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PubMed1992

A multicentre trial of cefaclor advanced formulation versus cefaclor in the treatment of acute bronchitis.

Two prospective randomized, double-blind, parallel studies were carried out in Europe to compare cefaclor advanced formulation (cefaclor AF) with cefaclor in the treatment of acute bronchitis caused by susceptible pathogens. A total of 1,321 patients suffering from acute bronchitis confirmed by clinical data and a negative chest X-ray were randomized for treatment in the two multicentre trials. Three doses of cefaclor AF were tested: 375 mg twice daily and 500 mg twice daily were compared with cefaclor 250 mg three times daily; and cefaclor AF 750 mg twice daily was compared with cefaclor 500 mg three times daily. Duration of therapy was seven days. Assessments (complete history, physical examination, sputum specimens for culture and Gram's stain, plus clinical and laboratory evaluations of safety) were carried out within 24 hours before the first dose, during therapy, within 72 hours after therapy completion and, in the 375 mg and 500 mg dose groups, 1-2 weeks after the end of therapy. There were no significant differences between the total evaluable cefaclor AF population and the total evaluable cefaclor population with regard to favourable post-therapy responses. Most favourable clinical and bacteriological response rates in the 375 and 500 mg doses were 80% or above. In the higher dose group, there was a favourable post-therapy symptomatic response in 100% of evaluable patients, with favourable bacteriological responses in 93.3% patients receiving cefaclor AF and 96.8% receiving cefaclor (no significant difference). Only one serious drug-related adverse event was reported (anaphylactic reaction). Adverse events related to the digestive system were reported by 4.7% of the cefaclor AF-treated patients and 4.5% of the cefaclor-treated patients during the entire study period. Cefaclor AF, at all three dose levels studies, was seen to be as safe as cefaclor in the treatment of acute bronchitis caused by Streptococcus pneumoniae, Haemophilus influenzae and Moraxella (Branhamella) catarrhalis.

Acute Disease↗
PubMed1992

Cefaclor AF versus cefaclor in acute exacerbations of chronic bronchitis.

The effectiveness and safety of cefaclor advanced formula (AF) compared with cefaclor in the treatment of acute exacerbations of chronic bronchitis were evaluated in multicentre trials in the United States and Europe. In the US study, patients were randomized to receive either cefaclor AF 375 mg twice daily or 500 mg twice daily or 250 mg cefaclor three times daily. Three dose levels of cefaclor AF were used in the European study: 375 mg, 500 mg and 750 mg twice daily; the comparative agent was cefaclor 250 mg three times daily in the 375 mg and 500 mg strata, and cefaclor 500 mg three times daily in the 750 mg stratum. The total number of patients receiving cefaclor AF was 667 versus 357 patients receiving cefaclor. Results showed that cefaclor AF administered twice daily at 375, 500 or 750 mg was as effective as cefaclor 250 mg three times daily for the treatment of acute exacerbations of chronic bronchitis. Evaluable patients receiving cefaclor AF in the US study had a clinical response rate of over 90% and a bacteriological response rate of over 85%. In the European study, patients receiving cefaclor AF had clinical response rates over 85% and bacteriological response rates ranging from 50% to 85%. The safety profile for cefaclor AF was similar to that reported for other beta-lactam antibiotics.

Adolescent↗
PubMedDate not supplied

Cefaclor advanced formulation versus cefaclor in the treatment of pneumonia.

The use of cefaclor advanced formulation (cefaclor AF) in the treatment of pneumonia caused by susceptible organisms was investigated in a multi-center trial conducted in the United Kingdom and the United States. A total of 266 patients were enrolled in this double-blind, double-dummy, randomized, parallel study; 132 patients were treated with cefaclor AF and 134 patients received the reference drug cefaclor. Inclusion criteria were a diagnosis of lobar pneumonia or bronchopneumonia, with a positive sputum culture and an infiltrate on chest roentgenogram. Patients received either cefaclor AF (750 mg twice daily) or cefaclor (500 mg three times daily) for 10 to 14 days. Forty patients in the cefaclor AF group and 45 in the cefaclor group were evaluable for efficacy, with 37 (92.5%) and 43 (95.6%), respectively, showing a favorable posttherapy clinical response. Proven or presumed pathogen elimination was achieved in 87.5% and 86.7% of cases, respectively. Both study drugs demonstrated high levels of activity against Streptococcus pneumoniae, Haemophilus influenzae (including beta-lactamase-producing strains), and Moraxella catarrhalis (including beta-lactamase-producing strains). There were no statistically significant differences between drugs in efficacy results. One or more side effects were reported by 42.4% of the patients treated with cefaclor AF and by 44.0% of those treated with cefaclor; diarrhea, nausea, headache, and respiratory disorders were the most common adverse events. No drug-related side effects were seen with a frequency or severity that would be unexpected with the use of oral cephalosporins. Cefaclor AF and cefaclor performed equally well with respect to clinical and bacteriologic response rates in the treatment of pneumonia.

Administration, Oral↗
PubMed1979

[Experience with cefaclor in the treatment of ear, nose and throat infections. Indications for cefaclor therapy (author's transl)].

The efficacy and tolerance of the new oral cephalosporin cefaclor was tested in 61 patients treated for a variety of moderate to severe ENT infections which were not expected to undergo a spontaneous remission without antibacterial therapy. The most frequently isolated pathogens were streptococci and Staphylococcus aureus. The dosage consisted of 500 mg cefaclor three times daily, and the treatment lasted between 4 and 43 days (average 14 days). In 35 cases, some of whom had already been treated unsuccussfully with another antibiotic, the results were very good. In 22 patients locally applied medicaments or surgery contributed to the good result. In four patients an unequivocal evaluation was not possible or therapy was not successful. The frequently noted rapid response to treatment with cefaclor was impressive. No relapses were recorded. In pharmacokinetic studies a cefaclor concentration of 2.8 mcg/g was obtained in the tonsils 90 minutes after oral administration of 1000 mg. Clinical examinations in 61 patients and a complete range of laboratory tests in 47 patients did not reveal any case of allergic reaction. One patient only complained of nausea and diarrhoea. In two patients temporary low grade thrombopenia and thrombocytosis respectively were observed. In several patients a slight transitory rise in transaminases was seen. Cefaclor thus proved to be an effective and well-tolerated antibiotic. Its indications in the treatment of ENT infections are discussed.

Adolescent↗
PubMed1990

[A double-blind comparative study of S 6472 (a long-acting cefaclor) versus a conventional cefaclor preparation in complicated urinary tract infections].

For an objective evaluation of the clinical efficacy, safety and usefulness of S 6472 (a long acting cefaclor) in non-catheterized patients with complicated urinary tract infections, a double-blind comparative study was performed using conventional cefaclor preparation (hereafter, CCL) as the control drug. S 6472 was administered orally at a single dose of 750 mg twice daily, and CCL at a single dose of 500 mg 3 time daily. The duration of the treatment was 5 days for either drug. Clinical efficacies were evaluated according to the criteria for evaluation of drug efficacy by the Japanese UTI Committee (3rd edition), and the following results were obtained. 1. The initial distribution of the patients' background characteristics was not significantly different between the S 6472 and CCL groups. 2. The overall clinical efficacy rates were 76.2% in the S 6472 group and 75.5% in the CCL group, indicating no significant difference between the 2 groups. When clinical efficacies evaluated according to different types of infections (UTI groups), the differences between the 2 drug groups were not significant in any of disease groups 2, 3, 4, and 6. 3. Clinical efficacy rates as evaluated by attending physicians were not significantly different between the 2 groups, either. 4. Bacteriological responses were evaluated as eradicated in 81.2% in the S 6472 group and 78.3% in the CCL group, suggesting no statistically significant difference. 5. The incidences of side effects were 2.9% (4/139) in the S 6472 group and 0.7% (1/141) in the CCL group, thus no significant differences existed between the 2 groups. On laboratory examination, 4 and 5 abnormal test values, respectively, were detected in 3/94 patients in the S 6472 group and 5/100 patients in the CCL group, but the difference was not significant between the 2 groups, either. All of these side effect symptoms and abnormal laboratory test values were mild in severity and transient. The results of the overall safety rating which was based on the evaluations of the side effects and laboratory test values indicated no significant difference between the 2 groups. 6. According to judgement by the attending doctors, the clinical usefulness rates evaluated based on the results of the efficacy and safety ratings were not significantly different between the S 6472 and CCL groups. These findings suggest that S 6472 produces excellent therapeutic results in complicated UTI patients without indwelling catheters and its clinical efficacy, safety, and usefulness are equal to those of the conventional CCL.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗
PubMed1985

[Clinical evaluation of sustained release preparations of cefaclor in dental infections. Comparative double blind clinical studies of sustained release preparations with a regular preparation of cefaclor].

In vitro viable cell count studies of sustained release preparations of cefaclor (CCL) conclude that the mixture of nonenteric and enteric coated granules of CCL in the ratio of 4 to 6 is the most appropriate form (4:6 form) for the sustained release preparation of CCL. In order to clinically confirm the above conclusion, comparative double blind clinical studies of 3 mixtures forms (2:8, 4:6 and 6:4 forms) with a regular preparation (CCL form) were conducted in dental infections regarding efficacy, safety, and usefulness of the 4 forms. Evaluable cases for efficacy and usefulness were 364 in total (96 cases for the 2:8 form group, 89 cases for the 4:6 form group, 89 cases for the 6:4 form group, and 90 cases for the CCL form group). Evaluable cases for safety were 404 cases in total (102 for the 2:8 form, 100 for the 4:6 form, 102 for the 6:4 form, and 100 for the CCL form). Daily dose of the 3 forms of sustained release preparations was 375 mg b.i.d. after breakfast and dinner and that of the CCL form 250 mg t.i.d. after breakfast, lunch and dinner. Following are the results of the clinical studies: There were no significant differences among the 4 patient-groups (2:8 form, 4:6 form, 6:4 form, and CCL form) regarding background factors of the patients and findings of their subjective and objective symptoms before the initiation of the administration, and it was therefore confirmed that there were no problems in conducting the comparative double blind clinical studies. Overall clinical effective rate determined by the efficacy evaluation criteria of the Japanese society of oral surgery (JSOS) were 89.5% at day 3 and 94.8% at day 5 in the 2:8 form group, 87.4% at day 3 and 95.5% at day 5 in the 4:6 form group, 86.4% at day 3 and 91.0% at day 5 in the 6:4 form group, and 93.3% at day 3 and 96.7% at day 5 in the CCL form group. The effective rate determined by the physicians who actually treated the patients were 84.4% in the 2:8 form group, 87.6% in the 4:6 form group, 84.1% in the 6:4 form group, and 87.8% in the CCL form group. In both judgments by the efficacy evaluation criteria of JSOS and the physicians, there were no significant differences among the 4 forms regarding overall clinical efficacy.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1985

[Clinical evaluation of S6472 (prolonged action preparation of cefaclor) in the treatment of skin and soft tissue infections. A double blind comparison of S6472 and cefaclor].

A double-blind comparative study of S6472 and cefaclor (CCL) was conducted to evaluate the therapeutic efficacy, safety and usefulness in the treatment of skin and soft tissue infections. Either 750 mg b.i.d. of S6472 or 750 mg t.i.d. of CCL was administered orally to patients for a period of 7 consecutive days. Of the 250 cases (123 cases of S6472 group and 127 cases of CCL group) recruited in this trial, 228 cases (114 cases of S6472 and 114 cases of CCL) were adopted by the committee members for the evaluation of therapeutic efficacy, 238 cases (118 cases of S6472 group and 120 cases of CCL group) for usefulness, and 245 cases (121 cases of S6472 group and 124 cases of CCL group) were adopted for the evaluation of side effects. The backgrounds of both patients group were almost similar. The results obtained were as follows: Overall clinical effectiveness Of the 114 patients treated with S6472, excellent clinical responses were obtained in 11 patients, good in 79, fair in 19, poor in 5 (efficacy rate 78.9%), and of the 114 patients treated with CCL, excellent were in 16, good in 78, fair in 13, poor in 7 (efficacy rate 82.5%). There was no statistically significant difference between the 2 groups. Clinical effectiveness classified by initial severity and bacteriological efficacy There was no significant difference between the 2 groups in the clinical effectiveness classified by initial severity and in the bacteriological efficacy. Side effects were noticed in 5 patients of 121 treated with S6472 (4.1%) and in 2 patients of 124 treated with CCL (1.6%), and other 13 patients developed some abnormal laboratory findings. But these undesirable reactions were mild, and developed no significant difference between the 2 groups in the incidence of side effects. There was no significant difference between the 2 groups in the usefulness of the drugs. Conclusively, 750 mg b.i.d. of S6472 is anticipative of the same clinical efficacy, safety and usefulness as compared with that of 750 mg t.i.d. of CCL in the treatment of skin and soft tissue infections.

Administration, Oral↗
PubMed1992

Pharmacokinetics of cefaclor AF: effects of age, antacids and H2-receptor antagonists.

The pharmacokinetics and bioavailability of cefaclor advanced formulation (cefaclor AF) were investigated in two studies, one comparing healthy elderly and younger volunteers and the other assessing the effects of an antacid and H2-receptor antagonist on cefaclor AF bioavailability. The pharmacokinetics of a 750 mg dose of cefaclor AF were studied in 30 subjects ranging in age from 65 to 84 years and 10 control subjects 21-45 years of age. Compared with controls, elderly subjects exhibited higher plasma concentrations of cefaclor which were attributed to lower plasma clearance. There was a strong association between age and renal function, and the plasma clearance of cefaclor was highly dependent upon renal function. Thus, elderly patients with impaired renal function had a reduced ability to eliminate cefaclor. Due to a short elimination half-life and wide therapeutic index, dosage adjustments are not necessary in patients exhibiting moderate renal dysfunction. The 15 healthy men in the second trial were crossed over to receive five treatments, including cefaclor AF (500 mg) alone, cefaclor AF with or preceded by cimetidine, cefaclor AF followed by Maalox TC and cefaclor immediate release (500 mg) alone. Cefaclor AF and immediate release cefaclor had similar bioavailability, but plasma concentrations were maintained for a longer period of time when cefaclor AF was administered. Cimetidine did not alter the bioavailability of cefaclor AF but Maalox TC, coadministered with cefaclor AF, reduced the extent of absorption. This suggests that cefaclor AF bioavailability is influenced by the antacid Maalox TC but not by H2-receptor antagonist cimetidine.

Adult↗
PubMed1992

Cefaclor AF in the treatment of streptococcal pharyngitis/tonsillitis.

Two double-blind, double-dummy, randomized multicentre studies compared the safety and efficacy of 10-day regimens of cefaclor advanced formulation (cefaclor AF) (375 mg twice daily) with cefaclor (250 mg three times daily) in the treatment of proven group A beta-haemolytic streptococcal pharyngitis/tonsillitis. Of the 1,138 patients enrolled, 764 (cefaclor AF:392; cefaclor: 372) were evaluated for efficacy. All patients enrolled in the studies (570 treated with cefaclor AF and 568 treated with cefaclor) were evaluated for safety. Clinical and bacteriological evaluations were performed on treatment days 4-6, and after completion of treatment within 3-5 days and 2-3 weeks. In evaluable patients, the post-therapy clinical success and bacteriological cure rates for cefaclor AF were 96.7% and 93.6%, respectively; the rates were 98.1% and 94.1% for cefaclor. Sixteen cefaclor AF-treated patients and 14 cefaclor-treated patients withdrew early from the trial because of adverse events. There were no significant differences between treatment groups in the overall number of adverse events reported. Diarrhoea was the most frequently reported adverse event (5.6%) in cefaclor AF-treated patients, and headache/migraine was the most frequently reported adverse event (5.6%) in the cefaclor-treated patients. Cefaclor AF (375 mg twice daily) is as effective and safe as cefaclor capsules (250 mg three times daily) in the treatment of streptococcal pharyngitis/tonsillitis.

Cefaclor↗
PubMed1992

Comparative trials of cefaclor AF in uncomplicated cystitis and asymptomatic bacteriuria.

Two different doses of cefaclor advanced formulation (AF), a new sustained-release formulation of cefaclor, were compared with the regular formulation of cefaclor for efficacy and safety in the treatment of uncomplicated cystitis and asymptomatic bacteriuria. A 7-day course of treatment was used, and the trials were double-dummy and double-blind. In one trial, cefaclor AF 500 mg once daily (at night) was compared with cefaclor 250 mg three times a day. Satisfactory clinical and bacteriological responses were found in 179/189 (94.7%) and 160/191 (83.8%) patients, respectively, given cefaclor AF and in 82/87 (94.3%) and 74/90 (82.2%) patients given cefaclor, 5-9 days after the end of treatment. In the other trial, cefaclor AF 375 mg twice daily was compared with cefaclor 250 mg three times a day. Satisfactory clinical and bacteriological responses were obtained in 164/180 (91.1%) and 156/184 (84.8%) patients, respectively, given cefaclor AF, and in 86/92 (93.5%) and 81/93 (87.1%) patients taking cefaclor, 5-9 days after the end of treatment. Very similar results were found in both studies in those patients who were assessable 3-5 weeks later. Only 4.3% and 2.4% of patients treated with cefaclor AF (375 mg and 500 mg, respectively) and 2.2% of cefaclor patients discontinued therapy due to adverse events. The three most commonly reported events were vaginal moniliasis or vaginitis (8.6%), headache (5.0%) and nausea (4.8%). No significant differences were found between clinical efficacy and safety parameters in the different study groups, and it was concluded that cefaclor AF in a twice-daily or once-daily dosage is as effective and as safe as the currently recommened three-times-a-day dosage of cefaclor.

Adolescent↗
PubMed1992

Comprehensive safety profile of cefaclor AF in respiratory, urinary tract and skin infections.

The safety of cefaclor advanced formulation (cefaclor AF) was evaluated in 3,272 patients participating in 11 controlled clinical trials in comparison with cefaclor (2,210 patients) for a variety of infectious illnesses. Daily doses of cefaclor AF ranged from 500 to 1500 mg, with a mean duration of treatment of 8.1 days (range 1-18 days). There were no significant differences between the cefaclor AF- and cefaclor-treated groups in the frequency of adverse events by body system for all events reported. The majority of adverse events related to therapy were mild and transient. Severe adverse events occurred in 2.1% of the cefaclor AF group and 2.7% of the cefaclor group. The most frequently reported adverse events for cefaclor AF were diarrhoea (3.4%), headache (3.2%), nausea (2.5%) and vaginal moniliasis (2.5% of females). Drug-related adverse events led to early discontinuations in 1.7% of cefaclor AF-treated patients and 1.6% of cefaclor-treated patients. Overall, there were few significant differences in the frequency of adverse reactions between older and younger patients. Notably, elderly patients reported significantly less diarrhoea and fewer hypersensitivity-type reactions. There were, however, more therapy discontinuations due to adverse effects in patients aged 65 years or older than in those less than 65 years of age. Many of the discontinuations were thought to be unrelated to therapy. Alterations in laboratory values in patients treated with cefaclor AF were similar to those seen with other beta-lactam antibiotics. The comprehensive data indicate that cefaclor AF is a safe therapeutic option for a variety of common bacterial infections.

Adolescent↗
PubMed1979

[Assay of cefaclor in serum and urine (including stability test) using high pressure liquid chromatography (author's transl)].

Using high pressure liquid chromatography (reverse phase method) a study was made of the stability of cefaclor dissolved in sodium citrate buffer, normal serum and urine and stored for different periods of time at 4 degrees C and 37 degrees C. In sodium citrate buffer (pH 4.0) and in urine (pH 6.0) no appreciable loss of activity of cefaclor occurred at either 4 degrees C or 37 degrees C, even after longer periods of storage (up to 24 h). Serum containing cefaclor stored at 37 degrees C lost about 4% of the active cefaclor after 30 min, 13% after 1 h and 20% after 2 h; no cefaclor could be detected after 24 h. The loss was lower during storage of serum containing cefaclor at 4 degrees C, and after 24 h 60% of the initial concentration of active cefaclor was found. Using a lichrosorb-NH2 column, it could be demonstrated that after 24 h storage of serum containing cefaclor, only phenylglycine, but not amino-chloro-cephem-carboxylic acid or cefaclor was present. After oral administration of 1 g cefaclor, cefaclor was present in the serum and urine of adult volunteers and only small amounts of phenylglycine and amino-chloro-cephem-carboxylic acid.

Adult↗
PubMedDate not supplied

Efficacy of cefaclor AF in the treatment of skin and skin-structure infections.

Cefaclor advanced formulation (cefaclor AF) was compared with cefaclor for the treatment of skin and skin-structure infections in a double-blind study at 28 centers in North America. Of the 563 patients originally randomized, 278 patients received cefaclor AF (375 mg twice daily) and 285 patients received cefaclor (250 mg three times daily). A total of 154 patients treated with cefaclor AF and 157 patients treated with cefaclor qualified for the efficacy analysis after completing 7 days of therapy. At the post-therapy visit, favorable clinical response rates for evaluable patients were 97.4% in the cefaclor AF group and 94.9% in the cefaclor group; favorable bacteriologic response rates were 85.7% and 84.1%, respectively. At the late post-therapy evaluation, 7 to 14 days after completion of therapy, favorable clinical response rates were 90.1% in the cefaclor AF group versus 89.9% in the cefaclor group, and favorable bacteriologic response rates were 88.7% and 86.9%, respectively. No significant difference was seen between the groups in clinical or bacteriologic efficacy at either evaluation or in the frequency of nature of side effects reported during the study.

Abscess↗
PubMed1992

Safety and efficacy of lomefloxacin versus cefaclor in the treatment of acute exacerbations of chronic bronchitis.

In two multicenter trials, lomefloxacin and cefaclor were compared as treatments for acute bacterial exacerbations of chronic bronchitis. In total, 522 adult outpatients were enrolled at 50 centers in the United States. Patients were randomized to treatment groups receiving either 400 mg lomefloxacin orally once daily (n = 259) or 250 mg cefaclor every 8 hours (n = 263) for 7-10 days. Both groups were comparable in terms of age, severity of exacerbation, smoking history, theophylline use, and baseline pathogens. The most common baseline pathogens were Haemophilus influenzae, found in 32% of patients in the lomefloxacin group and in 29% in the cefaclor group, Pseudomonas aeruginosa (13% and 16%, respectively), Moraxella (Branhamella) catarrhalis (12% and 13%), and Streptococcus pneumoniae (10% in both groups). Bacterial eradication rates 1-4 days after the completion of treatment for all patients with baseline pathogens were 81.8% in the lomefloxacin group and 62.7% in the cefaclor group (p less than 0.001). Clinical success (disappearance or improvement of presenting signs and symptoms) was noted in 80.0% of patients in the lomefloxacin group and 64.7% in the cefaclor group (p = 0.002). Eradication rates for the subgroup of patients who had pathogens susceptible in vitro to both study drugs and who completed treatment were 97.1% for lomefloxacin and 84.6% for cefaclor (p = 0.002). Clinical success rates in this subgroup were 92.4% for lomefloxacin and 90.1 for cefaclor (p = 0.585). Treatment-related adverse events were reported for 7% of patients in the lomefloxacin group and 5% in the cefaclor group. The most common adverse events in both groups were nausea and diarrhea. Six patients were withdrawn from treatment with lomefloxacin and four from the cefaclor group because of adverse events. There was no clinical or laboratory evidence of theophylline interaction with either treatment. Once-daily oral administration of 400 mg lomefloxacin was an effective, well-tolerated alternative to 250 mg of cefaclor three times daily in the treatment of acute exacerbations of chronic bronchitis.

Acute Disease↗
PubMed1998

Serum sickness-like reaction to cefaclor: lack of in vitro cross-reactivity with loracarbef.

OBJECTIVES: A lymphocyte-based in vitro rechallenge technique was used to examine the potential for cross-reactivity between loracarbef and cefaclor in children who had had adverse reactions to cefaclor. STUDY DESIGN: The study cohort included 10 patients (2.2 +/- 1.1 years old) with a serum sickness-like reaction to cefaclor, five patients (4.1 +/- 4.6 years old) with immediate-type hypersensitivity reactions to the drug, and five patients (1.5 +/- 0.9 years old) who had a delayed hypersensitivity reaction to cefaclor without joint involvement (i.e., not a serum sickness-like reaction). Peripheral blood mononuclear cells were isolated from each patient and were exposed to cefaclor, loracarbef, and the metabolites of each generated with phenobarbital-induced murine hepatic microsomes. RESULTS: Among patients with cefaclor-associated serum sickness-like reactions, lymphocyte killing (expressed as percentage cell kill above baseline) in the presence of cefaclor metabolites (83.6% +/- 42.2%) was significantly (p < 0.02) higher than that observed among the patients with either immediate-type (1.1% +/- 2.4%) or delayed hypersensitivity (0%) reactions. In contrast, loracarbef did not produce significant in vitro cytotoxicity among any of the patient subgroups. Our in vitro evidence was supported at therapeutic rechallenge with loracarbef among three children with cefaclor-associated serum sickness-like reactions who tolerated a full course of therapy without adverse reactions. CONCLUSION: The metabolite-mediated cytotoxicity associated with cefaclor among patients who had had serum sickness-like reactions after therapeutic administration of the drug was not shared with loracarbef. The extent to which the apparent lack of in vitro cross-reactivity between cefaclor and loracarbef may be predictive of clinical cross-reactivity is not known.

Cefaclor↗
PubMed1990

Comparison of cefprozil and cefaclor pharmacokinetics and tissue penetration.

The pharmacokinetics and tissue penetration, as judged by skin blister fluid, of cefprozil and cefaclor were examined in 12 healthy male volunteers. Doses of 250 and 500 mg of each drug were given to fasting subjects in a crossover fashion. Serially obtained plasma, skin blister fluid, and urine samples were analyzed for cefprozil or cefaclor by validated high-pressure liquid chromatographic methods. After oral administration of 250 and 500 mg of cefprozil, mean concentrations in plasma rose to peak levels (Cmax) of 6.1 and 11.2 micrograms/ml, respectively, and those of cefaclor were 10.6 and 17.3 micrograms/ml, respectively. The elimination half-life of cefprozil (1.3 h) was significantly longer than that of cefaclor (0.6 h), and as a result, the area under the curve for cefprozil was about two times greater than that for cefaclor. Both cephalosporins were primarily excreted unchanged in urine. The mean skin blister Cmax values were 3.0 and 5.8 micrograms/ml for cefprozil and 3.6 and 6.5 micrograms/ml for cefaclor after the 250- and 500-mg oral doses, respectively. The mean Cmax values in skin blister fluid for both cephalosporins were comparable and were significantly lower than the corresponding Cmax values in plasma. However, the levels of cefprozil and cefaclor in skin blister fluid declined more slowly than they did in plasma. The skin blister fluid half-life estimates for cefprozil were significantly longer than they were for cefaclor. Parallel to the observation in plasma, the mean skin blister fluid areas under the curve for cefprozil were significantly higher than they were for cefaclor. The plasma and skin blister fluid pharmacokinetic analyses suggest that the exposure of humans to cefprozil is significantly greater than that to cefaclor at the same dose.

Administration, Oral↗
PubMed1994

Serum sickness-like reactions to cefaclor: role of hepatic metabolism and individual susceptibility.

In an effort to explain the increased incidence of serum sickness-like reactions (SSLR) in patients receiving cefaclor, we used an in vitro murine microsomal system as a surrogate for in vivo hepatic drug biotransformation. Lymphocytes from three groups of subjects were exposed to a nonselective mixture of cefaclor metabolites. After an 18-hour incubation of lymphocytes with these metabolites, cells were examined for viability by trypan blue exclusion. The subject groups consisted of patients with a previous history of SSLR after cefaclor therapy (n = 19), patients who experienced adverse reactions to cefaclor suggestive of immediate hypersensitivity (n = 11), and control subjects who had previously tolerated at least two courses of cefaclor therapy without adverse effect (n = 9). Additionally, immediate family members of six subjects with cefaclor-associated SSLR were studied. Lymphocyte killing was 100% greater than baseline (i.e., a non-drug-containing control) in subjects with SSLR compared with those with immediate hypersensitivity reactions (4% cell death above baseline; p < 0.001) and nonaffected control subjects (6% cell death above baseline; p < 0.001). Family studies were consistent with a pattern of maternal inheritance; five of six mothers who had not received cefaclor had a positive (i.e., > or = 35% cell death above baseline) in vitro cytotoxic response. Other studies confirmed the requirement for biotransformation of the parent drug to elicit cell death, demonstrated specificity of the reaction to cefaclor, illustrated a lack of cross-reactivity to cephalexin in subjects with SSLR to cefaclor, and verified the reproducibility of the reaction over time in an affected subject. Our findings indicate that cefaclor associated SSLR may be a unique adverse drug reaction that requires biotransformation of the parent drug and may result from inherited defects in the metabolism of reactive intermediates. Furthermore, this condition can be retrospectively confirmed with an in vitro lymphocyte-based cytotoxicity assay.

Acetaminophen↗
PubMed1979

Summary of laboratory studies on the antibacterial activity of cefaclor.

Laboratory aspects of cefaclor, a new orally-effective cephalosporin antibiotic, are summarized. On the basis of data from a variety of studies, the useful antibacterial spectrum of cefaclor is shown to include all classes of bacteria that are generally susceptible to cephalothin and cephalexin. Cefaclor has a significant potency advantage over cephalexin against many Enterobacteriaceae, Haemophilus sp. and Streptococcus pneumoniae. Bacteria that are susceptible to cefaclor are killed by concentrations at or near the inhibitory concentration. In vitro enzymatic hydrolysis experiments have shown that cefaclor is a relatively good substrate for several beta-lactamases. Orally administered cefaclor is effective in protection of mice from the lethal effects of intraperitoneal challenges with cefaclor-susceptible bacteria. The chemical instability of cefaclor, test medium composition and inoculum density influence the results of in vitro susceptibility tests with cefaclor. Methods for routine susceptibility testing are described.

Animals↗