Cefprozil

Publisher Website
Google Scholar
Abstract
Cefprozil is an orally active cephalosporin which has demonstrated activity against a wide range of organisms in vitro. It is particularly active against the Gram-positive organisms Streptococcus pyogenes, pneumoniae and agalactiae and against methicillin-susceptible Staphylococcus aureus. Strains of methicillin-resistant S. Aureus are not susceptible to cefprozil. Cefprozil is also moderately active against Haemophilus influenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, many Enterobacteriaceae and certain anaerobic organisms, and is relatively stable to hydrolysis by a number of β-lactamases. In comparative trials, the clinical and bacteriological efficacy of cefprozil 500mg or 20 mg/kg administered once or twice daily has been comparable with multiple daily dosage regimens of erythromycin in patients with tonsillitis or pharyngitis, with cefaclor and amoxicillin/clavulanate in lower respiratory tract infections, with amoxicillin/clavulanate and erythromycin in skin and skin-structure infections and with cefaclor in acute uncomplicated urinary tract infections. The clinical efficacy of cefprozil is similar to that of cefaclor in patients with tonsillitis or pharyngitis but the bacteriological efficacy of cefprozil is significantly greater than that of cefaclor. Cefprozil is clinically more effective than cefuroxime axetil in the treatment of lower respiratory tract infections and demonstrated greater efficacy than cefaclor in one of 2 comparative studies when administered twice daily in patients with skin and skin-structure infections. In children with acute otitis media, cefprozil 15 mg/kg twice daily was as effective as cefaclor or amoxicillin/clavulanate 13.3 mg/kg 3 times daily and was as effective as cefixime 8 mg/kg once daily. The most frequently reported adverse effects associated with cefprozil, diarrhoea and nausea, are usually mild to moderate in severity and discontinuation of treatment is rarely necessary. Thus, cefprozil with its convenient administration regimen appears to be a suitable alternative to cefaclor, cefixime, amoxicillin/clavulanate or erythromycin for the treatment of upper and lower respiratory tract infections, skin and skin-structure infections, and otitis media in children. While cefprozil has shown similar efficacy to cefaclor in the treatment of uncomplicated urinary tract infections, well-controlled clinical trials comparing its efficacy with that of cotrimoxazole (trimethoprim + sulfamethoxazole) in this indication are required. Most tested strains of Citrobacter diversus and Proteus mirabilis and 50 to 90% of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Salmonella spp. and Shigella spp. are inhibited in vitro by cefprozil at concentrations ⩽ 8 mg/L. However, β-lactamase producing strains of E. coli and K. pneumoniae are either less susceptible or resistant to cefprozil. Cefprozil is generally inactive against Citrobacter freundii, Enterobacter spp. and Providencia spp. It has similar potency in vitro to cefaclor against Enterobacteriaceae, is generally more potent than cefalexin and less potent than cefixime. Strains of Neisseria gonorrhoeae, Moraxella catarrhalis, Listeria monocytogenes and Haemophilus influenzae are generally susceptible to cefprozil at concentrations ⩽ 16 mg/L, although some strains of N. gonorrhoea are resistant to the drug. β-Lactamase producing strains of H. influenzae are also susceptible to cefprozil although MICs are increased compared with β-lactamase negative strains. Other aerobes, including Yersinia enterolitica, Campylobacter jejuni, Bordetella pertussis and B. parapertussis are resistant to cefprozil. Cefprozil is highly active against Streptococcus pyogenes, pneumoniae and agalactiae with MIC90 values below 0.5 mg/L, which is at least 2-fold lower than the MICs of cefaclor and cefalexin. Penicillin-resistant strains of Streptococcus spp. are also susceptible to cefprozil. Strains of Enterococcus faecalis and Staphylococcus epidermidis are moderately susceptible to cefprozil (MIC90 16 mg/L) and the majority of Staphylococcus aureus and S. saprophyticus strains are susceptible. Methicillin-resistant strains of S. aureus are not susceptible to cefprozil. Cefprozil is more active than cefaclor, cefalexin and cefixime against Staphylococcus spp. The anaerobes Clostridium perfringens, C. difficile, Propionibacterium acnes and Bacteroides melaninogenicus are susceptible to cefprozil, whereas other strains of Bacteroides are resistant. 50% of strains of Peptostreptococcus spp. were susceptible to cefprozil (MIC50 ⩽ 4 mg/L). Cefprozil is stable to hydrolysis by several β-lactamases. Its stability is intermediate between that of cefalexin and cefaclor to β-lactamases types III, IV and V, and it was more stable than both drugs against types Ia, Ic and Id. Cefprozil has demonstrated antibacterial activity in vivo in murine models of infection. Against various common pathogens, its activity was superior or comparable with that of cefaclor and superior to that of cefalexin. Following a single oral dose of cefprozil 250 to 1000mg in healthy volunteers, peak plasma concentrations (Cmax) of 5.7 to 18.3 mg/L are attained in 1 to 2 hours and there is no evidence of drug accumulation during administration of multiple doses of up to 1000mg 3 times daily. The absorption kinetics of cefprozil are not significantly altered by the intake of food. In children, the pharmacokinetic properties of cefprozil 15 or 30 mg/kg were similar to those observed in adults given a 500 or 1000mg dose. Peak plasma concentrations of 11.2 and 15.9 mg/L were achieved 1.2 and 1.4 hours after children with infections received the lower or higher dose, respectively. The calculated absolute bioavailability of cefprozil is approximately 90%. A Cmax value of 3.0 mg/L was observed in blister fluid of healthy volunteers 2.5 hours after a single dose of cefprozil 250mg and after a single 500mg dose Cmax values of 5.8 and 4.9 mg/L were achieved within 2.5 and 3.5 hours, respectively. The ratio of blister fluid to plasma Cmax values was 0.51. Cefprozil achieved concentrations of about 0.5 to 3.8 mg/kg in tonsillar tissue and 0.4 to 4.9 mg/kg in adenoidal tissue in patients requiring tonsillectomy/adenoidectomy 0.3 to 3.17 hours after administration of a single 7.5 or 20 mg/kg dose. These concentrations were about 50 to 60% lower than those in plasma. Mean concentrations of cefprozil in breast milk did not exceed 3.4 mg/L 6 hours after a single 1000mg dose and only a small fraction of the dose was recovered in milk over a 24-hour period. Cefprozil is about 45% protein bound in healthy subjects. Maximum urinary cefprozil concentrations ranging from 175 to 658 mg/L were reported during the first 4 hours following a single dose of cefprozil 250, 500 or 1000mg. About 60 to 70% of an administered dose was recovered unchanged in the urine of healthy volunteers and the mean elimination half-life during the terminal phase was about 1.3 hours. This was longer in paediatric patients (about 1.8 hours) and was slightly longer in elderly and middle-aged individuals compared with young adults. The elimination half-life of cefprozil is prolonged in patients with renal impairment whereas hepatic impairment does not significantly affect the pharmacokinetics of cefprozil. Haemodialysis removed about 50% of the drug from the body. The clinical and bacteriological efficacy of cefprozil has been investigated in the treatment of otitis media in children, pharyngitis/tonsillitis, skin and skin-structure infections and uncomplicated urinary tract infections in adults and children, and in uncomplicated bacterial sinusitis and lower respiratory tract infections in adults. The majority of clinical trials were multicentre, open and randomised. Cefprozil has been compared with the cephalosporins cefaclor, cefixime and cefuroxime axetil, and also with erythromycin and amoxicillin/clavulanate. Cefprozil 15 mg/kg twice daily and amoxicillin/clavulanate 13.3 mg/kg 3 times daily demonstrated comparable clinical and bacteriological efficacy in 2 studies involving a total of 334 children with acute otitis media. Satisfactory clinical response rates of 84 and 97% were achieved with cefprozil and rates of 78 and 85% were achieved with amoxicillin/clavulanate in the respective studies. Causative pathogens which included S. pneumoniae, H. influenzae and M. catarrhalis were eradicated in 85 and 95% of patients treated with cefprozil and in 82 and 92% of patients treated with amoxicillin/clavulanate. Cefprozil 15 mg/kg twice daily also demonstrated comparable clinical response rates with cefaclor 13.3 mg/kg 3 times daily and cefixime 8 mg/kg once daily in children with otitis media. Satisfactory clinical response rates of 85, 89 and 85% were achieved in the 3 treatment groups, respectively. Subsequent relapse rates ranged between 3 and 20% following cefprozil treatment and were similar to rates in patients treated with the comparator drugs. In patients with pharyngitis and/or tonsillitis, clinical response rates were similar in comparisons of cefprozil 500mg or 20 mg/kg once daily and cefaclor 250mg or 6.6 mg/kg 3 times daily, ranging from 84 to 89%. Bacteriological response rates were significantly higher in patients treated with cefprozil than in patients treated with cefaclor in one study (83 vs 76%; p = 0.035) and overall response rates were also significantly higher in cefprozil treated patients (80 vs 72%; p = 0.018). Cefprozil 20 mg/kg once daily demonstrated similar efficacy to erythromycin 7.5 mg/kg 4 times daily in patients with pharyngitis/tonsillitis. Clinical responses were achieved in approximately 95% of patients in both treatment groups and bacteriological eradication was achieved in all cefprozil patients and in 95.5% of erythromycin patients. A single open, nonrandomised study examined the clinical efficacy of cefprozil 250 or 500mg twice daily in uncomplicated bacterial sinusitis. Satisfactory clinical response rates in the low and high dose treatment groups were 87 and 100%, respectively, and the corresponding rates of bacteriological eradication were 90 and 94%. Cefprozil 500mg twice daily demonstrated similar efficacy to cefaclor 500mg 3 times daily in patients with mild-to-moderate lower respiratory tract infections. Clinical response and bacteriological eradication rates in patients treated with cefprozil were 84 and 82%, respectively and were 79 and 78%, respectively, in patients treated with cefaclor. Cefprozil 500mg twice daily achieved a significantly higher clinical response rate than cefuroxime axetil 500mg twice daily (96 vs 82.5%; p = 0.032), whereas bacteriological eradication rates in the 2 treatment groups were similar (100 and 92%, respectively). There were no differences in clinical response or bacteriological eradication rates in patients treated with cefprozil 500mg twice daily or amoxicillin/clavulanate 500mg 3 times daily. Clinical response rates in the 2 treatment groups were 91 and 87%, respectively and bacteriological eradication rates were 95 and 96%. Cefprozil 250mg twice daily achieved a greater clinical response than cefaclor 250mg 3 times daily in patients with skin and skin-structure infection (95 vs 78%; p = 0.001) in one study, whereas in a larger study, no difference in response rate was observed in patients treated with cefprozil 500mg or 20 mg/kg once daily or cefaclor 250mg or 6.6 mg/kg 3 times daily (92%). In the smaller study, pathogens were eradicated in 86% of patients treated with cefprozil and in 74% of cefaclor patients, although this difference was not statistically significant. When cefprozil 500mg once daily was compared with erythromycin 400mg 4 times a day, clinical response rates were similar in the 2 treatment groups (92 and 91%, respectively) as were bacteriological response rates (89 and 100%, respectively). Cefprozil 500mg once daily also demonstrated similar efficacy to amoxicillin/clavulanate 250/125mg 3 times daily in the treatment of skin and skin-structure infections. Clinical response rates were 85 and 86%, respectively, and bacteriological eradication rates were 88 and 92%. The clinical and bacteriological efficacy of cefprozil 500mg or 20 mg/kg once daily was comparable with that of cefaclor 250mg or 6.6 mg/kg 3 times daily in patients with acute, uncomplicated urinary tract infections. Clinical response rates were between 87 and 94% in cefprozil treated patients and between 78 and 94% in cefaclor treated patients. Corresponding bacteriological eradication rates for the 2 drugs were 80 to 93% and 82 to 94%, respectively. Adverse effects reported in patients treated with cefprozil are generally transient and mild to moderate in severity with only about 2% of patients requiring discontinuation of treatment. The main adverse events reported in both adult and paediatrie patients are gastrointestinal disturbances of which diarrhoea and nausea are the most common, occurring in 3.0 and 2.3% of patients, respectively. Vomiting and abdominal pain are also reported in 1.4 and 0.9% of patients, respectively. Urogenital pruritus (0.8%) and vaginitis (0.7%) have been reported in female patients during treatment with cefprozil, and rash, including diaper rash in infants, occurred in 1.2% of all patients. Alterations in liver enzymes, eosinophil count, platelets, prothrombin time and blood urea nitrogen were reported rarely (⩽ 1%), and isolated instances of leucopenia, neutropenia, and thrombocytosis resolved upon completion of therapy. The overall incidence of adverse effects with cefprozil is similar to that observed with cefaclor or cefuroxime axetil, while comparative studies revealed a significantly higher incidence of diarrhoea in patients treated with cefixime or amoxicillin/clavulanate than with cefprozil. Cefprozil is administered orally, usually for 10 days. In adults, the recommended dosage for pharyngitis/tonsillitis is 500mg once daily. A higher dosage of 1000mg daily in 2 equally divided doses is recommended for secondary bacterial infection of acute bronchitis and acute bacterial exacerbations of chronic bronchitis. For uncomplicated skin and skin-structure infections dosage regimens of either 500mg once daily, 250mg twice daily or 500mg twice daily may be used. Cefprozil 30 mg/kg in 2 divided doses for 10 days is recommended for acute otitis media and pharyngitis/tonsillitis in infants and children. In patients with severe renal impairment (creatinine clearance < 1.8 L/h), half the standard dose of cefprozil should be administered. Dosage supplementation is recommended following haemodialysis.

This publication has 39 references indexed in Scilit: