舒巴坦联合9种抗菌药物对耐碳青霉烯类鲍曼不动杆菌体外抗菌活性研究

目的：评价舒巴坦与9种临床常用抗菌药物联合用药对耐碳青霉烯类鲍曼不动杆菌（CRAB）的体外抗菌效应。方法：从临床分离得到24株CRAB。采取微量肉汤稀释法测定10种抗菌药物单一用药对CRAB的最低抑菌浓度（MIC）。采用棋盘法设计,微量肉汤稀释法测定舒巴坦分别联合9种抗菌药物对CRAB的MIC,并计算部分抑菌浓度指数（FIC）判定联合效应。结果：9种抗菌药物联用舒巴坦后的MIC均比单用时降低;联用后替加环素、多西环素、环丙沙星、左氧氟沙星的MIC₅₀均低于对应单药敏感折点,替加环素的MIC₉₀达到单药的敏感折点。舒巴坦与9组联合用药均未出现拮抗作用;舒巴坦联合阿米卡星的协同作用最强,其次为美罗培南、帕尼培南、亚胺培南、多西环素、替加环素。结论：与单药相比,9种药物联用舒巴坦对CRAB的体外抑菌作用均有增强效果。9种抗菌药物联合舒巴坦有效地降低MIC值,其中多西环素、替加环素、环丙沙星和左氧氟沙星,可使其MIC值降至敏感范围内。     

In vitro activity of tigecycline and comparators against Gram-positive and Gram-negative isolates collected from the Middle East and Africa between 2004 and 2011

The Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) was established in 2004 to monitor longitudinal changes in bacterial susceptibility to numerous antimicrobial agents, specifically tigecycline. In this study, susceptibility among Gram-positive and Gram-negative isolates between 2004 and 2011 from the Middle East and Africa was examined. Antimicrobial susceptibilities were determined using Clinical and Laboratory Standards Institute (CLSI) interpretive criteria, and minimum inhibitory concentrations (MICs) were determined by broth microdilution methods. US Food and Drug Administration (FDA)-approved breakpoints were used for tigecycline. In total, 2967 Gram-positive and 6322 Gram-negative isolates were examined from 33 participating centres. All Staphylococcus aureus isolates, including meticillin-resistant S. aureus, were susceptible to tigecycline, linezolid and vancomycin. Vancomycin, linezolid, tigecycline and levofloxacin were highly active (>97.6% susceptibility) against Streptococcus pneumoniae, including penicillin-non-susceptible strains. All Enterococcus faecium isolates were susceptible to tigecycline and linezolid, including 32 vancomycin-resistant isolates. Extended-spectrum β-lactamases were produced by 16.6% of Escherichia coli and 32.9% of Klebsiella pneumoniae. More than 95% of E. coli and Enterobacter spp. were susceptible to amikacin, tigecycline, imipenem and meropenem. The most active agents against Pseudomonas aeruginosa and Acinetobacter baumannii were amikacin (88.0% susceptible) and minocycline (64.2% susceptible), respectively; the MIC₉₀ (MIC required to inhibit 90% of the isolates) of tigecycline against A. baumannii was low at 2 mg/L. Tigecycline and carbapenem agents were highly active against most Gram-negative pathogens. Tigecycline, linezolid and vancomycin showed good activity against most Gram-positive pathogens from the Middle East and Africa.     

Characterisation of successive Acinetobacter baumannii isolates from a deceased haemophagocytic lymphohistiocytosis patient

In this study, 38 Acinetobacter baumannii isolates successively isolated from blood, skin swabs and tracheal aspirates from a single patient who died from haemophagocytic lymphohistiocytosis were investigated. The isolates were collected between March 2012 and August 2012. A. baumannii genotypes were determined by multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). In vitro antimicrobial susceptibility testing was performed and colistin heteroresistance and persistence were evaluated. The structure of AbaR resistance islands was explored, and serum sensitivity was determined. Based on MLST analysis, all 38 A. baumannii isolates showed the same sequence type (ST138). However, PFGE analysis showed that isolates from blood samples belonged to different genotypes depending on the isolation time: whilst blood isolates obtained at the early stages showed restriction patterns similar to those of isolates from other sources, isolates obtained at later stages exhibited a distinct pattern. All isolates were resistant to imipenem, cefepime, ciprofloxacin and piperacillin/tazobactam. Five isolates from tracheal aspirates and one from a skin swab were resistant to polymyxins, and two isolates from skin swabs and one from another source were non-susceptible to tigecycline. All colistin-susceptible isolates showed heteroresistance to colistin, and four were persisters. Isolates from blood showed higher survival rates against human serum than those from other sources. This study shows that the patient was infected with more than one A. baumannii strain. Heteroresistance, persistence or evasion of the innate immune response may explain the failure of antimicrobial treatments in this patient.     

Mohnarin 2006-2007年度报告：非发酵革兰阴性杆菌耐药性监测

目的了解2006~2007年度全国84家医院中非发酵革兰阴性杆菌的分布情况及对各类抗菌药物的耐药性。方法药物敏感性试验采用纸片扩散法,耐药性数据分析采用WHONET5.4软件进行统计分析。结果共收集非发酵革兰阴性杆菌分离株22983株,菌株数列前6位的菌种为假单胞菌属(48.2%)、不动杆菌属(31.4%)、嗜麦芽寡养单胞菌(11.5%)、伯克霍尔德菌属(2.9%)、金黄杆菌属(2.1%)和产碱杆菌属(1.4%)。铜绿假单胞菌对左氧氟沙星、哌拉西林、头孢哌酮/舒巴坦、环丙沙星、头孢吡肟、头孢他啶、哌拉西林/三唑巴坦、美罗培南和阿米卡星敏感性范围从56.3%至73.8%;不动杆菌对亚胺培南和美罗培南的敏感率分别为77.3%和75.6%;头孢哌酮/舒巴坦69.9%,米诺环素69.4%。不动杆菌对本次研究中的其它抗菌药物耐药率高于38.8%。嗜麦芽寡养单胞菌对米诺环素、复方磺胺甲口恶唑和左氧氟沙星的敏感性分别为96.8%、82.8%和82.2%;洋葱伯克霍尔德菌对米诺环素、复方磺胺甲口恶唑、头孢他啶和美罗培南的敏感性分别为89.3%、72.9%、65.4%和62.9%。结论非发酵菌在临床分离比重大,细菌耐药明显,临床应采取积极措施,合理使用抗菌药物,减少耐药菌发生。     

Enhanced bacterial killing with colistin/sulbactam combination against carbapenem-resistant Acinetobacter baumannii

Aims: Polymyxin-based combination therapy is often used to treat carbapenem-resistant Acinetobacter baumannii (A. baumannii) infections. Although sulbactam is intrinsically active against A. baumannii, few studies have investigated colistin/sulbactam combinations against carbapenem-resistant A. baumannii.Methods: Whole genome sequencing was undertaken on eight carbapenem-resistant (colistin-susceptible) isolates of A. baumannii from Chinese patients. Bacterial killing of colistin and sulbactam, alone and in combination, was examined with checkerboard (all isolates) and static and dynamic time-kill studies (three isolates). In the dynamic studies, antibiotics were administered in various clinically-relevant dosing regimens that mimicked patient pharmacokinetics.Results: The eight isolates consisted of ST195, ST191 and ST208 belonging to clonal complex 208, which is the most epidemic clonal type of A. baumannii globally. All isolates possessed Acinetobacter-derived cephalosporinase (ADC-61 or ADC-78) and seven of eight isolates contained the carbapenem-resistance gene bla_OXA-23. The colistin/sulbactam combination was synergistic against two of eight isolates in checkerboard studies. In time-kill studies, rapid bacterial killing of ca. 3–6 log₁₀ CFU/mL was observed with colistin monotherapy, followed by steady regrowth. Sulbactam monotherapy was generally ineffective. Substantially enhanced bacterial killing was observed with colistin/sulbactam combinations in both static and dynamic models, especially with the higher sulbactam concentration (2 g) and/or longer sulbactam infusion time (2 hours) in the dynamic model.Conclusions: This study was the first to use a pharmacokinetics/pharmacodynamics model to investigate synergistic activity of colistin/sulbactam combinations against A. baumannii. It showed that clinically-relevant dosing regimens of colistin combined with sulbactam may substantially improve bacterial killing of multidrug-resistant and carbapenem-resistant A. baumannii.     

Geographic patterns of carbapenem-resistant,multi-drug-resistant and difficult-to-treat Acinetobacter baumannii in the Asia-Pacific region: results from the Antimicrobial Testing Leadership and Surveillance (ATLAS) program, 2020

This study evaluated the in-vitro activity of multiple classes of antibiotics, including novel β-lactam combination agents, tigecycline and colistin, against carbapenem-resistant (CRAB), multi-drug-resistant (MDRAB) and difficult-to-treat (DTRAB) Acinetobacter baumannii. Minimum inhibitory concentrations (MICs) were determined using the broth microdilution method. Susceptibility profiles and the distribution of selected antimicrobials among countries were illustrated and examined based on the breakpoints of the Clinical and Laboratory Standards Institute, European Committee on Antimicrobial Susceptibility Testing and the US Food and Drug Administration. In total, 847 A. baumannii isolates were evaluated, and 692 isolates were characterized as CRAB, MDRAB or DTRAB. The prevalence of drug-resistant A. baumannii was >70.0% in South Korea, India and China, while the resistance rate of tigecycline was <5.5%. The MICs of meropenem and meropenem/vaborbactam for drug-resistant A. baumannii were equal (both MIC₅₀ and MIC₉₀ were 32 mg/L, range 0.25–32 mg/L). The overall resistance rate remained high for multiple classes of antibiotics, including penicillins, cephalosporins, carbapenems, quinolones and aminoglycosides (>84.0%, >96.0%, >98.0%, >88.0% and >87.0%, respectively), but not colistin or tigecycline (1.1% and 4.3%, respectively). China showed the lowest susceptibility to tigecycline for drug-resistant A. baumannii isolates compared with other countries. In conclusion, the resistance rate of drug-resistant A. baumannii remains high against multiple classes of antimicrobials. Colistin was the most potent agent, followed by tigecycline. The geographic pattern of tigecycline-resistant A. baumannii varied among countries. Therefore, continuous surveillance of A. baumannii resistance profiles in different regions is required.     

替加环素与临床常用抗菌药物对碳青霉烯类耐药肠杆菌科细菌的协同作用研究

目的评价替加环素与临床常用抗菌药物对碳青霉烯类耐药肠杆菌科细菌(CRE)的协同作用。方法收集2014—2016年临床分离的非重复CRE共235株。琼脂稀释法进行药物敏感性试验并分析替加环素和9种常用抗菌药物的耐药率。选取替加环素非敏感的35株作为研究对象,并采用棋盘稀释法检测替加环素联合其他9种抗菌药物(亚胺培南、美罗培南、头孢他啶、头孢噻肟、氨曲南、左氧氟沙星、阿米卡星、哌拉西林/三唑巴坦和头孢哌酮/舒巴坦)对CRE的协同作用。结果肺炎克雷伯菌、沙雷菌属、产气肠杆菌、阴沟肠杆菌对替加环素的耐药率较高,分别是5.1%(7/137)、5.6%(1/18)、7.7%(1/13)和8.3%(1/12)。替加环素与头孢他啶、哌拉西林/三唑巴坦联合效果最明显,协同百分比都是28.6%(10/35)。替加环素与头孢噻肟(9/35,25.7%)、左氧氟沙星(8/35,22.9%)和头孢哌酮/舒巴坦(7/35,20.0%)也显示出较好的协同作用。研究中未出现药物拮抗的作用。结论替加环素与头孢他啶、哌拉西林/三唑巴坦联合对CRE的协同作用比较明显。替加环素的联合治疗可能比单用更为有效。     

肛周脓肿感染肠杆菌科细菌分布及药敏试验结果分析

目的通过对肛周脓肿患者感染肠杆菌科细菌的分布情况及其药敏分析,为临床合理使用抗生素提供依据。方法选取大理白族自治州中医医院2016年1月至2018年12月收治的638例肛周脓肿的患者作为研究对象,分析肛周脓肿穿刺液培养检出肠杆菌科细菌的结果。结果557株肠杆菌科细菌中大肠埃希菌464株(83.3%),产超广谱β-内酰胺酶157株(33.8%);其次是肺炎克雷伯菌54株(9.69%),产超广谱β-内酰胺酶1株(1.9%);奇异变形杆菌18株(3.23%),产超广谱β-内酰胺酶1株(5.6%)。大肠埃希菌敏感率大于80.0%的抗菌药物有阿米卡星、厄他培南、美罗培南、头孢他啶、头孢西丁、头孢哌酮/舒巴坦、亚胺培南、哌拉西林/三唑巴坦。肺炎克雷伯菌敏感率大于80.00%的抗菌药物有阿米卡星、阿莫西林/克拉维酸、氨曲南、厄他培南、环丙沙星、氯霉素、美罗培南、庆大霉素、替卡西林/克拉维酸、头孢他啶、头孢西丁、头孢呋辛、头孢吡肟、头孢哌酮、头孢哌酮/舒巴坦、头孢噻肟、妥布霉素、亚胺培南、左氧氟沙星、哌拉西林/三唑巴坦。奇异变形杆菌敏感率大于80.0%的抗菌药物有阿米卡星、阿莫西林/克拉维酸、厄他培南、氯霉素、美罗培南、庆大霉素、替卡西林/克拉维酸、头孢哌酮/舒巴坦、亚胺培南、哌拉西林/三唑巴坦、氨苄西林/舒巴坦。结论治疗大肠埃希菌、肺炎克雷伯菌和奇异变形杆菌引起的肛周脓肿,经验使用抗菌药时,可选用头孢他啶、头孢西丁、阿米卡星,对于存在多重耐药菌感染高风险的患者,需考虑产超广谱β-内酰胺酶细菌感染可能,可选用头孢哌酮/舒巴坦、哌拉西林/三唑巴坦,重症感染时首选亚胺培南、美罗培南进行抗感染治疗。     

耐碳青霉烯类鲍曼不动杆菌耐药性与毒力基因的相关性分析

摘要：目的 探讨耐碳青霉烯类鲍曼不动杆菌耐药性与毒力基因的相关性。方法 收集2018年11月至2019年11月安徽医 科大学第一附属医院173株非重复的鲍曼不动杆菌菌株,分析其对碳青霉烯类抗生素的耐药性。采用PCR检测耐药相关基因 (blaOXA-23、blaOXA-51、blaKPC、blaOXA-24、blaIMP、blaOXA-58、blaVIM和blaSIM)和毒力基因(cusE、bap、abaI和bfmS)。分析鲍曼不 动杆菌耐药性与毒力基因的关系。结果 经筛选后有84株耐碳青霉烯类鲍曼不动杆菌对哌拉西林/舒巴坦、头孢他啶、头孢吡 肟、头孢噻肟、头孢曲松、庆大霉素、阿米卡星、环丙沙星、左氧氟沙星、加替沙星、复方磺胺甲恶唑、米诺环素、替加环 素、亚胺培南和美罗培南的耐药率分别为95.23%、94.04%、94.04%、96.42%、95.23%、95.23%、84.52%、96.42%、76.19%、 79.76%、97.61%、57.14%、0、100.00%和100.00%;其中检测出带有耐药基因blaOXA-23有76株;带有耐药基因blaOXA-51有84株, 未检测出blaKPC、blaOXA-24、blaIMP、blaOXA-58、blaVIM、blaSIM基因;不同毒力基因的鲍曼不动杆菌均具有较高的耐药性,其中 含有毒力基因abaI和bfmS的鲍曼不动杆菌与不含abaI和bfmS基因的耐药性比较存在明显差异(P<0.05)。结论 本院鲍曼不动杆菌 对碳青霉烯类抗生素耐药严重,主要携带blaOXA-23和blaOXA-51耐药基因。耐药性与毒力基因abaI和bfmS密切相关。     

In vitro efficacy of imipenem in combination with six antimicrobial agents against Mycobacterium abscessus

Antimicrobial therapy of Mycobacterium abscessus infection is difficult because there are relatively few effective treatment regimens and single-agent therapy frequently fails clinically. In light of the lack of data on the susceptibility profile of M. abscessus strains recovered from infections in Japan, the in vitro activity of imipenem in combination with clarithromycin, levofloxacin, moxifloxacin, minocycline, amikacin or tobramycin was investigated by the checkerboard method and compared with the combination amikacin and cefoxitin. The combination of imipenem with moxifloxacin, levofloxacin or clarithromycin had a higher synergistic and/or additive effect than amikacin and cefoxitin. A decrease in the MIC(90) value (minimum inhibitory concentration for 90% of the organisms) was observed in the presence of imipenem for clarithromycin, minocycline, levofloxacin and moxifloxacin. The data suggest that a combination regimen including imipenem may be a good choice in empirical treatment of M. abscessus infection.     

Antimicrobial activity of carbapenems and the combined effect with aminoglycoside against recent clinical isolates of Pseudomonas aeruginosa

The carbapenem susceptibility of 32 strains of Pseudomonas aeruginosa recently isolated in Kakogawa municipal hospital was investigated. The MIC ranges of imipenem, panipenem, and meropenem were 0.25-16 mg/L, 0.5-16 mg/L, and < 0.03-4 mg/L, respectively, and meropenem showed the highest antipseudomonal activity among the three carbapenems tested. In the analysis based on the MIC interpretive standards established by NCCLS, the resistance rates of test strains for imipenem, panipenem, and meropenem were 6.3%, 15.6%, and 0%, respectively. We also investigated the in vitro combined effect of imipenem or meropenem with amikacin against another 20 isolates of P. aeruginosa by checkerboard titration assay. Antagonism (minimum FIC index > 2) was not observed in any combinations against all strains tested. Super-additive effects (minimum FIC index < 1) in the combination of imipenem and amikacin were observed in eight (40%) strains tested. In contrast, in the combination of meropenem and amikacin, super-additive effects were observed in 14 isolates (70%). These results suggested that meropenem is superior to imipenem in combined effect with amikacin against P. aeruginosa. In conclusion, meropenem showed higher antipseudomonal activities than other carbapenems tested in both conditions, alone and in combination with amikacin. With regard to the clinical efficacy and prevention of antibiotic resistance, meropenem monotherapy or combination therapy with aminoglycoside is the most superior treatment for pseudomonal infections, and the findings in this study suggest that meropenem is still clinically very useful.     

2011—2017年河南中医药大学第三附属医院心血管科鲍曼不动杆菌的分布及耐药性分析

目的 探讨河南中医药大学第三附属医院心血管疾病住院患者鲍曼不动杆菌感染的分布及耐药情况,为临床治疗提供指导性意见。方法 选取河南中医药大学第三附属医院心血管内科2011年1月—2017年12月确诊的医院感染性鲍曼不动杆菌患者103例,统计分析发生感染患者的疾病分布、标本来源及其耐药情况。结果 共分离出103株鲍曼不动杆菌,其中住院患者原患疾病主要为急性心肌梗死（43.69%）和冠心病(20.39%);标本来源依次为晨痰及下呼吸道分泌物、胸水、血液、尿液;鲍曼不动杆菌对磺胺甲（口恶）唑/甲氧苄啶、奈替米星的耐药率均在60%以上,对头孢他啶、环丙沙星的耐药率均在50%以上;对阿米卡星、美罗培南、亚胺培南、米诺环素的耐药率均在20%～30%。结论 鲍曼不动杆菌对阿米卡星、美罗培南、亚胺培南、米诺环素的耐药率相对较低,临床上应根据药敏结果合理用药。     

Combination carbapenem-sulbactam therapy for critically ill patients with multidrug-resistant Acinetobacter baumannii bacteremia: four case reports and an in vitro combination synergy study

Infections caused by multidrug-resistant Acinetobacter baumannii have become a therapeutic challenge for clinicians worldwide. Although colistin and tigecycline have been successful in treating patients with these infections, these agents are not available on a worldwide basis. We describe four critically ill patients in Taiwan who were diagnosed with multidrug-resistant Acinetobacter baumannii bacteremia. All bacterial isolates from these patients were resistant to commonly available antibiotics, including carbapenems and sulbactam; however, combination therapy with a carbapenem and sulbactam led to favorable clinical outcomes in all four patients. We also conducted an in vitro study using isolates from these patients that showed that this drug combination had a synergistic effect with enhanced antibacterial activity against the isolates. Thus, a carbapenem-sulbactam combination may be a therapeutic alternative for multidrug-resistant Acinetobacter baumannii bacteremia in countries where colistin and tigecycline are not available for clinical use.     

常见革兰氏阴性菌耐药性动态变化特征及分析

目的 分析本地区2003年1月～2006年6月期间最常见革兰氏阴性茵(大肠埃希茵、肺炎克雷伯菌、铜绿假单胞菌和鲍曼不动杆菌)耐药性的变化,为指导临床合理使用抗菌素提供可靠依据.方法 应用回顾性调查分析方法对我院该期间临床标本分离的大肠埃希菌、肺炎克雷伯菌、铜绿假单胞菌和鲍曼不动杆菌的药敏试验进行对比统计分析.结果 近4年来,该4种细菌对常用抗菌药物的耐药率总体呈上升趋势.大肠埃希茵对头孢呋辛、头孢他啶、头孢噻肟、头孢吡肟耐药率变化显著,对大肠埃希茵保持较强抗茵活性而耐药率＜30%的抗菌药物有阿莫西林-克拉维酸、哌拉西林-三唑巴坦、亚胺培南、美诺培南、阿米卡星;肺炎克雷伯茵对哌拉西林、替卡西林-克拉维酸、头孢他啶、头孢噻肟、头孢呋辛、环丙沙星耐药率变化显著,对肺炎克雷伯菌保持较强抗菌活性而耐药率＜30%的抗菌药物有阿莫西林-克拉维酸、哌拉西林-三唑巴坦、亚胺培南、美诺培南、阿米卡星、奈替米星、妥布霉素;铜绿假单胞菌对妥布霉素、阿米卡星、庆大霉素、环丙沙星耐药率变化显著,对铜绿假单胞菌保持较强抗菌活性而耐药率＜30%的抗菌药物有替卡西林-克拉维酸、哌拉西林-三唑巴坦、头孢他啶、亚胺培南、美诺培南、阿米卡星、庆大霉素、妥布霉素、环丙沙星、多粘菌素E;对鲍曼不动杆菌保持较强抗茵活性而耐药率＜30%的抗茵药物有哌拉西林-三唑巴坦、头孢他啶、亚胺培南、美诺培南、阿米卡星.结论 本地区大肠埃希菌、肺炎克雷伯茵、铜绿假单胞菌和鲍曼不动杆菌对常用抗菌药物耐药率高,多重耐药现象严重,根据药敏结果选择抗菌药物,可有效控制和减缓细茵耐药性的增长.     

Mechanisms of resistance to ciprofloxacin,ampicillin/sulbactam and imipenem in Acinetobacter baumannii clinical isolates in Taiwan

Nosocomial infections caused by multidrug-resistant (MDR) Acinetobacter baumannii have been increasing in recent years, posing a threat to public health worldwide. The susceptibility to eight antimicrobial agents of 35 clinical A. baumannii isolates from Taiwan was tested. Isolates were examined by polymerase chain reaction (PCR) and sequencing for β-lactamase genes and mutations in the gyrA and parC genes. Expression of AdeB, an efflux pump protein, was evaluated by real-time quantitative PCR. The level of adeB expression correlated with resistance to ciprofloxacin and ampicillin/sulbactam in A. baumannii isolates. Almost all isolates with full resistance to ciprofloxacin had both high adeB expression and point mutations in parC and gyrA, but 4 intermediate-resistant isolates had only high adeB expression without point mutations in gyrA or parC, in contrast to 18 susceptible isolates with low adeB expression and without mutations in gyrA or parC. Sixteen isolates (45.7%) carrying a type 1 integron were MDR as well as being more resistant to imipenem, amikacin, gentamicin, ceftazidime or cefepime than those without the integron. The class 1 integron in A. baumannii carried different resistance gene cassettes, including 5′CS-bla_IMP-1–aadA4–3′CS, 5′CS–aacA4–aadA1–3′CS and 5′CS–aacC1–aadA1–3′CS. In conclusion, expression of the adeB gene was associated with resistance to ciprofloxacin and ampicillin/sulbactam in A. baumannii. Multiple mutations in gyrA and parC also played a role in ciprofloxacin resistance. The major metallo-β-lactamase contributing to imipenem resistance in A. baumannii in Taiwan was bla_IMP-1, which was carried by the class 1 integron. The class 1 integron was associated with the MDR phenotype in A. baumannii.     

2013-2015年重庆市荣昌区中医院常见病原菌分布及耐药性分析

目的 了解重庆市荣昌区中医院临床常见病原菌的分布及耐药情况,为临床合理用药提供参考。方法 收集重庆市荣昌区中医院2013年9月-2015年9月检验科分离的病原菌及药敏试验结果进行统计分析。结果 共分离出病原菌600株,其中革兰阴性菌428株,占71.33%;革兰阳性菌172株,占28.67%。标本主要来自痰液,构成比为75.08%。革兰阳性菌中,葡萄球菌检出率高且耐药较严重,金黄色葡萄球菌敏感的药物有万古霉素、多西环素、阿米卡星和呋喃妥因。未发现耐万古霉素的葡萄球菌。革兰阴性菌中肺炎克雷伯菌对氨苄西林耐药率为100.0%,对其他均敏感;大肠埃希菌对头孢哌酮/舒巴坦钠、哌拉西林/他唑巴坦、亚胺培南较敏感。铜绿假单胞菌、洋葱伯克霍尔德菌和嗜麦芽寡养单胞菌呈现出多重耐药性,对常见抗菌药物均有不同程度的耐药;鲍曼不动杆菌对头孢哌酮/舒巴坦钠、哌拉西林/他唑巴坦、美罗培南、复方新诺明、米诺环素敏感。结论 重庆市荣昌区中医院常见病原菌耐药严重,临床应重视病原菌检查,同时加强监管,以降低细菌耐药性。     

Comparative activities of colistin, rifampicin, imipenem and sulbactam/ampicillin alone or in combination against epidemic multidrug-resistant Acinetobacter baumannii isolates producing OXA-58 carbapenemases

This study evaluated the activity of colistin, rifampicin, imipenem and sulbactam/ampicillin alone or in combination against nine epidemic multidrug-resistant Acinetobacter baumannii isolates producing OXA-58 carbapenemase in Naples, Italy. The isolates were susceptible to colistin but differed in their resistance to imipenem and rifampicin. Time–kill studies showed a bactericidal effect for colistin but not for imipenem, rifampicin or sulbactam/ampicillin used as single agents. Synergism was observed with combinations of rifampicin + imipenem or sulbactam/ampicillin for all isolates and with colistin + rifampicin for isolates showing higher minimum inhibitory concentrations for rifampicin. Combined use of the antimicrobials tested may provide good therapeutic options for OXA-58 carbapenemase-producing A. baumannii infections.     

Genomic analysis of in vivo acquired resistance to colistin and rifampicin in Acinetobacter baumannii

Acinetobacter baumannii is an opportunistic pathogen in healthcare facilities responsible for nosocomial infections mostly in immunocompromised patients. Colistin resistance is increasingly reported worldwide in A. baumannii. Here we describe the in vivo selection of colistin and rifampicin resistance in carbapenem-resistant A. baumannii. Antimicrobial susceptibility testing, plasmid analysis and whole-genome sequencing (WGS) were performed to fully characterise the resistome of two clinical isolates (AbS1 and AbS2) selected during treatment. Clinical isolate AbS1 remained susceptible to colistin, rifampicin and tigecycline, whilst AbS2 was susceptible only to tigecycline. PCR analysis revealed the presence of a bla_OXA-23-like carbapenemase gene. Kieser extraction revealed an ca. 74?kb plasmid harbouring bla_OXA-23. WGS revealed genomes of 3.8 Mbp in size with a G?+?C content of 38.9%, and both belonged to ST281 according to the Oxford MLST scheme and ST641 according to the Institut Pasteur scheme. The resistome was also composed of naturally occurring β-lactamases, i.e. ADC-25 cephalosporinase and OXA-82 oxacillinase, aminoglycoside resistance genes [aac(3)-Ia, aadA1 and aph(3')-VIa (aphA6)], and mutations in DNA gyrases explaining fluoroquinolone resistance. Single nucleotide polymorphism analysis revealed that both isolates were identical except for a 30-nucleotide duplication within the pmrB gene and a point mutation in the rpoB gene resulting in colistin and rifampicin resistance, respectively. This study highlights the genomic plasticity of A. baumannii under antibiotic pressure. The 10-amino acid duplication in PmrB affects colistin susceptibility by regulating lipopolysaccharide modification through the PmrAB two-component system. These findings provide further information on the molecular mechanisms leading to colistin resistance in A. baumannii.     

250株鲍曼不动杆菌对14种抗菌药物的药敏测定

目的对2005年1月至2007年3月,本院分离的鲍曼不动杆菌耐药状况进行分析。方法收集临床分离的鲍曼不动杆菌,培养鉴定。采用纸片扩散法(K-B法),根据美国临床实验室标准化委员会(NCCLS)相关文件判断结果。结果期间分离出250株鲍曼不动杆菌,对14种抗菌药物体外敏感试验结果显示,对氨曲南耐药率为88%、头孢哌酮72%、复方磺胺甲口恶唑56.4%、替卡西林/克拉维酸55.6%、哌拉西林53.2%、庆大霉素51.2%、头孢吡肟50.4%、左氧氟沙星48.8%、头孢他啶48.4%、哌拉西林/他唑巴坦46.8%、妥布霉素44.8%、阿米卡星42%、头孢哌铜/舒巴坦14%、亚胺培南13.6%。结论鲍曼不动杆菌对14种抗菌药物均有不同程度的耐药。     

Current review of antimicrobial treatment of nosocomial pneumonia caused by multidrug-resistant pathogens

Nosocomial pneumonia (including ventilator-associated pneumonia; VAP), a consistently difficult-to-treat entity, is frequently caused by multidrug-resistant (MDR) or pandrug-resistant (PDR) bacteria. Given the high mortality rates caused by drug-resistant bacteria and the difficulty of developing new potent antibiotics to target the problematic pathogens, combination regimens are under ardent evaluation as new strategies to overcome increasing drug resistance. Adjustment of the administration method of certain β-lactams (meropenem, or imipenem/cilastatin), or combination of tigecycline with some agents, may show promise with regard to successful management of MDR or PDR Acinetobacter baumannii pneumonia. Additionally, vancomycin plus rifampicin is an effective regimen against nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) responding poorly to vancomycin monotherapy. The clinical appropriateness of parenteral colistin against pneumonia caused by MDR A. baumannii has been established in a clinical trial. Facing the decline of clinical vancomycin efficacy after initial use, linezolid might be the drug of choice with regard to the treatment of MRSA-VAP. The role of tigecycline monotherapy for the management of nosocomial pneumonia caused by MRSA and extended-spectrum β-lactamase-producing Enterobacteriaceae needs to be cautiously evaluated.