铜绿假单胞菌肺部感染78例抗菌治疗分析

铜绿假单胞菌是革兰阴性杆菌感染中仅次于大肠杆菌、克雷伯菌的常见病原菌。其感染主要发生于６０岁以上,免疫功能低下及使用抗生素、激素,或化疗介入性诊疗时导致的院内感染。尤以肺部感染或在呼吸道寄生多见［３］。且该菌肺部感染的治疗,由于其复杂的耐药机制,生物膜的包裹和多重耐药变得越来越困难,病死率高。近年来受到医学界高度重视。自１９９７年１月～１９９９年１２月,我院从院内肺部感染病人的下呼吸道获铜绿假单胞菌８６株。本文对其中临床资料完整的７８例进行了总结,并分析了８６株分离菌的体外药物敏感性,以了解肺部铜绿假…     

铜绿假单胞菌医院感染分布及体外抗菌活性分析

[目的]了解铜绿假单胞菌（Pseudomonas aeruginosa）的感染分布及其耐药性，为临床治疗提供实验室依据。[方法]采用回顾性的方法统计分析254株铜绿假单胞菌的标本来源，感染科室分布及耐药状况。[结果]254株铜绿假单胞菌有159株来自伤口分泌物，有83株来自痰及气道分泌物，其余来自血液、静脉导管尖端和尿液。分离铜绿假单胞菌的科室分别为烧伤科占62．6％、内科24．8％、脑系科5．1％、外科3．9％、骨科1．6％。药敏结果显示铜绿假单胞菌对β-内酰胺类、氨基糖苷类、喹诺酮类、磺胺类抗菌药物均有很高的耐药性，均接近或大于60％，而对碳青酶烯类和单环β-内酰胺类有较低的耐药率，最低者是氨曲南42．9％其次是亚胺培南49．5％。[结论]铜绿假单胞菌临床分离株多来自我院烧伤病人的伤口创面。并对多种抗菌药物的耐药率较高，多重耐药明显，临床应加强对铜绿假单胞菌耐药性的监控并防治耐药菌株的传播流行。     

铜绿假单胞菌感染的药物治疗进展

正铜绿假单胞菌(PA)是一种革兰阴性杆菌,也是临床最常见的非发酵菌,在自然界广泛分布,可作为正常菌群在人体皮肤表面分离到,还可污染医疗器械甚至消毒液,从而导致医源性感染,是医院获得性感染重要的条件致病菌,具有易定植、易变异和多耐药的特点。PA正常情况下是一种无害细菌,于自     

铜绿假单胞菌血流感染患者细菌耐药性及预后影响因素分析

目的探讨铜绿假单胞菌血流感染患者细菌耐药性及预后的影响因素。方法回顾性分析2016年1月-2018年12月浙江大学医学院附属第一医院137例确诊为铜绿假单胞菌血流感染患者的临床资料。单因素分析多重耐药(MDR)菌株感染相关因素。根据28 d预后分为死亡组(40例)和生存组(97例),多因素logistic回归分析死亡独立危险因素。结果纳入137例患者,28 d病死率29.2%。单因素分析显示外科手术、动静脉置管、导尿管留置、高白细胞计数、低白蛋白血症、起病时高急性生理与慢性健康(APACHEⅡ)评分与MDR菌株感染有关(P值分别为0.023、0.015、0.019、0.013、0.005、0.011)。logistic回归分析显示起病时高APACHEⅡ评分(OR=1.167,P=0.025)、低白蛋白血症(OR=0.785,P=0.004)、感染性休克(OR=5.434,P=0.036)是铜绿假单胞菌血流感染患者死亡的独立危险因素。MDR菌株血流感染患者抗菌治疗方案中,含有多黏菌素B的治疗组28 d病死率与不含多黏菌素B的治疗组28 d病死率相同,差异无统计学意义(P>0.05)。结论铜绿假单胞菌血流感染病死率高,起病时高APACHEⅡ评分、合并低白蛋白血症、感染性休克提示预后差。多黏菌素B治疗MDR铜绿假单胞菌血流感染有待大样本临床数据进一步研究。     

118株铜绿假单胞菌医院感染分布与耐药性分析

目的了解医院铜绿假单胞菌在临床分布情况与耐药情况,为临床合理选择抗菌药物提供依据。方法对2011年度医院感染患者临床标本中所分离的118株铜绿假单胞菌的标本类型、临床科室分布、药敏试验结果进行分析。结果感染铜绿假单胞菌标本中呼吸道标本占69.5%;临床科室中重病监护病房（ICU）50株（42.4%）,呼吸内科32株（27.1%）,脑外科18株（15.3%）;亚胺培南和头孢哌酮/舒巴坦耐药率在11%～14%。结论呼吸道是铜绿假单胞菌医院感染的高发部位;ICU、呼吸内科、脑外科为铜绿假单胞菌医院感染的高危科室;铜绿假单胞菌对多种抗菌药物具有较高的耐药性,应加强药物监测,指导临床合理使用抗菌药物,控制医院感染。     

铜绿假单胞菌对常用抗菌药物的耐药性分析

目的了解铜绿假单胞菌对常用抗菌药物的耐药性，为临床合理用药提供依据。方法采用琼脂纸片扩散法（K—B法）进行药敏试验。结果铜绿假单胞菌对亚胺培南、头孢哌酮／舒巴坦、丁胺卡那霉素的耐药率较低，分别为12．7％、22．8％和30．5％；对氨苄西林、氨苄西林／舒巴坦、复方新诺明、头孢唑啉的耐药率较高，分别为100.0％、99．2％、97．3oA和92．3％。结论临床医生应依据药敏试验结果合理使用抗菌药物，从而减少或避免耐药菌株的增加。     

徐州地区铜绿假单胞菌药敏试验结果分析

目的了解铜绿假单胞菌的耐药特点及指导临床抗菌药物选择。方法收集徐州市第一人民医院2013年临床分离出的335株铜绿假单胞菌进行药敏分析,并用WHONET5.6软件对实验结果和数据进行分析。结果临床分离出的335株铜绿假单胞菌对15种抗菌药物存在不同程度的耐药,其中对哌拉西林/他唑巴坦、丁胺卡那霉素、妥布霉素、环丙沙星、左氧氟沙星、头孢他啶、头孢吡肟、庆大霉素对铜绿假单胞菌的敏感性较高;对氨苄西林/舒巴坦、头孢曲松、氨苄西林、头孢噻肟耐药率高达97%以上。同一患者多次检测出该菌的,哌拉西林/他唑巴坦、头孢他啶、头孢吡肟、亚胺培南、庆大霉素药敏结果存在较大的波动性,同时铜绿假单胞菌的耐药谱有一定的趋向性。结论加强铜绿假单胞菌连续性病原学和耐药性监测,以应对急性耐药的发生和医院感染扩散,同时指导临床治疗。     

铜绿假单胞菌血流感染27例临床分析

目的探讨铜绿假单胞菌血流感染的临床特点及细菌耐药性。方法回顾性分析北京大学第三医院2006年1月—2009年12月铜绿假单胞菌血流感染患者的临床及微生物学资料。结果 27例患者纳入分析。患者基础疾病评分(Charlson评分)为4.48±2.10;发生血流感染时均有发热、外周血白细胞减少或升高;9例患者发生感染中毒性休克,9例患者住院死亡。患者血流感染来源于下呼吸道感染最多,其次为中心静脉内导管相关感染。发生多重耐药(MDR)菌株感染6例。与非MDR组相比较,MDR组患者入院时的急性生理与慢性健康评估(APACHE)Ⅱ评分和感染相关器官衰竭评分(SOFA评分)显著升高,入住ICU时间显著延长,入院至血培养阳性前接受2类或2类以上抗菌药物治疗比率显著升高,血培养阳性后的适当经验性抗菌药物治疗率显著降低;两组Charlson评分、临床表现、抽取血培养时的APACHEⅡ评分与SOFA评分、住院病死率等差异无统计学意义。结论铜绿假单胞菌血流感染患者病情较重,病死率较高,该菌MDR菌株感染患者入院时病情多重于非MDR感染者,两者临床表现相似,应积极行病原学检查,尽早选用敏感抗菌药物治疗以降低病死率。     

311株铜绿假单胞菌感染与耐药分析

目的:研究铜绿假单胞菌感染现状、分布特征及其耐药性,指导临床合理用药。方法:收集四川大学华西医院2003年1月~2003年12月临床分离铜绿假单胞菌311株,用美国DADE BEHRING公司Microscan walkAway40型全自动细菌鉴定分析系统对临床标本中分离的铜绿假单胞菌进行鉴定,并采用MIC法对临床分离铜绿假单胞菌选用13种抗菌药物进行敏感性测定。分析其感染分布、耐药性与多重耐药性。结果:共检出311株铜绿假单胞菌。感染部位依次为呼吸道、血液、胆汁、伤口等。耐药率:头孢吡肟(11.6%)、哌拉西林-他唑巴坦(11.6%)、阿米卡星(11.6%)、头孢哌酮-舒巴坦(16.1%)、环丙沙星(23.8%)、哌拉西林(24.8%)、庆大霉素(29.3%)、妥布霉素(30.1%)头孢他啶(30.9%)、氨曲南(33.4%)、亚胺培南(34.4%),其余抗生素耐药率更高。耐药菌株存在较严重的交叉耐药及多重耐药现象。结论:铜绿假单胞菌耐药及多重耐药现象严重,应加强对铜绿假单胞菌耐药性的监测,合理使用抗菌药物,以减少耐药菌株的出现和扩散。     

Characterization of the Polymyxin B Resistome of Pseudomonas aeruginosa

Multidrug resistance in Pseudomonas aeruginosa is increasingly becoming a threat for human health. Indeed, some strains are resistant to almost all currently available antibiotics, leaving very limited choices for antimicrobial therapy. In many such cases, polymyxins are the only available option, although as their utilization increases so does the isolation of resistant strains. In this study, we screened a comprehensive PA14 mutant library to identify genes involved in changes of susceptibility to polymyxin B in P. aeruginosa. Surprisingly, our screening revealed that the polymyxin B resistome of this microorganism is fairly small. Thus, only one resistant mutant and 17 different susceptibility/intrinsic resistance determinants were identified. Among the susceptible mutants, a significant number carried transposon insertions in lipopolysaccharide (LPS)-related genes. LPS analysis revealed that four of these mutants (galU, lptC, wapR, and ssg) had an altered banding profile in SDS-polyacrylamide gels and Western blots, with three of them exhibiting LPS core truncation and lack of O-antigen decoration. Further characterization of these four mutants showed that their increased susceptibility to polymyxin B was partly due to increased basal outer membrane permeability. Additionally, these mutants also lacked the aminoarabinose-substituted lipid A species observed in the wild type upon growth in low magnesium. Overall, our results emphasize the importance of LPS integrity and lipid A modification in resistance to polymyxins in P. aeruginosa, highlighting the relevance of characterizing the genes that affect biosynthesis of cell surface structures in this pathogen to follow the evolution of peptide resistance in the clinic.     

Emergence of Polymyxin B Resistance Influences Pathogenicity in Pseudomonas aeruginosa Mutators

The interplay between polymyxin B pharmacodynamics and pathogenicity was examined in Pseudomonas aeruginosa PAO1 and isogenic DNA repair-deficient mutators (mutM and mutS strains). Against mutS mutators, polymyxin B initial killing was concentration dependent, with >99.9% bacterial reduction at 2 h followed by regrowth and resistance. The pre- versus postexposed strains were inoculated real time into Galleria mellonella waxworms, resulting in increased median survival times from 20 h to 23 h (P < 0.001). Emergence of resistance in mutS P. aeruginosa resulted in attenuation of virulence.     

Polymyxin B in Combination with Antimicrobials Lacking In Vitro Activity versus Polymyxin B in Monotherapy in Critically Ill Patients with Acinetobacter baumannii or Pseudomonas aeruginosa Infections

There is no clinical evidence supporting the use of polymyxin B in combination with another antimicrobial for infections caused by extensively drug-resistant Acinetobacter baumannii or Pseudomonas aeruginosa isolates. We developed a cohort study of patients in two intensive care units from teaching hospitals to evaluate treatment with intravenous polymyxin B for ≥48 h for severe A. baumannii or P. aeruginosa infections. Covariates potentially associated with 30-day mortality were evaluated in a Cox proportional hazards model. A total of 101 patients were included; 33 (32.7%) were treated with polymyxin B in combination with an antimicrobial lacking in vitro activity and 68 (67.3%) with polymyxin B in monotherapy. The overall 30-day mortality was 59.4% (60 patients), comprising 42.4% (14 of 33) and 67.6% (46 of 68) in combination and monotherapy groups, respectively (P = 0.03). The mortality rates were 18.5/1,000 patient days and 36.4/1,000 patient days in the combination and monotherapy groups, respectively (P = 0.02). Combination therapy was independently associated with lower 30-day mortality (hazard ratio, 0.33; 95% confidence interval, 0.17 to 0.64; P = 0.001). Creatinine clearance of ≥60 ml/min was also a protective factor, while a higher acute physiology and chronic health evaluation (APACHE II) score and polymicrobial infection were associated with increased mortality. The results did not change after adding a propensity score for prescribing combination therapy into the model. The protective effect remained when only combination with β-lactam or carbapenem was considered and in both subgroups of patients: those with A. baumannii infection and those with lower respiratory tract infections. To our knowledge, this is the first clinical study to show a benefit of combination over monotherapy with polymyxin B for severe extensively drug-resistant A. baumannii or P. aeruginosa infections.     

Optimization of Polymyxin B in Combination with Doripenem To Combat Mutator Pseudomonas aeruginosa

Development of spontaneous mutations in Pseudomonas aeruginosa has been associated with antibiotic failure, leading to high rates of morbidity and mortality. Our objective was to evaluate the pharmacodynamics of polymyxin B combinations against rapidly evolving P. aeruginosa mutator strains and to characterize the time course of bacterial killing and resistance via mechanism-based mathematical models. Polymyxin B or doripenem alone and in combination were evaluated against six P. aeruginosa strains: wild-type PAO1, mismatch repair (MMR)-deficient (mutS and mutL) strains, and 7,8-dihydro-8-oxo-deoxyguanosine system (GO) base excision repair (BER)-deficient (mutM, mutT, and mutY) strains over 48 h. Pharmacodynamic modeling was performed using S-ADAPT and facilitated by SADAPT-TRAN. Mutator strains displayed higher mutation frequencies than the wild type (>600-fold). Exposure to monotherapy was followed by regrowth, even at high polymyxin B concentrations of up to 16 mg/liter. Polymyxin B and doripenem combinations displayed enhanced killing activity against all strains where complete eradication was achieved for polymyxin B concentrations of >4 mg/liter and doripenem concentrations of 8 mg/liter. Modeling suggested that the proportion of preexisting polymyxin B-resistant subpopulations influenced the pharmacodynamic profiles for each strain uniquely (fraction of resistance values are −8.81 log₁₀ for the wild type, −4.71 for the mutS mutant, and −7.40 log₁₀ for the mutM mutant). Our findings provide insight into the optimization of polymyxin B and doripenem combinations against P. aeruginosa mutator strains.     

Polymyxin Susceptibility in Pseudomonas aeruginosa Linked to the MexXY-OprM Multidrug Efflux System

The ribosome-targeting antimicrobial, spectinomycin (SPC), strongly induced the mexXY genes of the MexXY-OprM multidrug efflux system in Pseudomonas aeruginosa and increased susceptibility to the polycationic antimicrobials polymyxin B and polymyxin E, concomitant with a decrease in expression of the polymyxin resistance-promoting lipopolysaccharide (LPS) modification loci, arnBCADTEF and PA4773-74. Consistent with the SPC-promoted reduction in arn and PA4773-74 expression being linked to mexXY, expression of these LPS modification loci was moderated in a mutant constitutively expressing mexXY and enhanced in a mutant lacking the efflux genes. Still, the SPC-mediated increase in polymyxin susceptibility was retained in mutants lacking arnB and/or PA4773-74, an indication that their reduced expression in SPC-treated cells does not explain the enhanced polymyxin susceptibility. That the polymyxin susceptibility of a mutant strain lacking mexXY was unaffected by SPC exposure, however, was an indication that the unknown polymyxin resistance ‘mechanism’ is also influenced by the MexXY status of the cell. In agreement with SPC and MexXY influencing polymyxin susceptibility as a result of changes in the LPS target of these agents, SPC treatment yielded a decline in common polysaccharide antigen (CPA) synthesis in wild-type P. aeruginosa but not in the ΔmexXY mutant. A mutant lacking CPA still showed the SPC-mediated decline in polymyxin MICs, however, indicating that the loss of CPA did not explain the SPC-mediated MexXY-dependent increase in polymyxin susceptibility. It is possible, therefore, that some additional change in LPS promoted by SPC-induced mexXY expression impacted CPA synthesis or its incorporation into LPS and that this was responsible for the observed changes in polymyxin susceptibility.     

Susceptibility of 1,500 Isolates of Pseudomonas aeruginosa to Gentamicin, Carbenicillin, Colistin, and Polymyxin B

A series of 1,500 strains of Pseudomonas aeruginosa was collected from a variety of sources to provide a group of strains which would truly represent the species. All of them were pyocine typed, and a wide range of types was included among the isolates from each source. The gentamicin, carbenicillin, colistin, and polymyxin minimal inhibitory concentration of each strain was measured by the agar dilution method employing the Steers inocula replicator. Over 99% of strains were inhibited by 8 mug of gentamicin per ml, by 256 mug of carbenicillin per ml, and by 4 mug of colistin per ml. The small number of strains more resistant to each antibiotic comprised a variety of different pyocine types. Few strains were found to be susceptible to tetracycline, chloramphenicol, kanamycin, or streptomycin at the single concentration tested.     

Polymyxin B versus colistin: an update

Polymyxin B and colistin (polymyxin E) are polypeptide antibiotics that were developed in the 1940s, but fell into disfavor due to their high toxicity rates. These two antibiotics were previously regarded to be largely equivalent, due to similarities in their chemical structure and spectrum of activity. In recent years, several pertinent differences, especially in terms of potency and disposition, have been revealed between polymyxin B and colistin. These differences are mainly attributed to the fact that polymyxin B is administered parenterally in its active form, while colistin is administered parenterally as an inactive pro-drug, colistimethate. In this review, we summarize the similarities and differences between polymyxin B and colistin. We also discuss the potential clinical implications of these findings, and provide our perspectives on how polymyxins should be employed to preserve their utility in this era of multi-drug resistance.     

Comparison of bactericidal activity of selected beta-lactam antimicrobials against Pseudomonas aeruginosa

The efficacy of ceftazidime, piperacillin, tobramycin and ticarcillin was tested in vitro against 102 clinical isolates of Pseudomonas aeruginosa. The MIC and MBC of each agent alone were determined. In addition, the rate of killing of 27 isolates by each beta-lactam agent was tested both singly and in combination with tobramycin. The concentrations of beta-lactams and of tobramycin were tailored to each organism; these were double the MBC in the case of the beta-lactams and half the MBC for tobramycin. Although 85.2% of isolates were susceptible to piperacillin and only 58.8% were susceptible to ticarcillin, the MBC90 was higher for piperacillin (greater than 256 mg/l) than ticarcillin (199.7 mg/l). The addition of tobramycin in sublethal concentrations increased the rapidity of killing of bacteria.