Piperacillin/tazobactam plus tobramycin versus ceftazidime plus tobramycin as empiric therapy for fever in severely neutropenic patients

The objective of this trial was to evaluate the potential advantages of the combination of piperacillin and tazobactam in the control of fever in neutropenic patients. In this single-center study, patients who experienced a total of 247 febrile episodes were prospectively randomized to receive either our standard regimen, ceftazidime 3 g/day (1 g t.i.d.) plus tobramycin 3 mg/kg per day (1.5 mg/kg b.i.d.), or piperacillin 12 g/day plus tazobactam 1.5 g/day (4 g+0.5 g t.i.d.) plus tobramycin 3 mg/kg per day (1.5 mg/kg b.i.d.). Vancomycin was added in all cases of persistent fever in the ceftazidime arm, but only when there was microbiologically documented resistance in the piperacillin/tazobactam arm. All 247 episodes were evaluable by "intent-to-treat" analysis. The two populations were well matched in terms of age, gender, underlying disease, chemotherapy received, oral decontamination, clinical and bacterial documentation, and severity and duration of neutropenia. Initial antibacterial therapy was successful (apyrexia at 72 h, without antibiotic change) more frequently (P=0.008) with the regimen containing piperacillin/tazobactam (54.4%) than with the one including ceftazidime (37.6%). Fewer (P=0.02) major infectious events (infectious death or delay in treatment of underlying disease due to infection) were observed during piperacillin/ tazobactam treatment (2.6%) than with the ceftazidime regimen (11.3%), despite a lower frequency of glycopeptide addition when piperacillin/tazobactam was used (54.4% versus 77.4%) according to the rules adopted. This trial confirmed the efficacy of the piperacillin/tazobactam combination for empirical treatment of febrile neutropenic patients. This antibiotic combination permitted a dramatic decrease in empiric glycopeptide antibiotic administration in such patients. Electronic publication: 12 January 1999     

Piperacillin/tazobactam in the treatment of community-acquired and nosocomial respiratory tract infections: A review

Investigators assessed the efficacy and safety of piperacillin/tazobactam therapy in a study of patients with community-acquired lower respiratory tract infections and a study of patients with nosocomial, severe lower respiratory tract infections. Piperacillin 4 g/tazobactam 500 mg was given intravenously every 8 h to 193 hospitalized lower respiratory tract infection patients for a minimum of 5 days. There was a favorable response rate of 97% and eradication of the causative pathogen was documented or presumed in 93% of patients. There was a low incidence of adverse experiences and the combination was well tolerated. Seventy-one intensive care patients with severe lung disease received 4 g piperacillin/500 mg tazobactam intravenously every 6 h; afterward they were given amikacin 7.5 mg/kg every 12 h. Minimum duration of treatment was 5 days. Therapy with piperacillin/tazobactam plus amikacin was well-tolerated, produced a 74% favorable clinical response rate, and eradicated the responsible pathogen in 70% of patients.     

Comparative efficacy of ceftriaxone versus ceftazidime in the treatment of nosocomial lower respiratory tract infections.

Seventy-two hospitalized patients with pneumonia or bacteremia were randomly allocated to receive ceftriaxone 2 g once daily i.v. or ceftazidime 2 g twice a day i.v. At the end of the study 60 patients were evaluable, 31 in the ceftazidime group and 29 in the ceftriaxone group. Thirty-four patients (ceftazidime = 15, ceftriaxone = 19) yielded one or more pathogens, of which 64% were gram-negative bacilli. Clinical cure or improvement was observed in 90% of patients in both groups. All 3 cases of bacteremia were cured. Three patients in each group failed to respond to the administered drug. Eradication of the pathogen(s) was observed in 82% of the ceftazidime group and in 86% of the ceftriaxone group. Two episodes of superinfection due to Pseudomonas aeruginosa were recorded in the ceftriaxone group, while Candida spp. was isolated from the sputum in 2 patients in the ceftazidime group. Three strains of P. aeruginosa (2 in the ceftazidime group, 1 in the ceftriaxone group) persisted despite the treatment. No side effects were seen except for skin rash in 2 patients receiving ceftazidime. Compliance was good in both groups, particularly with the once daily administration of ceftriaxone. Overall ceftriaxone and ceftazidime appear to be equally effective in the treatment of nosocomial pneumonia, with the exception of P. aeruginosa infection.     

Intravenous fleroxacin versus ceftazidime for lower respiratory tract and skin and soft-tissue infections.

Fleroxacin, a new quinolone antimicrobial agent, was evaluated as part of a multicenter, comparative, open-label, randomized trial with ceftazidime in the treatment of lower respiratory tract infections and skin and soft-tissue infections. After written informed consent was obtained, 20 patients were entered at our center. Twelve patients were assigned to the fleroxacin group; 6 in each infection category. Of these 12 patients, 2 with pneumonia and 3 with skin and soft-tissue infection were not clinically evaluable. The mean duration of therapy was 5.7 +/- 3.0 days in the fleroxacin group versus 7.9 +/- 2.0 days in the ceftazidime group. The gram-positive organisms responsible for those infections not evaluable were methicillin-resistant Staphylococcus aureus, Streptococcus pneumoniae, and group F streptococcus, all of which were resistant to fleroxacin. In total, 6 gram-positive isolates were resistant to fleroxacin. All but 2 S aureus isolates were susceptible to ceftazidime. Adverse reactions in both groups were negligible. Fleroxacin was found to be as effective as ceftazidime against a variety of gram-negative pathogens, but local susceptibility patterns for quinolones should be checked before empiric use of fleroxacin against gram-positive pathogens such as streptococci.     

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.     

A prospective randomized trial of ceftazidime versus cefazolin/tobramycin in the treatment of hospitalized patients with pneumonia

Ceftazidime and cefazolin/tobramycin were compared in the treatment of hospitalized patients with pneumonia. Iv doses 8-hourly were: ceftazidime--2 g, cefazolin--1.5 g, tobramycin--1.7 mg/kg. For patients with pseudomonas infection randomized to cefazolin/tobramycin, ticarcillin (3 g iv 4-hourly) was used instead of cefazolin. One hundred and ten of 129 patients were evaluable (ceftazidime = 52, cefazolin/tobramycin = 58). Seventy five cases (68%) had documented pathogens of which 81% were aerobic Gram-negative bacilli. Analysis of clinical response showed no difference in overall results (P = 0.77), or separate outcomes: cured (P = 0.85), improved (P = 0.62), failed (P = 0.53), or relapsed (P = 0.50). No differences in bacteriological response were noted either: eradication (P greater than 0.10), elimination with recurrence (P greater than 0.10), persistence (P greater than 0.10). The incidence of enterococcal and fungal colonization and superinfection was the same for both regimens. There was a greater incidence of Coombs' test positivity with ceftazidime (P less than 0.01) but greater nephrotoxicity with cefazolin/tobramycin (P less than 0.02). Ceftazidime appears to be as efficacious as cefazolin/tobramycin in the treatment of hospitalized patients with pneumonia, and is less nephrotoxic.     

Piperacillin/tazobactam in the treatment of polymicrobial infections

Polymicrobial infections are characterized by the presence of micro-organisms from more than one group of bacteria. Empirical treatment of polymicrobial infections requires an agent active against both anaerobic and aerobic/facultative bacteria. An aminoglycoside used in combination with an anti-anaerobe agent is commonly used to treat polymicrobial infections. However, aminoglycoside nephrotoxicity and treatment failures raise questions about the use of such regimens. Among non-aminoglycoside treatment regimens such as penicillin and cephalosporins, effectiveness has been compromised by bacteria producing extended spectrum -lactamases. Cefoxitin shows satisfactory results for treatment of intra-abdominal infections. Other studies have shown good results with imipenem, cefotetan and piperacillin used as single agents. Piperacillin/tazobactam, a new combination broad-spectrum antibiotic and potent -lactamase inhibitor, can be used for the treatment of infections caused by piperacillin-sensitive microorganisms as well as -lactamase-producing, piperacillin-resistant organisms. This broad-spectrum activity is appropriate for infections traditionally treated empirically by double or triple antibiotic therapy.     

Piperacillin/tazobactam in the treatment of polymicrobial infections

Polymicrobial infections are characterized by the presence of micro-organisms from more than one group of bacteria. Empirical treatment of polymicrobial infections requires an agent active against both anaerobic and aerobic/facultative bacteria. An aminoglycoside used in combination with an anti-anaerobe agent is commonly used to treat polymicrobial infections. However, aminoglycoside nephrotoxicity and treatment failures raise questions about the use of such regimens. Among non-aminoglycoside treatment regimens such as penicillin and cephalosporins, effectiveness has been compromised by bacteria producing extended spectrum β-lactamases. Cefoxitin shows satisfactory results for treatment of intra-abdominal infections. Other studies have shown good results with imipenem, cefotetan and piperacillin used as single agents. Piperacillin/tazobactam, a new combination broad-spectrum antibiotic and potent β-lactamase inhibitor, can be used for the treatment of infections caused by piperacillin-sensitive microorganisms as well as β-lactamase-producing, piperacillin-resistant organisms. This broad-spectrum activity is appropriate for infections traditionally treated empirically by double or triple antibiotic therapy.     

Pefloxacin in the treatment of nosocomial lower respiratory tract infections in intensive care patients

Pefloxacin was used to treat nosocomial pulmonary infections in 46 mechanically ventilated patients. All patients had one or more underlying diseases and were given pefloxacin at a dose of 800 mg or 1200 mg daily in two or three divided doses. The commonest bacterial isolates were Staphylococcus aureus, Pseudomonas aeruginosa and enterobacteria. Of these patients, 33 (72%) showed a favourable response, one patient relapsed and 12 (26%) were considered failures. Superinfections occurred in 10 (22%). Of the 62 isolated potential pathogens, 53 (85%) were completely eradicated. Side effects were mild and treatment was withdrawn in only three patients. Pefloxacin can be considered as a possible therapeutic agent for the treatment of nosocomial pulmonary infections.     

Cefoperazone sodium/sulbactam sodium vs piperacillin sodium/tazobactam sodium for treatment of respiratory tract infection in elderly patients

BACKGROUNDRespiratory tract infections in the elderly are difficult to cure and can easily recur, thereby posing a great threat to patient prognosis and quality of life.AIMTo investigate the therapeutic effects of different antibiotics in elderly patients with respiratory tract infection. METHODSSeventy-four elderly patients with respiratory tract infection were randomly allocated to a study (n = 37; treated with cefoperazone sodium/sulbactam sodium) or control (n = 37; treated with piperacillin sodium/tazobactam sodium on the basis of routine symptomatic support) group. Both groups were treated for 7 d. Time to symptom relief (leukocyte recovery; body temperature recovery; cough and sputum disappearance; and rale disappearance time), treatment effect, and laboratory indexes [procalcitonin (PCT), C-reactive protein (CRP), white blood cell count (WBC), and neutrophil percentage (NE)] before and 7 d after treatment and the incidence of adverse reactions were assessed.RESULTSIn the study group, the time to WBC normalization (6.79 ± 2.09 d), time to body temperature normalization (4.15 ± 1.08 d), time to disappearance of cough and sputum (6.19 ± 1.56 d), and time to disappearance of rales (6.68 ± 1.43 d) were shorter than those of the control group (8.89 ± 2.32 d, 5.81 ± 1.33 d, 8.77 ± 2.11 d, and 8.69 ± 2.12 d, respectively; P = 0.000). Total effective rate was higher in the study group (94.59% vs 75.68%, P = 0.022). Serum PCT (12.89 ± 3.96 μg/L), CRP (19.62 ± 6.44 mg/L), WBC (20.61 ± 6.38 × 10⁹/L), and NE (86.14 ± 7.21%) levels of the study group before treatment were similar to those of the control group (14.05 ± 4.11 μg/L, 18.79 ± 5.96 mg/L, 21.21 ± 5.59 × 10⁹/L, and 84.39 ± 6.95%, respectively) with no significant differences (P = 0.220, 0.567, 0.668, and 0.291, respectively). After 7 d of treatment, serum PCT, CRP, WBC, and NE levels in the two groups were lower than those before treatment. Serum PCT (2.01 ± 0.56 μg/L), CRP (3.11 ± 1.02 mg/L), WBC (5.10 ± 1.83 × 10⁹/L), and NE (56.35 ± 7.17%) levels were lower in the study group than in the control group (3.29 ± 0.64 μg/L, 5.67 ± 1.23 mg/L, 8.13 ± 3.01 × 10⁹/L, and 64.22 ± 8.08%, respectively; P = 0.000). There was no significant difference in the incidence of adverse reactions between the groups (7.50% vs 12.50%, P = 0.708).CONCLUSIONPiperacillin sodium/tazobactam sodium is superior to cefoperazone sodium/ sulbactam sodium in the treatment of elderly patients with respiratory tract infection with a similar safety profile.     

重症监护病房患者下呼吸道院内感染细菌及其耐药性分析

目的探讨重症监护病房患者院内感染细菌分布特点及耐药情况。方法回顾性总结2004年5月至2006年6月本院重症监护病房103例院内感染(nosocomial infection,NP)患者的临床资料、感染病原菌谱及耐药性,并对相关因素进行分析。结果103例感染患者共分离出细菌117株,以G-杆菌为主(占68.4%),球菌比例较低(占21.4%)。G-杆菌中铜绿假单胞菌占第一位(31.6%),其次为大肠埃希氏菌(18.8%)、肺炎克雷伯菌(17.1%)。球菌主要为金黄色葡萄球菌,其中耐甲氧西林金黄色葡萄球菌(methicillin resistant staphylococcus aureus,MRSA)占46.2%。G 菌占35.2%,真菌占18.3%。结论ICU患者下呼吸道感染的病原菌以G-杆菌为主,病原菌显示多重耐药,G-杆菌对亚胺培南敏感性较好,而G 菌对万古霉素敏感应根据药敏选择抗菌素。     

原发性肾病综合征继发甲状腺功能减退18例临床分析

目的探讨依诺沙星治疗老年下呼吸道细菌感染的疗效及安全性.方法依诺沙星组用量0.2g/次,2次/d;头孢噻肟组2.0g/次,2次/d,均静脉滴注,疗程7～14天.结果依诺沙星组痊愈率、有效率、细菌清除株数及副作用发生率与头孢噻肟组比较,无显著性差异(P＞0.05).结论依诺沙星是有效和安全的治疗老年下呼吸道感染抗菌药物.     

依诺沙星治疗老年下呼吸道感染

目的 探讨依诺沙星治疗老年下呼吸道细菌感染的疗效及安全性。方法 依诺沙星组用量0.2g/次,2次/d;头孢噻肟组2.0g/次,2次／d,均静脉滴注,疗程7－14天。结果 依诺沙星组痊愈率、有效率、细菌清除株数及副作用发生率与头孢噻肟组比较,无显著性差异（P＞0．05）。结论 依诺沙星是有效和安全的治疗老年下呼吸道感染抗菌药物。     

Oral ofloxacin therapy for lower respiratory tract infection.

We made an open, noncomparative evaluation of ofloxacin, 400 mg orally bid for 10 days, in 98 subjects with community-acquired pneumonia or pathogen-confirmed bronchitis. Thirty-nine (40%) of the subjects were treated in the hospital and 59 (60%) were treated as outpatients. The mean age of those treated was 56.2 years; 73 (74%) of the subjects either were more than 60 years old or had a history of chronic obstructive pulmonary disease, or both. There were 95 organisms initially isolated in sputum, aspirate, or lavage fluid; all were susceptible to ofloxacin, and none acquired resistance during therapy. Haemophilus influenzae was the most common pathogen (19 isolates), followed by Streptococcus pneumoniae (18) and Staphylococcus aureus (10). Clinical responses included cure in 70 patients (71%), improvement in 26 (27%), and failure in two (2%). After 10 days of therapy, pathogens persisted in two cases; in one case, Streptococcus salivarius was isolated, though it remained susceptible to ofloxacin, and in the other, Klebsiella pneumoniae was accompanied by superinfection due to a resistant strain of Serratia marcescens. We included in this study three confirmed cases of atypical pneumonia successfully treated with ofloxacin, two of them due to Mycoplasma pneumonia and one to Legionella pneumophila. Ofloxacin was well tolerated. Our data indicate that ofloxacin is effective and safe as specific and empiric treatment for many lower respiratory tract infections.     

Moxalactam versus clindamycin plus tobramycin for the treatment of puerperal infections

Sixty women with the diagnosis of puerperal endometritis were randomized to receive either moxalactam (n = 29) or the combination of clindamycin and tobramycin (n = 31) as therapy for their infection. Endometrial bacteriology consisted of mixed flora, both aerobic and anaerobic gram-positive and gram-negative organisms. Clinical cure was achieved in 27 (93%) of the moxalactam-treated patients and 28 (90%) of those given combination therapy. The two failures of moxalactam therapy were associated with enterococcal infection. Failures of clindamycin/tobramycin therapy were due to enterococcal infection, abscess formation, and moderately severe diarrhea. This study indicates that moxalactam is as effective and safe as the combination of clindamycin/tobramycin for the treatment of postpartum endometritis.     

呼吸道病毒与成人下呼吸道感染相关性探讨

目的:探讨成人下呼吸道感染患者病毒感染状况.方法:采集健康体检者106例(对照组)和1年期内下呼吸道感染住院患者208例(观察组)鼻咽拭子,采用多重PCR技术检测常见的7种(11个亚型)呼吸道病毒.结果:对照组106例中4例阳性.其中流感病毒A型3例,鼻病毒1例.观察组208例患者中88例检出107株病毒,患者阳性率42.3%.病毒株检出率51.4%.检出病毒以流感病毒A型、鼻病毒、副流感病毒1型为高,三者占检出病毒株的81.3%(87/107),人偏肺病毒和人博卡病毒未见阳性.13例患者同时检出2种以上病毒:1例同时检出5种病毒,3例同时检出3种病毒,9例同时检出2种病毒.病毒感染者中临床诊断社区获得性肺炎占34.8%(39/112),急性支气管炎47.5%(19/40),慢性阻塞性肺病急性加重55.0%(22/40),支气管扩张50.0%(8/16).病毒尤其是流感病毒A型、副流感病毒1型感染时间分布以一季度为高.结论:深圳地区成人下呼吸道感染患者中病毒感染具有较高比例,以流感病毒A型、鼻病毒、副流感病毒1型为主,且具有一定比例的2种以上病毒混合感染率.     

哌拉西林钠/他唑巴坦钠联合莫西沙星治疗COPD合并急性下呼吸道感染的临床观察

目的观察哌拉西林钠/他唑巴坦钠联合莫西沙星治疗COPD合并急性下呼吸道感染患者的临床疗效。方法选取120例COPD合并急性下呼吸道感染患者随机分为3组,对照1组(40例)给予哌拉西林钠/他唑巴坦抗感染治疗;对照2组(40例)给予莫西沙星抗感染治疗;联合治疗组(40例)给予哌拉西林钠/他唑巴坦联合莫西沙星联合治疗。分别于治疗前后比较急性生理与慢性健康评分(APACHEⅡ)及呼吸困难评分;并分析痰样本,对比治疗后的细菌清除率、真菌感染率及临床疗效。结果联合治疗组的总有效率为87.5%,对照1组和对照2组总有效率分别为57.5%和62.5%,组间比较差异显著(P0.05);联合治疗组APACHEⅡ和呼吸困难得分低于对照1组和对照2组(P0.01)。联合治疗组细菌清除率高于对照1组和对照2组(P0.01)且联合治疗组在抗感染方面体现极显著优越性(P0.01)。结论联合使用抗生素治疗COPD合并急性下呼吸道感染可减少不必要的细菌侵入,可有效地防治COPD患者的真菌感染,改善其预后。     

Efficacy and tolerability of piperacillin/tazobactam versus ceftazidime in association with amikacin for treating nosocomial pneumonia in intensive care patients: a prospective randomized multicenter trial

OBJECTIVE: To compare clinical and bacteriological efficacy as well as tolerability of two regimens of broad-spectrum antibiotics (ceftazidime versus piperacillin/tazobactam) combined with amikacin in the treatment of nosocomial pneumonia in intensive care patients. DESIGN: Open label, prospective, multicenter, and randomized phase III clinical trial. SETTING: Medical or surgical intensive care units (ICUs) of nine acute-care teaching hospitals in Spain. PATIENTS AND PARTICIPANTS: One hundred and twenty-four ICU patients with nosocomial pneumonia and requiring mechanical ventilation were included. They were randomized to receive amikacin (15 mg/day divided into two doses) combined with either piperacillin (4 g every 6 h) and tazobactam (0.5 g every 6 h) (n = 88) or ceftazidime (2 g every 8 h) (n = 36). MEASUREMENTS AND RESULTS: The causative pathogen was determined in 60.2% of patients in the group of amikacin plus piperacillin/tazobactam and in 76.9% in the group of amikacin plus ceftazidime. A total of 94 bacterial organisms were isolated among which gram-negative bacilli predominated, Pseudomonas aeruginosa being the most frequent. Clinical response at the end of antibiotic therapy was considered satisfactory (cure and/or improvement) in 63.9% of patients in the amikacin plus piperacillin/tazobactam group and in 61.5% in the amikacin plus ceftazidime (odds ratio 1.1; 95% confidence interval 0.44-2.75). Eradication or presumptive eradication rates for each pathogen and for either gram-negative or gram-positive bacteria were similar in both antibiotic combinations (odds ratio 1.2; 95% confidence interval 0.39-3.66). A total of 21 adverse effects (23.9%) occurred in the amikacin plus piperacillin and tazobactam group and six (16.7%) in the amikacin plus ceftazidime group, thrombocytosis, renal dysfunction, and hepatic cytolysis being the most common. The efficacy and tolerability of the two therapeutic regimens were similar not only in the whole study population, but also in the subset of P. aeruginosa-related pneumonia (odds ratio 1; 95% confidence interval 0.08-13.37). CONCLUSIONS: Amikacin associated with either ceftazidime or piperacillin and tazobactam has shown comparable efficacy and tolerability in the treatment of ICU patients with nosocomial pneumonia.