
    25.胡莹,陈端.AmpC 酶及其分子生物学检测.微生物学免疫学进展, 2004,32(2):72-75.
    26.尹辉,陈群.质粒介导的AmpCβ-内酰胺酶的研究进展.国外医药抗生素分册,2003,24(6):257-260.
    27.Alain Philippon, Guillaume Arlet, George A Jacoby. P lasmid DeterminedAmpC-Type β-Lactamases. Antimicroblal agents and chemotherpy, 2002, 1,46(6):1-11.
    28.Bae IK, Lee BH, Hwang HY, et al. A novel ceftazidime-hydrolysingextended-spectrum bata-lactamase, CTX-M-54, with a single amino acidsubstitution at position 167 in the omega loop[J]. J Antim icrob Chemother ,2006,58(2):315-319.
    29.李远志, 白晓梅, 贺智英.细菌的耐药机制.延安大学学报,2007,5(1):1-2.
    30.陈接根,吕建新,楼永良,等.大肠埃希菌氨基糖苷类耐药株aac(3)-II 基因保守区分析.遗传,2004,26(2):202-204.
    31.Johansen K, Storgard M, Carstensen N, et al. An international study on theoccurrence of multiresistant bacteria and aminoglycoside consumptionpatterns. Infection,1988,11, 16(5): 313-322.
    32.王睿, 柴栋.细菌耐药机制与临床治疗对策.国外医药[J], 抗生素分册,2003,24(3): 972-1031.
    33.黄世杰.细菌的抗生素耐药: 作用靶点的修饰.国外医学药学分册,2006,2,33(1):25-27.
    34.孙长贵.细菌对抗菌药物耐药性研究进展.临床检验杂志,2002,20(特刊):70-73.
    35.Jacoby GA, Archer GL. New mechanisms of bacterial resistance toantimicrobial agents[J].N Engl J med,1991,324(9):601-612.
    36.Fisher LM, Screedharan S, Oram M, et al. DNA gyrase gyrA mutations inciprofloxacin-resistant strains of Staphylococcus aureus: close similaritywith quinolone resistance mutations in Escherichia coli[J].J bacteriol, 1990,172(12):7260-7262.
    37.杨世杰,王怀良.病理学(M).七年制教材.北京:人民出版社,2001,8.
    38.Piddock LJ.Multidrug-resistance efflux pumps - not just for resistance. NatRev Microbiol.2006,4 (8):629-636.
    39.Costerton JW, Stewart PS, Greenberg EP. Bacterial biofilms:a commoncause of persistent infections[J].Science,1999, 284(5418):1318-1322.
    40.彭青,钱元恕.细菌生物膜及其相关感染的研究进展[J].中国抗感染化疗杂志, 2004,4(2):126-128.
    41.Lewis K. Riddle of Biofilm Resistance[J]. Antimicrob Agents Chemother,2001,45(4):999-1007.
    42.常桂娇, 王艾琳.细菌生物膜及其与细菌耐药性关系的研究进展.山东医药,2007,47(5):80-82.
    43.Lewis K. Riddle of Biofilm Resistance [J]. Antimicrob Agents Chemother,2001,45:999-1007.
    44.王杰,周建英.生物被膜菌耐药机制及治疗进展.国外医学流行病学传染病分册,2003,30(6):358-361.
    45.Anwar H,Strap JL,Chen K,Costerton JW. Dynamic interactions of biofilmsof mucoid Pseudomonas aeruginosa with tobramycin and piperacillin.Antimicrob Agents Chemother.1992,36(6):1208-1214.
    46.Drenkard E.Antimicrobial resistance of Pseudomonas aeruginosa biofilms.Microbes Infect.2003 ,5 (13):1213 -1219.
    47.贾宁,徐志凯.细菌生物被膜对抗生素耐药机制的研究进展.微生物学通报,2006,33(1):184-187.
    1.Fuso L,Incalzi RA,Pistrelli R,et al. Predicting mortali ty of patientshospitalized for acutely exacerbated chronic obstructive pulmonary disease[J].Am J Med,1995,98:272-277.
    2.Celli BR, MacNee W, and Committee members. Standards for the diagnosisand treatment of patients with COPD. Eur Respir J, 2004,23:932 -946.
    3.高美英.抗生素耐药的起源传播和对象.抗感染药学,2005,2(1):1-3.
    4.中华医学会呼吸病学分会,慢性阻塞性肺疾病学组.慢性阻塞性肺疾病诊治指南[J].中华结核和呼吸杂志,2002,25(8):453-460.
    5.王吉耀,廖二元,胡品津.内科学.北京:人民出报社,2005,8.
    6.高雷山.慢性阻塞性肺疾病急性发作期患者下呼吸道病原菌感染及耐药性分析.中国综合临床,2004,20(5):390-391.
    7.钟南山,府军,朱元珏.现代呼吸病进展. 北京:中国医药科技出版社,1994,165-171.
    8.刘小平,蒋燕,徐安平.痰液细菌培养标本的质量监督和质量评价.中华医学研究杂志,2004,4(8):23-24.
    9.Sewell D, Maclowry. Laboratory management. In :Murry PR, Baron EJ,Pfaller MA, etal. Eds:Manual of Clinical Microbiology. ASM Press,1999,4-22.
    10.Beck-Sague C, J arvis WR. Secular trends in the epidemiology ofnosocomial fungal infections in the United States, 1980 -1990. NationalNosocomial Infections Surveillance System[J]. J Infect Dis, 1993, 167(5) :1247-1251.
    11.Wisplinghoff H, Seifert H , Tallent SM, et al. Nosocomial bloodstreaminfections in pediatric patients in United States hospitals :epidemiology,clinical features and susceptibilities [J]. Pediatr Infect Dis J,2003, 22(8):686-691.
    12.曹作炎,鲜云艳,田素梅,等.186 例慢性肺心病继发真菌感染临床分析.临床内科杂志,2002,19(5):382-383.
    13.Sch?nheyder HC, S?gaard M. Hospital-acquired bacteraemia andfungaemia. A regional study with national implications . Ugeskr Laeger,2007,26,169(48):4175-4159.
    14.王扬,夏丽萍,康健,等. 慢性阻塞性肺疾病急性发作期病原菌感染及耐药性分析.中国实用内科杂志,2004,24(11):692-693.
    15.Lodge JM , Minchin SD, Piddock LJ, et al. Cloning, sequencing andanalysis of the structural gene and reg ulatory region of the Pseudomonasaeruginosa chromosomal ampC beta -lactamase [J]. Biochem J, 1990,15,272(3): 627-631.
    16. 徐俊芳, 吴菊芳. 多重耐药铜绿假单胞菌感染. 中国感染与化疗杂志,2007,4,7(2):141-144.
    17.曹敬荣, 沈定霞.铜绿假单胞菌多药主动外排系统研究进展.中国感染与化疗杂志.2006,6(2):135-139.
    18. 吕萍, 沈叙庄. 肠球菌的耐药性研究进展. 国外医药抗生素分册,2006,27(3):132-135.
    19.方小龙,陈群.肠球菌耐药机制研究进展.医学综述,2006,10, 12(19):1165-1168.
    20.杜蓉,冯萍.肠球菌的耐药机制研究进展.华西医学,2006,21(2):395-396.
    21.费艳秋,施安国,王平全.耐万古霉素肠球菌的研究进展. 医学综述, 2001,7(3):129.
    22.Onodera Y, Okuda J, Yanaka M, et al. Inhibitory activities of quinol onesagainst DNA gyrase and topoisomerase IV of Enterococcus faecalis[J].Antimicrob Agents Chemother, 2002, 46(6):1800 -1804.
    23.张媛,张鹏乙,吴尚为.耐万古霉素肠球菌耐药机制及实验室检测的研究进展.中华医院感染学杂志,2007,17(9):1178-1180.
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