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PubMed1994

Activity of WY-49605 compared with those of amoxicillin, amoxicillin-clavulanate, imipenem, ciprofloxacin, cefaclor, cefpodoxime, cefuroxime, clindamycin, and metronidazole against 384 anaerobic bacteria.

The National Committee for Clinical Laboratory Standards agar dilution method was used to compare the in vitro activity of WY-49605 (also called SUN/SY 5555 and ALP-201), a new broad-spectrum oral penem, to those of amoxicillin, amoxicillin-clavulanate, imipenem, ciprofloxacin, cefaclor, cefpodoxime, cefuroxime, clindamycin, and metronidazole against 384 clinically isolated anaerobes. These anaerobic organisms included 90 strains from the Bacteroides fragilis group, 87 Prevotella and Porphyromonas strains, non-B. fragilis group Bacteroides strains, 56 fusobacteria, 55 peptostreptococci, 49 gram-positive non-spore-forming rods, and 47 clostridia. Overall, WY-49605 had an MIC range of 0.015 to 8.0 micrograms/ml, an MIC at which 50% of the isolates are inhibited (MIC50) of 0.25 microgram/ml, and an MIC at which 90% of the isolates are inhibited (MIC90) of 2.0 micrograms/ml. Good activity against all anaerobe groups was observed, except for Clostridium difficile and lactobacilli (MIC50s of 4.0 and 2.0 micrograms/ml, respectively, and MIC90s of 8.0 and 2.0 micrograms/ml, respectively). Imipenem had an MIC50 of 0.03 microgram/ml and an MIC90 of 0.25 microgram/ml. Ciprofloxacin was much less active (MIC50 of 2.0 micrograms/ml and MIC90 of 16.0 micrograms/ml). By comparison, all oral beta-lactams were less active than WY-49605, with susceptibilities as follows: amoxicillin MIC50 of 8.0 micrograms/ml and MIC90 of > 256.0 micrograms/ml), amoxicillin-clavulanate MIC50 of 1.0 microgram/ml and MIC90 of 8.0 micrograms/ml, cefaclor MIC50 of 8.0 micrograms/ml and MIC90 of > 32.0 micrograms/ml, cefpodoxime MIC50 of 4.0 micrograms/ml and MIC90 of > 32.0 micrograms/ml, and cefuroxime MIC50 of 4.0 micrograms/ml and MIC90 of > 32.0 micrograms/ml. Clindamycin was active against all groups except some members of the B. fragilis group, Fusobacterium varium, and some clostridia ( overall MIC50 of 0.5 micrograms/ml and overall MIC90 of 8.0 micrograms/ml). Metronidazole was active (MIC of less than or equal to 4.0 micrograms/ml) against all gram-negative anaerobic rods, but most gram-positive non-spore-forming rods, some peptostreptococci, and some clostridia were less susceptible. To date, WY-49605 is the most active oral beta-lactam against anaerobes: these results suggest clinical evaluation for clinical indications suitable for oral therapy.

Anti-Bacterial Agents↗

PubMed2002

Effects of amino acid alterations in penicillin-binding proteins (PBPs) 1a, 2b, and 2x on PBP affinities of penicillin, ampicillin, amoxicillin, cefditoren, cefuroxime, cefprozil, and cefaclor in 18 clinical isolates of penicillin-susceptible, -intermediate, and -resistant pneumococci.

Amino acid alterations in or flanking conserved motifs making up the active binding sites of penicillin-binding proteins (PBPs) 1a, 2b, and 2x of pneumococci were correlated with changes in affinities of penicillin, ampicillin, amoxicillin, cefditoren, cefuroxime, cefprozil, and cefaclor for these PBPs. Four penicillin-susceptible (PSSP), eight penicillin-intermediate (PISP), and six penicillin-resistant (PRSP) pneumococci were studied by DNA sequencing of the penicillin-binding sites of the pbp1a, -2x, and -2b genes of strains and by determining 50% inhibitory concentrations of the seven agents for PBP1a, -2x, and -2b. Two PSSP strains had alterations in PBP2x (L(546)-->V) (one strain) or PBP2b (T(445)-->A) (one strain). All eight PISP strains had at least two alterations--T(338)-->P or A or H(394)-->Y in PBP2X and T(445)-->A in BPB2b. All PRSP strains had the same changes seen in PISP strains, as well as T(371)-->A or S substitutions in PBP1a. The two most resistant PRSP strains had a second change in PBP2x (M(339)-->F) in a conserved motif. The affinities of penicillin and ampicillin for all three PBPs were decreased for PRSP and most PISP strains. The affinity of amoxicillin for PBP1a and -2x was decreased only for PRSP. Cefaclor and cefprozil showed decreased affinity of PRSP but not PISP for all three PBPs. Cefuroxime showed decreased affinity of PISP and PRSP for PBP1a and -2x but no change for PBP2b. Cefditoren showed no difference in PBP affinity based on penicillin or cefditoren MICs, indicating a different PBP target for this agent. Overall, the MICs for and PBP affinities of the strains correlated with the changes found in the PBP active binding sites.

Adult↗

PubMed2005

Activity of ceftibuten, cefaclor, azithromycin, clarithromycin, erythromycin and telithromycin against Streptococcus pyogenes clinical isolates with different genotypes and phenotypes.

BACKGROUND: The growing number of macrolide-resistant strains of Streptococcus pyogenes represents an increasing worldwide problem. Macrolide resistance in S. pyogenes is mediated by several different genes, which determine different levels of resistance to macrolides, lincosamides and streptogramin B (MLS). METHODS: This study compared the in vitro antimicrobial activity of azithromycin, clarithromycin, erythromycin, ceftibuten, cefaclor, and telithromycin against 287 strains of S. pyogenes by the broth microdilution method. All strains were characterized both phenotypically and genotypically for erythromycin resistance and most of them have been M-typed by means of PCR. RESULTS: Ceftibuten and cefaclor showed the best antimicrobial activity, while MIC values for telithromycin were higher against constitutively MLS (cMLS)-resistant strains rather than against the other phenotypes. CONCLUSION: Oral cephalosporins retain the best activity against S. pyogenes; showing good activity except for cMLS-resistant strains, telithromycin is a valid alternative to these antimicrobials.

Anti-Bacterial Agents↗

PubMed1979

Cefaclor: summary of clinical experience.

Cefaclor, a new semisynthetic cephalosporin antibiotic for oral use, was studied by 62 clinical investigators in six countries in 1493 adult and paediatric patients. The pooled data reveal that satisfactory clinical responses were obtained in 80% of urinary tract infections, 87% of upper respiratory tract infections, 90% of cases of otitis media, 99% of lower respiratory tract infections, and 96% of skin and skin structure infections. Administration of this antibiotic was associated with a low incidence of adverse reactions including gastrointestinal (2.6%) and hypersensitivity (1.5%). Of particular clinical interest were the outstanding results obtained in the treatment of otitis media and lower respiratory tract infections.

Adult↗

PubMed1994

Comparative efficacy and safety of cefprozil versus penicillin, cefaclor and erythromycin in the treatment of streptococcal pharyngitis and tonsillitis.

Cefprozil is a new oral cephalosporin with an enhanced in vitro spectrum of activity that includes group A beta-hemolytic streptococci (GABHS). Four multicenter randomized clinical trials were conducted to compare the clinical efficacy and safety of cefprozil administered once or twice a day for the treatment of mild to moderate GABHS tonsillitis and pharyngitis. A total of 1597 patients were enrolled in the trials. Patient demographics and severity of infection were similar for all treatment groups. In Study 1, cefprozil administered at 20 mg/kg once daily was clinically, in 68 of 76 patients (89%) and bacteriologically, in 66 of 74 patients (89%) superior to penicillin -51 of 69 (74%) and 46 of 69 (67%)--administered three times a day in patients of two to 12 years of age. In Study 2, the patients enrolled were 13 years of age and older, and cefprozil administered at 20 mg/kg once a day had similar clinical (93% vs. 90%) and bacteriological (95% vs. 94%) response rates as cefaclor administered three times a day. Study 3 demonstrated that cefprozil administered twice daily was similar to penicillin given three times a day, the clinical satisfactory response being 164 of 175 (94%) for cefprozil and 146 of 165 (88%) for penicillin. In Study 4, identical clinical and bacteriologic responses (95%) were observed for cefprozil administered once a day and erythromycin ethylsuccinate administered four times a day in children over two years of age. There were no significant differences in the incidence or severity of drug-related adverse events, which, when reported, were mild and transient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1994

Multi-investigator evaluation of the efficacy and safety of cefprozil, amoxicillin-clavulanate, cefixime and cefaclor in the treatment of acute otitis media.

Cefprozil was evaluated in the treatment of acute otitis media with effusion in three open, randomized, multicenter comparative clinical trials. In two trials, 891 pediatric patients were enrolled to either cefprozil or amoxicillin-clavulanate dosage regimens. The treatment groups were comparable in demographic characteristics, and presented with otalgia, middle-ear effusion, or inflamed or bulging tympanic membrane on otoscopic examination. In all patients, tympanocentesis and a culture were required. Two cefprozil oral doses were evaluated, 30 mg/kg/day and 40 mg/kg/day divided into two equal doses (b.i.d.). Amoxicillin-clavulanate was administered at 40 mg/kg/day in three divided doses (t.i.d.). The recommended duration of therapy was ten days. The predominant bacteria isolated were Haemophilus influenzae and Moraxella catarrhalis. The overall satisfactory clinical response rates were similar for cefprozil (83%) and amoxicillin-clavulanate (81%). The bacteriological response rates did not differ significantly, at 84% and 82%. Cefprozil eradicated the most common pathogen, Streptococcus pneumoniae, more often at 91%, vs. 84% for amoxicillin-clavulanate. The eradication rates were similar against Haemophilus influenzae and Moraxella catarrhalis. The patients treated with cefprozil had a lower rate of adverse clinical events (11%) compared to those with amoxicillin-clavulanate (20%). More gastrointestinal adverse experiences, including diarrhea, were reported in the amoxicillin-clavulanate-treated patients. In Study 3, cefprozil 30 mg/kg/day (b.i.d.) was compared to cefaclor 40 mg/kg/day (t.i.d.) and cefixime 8 mg/kg/day (q.d) in the treatment of acute otitis media in 388 pediatric patients. The patients were treated for 10 days, with a follow-up of 18 days. The overall clinical cure rates were 85%, 89% and 85%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

PubMed1991

High-performance liquid chromatographic determination of loracarbef, a potential metabolite, cefaclor and cephalexin in human plasma, serum and urine.

A high-performance liquid chromatographic (HPLC) method is reported for the determination of a new carbacephem antibiotic, loracarbef, a hydroxylated analogue, and two cephalosporins, cefaclor and cephalexin, in plasma, serum, and urine. The antibiotics are extracted from plasma by means of C18 solid-phase cartridges. Urine samples are diluted with water and directly injected on the HPLC system. The HPLC system utilizes a Supelcosil LC-18-DB (250 mm x 4.6 mm I.D.) reversed-phase column and ultraviolet detection at 265 nm. The limit of quantitation is 0.5 micrograms/ml for each compound. Excellent correlation of plasma concentrations is shown between results determined by HPLC and those obtained by microbiological agar-well diffusion assays. Stability studies of loracarbef in human plasma show the antibiotic to be stable for at least 24 h at room temperature and for at least twelve months at -20 degrees C.

Cefaclor↗

PubMed1998

Hypersensitivity myocarditis caused by an allergic reaction to cefaclor.

An adolescent girl was seen with acute heart failure 6 days after the onset of a viral illness and otitis media treated with cefaclor. An endomyocardial biopsy specimen revealed active myocarditis with an eosinophilic infiltrate typical of hypersensitivity myocarditis. The patient showed dramatic improvement within 48 hours after withdrawal of the drug and administration of corticosteroids and immunoglobulin.

Biopsy↗

PubMed2003

Sensitive determination of a beta-lactam antibiotic, cefaclor by liquid chromatography with chemiluminescence detection.

We present a sensitive method for the determination of cefaclor (CCL), a beta-lactam antibiotic. It was based on the chemical derivatization of the drug with 4-(2'-cyanoisoindolyl)phenylisothiocynate (CIPIC) under the reaction conditions with heating at 80 degrees C for 7 min in the presence of pyridine. The CIPIC reagent could react with the primary amino group of the drug to form the CIPIC-conjugated CCL. The derivatives emitted not only fluorescence (FL) at maximum emission wavelength of 410 nm with irradiation at 310 nm, but also chemiluminescence (CL) in the presence of H(2)O(2), borate buffer (pH 9.6) and acetonitrile. After separation of the CIPIC derivatives of CCL and cephradine as internal standard in human serum by reversed-phase liquid chromatography, the derivatives could be monitored with both FL and CL detections. The detection limit (S/N=3) in the chromatograph was 1 pmol by the CL detection and 10 pmol by the FL detection. The proposed CL method permitted the most sensitive determination of CCL in the human serum after its oral administration.

Adult↗

PubMed1997

Isolation and structure elucidation of the major degradation products of cefaclor formed under aqueous acidic conditions.

The aqueous acidic degradation of the oral cephalosporin cefaclor was investigated. A number of degradation products were isolated and characterized. The degradation products can be loosely classified into three categories: thiazole derivatives, pyrazine derivatives, and simple hydrolysis or rearrangement products. Degradation pathways are proposed that involve (1) hydrolysis of the beta-lactam carbonyl with subsequent rearrangement, (2) ring contraction of the six-membered cephem nucleus to five-membered thiazole derivatives through an episulfonium ion intermediate, and (3) attack of the primary amine of the phenylglycyl side chain on the "masked aldehyde" at carbon-6 to form fluorescent substituted pyrazines.

Cefaclor↗

PubMed2003

Enhanced enzymatic synthesis of a semi-synthetic cephalosprin, cefaclor, with in situ product removal.

In the enzymatic synthesis of cefaclor, 3-chloro-7-d-(2-phenylglycinamide)-3-cephem-4-carboxylic acid, from phenylglycine methyl ester and 7-aminodesacetoxymethyl-3-chlorocephalosporanic acid, the in situ product could influence both the overall conversion and hydrolysis of the ester. Optimization of the parameters, such as pH 6.2, 5 degrees C and substrate molar ratio of 2:1, made in situ product removal improve the overall conversion from 64% to 85% (mol/mol).

Bioreactors↗

PubMed1982

Penetration of amoxicillin, cefaclor, erythromycin-sulfisoxazole, and trimethoprim-sulfamethoxazole into the middle ear fluid of patients with chronic serous otitis media.

Penetration into the middle ear of four antibiotics commonly used in treatment of otitis media was studied by administering a single oral dose of amoxicillin, cefaclor, erythromycin-sulfisoxazole, or trimethoprim-sulfamethoxazole to 83 children with chronic serous otitis media. The antibiotic was given 15-240 min before the removal of middle ear fluid (MEF) by ventilation tubes inserted through the tympanic membrane. At the time MEF was obtained, a sample of blood was drawn from the patient, and concentrations of antibiotic in both specimens were assayed either microbiologically by a disk diffusion method or by high-pressure liquid chromatography. Amoxicillin had the highest ratio of mean peak concentration in MEF to minimal inhibitory concentration (MIC) for the three most common pathogens of otitis media (Streptococcus pneumoniae, ampicillin-sensitive Haemophilus influenzae, and Streptococcus pyogenes), whereas trimethoprim-sulfamethoxazole had the highest ratio of mean peak concentration in MEF to MIC for ampicillin-resistant Haemophilus influenzae.

Amoxicillin↗

PubMed1991

Comparative efficacy and safety of cefprozil and cefaclor in the treatment of acute uncomplicated urinary tract infections.

Cefprozil is a new oral semi-synthetic cephalosporin with broad antibacterial spectrum and prolonged serum elimination half-life. In vitro, cefprozil demonstrates excellent activity against common urinary tract pathogens such as Escherichia coli and Klebsiella pneumoniae. Cefprozil, 500 mg once a day, was compared to cefaclor, 250 mg three times a day, in an open, randomized, comparative, clinical trial for the treatment of acute, uncomplicated, urinary tract infection. One hundred and two adult patients were eligible for safety evaluation; four patients were excluded due to side-effects (abdominal discomfort, nausea and vomiting). Ninety-eight patients were eligible for evaluation of efficacy. Clinical and bacteriological responses were comparable for both antibiotics. Leucopenia, nausea, and vaginal yeast infections were slightly more common in the cefprozil group. Cefprozil, 500 mg once daily, appears to be an appropriate alternative for the treatment of acute, uncomplicated urinary tract infections.

Acute Disease↗

PubMedDate not supplied

Association of auxotypes of Neisseria gonorrhoeae and susceptibility to penicillin G, spectinomycin, tetracycline, cefaclor, cefoxitin, and moxalactam.

Isolates of Neisseria gonorrhoeae from 304 patients attending a venereal disease clinic were examined by a plate dilution method for their susceptibility to six antibiotics: penicillin G, spectinomycin, tetracycline, cefaclor, cefoxitin, and moxalactam. The isolates were also characterized by gonococcal auxotyping. The most frequent auxotypes were Nonrequiring, 58%; Pro-, 14%; Pro- Arg (Orn*) Ura-, 14%; Arg- Hyx- Ura-, 6%; and a miscellaneous group consisting of 8% of the isolates. If the entire group of isolates were examined, moxalactam was the most active of the antibiotics; 94% of the isolates were inhibited by less than or equal to 0.25 microgram/ml. The Pro- Arg (Orn*) Ura- isolates were relatively resistant to penicillin G and cefoxitin. The Arg- Hyx- Ura- group of isolates was the most susceptible of the auxotypes to all of the antibiotics except spectinomycin. The uncommon auxotype Arg (Orn*) Ura- has a requirement for arginine that is satisfied by citrulline but not by ornithine. The results of the present study indicate that the nutritional requirements of gonococci may be associated with their response to certain antibiotics.

Amino Acids↗

PubMed1990

Comparison of cefuroxime axetil, cefaclor, and amoxicillin-clavulanate potassium suspensions in acute otitis media in infants and children.

In this randomized, blinded, multicenter comparison study, 377 infants and children with acute otitis media (AOM) received a 10-day course of an oral suspension of one of the following: cefuroxime axetil (CAE), 30 mg/kg/day; cefaclor (CEC), 40 mg/kg/day; or amoxicillin-clavulanate potassium (AMX-CL), 40 mg/kg/day. Clinical efficacy was determined by pneumatic otoscopy and tympanometric testing 3 to 5, 11 to 14, and 22 to 26 days after the initiation of therapy. There was a statistically significant difference among the three treatment groups with respect to clinical outcome; more patients in the CAE group (62%) than in the CEC group (46%) or the AMX-CL group (52%) had complete resolution of signs and symptoms of AOM (including effusion). Paired comparisons revealed a significant difference in efficacy between CAE and CEC and a nearly significant difference between AMX-CL and CEC. Taste acceptability was highest for CEC and lowest for this formulation of CAE. Significantly more patients in the AMX-CL group than in the CAE or CEC group had a side effect, primarily diarrhea, vomiting, or diaper rash. We conclude that CAE suspension has greater clinical efficacy than CEC and fewer side effects than AMX-CL.

Acoustic Impedance Tests↗

PubMed1992

Serum sickness-like syndrome associated with cefaclor therapy.

We describe 2 cases of paediatric patients who developed the main clinical features of a serum sickness reaction, while on treatment with cefaclor. A decrease in complement values was observed in both cases. Physicians should be aware of the possibility of such drug adverse reaction.

Cefaclor↗

PubMed1993

[The effect of cefaclor on the nasopharyngeal pathogens in children].

Nasopharyngeal specimens were taken from 29 children with acute otitis media, 14 children with chronic sinusitis at acute exacerbation and 2 children with streptococcal pharyngitis who had received cefaclor for 14 days. The study was designed to compare the microbiologic flora of the nasopharynx before the treatment of these diseases with that after the treatment. In this report the subjects were limited to the children who had not received antibiotics within 1 month. Pathogens detected on initial examination were 49 strains consisting of 40 strains of H. influenzae, 3 strains of S. aureus, 5 strains of S. pyogenes, and 1 strain of S. pneumoniae. Two strains were detected in 4 patients. Pathogens remained after treatment in 29 patient, with an unchanged number of pathogens in 12 patients, a decreased number in 14, and microbial substitution in 3. All of the remaining pathogens were H. influenzae, and minimum inhibitory concentration (MIC) changed in 5 of the 26 patients in whom H. influenzae was detected before and after treatment. In a patients with increased MIC, the strain changed from a sensitive strain with an MIC of lower than 3.13 micrograms/ml to a highly resistant strain with an MIC of 25.0 micrograms/ml or higher. By contrast, in 2 patients with decreased MIC, the strain changed from a highly resistant strain with an MIC of 12.5 micrograms/ml or higher to a sensitive strain with an MIC of lower than 3.13 micrograms/ml. In the other patient, MIC decreased to 3.13 micrograms/ml after it had increased from 3.13 micrograms/ml to 25.0 micrograms/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1982

Susceptibility of Haemophilus influenzae type b to cefaclor and influence of inoculum size.

Cefaclor appeared to be an effective antibiotic against both beta-lactamase-positive and beta-lactamase-negative strains of Haemophilus influenzae type b when tested with 10(5) colony-forming units per ml. With inocula in excess of 10(6) colony-forming units per ml, these organisms were neither inhibited nor killed at concentrations of 400 micrograms/ml. This inoculum effect was also demonstrated in time-kill curve studies.

Cefaclor↗