田磊，孫自鏞，陳中舉，李麗，張蓓，朱旭慧，簡翠，閆少珍

(華中科技大學(xué)同濟(jì)醫(yī)學(xué)院附屬同濟(jì)醫(yī)院檢驗(yàn)科，武漢 430030)

·用藥指南·

下呼吸道感染常見病原菌分布及耐藥性

田磊，孫自鏞，陳中舉，李麗，張蓓，朱旭慧，簡翠，閆少珍

(華中科技大學(xué)同濟(jì)醫(yī)學(xué)院附屬同濟(jì)醫(yī)院檢驗(yàn)科，武漢 430030)

耐藥性；感染，下呼吸道；病原菌

下呼吸道感染，尤其是肺實(shí)質(zhì)性炎癥的肺炎和支氣管黏膜炎癥的支氣管炎，是臨床上常見病死率較高的感染性疾病。近年來隨著侵入性診療技術(shù)的發(fā)展，以及各種抗菌藥物的大量使用，病原菌對(duì)抗菌藥物的耐藥現(xiàn)象愈演愈烈。為此，筆者回顧分析我院2013年患者下呼吸道感染病原菌的分布及耐藥性，為臨床醫(yī)師經(jīng)驗(yàn)治療下呼吸道感染提供參考依據(jù)。

1 材料與方法

1.1 細(xì)菌來源 2013年1月1日—2013年12月31日我院重癥監(jiān)護(hù)室(ICU)及非ICU患者下呼吸道標(biāo)本(包括痰標(biāo)本、纖支鏡沖洗液和肺泡灌洗液)分離的病原菌，剔除同一患者相同部位的重復(fù)分離菌株。痰標(biāo)本接種前進(jìn)行標(biāo)本質(zhì)量的評(píng)估，將痰涂片進(jìn)行革蘭染色和鏡檢，菌株分離和收集來源剔除不合格的痰標(biāo)本。

1.3 病原菌鑒定及藥敏試驗(yàn) 病原菌按照常規(guī)方法(氧化酶、觸酶、克氏雙糖、脲酶、動(dòng)力、枸櫞酸鹽利用、七葉苷水解、吲哚、血漿凝固酶等手工試驗(yàn))進(jìn)行分離培養(yǎng)和鑒定，疑難菌株采用VITEK-2-COMPACT鑒定系統(tǒng)。藥敏試驗(yàn)采用紙片擴(kuò)散法，判斷標(biāo)準(zhǔn)按照CLSI 2013年頒布的標(biāo)準(zhǔn)。

1.4 質(zhì)控菌株 紙片擴(kuò)散法質(zhì)控菌株為大腸埃希菌(ATCC25922，35218)、金黃色葡萄球菌(ATCC-25923)、肺炎克雷伯菌(ATCC700603)、銅綠假單胞菌(ATCC27853)、白念珠菌(ATCC90028)，萬古霉素E試驗(yàn)的質(zhì)控菌株為ATCC29213，照CLSI指南進(jìn)行室內(nèi)質(zhì)控。

2 結(jié)果

2.1 病原菌分布 ICU患者下呼吸道共分離病原菌956株，其中革蘭陽性菌231株(24.2%)，革蘭陰性菌680株(71.1%)，真菌45株(4.7%)；非ICU患者共分離病原菌4 464株，革蘭陽性菌1 090株(24.4%)，革蘭陰性菌3 226株(72.3%)，真菌148株(3.3%)。病原菌分布情況見表1。

表1 ICU與非ICU患者下呼吸道感染常見病原菌分布

Tab.1 Species distribution of clinical strains isolated from lower respiratory tract infection from ICU and non-ICU departments

病原菌(ICU)菌株數(shù)金黃色葡萄球菌223鮑曼不動(dòng)桿菌213銅綠假單胞菌140不動(dòng)桿菌屬116嗜麥芽窄食單胞菌74肺炎克雷伯菌65白念珠菌31大腸埃希菌23陰溝腸桿菌11假單胞菌屬8病原菌(非ICU)菌株數(shù)金黃色葡萄球菌866銅綠假單胞菌615鮑曼不動(dòng)桿菌582肺炎克雷伯菌554不動(dòng)桿菌屬354大腸埃希菌278流感嗜血桿菌220肺炎鏈球菌184嗜麥芽窄食單胞菌169卡他莫拉菌115

2.2 病原菌的耐藥性分析

2.2.2 鮑曼不動(dòng)桿菌和銅綠假單胞菌的耐藥性分析 鮑曼不動(dòng)桿菌耐藥現(xiàn)象嚴(yán)重，對(duì)常用抗菌藥物的敏感率均<40.0%。ICU患者分離的銅綠假單胞菌耐藥現(xiàn)象嚴(yán)重，對(duì)常用抗菌藥物的敏感率均<50.0%，非ICU分離的銅綠假單胞菌對(duì)哌拉西林/他唑巴坦、頭孢他啶、美羅培南、阿米卡星、妥布霉素和環(huán)丙沙星的敏感率較高(均>70.0%)。見表3。

表2 金黃色葡萄球菌對(duì)常用抗菌藥物的耐藥率和敏感率

Tab.2 Resistance and sensitivity of Staphylococcus aureus to common antibiotics %

R.耐藥；S.敏感

R.resistance; S.sensitivity

表3 銅綠假單胞菌和鮑曼不動(dòng)桿菌對(duì)常用抗菌藥物的耐藥率和敏感率

Tab.3 Resistance and sensitivity of Pseudomonas aeruginosa and Acinetobacter baumannii to common antibiotics %

R.耐藥；S.敏感；“-”未檢出

R.resistance; S.sensitivity；“-” not chect out

表4 嗜麥芽窄食單胞菌對(duì)常用抗菌藥物的耐藥率和敏感率

Tab.4 Resistance and sensitivity of Stenotrophomonas maltophilia to common antibiotics %

R.耐藥；S.敏感

R.resistance; S.sensitivity

2.2.4 肺炎克雷伯菌和大腸埃希菌的耐藥性分析 肺炎克雷伯菌除了對(duì)美羅培南和亞胺培南保持較高的敏感率外，ICU分離株對(duì)哌拉西林/他唑巴坦、頭孢西丁和阿米卡星，非ICU分離株對(duì)阿米卡星和左氧氟沙星敏感率也較高(>80.0%)。非ICU患者分離的大腸埃希菌對(duì)哌拉西林/他唑巴坦和阿米卡星敏感率也較好(>80.0%)。見表5。

2.2.5 流感嗜血桿菌的耐藥性分析 流感嗜血桿菌對(duì)頭孢噻肟、環(huán)丙沙星、左氧氟沙星、阿奇霉素和氯霉素的敏感率較高(>80.0%)。見表6。

2.2.6 肺炎鏈球菌的耐藥性分析 肺炎鏈球菌對(duì)青霉素、左氧氟沙星、莫西沙星和萬古霉素的敏感率較高(>80.0%)。見表7。

3 討論

我院2013年下呼吸道感染病原菌監(jiān)測(cè)資料顯示，ICU和非ICU患者下呼吸道感染最常見的病原菌均為金黃色葡萄球菌、鮑曼不動(dòng)桿菌和銅綠假單胞菌，在ICU患者中，真菌引起的下呼吸道感染不容忽視，白念珠菌在ICU患者下呼吸道感染病原譜中排第7位。在非ICU患者下呼吸道感染中，苛養(yǎng)菌引起的感染比例較高。流感嗜血桿菌、肺炎鏈球菌和卡他莫拉菌均排在非ICU患者下呼吸道感染病原譜的前十位。由于地域性差異以及監(jiān)測(cè)的人群不同，我院病原譜的分布情況不同于某些地區(qū)的報(bào)道。廣西醫(yī)科大學(xué)附屬第四醫(yī)院監(jiān)測(cè)數(shù)據(jù)顯示，ICU患者下呼吸道感染檢出的病原菌主要是鮑曼不動(dòng)桿菌、銅綠假單胞菌和大腸埃希菌，而呼吸科主要是大腸埃希菌、銅綠假單胞菌和肺炎克雷伯菌[1]。復(fù)旦大學(xué)附屬兒科醫(yī)院2006年—2009年患兒呼吸道感染，常見的病原菌為化膿性鏈球菌、肺炎鏈球菌、金黃色葡萄球菌、流感嗜血桿菌和卡他莫拉菌[2]。社區(qū)獲得性呼吸道感染的主要致病菌為肺炎鏈球菌、流感嗜血桿菌、卡他莫拉菌、肺炎衣原體、肺炎支原體和軍團(tuán)菌等[3]。

表5 肺炎克雷伯菌和大腸埃希菌對(duì)常用抗菌藥物的耐藥率和敏感率

Tab.5 Resistance and sensitivity of Klebsiella pneumoniae and Escherichia coli to common antibiotics %

R.耐藥；S.敏感

R.resistance; S.sensitivity

表6 流感嗜血桿菌對(duì)常用抗菌藥物的耐藥率和敏感率

Tab.6 Resistance and sensitivity of Haemophilus influenzae to common antibiotics %

R.耐藥；I.中等；S.敏感；對(duì)頭孢噻肟、環(huán)丙沙星、左氧氟沙星和阿奇霉素，CLSI僅有敏感和非敏感折點(diǎn)

R.resistance; I.medium; S.sensitivity; only sensitive and non-sensitive criterion existed in CLSI for cefotaxime，ciprofloxacin，levofloxacin and azithromycin

表7 肺炎鏈球菌對(duì)常用抗菌藥物的耐藥率和敏感率

Tab.7 Resistance and sensitivity of Streptococcus pneumoniae to common antibiotics %

R.耐藥；I.中等；S.敏感；對(duì)苯唑西林，CLSI僅有敏感和非敏感折點(diǎn)；*1按口服青霉素折點(diǎn)判定，MIC≤0.064 μg·mL-1敏感，MIC≥2.0 μg·mL-1耐藥；*2按非腦膜炎折點(diǎn)判定，MIC≤2.0 μg·mL-1敏感，MIC≥8.0 μg·mL-1耐藥；*3按腦膜炎折點(diǎn)判定，MIC≤0.064 μg·mL-1敏感，MIC≥0.12 μg·mL-1耐藥；*4按非腦膜炎折點(diǎn)判定，MIC≤1.0 μg·mL-1敏感，MIC≥4.0 μg·mL-1耐藥；*5按腦膜炎折點(diǎn)判定，MIC≤0.5 μg·mL-1敏感，MIC≥2.0 μg·mL-1耐藥

R.resistance; I.medium; S.sensitivity; Only sensitive and non-sensitive criterion existed in CLSI for Oxacillin；*1the MIC≤0.064 μg·mL-1and MIC≥2.0 μg·mL-1should be classified as sensitive and resistant respectively by the criterion of oral Penicillin；*2the MIC≤2.0 μg·mL-1and MIC≥8.0 μg·mL-1should be classified as sensitive and resistant respectively by the criterion of non-meningitis；*3the MIC≤0.064 μg·mL-1and MIC≥0.12 μg·mL-1should be classified as sensitive and resistant respectively by the criterion of meningitis；*4the MIC≤1.0 μg·mL-1and MIC≥4.0 μg·mL-1should be classified as sensitive and resistant respectively by the criterion of non-meningitis；*5the MIC≤0.5 μg·mL-1and MIC≥2.0 μg·mL-1should be classified as sensitive and resistant respectively by the criterion of meningitis

大腸埃希菌和肺炎克雷伯菌藥敏數(shù)據(jù)顯示，碳青霉烯類藥物亞胺培南和美羅培南保持較高的敏感率。但是隨著碳青霉烯類藥物的廣泛使用，已經(jīng)出現(xiàn)了碳青霉烯類抗生素耐藥的腸桿菌科細(xì)菌，而且對(duì)多數(shù)臨床使用的抗菌藥物呈現(xiàn)高度耐藥，給臨床治療帶來嚴(yán)峻挑戰(zhàn)[7]。關(guān)于肺炎克雷伯菌，ICU分離株對(duì)哌拉西林/他唑巴坦、頭孢西丁和阿米卡星，非ICU分離株對(duì)阿米卡星和左氧氟沙星敏感率也較高(>80.0%)。非ICU患者分離的大腸埃希菌對(duì)哌拉西林/他唑巴坦和阿米卡星敏感率也較好(>80.0%)。針對(duì)大腸埃希菌和肺炎克雷伯菌引起的呼吸道感染，可以選用上述敏感藥物用于經(jīng)驗(yàn)治療。

白念珠菌在ICU患者下呼吸道感染分離病原菌中排第7位，可能和ICU患者多為重癥肺部感染及呼吸機(jī)相關(guān)肺炎，由于病情危重及免疫功能低下，多采用復(fù)雜的介入治療及大量使用廣譜抗菌藥物有關(guān)。在非ICU患者下呼吸道感染病原菌中，苛養(yǎng)菌分離率高，本次監(jiān)測(cè)數(shù)據(jù)顯示，肺炎鏈球菌、流感嗜血桿菌和卡他莫拉菌均在分離病原菌的前十位。藥敏數(shù)據(jù)顯示：流感嗜血桿菌對(duì)頭孢噻肟、環(huán)丙沙星、左氧氟沙星、阿奇霉素和氯霉素的敏感率較高(>80.0%)，肺炎鏈球菌對(duì)青霉素、左氧氟沙星和莫西沙星的敏感率均較高(>85.0%)，所以對(duì)于流感嗜血桿菌和肺炎鏈球菌引起的下呼吸道感染可以選用上述敏感藥物用于經(jīng)驗(yàn)治療。

本次監(jiān)測(cè)未包括肺炎衣原體、肺炎支原體、軍團(tuán)菌以及引起呼吸道感染的病毒，如副流感病毒、呼吸道合胞病毒、偏肺病毒、腺病毒、博卡病毒、鼻病毒及冠狀病毒等的檢測(cè)，在以后的工作中，將逐步開展其他病原體的檢測(cè)，繪制出完整的下呼吸道感染的病原譜。

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[2] 付盼，何磊燕，王愛敏，等.2006至2009年復(fù)旦大學(xué)附屬兒科醫(yī)院呼吸道感染患兒5種常見細(xì)菌構(gòu)成比和耐藥性分析[J].中國循證兒科雜志，2010，5(5)：371-376.

[3] 俞云松.社區(qū)獲得性呼吸道感染主要致病菌及其耐藥性變化[J].中國實(shí)用內(nèi)科雜志，2011，31(8)：647-650.

[4] 郭燕，朱德妹，胡付品，等.2010年中國CHINET葡萄球菌屬細(xì)菌耐藥性監(jiān)測(cè)和分析[J].中國感染與化療雜志，2013，13(2)：86-92.

[5] 朱德妹，汪復(fù)，郭燕，等.2012上海地區(qū)細(xì)菌耐藥性監(jiān)測(cè)[J].中國感染與化療雜志，2013，13(6)：409-419.

[6] 李光輝，朱德妹，汪復(fù)，等.2011年中國CHINET血培養(yǎng)臨床分離菌的分布及耐藥性[J].中國感染與化療雜志，2013，13(4)：241-247.

[7] 胡付品，朱德妹，汪復(fù)，等.CHINET監(jiān)測(cè)2010年碳青霉烯類抗生素耐藥腸桿菌科細(xì)菌的分布特點(diǎn)和藥物敏感性[J].中國感染與化療雜志，2013，13(1)：1-7.

DOI 10.3870/yydb.2015.08.029

Distribution and Drug Resistance of Pathogenic Bacteria in Lower Respiratory Tract Infection

TIAN Lei,SUN Ziyong,CHEN Zhongju,LI Li,ZHANG Bei,ZHU Xuhui,JIAN Cui,YAN Shaozhen

(DepartmentofClinicalLaboratory,TongjiHospital,TongjiMedicalCollege,HuazhongUniversityofScienceandTechnology,Wuhan430030,China)

Objective To investigate distribution and drug resistance of pathogenic bacteria in lower respitatory tract infection. Methods Distribution and drug resistance of pathogenic bacteria in lower respitatory tract infection of patients in ICU and non-ICU of our hospital during 2013 were retrospectivly analyzed.The pathogens were identified by manual methods routinely and those difficult to be identified were analyzed by using the VITEK-2-COMPACT instrument.Antimicrobial susceptibility of these isolates were tested by Kirby-Bauey methods routinely. Results In total, 956 strains were isolated from lower respitatory tract infection of patients in ICU, including 231 strains of gram-positive cocci (24.2%), 680 strains of gram-negative bacteria (71.1%), 45 strains of fungi (4.7%).In patients of non-ICU, 4 464 strains were isolated, including 1 090 strains of gram-positive cocci (24.4%), 3 226 strains of gram-negative bacteria (72.3%), and 148 strains of fungi (3.3%).Staphylococcusaureus,acinetobacterbaumanniiandpseudomonasaeruginosawere the most frequent isolates in patients of ICU and non-ICU.The overall prevalence ofmethicillinresistantstaphylococcusaureus(MRSA) instaphylococcusaureuswas 87.0% in ICU and 74.0% in non-ICU.MSSA was sensitive to the most antibiotics (more than 80.0% of the strains were sensitive to common antibiotics) except penicillin, erythromycin and clindamycin.MRSA was sensitive to trimethoprim-sulfamethoxazole and fosfomycin (more than 75.0% of the strains were sensitive to the antibiotics) except for vancomycin, teicoplanin and linezolid.Acinetobacterbaumanniiwas more resistant to the antibiotics (less than 40.0% of the strains were susceptible to the antibiotics).Pseudomonasaeruginosafrom ICU was more resistant to the antibiotics (less than 50.0% of the strains were sensitive to the antibiotics) than that from non-ICU.Stenotrophomonasmaltophiliawas sensitive to trimethoprim-sulfamethoxazole, levofloxacin and minocycline (more than 80.0% of the strains were sensitive to the antibiotics).EscherichiacoliandKlebsiellapneumoniaewere sensitive to Piperacillin-tazobactam and Amikacin except for meropenem and imipenem (more than 80.0% of the strains were sensitive to the antibiotics). Conclusion Gram-negative bacteria was the most frequent isolate in lower respitatory tract infection of our hospital during 2013.Staphylococcusaureus,acinetobacterbaumanniiandpseudomonasaeruginosawere the most frequent isolates in ICU and non-ICU.Resistance to the antibiotics was more common in ICU than in non-ICU.Antibiotics should be prescribed according to bacterial resistance results reasonably in order to prevent the spread of drug-resistant strains.

Antibiotic resistance；Infection, lower respitatory tract；Pathogenic bacteria

2014-07-08

2014-08-10

田磊(1980-)，男，河北晉州人，主管技師，碩士，研究方向：細(xì)菌耐藥性監(jiān)測(cè)及耐藥機(jī)制研究。電話：(0)15926257254，E-mail：iso15189@126.com。

孫自鏞(1963-)，女，上海人，教授，博士生導(dǎo)師，博士，研究方向：病原微生物及分子流行病學(xué)。電話：027-83663639，E-mail：zysun@tjh.tjmu.edu.cn。

R978.1；R562

B

1004-0781(2015)08-1094-06