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Medical research on cefzil
Paediatr Drugs. 2008; 10(6): 391-7
Pichichero ME, Doern GV, Kuti JL, Nicolau DP
OBJECTIVE: To define contemporary levels of resistance of Haemophilus influenzae to antibacterials commonly used to treat children for bacterial respiratory infections, and to assess the probability of achieving the requisite pharmacodynamic exposures for regimens against recent respiratory H. influenzae isolates using Monte Carlo simulation. METHODS: 233 H. influenzae isolates obtained from pediatric outpatients with acute otitis media (n = 55), sinusitis (n = 58), or lower respiratory tract infections ( n = 120) from 1 November 2004 to 30 April 2005 were characterized for beta-lactamase production and susceptibility to a panel of 10 beta-lactam antimicrobials. 5000 concentration-time profiles were simulated for US FDA-approved doses of oral amoxicillin, amoxicillin/clavulanic acid, cefpodoxime, cefprozil, ceftibuten, and cefuroxime using pharmacokinetics and weights of 5-year old male children. The probability of attaining free drug concentrations above the minimum inhibitory concentration (MIC) for 50% of the dosing interval (50% fT>MIC) was assessed for each regimen against this population of H. influenzae. RESULTS: beta-Lactamase production was demonstrated in 67 (28.8%) of the H. influenzae isolates and varied by isolation site (38% acute otitis media, 36% sinusitis, and 21% lower respiratory tract infections). Regarding susceptibility, the rank order of the tested antimicrobials was ceftriaxone = cefixime (100%) > cefpodoxime (99.6%) > ceftibuten = amoxicillin/clavulanic acid (99.1%) > cefdinir (98.7%) > cefuroxime (97.4%) > cefprozil (93.1%) > cefaclor (92.3%) > amoxicillin (63.1%). The most active agents based on pharmacodynamic assessment (50% fT>MIC) were cefpodoxime (98.9%), ceftibuten (95.3%), and high-dose amoxicillin/clavulanic acid (90.4%). Several amoxicillin regimens also achieved a high likelihood of pharmacodynamic target attainment (91.8- 98.6%) when beta-lactamase-positive strains were excluded from the analysis. CONCLUSION: Against H. influenzae, the antibacterials most likely to achieve optimal in vivo exposures in children are cefpodoxime, ceftibuten, and amoxicillin/clavulanic acid.
Paediatr Drugs. 2008; 10(5): 329-35
Fallon RM, Kuti JL, Doern GV, Girotto JE, Nicolau DP
OBJECTIVE: To determine the probability of oral beta-lactam regimens achieving bactericidal pharmacodynamic exposure against pathogens causing acute otitis media (AOM) given contemporary prevalence and resistance rates. METHODS: A 5000-patient Monte Carlo simulation was used to recreate steady-state concentration-time profiles for oral drug administration regimens of amoxicillin, amoxicillin/clavulanic acid, cefpodoxime, cefprozil, ceftibuten, and cefuroxime in a population of 12.5-month-old children. The percent of simulated children in whom free drug concentrations above the minimum inhibitory concentration (MIC) for 50% of the drug administration interval (50% fT>MIC) were achieved was determined; 180 middle ear fluid isolates (56 Haemophilus influenzae and 124 Streptococcus pneumoniae) collected during the 2004 Global Respiratory Antimicrobial Surveillance Project (GRASP) were used. The cumulative fraction of response (CFR) was calculated and weighted against the prevalence of organisms causing AOM extrapolated from the literature. The contribution of a 'Pollyanna phenomenon' for each organism was also incorporated to estimate clinical effectiveness. RESULTS: Against S. pneumoniae isolates, amoxicillin 30 mg/kg every 8 hours (84.7%) achieved the greatest CFR followed by amoxicillin/clavulanic acid and the other amoxicillin-based regimens. Against H. influenzae isolates, cefpodoxime, ceftibuten, and amoxicillin/clavulanic acid each achieved a CFR of >90%. When weighted by the prevalence of AOM-causing pathogens, CFR was highest for cefpodoxime (87.5%), amoxicillin/clavulanic acid (85.7%), and amoxicillin 30 mg/kg every 8 hours (70.8%). The contribution of a 'Pollyanna phenomenon' increased the probability of clinical effectiveness for all agents, with amoxicillin/clavulanic acid (90.2%) and cefpodoxime (90.1%) having the highest weighted CFR. CONCLUSIONS: Based on the recent epidemiologic and resistance profiles of S. pneumoniae and H. influenzae, amoxicillin/clavulanic acid (45 mg/kg every 12 hours) and cefpodoxime (5 mg/kg every 12 hours) provide the greatest likelihood of achieving optimal pharmacodynamic exposures empirically in children with AOM.
The stability of cefprozil in oral suspension CEFZIL.
Acta Pol Pharm. 2008 Mar-Apr; 65(2): 261-5
Jelińska A, Medenecka B, Zajac M, Knajsiak M
The stability of cefprozil in oral suspension CEFZIL was studied by means of the stress stability test. Degradation was evaluated by using an HPLC method with UV detection (280 nm), as described in the monograph of Cefprozil for Oral Suspension, in USP 25. At increased temperature and relative air humidity the degradation of cefprozil in CEFZIL occurs as reversible-consecutive and parallel reactions. The reversible reaction of isomerization is approx. 10 times faster than the parallel degradation reaction of individual isomers. The first-order rate constants of the parallel reactions Z-cefprozil --> product 1 and E-cefprozil --> product 2 were determined at RH = 76.4% at T = 333, 338, 343, 348 and 353 K, and at T = 333 K and RH = 50.9, 66.5, 76.4 and 90.0%. The thermodynamic parameters E(a), deltaH(double dagger) and deltaS(double dagger) of these reactions were calculated.
Turk J Pediatr. 2008 Mar-Apr; 50(2): 120-5
Yildirim I, Ceyhan M, Gür D, Kaymakoğlu I
Bacteriological failure with penicillin that has been used widely for years in group A beta hemolytic streptococcal (GABHS) tonsillopharyngitis is being reported as high as 30%. Because of this unresponsiveness, many different agents are being used as alternative options. We evaluated the effect of clarithromycin, amoxicillin/clavulanate (CAM), cefprozil and benzathine penicillin G (Pen G) on the bacteriological cure, beta-lactamase production, pharyngeal microflora and alpha hemolytic streptococci (AHS) when used in the treatment of pediatric GABHS tonsillopharyngitis. Intramuscular Pen G and oral clarithromycin, CAM and cefprozil were administered to 70 patients who were between 2-16 years of age. Three throat swabs were obtained from each patient (before treatment, and 3 days and one month after treatment). The cultures were evaluated for aerobic and anaerobic bacteria, beta lactamase production, AHS and fungi isolation. Bacteriological cure rates were similar in the four treatment groups (p>0.05). Isolation rates of AHS were 97.1% and 77.9% in clarithromycin group, 100% and 83.8% in CAM group, 97.2% and 98.6% in cefprozil group and 100% and 83.8% in the Pen G group before and after treatment, respectively. The most prominent inhibitory effect on AHS was observed with CAM, while cefprozil had the least effect (p
Southeast Asian J Trop Med Public Health. 2008 May; 39(3): 461-6
Srifuengfung S, Tribuddharat C, Champreeda P, Daniels J, Chokephaibulkit K, Wongwan N, Polwichai P
A total of 400 clinical Streptococcus pneumoniae strains from patients with respiratory diseases were collected from January 2002 to December 2005. In this study, an increased prevalence of penicillin-nonsusceptible S. pneumoniae (PNSP) from 63% in 2002-2003 to 69% in 2004-2005 was found. During 2004-2005, 56% were erythromycin-nonsusceptible S. pneumoniae (ENSP) and 54% were both PNSP and ENSP. The PNSP, ENSP and PNSP+ENSP groups showed similar trends, ie, sensitive to amoxicillin/clavulanate (range 97.2-98.5%), levofloxacin (range 90.7-92.4%), ceftriaxone (range 87.1-89.4%), and ofloxacin (range 64.8-66.1%). Lower levels of susceptibility were detected for azithromycin, clarithromycin, cefdinir, cefprozil, clindamycin, co-trimoxazole, chloramphenicol and tetracycline in penicillin and erythromycin-nonsusceptible strains. Of the macrolide-resistant S. pneumoniae, 55% of strains exhibited the M phenotype and 45% the constitutive MLS(B) phenotype. No pneumococci with the inducible MLS(B) phenotype were detected in Thailand.
J Chemother. 2008 Apr; 20(2): 170-4
Fritsche TR, Biedenbach DJ, Jones RN
Cefditoren and other orally administered cephalosporins are infrequently included in resistance surveillance studies. Here we evaluated 359 contemporary (2004-2006) strains of Streptococcus pneumoniae, including penicillin-intermediate (12.0%) and -resistant (22.8%) subsets from United States patients by reference broth microdilution methods. Cefditoren was the most potent cephalosporin tested (MIC(50), 0.015 mg/L), including against penicillin-intermediate strains (MIC(50), 0.12 mg/L), and was two-, four- and eight-fold more active than cefuroxime, cefdinir and cefprozil, respectively. Penicillin-resistant strains were largely resistant to all tested ss-lactams. We confirm the continued spectrum and potency for cefditoren against S. pneumoniae that surpasses that of other orally administered cephalosporins.
Cefprozil versus Cefuroxime Axetil in the Treatment of Acute Sinusitis.
Clin Drug Investig. 1998; 15(2): 81-90
Brankston ER, Conter HS, Corriveau R, Martel JM, Laroche C, Roy R, Savard C, Roy D, Kelly R, Forget P, Rivard M, Boulerice F
The objective of this multicentre, randomised, open-label, general practice (GP) study was to evaluate the efficacy and tolerability of cefprozil (Cefzil(trade mark), Bristol-Myers Squibb) compared with that of cefuroxime axetil (Ceftin((R)), Glaxo Wellcome) in the treatment of adult subjects with acute sinusitis. Typical of the GP setting, diagnosis was made based solely on clinical signs and symptoms of acute disease. Sinus radiography was performed post-randomisation. A total of 381 adolescent and adult patients were randomly assigned to 10 days' treatment with either cefprozil, 500mg orally twice daily (n = 191), or cefuroxime axetil, 250mg orally twice daily (n = 190). Based on predefined criteria, treatments were found to be equally effective in terms of proportions of patients in the per-protocol population that were cured, improved or failed (p = 0.20). Similar results were observed when the evaluation was performed on the subset of patients with radiographic evidence of sinusitis and when the evaluation was based on the investigator's judgement. Similar rates of adverse events were observed in the two treatment groups. In summary, cefprozil 500mg twice daily is as well tolerated and as effective as cefuroxime axetil 250mg twice daily for the treatment of adolescent and adult patients with clinical signs and symptoms of acute sinusitis.
Diagn Microbiol Infect Dis. 2008 Jun; 61(2): 240-4
Biedenbach DJ, Jones RN, Fritsche TR
Among orally administered cephalosporins, aminopenicillins (+/- clavulanate), and macrolides, cefditoren was the most potent agent against Haemophilus influenzae (MIC(50/90), < or =0.008/0.03 microg/mL; 316 isolates including 100 beta-lactamase-positive and 10 beta-lactamase-negative ampicillin-resistant [BLNAR]) and was 32-, 64-, and 512-fold more potent than cefdinir, cefuroxime, and cefprozil, respectively. Cefditoren (MIC(50), 0.03 microg/mL) was also > or =32-fold more active against BLNAR phenotypes, although newer macrolides provided complete coverage against these strains. All Moraxella catarrhalis isolates were inhibited by cefditoren (0.5 microg/mL), including beta-lactamase producers (MIC(50), 0.12 vs < or =0.008 microg/mL). Cefditoren retains potent activity against respiratory tract isolates in the United States, including those with resistance phenotypes.
Antimicrob Agents Chemother. 2008 May; 52(5): 1880-3
Takahata S, Kato Y, Sanbongi Y, Maebashi K, Ida T
Horizontal transfer of the mutated ftsI gene from beta-lactamase-nonproducing ampicillin-resistant (BLNAR) Haemophilus influenzae to a susceptible strain was examined in vitro under selection with nine oral beta-lactams (ampicillin, amoxicillin, cefprozil, cefuroxime, cefpodoxime, cefdinir, cefcapene, cefditoren, and tebipenem). Compared to the penicillins and the carbapenem, the cephalosporins showed a wide selection window for the genetic transfer.
Antimicrobial resistance of Esherichia coli urinary isolates from primary care patients in Greece.
Med Sci Monit. 2008 Feb; 14(2): CR75-79
Falagas ME, Polemis M, Alexiou VG, Marini-Mastrogiannaki A, Kremastinou J, Vatopoulos AC
BACKGROUND: Most of antimicrobial susceptibility surveillance studies focus on isolates from hospitalized patients. A retrospective analysis of microbiological data of the antimicrobial susceptibility of Escherichia coli urinary isolates from primary care patients in Greece was performed here. MATERIAL/METHODS: The in vitro susceptibility to ampicillin, amoxicillin/clavulanate, cefaclor, cefprozil, trimethoprim-sulfamethoxazole (cotrimoxazole), amikacin, and norfloxacin of 2460 E. coli isolates (01/2005-06/2005) from the urine specimens of patients tested at the laboratories of three Greek primary care diagnostic centers were analyzed. Only the first isolate per patient (2074 females and 386 males) were included in the analysis. RESULTS: The proportion of E. coli urinary isolates that were resistant to cotrimoxazole was 20.8% and 26.4% for females and males, respectively. There were noteworthy differences between age groups; 37.8% isolates from females 55-year-old females, respectively (P55 years old). CONCLUSIONS: These findings offer help to clinicians in deciding the appropriate empirical treatment for primary care patients with urinary tract infection and emphasize the increasing problem of antimicrobial resistance even in the primary care setting in Greece.