Reduced virulence in ciprofloxacin-resistant variants of Pseudomonas aeruginosa strains

Pseudomonas aeruginosa strains resistant to ciprofloxacin were obtained from parental strains by serial transfer through subinhibitory concentrations of the drug. They showed reduced virulence for mice, and also increased sensitivity to aminoglycosides.     

In vitro synergy of ciprofloxacin and gatifloxacin against ciprofloxacin-resistant Pseudomonas aeruginosa

Multidrug-resistant Pseudomonas aeruginosa with combined decreased susceptibility to ceftazidime, ciprofloxacin, imipenem, and piperacillin is increasingly being found as a cause of nosocomial infections. It is important to look for combinations of drugs that might be synergistic. Ciprofloxacin resistance by P. aeruginosa is mediated in part by an efflux pump mechanism. Gatifloxacin, an 8-methoxyfluoroquinolone, inhibits a staphylococcal efflux pump. An earlier in vitro study using an Etest synergy method and time-kill assay suggested synergy of ciprofloxacin and gatifloxacin against P. aeruginosa. Synergy testing was performed by Etest and time-kill assay for 31 clinically unique, plasmid DNA distinct, U.S. P. aeruginosa isolates. Etest MICs for ciprofloxacin were 4 to >32 microg/ml, and for gatifloxacin they were >32 microg/ml. Ciprofloxacin plus gatifloxacin showed synergy by the Etest method for 6 (19%) of the 31 P. aeruginosa isolates using a summation fractional inhibitory concentration of < or = 0.5 for synergy. Synergy was demonstrated for 13/31 (42%) of isolates by time-kill assay. No antagonism was detected. The remaining isolates were indifferent to the combination. The Etest method and time-kill assay were 65% (20/31) concordant. The mechanism of the in vitro synergy may include P. aeruginosa ciprofloxacin efflux pump inhibition by gatifloxacin.     

某三级医院铜绿假单胞菌临床分布及耐药性研究

摘要 目的 了解临床分离出的铜绿假单胞菌(PA)的分布及其耐药性,为临床合理选用抗菌药物提供参考。方法 回顾性分析某大学附属医院住院患者送检标本中培养出的PA的临床分布及耐药特点并进行总结分析。结果 2013-2015年共分离出PA 439株,主要来源于痰液、咽喉、尿液及脓液,分别占79.17%、 8.20%、 6.61%和4.78%;PA的检出主要分布于呼吸内科、综合I科、神经内科和泌尿外科,分别占27.11%、23.69%、10.71%和9.11%;2013-2015年,PA对氨曲南和头孢他啶耐药率呈增加趋势,对哌拉西林他唑巴坦耐药率先降后升,对头孢哌酮舒巴坦耐药率呈先升后降趋势,对其他常用抗PA抗菌药耐药率无明显变化。结论 PA的检出来源主要为痰标本,临床主要分布于呼吸内科,PA对部分临床使用强度较高的抗PA抗菌药物耐药率有增加趋势,且耐药率的升高滞后于使用强度的增加。     

Comparative pharmacodynamics and antimutant potentials of doripenem and imipenem with ciprofloxacin-resistant Pseudomonas aeruginosa in an in vitro model

To compare the antipseudomonal efficacy of doripenem and imipenem as well as their abilities to restrict the enrichment of resistant Pseudomonas aeruginosa, multiple-dosing regimens of each drug were simulated at comparable values of the cumulative percentages of a 24-h period that the drug concentration exceeds the MIC under steady-state pharmacokinetic conditions (T(>MIC)) and ratios of the 24-hour area under the curve (AUC(24)) to the MIC. Three clinical isolates of ciprofloxacin-resistant P. aeruginosa (MIC of doripenem, 1 μg/ml; MICs of imipenem, 1, 2, and 2 μg/ml) were exposed to thrice-daily doripenem or imipenem for 3 days at AUC(24)/MIC ratios of from 50 to 170 h (doripenem) and from 30 to 140 h (imipenem). The antimicrobial effects for susceptible and resistant subpopulations of bacteria were expressed by the areas between control growth and time-kill curves (I(E)s) and areas under the bacterial mutant concentration curves (AUBC(M)s), respectively. With each antibiotic, the I(E) and AUBC(M) versus log AUC(24)/MIC relationships were bacterial strain independent. At similar AUC(24)/MIC ratios, doripenem was slightly less efficient than imipenem against susceptible and resistant subpopulations of bacteria. However, doripenem appeared to be somewhat more efficient than imipenem at clinically achievable AUC(24)s related to the means of the MICs for the three studied strains and had higher antimutant potentials for two of the three strains.     

医院分离铜绿假单胞菌的分布情况与耐药性分析

目的了解医院临床分离铜绿假单胞菌的分布情况及耐药现状,为临床医生合理使用抗菌药物提供依据。方法收集2008年7月至2009年6月临床各科送检标本,采用梅里埃公司的Vitek2compact全自动微生物鉴定和药敏分析仪同时进行菌株鉴定与药敏测定。结果共分离出铜绿假单胞菌381株,其中痰标本中分离出铜绿假单胞菌最多,占62.2%;重症医学科、儿科和呼吸内科分离的菌株数居前3位;铜绿假单胞菌对阿米卡星的敏感性较高,耐药率为4.5%,对庆大霉素和妥布霉素这类氨基糖甙类抗菌药物敏感性均较好,耐药率低于10%,头孢吡肟和哌拉西林/他唑巴坦对铜绿假单胞菌具有较好的抗菌活性,耐药率分别为11.3%和11.8%。结论铜绿假单胞菌对抗菌药物的耐药性呈上升趋势,加强医院感染病原菌的耐药性监测,对合理使用抗菌药物及减缓多药耐药菌的产生尤为重要。     

Outbreak by meropenem-resistant Pseudomonas aeruginosa producing IMP-6 metallo-beta-lactamase in a Korean hospital

Pseudomonas aeruginosa isolates containing the bla(IMP-6) gene were recovered from 5 patients hospitalized at a tertiary-care hospital in Korea. The bla(IMP-6) gene was in a class 1 integron containing 5 different insert gene cassettes. All of the isolates showed identical pattern in SpeI macrorestriction analysis.     

Molecular epidemiology of outbreaks and containment of drug-resistant Pseudomonas aeruginosa in a Tokyo hospital

We witnessed outbreaks of multidrug-resistant (MDR) and drug-resistant Pseudomonas aeruginosa at a hospital in Tokyo, Japan, during the period September 2004 through May 2005. The first outbreak occurred in September and October 2004. Three isolates of MDR P. aeruginosa were identified from urine samples obtained from three nonambulatory immunodeficient patients in one ward. After 3 weeks, another outbreak of P. aeruginosa occurred in the hematology ward on the same floor of the hospital. During the outbreaks, environmental surveys were conducted twice in each of the two wards, at 2-week intervals, to identify the sources of the pathogens. A total of 23 P. aeruginosa isolates, including 11 from environmental sources, were analyzed for chromosomal DNA typing by pulsed-field gel electrophoresis, for O-antigen serotyping, and for other typing. Results revealed two causative clones, as well as environmental contamination by P. aeruginosa clones on the surfaces of urine volume-measuring devices in rooms where urine is handled, which may have been sources of the pathogens during the outbreaks. To prevent further outbreaks, we performed the following: (a) environmental surface monitoring for drug-resistant P. aeruginosa, (b) active surveillance of specimens, (c) strict isolation of infected patients or carriers of MDR P. aeruginosa, (d) rigorous contact precautions, and (e) disinfection with 70% alcohol on the surfaces of apparatuses contaminated by MDR or drug-resistant P. aeruginosa and in the rooms where urine is handled. As a result, the outbreaks were contained.     

Isolation of Pseudomonas aeruginosa producing OXA-4 β-lactamase in a Japanese hospital in 1996

One-hundred and fifty isolates of Pseudomonas aeruginosa were collected from different patients' specimens at Showa University Fujigaoka Hospital between April and August 1996. The 23 isolates resistant to piperacillin (minimum inhibitory concentration, ≥100 μg/ml) were widely distributed in the hospital wards. Using polymerase chain reaction–single-strand conformation polymorphism (PCR-SSCP) and isoelectric focusing (IEF) methods, we detected OXA-4β-lactamase hydrolyzing penams in 4 of the resistant isolates (17%) with O-serotype E. However, no other external β-lactamase was detected by the IEF method. The hybridization results showed that the OXA-4 genes were located in chromosome, but not in plasmid. Furthermore, the isolation rate was significantly lower than that found between 1992 and 1993 (61%; P < 0.01; χ²-test), suggesting a decreased rate of hospital infection caused by P. aeruginosa producing the OXA-4 enzyme. Received: March 31, 2000 / Accepted: July 25, 2000     

Susceptibility of Pseudomonas aeruginosa to antimicrobials: a 2004 French multicentre hospital study

OBJECTIVES: Pseudomonas aeruginosa is a major causative agent of hospital infections. The purpose of this study was to determine the antibiotic susceptibility of P. aeruginosa in a French multicentre study and to investigate the mechanisms of beta-lactam resistance. METHODS: Four hundred and fifty non-repetitive strains of P. aeruginosa were collected in 15 French university hospitals in 2004. MICs of antibiotics were measured by agar dilution methods. For all the strains with MICs of ticarcillin >16 mg/L, detection and identification of the beta-lactamases, quantitative determination of cephalosporinase and overproduction of the MexAB-OprM efflux pump were evaluated. RESULTS: The percentages of susceptible isolates were as follows: ticarcillin, 62%; ticarcillin + clavulanic acid, 61%; piperacillin, 78%; piperacillin + tazobactam, 80% (MICs 相似文献   

铜绿假单胞菌医院感染现状及分子流行病学研究

目的总结本地区2010年1月-2011年12月共6400份临床细菌标本的培养及药敏结果,了解铜绿假单胞菌医院感染现状;建立随机扩增多态性DNA(RAPD)基因分型方法检测铜绿假单胞菌,调查铜绿假单胞菌医院感染流行病学的情况,为控制院内感染提供直接可靠的参考依据。方法对2010年至2011分离的240株铜绿假单胞菌进行统计分析及其临床分布;采用PAPD基因分型方法进行分析。结果 240株标本主要来自ICU,呼吸内科,普外科等;铜绿假单胞菌感染标本分布依次为:痰标本占72.5%,伤口分泌物标本占15.0%、中段尿占10.0%,其它类型标本占2.5%;240株铜绿假单胞菌的多重耐药情况非常严重,对亚胺培南/美罗培南耐药率分别为32.0%和35.0%,对其它大多数抗菌药物的耐药率为70%以上;240株PA用RAPD分型共分为7种类型:A-G。结论分离的铜绿假单胞菌多具有多重耐药性;本地区铜绿假单胞菌分为7个基因型,其中主要以A、B 2型为主,表明本地区医院感染铜绿假单胞菌可能存在院内的克隆传播。     

某老年病医院2013-2016年铜绿假单胞菌临床分布及耐药性分析

目的了解2013-2016年某老年病医院铜绿假单胞菌临床分布及耐药性变化趋势,为临床合理使用抗菌药物及医院感染控制提供依据。方法采用回顾性分析,对2013-2016年该医院铜绿假单胞菌临床分离株进行标本来源、科室分布和耐药性分析。结果 4年共分离细菌11 188株,其中铜绿假单胞菌2 548株(分离率22.77%);标本来源主要为痰(2 202株,86.43%)、尿液(214株,8.40%);获得分离株较多的科室有呼吸内科(822株,32.26%)、重症监护室(713株,27.98%)、神经内科(423株,16.60%);药敏分析表明,耐药率<30%的有阿米卡星、头孢哌酮/舒巴坦、哌拉西林、头孢吡肟、头孢他啶、环丙沙星、左氧氟沙星;对亚胺培南和美罗培南的耐药率分别为46.21%和43.74%;对头孢曲松和头孢噻肟耐药率高达97.68%、99.35%。结论该院铜绿假单胞菌4年检出率位居所有检出革兰阴性菌的首位;分离菌主要来源于痰标本,科室分布主要在呼吸内科、重症监护室和神经内科;对碳青霉烯类耐药率较高,应促进抗菌药物合理使用,控制院内感染和传播。     

某医院临床分离铜绿假单胞菌的分布及耐药性研究

目的 研究临床分离的铜绿假单胞菌感染分布及其耐药性,为临床医师合理使用抗菌药物提供参考。 方法 采用细菌分离鉴定技术和药敏试验方法,对某医院住院及门诊患者送检的病原学标本进行细菌检测与评价。 结果 从该医院临床送检标本中共分离出铜绿假单胞菌 506株,主要分离自痰液、分泌物和尿液标本,构成比依次为68.8%、11.7%和9.1%。送检标本数量居前3位的科室分别是重症监护病房、呼吸内科和脑外科,构成比依次为24.3%、22.7%和15.0%。临床分离的铜绿假单胞菌对所试验的14种抗菌药物全部产生不同程度耐药,耐药率最低的是妥布霉素、阿米卡星和庆大霉素。 结论 该医院临床分离出的铜绿假单胞主要为呼吸道感染,对临床常用抗菌药物均不同程度耐药,应加强耐药菌监测和抗菌药物管理。     

2162株铜绿假单胞菌医院感染的临床分布及耐药性分析

目的了解成都大学附属医院近3年铜绿假单胞菌的分布及对各种抗菌药物的耐药性,为临床合理使用抗生素提供指导。方法回顾性分析2011年1月至2013年12月住院患者送检标本所分离的铜绿假单胞菌的耐药率,使用WHONET 5.5软件进行耐药性分析。结果分离的2162株铜绿假单胞菌中有1583株来自呼吸道,占73.22%;主要分布在ICU、呼吸内科,分别占27.80%和20.58%;铜绿假单胞菌对头孢噻肟和头孢曲松耐药率最高,分别为67.30%和62.12%;对头孢哌酮/舒巴坦耐药率最低,为18.59%。对碳青霉烯类亚胺培南耐药率为32.10%,其中292株为多药耐药铜绿假单胞菌(MDRPA),检出率为13.51%,119株为泛耐药铜绿假单胞菌,检出率为5.50%。结论铜绿假单胞菌感染以ICU和呼吸内科为主,应对铜绿假单胞菌的耐药性进行重点监测,以便更好地控制铜绿假单胞菌的感染,为临床合理使用抗菌药物提供科学依据。     

Rapid nighttime evacuation of a veterans hospital

Loss of essential utilities and danger of explosion forced a rapid nighttime winter evacuation of 229 patients from an acute-care Veterans Administration hospital. Although distribution of patients to recipient hospitals was not optimal, and the location of several patients could not be documented for more than 24 hours, the evacuation in subfreezing weather went smoothly. Continuity of care and careful planning permitted an orderly return to the hospital five days later. Although financial costs were high, no excess mortality or morbidity was associated with the evacuation. No changes in pharyngeal gram-negative bacterial flora of the patients were noted. Further, a critique is presented to aid in planning for similar emergencies elsewhere.     

铜绿假单胞菌耐药基因分子流行病学调查

目的了解云南省昆明某医院临床铜绿假单胞菌分离株耐药特征及耐药基因分子流行病学特征,为临床治疗与控制院内感染提供依据。方法 2013年6 9月共收集全院不同病区感染患者28株铜绿假单胞菌。微生物自动分析仪鉴定菌株及耐药分析。PCR扩增及序列分析β-内酰胺酶bla基因、氟喹诺酮类及氨基糖苷类耐药基因及IS插入元件及整合子。脉冲场凝胶电泳(pulsed field gel electrophoresis,PFGE)分析菌株间遗传变异关系。结果全部菌株呈现多重耐药且存在有广泛耐药性(extensively drug-resistant,XDR)及泛耐药性(pendrug-resistant,PDR)菌。100%(28/28)菌株对一代/二代及大部分三代/四代头孢霉素、磺胺类及叶酸代谢途径抑制剂耐药。85.7%(24/28)菌株对碳青霉烯类抗生素美罗培南(MEM)、亚胺培南(IMP)耐药,50.0%(14/28)菌株对厄他培南(ETP)耐药。92.9%(26/28)菌株同时携带β-内酰胺酶基因、氟喹诺酮类及氨基糖苷类耐药基因,且菌株间基因谱存在较大不同。blaFOX/qnr B/aac A4为主要耐药基因谱(21.4%,6/28)。57.1%(16/28)菌株携带int1整合酶基因,21.4%(6/28)菌株携带ISCR1插入元件,35.7%(10/28)菌株携带ISEcp1插入元件。PFGE显示14株菌株分为8个克隆群。结论本研究铜绿假单胞菌分离株存在较高耐药率,多种耐药基因存在不同克隆菌株中,提示耐药基因在菌株间及不同菌种间存在快速传播风险。     

bla(VIM-2) cassette-containing novel integrons in metallo-beta-lactamase-producing Pseudomonas aeruginosa and Pseudomonas putida isolates disseminated in a Korean hospital

We investigated the phenotypic and genetic properties of metallo-beta-lactamase-producing Pseudomonas isolates collected at a tertiary-care hospital in Korea since 1995. The prevalence of imipenem resistance among Pseudomonas aeruginosa isolates reached 16% in 1997, when 9% of the resistant organisms were found to produce VIM-2 beta-lactamase, a class B enzyme previously found only in P. aeruginosa isolates from Europe. VIM-2-producing isolates of Pseudomonas putida were also detected. Resistance was transferable from both these species to P. aeruginosa PAO4089Rp by filter mating, although the resistance determinant could not be found on any detectable plasmid. Serotyping showed that many of the VIM-2-producing P. aeruginosa isolates belonged to serotypes O:11 and O:12, and pulsed-field gel electrophoresis of XbaI-digested genomic DNA revealed that many had identical profiles, whereas the P. putida isolates were diverse. Sequencing showed that the bla(VIM-2) genes resided as cassettes in class 1 integrons. In contrast to previous VIM-encoding integrons, the integron sequenced from a P. aeruginosa isolate had bla(VIM) located downstream of a variant of aacA4. bla(VIM) also lay in a class 1 integron in a representative P. putida strain, but the organization of this integron was different from that sequenced from the P. aeruginosa strain. In conclusion, the metallo-beta-lactamase produced by these imipenem-resistant Pseudomonas isolates was VIM-2, and the accumulation of producers reflected clonal dissemination as well as horizontal spread. Strict measures are required in order to control a further spread of resistance.     

Prospective survey of beta-lactamases produced by ceftazidime- resistant Pseudomonas aeruginosa isolated in a French hospital in 2000

In 2000, at the Université d'Auvergne teaching hospital in Clermont-Ferrand, France, 44 (6.2%) strains of Pseudomonas aeruginosa were found to be resistant to ceftazidime. After genotyping, 34 strains were selected. Nine had an additional beta-lactamase: OXA-21 (n = 6), PSE-1 (CARB-2) (n = 2), or PER-1 (n = 1). Ceftazidime resistance was related solely to the overproduction of the cephalosporinase in 30 strains. Sequencing of five bla(AmpC) genes encoding cephalosporinases with different pIs showed 99% identity with the ampC gene of P. aeruginosa PAO1.