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[The antibacterial efficacy of cefaclor in routine testing of clinical material from two Berlin hospitals (author's transl)].

The agar diffusion method was used to test the antibacterial efficacy of cefaclor against bacterial strains isolated routinely from patients in two hospitals in Berlin. A comparison was made with the efficacy of oxacillin, azlocillin, amikacin, gentamicin, ampicillin, co-trimoxazole, tetracycline, penicillin, cefazolin, nalidixic acid and nitrofurantoin. A total of 1235 strains of Staphylococcus aureus, enterococci, Escherichia coli, Klebsiella, Enterobacter, Proteus species, Citrobacter and Pseudomonas aeruginosa were tested. Cefaclor was superior to the other substances in its activity against E. coli, Klebsiellae, and Proteus mirabilis. Co-trimoxazole and tetracycline, on the other hand, proved more effective against indole-positive Proteus species and Citrobacter. Tetracycline was also more effective against Enterobacter. Ampicillin was the most effective agent against enterococci, and oxacillin the most effective against S. aureus. Cefaclor showed good antibacterial activity against strains which were resistant to the orally administrable agents ampicillin, tetracycline and co-trimoxazole.

Bacteria↗

[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.

Adult↗

Effects of prophylactic administration of cefaclor on transient bacteremia after dental extraction.

This study was undertaken to investigate the effects of prophylactic administration of cefaclor on bacteremia after dental extraction. Thirty-nine patients were randomly assigned to receive either 1 g cefaclor (19 patients) or placebo (20 patients) 1 h prior to dental extraction. Blood samples for microbiological investigation were collected before, during, and 10 min after surgery, and were processed by lysis filtration under anaerobic conditions. The incidence of bacteremia with viridans streptococci was 79% in the cefaclor group and 50% in the placebo group during extraction. No difference in the incidence or magnitude of bacteremia was observed when the two patient groups were compared.

Adult↗

Acute interstitial nephritis and non-oliguric renal failure after cefaclor treatment.

A case of acute interstitial nephritis (AIN) developing after cefaclor treatment is reported. Diagnosis was proofed by kidney biopsy and lymphocyte transformation test. The clinical course of the patient with non-oliguric renal failure was favourable. Four weeks after discontinuation of cefaclor treatment the renal function was completely restored and remained stable over the ten-month follow-up period. It is concluded that cefaclor can cause hyperallergic AIN and acute renal failure.

Acute Kidney Injury↗

A comparative trial of low dose cefaclor and macrocrystalline nitrofurantoin in the prevention of recurrent urinary tract infection.

One hundred and twenty women, aged between 18 and 90 years, with a history of at least four episodes of symptomatic urinary tract infection in the preceding 12 months, were randomized in an open, prospective study to prophylactic treatment with cefaclor 250 mg at bedtime or macrocrystalline nitrofurantoin 50 mg at bedtime for 12 months. Ninety-seven (49 taking cefaclor, 48 taking macrocrystalline nitrofurantoin) were assessed for efficacy; 80% of these were symptomatically improved and remained abacteriuric during the period of prophylaxis. Symptomatic attacks while patients were taking prophylaxis occurred at least five times less often than before prophylaxis had started. Seventy percent of the patients continued in an improved condition after having stopped prophylaxis. All 120 patients were assessed for adverse events; these were twice as frequent in patients taking macrocrystalline nitrofurantoin (20% vs. 10%), but only 11 patients (three taking cefaclor, eight taking macrocrystalline nitrofurantoin) withdrew from the study. Due to the small numbers of patients experiencing adverse events, these differences are not statistically significant. No significant changes in haematological or biochemical parameters were found during or after the end of the 12-month course. The 22 patients assessable for efficacy who had a non-obstructive radiological abnormality responded as well to prophylaxis as those with no detectable abnormality. Long-term, low-dose prophylaxis with a suitable antimicrobial agent is highly effective management for patients with recurrent urinary tract infections, and can appropriately be provided by the family doctor. Prophylaxis given for 1 year gives better results than when given for 6 months.

Adolescent↗

In vitro susceptibility of Haemophilus influenzae to cefaclor, cefixime, cefetamet and loracarbef.

The susceptibility of 2,212 Haemophilus influenzae isolates cultured in UK clinical laboratories in 1991 was determined for four orally-administered beta-lactam drugs. These isolates included 1,893 ampicillin-susceptible, 191 beta-lactamase-positive and 128 ampicillin-resistant, beta-lactamase-negative Haemophilus influenzae. While 150 (6.8%) isolates were resistant to cefaclor (MIC > or = 16 mg/l) and 85 (3.8%) to loracarbef, all were inhibited by < or = 2 mg/l cefetamet and < or = 1 mg/l cefixime and were therefore susceptible to these agents. Ranges and modes of inhibition zone diameters and MICs indicated that the susceptibility of a variable proportion of the 191 beta-lactamase-positive isolates to cefaclor, loracarbef and cefetamet was reduced compared with the fully susceptible population. In contrast, a major reduction in susceptibility to all four antimicrobial agents was seen among the 128 ampicillin-resistant (MIC 1-64 mg/l) beta-lactamase-negative isolates such that these accounted for 53% and 67% of the total number of organisms resistant to cefaclor and loracarbef respectively. In addition, 23 of 25 isolates inhibited only by > or = 1 mg/l cefetamet and all eight inhibited only by > or = 0.5 mg/l cefixime showed this type of resistance to ampicillin. Results indicate the importance of detecting non-beta-lactamase-mediated resistance to ampicillin and any concomitant diminished susceptibility to other beta-lactam drugs.

Ampicillin Resistance↗

Single-dose cefaclor therapy of urinary tract infection. Evaluation of antibody-coated bacteria test and C-reactive protein assay as predictors of cure.

The efficacy of single-dose (cefaclor, 2 g orally) and multidose (cefaclor, 250 mg orally three times a day for 10 days) antibiotic regimens in the therapy of acute uncomplicated urinary tract infections (UTI) in nonpregnant women were compared. The patient's clinical status and results of urine cultures were compared in retrospect with the results of the antibody-coated bacteria (ACB) test and C-reactive protein (CRP) test in order to determine if either test would predict the patient's response. Overall, 10 of 30 patients (33 percent) and 18 of 22 patients (81 percent) given single doses and multidoses, respectively, had negative urine cultures four weeks after completion of therapy. A negative urine culture at four weeks correlated with a negative ACB test utilizing the less inclusive criteria for negativity (less than 5 bacteria with fluorescence in 5 minutes of search) but not with a negative ACB test utilizing the more inclusive criteria (less than 10 percent bacteria with fluorescence) or with a negative CRP test. The cure rate in the ACB-negative single-dose group (7 of 9 patients) utilizing the less inclusive criteria for negativity was similar to the cure rate in the ACB-negative multidose group (8 of 10 patients). This study suggests that the ACB test, if properly standardized, might permit identification of a population of patients with UTI who would respond to single-dose cefaclor therapy.

Adult↗

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

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. The peak times of serum, gingiva, mandibular bone, and dental follicle were 1.5, 2, 2, and 1.5 hr, respectively. 3. The mean peak concentrations of serum, gingiva, mandibular bone, and dental follicle were 7.58 micrograms/ml, 3.71, 1.59 and 2.42 micrograms/g, respectively. 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. 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.

Administration, Oral↗

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

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. 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 micrograms/ml, respectively. 3. The mean ratio of pus:serum concentration at the peak time was 0.10. 4. Most cefaclor concentrations in pus at the peak time (seven of nine cases) exceeded the MIC for 90% of oral streptococci (0.5 micrograms/ml).

Administration, Oral↗

Susceptibility of Haemophilus influenzae to amoxicillin/clavulanic acid, erythromycin, cefaclor, and trimethoprim/sulfamethoxazole.

A total of 126 strains of Haemophilus influenzae were examined for susceptibility to amoxicillin/clavulanic acid, trimethoprim/sulfamethoxazole, cefaclor, and erythromycin by an agar dilution procedure. Fifty strains (eight type B, 42 non-type B), all with ampicillin minimal inhibitory concentrations (MIC) of greater than or equal to 6.2 micrograms/ml, produced beta-lactamase. The remaining 76 strains (18 type B, 59 non-type B) were beta-lactamase-negative. All of these strains had ampicillin MICs of less than or equal to 0.8 micrograms/ml. The combination of amoxicillin and clavulanic acid (2:1) was highly active against all strains tested. With the exception of two strains with amoxicillin/clavulanic acid MICs of 1.6/0.8 ug/ml, all strains were inhibited by concentrations of less than or equal to 0.8/0.4 ug/ml. Trimethoprim/sulfamethoxazole was also found to be highly active (MICs uniformly less than or equal to 0.1/1.9 ug/ml). Cefaclor and erythromycin were the least active of the agents tested. Fourteen strains (10.6%) had cefaclor MICs of greater than 32 ug/ml. Forty-seven strains (35.6%) had erythromycin MICs of greater than 8 micrograms/ml. With the exception of amoxicillin/clavulanic acid beta-lactamase production did not seem to influence the activity of any of the antimicrobials tested. Minimum inhibitory concentrations of amoxicillin/clavulanic acid, although still well within achievable serum levels, were approximately one twofold dilution higher with beta-lactamase-producing H. influenzae type B strains than with beta-lactamase-negative strains.

Amoxicillin↗

Cefaclor versus ampicillin for outpatient treatment of urinary tract infections.

An unblinded, randomized, prospective clinical trial of cefaclor, 250 mg twice daily, versus ampicillin, 500 mg four times daily, for a total of ten days of therapy, was conducted with 100 patients presenting to an emergency department with signs, symptoms, and urinalysis results suggestive of urinary tract infection (UTI). Eighty patients had a UTI proven by pre-therapy urine culture. Significantly more of the bacteria isolated were sensitive to cefaclor (96.3%) than to ampicillin (78.0%), P less than 0.01. Seventy-one patients returned for all follow-up visits and urine cultures. The overall success rate in the cefaclor group was 75.7% and in the ampicillin group 79.4%. There was a 10% failure rate in treating clinical cystitis with both regimens, and the satisfactory outcome rate for pyelonephritis and cystitis was similar in both treatment groups.

Ampicillin↗

Streptococcus pneumoniae in vitro development of resistance to amoxicillin/clavulanic acid, cefaclor, levofloxacin and azithromycin.

The purpose of this study was to determine effect of repeated exposure to sub-inhibitory concentrations of amoxicillin/clavulanic acid on the development of resistance in Streptococcus pneumoniae. Other agents, azithromycin, cefaclor and levofloxacin, were also tested. Twenty S. pneumoniae were passaged for 9 days in the presence of sub-inhibitory concentrations of each antimicrobial agent and MICs determined by NCCLS macro-dilution method. There was a four-fold increase in amoxicillin/clavulanic acid MICs for 2 of 20 isolates. Three of 9 tested against cefaclor, 11 of 13 tested against azithromycin and 9 of 20 tested against levofloxacin showed > or =4-fold increase. Amoxicillin/clavulanic acid was the most stable of the agents tested. Cefaclor MICs were also fairly stable. Azithromycin and levofloxacin MICs were most affected.

Amoxicillin-Potassium Clavulanate Combination↗

Treatment of acute maxillary sinusitis in childhood: a comparative study of amoxicillin and cefaclor.

Maxillary sinus aspiration and quantitative culture of the aspirate were performed in 50 patients, ranging in age from 1 to 16 years, with clinical and radiographic evidence of acute sinusitis. Of 79 sinuses aspirated, at least one was found to be infected in 35 (70%) children. Streptococcus pneumoniae, Branhamella catarrhalis, and Haemophilus influenzae were the most common organisms recovered. All H. influenzae were nontypeable. Twenty percent of the H. influenzae and 27% of the B. catarrhalis organisms were beta-lactamase positive and amoxicillin resistant. The subjects received either amoxicillin or cefaclor at a dose of 40 mg/kg/day in three doses for 10 days. The clinical cure rate with amoxicillin was 81%, compared to 78% with cefaclor. Radiographic improvement was similar in both treatment groups. Antibiotic therapy failed in four patients; three had been given amoxicillin, and one cefaclor. In three of these, a beta-lactamase-positive antibiotic-resistant bacterial species was recovered from the maxillary sinus aspirate; the fourth aspirate was sterile.

Acute Disease↗

Pharmacologic and clinical comparison of cefaclor in immediate-release capsule and extended-release tablet forms.

A new controlled-delivery, extended-release 500-mg formulation of cefaclor that is administered twice daily may improve patient compliance compared with the older, immediate-release 250-mg formulation that is administered three times daily. When the extended-release tablet is administered with food, peak plasma cefaclor concentrations are achieved about 2.5 hours after the dose compared with about 1 hour after a dose with the immediate-release capsule. However, the two formulations have an equivalent extent of absorption and equivalent pharmacokinetics after absorption. Cefaclor has retained its excellent in vitro activity against the pathogens most commonly associated with acute exacerbations of chronic bronchitis, namely, Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae. Clinical trials show similar efficacy of the two formulations in patients with acute exacerbations of chronic bronchitis caused by these organisms, but for this indication a 7-day regimen may be used with the extended-release 500-mg formulation compared with a 10-day dosing regimen with the 250-mg capsule. The shorter course of treatment with the new formulation may also improve patient compliance.

Bronchitis↗

Cefaclor concentration in radicular granuloma after a single oral administration.

1. Cefaclor concentrations in radicular granuloma and serum in nonfasting patients after a single oral administration of 500-mg cefaclor were assayed. 2. The mean peak concentrations in radicular granuloma and serum were 2.57 mcg/g and 7.41 mcg/ ml, respectively. The mean ratio of granuloma/serum concentration at the peak time was 0.35. 3. All cefaclor concentrations in radicular granuloma at the peak time exceeded the minimal inhibitory concentration for 90% of oral streptococci (1 mcg/ml) isolated from odontogenic infection.

Administration, Oral↗

Determination of cefaclor by selective sample enrichment/clean-up on silica gel bonded polyelectrolyte in ion-exchange column chromatography.

A silica gel-bound cationic polyelectrolyte, poly[N-chloranil N,N,N',N'- tetramethylethylene diammonium dichloride], modified as ion-exchanger capable of molecular recognition of beta-lactam antibiotic, was used in solid phase extraction through column chromatography for a sample clean-up and enrichment of analyte from a dilute solution. The optimum and selective sorption conditions for a model antibiotic, cefaclor, were established. The high selectivity of polymer at pH 9.5 and flow rate as high as 5 ml/min were observed for the quantitative sorption of cefaclor. The desorption by 0.1 N HCl at flow rate of 0.1 ml/min and subsequent heating at 80 degrees C for 2 h allowed the antibiotic to be detected as corresponding oxazolone form in UV-spectrophotometric and differential pulse adsorptive stripping voltammetric measurements. The potential of the suggested approach was illustrated by estimating cefaclor in urine and blood plasma samples.

Cefaclor↗

A double-blind comparison of the effects of cefaclor and amoxycillin on respiratory tract and oropharyngeal flora and clinical response in acute exacerbations of bronchitis.

Fifty-one patients admitted to hospital with severe exacerbations of chronic bronchitis entered a double-blind trial of treatment with cefaclor (500 mg tds) compared with amoxycillin (500 mg tds) for 7 days. Twenty-six patients received cefaclor and 25 amoxycillin. Sputum and throat swabs were collected on admission, after 7 days of therapy and at outpatient follow-up, 3 weeks after treatment had finished. Clinical status and spirometry were assessed on admission and at the third, seventh and 28th day. There was no significant difference between the two regimes for clinical outcome, spirometry or numbers of infecting pathogens. Opportunistic colonization with resistant Gram-negative organisms and Candida species was highly prevalent on admission (56%) in both groups, perhaps because of previous antibiotic administration and general debility of the majority of patients. The high prevalence of opportunistic colonizing organisms persisted at follow-up (48%) with a significant excess of new organisms (Enterobacter cloacae, Klebsiella species and Candida species) present in sputum in the amoxycillin-treated patients. Cefaclor may be less damaging to normal flora than amoxycillin with a consequently reduced risk of colonization and superinfection of the respiratory tract with resistant Gram-negative organisms and yeasts.

Acute Disease↗

Determination of cefaclor in human plasma by a sensitive and specific liquid chromatographic-tandem mass spectrometric method.

A sensitive and specific liquid chromatographic-tandem mass spectrometric method is described for the determination of cefaclor in human plasma. The plasma samples were treated by two sample preparation procedures, i.e. protein precipitation (PPT) and solid-phase extraction (SPE). The pretreated samples were analyzed on a C(18) HPLC column interfaced with a triple quadrupole tandem mass spectrometer. Positive electrospray ionization (ESI) was employed as the ionization source. The analyte and internal standard ampicillin (for PPT) or cefetamet (for SPE) were detected by use of selected reaction monitoring (SRM) mode. The lower limit of quantitation obtained as a result of the PPT procedure was 100 ng/ml. The intra- and inter-run precision, calculated from quality control (QC) samples was less than 12% for cefaclor. The accuracy as determined from QC samples was within +/-3% for the analyte. The SPE procedure could provide the lower limit of quantitation of 2 ng/ml. The precision and accuracy were measured to be below 7.1% and between -3.6% and 1.1%, respectively, for all QC samples. The method was applied for the evaluation of the pharmacokinetic profiles of cefaclor sustained-release formulation.

Anti-Bacterial Agents↗