某院1998—2010年两种非发酵菌耐药率情况及与抗生素使用相关性分析

目的研究1998—2010年铜绿假单胞菌、鲍曼不动杆菌两种非发酵菌耐药性水平变化情况,以及耐药率与抗生素使用之间的相关关系。方法回顾性调查1998—2010年本院铜绿假单胞菌、鲍曼不动杆菌两种非发酵菌分离及耐药情况,同时调查同期抗生素的使用消耗情况,采用世界卫生组织(WHO)推荐的限定日剂量(DDD)法分析抗生素的用药频度(DDDs),用SPSS13.0统计软件统计抗生素使用与细菌耐药之间的相关分析。结果铜绿假单胞菌对丁胺卡那、头孢他啶较敏感,耐药率在20%左右,对其他抗生素的耐药率都超过了30%。鲍曼不动杆菌对亚胺培南、美洛培南耐药率上升较快,到2010年接近40%,耐药率较低的为头孢哌酮舒巴坦,但也超过了30%。统计结果显示亚胺培南、氨曲南的使用DDDs与铜绿假单胞菌的耐药率呈正相关;亚胺培南、美洛培南、头孢哌酮/舒巴坦、哌拉西林/他唑巴坦的使用DDDs与鲍曼不动杆菌的耐药率呈正相关。铜绿假单胞菌与不同类抗生素累计DDDs之间相关性统计显示头孢类抗生素的使用与头孢哌酮、氨曲南及亚胺培南的耐药率之间,复方制剂的使用与环丙沙星、左氧氟沙星的耐药率之间,碳青霉素类抗生素的使用与头孢哌酮、氨曲南及亚胺培南的耐药率之间呈正相关关系。鲍曼不动杆菌耐药率与不同类抗生素累计DDDs之间相关性统计显示,头孢类抗生素的使用与亚胺培南、头孢噻肟及哌拉西林钠他唑巴坦的耐药率之间,复方制剂的使用对头孢他啶、环丙沙星及头孢哌酮/舒巴坦耐药率之间,碳青霉烯类抗生素的使用对亚胺培南、美洛培南、头孢噻肟及哌拉西林/他唑巴坦耐药率之间呈正相关。结论抗菌药物的使用对两种非发酵菌造成了很大压力,耐药现象严重。     

2008～2013年ICU中非发酵菌属感染及药物敏感情况研究

目的分析本院2008~2013年重症监护室(ICU)中非发酵菌分布和药物敏感情况。方法回顾性分析本院ICU 2008~2013年非发酵菌属感染菌株分布和药敏试验结果。结果共检出非发酵菌1366株,占39.98%,前3位分别是铜绿假单胞菌(Pseudomonas aeruginosa)、鲍曼不动杆菌(Acinetobacter baumanni)、嗜麦芽寡养单胞菌(Stenotrop homnasmaltophilia);铜绿假单胞菌对美罗培南、头孢吡肟的耐药率较低,对复方新诺明、氨苄西林/舒巴坦的耐药率较高;鲍曼不动杆菌对亚胺培南、美罗培南耐药率较低,对庆大霉素、氨曲南、头孢哌酮耐药率较高;嗜麦芽寡养单胞菌对环丙沙星耐药率较低,对庆大霉素、氨曲南、亚胺培南、美罗培南耐药率均较高。结论铜绿假单胞菌、鲍曼不动杆菌等是主要的非发酵菌,且对大部分抗菌药敏感性较低,应结合药敏试验结果选取敏感性较高抗菌药物,并加强致病菌耐药性监测。     

老年下呼吸道感染患者铜绿假单胞菌120例临床检测与耐药性调查分析

目的 探讨老年下呼吸道感染患者铜绿假单胞菌120例临床检测结果,对耐药性调查结果进行分析.方法 选取本院自2010年12月～2012年12月收治的120例老年下呼吸道感染患者的痰标本进行分析,培养出120株铜绿假单胞菌菌株,同时进行体外药敏试验,观察其耐药性.结果 铜绿假单胞菌对多种抗生素药物均有耐药性,其中对庆大霉素、氨苄西林、舒巴坦、环丙沙星、妥布霉素药物的耐药率超出40％,对氨曲南、亚胺培南敏感性较好,耐药率分别为16.7％、15％、β-内酰胺酶阳性菌对庆大霉素、妥布霉素、氨苄西林/舒巴坦、哌拉西林、环丙沙星100％耐药,对阿米卡星、头孢吡肟、他唑巴坦/哌拉西林的耐药性均在70％以上,对氨曲南、亚胺培南敏感性较好,耐药性约为11.7％、15.8％.结论 氨曲南及亚胺培南抑制铜绿假单胞菌作用较强,在老年下呼吸道感染铜绿假单胞菌治疗中能够作为首选药物使用.     

铜绿假单胞菌的分离与耐药性分析

目的了解我院临床感染患者铜绿假单胞菌耐药谱的变化,指导临床合理用药.方法应用回顾性调查方法对临床感染患者两年送检标本分离的135株铜绿假单胞菌药敏试验进行统计分析.结果从ICU病房和呼吸科患者送检标本分离出铜绿假单胞菌比例最高,占84.5%.铜绿假单胞菌对亚胺培南/西司他丁、环丙沙星、头胞他啶、阿米卡星、氨曲南、哌拉西林的敏感率在70%左右;对复方磺胺的敏感率最低,在10%左右.铜绿假单胞菌对常用的10种抗生素的耐药性呈上升趋势.结论铜绿假单胞菌耐药现象严重,临床应注意铜绿假单胞菌耐药性的监测.     

重症监护病房院内感染致病菌及其耐药性研究

目的:分析重症监护病房常见致病菌及其耐药性。方法:收集某大型三甲医院2005年重症监护病房院内感染致病菌,药敏测定采用CLSI所提供的标准K-B法及其判读标准。结果:该医院重症监护病房2005年共分离致病菌300株,铜绿假单胞菌、不动杆菌属占41.00%和15.33%,金黄色葡萄球菌、凝固酶阴性葡萄球菌分别占7%～9%。铜绿假单胞菌对亚胺培南、美罗培南的耐药率为65%,不动杆菌属对青霉素类、头孢菌素类、氨基糖苷类、氟喹诺酮类的耐药率超过50%,甲氧西林耐药金黄色葡萄球菌分离率达95.65%,同时对大环内酯类、氨基糖苷类、氟喹诺酮类以及四环素高度耐药。结论:重症监护病房的主要致病菌为铜绿假单胞菌、不动杆菌属、葡萄球菌属,均存在严重的多重耐药现象。     

2010-2012年我院铜绿假单胞菌的耐药性分析

目的：分析2010年1月-2012年12月该院分离的铜绿假单胞菌耐药性与耐药趋势。方法采用法国生物梅里埃公司 Vitek 32细菌分析系统进行菌株鉴定及药物敏感性测试，耐药性数据分析采用 wHONET5软件。结果3年内共检出铜绿假单胞菌536株，其对12种抗菌药物活性较好的是阿米卡星、头孢哌酮舒巴坦、亚胺培南、美罗培南，耐药率为17.16%、19.96%、27.99%、29.85%；耐药率较高的是氨曲南61.19%、头孢噻肟76.31%、头孢曲松84.51%。其对氨曲南的耐药率从2010年55.71%升至2012年66.97%，同期对头孢噻肟的耐药率从71.42%升至81.45%，对头孢曲松的耐药率从78.57%升至97.74%，升幅分别为11.26%、10.03%、19.17%。美罗培南的耐药率有下降趋势，从2010年43.57%下降至2012年16.74%。结论监测结果显示铜绿假单胞菌对氨基糖苷类、碳青霉烯类、β-内酰胺酶抑制剂复合药物保持较好的敏感性，对三代头孢的敏感性较差，还需加强对铜绿假单胞菌耐药率有计划地连续监测。     

氟喹诺酮等抗菌药对我院常见菌株耐药情况分析

目的:了解我院2003年11月～2004年4月分离的细菌菌株对氟喹诺酮等抗菌药物的耐药情况.方法:药物药敏性试验采用纸片扩散法.结果:铜绿假单胞菌、鲍曼不动杆菌和大肠埃希菌是我院常见菌株.铜绿假单胞菌对氟喹诺酮类药物、阿米卡星、氨曲南敏感性较高;鲍曼不动杆菌对阿米卡星、左氧氟沙星敏感性较高;大肠埃希菌对阿米卡星、左氧氟沙星、氨曲南敏感性较高.结论:了解我院常见感染的病原学特点和耐药状况,对有效控制感染,降低患者死亡率具有重要意义.     

我院铜绿假单胞菌的临床分布及耐药性分析

目的 了解我院铜绿假单胞菌感染的临床分布及耐药性分析,为抗菌药物使用及干预措施提供参考依据.方法 收集2011年1月~2014年12月医院共3641株铜绿假单胞菌,对其进行分离鉴定和药敏试验,对其标本来源、科室分布、常用抗菌药物的耐药率监测以及感染患者年龄进行分析统计.结果 3641株铜绿假单胞菌主要分离自唾液标本占70.5%;对PAE感染分布情况进行分析,结果 显示铜绿假单胞菌感染在重症医学科占85.0%,其次,呼吸内科占67.4%.根据药敏结果 显示:复方新诺明耐药率高,连年来耐药率平均值达91.7%,其次为米诺环素近年来出现快速增长且幅度高.而妥布霉素、阿米卡星则一直处于低耐药水平,敏感率最好;头孢他啶、氨曲南、亚胺培南耐药性有小幅度上升趋势.环丙沙星、左氧氟沙星耐药率也较低,并且呈现有下降趋势.哌拉西林、哌拉西林他唑巴耐药性保持基本平稳,敏感率较好.头孢哌酮、氨曲南近年来出现较小波动,总体来看差异不大.感染患者年龄来看,60岁以上的老年患者最易感染,其占总体的59.3%.结论 铜绿假单胞菌的易感染人群为危重的老年患者,呼吸道为铜绿假单胞菌最常见的感染部位,铜绿假单胞菌临床耐药总体不错,还需做好耐药性检测,加强院内感染的控制和合理使用抗菌药物具有十分重要的意义.     

2007—2011年铜绿假单胞菌的构成比及耐药变迁

目的比较2007~2011年间铜绿假单胞菌分离情况及其耐药性变化趋势。方法细菌菌株采集自2007年1月—2011年12月,对分离出的菌株用VITEK-Compoct2全自动微生物鉴定系统进行鉴定,药敏试验采用琼脂扩散法进行。并根据美国国家临床实验标准委员会(CLSI 2011)指定的指导原则,判定细菌耐药率。采用回顾性分析、目标性监测进行耐药变迁分析。结果在2007~2011年间,铜绿假单胞菌在临床菌株中的构成比每年呈上升趋势。对于头孢他啶和氨曲南,其敏感率由2007年的80.9%和54.9%分别降至2011年的54.2%和34.4%,头孢哌酮/舒巴坦由77.7%降至47.3%,而亚胺培南和美罗培南,也由82.3%和89.6%分别降至57.0%和57.9%。但哌拉西林/三唑巴坦例外,其敏感率始终维持在50%左右而没有明显下降,铜绿假单胞菌对三代、四代头孢菌素、氨曲南、头孢哌酮/舒巴坦和碳青酶烯类抗生素的敏感率每年均在下降,且对环丙沙星的敏感率也在下降,而哌拉西林/三唑巴坦和阿米卡星的敏感率下降不明显。结论铜绿假单胞菌的构成比例在逐年增加,同时铜绿假单胞菌对常用抗生素的耐药率也在逐年上升,这与细菌产生多种β-内酰胺酶及整合子可介导耐药基因横向播散相关,对控制铜绿假单胞菌在院内流行要施实持续性监控,根据本院耐药变迁合理选择抗菌药物,及时有效地切断耐药菌株的传播,防止出现严重的医院感染具有重要作用。     

2007—2010年肿瘤患者感染铜绿假单胞菌分离株耐药变迁的研究

目的了解我院4年间铜绿假单胞菌在肿瘤患者中感染和耐药变迁,为临床治疗提供依据。方法分析2007-2010年检出的692株铜绿假单胞菌对12种抗生素的耐药性,采用K-B纸片扩散法结合VITEK II MIC法进行药敏试验,按美国临床实验室标准化委员会(CLSI)标准判断结果。结果近4年分离出铜绿假单胞菌菌株数不断上升,痰标本分离率最高(62.46%),其次是分泌物、引流液分别为13.86%、8.10%。对12种抗菌药物的药敏结果显示:氨曲南耐药率最高,每年耐药率均超过30%。环丙沙星、左氧氟沙星、哌拉西林耐药率相对稳定,而亚胺培南、美洛培南、头孢他啶、头孢吡肟、妥布霉素、庆大霉素耐药率呈上升趋势。结论铜绿假单胞菌是引起医院感染的重要病原菌之一,应合理使用抗菌药物,加强医院感染管理,避免交叉感染。     

氨曲南的合成

目的：以L-苏氨酸为起始原料，经N-Boc保护合成氨曲南。方法：以三．苏氨酸为原料，经酯化、氨解、氨基保护、保护羟基、磺化、环合、脱保护7步反应，制得氨曲南主环，并最终合成氨曲南。结果和结论：目标化合物经核磁共振氢谱确证其化学结构，收率60．4％（以氨曲南主环计）。该法工艺简单，反应效率提高。     

Clinical pharmacokinetics of aztreonam

Aztreonam (azthreonam) is practically completely absorbed after intramuscular injection. After intravenous injection plasma concentrations follow a 2-compartment open model, with a t1/2 alpha of 0.20 hours. Volume of distribution at steady-state (Vdss) after intravenous or intramuscular injection is about 0.16 L/kg (0.42 L/kg for the free drug). After oral administration less than 1% of the drug is absorbed. Over a large dosage range plasma concentrations increase linearly with dose. No accumulation occurs after multiple dosing. Plasma binding in healthy subjects is about 56% and is not concentration dependent. Diffusion into tissues is generally slow, and the ratio between mean tissue and plasma concentration seems to depend mainly on the composition of the tissue. In inflamed meninges, penetration of aztreonam into CSF is more rapid than with uninflamed meninges. Diffusion through the placenta is poor, as is diffusion into breast milk. The main route of elimination of aztreonam is by the kidney, partly by active tubular excretion, but this can be inhibited by probenecid. Extrarenal clearance is probably due to excretion by the liver. Metabolism occurs to a very limited extent. Total plasma clearance in healthy adults is about 140 ml/min (8.4 L/h) or 2 ml/min/kg (0.12 L/h/kg), and terminal half-life is 1.7 hours. In children clearance is similar to that in adults when expressed as a function of bodyweight, but in neonates, especially in low birthweight infants, it is less [about 1 ml/min/kg (0.06 L/h/kg)]. In various disease states the Vdss of aztreonam is not appreciably different from that found in healthy individuals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Stability of aztreonam in AZACTAM

The influence of temperature and relative humidity on the stability of aztreonam in AZACTAM was investigated. Changes of the concentration of aztreonam were followed using the HPLC method with UV detection. The first-order rate constants of the reversible reaction of isomerization Z-aztreonam right harpoon over left harpoonE-aztreonam and the parallel reaction Z-aztreonam-->products were determined at RH=76.4% and T=313, 323, 333, 343 and 353 K, and at T=343 K and RH=50.9%, 60.5%, 66.5% and 76.4%. The thermodynamic parameters-energy, enthalpy and entropy of these reactions were calculated.     

Clinical experience on aztreonam

Aztreonam (AZT), a new monobactam antibiotic, was studied for clinical efficacy in the field of gynecologic infection. AZT was administered at a daily dose of 2 g in 2 divided doses by single shot intravenous injection. The subjects were patients with the following infections: adnexitis (6), pelvic peritonitis (5), endometritis (1) and wound abscess (1). Good response was seen in 10 patients out of 13. The overall efficacy rate of 76.9% was obtained. Slight increase in GOT, GPT and Al-P was seen in 1 case. It was normalized on 6th day after completion of the therapy. No notable side effects were observed.     

Pharmacokinetics of aztreonam on hemodialysis

We studied the pharmacokinetics of aztreonam (AZT) in 6 patients with renal insufficiencies during nonhemodialysis and hemodialysis. After intravenous injection of 1 g AZT, it was found that serum AZT concentrations during hemodialysis were different from those during nonhemodialysis and serum half-lives (T 1/2 beta) were 3.44 hours and 16.97 hours, respectively. AZT clearance changed from 0.762 L/hr during hemodialysis to 3.360 L/hr during nonhemodialysis. These findings suggest that hemodialysis patients should receive the standard dose of AZT as a loading dose, followed by one-half the loading dose per day and receive a supplemental dose equal to half their usual maintenance dose after each dialysis session.     

Studies of aztreonam in neonates

Absorption and excretion of aztreonam (AZT) in neonates were studied and its clinical evaluation in 10 cases of neonates was performed using 1 hour intravenous drip infusion. 1. Serum concentrations of AZT in 7 neonates younger than 11 days of age were lower than those in infants. 2. Serum concentrations of AZT in 5 neonates given 20 mg/kg reached their peaks at the end of intravenous drip infusion with an average value of 45.8 +/- 10.41 micrograms/ml, and T 1/2 was 2.77 +/- 0.32 hours on the average. 3. Serum concentrations of AZT in 2 neonates given AZT 25 mg/kg reached their peaks at the end of intravenous drip infusion at 31.1 and 33.4 micrograms/ml with little difference from the 20 mg/kg group. Half-lives of serum AZT in the 2 cases were 1.87 hours and 3.23 hours, respectively. 4. Urinary excretion rates of AZT in 7 neonates younger than 11 days of age in the first 6 to 8 hours after the administration were 18.8 to 50.0%, or 31.7% on the average, which was lower than the average excretion rate found with infants. 5. All the cases given AZT showed clinical results rated better than "effective". Effect of AZT was excellent on 3 UTI cases caused by Escherichia coli and Klebsiella pneumoniae, but bacterial replacement (superinfection) of Enterococcus faecalis was observed when AZT was administered. 6. Transient elevations of GOT and GPT were seen in 2 cases when AZT administration was continued at length. Clinical side effect was not observed. 7. The most appropriate dosage and administration scheme of AZT against Gram-negative infections in neonates seems to be 40-60 mg/kg/day, b.i.d. or t.i.d.     

Susceptibility of clinical isolates to aztreonam

In vitro antibacterial activities of 9 antibiotics including aztreonam (AZT) against clinically isolated Gram-negative bacteria were determined using MIC-2000 plus system. Bacteria were isolated from clinical materials in Saga Medical School during a period from May 1987 to March 1988. Summarized results were as follows: 1. AZT showed excellent antibacterial activities against Escherichia coli, Klebsiella pneumoniae, Proteus sp. and Haemophilus influenzae, and MIC80 values of AZT against these organisms were lower than 0.20 microgram/ml. 2. Antibacterial activities of AZT were superior to cephem antibiotics compared against Enterobacter aerogenes, Enterobacter cloacae, Citrobacter freundii and Serratia marcescens. 3. The MIC50 and MIC80 of AZT against Pseudomonas aeruginosa were 12.5 micrograms/ml and 25 micrograms/ml, respectively. 4. AZT did not show any antibacterial activity against Acinetobacter sp. and Xanthomonas maltophilia.     

Clinical evaluation of aztreonam in children

Clinical usage of aztreonam (AZT), a newly synthesized antibiotic which belongs to monobactam, was evaluated for its efficacy and safety in 22 patients aged from 1 month-old to 13 year-5 month-old with bacterial infections and the following results were obtained. AZT was administered to 4 patients with pyelonephritis and 10 patients with tonsillitis at a daily dosage of 40.4-120.9 mg/kg and to 5 patients with clinical sepsis associated with agranulocytosis caused by intensive antileukemic therapy at a daily dosage of 142.4-171.4 mg/kg, divided into 3 or 4, by intravenous injection or by 30 minutes drip infusion. The clinical results of these 19 evaluable patients were as follows: excellent; 10 cases, good; 5 cases, fair; 2 cases, poor; 2 cases. The over all efficacy rate was 78.9% and that of pyelonephritis and tonsillitis was 100.0%. No clinical side effects were observed in any 23 patients, including a patient who proved to be suffering from Mycoplasma pneumoniae infection, and no abnormal laboratory findings caused by AZT was noticed. The MICs of AZT against 9 strains isolated from patients with pyelonephritis and those with tonsillitis were as follows: MICs against all of 3 strains of K. pneumoniae were less than 0.05 microgram/ml. MICs against 2 out of 4 strains of H. influenzae were less than 0.05 microgram/ml and those of the remaining 2 strains were 0.10 microgram/ml. MIC against 1 strain of S. aureus was 1.56 microgram/ml. MIC against 1 strain of S. epidermidis was more than 100 micrograms/ml.(ABSTRACT TRUNCATED AT 250 WORDS)     

Susceptibility of clinical isolates to aztreonam

Aztreonam (AZT), which has a newly developed and synthetic structure belonging to the group of monobactams, possesses excellent antibacterial activity against a broad range of Gram-negative bacteria (including the beta-lactamase producing strains). Antibacterial activities of AZT were examined and compared with those of 5 antibiotics (cefoperazone (CPZ), latamoxef (LMOX), cefotaxime (CTX), cefmetazole (CMZ) and cefsulodin (CFS) against 296 strains of clinical isolates. The evaluation of antibacterial activities was determined with the inhibition zone diameter obtained by the single disc method. The results can be summarized by three categories as follows: 1. Susceptibility of clinical isolates to AZT and other antibiotics AZT and other 3rd-generation antibiotics (CPZ, LMOX, CTX) showed excellent antibacterial activities against most strains. Especially AZT was more active against Enterobacter cloacae and Serratia marcescens than reference drugs. Against Pseudomonas aeruginosa, the activity of AZT was similar to that of CFS. AZT showed as excellent activity against P. aeruginosa as CFS. 2. Susceptibility of strains isolated from different clinical materials and different clinics AZT showed the highest antibacterial activity against the clinical isolates from sputum, pharynx, urine, pus, bile, puncture fluid, blood and others. AZT exhibited the most potent activity against isolates in the 7 clinics we tested. 3. Susceptibility of strains isolated from inpatients and outpatients AZT demonstrated the highest antibacterial activity (the rate of susceptibility: 87.0%) against strains obtained from inpatients (except for P. aeruginosa). The activity of AZT (81.4%) against P. aeruginosa was as active as that of CFS (81.4%), and it was the highest in all drugs. Antibacterial activity of these antibiotics against bacteria was rated as follows: AZT greater than LMOX greater than CPZ greater than CTX greater than CMZ AZT showed the highest antibacterial activity (100%) against strains isolated in all the materials and at all the clinics tested of outpatients. Antibacterial activity of these antibiotics against isolates from outpatients was rated as follows: AZT greater than CPZ greater than LMOX greater than CTX greater than CMZ.