Susceptibility of Respiratory and Urinary Pathogens to Ceftibuten and Other Comparative Drugs: Results of an Italian Multicenter Survey

Summary

A survey aimed at assessing the ability of ceftibuten, a new oral third-generation cephalosporin, to eradicate in Vitro selected bacterial pathogens was conducted in 1991 in 17 microbiology laboratories evenly distributed in Italy. Over 8700 organisms collected from in- and outpatients affected mainly by respiratory and urinary tract infections were analyzed. This collection of bacteria did not include staphylococci, enterococci, Pseudomonta and other oxidative species naturally refractory to the action of most antibiotics employed.

Susceptibility to ceftibuten, cefaclor, cefuroxime, amoxicillin, amoxicillin-clavulanate, cotrimoxazole and erythromycin was assessed using a standardized agar-diffusion method. Production of β-lactamases was confirmed by the nitrocefin test. Among the microorganisms studied E. coli (32.1%) prevailed, followed by P. mirabilis (17.1%), K. pneumoniae (10.9%), 5. pyogenes (6.6%), E. cloacae (5.1%), Serratia spp. (4.5%), Enterobacter spp. (4.2%), H. influenzae (3.6%), S. pneumoniae (2.2%) and Af. catarrhalis (2%). Within this group of pathogens amoxicillin resistance, often mediated by synthesis of P-lactamases, was widely diffused (46.2%). The overall inhibitory activity of the drugs tested decreased as follows: ceftibuten (90.4%), cefuroxime (80.4%), amoxicillin-clavulanate (77.4%), cotrimoxazole (75.3%), cefaclor (72.6%), amoxicillin (53.8%) and erythromycin (32.8%). When the efficacy of the antibiotics was assessed against the collection of respiratory isolates producing β-lactamases only ceftibuten maintained the same overall potency manifested against the general population while the comparative agents were far less effective. The results of this national survey indicate that, given the low incidence of resistance among the most prevalent causative agents of respiratory and urinary tract infections, ceftibuten can be safely used at present in the empiric therapy of these conditions especially when they occur in community settings.     

Cefaclor: A Contemporary Look at Susceptibility of Key Pathogens from Around the Globe

Abstract

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.     

Hepatocyte growth factor protects the liver against hepatitis C virus in patients on regular hemodialysis

Abstract

Propolis is produced by bees and is reported to have several pharmaceutical properties. Its antibacterial activity against strains causing upper respiratory tract infections is particularly important: Propolis might be used as a therapeutic agent to prevent the bacterial infections that sometimes overlap viral infections.

In this study the in vitro activity of both an alcoholic solution and a hydroglyceric extract of Propolis as well as its active principles, was tested against bacteria responsible for respiratory infections (Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis and Streptococcus pyogenes).

We also evaluated the in vitro activity of a combination of propolis and its active principles and some beta-lactams, macrolides and fluoroquinolones. Our results, though not demonstrating a clearly synergistic activity between antibiotics and Propolis and its constituents, show the possibility of using natural preparations, due to their antimicrobial and anti-inflammatory properties, to enhance antibacterial therapy.     

Rationale for Treating Community-Acquired Lower Respiratory Tract Infections with Amoxicillin/Sulbactam Combination Through Pharmacodynamic Analysis in the Setting of Aminopenicillin-Resistant Organisms

Abstract

In order to establish a rationale for treating community-acquired lower respiratory tract infections, we assess here the pharmacodynamics of amoxi-cillin/sulbactam, 500mg/500mg, a formulation marketed in Argentina since 1988 and currently available in 17 countries, against the major pathogens, in comparison with that of a novel formulation (875mg/125mg, see J Chemother 2000; 12: 223-227). In time-kill studies, both bactericidal and inhibitory activity were seen in the 1.5- and 6-h sera, obtained from 12 volunteers after a single oral dose, against both a penicillin-susceptible and an -intermediate Streptococcus pneumoniae strain, as well as against Moraxella catarrhalis and a β-lactamase-negative Haemophilus influenzae strain. Only the 1.5-h sera proved bactericidal against a penicillin-resistant S. pneumoniae strain (MIC, 2 μg/ml) and a β-lactamse-positive H. influenzae isolate. This study suggests that amoxicillin/sulbactam (500mg/500mg) is still a suitable option for treating community-acquired lower respiratory tract infections, allowing a b.i.d. dosing schedule. Caution should be taken with pneumonia caused by β-lacta-mase-positive H. influenzae or penicillin-resistant (MIC >2 μg/ml) S. pneumoniae isolates. Either shorter dosing intervals (t.i.d.) or a higher amoxicillin content in the formulation (i.e. 875 mg) may be required in these situations.     

Comparative In Vitro Activity of Telithromycin and β-Lactam Antimicrobials Against Bacterial Pathogens from Community-Acquired Respiratory Tract Infections: Data from the First Year of PROTEKT (1999-2000)

Abstract

The In Vitro activity of telithromycin, a new ketolide, was compared with β-lactam antimicrobials against pathogens commonly associated with community-acquired respiratory tract infections. These pathogens were collected during 1999-2000 as part of the ongoing PROTEKT surveillance study. Globally, penicillin non-susceptibility among Streptococcus pneumoniae (n=3362) was 36.3%, ranging from 21.5% (Australasia) to 68.0% (Far East). Telithromycin showed higher potency (MIC₉₀ 0.12 mg/L) than β-lactams against S. pneumoniae; 99.9% of all and 99.6% of multi-resistant isolates were susceptible to telithromycin. Among Streptococcus pyogenes isolates (n=1485), 100% were susceptible to β-lactams, and the telithromycin MIC₅₀ and MIC₉₀ were both 0.015 mg/L. Among Haemophilus influenzae (n=2948), 16.6% produced β-lactamase, which reduced the activity of ampicillin, cefaclor and cefprozil. 99.9% of H. influenzae were susceptible to telithromycin and the MIC range for M. catarrhalis was 0.004-0.5 mg/L. The first year results of PROTEKT confirmed high potency for telithromycin against common respiratory tract pathogens, including β-lactam-resistant strains.     

A Comparison of the Activity of Ciprofloxacin and Levofloxacin with Other Agents Against Respiratory Tract Pathogens

Abstract

In a study involving 15 UK hospitals, sequential respiratory tract isolates of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis were studied. The susceptibility of these strains to two fluoro-quinolones, ciprofloxacin and levofloxacin were compared to those of currently used macrolides and β-lactams.

The activity of ciprofloxacin and levofloxacin against S. pneumoniae was not statistically significantly different (geometric mean MIC 0.978 and 0.95 mg/L respectively). β-lactam resistance did not affect fluoroquinolone susceptibility. H. influenzae and M. catarrhalis were highly susceptible to both fluoro-quinolones.     

In vitro and in vivo pharmacokinetic/pharmacodynamic activity of clofoctol

Abstract

The aim of the study was to examine the in vitro susceptibility of clinical isolates of respiratory pathogens to clofoctol compared with amoxicillin and erythromycin, and to characterize the pharmacokinetic/pharmacodynamic (PK/PD) relationships of clofoctol using a murine pneumonia infection model. Strains clinically isolated from patients between 2005 and 2009 were used to examine susceptibility: penicillin-susceptible Streptococcus pneumoniae, penicillin-resistant S. pneumoniae, Streptococcus pyogenes, methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus, and Haemophilus influenzae. The in vitro activity of clofoctol against clinical isolates has essentially remained unchanged over recent years. The MIC₅₀ and MIC₉₀ of clofoctol against penicillin-resistant S. pneumoniae are lower than that of amoxicillin and erythromycin. The area under curve/minimum inhibitory concentration (AUC/MIC) ratio is the PK/PD parameter that best correlates with in vivo clofoctol efficacy; the value of AUC/MIC required to achieve the maximum effect in this study was 75·5.     

Annual Author and Subject Indexes Volume 18-2006

Abstract

Resistant clones/phenotypes are putting into question the activity of commonly used β-lactams, thus prompting the need for alternative options. A 500 mg levofloxacin vs. azithromycin once daily pharmacodynamic simulation was performed against 10⁸ cfu/ml of four Streptococcus pneumoniae strains (exhibiting higher amoxicillin than penicillin MIC) and four Haemophilus influenzae strains: β-lactamase producing, BLNAR (β-lactamase-negative ampicillin-resistant) and BLPACR (β- lactamase-positive amoxicillin/clavulanate-resistant). High levofloxacin AUC/MIC values for H. influenzae, and values of 50-100 for S. pneumoniae produced a >5 log₁₀ reduction at 24h for all strains. Azithromycin AUC/MIC values of ?10 were needed to obtain a 2-3 log₁₀ reduction of S. pneumoniae initial inocula, but lower AUC/MIC values (of ?6) obtained ≥3 log₁₀ reduction against all strains of H. influenzae. While in vitro simulated serum concentrations of levofloxacin were bactericidal at the end of the dosing interval against all S. pneumoniae strains and azithromycin against the susceptible ones, both antimicrobials achieved this endpoint against the BLNAR and BLPACR strains.     

A Pharmacodynamic Model to Support a 12-Hour Dosing Interval for Amoxicillin/Sulbactam,a Novel Oral Combination,in the Treatment of Community-Acquired Lower Respiratory Tract Infections

Abstract

We evaluated, by time-kill studies, the pharmacodynamics of amoxicillin/sul-bactam (AMX/SUL, 875 mg/125 mg), a novel oral combination, against the major respiratory pathogens in 12 volunteers receiving a single dose. The sera corresponding to 50% of a 12-h dosing interval displayed either bactericidal or inhibitory activity against both a penicillin-susceptible and a penicillin-intermediate Streptococcus pneumoniae strain (penicillin MIC of 0.03 and 0.25 μg/ml, respectively), as well as against a β-lactamase-positive Moraxella catarrhalis and a β-lactamase-negative Haemophilus influenzae strain. Both the peak samples and those corresponding to 4 h after dose (i.e. 33% of a 12-h dosing interval) proved active against both a penicillin-resistant S. pneumoniae (MIC, 2 μg/ml) and a β-lactamase-positive H. influenzae strain. The AMX-SUL formulation evaluated in this study showed pharmacodynamic features that support clinical trials to assess its efficacy in the treatment of lower respiratory tract infections with a 12-h dosing interval regimen.     

In vitro Activity of Ertapenem against Common Clinical Isolates in Relation to Human Pharmacokinetics

Abstract

The In vitro activity of ertapenem against bacterial pathogens isolated from patients with moderate to severe complicated intra-abdominal, complicated skin/skin structure, acute pelvic, or complicated urinary tract infection or community acquired pneumonia was compared to ceftriaxone and piperacillintazobactam and related to known plasma concentrations of the three agents. Ertapenem was more potent against methicillin-susceptible Staphylococcus aureus (MSSA) than ceftriaxone and piperacillin-tazobactam and was more potent and more active than both of these agents against Enterobacteriaceae and anaerobes. Piperacillin-tazobactam was the most active agent against enterococci and Pseudomonas aeruginosa. All isolates of Enterobacteriaceae (n=1088), Streptococcus pyogenes (n=37), Streptococcus agalactiae (n=48), MSSA (n=187), Haemophilus influenzae (n=59), and Moraxella catarrhalis (n=9) were susceptible to ertapenem; <1% of 1284 anaerobes and only 1 of 113 Streptococcus pneumoniae (a penicillin-resistant isolate) were resistant to ertapenem. The MIC value at which 90% of all Enterobacteriaceae, streptococci, MSSA, H. influenzae, M. catarrhalis, and anaerobes were inhibited (MIC₉₀) was ≤μg/ml and below the mean plasma concentration of total ertapenem following a 1 g intravenous infusion for at least 24 hours, i.e., the entire recommended dosing interval, and below the free drug concentration for at least 8 h.     

In-vitro activity of cefpodoxime proxetil (RU 51807): a comparative disk diffusion study on isolates from geriatric patients

997 strains isolated from clinical specimens arrived at the "Pio Albergo Trivulzio" microbiology laboratory were tested using disks of cefpodoxime, amoxicillin + clavulanic acid, cefaclor, cefuroxime, ofloxacin, cotrimoxazole, ceftriaxone and cefalexin. Gram-positive strains were tested also with erythromycin, while gram-negative bacteria were tested against aztreonam. Cefpodoxime overall activity was well above the effectiveness of the other oral cephalosporins and on the same order as ceftriaxone and ofloxacin. Cefpodoxime proved to be also more active than the combination amoxicillin-clavulanic acid.     

Antibiotic Susceptibility of Respiratory Pathogens Recently Isolated in Italy: Focus on Cefditoren

Abstract

The aim of this study was to evaluate the in vitro antibiotic susceptibility of respiratory pathogens recently isolated in italy to commonly used antibiotics including cefditoren. Six clinical microbiological laboratories collected, between January and September 2009, a total of 2,510 respiratory pathogens from subjects with community- acquired respiratory tract infections (CARTI). Cefditoren, out of all the beta-lactams studied, had the lowest MIC₉₀ against 965 strains of Streptococcus pneumoniae examined, followed by cefotaxime and ceftriaxone (2% resistance in penicillin-resistant S. pneumoniae (PRSP)). Against 470 Haemophilus influenzae, independently of their production of beta-lactamases or ampicillin resistance, cefditoren was the oral cephalosporin with the best in vitro activity, comparable to that of the injectable cephalosporins and levofloxacin. Higher MIC₉₀s were found for the macrolides (4 - 16 mg/L) and cefaclor (4 - 32 mg/L). As was foreseeable, Streptococcus pyogenes (225 strains) was uniformly sensitive to all the beta-lactam antibiotics, but the elevated miC90 values reduced (<75%) susceptibility of this pathogen to macrolides. Beta-lactamase-negative Moraxella catarrhalis (100 strains) had reduced susceptibility only to the macrolides, while the 250 beta-lactamase-producing strains also had reduced susceptibility to cefuroxime. Levofloxacin showed the lowest MIC₅₀/MIC₉₀ values in the producing strains, whereas cefditoren, cefotaxime and ceftriaxone in the non-producers. As regards the enterobacteriaceae, cefditoren and levofloxacin had the lowest MIC₉₀s against Klebsiella pneumoniae. Cefditoren and the third-generation injectable cephalosporins had the lowest MIC₉₀s against Escherichia coli (100% susceptibility) while levofloxacin was less active (86% susceptibility).

In conclusion, cefditoren's wide spectrum and high intrinsic activity, as well as its capacity to overcome most of the resistance that has become consolidated in some classes of antibiotics widely used as empiric therapy for CARTI, allows us to suggest that cefditoren might be included in the european guidelines as one of the first-choice antibiotics in the treatment of CARTI.     

Antibacterial Activity of Cefditoren Against Major Community-Acquired Respiratory Pathogens Recently Isolated in Italy

Abstract

In this study we evaluated the in vitro activities of cefditoren - a broad-spectrum oral cephalosporin - and other comparator agents against 2,396 fresh isolates from community-acquired respiratory tract infections, collected from 6 clinical Italian microbiology laboratories.

On penicillin-susceptible pneumococci and Streptococcus pyogenes, cefditoren demonstrated to be the most active antibiotic (MIC₉₀ values of 0.03 and 0.06 mg/L respectively), showing only a slight decrease in potency on penicillin-intermediate and re-sistant pneumococci (MIC₉₀ value 0.5 mg/L, 1.0 mg/L respectively). All the other comparators displayed MIC₉₀ values of 4 - 8 mg/L for penicillins and of 4 to >64 mg/L for the oral cephalosporins. Cefditoren and levofloxacin were the most active against MSSA (MIC₉₀ 0.5 mg/mL). Cefditoren displayed a uniformly potent inhibitory activity (MIC₉₀ of 0.03 mg/L) against all strains of Haemophilus influenzae, regardless of their ampicillin resistance (mediated or not by beta-lactamase production), while against Moraxella catarrhalis MIC₉₀ values were higher against beta-lactamase-positive (0.25 mg/L). Cefditoren was active also against Klebsiella pneumoniae and Escherichia coli: in this case its activity was comparable with that of levofloxacin.

In conclusion, cefditoren, due to its potent activity, is a new effective therapeutic option for the treatment of respiratory tract infections.     

In- Vitro Activity of Ampicillin/Sulbactam and Other Antibiotics against Clinical Isolates of Haemophilus sp. and Branhamella catarrhalis

Summary

The ampicillin/sulbactam combination is one of several such drug combinations of a beta-lactam and suicide inhibitor having a wide spectrum of activity.

These characteristics induced us to evaluate the in vitro activity of this combination towards 54 strains of Haemophilus sp. (38 beta-lactamase producers) and 20 strains of Branhamella catarrhalis (16 beta-lactamase producers).

All strains were isolated from sputum, sinusal aspiration and tympanocentesis.

In the case of Haemophilus sp beta-lactamase producers, minimal inhibitory concentrations of ampicillin were reduced 8 times by the use of the inhibitor; good results were also obtained for B. catarrhalis.

Haemophilus influenzae, B. catarrhalis together with Streptococcus pneumoniae are recognized as the major pathogens involved in upper respiratory tract infections. The increasing frequency of beta-lactamase producing strains has impaired the use of aminopenicillins.

The combination of an inhibitor and beta-lactam restore the activity of the latter, suggesting that this combination can serve as first choice in therapy.     

Comparative Evaluation of Orally Active Antibiotics against Community-Acquired Pathogens: a Multi-Center Study in Five Mediterranean Countries

Abstract

In 5 Mediterranean countries 7902 pathogens, all isolated in 1992 and 1993 from community-acquired infections, were studied for susceptibility to the following orally active antibiotics: penicillin G, ampicillin, ampi-cillin + sulbactam, amoxycillin + clavulanic acid (both 2:1 ratio), cefalexin, cefaclor, cefuroxime, cefetamet, doxycycline and erythromycin. Ten centers in Italy, 4 centers in Greece, 3 centers in Spain, and 1 center in Lebanon and Saudi Arabia contributed to this study; all centers used preformed standardized microtiter panels (Sceptor^®, BBL, Heidelberg, FRG). The most frequently isolated pathogens were Escherichia coli (n=1267), Proteus mirabilis (n = 843), Klebsiella pneumoniae (n=771), enteric Salmonella spp. (n=629), Enterobacter cloacae (n = 486), Citrobacter freundii (n = 383), Streptococcus agalactiae (n=346), Haemophilus influenzae (n=298), Streptococcus pyogenes (n=294), Streptococcus pneumoniae (n=246), Klebsiella oxytoca (n=243), and Shigella spp. (n=185). Statistical analysis was performed for each of the above countries and for all pooled data available. The penicillin antibiotics were the most active compounds against the gram-positive cocci, exceeding the MIC₉₀ values 2- to 8-fold over all cephalosporins. Regarding the gram-negatives (above all Klebsiella spp.) cefetamet was by far the most active compound (MIC₉₀ = 1 mg/1). Regarding the percentage of resistant isolates, there were no striking discrepancies between the centers and countries involved in this study. There was, however, complete cross-resistance in penicillin-resistant S. pneu moniae isolates (MIC₉₀ = 2 mg/l). By far the majority of the penicillin-resistant pneumococci showed additional resistance to doxycycline and erythromycin. Regarding all 11 compounds included in this study cefetamet was the only agent with well balanced activity against both gram- positive and gram-negative pathogens.     

Update of the Activity of Cefditoren and Comparator Oral β-lactam Agents Tested Against Community-Acquired Streptococcus pneumoniae Isolates (USA, 2004-2006)

Abstract

Cefditoren and other orally administered cephalosporins are infrequently included in resistance surveillance studies. Here we evaluated 359 contemporary (2004-2006) strains of Streptococcus pneumoniae, including penicillin-intermediate (12.0%) and -resistant (22.8%) subsets from United States patients by reference broth microdilution methods. Cefditoren was the most potent cephalosporin tested (MIC₅₀, 0.015 mg/L), including against penicillin-intermediate strains (MIC₅₀, 0.12 mg/L), and was two-, fourand eight-fold more active than cefuroxime, cefdinir and cefprozil, respectively. Penicillin- resistant strains were largely resistant to all tested β-lactams. We confirm the continued spectrum and potency for cefditoren against S. pneumoniae that surpasses that of other orally administered cephalosporins.     

Do Different Susceptibility Breakpoints Affect the Selection of Antimicrobials for Treatment of Uncomplicated Cystitis?

Abstract

An In Vitro model simulating amoxicillin-clavulanic acid (co-amoxiclav) versus oral cephalosporin serum concentrations was used to explore activity over time against penicillin-susceptible and non-susceptible Streptococcus pneumoniae. Initial inoculum reduction > 4 log cfu/ml (>99.9%) was obtained with coamoxiclav against both strains. Cefuroxime, cefpodoxime and cefaclor achieved a similar reduction against the susceptible strain, but no reduction against the non-susceptible strain.     

In Vitro Activity of YTR 830

Summary

YTR 830, now known as tazobactam, is a new penicillanic acid sulfone beta-lactamase inhibitor. The in vitro activity of YTR 830 combined with various penicillins was determined and compared to that of clavulanate and sulbactam combined with the same agents. Combined with ampicillin or amoxicillin, all three inhibitors were active against beta-lactamase producing strains of Staphylococcus aureus, Haemophilus influenzae, Klebsiella, Citrobacter diversus, and all anaerobes except for Bacteroides fragilis homology group II. YTR 830 was also effective against Escherichia coli and indolepositive Proteus, The inhibitors had no effect against Enterobacter or Serratia. Overall, the activity of YTR 830 was comparable to that of clavulanate, and superior to that of sulbactam.     

In Vitro Antimicrobial Activity of Propolis Dry Extract

Abstract

In this study the antibacterial and antifungal properties of propolis, a natural product of bees, have been investigated against different pathogens. Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were determined according to NCCLS standards on 320 strains including Staphylococcus aureus, Group A beta-hemolytic streptococci, Streptococcus pneumoniae, Moraxella catarrhalis, Haemophilus influenzae, Klebsiella pneumoniae, Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa and Candida albicans. Time-kill curves were assessed for susceptible microorganisms, testing 0, 0.5, 1, 2, 4 × MIC for propolis, by counting viable bacteria after 0, 3, 6, 24 hours and viable yeasts after 0, 3, 6, 24 and 48 hours. Propolis showed good antimicrobial activity against most of the isolates, particularly S. pneumoniae, H. influenzae and M. catarrhalis, but not against Enterobacteriaceae. Time-kill curves demonstrated bacteriostatic rather than bactericidal activity of propolis, the latter being evident only at high concentrations.     

Comparison of Cefaclor and Cefuroxime Axetil in the Treatment of Acute Otitis Media with Effusion in Children Who Failed Amoxicillin Therapy

Abstract

This trial compared the efficacy and safety of a 10-day treatment course of cefaclor and cefuroxime axetil in the treatment of acute otitis media with effusion in children who failed therapy with amoxicillin.

This was an investigator-blind, randomized, parallel treatment group study. To be included, patients must have received treatment with a standard clinical regimen of amoxicillin for at least 48 hours and not more than 10 days, with the last dose within 72 hours of randomization. Patients who met the entry criteria were randomly assigned to one of two antibiotic treatment groups. Cefaclor and cefuroxime axetil suspensions were administered twice daily for a total daily dose of 40 mg/kg and 30 mg/kg, respectively. Physical examination, pneumatic otoscopy and tympanogram were performed to evaluate efficacy to therapy. Therapeutic equivalence was established by ruling out a difference (cefaclor minus cefuroxime axetil) of 15% in percentages of clinical success (cure plus improvement). Safety evaluation was performed by assessment of clinical adverse events.

In the intent-to-treat analysis post-therapy (1-6 days after completion of therapy), 96 of 104 (92.3%) cefaclor-treated patients had clinical success compared to 90 of 101 (89.1%) cefuroxime axetil patients. The 95% confidence limits on the difference between proportions of favorable outcomes (cefaclor minus cefuroxime axetil) was from ?4.8% to +11.2%. At termination of the study (day 10-16 after completion of therapy), 86 of 104 (82.7%) cefaclor patients and 84 of 101 (83.2%) cefuroxime axetil patients had favorable clinical outcomes (95% confidence interval: ?10.8% to +9.9%). Thirty-two (30.8%) of the 104 patients in the cefaclor treatment group reported at least one adverse event, with rhinitis reported in 9 (8.7%) patients and cough increased in 7 (6.7%) patients. Thirty-six (35.6%) of the 101 patients in the cefuroxime axetil treatment group reported at least one event, with diarrhea reported in 11 (10.9%) of patients and rhinitis in 10 (9.9%) patients.

Cefaclor and cefuroxime axetil were equally effective in the treatment of patients with acute otitis media with effusion who had failed therapy with amoxicillin. Significantly fewer patients treated with cefaclor reported diarrhea, which is the most frequently reported adverse event in children treated with antibiotics for this disease.