THE EFFECT OF CEFACLOR AND CEFIXIME ON NASOPHARYNGEAL PATHOGENS IN CHILDREN
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Changes in nasopharyngeal flora were investigated in children with acute otitis media and with acute exacerbations of chronic sinusitis in whom antibiotic therapy of relatively long duration was required until substantial improvement in clinical findings was achieved.1. The antibiotics used were two cephalosporins, i.e., cefaclor (CCL) and cefixime (CFIX), administered to 18 patients each for 1 week and to 26 and 20 patients, respectively, for 2 weeks. Bacteriologic examination of the nasopharyngeal mucosa was performed at the first visit and at 1 week in those who underwent antibiotic therapy for 1 week, and at the first visit and at 1 and 2 weeks in those treated with antibiotics for 2 weeks.2. The elimination rates for the infecting microorganisms in the patients in the CCL-treated group were 30% for Haemophilus influenzae. 83% for Staphylococcus aureus, 100% for Streptcoccus pyogenes and 100% for Streptcoccus pneumoniae at 1 week, and 18% for H. influenzae, 100% for S. aureus and 100% for S. pyogenes at 2 weeks of antibiotic therapy. Replacement of S. aureus and S. pyogenes by H. influenzae was observed.3. The elimination rates for infecting bacteria in the patients in the CFIX-treated groups were 61% for H. influenzae. 50% for S. aureus, 75% for S. pyogenes, 80% for S. pneumoniae and 100% for Moraxella catarrhalis at 1 week, and 72% for H. influenzae, 0% for S. aureus, 100% for S. pyogenes, and 0% for S. pneumoniae at 2 weeks of antibiotic therapy. The elimination rate for H. influenzae at 2 weeks was significantly higher than the corresponding value for the CCL-treated group. Replacement of H. influenzae by S. aureus and S. pneumoniae and of S. pyogenes by S. aureus was detected.4. There was one patient with acute otitis media in the CFIX-treated group in whom a clinical relapse occurred due to H. influenzae persisters in the nasopharynx. Thus the diagnosis in this patient was so-called "recurrent otitis media".5. H. influenzae tended to persist after exposure to therapeutically adequate concentrations of CCL, as did S. aureus and S. pneumoniae following treatment with CFIX. Thus, it would seem that ample heed must be given to persistence, particularly of H. influenzae and S. pneumoniae, the most common causative agents of acute otitis media in childhood.6. A significant rise in the MICs of the cephalosporins was observed in 4 of 43 patients in whom the same type of organism was isolated from the nasopharynx at weekly intervals during antibiotic therapy. Since cephalosporin therapy brought about a substantial improvement in clinical symptoms in all 4 of these patients with a definite reduction in the infecting bacterial population, the development of drug resistance was considered to be due to selection of a small number of resistant strain among the drug susceptible majority of the microbial population against which the cephallosporins were destructive.Keywords:
Cefixime
Cefaclor
Streptococcus Pyogenes
The orally administered cephalosporin antibiotic, cefaclor, has been available for clinical use in many countries since 1979. Because widespread antibiotic use is often cited as a factor in the emergence of bacterial resistance to antibiotics, we sought to determine the degrees of resistance to cefaclor expressed by key pathogens recently isolated in 10 countries widely distributed around the world. Using the E-test ®, minimal inhibitory concentrations (MIC) were determined for cefaclor and several comparator antibiotics against approximately 700 fresh clinical isolates of each of six bacterial species. The results demonstrated that > 90% of Haemophilus influenzae (β-lactamase producing and non-producing), Haemophilus parainfluenzae (β-lactamase producing and non-producing), Moraxella catarrhalis (> 90% β-lactamase producing), and methicillin-susceptible Staphylococcus aureus, and 85% of Escherichia coli were susceptible to cefaclor at the NCCLS interpretive breakpoints. MIC distributions showed that there has been no change in the activity of cefaclor against penicillin-susceptible strains of Streptococcus pneumoniae since 1977.
Cefaclor
Haemophilus parainfluenzae
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In a double-blind study cefixime, an oral cephalosporin of the third generation, was compared to cefaclor in the treatment of acute otitis media in 397 children aged 6 months to 12 years. Clinical evaluation was carried out at the beginning, at day 10–12 and day 28–35 after the start of the treatment. Specimens for bacterial culture and sensitivity testings were taken from the nasopharynx at the initial visit. Patients were randomized either to cefixime in a dose of 8 mg/kg/day or cefaclor in a dose 40 mg/kg/day in the proportion of 2 cefixime patients to 1 cefaclor patient. Two daily doses were administered for 7 days. At day 10–12, 93.5% in the cefixime group and 90.5% in the cefaclor group (p=0.08) were clinically cured or improved. At day 28–35 the rate of cured or improved patients had decreased, mostly due to reinfections, to 90.1% in the cefixime group and to 86.6% in the cefaclor group (p=0.12), respectively. 375 patients (69.9%) had positive bacterial culture in the nasopharynx of at least one strain of Haemophilus influenzae, Streptococcus pneumoniae, Branhamella (Moraxella) catarrhalis or combinations of these 3. 73.6% of the B. catarrhalis strains were beta-lactamase producing and 11.4% of the H. influenzae strains, respectively. All isolated bacteria were sensitive to cefixime. Adverse events were reported in 17.9% in the cefixime and 10.6% in the cefaclor group. Most reactions were of moderate or mild nature and mostly affected skin or the gastrointestinal region. No serious adverse experiences occurred. In view of the good clinical results obtained cefixime seems to be at least as effective as cefaclor in the treatment of acute otitis media in children.
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Cefaclor
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Influences of cefixime and cefaclor, oral antibiotics, were studied in 50 children (age range, 11 months to 13 years) with pharyngitis. Daily doses of cefixime were 6 to 10 mg/kg in 25 children and those of cefaclor were 40 to 50 mg/kg in 25 children. Pharyngeal swabs were taken before and after 3 to 7 days of the antibiotic treatment. Pathogenic organisms, such as Streptococcus pyogenes, Haemophilus influenzae and Streptococcus pneumoniae, were isolated in 14 children before and in 1 child after cefixime use. But these bacteria were isolated in 15 children before and in 9 children, and 3 strains of H. influenzae and 3 strains of S. pneumoniae were newly isolated after cefaclor use. An isolation rate of Gram-negative bacilli, such as Acinetobacter spp., were increased after use of cefixime. In both antibiotics, isolation rates of yeasts were slightly increased. An isolation rate of alpha-hemolytic streptococci was increased from 16% to 48% by cefixime treatment and from 24% to 52% by cefaclor treatment. The MIC50 of cefixime and cefaclor against alpha-hemolytic streptococci isolated after treatment was higher than that isolated before. Effects of cefixime and cefaclor was less extensive than that of ampicillin in previous reports.
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Cefixime
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The pathogens Streptococcus pyogenes and Moraxella catarrhalis colonize overlapping regions of the human nasopharynx. We have found that M. catarrhalis can dramatically increase S. pyogenes adherence to human epithelial cells and that species-specific coaggregation of these bacteria correlates with this enhanced adherence.
Streptococcus Pyogenes
Moraxella (Branhamella) catarrhalis
Human pathogen
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The efficacy of cefixime was compared with that of cefaclor in the treatment of 63 patients with acute otitis media. Patients received either a single dose of cefixime (8 mg/kg/day) or 3 divided doses of cefaclor (40 mg/kg/day). On the basis of otoscopic and tympanometric results at 10 to 14 days after the start of treatment, 28 (97%) of 29 cefixime-treated patients and 25 (78%) of 32 cefaclor-treated patients had resolution of acute otitis media. The clinical cure rate associated with all organisms was 94% for cefixime (16 of 17 isolates) and 68% (13 of 19 isolates) for cefaclor. The cure rate for Streptococcus pneumoniae was 12 of 12 (100%) for cefixime and 1 oil (100%) for cefaclor; the cure rate for Haemophilus influenzae (which includes 2 patients with mixed infections) was 3 of 4 (75%) for cefixime and 2 of 7 (29%) for cefaclor. One clinical relapse occurred among 29 cefixime-treated patients; however, at 28 days 9 recurrences were observed. Three of 25 (9%) cefaclor-treated patients failed and 4 (13%) relapsed at 10 to 14 days, an additional 2 (10%) experienced recurrence by Day 28. Eight (28%) cefixime-treated patients experienced adverse events (7 gastrointestinal and 1 diarrhea and rash); 8 (25%) cefaclor-treated patients experienced adverse events (all gastrointestinal). Our data suggest that both at end of therapy and for 14 days thereafter, cefixime given once a day for acute otitis media is clinically equivalent to cefaclor given 3 times a day.
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Cefixime
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Objective: The etiology and pathogenesis of otitis media with effusion (OME) is still unclear despite many studies within the last four decades. Polymerase chain reaction (PCR) based procedures are suggested for detection of the causative bacteria supposed to inflict multiple infections. In the current study, culture and PCR based approaches were used to detect the frequency of Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis, which have been known as common pathogens in middle ear effusions (MEE) of patients with otitis media. Material and Methods: The DNAs of these three bacteria were detected by standard and multiplex PCR techniques in MEE specimens and their diagnostic values were evaluated in comparison to the conventional culture method. Results: Samples from 67 OME suspected children were analysed retrospectively. Two H. influenzae and two M. catarrhalis isolates were recovered by conventional culture method (6.0%; 4/67). Out of the 67 samples, seven S. pneumoniae, nine H. influenzae, and eleven M. catarrhalis isolates were detected vith PCR. In five samples, two concurrent bacteria were detected in following combinations: two S. pneumoniae and H. influenzae, two S. pneumoniae and M. catarrhalis, and one H. influenzae and M. catarrhalis. Sensitivity, specificity, positive predictive value and negative predictive value rates of the PCR technique were 100.0%, 71.4%, 18.2% and 100.0%, respectively. The difference between culture and PCR was statistically significant (p<0.001). Conclusion: Although the specificity and positive predictive values are low, PCR, which allows rapid screening is feasible for detecting the most common fastidious bacteria that lead to OME.
Fastidious organism
Moraxella (Branhamella) catarrhalis
Microbiological culture
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The in vitro activity of a new orally administered carbacephem analog of cefaclor, loracarbef (LY163892), was compared with those of cefaclor and several other oral antimicrobial agents against recent clinical isolates of Haemophilus influenzae and Moraxella catarrhalis. Loracarbef was found to be slightly more active than cefaclor against H. influenzae and had activity essentially equivalent to that of cefaclor for M. catarrhalis. Resistance to loracarbef was uncommon and was noted only with rare beta-lactamase-producing strains of H. influenzae. On the basis of these observations, loracarbef may be of utility in the management of localized, non-life-threatening infections caused by H. influenzae and M. catarrhalis.
Cefaclor
Moraxella (Branhamella) catarrhalis
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Haemophilus influenzae , Streptococcus pneumoniae and Moraxella catarrhalis are bacterial species which frequently co-colonise the nasopharynx, but can also transit to the middle ear to cause otitis media. Chronic otitis media is often associated with a polymicrobial infection by these bacteria. However, despite being present in polymicrobial infections, the molecular interactions between these bacterial species remain poorly understood. We have previously reported competitive interactions driven by pH and growth phase between H . influenzae and S . pneumoniae . In this study, we have revealed competitive interactions between the three otopathogens, which resulted in reduction of H . influenzae viability in co-culture with S . pneumoniae and in triple-species culture. Transcriptomic analysis by mRNA sequencing identified a central role of arginine in mediating these interactions. Arginine supplementation was able to increase H . influenzae survival in a dual-species environment with S . pneumoniae , and in a triple-species environment. Arginine was used by H . influenzae for ATP production, and levels of ATP generated in dual- and triple-species co-culture at early stages of growth were significantly higher than the combined ATP levels of single-species cultures. These results indicate a central role for arginine-mediated ATP production by H . influenzae in the polymicrobial community.
Moraxella (Branhamella) catarrhalis
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A randomized controlled study design was used to compare the efficacy of cefixime versus cefaclor in 30 patients suffering from lower respiratory tract infections. Patients were treated with a 10 to 11 day course of cefixime 200 mg b.i.d. or cefaclor 500 mg t.i.d. The overall clinical response (cured and improved) in the 13 evaluable patients of the cefixime group was 100%. 12 of the 14 patients of the cefaclor group were cured or improved. In the two other patients the symptoms remained unchanged. The bacteriological efficacy in both groups was comparable. Adverse effects were not reported during the study.
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Cefixime
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