Cefpodoxime proxetil. A review of its antibacterial activity, pharmacokinetic properties and therapeutic potential.

Cefpodoxime proxetil is an orally administered prodrug which is absorbed and de-esterified by the intestinal mucosa to release the third generation cephalosporin, cefpodoxime. Cefpodoxime is stable towards the most commonly found plasmid-mediated beta-lactamases and the drug has a broad spectrum of antibacterial activity encompassing both Gram-negative and Gram-positive bacteria, rendering it a possible option for empirical use in a wide range of community acquired infections in both adult and paediatric patients. The extended plasma half-life of cefpodoxime (1.9 to 3.7 h) permits twice daily administration. In comparative trials, twice daily cefpodoxime proxetil (dose equivalent cefpodoxime 100 to 400 mg) was as effective as a 3- to 4-times daily regimen of phenoxymethylpenicillin in pharyngotonsillitis, as well as thrice daily amoxicillin (with or without clavulanic acid) or cefaclor against infections of the ear, the upper and lower respiratory tract, the urinary tract and those of the skin and soft tissues. The latter reflects the enhanced antistaphylococcal activity of cefpodoxime, which distinguishes it from other orally active third generation cephalosporins such as cefixime. Most notably, an oral regimen of cefpodoxime proxetil was as efficacious as parenterally administered ceftriaxone for the treatment of bronchopneumonia in hospitalised patients at risk due to the presence of underlying diseases, addictions or advancing age. A single oral dose of cefpodoxime was also as efficacious as ceftriaxone in uncomplicated anogenital gonococcal infections. Cefpodoxime proxetil is generally well tolerated, with mild to moderate gastrointestinal disturbances occurring in 4 to 15% of patients treated with therapeutic doses. Thus, a convenient twice daily oral regimen of cefpodoxime proxetil can be prescribed as an effective alternative to established beta-lactam therapies in the empirical outpatient treatment of infections of the respiratory and urinary tracts as well as those of the skin and soft tissues.     

Clinical studies of cefpodoxime proxetil in respiratory tract infections

Twelve patients with respiratory tract infections were treated with cefpodoxime proxetil (CS-807, CPDX-PR), a new cephem antibiotic. It was given orally at a dose of 200 mg 2 times a day for 4 approximately 15 days. Its clinical effects were evaluated as excellent in 1 case, good in 9 cases and poor in 2 cases. The efficacy rate was 83.3%. Its bacteriological effects were evaluated as eradication in 5 strains and decrement in 1 strain. The eradication rate was 83.3%. No adverse reactions and disorder of laboratory findings due to CPDX-PR were observed.     

Cefpodoxime proxetil: a review of its use in the management of bacterial infections in paediatric patients

Cefpodoxime proxetil is an oral third generation cephalosporin with a broad spectrum of antibacterial activity. The drug has in vitro activity against many common Gram-positive and Gram-negative pathogens associated with common paediatric infections, making the drug a useful option for empirical therapy. In randomised controlled trials conducted in children with acute otitis media, oral cefpodoxime proxetil 8 to 10 mg/kg/day (usually administered in 2 divided doses) for 5 to 10 days was at least as effective as standard regimens of amoxicillin/ clavulanic acid, cefixime, cefuroxime axetil or cefaclor as assessed by either clinical or bacteriological criteria. Cefpodoxime 8 to 10 mg/kg/day (administered in 2 divided doses) for 5 to 10 days was at least as effective as standard 10-day regimens of penicillin V in the treatment of children with pharyngitis and/or tonsillitis. Significant differences in favour of cefpodoxime proxetil were demonstrated in terms of clinical (1 study) and bacteriological (2 studies) criteria. The clinical efficacy of 5 days of treatment with cefpodoxime proxetil is similar to that of 10 days of treatment with penicillin V. In children with lower respiratory tract infections (primarily pneumonia), clinical and bacteriological efficacy rates achieved with cefpodoxime proxetil treatment were similar to those produced by cefuroxime axetil or amoxicillin/clavulanic acid in randomised controlled trials. Cefpodoxime proxetil also demonstrated clinical efficacy in paediatric patients with skin and soft tissue infections. In randomised studies that included both adults and children with a variety of infections (e.g. abscess, atheroma, furuncle and carbuncle, infected wounds, cellulitis), cefpodoxime proxetil showed efficacy similar to that of cefuroxime axetil or cefaclor. Cefpodoxime proxetil is well tolerated by paediatric patients, with adverse events (primarily gastrointestinal tract disturbances and skin rashes) that are consistent with those reported for other oral cephalosporins. CONCLUSION: Cefpodoxime proxetil is a third generation cephalosporin with a broad spectrum of antibacterial activity and a favourable pharmacokinetic profile which allows twice-daily administration. It is generally well tolerated and demonstrates good bacteriological and clinical efficacy in paediatric patients with various infectious diseases, including acute otitis media, tonsillitis and/or pharyngitis. Based on these characteristics, cefpodoxime proxetil is a suitable option for the treatment of paediatric patients with various common bacterial infections.     

Cefpodoxime proxetil, its in vitro antibacterial activity, affinity to bacterial penicillin-binding proteins, and synergy of bactericidal activity with serum complement and mouse-cultured macrophages

Cefpodoxime proxetil (CS-807) is an orally active prodrug of an oxime-type cephem antibiotic. The MIC60 values of cefpodoxime (R-3746) the active form of CS-807, were 3.13, 6.25, 0.05, 0.38, 0.2, 0.1, 3.13, 3.13, 6.25, 6.25, 0.1 and 12.5 micrograms/ml against S. aureus, coagulase-negative staphylococci, S. pneumoniae, E. coli carrying R plasmids, P. vulgaris, P. rettgeri, C. freundii, S. marcescens, A. calcoaceticus, P. cepacia, ampicillin-resistant H. influenzae and B. fragilis, respectively. Its activity was stronger than that of cefaclor and ampicillin. R-3746 manifested little activity against P. aeruginosa, methicillin-resistant S. aureus, and Enterococcus spp. R-3746 showed stronger binding affinity than cefaclor with the PBP2 of S. aureus, PBPs 1a, 1bs, 2 and 3 of E. coli, PBPs 1b, 1c and 3 of P. rettgeri, and the PBP3 of P. aeruginosa than cefaclor. Synergy of the bactericidal effect between R-3746 and serum complement was moderate, although the cells of E. coli NIHJ-JC2 and S. aureus 209P were well engulfed and rapidly digested by mouse-cultured macrophages in the presence of greater than 1/8 MIC of R-3746. Good clinical efficacy can be expected of CS-807 provided its pharmacokinetics prove to be good.     

The use of macrolides in respiratory tract infections

Macrolides have enjoyed continued use for over 40 years, being increasingly used for the treatment of respiratory tract infections. Newer macrolides have been introduced that show improved absorption after oral administration, better gastrointestinal tolerance, and delivery of increased amounts of drug to the infection site. Macrolides are commonly used in community-acquired pneumonia, as well as in atypical pneumonia and legionellosis. The newer macrolides, in comparative studies, have been shown to be as affective as the conventional therapies for treating acute otitis media, acute sinusitis and acute pharyngitis, with a low incidence of side-effects. However, dosing can be simplified because of their unique pharmacokinetic properties. Limitations in the use of macrolides for respiratory infections include rather marginal activity in the most severe cases of Haemophilus influenzae infections, lack of activity against Klebsiella and other coliforms, which precludes their use as single agents in the therapy of pneumonia in patients with significant underlying disease or in the elderly, and development of resistance in streptococci and staphylococci.     

In vitro antibacterial activity and pharmacokinetics of ofloxacin in chronic respiratory tract infections

Serum and sputum levels of ofloxacin (OFLX) were measured in 5 patients with chronic respiratory tract infections and were compared with antibacterial activity in vitro. Sputum OFLX levels higher than the MIC's against H. influenzae and K. pneumoniae were maintained during the period when daily oral administrations were continued. The MIC70 of OFLX against S. aureus was under 0.78 microgram/ml and the MIC70 of OFLX against P. aeruginosa was 1.56 micrograms/ml. The maximum OFLX levels in sputum were higher than these MIC's during the period when 200-300 mg X 2 times/day oral administrations were maintained. From these results, OFLX was considered to be effective and useful for the treatment of patients with chronic respiratory tract infections.     

Prulifloxacin: a review focusing on its use beyond respiratory and urinary tract infections

Prulifloxacin is a fluoroquinolone antibiotic that has been approved in several European countries for the treatment of lower urinary tract infections and exacerbations of chronic bronchitis. In this review, PubMed and Scopus databases were searched for potential uses of prulifloxacin beyond respiratory and urinary tract infections. Nine individual articles (eight randomised controlled trials and one cohort study) were regarded as eligible for inclusion in the review. Three of the studies were double-blinded, whilst six were open-label trials. Three studies referred to the treatment of patients with chronic bacterial prostatitis (CBP), one to prophylaxis of patients undergoing transrectal prostate biopsy, one to prophylaxis of women undergoing surgical abortion, two to patients with traveller's diarrhoea, one to diabetic patients with soft tissue infections or osteomyelitis, and one to improving tolerance of Bacillus Calmette-Guérin (BCG) instillations in patients with bladder cancer. Regarding CBP, prulifloxacin was non-inferior to its comparators, with a trend towards better microbiological outcomes at follow-up. Regarding traveller's diarrhoea, prulifloxacin resulted in better clinical and microbiological outcomes compared with placebo. Finally, prulifloxacin decreased the adverse events associated with BCG instillations in patients with bladder cancer, without affecting cancer recurrence rates. In summary, prulifloxacin appears to be a promising agent for the treatment of bacterial prostatitis and traveller's diarrhoea.     

Cefotaxime therapy of lower respiratory tract infections in intensive-care patients

Cefotaxime is one of two third-generation cephalosporins (the other being ceftriaxone) that undergo significant metabolism and is the only third-generation cephalosporin for which an active metabolite has been identified. Cefotaxime was administered intravenously in doses of 6 g per day to 20 patients with serious infections of the lower respiratory tract due to organisms susceptible to cefotaxime (isolates of Enterobacteriaceae and of Pseudomonas aeruginosa). It was administered with gentamicin in some high-risk patients. Cefotaxime resulted in mean peak concentrations of 32 mu/ml (cv% = 53) and of 29.5 micrograms/ml (cv% = 65) respectively after the first and after the last dose of a regimen of 2 g every 8 hours. The half-life value averaged 1.8 h and 6.4 h for cefotaxime and its desacetyl metabolite respectively. The average value of the metabolite at the end of short infusion was 11.5 micrograms/ml (cv% = 31) after the initial dose and 15.5 micrograms/ml (cv% = 37) after the last administered dose. Overall results were 75% patients cured or improved; 83% of the patients with nosocomial pulmonary infections due to Enterobacteriaceae were cured; 50% of the patients with Pseudomonas aeruginosa infections were cured and 25% improved despite the pathogen not being eradicated. No serious toxicity was observed.     

舒美特治疗下呼吸道感染的疗效和安全性观察

观察舒美特在治疗下呼吸道感染中的临床疗效，体外药物敏感率及病原菌清除情况，了解其在治疗中引起的不良反应。采用舒美特（５００ｍｇ－日１次，连用３天）口服治疗，用药前后对病人进行痰液细菌学，肝肾功能及相应实验室检查，记录治疗前后病人症状体征的变化情况及用药过程中出现的不良反应。治疗后总有效率为９３．３％，细菌清除率为８１．８１％，不良反应较少。结果表明舒美特在轻、中度下呼吸道感染治疗中是一种有效的抗生素，用药方便，安全，不良反应较少。     

The effect of anticholinergic bronchodilator therapy on cough during upper respiratory tract infections.

1. Oxitropium bromide (Oxivent), an anticholinergic bronchodilator, inhibits coughing induced by hypotonic aerosols in both asthmatic and non-asthmatic individuals. We have now extended this work to investigate whether this antitussive activity is reproducible in cough associated with viral infection. 2. The effect of oxitropium bromide (200 micrograms three times daily) on cough and pulmonary function has been studied in 56 non-asthmatic volunteers with upper respiratory tract infections (URTI) in a double-blind, randomised, parallel group, placebo controlled study over 10 days. 3. Lung function, symptom questionnaire and cough response to ultrasonically nebulised distilled water (UNDW) inhalation were initially recorded within 72 h of development of cough and again after the 10 day treatment period. By use of a diary card at home, frequency and severity of cough, nocturnal symptoms and general malaise were assessed daily throughout the treatment period using 5 cm visual analogue scales (VAS). Peak expiratory flow rate (PEFR) was recorded thrice daily before treatment over this 10 day period. 4. VAS scores of symptoms and UNDW-induced cough frequency all decreased over the 10 days of observation whether oxitropium bromide or placebo was administered. The mean PEFR showed a statistically significant fall in morning values during the early stages of infection which lessened with recovery but no effect of treatment with oxitropium bromide was observed (P > 0.05). 5. Oxitropium bromide, which inhibits the cough response to UNDW, does not offer an effective therapy for cough associated with an upper respiratory tract viral infection.     

A randomised, multicentre study of ceftriaxone versus standard therapy in the treatment of lower respiratory tract infections.

In this study the efficacy and cost-effectiveness of i.v. ceftriaxone 1 g once daily (CTX) was compared with standard i.v. antibiotic treatment (STD) for lower respiratory tract infections (LRTI). STD was given according to the guidelines of the American Thoracic Society and consisted of either cefuroxime 1500 mg three times daily (q8h), amoxicillin/clavulanic acid 1200 mg q8h or ceftriaxone 2 g once daily; each with or without a macrolide. After a minimum of 5 days i.v. therapy, patients could be switched to oral therapy. One hundred patients were enrolled in the study; 52 patients received CTX and 48 STD. Groups were comparable with respect to demographic and baseline characteristics. Seventy patients had a confirmed diagnosis of pneumonia. Twenty-nine patients had a severe type I exacerbation of chronic bronchitis. In one patient the diagnosis of LRTI could not be confirmed. In approximately 50% of the patients a microbiological diagnosis could be made. The most important isolated pathogens from sputum and blood were (positive blood cultures in brackets): Streptococcus pneumoniae 14 (9) and Haemophilus influenzae 16. Mean duration of i.v. therapy was 7.4 days in both groups. Average duration of hospitalisation was 15.0 days for CTX patients and 15.9 days for STD patients. Overall cure and improvement rate at the end of treatment was 47 (90%) for patients receiving ceftriaxone 1 g compared to 37 (77%) for patients receiving standard therapy. Pathogens were eradicated or presumed to be eradicated in 84% of the CTX patients and in 76% of the STD patients. Mean total costs per treatment were lower for CTX than for STD treatment: NLG 169 versus 458. These results show, that i.v. ceftriaxone 1 g once daily is as effective as standard therapy in the treatment of LRTI and that its use reduces treatment costs, in view of the multiple daily dosing regimens of most standard therapies.     

评价氨曲南对泌尿道、胆道和下呼吸道感染的抗菌活性

目的评价氨曲南对泌尿道、胆道及下呼吸道的抗菌活性。方法用自动细菌鉴定和药敏系统，部分药敏试验用纸片扩散法。从氨曲南对泌尿道、胆道和下呼吸道分离革兰阴性致病细菌的体外敏感试验结果，评价其临床应用价值。结果氨曲南对引起泌尿道感染的前3位致病菌(包括大肠埃希氏菌、肺炎克雷伯菌和奇异变形杆菌)的敏感率分别为97％，99％和93％；对胆道感染前5位致病菌(包括大肠埃希氏菌、肺炎克雷伯菌、枸橼酸杆菌、沙雷菌和铜绿假单胞菌)的敏感率分别为97％，90％，70％，77％和71％；对下呼吸道感染分离的细菌(包括铜绿假单胞菌、大肠埃希氏菌和肺炎克雷伯菌)的敏感率分别为60％，67％和60％。结论氨曲南对严重泌尿道和胆道感染有效、安全。     

Lopinavir/ritonavir: appraisal of its use in HIV therapy

Recommendations for a highly active antiretroviral therapy in either pretreated patients or symptomatic patients with an AIDS-defining event include at least one protease inhibitor. The majority of currently available protease inhibitors are coadministrated with low-dose ritonavir, a pharmacoenhancer that significantly increases protease inhibitor plasma concentrations. In the class of protease inhibitors lopinavir plus ritonavir is the only coformulation. This coformulation was designed to overcome the problems of earlier agents of this class of drugs concerning unfavorable pharmacokinetics with a higher frequency of dosing and therapy failure. The pharmacoenhancing effect of ritonavir on lopinavir resulted in a highly potent, clinically effective antiretroviral drug with a high genetic barrier to viral resistance. Safety concerns have taken a backseat, focusing instead on the favorable efficacy of lopinavir, which recently led to the evaluation of its use in boosted double-protease-inhibitor regimens, as a once-daily application and even in HIV monotherapy. Nevertheless, since HIV infection became a chronic but controllable disease, side effects like metabolic disorders and cardiovascular disease have begun to draw increased attention in the long-term treatment with protease inhibitors. Coformulated lopinavir/ritonavir is available as a soft gelatin capsule (133.33/33.33 mg), liquid formulation (80/20 mg/ml) and recently approved melt-extrusion tablet (200/50 mg). Lopinavir/ritonavir is recommended for first- and second-line therapy in HIV-1 infection, in children as well as adolescents and adults.     

Clinical studies of ceftizoxime suppositories in respiratory tract infections and urinary tract infections in children

A fundamental and clinical study of ceftizoxime (CZX) suppositories was performed in pre-school and school-age children. The average time courses of CZX serum and urinary concentrations after administration of CZX suppository 250 mg (i.e. per kg body weight doses of 8.3-10.9 mg) to 4 school-age children were as follows. Serum concentrations: 6.1 micrograms/ml at 15 minutes, 6.3 micrograms/ml at 30 minutes, 3.8 micrograms/ml at 1 hour, 1.7 microgram/ml at 2 hours, 0.5 microgram/ml at 4 hours and 0.2 microgram/ml at 6 hours with a biological half-life of 1.43 hours. Urinary concentrations: 885 micrograms/ml for 0-2 hours, 209 micrograms/ml for 2-4 hours and 112 micrograms/ml for 4-6 hours with an average 6-hour urinary recovery rate of 25.6%. The clinical and biological effectiveness and adverse reactions were studied in 11 infants and school-age children afflicted with various infections (acute purulent tonsillitis, 1; acute bronchitis, 3; acute pneumonia, 4; and UTI, 3). The clinical responsiveness was "excellent" in 8, "good" in 2, and "failure" was recorded in 1, with an overall efficacy of 90.9% inclusive of "excellent" and "good". The microbiological effectiveness of CZX suppositories on presumed pathogenic organisms comprising 4 strains of H. influenzae, 1 strain of H. parainfluenzae, and 3 strains of E. coli was satisfactory, as evidenced by the substantially high eradication rate of 87.5%. The only organism that survived CZX suppository treatment was 1 strain of H. influenzae which however was greatly decreased. The only side effect was diarrhea in 1 patient, which however did not necessitate withdrawal of the drug. The only laboratory test abnormality was GOT and GPT elevation in 1 patient which was normalized within 8 days. In conclusion, CZX suppositories were found to be efficacious and safe for treatment of bacterial infections in children.     

Imipenem/cilastatin: a pharmacoeconomic appraisal of its use in intra-abdominal infections

Imipenem/cilastatin possesses a very broad spectrum of antibacterial activity that encompasses the range of Gram-negative and Gram-positive aerobes and anaerobes usually associated with intra-abdominal and other polymicrobial infections. Its therapeutic efficacy is comparable to that of aminoglycoside/antianaerobe combination regimens, and the most commonly reported adverse effects are similar to those of other beta-lactam antibacterials and are generally of a non-serious nature. The acquisition cost of imipenem/cilastatin is generally greater than that of aminoglycoside/antianaerobe combination regimens, but treatment with the latter incurs the additional costs of multiple intravenous administration, aminoglycoside pharmacokinetic and other monitoring, and possible nephrotoxicity and ototoxicity. The available pharmacoeconomic studies show a trend towards lower total treatment costs with imipenem/cilastatin compared with gentamicin plus clindamycin. Results from other sources suggest that imipenem/cilastatin may achieve further cost savings through reduced duration of hospitalisation. Although further study is required to confirm these trends, it appears that the total treatment cost of imipenem/cilastatin does not exceed that of usual combination therapy and the risk of aminoglycoside-induced toxicity is avoided.     

474例下呼吸道感染病人应用抗菌药物的费用--效果分析

目的：了解下呼吸道感染病人抗菌药物应用情况，评价其用药合理性。方法：对2002年10月-2003年5月期间474例下呼吸道感染病人住院期间应用药物的资料作回顾性统计，并按应用抗菌药物的费用分档．对相关费用比、DDD值、治愈率等因素进行分析和评价。结果：人均应用抗菌药费用1838．63元，住院费、药费、抗菌药费比为1：044：021。结论：本组抗菌药物应用基本合理。