Concentrations Of Cefaclor Research Articles

Cefaclor concentration in pus from abscess caused by odontogenic infection after a single oral administration

1. 1. Cefaclor concentrations in serum and pus from abscess of odontogenic infection after a single oral administration of 500-mg cefaclor were assayed and pus concentrations were compared with minimum inhibitory concentration (MIC) of oral streptococci isolated from odontogenic infection. 2. 2. The mean peak concentrations in serum and pus were found at identical times, 1.5 hr after administration, which were 7.22 and 0.72 μg/ml, respectively. 3. 3. The mean ratio of pus:serum concentration at the peak time was 0.10. 4. 4. Most cefaclor concentrations in pus at the peak time (seven of nine cases) exceeded the MIC for 90% of oral streptococci (0.5 μg/ml).

The incidence and epidemiology of beta-lactam resistance in Haemophilus influenzae.

Consecutive isolates of Haemophilus influenzae were collected by the Public Health Laboratory, Bath between 1 June 1992 and 31 May 1993. Of 379 apparently distinct isolates, 216 originated from the respiratory tract, 102 from eyes and 61 from other sites. The minimum inhibitory concentrations of amoxycillin, amoxycillin/clavulanate, cefaclor, cefuroxime, cefotaxime and cefpodoxime were determined for each isolate. Forty strains (10.6%) were beta-lactamase producers. MIC50 and MIC90 values and the range of MICs were determined for all isolates. The overall resistance rates were: amoxycillin (MIC > 1.0 mg/L), 22.7%; amoxycillin/clavulanate (MIC > 1.0 mg/L), 14.8%; cefuroxime (MIC > 1.0 mg/L), 18.5%, (MIC > 4.0 mg/L), 5.5%; cefaclor (MIC > 8 mg/L), 15.6%; cefpodoxime (MIC > 1.0 mg/L), 0.3%; cefotaxime (MIC > 1.0 mg/L), 0%. Twenty non-beta-lactamase producing but beta-lactam resistant strains (cefuroxime MIC > 4.0 mg/L) were matched with 20 susceptible strains on the basis of patient age, sex, and specimen type. The strains were characterised by outer-membrane protein (OMP), random amplified polymorphic DNA (RAPD) and ribotyping patterns. Eleven of the 20 resistant strains were indistinguishable by the methods used, suggesting spread of a single beta-lactam resistant, non-beta-lactamase producing clone. The distribution of resistant strains within the local community was plotted geographically.

Development of beta-lactamase-mediated resistance to penicillin in middle-ear isolates of Moraxella catarrhalis in Finnish children, 1978-1993.

The frequency of beta-lactamase production was analyzed in a study of 1,452 strains of Moraxella catarrhalis and 2,738 strains of Haemophilus influenzae isolated from middle-ear fluid of children < 6 years of age at Tampere University Hospital in Tampere, Finland, between 1978 and 1993. In addition, 401 isolates of M. catarrhalis from similar samples collected in different parts of Finland in 1988-1990 were tested for beta-lactamase production; minimal inhibitory concentrations of ampicillin, cefaclor, cephalothin, erythromycin, tetracycline, and trimethoprim-sulfamethoxazole for these strains were determined. These data were compared with figures for the annual consumption of beta-lactam antimicrobials in the community in 1978-1993. A bimodal increase in the proportion of strains of M. catarrhalis producing beta-lactamase was detected: from 0 to 60% in 1978-1983 and from 60% to 80% in 1988-1990. Concurrently with the second increase, the consumption of cephalosporins increased substantially in the community. The frequency of beta-lactamase-producing strains of H. influenzae did not increase between 1978 and 1993.

Role of beta-lactamase of methicillin-susceptible Staphylococcus aureus in resistance to first-generation oral cephems both in vitro and in vivo.

Cefaclor, among the oral cephalosporins tested, showed the largest inoculum effect with respect to MIC values for 61 clinical isolates of methicillin-susceptible Staphylococcus aureus, including 39 beta-lactamase producing strains. These 39 strains were divided into eight type A, 29 type B or C, and two type D producers, by comparisons of specific activities to three substrates. Two producers, one each of types A and C, were further studied to investigate the effect of beta-lactamase on staphylococcal resistance to several beta-lactams. Concentrations of cefaclor and cephalexin in cultures of these strains decreased rapidly, whereas hydrolysis of these drugs by the purified beta-lactamases was moderate to low as detected by spectrophotometric assay. Cefaclor showed high affinities for penicillin-binding proteins 1, 2, and 3 of both beta-lactamase producers and their respective penicillinase-non-producing mutants. In experimental intraperitoneal infections in mice, cefaclor was therapeutically effective against both mutants, showing 50% effective doses of less than 10 mg/kg/dose. In contrast, it was not satisfactory against the parent strains, requiring greater-than-10-fold increases in concentration for the same degree of survival. We concluded that resistance to first-generation oral cephems seen both in vitro and in vivo was due mainly to the beta-lactamase production.

Antimicrobial susceptibilities of Haemophilus influenzae isolated from the nasopharynx of children

Changes in susceptibilities to oral antimicrobials were investigated in 189 children, in whom Haemophilus influenzae was detected by nasopharyngeal culture, among the children who were diagnosed as having acute otitis media or chronic sinusitis with acute exacerbation in the Department of Otolaryngology in 1986, 1988 and 1991. The minimum 50% inhibitory concentration (MIC50) and minimum 90% inhibitory concentration (MIC90) of ampicillin (ABPC), cefaclor (CCL) and erythromycin (EM) in the subjects examined in 1986 were almost the same as the levels in those examined in 1991. The MIC50 level of minocycline (MINO) in the subjects examined in 1991 was lower by 2 test tubes than that determined in 1986, showing improvement in susceptibilities. The prevalence of resistance to antimicrobials was compared between 1986 and 1991. The prevalence to ABPC tended to decrease very slightly, while the prevalence to CCL tended to increase very slightly. The prevalence of EM tended to increase slightly. Many CCL-resistant strains detected in 1991 showed resistance to ABPC and EM, but showed favorable susceptibilities to cefixime and norfloxacin. Future trends of CCL-resistant strains should be carefully observed. There was no marked change in the prevalence of resistance to ABPC or CCL. ABPC and CCL were considered to be the first choice drugs, even at present, for pediatric patients with acute otitis media due to infection with H. influenzae and in those with acute exacerbation of chronic sinusitis due to the infection.

Molecular basis of the efficacy of cefaclor against Haemophilus influenzae.

Cefaclor sustained its inhibitory activity against a beta-lactamase-producing strain of Haemophilus influenzae. Although a relatively high permeability coefficient was calculated for ampicillin compared with that calculated for cefaclor, the resulting periplasmic concentration of cefaclor was 5.7 times that of ampicillin. The efficacy of cefaclor may be due to its higher beta-lactamase resistance, which allows it to achieve a greater periplasmic concentration and adequate binding to crucial penicillin-binding proteins.

Cefaclor concentrations in human serum, gingiva, mandibular bone, and dental follicle following a single oral administration

1. 1. Cefaclor concentrations in human serum ( n = 59), gingiva ( n = 46), mandibular bone ( n = 39), and dental follicle ( n = 42) following a single oral administration of cefaclor (500 mg) were measured by the paper disk method. 2. 2. The peak times of serum, gingiva, mandibular bone, and dental follicle were 1.5, 2, 2, and 1.5 hr, respectively. 3. 3. The mean peak concentrations of serum, gingiva, mandibular bone, and dental follicle were 7.58 μg/ml, 3.71, 1.59 and 2.42 μg/g, respectively. 4. 4. The concentration ratios of gingiva/serum, mandibular bone/serum, and dental follicle/serum at peak times of the tissues were 0.49, 0.18, and 0.32, respectively. 5. 5. Mean cefaclor concentrations in gingiva, mandibular bone, and dental follicle at peak times exceeded MIC for 90% for clinically isolated strains of alpha-hemolytic Streptococci.

Pharmacokinetic analysis of the effects of different foods on absorption of cefaclor

Cefaclor is an oral cephalosporin antibiotic which has a broad antibacterial spectrum. The purpose of this study was to investigate the effect of food on the absorption of cefaclor and to analyze kinetically the absorption process of this drug. Cefaclor was given to eight volunteers at five test times: after overnight fasting, after two rice meals (350 and 700 cal [1 cal = 4.184 J]), and after two bread meals (500 and 1,000 cal). Urinary recoveries of cefaclor and concentrations of the drug in plasma were determined for each administration. Areas under the concentration-time curves and urinary recoveries were not affected by food intake, but the maximum concentration of drug in serum was reduced and the time to maximum concentration of drug in serum was prolonged depending on the type and the quantity of the meal. The larger the quantity of the meal, the more the maximum concentration of drug in serum and the time to maximum concentration of drug in serum were affected. The rice meals affected the absorption process of cefaclor more than the bread meals. The concentrations of cefaclor in plasma following administration after overnight fasting were well fitted to a conventional one-compartment model with a first-order absorption process, but those after the other administrations were not fitted to the model. For the pharmacokinetic analysis of those data, it was necessary to introduce a transfer process from administration site to absorption site to the conventional model. The concentrations in plasma after rice and bread meals were best fitted to the model with a zero-order transfer process than to that with a first-order process. The velocity of the transfer process depended on the type and volume of the meal.

Pharmacokinetics of cefuroxime axetil and cefaclor: relationship of concentrations in serum to MICs for common respiratory pathogens

The pharmacokinetics of single doses of cefaclor at 250 and 375 mg and cefuroxime axetil at 250 mg administered under optimal conditions (i.e., cefuroxime axetil after food and cefaclor in the fasted state) were studied in 24 healthy male volunteers. Drug concentrations in serum were related to MICs for common respiratory tract pathogens by using data generated from a recently completed national survey. The time the concentrations in serum exceeded the MICs for Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella (formerly Branhamella) catarrhalis were significantly greater (P less than 0.05) for cefuroxime axetil at 250 mg than for cefaclor at 250 or 375 mg. With the recommended dosing regimens (cefuroxime axetil at 250 mg and cefaclor at 375 mg twice daily or cefaclor at 250 mg three times daily), cefuroxime concentrations exceed the MIC for 90% of the strains tested for a greater time period than cefaclor concentrations with either regimen. The reasons for this difference are (i) the greater potency and slower clearance of cefuroxime compared with those of cefaclor and (ii) the greater sensitivity of these pathogens to cefuroxime.

Clinical pharmacokinetics of five oral cephalosporins in calves

The minimal inhibitory concentrations (MIC) of cephalexin, cephradine, cefaclor, cefatrizine and cefadroxil for Salmonella species, Escherichia coli and Pasteurella multocida isolated previously from young calves were determined. The MIC90 values for cephalexin, cephradine and cefadroxil ranged between 3.12 micrograms ml-1 and 12.5 micrograms ml-1, whereas those of cefatrizine and cefaclor were 3.12 micrograms ml-1 and 0.78 microgram ml-1, respectively. Each drug was administered intravenously and orally to groups of pre-ruminating calves and orally to early ruminating calves. Although the pharmacokinetic characteristics of the drugs after intravenous injection were similar to other beta-lactam antibiotics, significant differences between the cephalosporins examined were found in respect of certain kinetic parameters. The drugs showed rapid absorption into the systemic circulation after oral administration to pre-ruminating calves but the elimination half-life values (t1/2 beta) varied between three hours (cefaclor and cefadroxil) and nine hours (cefatrizine). The bioavailability of the drugs was about 35 per cent of the administered dose. Co-administration of probenecid with each antibiotic caused a twofold or greater increase in peak serum drug concentrations (Cmax) but the effect on t1/2 beta was variable. Cephalexin, cephradine and cefaclor given to the ruminating calves resulted in very low serum or plasma concentrations and their use should be restricted to younger calves. Cefadroxil was found to give the highest serum concentrations in this age group but had significantly lower bioavailability when compared with the unweaned calves. Provisional oral dosage regimens were computed for each cephalosporin on the basis of the MIC data and the kinetic parameters derived from intravenous and oral drug administration.

1059 CEFACLOR AND AMOXICILLIN ACTIVITY AGAINST ACUTE OTITIS MEDIA (AOM) BACTERIA

56 infants and children (4 months-8 years) with AOM were randomly assigned to be treated for 14 days each with either cefaclor 40 mg/kg/d BID (n=21), cefaclor 40 mg/kg/d TID (n=15), or amoxicillin 40 mg/kg/d TID (n=20). Each patient had a diagnostic unilateral tympanocentesis before initiation of therapy. Thirty patients (53.6%) had positive middle ear fluid (MEF) cultures. Twenty-two of the thirty organisms recovered were considered pathogenic. The minimal inhibitory concentration(MIC) of cefaclor and amoxicillin against 18 organisms were as follows: 15 patients with positive MEFs responded to cefaclor treatment (cefaclor MICs: 0.06-2.0 μg/ml). Amoxicillin was successful in the treatment of the other 7 patients with positive MEFs (amoxicillin MICs: 0.12-0.5 μg/ml). Our data indicate that amoxicillin has a better in vitro activity than cefaclor against AOM bacteria. However, the clinical outcome indicate that both antibiotics are effective.

Penetration of cefaclor into bronchial mucosa.

Bronchial mucosal biopsy specimens were obtained during fibreoptic bronchoscopy in 30 patients receiving a new oral cephalosporin antibiotic, cefaclor (10 had 250 mg, 10 had 500 mg, and 10 had 1000 mg every eight hours). In 10 patients (from all dosage groups) cefaclor was undetectable in the bronchial mucosa but in every case the serum concentration was low, suggesting incomplete absorption. The mean (SD) bronchial mucosal concentration after 250 mg was 3.78 (1.77) micrograms/g (range 2.1-5.8 micrograms/g, n = 4), after 500 mg 4.43 (2.04) micrograms/g (range 2.0-7.1 micrograms/g, n = 8), and after 1000 mg 7.73 (2.76) micrograms/g (range 5.0-12.7 micrograms/g, n = 6). A significantly higher concentration in the bronchial mucosa was achieved with 1000 mg than with 250 mg (p less than 0.05) or 500 mg (p less than 0.025). These concentrations should be effective against Streptococcus pneumoniae, most strains being inhibited below 1.0 microgram/ml. The concentrations were within one dilution of the minimal inhibitory concentration for Haemophilus influenzae, most strains being inhibited below 4.0 micrograms/ml. Some strains of H influenzae will not be inhibited by the concentrations of cefaclor found in the bronchial mucosa, particularly those that are ampicillin resistant.

NORFLOXACIN: IN VITRO ACTIVITY COMPARED WITH THAT OF SEVEN OTHER ANTIBACTERIAL AGENTS AGAINST URINARY TRACT PATHOGENS

The minimal inhibitory concentrations (MICs) of norfloxacin, nalidixic acid, ampicillin, amoxycillin/clavulanic acid (4:1), mecillinam, cefaclor , sulphamethoxazole/trimethoprim (20:1) and netilmicin against 435 clinical isolates of bacterial urinary tract pathogens have been determined. An agar dilution method was employed. Norfloxacin was the most active agent in the study on a weight-for-weight basis. The drug was highly active against Enterobacteriaceae. Norfloxacin was more active than netilmicin against Pseudomonas aeruginosa (MICs less than or equal to 2 mg/l and less than or equal to 4 mg/l, respectively). Norfloxacin was also active against Gram-positive bacteria including enterococci and Staphylococcus saprophyticus (MICs less than or equal to 4 mg/l). Norfloxacin may well become a useful agent for the oral treatment of urinary tract infection, particularly as a drug for the treatment of infections caused by multiresistant organisms.

Pharmacokinetics of cefadroxil and cefaclor during an eight-day dosage period.

The concentrations of cefadroxil and cefaclor in serum were studied in eight healthy volunteers receiving 1,000 mg of both substances three times per day for 8 days. Intraindividual comparisons showed an increase in peak serum levels of cefadroxil from days 1 to 8 in seven of eight volunteers. Cefaclor peak concentrations did not rise during the 8 days.

In vitro activity of cefaclor against haemophilus influenzae in comparison to cephalexin, cephradine, cefadroxil, cefatrizine and ampicillin

The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of cefaclor were compared with those of cephalexin, cephradine, cefadroxil, cefatrizine, and ampicillin for 50 strains ofHaemophilus influenzae. The activity of cefaclor and cefatrizine was 8–16 times higher than that of the other cephalosporins and 1/8 that of ampicillin. Cross-resistance between ampicillin and the cephalosporins tested was observed for one strain which did not produce beta-lactamase. No cross-resistance was found for beta-lactamase-producing strains. The killing kinetics of 4 mg/l cefaclor did not differ in two ampicillin-sensitive strains and one beta-lactamase-producing strain which was slightly resistant to ampicillin. The survival rate varied from 10% to 1% after six to seven hours.

Pharmacokinetics of cefaclor in chronic middle ear effusions.

Fifty children aged 1 to 13 years with chronic or recurrent otitis media with effusion received a single dose of cefaclor (15 mg/kg body weight) by the oral route 30 minutes to seven hours before the removal of middle ear effusion and insertion of tympanostomy tubes. Serum and middle ear aspirate concentrations of the antibiotic were determined employing a microbiological assay technique by a disk diffusion method. Middle ear specimens were also cultured for aerobic bacteria. The mean peak serum concentration level (8.49 +/- 7.89 micrograms/ml) was observed after 30 minutes, whereas the middle ear peak level (0.47 +/- 0.78 micrograms/ml) occurred after one hour. Of the 87 middle ear specimens, 37 had cefaclor concentrations which were detectable within the resolution of the bioassay method (greater than 0.16 micrograms/ml). There was no correlation between the type of middle ear effusion (mucoid or serous) and the concentration of cefaclor in the middle ear. Only 18% of the middle ear cultures were positive for aerobic bacteria; Hemophilus influenzae was the most common organism.

Concentration of cefaclor in human prostatic tissue

Concentration of cefaclor, a new oral cephalosporin, was measured in prostatic tissue of ten patients undergoing suprapubic prostatectomy. The average prostatic tissue concentrations were 0.51 ± 0.22 microgram and 0.74 ± 0.67 microgram per gram of tissue following the oral administration of 250-milligram and 500-milligram doses, respectively. The prostate/plasma ratios of cefaclor were approximately 0.7 indicating no evidence of accumulation of the drug in prostatic tissue. Levels of cefaclor achieved in human prostatic disease are equal to or less than the minimum inhibitory concentration of most strains of known facultative bacterial pathogens associated with prostatitis.

Evaluation of cefaclor

The chemistry, pharmacology, pharmacokinetics, bacterial spectrum, clinical use, dosage, adverse reactions, and dosage forms and cost of cefaclor are reviewed. Cefaclor, a congener of cephalexin monohydrate, is a new semisynthetic cephalosporin antibiotic. It is well absorbed when given orally on an empty stomach; absorption is delayed by the presence of food. Although metabolism may play a role in the disposition of cefaclor, elimination is primarily renal. Cefaclor's spectrum of activity is similar to that of cefalexin, including a wide range of gram-negative and gram-positive bacteria; in particular, Escherichia coli, Klebsiella spp., Proteus mirabilis, Salmonella spp., and Haemophilus influenzae are more susceptible to clinically achievable concentrations of cefaclor than cephalexin. Cefaclor has been demonstrated to be effective against beta-lactamase-producing H. influenzae resistant to ampicillin, but further studies are needed to establish the clinical significance of this activity. Efficacy of cefaclor has been demonstrated in urinary tract, upper and lower respiratory tract, and skin and soft tissue infections in adults and children as well as in pediatric otitis media. Adverse reactions, mostly gastrointestinal, are generally mild and occur in few patients. Usual doses are 250-500 mg every eight hours in adults and 20--40 mg/kg/day in children, although this pediatric dose may be two low for otitis media. Clinical superiority of cefaclor over less expensive antibiotics has not been demonstrated.

Investigations on the excretion of cefaclor in human bile (author's transl)

The concentration of cefaclor in serum and bile was determined for up to 360 minutes after a single oral dose of 1 g cefaclor in 18 patients with continuous T-drainage of the bile duct. The rate of absorption varied, there being marked differences in the time. The peak bile concentration of 12.1 mcg/ml was reached after 120 min; the peak serum concentration of 12.3 mcg/ml, on the other hand, was reached after only 90 min. There was no accumulation of cefaclor in the bile.

Comparative study of cefaclor and amoxicillin in treatment of urinary tract infection

Cefaclor or amoxicillin was given to 51 randomly assigned patients with urinary tract infections. Inclusion in the study required two pretreatment urine cultures yielding the same organism (susceptible to both antibiotics) in concentrations ⩾ 10 5/ml. Both drugs were administered as 250 mg. orally every eight hours for ten days. Cefaclor was given to 27 patients and amoxicillin to 24. Most patients in both groups had negative urine cultures at five to nine days and four to six weeks following therapy. One patient in each group was unsuccessfully treated. Relapse or reinfection occurred with similar frequency in both treatment groups. Both antibiotics were well tolerated. Minimal inhibiting concentrations (MICs) of cefaclor, amoxicillin, cephradine, and cephalexin were determined by an agar dilution technique for the 44 available pretreatment isolates (41 Escherichia coli and 3 Proteus mirabilis). Mean MICs (μg./ml., ± SD) were 2.2 ± 1.4 for cefaclor, 4.4 ± 2.0 with amoxicillin, 8.1 ± 4.2 for cephradine, and 5.7 ± 3.0 with cephalexin. Cefaclor is highly active in vitro against those gram-negative bacteria which are commonly isolated from urine. Cefaclor is as effective as amoxicillin when administered three times daily for the treatment of urinary tract infection.