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PubMed1994

A critical review of the new oral cephalosporins. Considerations and place in therapy.

Oral cephalosporins are key antimicrobials in the family physician's therapeutic armamentarium. The list of available agents within this class has been recently expanded to include cefixime, cefprozil, cefpodoxime proxetil, and loracarbef. Each of these antibiotics has differing antimicrobial coverage patterns and approved therapeutic uses. Compared with older, more established antimicrobials such as penicillin, amoxicillin, cefaclor, a combination of amoxicillin and clavulanate potassium, and erythromycin, the newer cephalosporins offer little, if any, therapeutic advantage. Clinical efficacy has been shown to be equal in virtually all studies comparing the newer cephalosporins with traditional agents for various community-acquired infections. While the four newer agents may be given less often, they are relatively expensive. In light of the available clinical data, the newer oral cephalosporins should be reserved as second- or third-line choices.

Administration, Oral↗
PubMed1994

Cefuroxime axetil in the treatment of sinusitis. A review.

Cefuroxime axetil is a beta-lactamase-stable, second-generation, oral cephalosporin that penetrates sinus tissue in concentrations exceeding the MIC90 values (the minimum concentration of drug needed to inhibit the growth of 90% of an isolate of a particular microorganism) for pathogens most commonly associated with acute sinusitis, including Streptococcus pneumoniae and Haemophilus influenzae. A review of all clinical data published to date demonstrates that cefuroxime axetil has been evaluated in the treatment of acute sinusitis and acute exacerbations of chronic sinusitis ("acute-on-chronic sinusitis") in 18 clinical trials involving 1516 assessable patients. In 12 randomized, comparative trials, the rates of satisfactory clinical outcomes (cure or improvement, 79% to 100%) and bacteriologic eradication (84% to 100%) reported with the use of 250 mg of cefuroxime axetil twice daily were similar to those observed with the use of amoxicillin, amoxicillin/clavulanate potassium, cefaclor, cefadroxil, cefixime, clarithromycin, and doxycycline. In these comparisons, no antibiotic demonstrated any therapeutic advantages over cefuroxime axetil regarding time to symptom abatement. Cefuroxime axetil was at least as well tolerated as the other antibiotics. Overall, the role of cefuroxime axetil in the treatment of sinusitis appears to be as one of the broad-spectrum antibiotics that can be used for infections due to the most commonly implicated sinus pathogens, especially those due to the increasing number of relatively penicillin-resistant strains of S pneumoniae and beta-lactamase-producing strains of H influenzae and Moraxella catarrhalis.

Acute Disease↗
PubMed1983

Bacteriology of acute otitis media in Japanese children.

Bacteriologic investigations were performed on 100 children with acute otitis media by culturing the fluid from a myringotomy site. Patients ranged in age from 7 months to 14 years, and 91 were younger than 6 years old. Bacterial isolates were yielded from cultures in 83 cases, and mixtures of two or three organisms were obtained from 15 patients. Among the total of 100 isolates, the most predominant organism was Streptococcus pneumoniae (28), followed by Hemophilus influenzae (26), Staphylococcus aureus (19), and Streptococcus pyogenes (six). Minimal inhibitory concentrations (MICs) of ampicillin sodium against S pneumoniae and H influenzae were 0.016 to 0.032 and 0.25 to 0.5 mg/L, respectively. None of the strains of H influenzae were resistant to ampicillin. The MICs of dicloxacillin sodium, cephalexin monohydrate, cefaclor, and erythromycin to H influenzae were 8 to 32, 8 to 16, 2 to 8, and 2 to 8 mg/L, respectively. The preferred drug for acute otitis media would be ampicillin in Japan, but we have to consider antistaphylococcal antibiotics for the patients who do not respond to 48 hours of treatment.

Acute Disease↗
PubMed1983

Treatment of Staphylococcus aureus infections in children in office practice.

One hundred five Staphylococcus aureus infections occurring in 79 children who were seen in a private office practice were evaluated for response to antibiotic therapy. The value of in vitro disk susceptibility testing in directing antibiotic selection in treatment failures was also examined. Of the total episodes studied, the types of infection studied included vesicular pyoderma (48%), secondary pyoderma (13%), bullous pyoderma (5%), furunculosis (14%), carbunculosis (12%), cellulitis (3%), suppurative otitis media (4%), and paronychia (2%). Comparative treatment efficacy was obtained with perioral erythromycin estolate and erythromycin ethylsuccinate, cefaclor and cephalexin, and clindamycin hydrochloride and dicloxacillin sodium. Penicillin V potassium, ampicillin, and topical bacitracin were generally ineffective. In 23 patients, 27/105 infections were initial treatment failures. Antibiotic disk susceptibility testing predicted these clinical failures and/or the antibiotic that would produce a clinical response in 21 of these 23 patients, suggesting that this office procedure can be of considerable value.

Adolescent↗
PubMed1995

Practice variations among pediatricians and family physicians in the management of otitis media.

OBJECTIVES: To determine theoretical practice patterns and Medicaid practices in the management of persistent and recurrent otitis media by family physicians and pediatricians in Colorado. METHODS: Members of the Colorado chapters of the American Academy of Pediatrics and the Colorado Academy of Family Medicine were surveyed with the use of two hypothetical case management scenarios for which they were asked to indicate which International Classification of Diseases, Ninth Revision, Medicaid codes they would use. Physicians were presented with two case scenarios (one involving a persistent asymptomatic middle ear effusion and the second involving recurrent otitis media) and were asked to choose from a variety of management options, including observation, antibiotic therapy, decongestants, corticosteroids, antibiotic prophylaxis, and referral for ventilation tube surgery. RESULTS: Family physicians would have prescribed high-cost antibiotics (amoxicillin plus clavulanate potassium, cefaclor, or cefixime) to treat persistent middle ear effusions twice as often as pediatricians would have (P < .002). At the 6-week visit, 50 family physicians (43%) would administer an oral decongestant either alone or in combination with other therapy as compared with 16 (14%) of pediatricians (P < .001). Family physicians would refer patients for ventilating tube surgery three times more often than pediatricians at the 9-week visits (P < .001). Recurrent episodes of acute otitis media would be managed similarly by both physician groups. Respondents reported a wide variety of International Classification of Diseases, Ninth Revision, coding, often coding persistent effusions as acute otitis or as unspecified otitis media. CONCLUSIONS: The findings of this survey document the wide variation in practice patterns for treating children with persistent otitis media and children with recurrent otitis media in Colorado.

Child, Preschool↗
PubMed1998

Treatment of acute otitis media with a shortened course of antibiotics: a meta-analysis.

OBJECTIVE: To conduct a meta-analysis of randomized controlled trials of antibiotic treatment of acute otitis media in children to determine whether outcomes were comparable in children treated with antibiotics for less than 7 days or at least 7 days or more. DATA SOURCES: MEDLINE (1966-1997), EMBASE (1974-1997), Current Contents, and Science Citation Index searches were conducted to identify randomized controlled trials of the treatment of acute otitis media in children with antibiotics of different durations. STUDY SELECTION: Studies were included if they met the following criteria: subjects aged 4 weeks to 18 years, clinical diagnosis of acute otitis media, no antimicrobial therapy at time of diagnosis, and randomization to less than 7 days of antibiotic treatment vs 7 days or more of antibiotic treatment. DATA EXTRACTION: Trial methodological quality was assessed independently by 7 reviewers; outcomes were extracted as the number of treatment failures, relapses, or reinfections. DATA SYNTHESIS: Included trials were grouped by antibiotic used in the short course: (1) 15 short-acting oral antibiotic trials (penicillin V potassium, amoxicillin [-clavulanate], cefaclor, cefixime, cefuroxime, cefpodoxime proxetil, cefprozil), (2) 4 intramuscularceftriaxone sodium trials, and (3) 11 oral azithromycin trials. The summary odds ratio for treatment outcomes at 8 to 19 days in children treated with short-acting antibiotics for 5 days vs 8 to 10 days was 1.52 (95% confidence interval [CI], 1.17-1.98) but by 20 to 30 days outcomes between treatment groups were comparable (odds ratio, 1.22; 95% CI, 0.98 to 1.54). The risk difference (2.3%; 95% CI,-0.2% to 4.9%) at 20 to 30 days suggests that 44 children would need to be treated with the long course of short-acting antibiotics to avoid 1 treatment failure. This similarity in later outcomes was observed for up to 3 months following therapy (odds ratio, 1.16; 95% CI, 0.90-1.50). Comparable outcomes were shown between treatment with ceftriaxone or azithromycin, and at least 7 days of other antibiotics. CONCLUSION: This meta-analysis suggests that 5 days of short-acting antibiotic use is effective treatment for uncomplicated acute otitis media in children.

Acute Disease↗
PubMed1998

Characterization of partitioning behavior of cephalosporins using microemulsion and micellar electrokinetic chromatography.

Electrokinetic chromatography (EKC) was introduced to determine the partitioning behavior of various cephalosporins (cefpim, cefpirom, cefaloridin, cefaclor, cephalexin, cefuroxim, cefotaxim) in microemulsions (ME) and micellar (MC) systems. The partitioning behavior of cephalosporins in microemulsions was characterized calculating the capacity factor. The required parameters for the determination of the capacity factor (micro(aq) and micro-me are the electrophoretic mobilities of the solutes in the aqueous phase and the microemulsion phase, micro(eff) is the effective mobility in the microemulsion solution) were measured by EKC using cationic and anionic microemulsion systems consisting of the surfactants/n-heptane/1-butanol/10 mM phosphate buffer solution, pH 7.0. Electrokinetic chromatography was shown to be a useful method to quantify the partitioning behavior of drugs in oil/water microemulsion. The logarithm of the capacity factor was correlated with the logarithm of the 1-octanol/water partitioning coefficients.

Cephalosporins↗
PubMed1982

Comparison of the antibacterial activity of norfloxacin (MK 0366, AM 715), a new organic acid, with that of other orally absorbed chemotherapeutic agents.

425 randomly selected, fresh clinical isolates were tested for susceptibility to norfloxacin and other orally absorbed agents, i.e. amoxicillin, ampicillin, carbenicillin (available commercially as the indanyl ester), cefaclor, cinoxacin, erythromycin, nalidixic acid, penicillin G, tetracycline, trimethoprim and co-trimoxazole. The results have shown norfloxacin to be the most potent agent in vitro against representative members of the family Enterobacteriaceae, Staphylococcus aureus, Pseudomanas aeruginosa, Acinetobacter spp., Neisseria gonorrhoeae and Haemophilus influenzae. Ninety percent of the isolates in these groups of bacteria were inhibited by less than 1 mg/l, 2 mg/l, 8 mg/l, 32 mg/l, 0.06 mg/l and 0.25 mg/l of norfloxacin, respectively. Although norfloxacin inhibited most streptococci and Ureaplasma at a concentration of 8 mg/l or less, penicillin G proved to be the most active against Streptococcus pygenes and Streptococcus pneumoniae; trimethoprim was the most active against Streptococcus faecalis, and tetracycline the most active against Ureaplasma.

Acinetobacter↗
PubMed1990

[Antibacterial activity and beta-lactamase stability of eleven oral cephalosporins].

Oral cephalosporins (cefixime, cefdinir, cefetamet, ceftibuten, cefpodoxime, loracarbef, cefprozil, cefuroxime, cefaclor, cefadroxil and BAY 3522) were compared by their antibacterial profile including stability against new beta-lactamases. Both activity and antibacterial spectrum of compounds structurally related to third generation parenteral cephalosporins (of the oximino class) were superior to established compounds. Activity against staphylococci was found to be highest for cefdinir, cefprozil and BAY 3522. Cefetamet, ceftibuten and cefixime demonstrate no clinically meaningful antistaphylococcal activity while the other compounds investigated demonstrate intermediate activity. The antibacterial spectrum was broadest for cefdinir and cefpodoxime. New oral cephalosporins are equally inactive as established compounds against Enterobacter spp., Morganella, Listeria, Pseudomonas and Acinetobacter spp., methicillin-resistant staphylococci, Enterococcus spp., penicillin-resistant pneumococci and anaerobes. New extended broad-spectrum betalactamases (TEM-3, TEM-5, TEM-6, TEM-7, SHV-2, SHV-3, SHV-4, SHV-5, CMY-1, CMY-2, and CTX-M) are active against the majority of oral cephalosporins. Ceftibuten, cefetamet, cefixime and cefdinir were stable against some of these enzymes even to a higher extent than parenteral cephalosporins. New oral cephalosporins should improve the therapeutic perspectives of oral cephalosporins due to their higher activity against pathogens marginally susceptible to established compounds (higher multiplicity of maximum plasma concentrations over MICs of the pathogens) and furthermore by including in their spectrum organisms resistant to established absorbable cephalosporins (e.g. Proteus spp., Providencia spp., Citrobacter spp., and Serratia spp.).

Administration, Oral↗
PubMed1979

[Therapy of chronic respiratory tract infections in children, including mucoviscidosis (author's transl)].

In respiratory tract infections in children a distinction must be made between frequently recurring infections and genuine chronic infections due to specific anatomical factors, immunological defects or congenital diseases such as mucoviscidosis. The most frequent pathogens are Haemophilus influenzae, pneumococci, Staphylococcus aureus, Streptococcus pyogenes, enterococci, Pseudomonas aeruginosa and Klebsiella, S. aureus predominates in infants. The same applies for mucoviscidosis, in which P. aeruginosa is the second most frequent pathogen, occurring frequently after a primary infection with staphylococci. In order to avoid frequent relapses in mucoviscidosis patients, uninterrupted long-term treatment with an antibiotic which is effective against staphylococci is recommended, commencing the moment the diagnosis has been established. Suitable antibiotics are co-trimoxazole or oral cephalosporins (e. g. cephalexin, cephradine or cefaclor). Other respiratory tract infections should be treated according to the antibiogramme with a suitable antibiotic once the diagnosis has been confirmed.

Cephalosporins↗
PubMedDate not supplied

In vitro activity of cefpodoxime in comparison with other oral beta-lactam antibiotics.

The aim of our study was to re-evaluate the in vitro activity of cefpodoxime in comparison with other oral beta-lactam antibiotics against bacteria causing respiratory tract infections. The study drugs were cefpodoxime, cefaclor, cefixime, cefuroxime, cefetamet, cefprozil, and the combination of amoxicillin and clavulanic acid (= augmentin). In addition, cefotaxime as the standard agent of parenteral third generation cephalosporins was examined. The organisms tested were Staphylococcus aureus, Streptococcus pyogenes, Streptococcus agalactiae, streptococci of serogroups C and G, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae and Proteus mirabilis. Minimal inhibitory concentrations of the antimicrobials were determined with the agar dilution procedure. Cefpodoxime showed the broadest spectrum and generally also the highest activity of the oral beta-lactam antibiotics examined. The drug was equally active against the major groups of beta-lactamase negative and positive bacteria causing respiratory tract infections. Against penicillin-resistant pneumococci, all beta-lactam agents exhibited reduced activity comparable to the reduced activity of penicillin.

Bacteria↗
PubMed1989

Comparative in vitro activity of the new oral penem ALP-201 against aerobic and anaerobic bacteria.

The in vitro activity of the new penem derivative ALP-201 against 226 aerobic and 350 anaerobic clinical bacterial isolates was determined using agar dilution techniques. For comparison amoxicillin, cefaclor, ceftazidime, doxycycline, erythromycin, imipenem and trimethoprim/sulfamethoxazole were also tested with aerobic bacteria, and cefoxitin, chloramphenicol, clindamycin, imipenem, metronidazole and piperacillin with anaerobic bacteria. ALP-201 was found to be highly active against Escherichia coli, Klebsiella spp., Enterobacter spp., Haemophilus influenzae, Branhamella catarrhalis, Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, anaerobic cocci, Propioni-bacterium acnes, Clostridium perfringens, Bacteroides fragilis, Bacteroides spp. and fusobacteria. Pseudomonas aeruginosa and Clostridium difficile were resistant to ALP-201. When tested against aerobic bacteria using a high inoculum or using the broth dilution technique, the activity of ALP-201 showed little dependence on inoculum size and the bactericidal activity was similar to the inhibitory activity. Further investigations are warranted with ALP-201, which is absorbed from the gastrointestinal tract after oral administration.

Administration, Oral↗
PubMed1990

In vitro activity and beta-lactamase stability of the new oral cephalosporin Bay v 3522.

The activity of the new oral cephalosporin Bay v 3522 was compared to that of six other beta-lactam agents. Bay v 3522 inhibited methicillin-susceptible Staphylococcus aureus and Staphylococcus epidermidis at less than or equal to 2 micrograms/ml, compared to MICs of greater than or equal to 8 micrograms/ml for the other cephalosporins tested. It was more active against Streptococcus pyogenes (MIC less than or equal to 0.06 microgram/ml) than cefuroxime, cefixime, cephalexin and cefaclor. Groups B, C and G streptococci were inhibited at less than or equal to 0.12 microgram/ml, while the MI"90 for Streptococcus bovis and viridans streptococci was 0.5 and 2 micrograms/ml, respectively. The MIC90 for enterococci and Listeria monocytogenes was 8 micrograms/ml. Clostridium perfringens was inhibited by 0.12 microgram/ml, but most Bacteroides spp. were resistant. The MIC90 for beta-lactamase positive Escherichia coli (producing primarily TEM-1) was greater than 64 micrograms/ml and for beta-lactamase negative strains 16 micrograms/ml. The MIC90 for high-level beta-lactamase producing Klebsiella pneumoniae was greater than 64 micrograms/ml versus 4 micrograms/ml for other isolates. The MIC90 for Moraxella catarrhalis was 2 micrograms/ml, for Haemophilus influenzae 1 micrograms/ml, and for Neisseria gonorrhoeae 4 micrograms/ml. Enterobacter cloacae, Citrobacter freundii, Proteus mirabilis, Providencia spp. and Pseudomonas aeruginosa were resistant. Bay v 3522 was destroyed by TEM-1, SHV-1, TEM-3 and P99 beta-lactamases.

Administration, Oral↗
PubMed1993

Evaluation of amoxicillin clavulanate twice daily versus thrice daily in the treatment of otitis media in children. Danish-Swedish Study Group.

A total of 311 children who had recurrent otitis media or who had experienced failure of initial treatment of acute otitis media with phenoxymethylpenicillin, amoxicillin, ampicillin esters or cefaclor were entered into a single-blind study in two parallel groups in order to compare the clinical efficacy and safety of amoxicillin/clavulanate suspension given b.i.d. or t.i.d. for seven days. The patients were examined prior to the start of treatment, at an early follow-up visit 9 to 12 days after the start of treatment and at a late follow-up visit about three weeks later. Specimens for bacteriological culture were taken from the nasopharynx at entry, at the early follow-up visit, and at the late follow-up visit if there were symptoms of otitis. Both treatment groups showed a similar response, 90% or more of the patients being cured or showing improvement at the time of the early follow-up visit. The initial nasopharyngeal cultures showed growth of Haemophilus influenzae in 53% of the patients, Moraxella catarrhalis in 43% and Streptococcus pneumoniae in 39%. After treatment, cultures showed elimination of the initial pathogens in 30% of patients in both groups and recolonization in 23% in both groups. Haemophilus influenzae was the bacteria most frequently found in the nasopharynx at the first follow-up visit. Adverse effects, which consisted mostly of gastrointestinal and dermatological reactions, tended to be more common in the b.i.d. group but the difference was not statistically significant.

Acute Disease↗
PubMed1990

Antimicrobial activity and beta-lactamase stability of BMY-28232, parent compound of an oral cephalosporin.

BMY-28232, an aminothiazolyl imino methoxy cephalosporin which is available as an orally absorbed acetoxyethyl ester, inhibited strains of methicillin-susceptible Staphylococcus aureus, hemolytic streptococci, Streptococcus pneumoniae, Escherichia coli, Klebsiella species, and many strains of Proteus and Providencia stuartii at concentrations less than 1 microgram/ml, including isolates resistant to cephalexin and cefaclor. It had activity similar to that of cefixime, but was more active against methicillin-susceptible staphylococci. BMY-28232 was a poor substrate for beta-lactamases but was destroyed by the new TEM-3 enzyme, and had less activity against Enterobacter species, Citrobacter freundii, and Proteus vulgaris isolates. Methicillin-resistant staphylococci, Pseudomonas species, enterococci, Listeria monocytogenes, Corynebacterium jeikeium, Bacteroides fragilus and some strains of Clostridium species were resistant to BMY-28232.

Bacteria↗
PubMed1990

Spread of non-typable multiply resistant Haemophilus influenzae in a South African hospital.

In July 1987 non-typable Haemophilus influenzae strains resistant to both ampicillin and chloramphenicol were isolated from the endotracheal aspirate of two children with pneumonia at Baragwanath Hospital, Johannesburg, South Africa. A study was therefore undertaken to determine the carriage rates of Haemophilus influenzae strains in the nasopharynx of children and staff in the index ward and in three control wards. Using a disc diffusion and an agar dilution method the susceptibility was determined of 100 isolates to ampicillin, chloramphenicol, erythromycin, rifampicin, amoxicillin/clavulanic acid, gentamicin, cefaclor, cefotaxime, tetracycline, sulphamethoxazole, trimethoprim and trimethoprim/sulphamethoxazole (1:19). The overall carriage rate of Haemophilus influenzae on admission was 76%. In the index ward, children carrying multiply resistant strains differed from the other children in that there was a longer mean duration of hospitalization, a lower proportion of males, and a higher proportion who had previously received antibiotics. All ampicillin resistant strains were shown to produce beta-lactamase. Only four isolates belonged to serotype b, of which three were ampicillin resistant and chloramphenicol sensitive while one was resistant to both drugs. Nasopharyngeal spread of resistant non-typable strains of Haemophilus influenzae was demonstrated to affect the management of paediatric patients in the hospital.

Ampicillin Resistance↗
PubMed1990

Disk diffusion susceptibility testing of Haemophilus influenzae using haemophilus test medium.

A three-center collaborative study was performed with the aim of determining the reproducibility of disk diffusion and broth microdilution susceptibility tests of Haemophilus influenzae with 19 different antimicrobial agents using a newly described medium, Haemophilus Test Medium. The results of both methods were found to be highly reproducible. Using Haemophilus Test Medium, inhibitory zone diameters and MICs were then determined for 150 test strains of Haemophilus influenzae, selected with an emphasis on known mechanisms of resistance. Regression analysis of zone diameter-MIC comparisons was used to define zone diameter interpretive criteria and MIC correlates for Haemophilus Test Medium disk diffusion tests performed with Haemophilus spp. for the following antimicrobial agents: ampicillin, amoxicillin/clavulanate, ampicillin/sulbactam, cefaclor, cefuroxime, cefamandole, ceftriaxone, cefotaxime, ceftizoxime, ceftazidime, cefixime, trimethoprim/sulfamethoxazole, rifampin, chloramphenicol, tetracycline, imipenem, aztreonam and ciprofloxacin.

Anti-Bacterial Agents↗
PubMed1991

In vitro activity of cefcanel versus other oral cephalosporins.

Cefcanel is a new orally absorbed cephalosporin. Its activity was compared with that of cefuroxime, cefaclor, cephalexin, and cefixime against gram-positive and negative aerobic and anaerobic bacteria. Cefcanel had excellent activity against methicillin-susceptible Staphylococcus aureus and Staphylococcus epidermidis, MIC90 1 micrograms/ml, superior to the other oral cephalosporins. However, methicillin-resistant staphylococci were resistant, MIC greater than or equal to 16 micrograms/ml. Streptococcus pyogenes and Streptococcus pneumoniae were inhibited by 0.015-1 micrograms/ml, concentrations comparable to other cephalosporins. Clostridium spp. were inhibited by 0.25 micrograms/ml, 8- to 128-fold lower concentrations than were found for other agents, but the MICs were greater than 64 micrograms/ml for Bacteroides spp. The MIC90 for Moraxella catarrhalis was 1 micrograms/ml, similar to cefuroxime but 16-fold greater than the MICs of cefixime. Escherichia coli and Klebsiella pneumonia which were high beta-lactamase producers were resistant, MICs greater than 64 micrograms/ml, and 50% of Enterobacter cloacae and Citrobacter freundii were resistant. Cefcanel was hydrolyzed by TEM-1, TEM-3 and Moraxella Bro-1 beta-lactamases. Escherichia coli containing TEM-1, 2, 3, 5, 7, and 9 had cefcanel MICs of greater than or equal to 16 micrograms/ml. Although cefcanel inhibited gram-positive species as well as or at lower concentrations than other cephalosporins, it lacked activity against gram-negative species that produced common plasmid beta-lactamase although it inhibited Haemophilus influenzae carrying TEM-1.

Administration, Oral↗