头孢吡肟联合阿米卡星治疗血液肿瘤粒缺期细菌性肺炎的疗效观察

目的：观察头孢吡肟联合阿米卡星治疗血液肿瘤粒缺期细菌性肺炎的疗效和不良反应。方法：120例入选患者随机分为治疗组和对照组,每组60例,分别接受头孢吡肟联合阿米卡星及头孢他啶联合阿米卡星治疗。其中,头孢吡肟或头孢他啶均为2g加入生理盐水100mL,每日2次,静脉点滴;阿米卡星0.4g,加入生理盐水500mL中,每日1次,静脉点滴,治疗持续一般1～2周。采用卫生部1993年抗菌药物临床研究指导原则进行判断疗效。结果：治疗组与对照组有效率分别为80%、76.7%,细菌清除率分别为91.9%、90.2%。两组比较差异无统计学意义（P〉0.05）。两组患者共分离出病原菌123株,药敏试验显示对头孢吡肟的敏感率为90.2%,显著高于头孢他啶69.7%,差异有统计学意义（P〈0.01）。不良反应主要有恶心及皮疹等,均可耐受。发生率分别为5%和11%,两组比较差异无统计学意义（P〉0.05）。结论：头孢吡肟联合阿米卡星治疗血液肿瘤粒缺期细菌性肺炎的疗效略优于头孢他啶组,体外抗菌活性显著优于头孢他啶组。     

头孢吡肟治疗重型脑外伤气管切开术后肺部感染的随机双盲对照临床研究

目的:探讨国产头孢吡肟治疗重型脑外伤气管切开术后肺部感染的疗效。方法:采用随机双盲平行对照研究方法,98例重型脑外伤气管切开术后肺部感染的患者随机分成两组,治疗组50例,给予头孢吡肟2.0 g加入生理盐水250 mL静脉滴注,1次/12 h;对照组48例,给予头孢他啶2.0 g加入生理盐水250 mL静脉滴注,1次/12 h,疗程均为7~10 d。结果:治疗组和对照组的痊愈率分别为48%和23%,有效率分别为84%和50%,细菌清除率分别为72%和48%;两组比较差异均有统计学意义(P<0.01);两组药物不良反应率分别是14%和13%,差异无统计学意义(P>0.05)。治疗组的疗效明显优于对照组,两组的药物不良反应相近。结论:头孢吡肟治疗重型脑外伤气管切开术后肺部感染安全有效。     

头孢吡肟治疗慢性阻塞性肺疾病下呼吸道感染的疗效观察

目的:观察头孢吡肟治疗慢性阻塞性肺疾病(慢阻肺)下呼吸道感染的临床疗效及安全性。方法:将65例慢阻肺伴下呼吸道感染患者随机分为两组,在常规治疗的基础上,治疗组32例,采用头孢吡肟2g,静脉滴注,每12 h1次;对照组33例,给予头孢他啶2g,静脉滴注,每12h1次,两组疗程均为7～14d。结果:头孢吡肟组治愈率为68.8％,有效率为90.6％,细菌清除率为91.2％;头孢他啶组治愈率为60.6％,有效率为87.9％,细菌清除率为90.3％,两组比较差异无显著性(P>0.05)。两组患者共分离出病原菌65株,药敏试验显示对头孢吡肟敏感率为89.2％,明显高于头孢他啶(78.5％)和头孢噻肟(7.4％,P<0.05)。结论:头孢哟肟的体外抗菌活性强于头孢他啶和头孢噻肟,其治疗慢阻肺伴下呼吸道感染疗效确切、使用安全。     

头孢吡肟治疗妇科细菌性感染的疗效观察评价

目的 评价头孢吡肟治疗妇科细菌性感染的疗效及安全性。方法 将235例妇科细菌性感染患者随机分为试验组118例,对照组117例,按照卫生部颁发的《抗菌药物临床研究指导原则》进行临床观察。对照组给予头孢他啶2.0g加入0.9%氯化钠注射液250 mL中静脉滴注,2次/d;试验组给予头孢吡肟2.0 g加入0.9%氯化钠注射液250 mL中静脉滴注,2次/d。2组疗程均为7~14 d。观察比较2组疗效及安全性。结果 试验组与对照组痊愈率分别为50.85%、37.61%;有效率分别为92.37%、79.49%;细菌清除率分别为90.83%、75.47%。2组比较差异均有统计学意义(P<0.01),临床研究中未发现试验药物的严重不良反应。结论 头孢吡肟治疗妇科细菌性感染安全、有效、疗效优于头孢他啶。     

国产头孢吡肟治疗急性细菌性下呼吸道感染的随机对照临床试验

目的评价国产头孢吡肟注射剂治疗急性细菌性下呼吸道感染的有效性与安全性。方法采用随机、单盲(患者)、阳性药物平行对照试验设计,试验组用国产头孢吡肟,对照组用进口头孢吡肟,用法均为中度感染2g/d,重度感染4g/d,分两次静滴,疗程7～10天。结果共入选31例,可评价疗效病例30例,每组各15例,试验组和对照组痊愈率分别为40.00%和26.67%,有效率分别为80.00%和86.67%;两组细菌清除率分别为92.31%和100%,药物不良反应发生率分别为12.5%和13.33%,两组比较均无显著差异(P>0.05)。结论国产头孢吡肟注射剂治疗急性细菌性下呼吸道感染疗效确切,不良反应较少。     

头孢吡肟治疗胸科术后重症肺部感染疗效分析

目的 观察头孢吡肟治疗胸科术后重症肺部感染的疗效及安全性。方法 19例胸科术后重症肺部感染患者采用头孢吡肟治疗。剂量1g，每8小时1次，静脉注射，疗程5～7天，结果 总有效率为89．4％，细菌阴转率为84．6％，细菌清除率为93．5％，无不良反应。3l株致病菌作药物敏感试验，头孢吡肟的敏感率为100％，与泰能抗菌活性相似，较头孢唑啉、头孢哌酮及环丙沙星的敏感率高。结论 头孢吡肟治疗胸科术后重症肺部感染安全、有效。     

急性白血病患者粒细胞缺乏时发热的经验治疗

目的：研究急性白血病患者粒细胞缺乏出现发热时，使用第三代头孢菌素头孢他啶加阿米卡星、碳青霉烯类抗生素亚胺培南或美罗培南治疗的临床疗效的比较。方法：应用回顾性分析方法，观察了106例急性白血病患者在造血干细胞移植预处理或化疗后粒细胞缺乏期出现发热时，对3种治疗方案的反应。结果：碳青霉烯类抗生素亚胺培南或美罗培南单药治疗中性粒细胞缺乏时严重感染的疗效较第三代头孢菌素头孢他啶加阿米卡星好。而美罗培南的不良反应较亚胺培南少。结论：碳青霉烯类抗生素是经验治疗中性粒细胞缺乏时发热的首选药物之一。     

国产头孢吡肟治疗中重度下呼吸道感染的临床观察

【目的】评价国产头孢吡肟治疗中重度下呼吸道感染的临床疗效和安全性。【方法】52例患者,随机分为国产头孢吡肟组和进口头孢吡肟组,两组用药剂量均为2.0 g,q 12 h,疗程7~14 d。【结果】国产头孢吡肟和进口头孢吡肟的临床有效率分别为70.4%、72.0%,细菌清除率为82.3%、88.2%,不良反应发生率为7.4%、8.0%,均无统计学差异(P>0.05)。【结论】国产头孢吡肟治疗中重度下呼吸道感染安全、有效。     

10例抗甲状腺药物致粒细胞缺乏伴重症感染的临床观察

目的:观察头孢哌酮钠他唑巴坦钠联合阿米卡星治疗抗甲状腺药物致粒细胞缺乏症伴重症感染的临床疗效和安全性。方法:10例因抗甲状腺药物所致粒细胞缺乏并重症感染的患者,静脉滴注头孢哌酮钠他唑巴坦钠2.0g/次,1次/12h;阿米卡星静脉滴注0.6g/次,1次/d,两药疗程7d～10d。结果:痊愈5例,显效2例,进步2例,无效1例,总有效率70%;2例出现不良反应,主要为胃肠反应,未经处理症状逐渐消失。结论:头孢哌酮钠他唑巴坦钠联合阿米卡星治疗抗甲状腺药物致粒细胞缺乏伴重症感染疗效明显,患者耐受性好,可作为经验性治疗中性粒细胞缺乏伴感染患者的首选方案。     

成都地区ICU肿瘤危重症患者呼吸机相关感染的病原菌分布及耐药性监测

目的探讨成都地区重症监护病房(ICU)肿瘤危重症患者呼吸机相关感染的病原菌分布及耐药性监测。方法选自成都地区2013年1月至2016年12月ICU收治的行机械通气治疗的肿瘤危急重症患者846例。采集呼吸机相关感染患者84例痰液标本,分离培养细菌,进行细菌鉴定,采用GN201法进行革兰阴性菌药敏试验,采用GP法进行革兰阳性菌药敏试验,药敏试验采用纸片扩散法。结果 84例呼吸机相关感染患者痰液标本中培养病原菌80株,其中革兰阴性菌54株(占67.50%),革兰阳性菌21株(占26.25%),真菌5株(占6.25%)。主要革兰阴性菌对头孢他啶和头孢吡肟耐药率较高,其中铜绿假单胞菌对头孢他啶和头孢吡肟耐药率分别为94.74%、89.47%,肺炎克雷伯菌对头孢他啶和头孢吡肟耐药率分别为87.50%、93.75%,鲍曼不动杆菌对头孢他啶和头孢吡肟耐药率分别为100.00%、83.33%;主要革兰阳性菌对青霉素和红霉素耐药率较高,其中金黄色葡萄球菌对青霉素和红霉素耐药率分别为80.00%、90.00%,溶血葡萄球菌对青霉素和红霉素耐药率分别为87.50%、75.00%。结论成都地区ICU肿瘤危急重症患者呼吸机相关感染的病原菌以革兰阴性菌为主,应引起重视,并针对相关因素采取有效地监测、预防措施。     

Cefepime plus amikacin versus piperacillin-tazobactam plus amikacin for initial antibiotic therapy in haematology patients with febrile neutropenia: results of an open,randomized, multicentre trial

BACKGROUND: Standard therapy for suspected infections in patients with profound neutropenia is the combination of a beta-lactam antibiotic plus an aminoglycoside. Cefepime's broad-spectrum activity makes it an option for initial empirical therapy in neutropenic patients. The aim of this study is to evaluate the efficacy and safety of cefepime plus amikacin compared with piperacillin-tazobactam plus amikacin for initial empirical treatment of fever in adult haematology patients with severe neutropenia. METHODS: In this prospective multicentre trial, 969 patients with 984 febrile neutropenic episodes were randomized to receive iv amikacin (20 mg/kg every 24 h) combined with either cefepime (2 g every 8 h) or piperacillin-tazobactam (4 g/500 mg every 6 h). Clinical response was determined at 72 h and at completion of therapy. RESULTS: Eight hundred and sixty-seven episodes were assessable for efficacy (432 cefepime, 435 piperacillin-tazobactam). The frequency of success without modification of the empirical therapy was nearly identical for cefepime plus amikacin (49%) compared with piperacillin-tazobactam plus amikacin (51%). Similar rates of success were found for microbiologically documented infection: 40% versus 39%, respectively. Antibiotic modification was necessary in 49% of cefepime and 44% of piperacillin-tazobactam patients. The overall response rate, with or without modification of the assigned treatment, was 94% in both groups. Drug-related adverse events were reported in 10% of cefepime plus amikacin versus 11% of piperacillin-tazobactam plus amikacin patients. Mortality due to infection occurred in a total of 10 patients (two cefepime, eight piperacillin-tazobactam). CONCLUSION: The empirical regimen of cefepime plus amikacin is equivalent to piperacillin-tazobactam plus amikacin in febrile adult haematology patients with severe neutropenia. Keywords: cefepime, piperacillin-tazobactam, amikacin, empirical antibiotic therapy, febrile neutropenia, haematological malignancy     

Ceftriaxone plus amikacin in neutropenic patients: a report on 100 cases.

100 febrile patients with chemotherapy-induced neutropenia (less than 0.5 x 10(9)/l) were empirically treated by ceftriaxone (2 g daily in adults, 50 mg/kg daily in children, as a once daily injection) and amikacin (15-20 mg/kg daily). The mean age was 41 years (range 8-72). 51 patients had acute leukemia, 29 non-Hodgkin's lymphoma, 12 Hodgkin's disease, 8 other disorders. 23 febrile episodes were bacteriologically documented (gram-positive: 13 patients; gram-negative: 8 patients; Candida: 2 patients) including 13 cases of bacteremia; 10 were clinically documented, and 67 remained of undetermined origin. Apyrexia was obtained in 39 patients by ceftriaxone plus amikacin alone (success), in 36 patients after the addition of vancomycin and/or amphotericin B (improvement), whereas in the remaining 25 patients it was necessary to substitute the study drug. The failure rate was correlated to the duration of neutropenia: 0/13 when neutropenia less than 6 days; 3/41 (7%) when 6-10 days; 22/46 (48%) when greater than 10 days. Only 2/20 (10%) of patients with neutropenia greater than 20 days were treated with ceftriaxone plus amikacin alone. 9 of the 23 bacteriologically documented episodes were successes (including 6 of the 11 cases due to Staphylococcus), 7 were improvements and 7 were failures (including the 3 cases due to Pseudomonas). No side effects were seen. Ceftriaxone plus amikacin is an effective firstline antibiotic combination in the treatment of febrile neutropenic patients.     

Monotherapy with piperacillin/tazobactam versus combination therapy with ceftazidime plus amikacin as an empiric therapy for fever in neutropenic cancer patients

Between July 1993 and September 1996, 107 consecutive febrile episodes in 83 neutropenic cancer patients with a median age of 41 years were randomized to treatment either with piperacillin/tazobactam 4.5 g every 8 h i.v. or ceftazidime 2 g every 8 h plus amikacin 15 mg/kg i.v. per day. In the case of fever >38° C 48 h after initiation of the antibiotic therapy, vancomycin 500 mg every 6 h i.v. was added. The study population was at serious risk of a poor outcome, since 67% of the patients had leukemia or lymphoma, 19% of the febrile events occurred after autologous bone marrow or blood stem cell transplantation, the median total duration of neutropenia was 16 days, and the median neutrophil count at study inclusion was 0.09 × 10⁹/l. The two patient groups were comparable in terms of risk factors. Bacteremia was found in 37%, other microscopically documented infections in 16%, and clinically documented infections in 26% of the febrile episodes. Most (96) febrile episodes were evaluable for response. No significant difference was found between piperacillin/ tazobactam and ceftazidime plus amikacin in terms of success rate (81% versus 83%), empirical addition of vancomycin (42% versus 38%), median time to fever defervescence (3.3 versus 2.9 days) or median duration of antibiotic therapy (7.2 versus 7.4 days). No patient died from the infection. Both antibiotic regimens were well tolerated, the study treatment being stopped only in 1 patient because of toxicity (cutaneous allergy to piperacillin/tazobactam). On the basis of the 107 febrile events encountered, we conclude that piperacillin/tazobactam is a safe and effective monotherapy. To define the definitive value of piperacillin/ tazobactam as a monotherapy for febrile neutropenic patients a large randomized trial is warranted.     

Comparison of cefepime versus ceftriaxone-amikacin as empirical regimens for the treatment of febrile neutropenia in acute leukemia patients

BACKGROUND: High-intensity regimes of chemotherapy have led to longer and more severe episodes of neutropenia with a resulting increase in morbidity and mortality due to infections. Which empiric antibiotic regimen to use in these cases is still under debate. METHODS: We performed a randomized comparative study to evaluate the efficacy of cefepime versus ceftriaxone plus amikacin as the initial treatment in an escalating, empirical, antibiotic therapy regimen in febrile neutropenic patients. Both adults and children were included. All patients had less than 500 neutrophils/microl at the time of infection. Patients were randomized to receive either cefepime or ceftriaxone plus amikacin. If infection continued 72 h later, patients in both groups received vancomycin, and if infection had not disappeared 7 days after starting antibiotics, amphotericin B was started. RESULTS: Twenty patients were included in each group. Both treatment and control groups were comparable for age and sex, among other factors. There were 18 cures in the cefepime group and 17 in the ceftriaxone plus amikacin group (p = 0.9). No patient discontinued therapy because of toxicity. CONCLUSIONS: Cefepime is a safe and very effective therapy for patients with acute leukemia and febrile neutropenia; in addition, it is a cheaper regimen in our country, and lacks the potential toxicity of the aminoglycosides.     

Pharmacodynamics of once-daily amikacin in various combinations with cefepime, aztreonam, and ceftazidime against Pseudomonas aeruginosa in an in vitro infection model.

The pharmacodynamics of once-daily amikacin administered as monotherapy and in combination with aztreonam, ceftazidime, and cefepime against Pseudomonas aeruginosa ATCC 27853 and clinical isolate 16690 (moderately susceptible to ceftazidime) were investigated with an in vitro model of infection over a 24-h period. Monotherapy with aztreonam, ceftazidime, and cefepime and combinations of aztreonam with cefepime or ceftazidime were also studied. MICs and MBCs were determined for viable organisms at 24 h to test for the development of resistance. Once-daily amikacin demonstrated killing activity over the initial 8 h superior to those of all other drugs administered as monotherapy against both strains tested (P < 0.01). Regrowth by 24 h was greatest for the amikacin regimen (P < 0.01) but was apparent for all monotherapy regimens against both strains. No changes in susceptibilities were observed. All combination therapies containing once-daily amikacin achieved 99.9% reductions in log10 CFU/ml by 2.0 h against both strains, with no regrowth of organisms at 24 h. Aztreonam-cefepime and -ceftazidime combinations required approximately 5 to 6 h to achieve a 99.9% reduction in log10 CFU/ml. Although there was no difference in time to the 99.9% kill between the aztreonam-cefepime and -ceftazidime regimens against either strain, the killing activity of these combinations was significantly less than those of regimens containing once-daily amikacin (P < 0.01). Minor differences in the initial susceptibilities of beta-lactams and the monobactam aztreonam against P. aeruginosa may not be important for therapeutic outcomes when used in combination with single-daily aminoglycoside therapy.     

In vitro activities of cefepime alone and with amikacin against aminoglycoside-resistant gram-negative bacteria.

The in vitro activity of cefepime was compared with those of ceftazidime, cefotaxime, and cefpirome against aminoglycoside-resistant gram-negative bacteria. Cefepime was the most active cephalosporin, with a MIC for 90% of strains tested for all non-Pseudomonas aeruginosa species of less than or equal to 4 micrograms/ml. No cefepime resistance was encountered among members of the family Enterobacteriaceae. Of the 40 aminoglycoside-resistant P. aeruginosa isolates, 15% were resistant to cefepime, compared with 18% for ceftazidime, 30% for cefpirome, and 35% for cefotaxime. Synergism between cefepime and amikacin was observed and occurred most frequently in P. aeruginosa strains resistant to cefepime but susceptible to amikacin. In no case did cefepime and amikacin exhibit antagonism against P. aeruginosa.     

Prospective randomized clinical trial of teicoplanin for empiric combined antibiotic therapy in febrile, granulocytopenic acute leukemia patients.

The increasing prevalence of bacteremia caused by gram-positive bacteria in granulocytopenic acute leukemia patients prompted us to evaluate, in a prospective randomized trial, the role of teicoplanin, a new glycopeptide antibiotic, when it was added to amikacin plus ceftazidime, as an empiric therapy of fever in these patients. Of 47 evaluable episodes, 22 were treated with the teicoplanin regimen and 25 were treated with the combination of amikacin and ceftazidime. The overall response to therapy of patients treated with teicoplanin was slightly better (82% improvement) than that obtained with amikacin plus ceftazidime (52%). The response rate of patients with gram-positive bacteremias was 80% (4 of 5) to the regimen that included teicoplanin; 25% (1 of 4) of the patients treated with amikacin plus ceftazidime responded to treatment; and for patients with gram-negative bacteremias, the response rates were, respectively, 100% (4 of 4) and 70% (7 of 10). The better results obtained with amikacin-ceftazidime-teicoplanin treatment were most evident in patients with profound (less than 100/mm3) and persistent neutropenia (83 versus 30% improvement). Furthermore, a good response rate of patients with gram-positive bacteremias (seven of eight; 87% improvement) was achieved in a small group of bone marrow transplant patients who were all treated with amikacin-ceftazidime-teicoplanin. No severe side effects were documented in any patient. Teicoplanin, as a drug administered as a single daily dose, seems to be a safe and useful anti-gram-positive agent when used in combination with amikacin-ceftazidime as an empiric therapy of febrile episodes in granulocytopenic acute leukemia patients.     

Ceftriaxone and amikacin versus ceftazidime and amikacin in febrile granulocytopenia.

The efficacy and safety of the two antibiotic combinations, ceftazidime plus amikacin and ceftriaxone plus amikacin were compared in an open randomized trial. 100 episodes of neutropenia caused by malignant diseases and/or cytostatic drugs were evaluated in 66 males and 34 females with a mean age of 49.4 years. The types of infections treated were: septicemia 38, fever of undetermined origin 26, pneumonia 13, ear, nose and throat infections 11 and others 12. 17 episodes were not evaluable (6 protocol violations, 6 doubtful infections and 5 non-bacterial infections). The overall results were comparable, with a 74% success rate for ceftazidime and a 70% rate for ceftriaxone (criteria of the European Organization for Research and Treatment of Cancer). In the patients with septicemia, the success rate was 64% in the ceftriaxone and 57% in the ceftazidime group. Eight patients died during the treatment, in 5 cases due to infectious complications. There were no differences between the two groups in respect of efficacy or toxicity.     

Monotherapy with intravenous followed by oral high-dose ciprofloxacin versus combination therapy with ceftazidime plus amikacin as initial empiric therapy for granulocytopenic patients with fever

The aim of the present study was to obtain clinical experience with the use of high-dose ciprofloxacin as monotherapy for the treatment of febrile neutropenia episodes (granulocyte count, <500/mm(3)) compared to a standard regimen and to clarify whether ciprofloxacin administration may be switched to the oral route. In a prospective randomized study ciprofloxacin was given at 400 mg three times a day (t.i.d.) for at least 72 h followed by oral administration at 750 mg twice a day (b.i.d). That regimen was compared with ceftazidime given intravenously at 2 g t.i.d. plus amikacin given intravenously at 500 mg b.i.d. The frequency of successful clinical response without modification at the end of therapy was almost identical for ciprofloxacin (50% [62 of 124 patients]) compared with that for ceftazidime plus amikacin (50.8% [62 of 122 patients]) in an intent-to-treat analysis; the frequencies were 48.3% (57 of 118 patients) versus 49.6% (56 of 113 patients), respectively, in a per-protocol analysis (P values for one-sided equivalence, 0.0485 and 0.0516, respectively; delta = 10%), with no significant differences among patients with bacteremia and other microbiologically or clinically documented infections and fever of unknown origin. For 82 (66.1%) patients, it was possible to switch from parenteral ciprofloxacin to the oral ciprofloxacin, and the response was successful for 61 (74.4%) patients. The efficacies of the regimens against streptococcal bacteremias were 16.6% (one of six patients) for the ciprofloxacin group and 33.3% (one of three patients) for the combination group (it was not statistically significant), with one breakthrough streptococcal bacteremia observed among the ciprofloxacin-treated patients. Adverse events were mostly self-limited and were observed in 27 (20.6%) ciprofloxacin-treated patients and 26 (19.7%) patients who were receiving the combination. This study demonstrates that high-dose ciprofloxacin given intravenously for at least 3 days and then by the oral route is therapeutically equivalent to the routine regimen of intraveneous ceftazidime plus amikacin even in febrile patients with severe neutropenia (polymorphonuclear leukocyte count, <100 mm(3)). However, it is very important that before an empirical therapy is chosen each hospital determine bacteriologic predominance and perform resistance surveillance.