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The use of cefaclor in the treatment of beta-haemolytic streptococcal throat infections in children.

Cefaclor was used as a therapeutic agent in beta-haemolytic streptococcal throat infections in children in 3 separate studies. Although the numbers of patients in these ongoing studies are too small for valid statistical analysis, cefaclor was found to be (1) an effective agent in a dose of 20 mg/kg/day, (2) as effective as phenoxymethyl penicillin at identical dosages, and (3) equally effective at doses administered twice daily or thrice daily. It was well accepted by the patients, had minimal side effects, and produced no adverse effects in the peripheral blood.

Adolescent↗

Treatment of acute bacterial bronchitis and pneumonia with cefaclor.

Sixty patients with pneumonia and/or bronchitis were treated with cefaclor, a new orally administered cephalosporin. Of those 60, 27 adults were treated with 500 mg every 8 hours, 26 adults with 250 mg every 6 hours, and 7 children with 50 mg/kg/day. In the adults, pneumonia was caused most frequently by Streptococcus pneumoniae and Haemophilus influenzae. The 7 children had pneumococcal pneumonia. All but 2 adults, both elderly patients with chronic obstructive pulmonary disease, were successfully treated. One instance of drug hypersensitivity occurred. All 7 children responded rapidly, with no side effects, to cefaclor therapy.

Acute Disease↗

[Effect of cefaclor in urinary tract infections (the first report)].

A part of our continuous investigation on the clinical effect of cefaclor against urinary tract infections was reported herein. Cefaclor, a daily dose of 0.75 g t.i.d., has been applied for the treatment of (I) 26 cases with the simple UTI and (II) 41 cases with the complicated. Rates of effectiveness were obtained 100% in (I) and 80% in (II). Side effects were noted in 8 cases (8.4%) out of total 95 cases.

Adolescent↗

[Comparison of the activity of cefaclor with amoxicillin, erythromycin and doxycycline in an in vitro model].

Bactericidal antibiotics like cefaclor and amoxicillin do have a better and prolonged effect on the reduction of the viable cellcount than bacteriostatic ones like erythromycin and doxycyclin, as has been demonstrated in the in vitro model. The influence of the production of beta-lactamases on the kill-kinetics could be studied in this model. While amoxillin became ineffective by the production of beta-lactamases of E. coli and S. aureus the activity of cefaclor was generally maintained. Only a marginal destruction of the drug by the enzymes was observed.

Amoxicillin↗

Comparison of in vitro antibacterial activity of four oral cephems: cephalexin, cefaclor, cefatrizine and cefadroxil.

The in vitro antibacterial activity of four oral cephems: cephalexin, cefaclor, cefatrizine and cefadroxil against clinical isolates of staphylococci, Enterobacteriaceae and Pseudomonas aeruginosa was compared by agar dilution method. All drugs had comparable antistaphylococcal activity. Cefatrizine and cefaclor were more active than cephalexin and cefadroxil against Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis. All four drugs were relatively inactive against isolates of Enterobacter species and indole-positive Proteus. However, cefatrizine demonstrated the greatest activity of the four oral cephems against these organisms. None of these oral cephems was active against Serratia marcescens or Pseudomonas aeruginosa.

Bacteria↗

Penetration of cefaclor to adenoid tissue and middle ear fluid in secretory otitis media.

Seventy-nine patients that had persistent or recurrent secretory otitis media for over 3 months and were scheduled for myringotomy and/or adenoidectomy received a single dose of cefaclor (20 or 40 mg/kg) orally 0.5-4 hours before surgery. Cefaclor concentrations were determined in serum, middle ear fluid and/or blood-free adenoid tissue homogenate using microbiological methods. Concentrations in adenoid homogenate ran parallel to those in serum, indicating a rapid penetration to adenoid tissue. Penetration to middle ear fluid was delayed in comparison. In the 51 patients receiving 20 mg/kg, peak levels occurred after 0.5 hour in serum as well as in adenoid homogenate and middle ear fluid with mean values of 29, 7.5 and 5.1 mg/l, respectively. Concentrations in the middle ear fluid were greater than 2.0 mg/l from 0.5 to 3 hours after this dose. In the 28 patients receiving 40 mg/kg, concentrations levelled after 0.5 hour in serum and in adenoid homogenate, with mean values of 21-33 mg/l and 6.3-12 mg/l, respectively. Concentrations in the middle ear fluid reached 7.8 mg/l 2 hours after this dose. A dose of 20 mg/kg appears to be suitable for treatment of respiratory tract infections on a b.i.d. basis.

Adenoids↗

Therapy of acute bacterial infections with cefaclor in a pediatric population: an open assessment.

Cefaclor, a new semisynthetic cephalosporin, was given orally as a suspension to 22 infants and children with acute otitis media and or/other infections, mainly of the respiratory tract, suspected to be of bacterial origin. The drug was found to be very easily accepted by the patients, and no side effects were encountered. Most patients became asymptomatic within 48 hours. Cefaclor is active against most bacteria producing acute otitis media, including ampicillin-resistant Hemophilus influenzae, and seems to be an effective bactericidal agent in the treatment of upper respiratory tract infections. Caution is recommended when used in bacteremic infants who do not respond promptly to therapy, in view of the poor cerebrospinal fluid levels of the drug and the danger of meningitis.

Acute Disease↗

A double-blind study comparing cefaclor and amoxycillin in the treatment of respiratory tract infections in general practice.

A prospective double-blind study was carried out to compare the efficacy of intermittent versus continuous levels of beta-lactam antibiotics. Two hundred and ninety-eight patients attending their general practitioner and requiring treatment for respiratory tract infections were randomly allocated to receive either 250 mg cefaclor 3-times daily (intermittent) or 500 mg amoxycillin 3-times daily (continuous). By most of the parameters used to assess outcomes, the group on cefaclor did better than the group on amoxycillin, although in no case was the difference statistically significant. This result confirms previous studies which have shown that the maintenance of continuous levels of antibiotic is not a necessary objective when using beta-lactam antibiotics.

Adult↗

[Bactericidal activity of amoxicillin and cefaclor in an "in vitro" kinetic model (author's transl)].

The bactericidal activity against Staphylococcus aureus 290-P, Escherichia coli NIHJ-JC2 and Klebsiella pneumoniae ATCC-10031 (10(6)/ml) was studied during 24 h, using an in vitro kinetic model which simulates the drug concentrations occurring in human serum after oral doses of amoxicillin (0.5 g or 1 g) or cefaclor (0.25 g or 0.50 g), 2 or 3 times a day. After the first antibiotic exposure, a high level of bactericidal activity (99-99.9%) was observed. Complete bactericidal activity was observed in all cases against S. aureus, but only after 3 times per day exposures in the case of E. coli and K. pneumoniae. Twice per day exposures of amoxicillin or cefaclor were invariably ineffective for these two species of Enterobacteriaceae (10(9) bacterial survivors/ml). These findings were related to subinhibitory concentrations which were or not able to prevent or reduce the bacterial regrowth after the first exposure of the antibiotics.

Amoxicillin↗

[A randomized control study on the treatment of 123 cases of bacterial infections with cefteram and cefaclor].

To evaluate the efficacy and the safety of cefteram in bacterial infections, a randomized control study of cefteram and cefaclor on the treatment of 123 patients with respiratory and urinary tract infections was carried out. The result showed that the effective and bacterial eradication rates were 92.1% and 91.4% for cefteram. 83.3% and 85.2% for cefalor. Adverse reactions were mainly gastrointestinal reactions, occurring in 4.6% of the cefteram group and 9.4% of the cefaclor group. Study of minimum inhibitory concentration displayed high antibacterial activity of cefteram for enterobacteriaceae and other Gram-negative organisms and its activity was higher than that of gentamyicin and ciprofloxacin for E. coli. It is concluded that cefteram was effective and safe in the treatment of respiratory and urinary tract infections.

Bacterial Infections↗

[Cefaclor therapy followed by serum sickness-like symptoms].

Cefaclor is an oral cefalosporin for a wide range of gram-positive and gram-negative infection. A retrospective study of cefaclor toxicoderma cases at the Department of Dermatology of Heim Pál Children's Hospital found 11 cases. After the administration of the drug, serum sickness like syndromes were observed. The characteristic symptoms were: erythema multiforme like urticaria, polyarticular swelling and oedema of joints and fever. Laboratory findings were: arised activity of the liver enzymes. After the acute symptoms urticaria factitia appeared.

Cefaclor↗

Pharmacologic studies with cefaclor, a new oral cephalosporin.

Cefaclor, a new oral cephalosporin, was administered to 18 normal human volunteers in either single or multiple doses of 250 and 500 mg. Mean serum concentrations of 6.09 and 12.8 microgram/ml were achieved 1 hour after single oral doses of 250 and 500 mg, respectively. The serum concentrations declined rapidly and no drug was detected at 4 hours. Very high concentrations of cefaclor were found in urine during the first 8 hours after ingestion of the drug. Forty-three per cent of the total dose was excreted in urine during the first 8 hours. There was no accumulation of drug in serum during the multiple-dose studies.

Administration, Oral↗

Antibacterial activity of cefpodoxime in comparison with cefixime, cefdinir, cefetamet, ceftibuten, loracarbef, cefprozil, BAY 3522, cefuroxime, cefaclor and cefadroxil.

The new oral cephalosporins cefpodoxime, cefixime, cefdinir, cefetamet and ceftibuten demonstrate enhanced activity against Enterobacteriaceae susceptible to the established compounds as well (e.g. cefuroxime, cefaclor, cefadroxil). In addition, cefpodoxime, cefixime, cefdinir, cefetamet and ceftibuten include in their spectrum species hitherto resistant to oral cephalosporins (Proteus vulgaris, Providencia spp., Yersinia enterocolitica). Besides, the majority of these compounds demonstrate relevant activity (MIC50 equal to or below 2 mg/l) against Enterobacter spp., Citrobacter freundii, Serratia spp. and Morganella morganii. Ceftibuten is the most potent oral cephalosporin against most of the Enterobacteriaceae. Non-fermentative bacilli (Acinetobacter spp., Pseudomonas spp.) remain completely resistant to oral cephalosporins (except some Acinetobacter species against cefdinir and Pseudomonas cepacia against ceftibuten). Antistaphylococcal activity for oral cephalosporins is highest for cefdinir followed by BAY 3522, cefprozil, cefuroxime and cefpodoxime. Loracarbef, cefaclor and cefadroxil are about equally active, while the other compounds are only weakly active (cefixime) or inactive (cefetamet, ceftibuten). Enterococci are insensitive to new generation oral cephalosporins as they have been to established compounds. The most active oral cephalosporins against hemolytic streptococci are cefdinir and cefprozil. Streptococcus pneumoniae, Streptococcus milleri and Streptococcus mitior are most susceptible to cefpodoxime, cefdinir, cefuroxime and BAY 3522. Penicillin resistant pneumococci have to be regarded as resistant to all oral cephalosporins. Fastidious pathogens like Haemophilus spp., Moraxella catarrhalis and Neisseria gonorrhoeae are more susceptible to cefpodoxime, cefixime, cefdinir, cefetamet and ceftibuten than to the other oral cephalosporins. The activity of oral cephalosporins is only weak against Listeria spp., Helicobacter pylori and anaerobic pathogens (except BAY 3522). Bordetella pertussis remains resistant to all absorbable cephalosporins. Progress in antibacterial activity of oral cephalosporins was mainly achieved by cefpodoxime, cefixime, cefdinir, cefetamet and ceftibuten against Enterobacteriaceae and the fastidious pathogens and against staphylococci and the nonenterococcal streptococci by cefdinir, BAY 3522, cefprozil and cefpodoxime.

Bacteria↗

In vitro susceptibility studies with cefaclor and cephalexin.

The in vitro activity of cefaclor and cephalexin against clinical isolates of four bacterial genera was compared. Both agents had a similar range of activity, but cefaclor was significantly more active by weight than cephalexin for most isolates tested.

Bacteria↗

Pharmacological evaluation of cefaclor in volunteers.

The plasma and urine concentrations of cefaclor were measured after oral administration of single and multiple doses to volunteers. Cefaclor was rapidly absorbed, rapidly excreted in the urine, well tolerated without toxicity, and failed to accumulate in the plasma with chronic dosing.

Adult↗

Concentration relationships of cefaclor in serum, interstitial fluid, bile, and urine of dogs.

The concentrations of cefaclor in the serum, urine, bile, and tissue fluids of the abdominal wall, kidney, and liver of dogs were compared over a 4-h period after oral administration of a single dose of this drug. The concentration of cefaclor in the soft-tissue interstitial fluid peaked 2 h after administration, thereby demonstrating a diffusion rate similar to those of other cephalosporins. Both urine and bile concentrations greatly exceeded the serum levels, whereas none of the tissue fluid concentrations were greater than the serum concentrations at the times of measurement.

Animals↗

Comparative susceptibility of Haemophilus species to cefaclor, cefamandole, and five other cephalosporins and ampicillin, chloramphenicol, and tetracycline.

The minimal inhibitory concentration of cefaclor, cephalexin, cephradine, cefamandole, cephalothin, cephapirin, cefazolin, ampicillin, chloramphenicol, and tetracycline for inhibition of 198 freshly isolated clinical strains of Haemophilus species (23 H. influenzae type b, 157 H. influenzae non-type b, 14 H. parainfluenzae, and 4 H. aphrophilus) was determined simultaneously by a slightly modified WHO-ICS agar dilution method. Nine strains were resistant to ampicillin. There was no correlation between ampicillin resistance and minimal inhibitory concentration of other antibiotics. All strains were susceptible to chloramphenicol, and all except five were susceptible to tetracycline. Cefaclor was the most active oral cephalosporin, and cefamandole was the most active parenteral cephalosporin. Among the seven cephalosporins tested, cefamandole was the most effective compound. All but two strains were inhibited by cefamandole at 2 mug or less per ml.

Ampicillin↗

Comparative pharmacokinetics of cephalexin, cefaclor, cefadroxil, and CGP 9000.

In a randomized crossover study, the pharmacokinetics of three new cephalosporin antibiotics, cefaclor, cefadroxil, and CGP 9000, in comparison to cephalexin, were determined after oral administration, by capsules, of 1,000 mg on an empty stomach in 12 normal subjects. Serum concentrations were measured during a period of 8 h, and urine recovery was measured during 24 h. The significant parameters of bioavailability of an orally administered substance were determined. The maximal serum concentrations (y(max)) for cephalexin, cefaclor, cefadroxil, and CGP 9000 (in milligrams per liter) were: 38.8 +/- 8.1; 34.6 +/- 7.8; 33.0 +/- 5.4; and 23.3 +/- 7.3, respectively. The areas under the curve (in hours x milligrams per liter) were: 93.0 +/- 14.8; 74.5 +/- 9.9; 70.1 +/- 9.0; and 108.5 +/- 18.4, respectively. In a further crossover study with six subjects, 1,000 mg of cephalexin and of cefadroxil were given during a standard breakfast. The y(max) of cephalexin decreased to 23.1 +/- 6.6 mg/liter, in contrast to cefadroxil, with an unchanged y(max) of 32.7 +/- 3.4 mg/liter.

Administration, Oral↗