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PubMed1992

In-vitro bactericidal activity of four oral antibiotics against pathogens responsible for acute otitis media in children.

This study was designed to test the in-vitro activity of four oral antibiotics against the four microorganisms most frequently isolated in acute otitis media: beta-lactamase-positive Haemophilus influenzae (N = 10), beta-lactamase-positive Moraxella catarrhalis (N = 10), penicillin-sensitive Streptococcus pneumoniae (N = 11) and methicillin-sensitive Staphylococcus aureus (N = 10), by the bactericidal curve method. Bactericidal kinetics were determined for concentrations of antibiotic equivalent to those found in the middle ear after treatment: amoxycillin-clavulanic acid (2.5 mg l-1/0.6 mg l-1 and 2.5 mg l-1/1.2 mg l-1), cefaclor (1 mg l-1), erythromycin (0.5 mg l-1) and erythromycin/sulfisoxazole (0.2/3 mg l-1). The inoculum was of 10(6) colony-forming units (cfu) ml-1. The bacterial counts were performed after 5 h and 24 h using a spiral inoculator system. The results showed that amoxycillin-clavulanic acid had rapid bactericidal activity (< 24 h) on the tested organisms at each of the doses used (reduction < or = 3 log10 cfu ml-1) which was not observed with the other antibiotics at either 5 or 24 h. Erythromycin alone or combined with sulfisoxazole had a bacteriostatic effect on Moraxella catarrhalis and Streptococcus pneumoniae but not on Haemophilus influenzae or Staphylococcus aureus. Cefaclor had no bactericidal action under these conditions.

Acute Disease↗
PubMed1999

Spectrofluorometric determination of alpha-aminocephalosporins in biological fluids and pharmaceutical preparations.

A selective and highly sensitive fluorometric method was developed for the determination of four alpha-aminocephalosporins, namely cefaclor, cefadroxil, cephalexin and cephradine. The method involves the reaction of the target compounds with fluorescamine at a specific pH, ranging from 7.8 to 8.4. The produced derivatives exhibit maximum fluorescence intensities at 472-478 nm after excitation at 370-372 nm. The method is highly specific because other alpha-aminocephalosporins whose alpha amino group was blocked do not react similarly and hence do not interfere. At the specific pH range of the reaction where no degradation may occur with that medium the proposed method can be utilised as a stability-indicating assay. The different experimental parameters affecting the derivatisation reaction were carefully studied and incorporated into the procedure. Under the described conditions, the proposed method is linear over the concentration range of 0.05(-1) microg/ml(-1) for both cefaclor and cephalexin, and 0.05-0.65 and 0.025-0.5 microg/ml(-1) for cefadroxil and cepharadine, respectively and the coefficients of determination were greater than 0.999 (n = 3). The recoveries of the title compounds from spiked serum ranged from 88.6 to 89.7% and from spiked urine from 92.2 to 93.3% with a limit of quantitation (LOQ) of 25-50 ng/ml(-1) and limit of detection (LOD) of 5 ng/ml(-1) (S/N = 2) for all drugs. The mechanism of the fluorometric reaction is proposed and the advantages of the proposed method are discussed.

Cefaclor↗
PubMed2000

Antimicrobial activity and in vitro susceptibility test development for cefditoren against Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus species.

Cefditoren, a third generation orally administered aminothiazolyl cephalosporin, has demonstrated bactericidal activity against many Gram positive and negative bacterial pathogens and stability against clinically important beta-lactamases. Cefditoren was compared to cefaclor, cefixime, and penicillins against 1 435 recently isolated strains of streptococci (312 Streptococcus pneumoniae, 165 viridans group streptococci, 142 beta-haemolytic streptococci), Haemophilus influenzae (521 strains), and Moraxella catarrhalis (295 strains). Streptococcus pneumoniae and viridans group streptococci had penicillin nonsusceptible rates of 37.8 and 35.8%, respectively. Cefditoren (MIC(90) in microg/ml/% susceptible) activity against all tested H. influenzae (0.03/100) and M. catarrhalis (0.06-0.5/100) was comparable to cefixime and significantly greater than cefaclor. Cefditoren (MIC(90), 0.5 microg/ml) was 4- to 128-fold more active than comparison beta-lactams against the pneumoococci and was the most potent beta-lactam (including penicillin) versus beta-haemolytic streptococci. Cefditoren pharmacokinetics demonstrate a T(1/2) of 1.5-2 h and C(max) values of 2.8 and 4.6 microg/ml, respectively with 200 or 400 mg doses of cefditoren pivoxil; plasma concentrations exceed 1 microg/ml for 4 to 6 hours (33-50% of dosing interval). Consequently, a susceptible MIC of </= 1 microg/ml or </= 2 microg/ml was proposed with zone diameter correlates of >/= 18 and >/= 15 mm (5-microg disk) for all cited fastidious species tested. Categorical agreement between MIC and disk tests was 94.6 to 100% with a correlation coefficient (r) range of 0.50 to 0.90 for streptococci. H. influenzae intermethod comparison results using the same interpretive criteria were in complete agreement, but exhibited a low r = 0.39. Cefditoren clearly possesses the most potent activity among currently studied oral cephalosporins or penicillin against commonly isolated bacterial pathogens causing bronchitis, pneumonia, sinusitis, or pharyngitis and was active against nearly all penicillin-resistant streptococci at </= 0.5 microg/ml. Expanded clinical investigations seem warranted.

Cefaclor↗
PubMed1983

Synthesis and antibacterial activities of new (alpha-hydrazinobenzyl)cephalosporins.

Some (alpha-hydrazinobenzyl)cephalosporins, I (R = Me, CH2OAc, Cl) and II (R = Me, CH2OAc), structurally related (formula; see text) to cephalexin, cephaloglycin, and cefaclor have been prepared and evaluated in vitro for their antimicrobial activity. The synthesis involves the condensation of the chloride hydrochloride III (R = H or Me) with the 7-aminocephem derivatives IV. The hydrazino compound I (R = Cl), an analogue of cefaclor, resulted in being the most active compound of the series.

Bacteria↗
PubMed1981

Estimation of the biliary excretion of different cephalosporins utilizing retrograde cholangio-pancreatography (ERCP).

In the present study 21 patients undergoing retrograde cholangio-pancreatography (ERCP) were given cefamandole, cefazolin or cefaclor, and plasma and bile concentrations were measured. The cannulation of the common bile duct was possible in most of the patients investigated, but no bile could be obtained in 7 of them. In the patients in whom bile was obtained, concentrations comparable to other studies were estimated, despite a wide variation in the individual patients. In addition, cefaclor, which is not known to be excreted in the bile, showed sufficiently high inhibitory bile concentrations. Using ERCP for the estimation of bile concentrations of different drugs useful information can be obtained about the excretion of certain substances. However, for sophisticated pharmacokinetic studies, the method has certain limitations as compared with classical T-tube sampling.

Adult↗
PubMed2001

Evaluation of oral antimicrobial agent levels in tooth extraction sites.

OBJECTIVE: The purpose of this study was to evaluate various oral antimicrobial agent levels in tooth extraction sites. STUDY DESIGN: The concentration of dental alveolar blood in extraction wounds after the oral administration of talampicillin (500 mg), cefaclor (500 mg), cefteram pivoxil (200 mg), cefuroxime axetil (250 mg), cefdinir (200 mg), and ofloxacin (100 mg) was determined in 338 patients and was assessed on the basis of its antimicrobial activity against Streptococcus isolated in odontogenic infections. RESULTS: The percentage of patients whose concentrations exceeded the minimum inhibitory concentration for 90% of Streptococcus was 62.5% to 100% for talampicillin at 30 to 360 minutes, 0% to 12.5% for cefaclor at 30 to 360 minutes, 18.2% to 100% for cefteram pivoxil at 30 to 480 minutes, 50% to 100% for cefuroxime axetil at 30 to 480 minutes, 0% to 50% for cefdinir at 16 to 290 minutes, and 0% to 40% for ofloxacin at 30 to 480 minutes. CONCLUSION: These results indicate that talampicillin, cefteram pivoxil, and cefuroxime axetil have minimum inhibitory concentration levels for 90% of Streptococcus in tooth sockets.

Administration, Oral↗
PubMed2001

Novel mechanism of hydrolysis of therapeutic beta-lactams by Stenotrophomonas maltophilia L1 metallo-beta-lactamase.

Stopped-flow tryptophan fluorescence under single turnover and pseudo-first-order conditions has been used to investigate the kinetic mechanism of beta-lactam hydrolysis by the Stenotrophomonas maltophilia L1 metallo-beta-lactamase. For the cephalosporin substrates nitrocefin and cefaclor and the carbapenem meropenem, a substantial quench of fluorescence is observed on association of substrate with enzyme. We have assigned this to a rearrangement event subsequent to formation of an initial collision complex. For the colorimetric compound nitrocefin, decay of this dark inter- mediate represents the overall rate-determining step for the reaction and is equivalent to decay of a previously observed state in which the beta-lactam amide bond has already been cleaved. For both cefaclor and meropenem, the rate-determining step for hydrolysis is loss of a second, less quenched state, in which, however, the beta-lactam amide bond remains intact. We suggest, therefore, that the mechanism of hydrolysis of nitrocefin by binuclear metallo-beta-lactamases may be atypical and that cleavage of the beta-lactam amide bond is the rate-determining step for breakdown of the majority of beta-lactam substrates by the L1 enzyme.

Catalysis↗
PubMed1992

Review of the experience with cefprozil for the treatment of lower respiratory tract infections.

A regimen of cefprozil (500 mg twice daily), a new oral cephalosporin with a broad in vitro spectrum of antimicrobial activity, was compared to standard regimens of cefaclor (500 mg three times daily), cefuroxime axetil (500 mg twice daily), or amoxicillin/clavulanate (500 mg/125 mg three times daily) for the treatment of lower respiratory tract infections (mainly bronchitis and acute exacerbations of chronic bronchitis) in adults in three open-label, randomized trials. In the first trial, in which bacterial pathogens were isolated in initial cultures for only one-third of the patients, 90% of the pathogens were susceptible to cefprozil. A satisfactory clinical response was noted for 84% of the evaluable patients who received cefprozil versus 79% of those who received cefaclor for treatment of lower respiratory tract infections; rates of bacteriologic efficacy were 82% and 78%, respectively. In the second study rates of satisfactory clinical response were 96% with cefprozil and 83% with cefuroxime axetil (P less than .03) for treatment of bronchitis; the respective bacteriologic response rates were 100% and 92%. In the third trial, clinical efficacy was 91% for cefprozil and 87% for amoxicillin/clavulanate for treatment of bronchitis; bacteriologic efficacy was 95% and 96%, respectively. Tolerability and safety profiles were comparable, except that there was a higher rate of diarrhea among patients who received amoxicillin/clavulanate (P = .03).

Acute Disease↗
PubMed1992

Clinical trials of cefprozil for treatment of skin and skin-structure infections: review.

Limitations of currently used antimicrobial agents for the treatment of skin and skin-structure infections (e.g., increased resistance to penicillin and erythromycin and inconvenient dosing schedules) have led to an adjustment in the kinds of antimicrobial agents prescribed for these diseases. Three recently completed clinical studies have demonstrated some therapeutic advantages of cefprozil, a new broad-spectrum oral cephalosporin, over cefaclor and erythromycin in the treatment of skin and skin-structure infections. Specifically, cefprozil offers clinical efficacy equivalent to those of cefaclor and erythromycin both at lower total doses and on a less frequent dosing schedule (once or twice daily vs. three to four times daily). The advantage of once-daily or twice-daily dosing with cefprozil may contribute to patient convenience and compliance.

Cefaclor↗
PubMed1998

Antimicrobial susceptibility of community-acquired lower respiratory tract bacterial pathogens isolated in the UK during the 1995-1996 cold season.

The antimicrobial susceptibility of 1078 isolates of Haemophilus influenzae, 348 Streptococcus pneumoniae and 258 Moraxella catarrhalis was determined. Overall 15.1% of H. influenzae produced beta-lactamase; 98.8% were susceptible to co-amoxiclav, 85.8% to cefaclor, 96% to clarithromycin and 100% to ciprofloxacin. The majority (94.2%) of M. catarrhalis produced beta-lactamase. The overall prevalence of low-level penicillin resistance (MIC = 0.12-1 mg/L) amongst isolates of S. pneumoniae was 3.4% and that of high-level resistance (MIC > or = 2 mg/L) was 3.7%. Most (96.3%) of the isolates of S. pneumoniae were susceptible to amoxycillin (MIC < or = 0.5 mg/L), 96% to cefaclor (MIC < or = 8 mg/L), 90.7% to clarithromycin (MIC < or = 0.25 mg/L) and 89% to ciprofloxacin (MIC < or = 1 mg/L).

Amoxicillin-Potassium Clavulanate Combination↗
PubMedDate not supplied

Treatment of osteomyelitis and septic arthritis with cefamandole.

Fourteen patients with bone and joint infections caused by a variety of bacterial pathogens were treated with intravenous cefamandole, 4 to 12 g/day; ten received additional therapy with 2 g/day of cefaclor and one with 2 g/day of cephalexin. Ten of 14 patients were cured. Of those cured, infecting pathogens had minimal inhibitory concentrations of cefamandole of 4 micrograms or less/ml. Of those who were not cured, two had recurrent infections that had not responded to other previously administered antibiotics, one had a mixed infection with resistant strains, and one had positive bone cultures five months after a favorable clinical response. Peak and valley cefamandole serum concentrations were 48.0 to 173.0 micrograms/ml and 23.4 micrograms or less/ml, respectively. Synovial fluid concentrations were 11.1 to 16.7 micrograms/ml and bone concentrations were 0.2 to 20.4 micrograms/g. Adverse effects included leukopenia in one and hepatic enzyme elevations in four patients. Cefamandole, with and without cefaclor, was efficacious in therapy of bone and joint infections caused by susceptible organisms.

Arthritis, Infectious↗
PubMed1988

Five vs. ten days of therapy for acute otitis media.

In a double blind study 175 patients with acute otitis media were randomized into 2 treatment groups: 10 days of therapy with cefaclor or 5 days of therapy followed by 5 days of placebo. The dosage of cefaclor was 40 mg/kg/day administered orally in equally divided doses at 12-hour intervals. Tympanocentesis before treatment yielded specimens that contained Streptococcus pneumoniae or Haemophilus influenzae or both in 55% of specimens. Branhamella catarrhalis was isolated from 21% of specimens. Culture of material from the ear canal of patients with spontaneous perforation of the tympanic membrane of less than 24 hours duration yielded pneumococci or H. influenzae or both in 38% of specimens and staphylococci in 31%. Patients were scheduled for follow-up examinations at 5 or 6, 10, 30, 60 and 90 days. Of the 175 children 151 were evaluable at 10 days. There were 123 patients with both tympanic membranes intact at the time of diagnosis. There were 6 (10%) treatment failures of therapy in the 59 patients assigned to 5 days of therapy and 4 (6%) failures and 1 (2%) early relapse in the 64 assigned to 10 days of therapy (difference not significant). There were 28 evaluable patients with spontaneous perforation. There were 8 (53%) failures in the 15 children assigned to 5 days of therapy and only 1 (8%) failure in the 13 children assigned to receive 10 days of therapy (P = 0.016, Fisher exact test). Rates of reinfection and persistent middle ear effusion at 10, 30, 60 and 90 days follow-up were not significant different in patients assigned to 5 to 10 days of therapy. In patients with acute otitis media with intact tympanic membranes we have not been able to show any advantage of the standard duration of 10 days of therapy over a shortened course of 5 days. A 5-day course of antibiotic therapy does not appear to be sufficient for children with acute otitis media and spontaneous purulent drainage.

Acute Disease↗
PubMed1988

Cost effectiveness in the choice of antibiotics for the initial treatment of otitis media in children: a decision analysis approach.

If the initial use of amoxicillin fails to cure otitis media, a family will be burdened with medical costs for a second medication, additional office visit fees and time lost from employment. For some families the initial choice of a more expensive but more effective antibiotic may be more cost effective. Using a decision analysis approach we compared the cost effectiveness of amoxicillin and cefaclor. As the amoxicillin efficacy rate decreases or as parental salaries are increased, the cost-effective advantage moves towards cefaclor. With the decision analysis method described, a practitioner can use costs and efficacy rates relevant to his or her practice to determine the most cost-effective initial antibiotic for a child with otitis media.

Amoxicillin↗
PubMed1993

Factors influencing outcome in children treated with antibiotics for acute otitis media.

Factors affecting outcome were analyzed from 3 antibiotic clinical trials that had identical case definition and outcome criteria. Overall 102 subjects with acute otitis media had an initial tympanocentesis, were enrolled in one of the clinical trials, were randomized to receive 10 days of oral treatment and had a posttherapy visit. The antibiotics used were cefixime (38), cefaclor (25), loracarbef (14), amoxicillin plus clavulanate (16) or amoxicillin (9). Fifty-five of the 102 (54%) study subjects were classified as cured or improved at the 21- to 28-day posttherapy visit. Factors analyzed in relation to outcome included antibiotic administered, isolation of a pathogen from the middle ear aspirate, study subject age and sex, history of recurrent otitis media, unilateral vs. bilateral involvement, season of enrollment and history of antibiotic administration in the month before enrollment. Univariate analysis identified the following four factors associated with higher posttherapy visit failure rates: a history of recurrent otitis media; enrollment during winter respiratory season (December through March); a history of being treated with an antibiotic during the month before enrollment; and administration of cefaclor compared with other antibiotics. However, only a history of recurrent otitis media and enrollment during the winter respiratory season met the 0.05 significance level for entry into a model derived from logistic regression to assess interactions among factors. Clinical guidelines for the management of otitis media should take into consideration that children with a prior history or recurrent otitis media and infection during the winter season more often fail to respond to antibiotic treatment and have a higher risk of developing a persistent middle ear effusion.

Acute Disease↗
PubMed1994

Management of chronic suppurative otitis media: superiority of therapy effective against anaerobic bacteria.

The aerobic and anaerobic microbiology and management of 69 children who had chronic suppurative otitis media were studied retrospectively. A total of 188 isolates (103 anaerobic and 85 aerobic) were recovered. Anaerobic organisms alone were isolated from 11 (16%), aerobic bacteria only in 21 (30%) and mixed aerobic and anaerobic flora was present in 37 (54%). Forty-five beta-lactamase-producing bacteria were recovered from 60 (58%) patients. The most rapid time for resolution was noticed with clindamycin (8.3 +/- 0.6 days) (P < 0.001), as compared with ampicillin (12.0 +/- 0.8 days), erythromycin (16.5 +/- 1.6 days) and cefaclor (14.6 +/- 2.3 days). Resolution of the infection was achieved in 16 of 20 (80%) of those treated with clindamycin, 12 of 24 (50%) treated with ampicillin, 6 of 13 (46%) treated with erythromycin, and 4 of 12 (33%) treated with cefaclor. Organisms resistant to the antimicrobial used were recovered in 26 of 31 of patients who failed to respond to therapy. These findings indicate the role of resistant aerobic and anaerobic organisms in the polymicrobial etiology of chronic otitis media in children and illustrate the superiority of therapy effective against anaerobic bacteria.

Ampicillin↗
PubMed1982

Benefits and risks of sequential parenteral--oral cephalosporin therapy for suppurative bone and joint infections.

Seventy-five infants and children with suppurative skeletal infections were managed with a sequential parenteral-oral regimen of cephalosporin antibiotic therapy. Initially, parenteral antibiotics (cefamandole for 48 patients and cefuroxime for 27 patients) were given for a median of 5 days. Oral therapy was with large doses of cefaclor (150 mg/kg/day) or cephalexin (100 mg/kg/day). Eight patients (11%) had inadequate serum bactericidal activity with cefaclor. Six of them were successfully managed with alternative oral antibiotics, and parenteral therapy resumed in one patient. Chronic disease developed in a child who was continued on oral cloxacillin therapy in spite of absent serum bactericidal activity. It is concluded that oral therapy can be successful for the majority of patients but that it is hazardous and not indicated if careful laboratory monitoring of compliance and serum bactericidal activity cannot be performed.

Acute Disease↗
PubMed1994

Effect of inoculum size on the in-vitro susceptibility to beta-lactam antibiotics of Moraxella catarrhalis isolates of different beta-lactamase types.

The effect of inoculum size on the results of agar dilution MIC tests was assessed for 20 Moraxella catarrhalis isolates with BRO-1 enzyme, 20 with BRO-2 enzyme and 15 isolates that did not produce beta-lactamase. The compounds tested were ampicillin, coamoxiclav, cefaclor, cefixime and cefetamet, and the inocula were 10(4), 10(5), 10(6) and 10(7) cfu/spot. The MICs of ampicillin for BRO-1 and BRO-2 producers were consistently higher than those for non-producers at inocula of 10(7) cfu/spot but overlapped with those for non-producers at lower inocula. A small beta-lactamase-related inoculum effect was seen with coamoxiclav; small inoculum effects also occurred with cefaclor and cefixime but were not related to enzyme presence or type. MICs of cefetamet were the least affected by the inoculum size. For all the compounds, the degree of correlation between MICs and the inhibition zones observed in disk diffusion tests was independent of the inoculum used in the MIC tests. These data suggest that high inocula should be used to determine MICs of ampicillin for M. catarrhalis but that this precaution is unnecessary with the cephalosporins tested or with coamoxiclav.

Amoxicillin↗
PubMed1996

A case of drug eruption due to simultaneous sensitization with three different kinds of drugs.

We reported a case of drug eruption induced by combined treatment with three different kinds of drugs, amoxapine, mexiletine hydrochloride and cefaclor. A 63-year-old Japanese woman suffering from 11 years of standing reflex sympathetic dystrophy developed multiple erythematous papules on her trunk and extremities after taking 14 kinds of drugs. The provocation challenge produced positive reactions to amoxapine, mexiletine hydrochloride, and cefaclor, but was negative to the other drugs. We discussed the mechanism of simultaneous sensitization to three different kinds of drugs in our case.

Amoxapine↗