Impact of ceftazidime restriction on gram-negative bacterial resistance in an intensive care unit

The present study included three periods: (1) a 12-month prerestriction and control period in 2001; (2) a 12-month restriction period with reduced ceftazidime prescribing in favor of piperacillin-tazobactam (2002); (3) and a 24 month postrestriction period (2003–2004). Note that, for results, P represents the difference between 2002 and 2001; P′, the difference between 2003 and 2001; and P″, the difference between 2004 and 2001. No changes in hygiene practices were observed during these three periods. The purpose of this study was to assess the effect of reducing ceftazidime use in an intensive care unit (ICU) upon Gram-negative bacterial resistance, particularly as regards Pseudomonas aeruginosa. During the three periods of the study, patients were similar concerning age, Simplified Acute Physiology Score (SAPSII), the site of nosocomial infection, and the requirements for mechanical ventilation (75% in 2001, 76% in 2002, 74% in 2003, and 85% in 2004). The most commonly isolated pathogens were P. aeruginosa, Acinetobacter baumannii, and Enterobacteriaceae. The use of ceftazidime decreased significantly from 12.6% in 2001 to 9% in 2002, to 3% in 2003 (P′ = 0.0009), and 2.6% in 2004 (P″ = 0.0001) in favor of piperacillin-tazobactam (0% 2001 to 3.7% in 2003; P′ = 0.002; and 5% in 2004; P″ = 0.0001). Simultaneously, we observed a significant decrease in isolates of P. aeruginosa resistant to piperacillin-tazobactam (P = 0.03; P′ = 0.004; P″ = 0.009), and those resistant to imipenem in 2003 (P′ = 0.008). We also noted a significant decrease in A. baumannii isolates resistant to ceftazidime (P′ = 0.01; P″ = 0.0004) and those resistant to imipenem in both 2002 and 2004 (P = 0.03; P″ = 0.04), and a considerable decrease in isolates of Klebsiella pneumoniae producing expanded spectrum betalactamase (ESBL) in 2003 and 2004 (P′ = 0.04; P″ = 6.10⁻⁵). In contrast, we noted an increase in penicillinase-producing isolates of K. pneumoniae, from 6% in 2001 to 16% in 2002 (p = 0.01), 20% in 2003 (P′ = 0.001), and 32% in 2004 (P″ = 10⁻⁶). We concluded that restriction of ceftazidime use was demonstrated to be efficient in reducing antimicrobial resistance, especially to K. pneumoniae ESBL.     

亚胺培南/西司他丁与头孢他啶治疗中、重度细菌感染疗效费用分析比较研究

对我院４５例确诊为中、重度细菌感染住院患者进行了亚胺培南／西司他丁与头孢他啶疗效费用分析比较研究。结果表明：２组病例有效率、死亡率无显著性差异；头孢他啶组较亚胺培南／西司他丁组疗程明显延长。亚胺培南／西司他丁每日所需费用明显高于头孢他啶；治疗结束时，前者全部费用并未超过后者；全部住院费用无明显差异。作者认为：决定２种药物全部费用的因素，除与药物单价和每日费用有关，还与药物疗程密切相关。选用药物抗菌作用越强，用药时间即相应缩短，住院时间必然缩短；最终患者住院费用降低     

国产与进口头孢他啶治疗小儿细菌性下呼吸道感染的成本-效果分析

目的对国产与进口头孢他啶治疗小儿细菌性下呼吸道感染进行成本—效果分析。方法对我院2008年10月-2009年10月间患小儿细菌性下呼吸道感染且单用头孢他啶治疗的住院患者136例进行回顾性分析,根据药品不同产地将其分为A、B两组,A组给与头孢他啶（国产）60mg/（kg·d）,分2次静脉滴注;B组给与头孢他啶（进口）60mg/（kg·d）,分2次静脉滴注,两组疗程均为7d,分别计算两组病人治疗后的细菌清除率、不良反应发生率,两组的治疗有效率和总成本,计算成本-效果比。结果疗程结束后A、B两组的药物治疗成本分别为：A组236.4元、B组982.5元,组间比较存在显著性差异（P〈0.05）;治疗有效率分别为：91.30%、94.03%;A、B两组的细菌清除率分别为：86.36%、90.70%;两组不良反应发生率分别为：5.80%、2.99%,组间比较差异均无显著性（P〈0.05）;两组成本-效果比分别为：2.59、10.45。结论国产头孢他啶的成本-效果比优于进口头孢他啶,为较佳的治疗方案。     

头孢吡肟和头孢他啶治疗重症下呼吸道感染疗效比较

目的 比较头孢吡肟和头孢他啶治疗重症下呼吸道感染的疗效和安全性。方法 选取住院治疗的重症下呼吸道感染患者62例进行随机比较,头孢吡肟组28例4g/d,头孢他啶组３４例4g/d,疗程７－１０天,静脉注射。结果 两组临床疗效差异有显著性（Ｐ＜0.05),分别为89.3%及70.6%。细菌清除率分别为８５％及67.9％。人体外药敏试验上看,细菌对头孢吡肟敏感率优于头孢他啶,尤其是革兰氏阳性球菌。两组患者无皮疹及其它副作用。结论 在治疗重症下呼吸道感染患者中,头孢吡较头孢他啶更加安全有效,而且对于革兰氏阳性球菌感染者疗效明显优于头孢他啶,可作为首选经验性用药。     

A comparison of ceftazidime and aminoglycoside based regimens as empirical treatment in 1316 cases of suspected sepsis in the newborn

We report a prospective, non-blind, randomised, multicentre, parallel group, multinational investigation to compare ceftazidime to aminoglycoside based regimens as empirical treatment in 1316 cases of suspected sepsis in the newborn. In each of the 15 study centres either ceftazidime alone (CAZ) or ceftazidime + ampicillin (CAZ+AMP) was compared to an aminoglyocoside/ampicillin combination (AG+AMP). In all cases treatment was based on an intention to treat. Bacteria considered to be pathogenic were isolated from 176/1316 (13.4%) patients. The incidence of proven infection varied from 39% in a Yugoslav centre to 6% in a British centre; a further 489/1316 (37.1%) patients fulfilled the criteria for clinically suspected sepsis. A total of 210 bacterial isolates from 197 infection sites in 176 patients were considered to be clinically significant. The cure rate for evaluable patients with proven infection who were treated with CAZ+AMP (97%, 30/31) was significantly higher than that for the corresponding patients treated with AG+AMP (66%, 26/39), (P<0.002). The difference in cure rate between CAZ monotherapy (79%, 34/43) and AG+AMP (86%, 32/37) was not significant. Treatment failed in 28/150 (18.7%) evaluable patients. There were significantly fewer failures (P<0.001) with CAZ+AMP than with AG+AMP therapy. There were 55 staphylococcal infections. Treatment was successful in 16/19 evaluable patients treated with CAZ or CAZ+AMP and in 16/29 evaluable patients treated with AG+AMP. None of the study centres encountered problems with ceftazidime resistant bacteria. The cure rate for patients with only clinical and radiological evidence of sepsis was greater than 94% in all treatment groups. Of the study population 65 (4.9%) died, 15 deaths were attributed to infection, pathogenic bacteria were only isolated from 10. The mortality rate for infected babies was 5.7% compared to 4.8% for those without confirmed infection. All the deaths associated with infection were due to Gram-positive bacteria. This study suggests that the practice of continuing antibiotic therapy once pretreatment cultures are known to be negative should be seriously reconsidered. It is concluded that CAZ+AMP is superior to either AG+AMP or ceftazidime monotherapy for the treatment of infection in the newborn. Further studies are required to confirm these observations in neonates with proven infection.The ESPID Neonatal Sepsis Study Group: Recruitment >=50 patients included Prof. R. Dagan, Soroka Medical Centre, Beer-Sheva, Israel; Dr. I. Tessin, Hospital of Molndal, Molndal, Sweden; Dr. D. Harvey and Dr. J. de Louvois, Queen Charlotte's and Chelsea Hospital, London, UK; Dr. B. Trollfors and Dr. K. Thiringer, Ostra Sjukuset, Goteborg, Sweden; Dr. A. Valido, Maternidade, Dr. Alfredo Costa, Lisbon, Portugal; Dr. H. Baumer, Freedom Fields Hospital, Plymouth, UK: Prof. J. Brines and Dr. Diez, University of Valencia, Valencia, Spain; Dr. L. Benic, Dr. J. Kajfes Hospital, Zagreb, Yugoslavia; and Prof. J. Badoual, Hopital St. Vincent de Paul, Paris, France.Recruitment <50 patients included Prof. L. Corbeel, UZ Gasthuisberg, Leuven, Belgium; Prof. R. Roos, Univ.-Kinderklinik, Munich, FRG; Dr. D. Kafetzisa, University of Athens, Athens, Greece; Dr. S. Pedersen, Kolding Sykehus, Kolding, Denmark; and Prof. A. Columbo, Ospedali Riunuti di Bergamo, Bergamo, Italy.     

三种抗生素治疗严重烧伤感染的效果对比分析

目的 :比较头孢他啶、头孢哌酮 舒巴坦与亚胺培南 西拉司丁 3种抗生素治疗严重烧伤感染的效果。方法 :选择严重烧伤患者90例 ,随机分为头孢他啶、头孢哌酮 舒巴坦和亚胺培南 西拉司丁 3组 ,每组各 3 0例。头孢他啶和头孢哌酮 舒巴坦组均为每次 1g ,静脉滴注 ,每日 3次 ,疗程 4～ 6天 ;亚胺培南 西拉司丁组每次 0 5g ,静脉滴注 ,每日 3次 ,疗程 4～ 6天。所有患者创面均做分泌物细菌培养、菌种鉴定和药敏试验。结果 :头孢他啶、头孢哌酮 舒巴坦及亚胺培南 西拉司丁组有效率分别为 60 0 %、73 3 %及93 3 % ;共培养细菌 2 0 0株 ,其中以铜绿假单胞菌 ( 3 0 5 % )和金黄色葡萄球菌 ( 2 2 0 % )最为常见。所有革兰阴性杆菌对头孢他啶、头孢哌酮 舒巴坦和亚胺培南 西拉司丁的敏感率分别为 69 0 %、76 0 %与 94 0 % ,所有革兰阳性球菌对头孢他啶、头孢哌酮 舒巴坦和亚胺培南 西拉司丁的敏感率分别为 68 0 %、70 0 %与 94 0 %。结论 :严重烧伤感染患者选择亚胺培南 西拉司丁的治疗效果优于头孢他啶和头孢哌酮 舒巴坦 ,亚胺培南 西拉司丁可作为治疗严重烧伤感染的首选药物     

头孢他啶联合氨溴索治疗小儿支原体肺炎的临床疗效

目的：探讨头孢他啶（复达欣）联合氨溴索（沐舒坦）治疗小儿支原体肺炎的临床效果。方法将在本院进行治疗的反复呼吸道感染的小儿患者随机分为对照组和治疗组，对照组采用氨溴索进行治疗，治疗组在对照组的基础上采用头孢他啶进行治疗，比较两组患者的临床疗效。结果治疗组的临床疗效明显优于对照组。结论头孢他啶联合氨溴索治疗小儿支原体肺炎，具有较好的临床效果，值得在临床上推广使用。     

Infections by multidrug-resistant Gram-negative Bacteria: What's new in our arsenal and what's in the pipeline?

The spread of multidrug-resistant bacteria is an ever-growing concern, particularly among Gram-negative bacteria because of their intrinsic resistance and how quickly they acquire and spread new resistance mechanisms. Treating infections caused by Gram-negative bacteria is a challenge for medical practitioners and increases patient mortality and cost of care globally. This vulnerability, along with strategies to tackle antimicrobial resistance development, prompts the development of new antibiotic agents and exploration of alternative treatment options. This article summarises the new antibiotics that have recently been approved for Gram-negative bacterial infections, looks down the pipeline at promising agents currently in phase I, II, or III clinical trials, and introduces new alternative avenues that show potential in combating multidrug-resistant Gram-negative bacteria.     

A model-based analysis of pharmacokinetic–pharmacodynamic (PK/PD) indices of avibactam against Pseudomonas aeruginosa

ObjectiveThe aim of the present work was to use a semi-mechanistic pharmacokinetic–pharmacodynamic (PK/PD) model developed from in vitro time–kill measurements with P. aeruginosa to compare different pharmacodynamic indices derived from simulated human avibactam exposures, with respect to their degree of correlation with the modelled bacterial responses.MethodsA mathematical model of the effect of ceftazidime–avibactam on the growth dynamics of P. aeruginosa was used to simulate bacterial responses to modelled human exposures from fractionated avibactam dosing regimens with a fixed ceftazidime dosing regimen (2 or 8 g q8h as a 2-h infusion). The relatedness of the 24-h change in bacterial density and avibactam exposure parameters was evaluated to determine exposure parameter that closely correlated with bacterial growth/killing responses.ResultsFrequent dosing was associated with higher efficacy, resulting in a reduction of avibactam daily dose. The best-fit PD index of avibactam determined from the simulation was fT > C_T of 1 mg/L avibactam and q8h was the longest dosing interval able to achieve 2-log kill: 41–87% (3.3 h to 7.0 h out of 8-h interval, respectively). The avibactam exposure magnitude required to achieve a 2-log kill in the simulations was dependent on the susceptibility of the bacterial isolate to ceftazidime.ConclusionsAvibactam activity in combination with ceftazidime against multidrug resistant P. aeruginosa correlated with fT > C_T. Setting a threshold avibactam concentration to 1 mg/L, superimposed over a simulated human-like exposure of ceftazidime, achieved at least 2-log kill for the clinical dose of 500 mg q8h avibactam as a 2-h infusion, depending on the minimum inhibitory concentration of ceftazidime alone.     

头孢类抗菌药物联合阿米卡星治疗白血病感染患者的疗效

目的探讨头孢类抗菌药物联合阿米卡星在治疗白血病患者化疗后粒细胞缺乏合并感染中的疗效,以提高临床诊治水平。方法选取2013年3月-2014年3月于医院接受治疗的白血病化疗后粒细胞缺乏合并感染患者92例,随机分为观察组与对照组,各46例,其中对照组给予头孢他啶联合阿米卡星治疗,观察组给予头孢吡肟联合阿米卡星治疗,对比分析两组的临床疗效。结果头孢他啶联合阿米卡星治疗后临床有效率80.43%,头孢吡肟联合阿米卡星治疗后临床有效率82.61%,两组比较差异无统计学意义;患者发生上呼吸道及肺部感染较为常见,两组感染部位比较差异无统计学意义;患者年龄(≥60岁或<60岁)、白血病治疗后缓解指标(完全缓解/部分缓解或无效)、粒细胞缺乏持续时间(≥10d或<10d)与疾病预后存在相关性(P<0.05)。结论头孢他啶联合阿米卡星与头孢吡肟联合阿米卡星治疗白血病化疗后粒细胞缺乏合并感染的临床有效率相当,且安全可靠,值得临床推广应用。