An open-label, double tympanocentesis, single-center study of trimethoprim sulfametoxasole in children with acute otitis media.

Trimethoprim sulfamethoxasole has been recommended for the treatment of acute otitis media. In this double tympanocentesis study, children aged 3 to 48 months with acute otitis media received trimethoprim sulfamethoxasole twice daily (40 mg/kg/d) for 10 days. All children had a baseline tympanocentesis and in culture-positive children, tympanocentesis was repeated at the on-therapy visit. Of 89 children enrolled, 51 (57%) were clinically and bacteriologically evaluable. Bacteriologic eradication was achieved in 80% (42 of 52) of children, and overall clinical response at the end of therapy was 78%. Clinical success was 69% for culture-positive children versus 91% for culture-negative children at baseline tympanocentesis (P = 0.03). In this study, trimethoprim sulfamethoxasole clinical response was unsatisfactory, especially among culture-'positive children.

In vitro activities of levofloxacin and comparable agents against middle ear fluid, nasopharyngeal, and oropharyngeal pathogens obtained from Costa Rican children with recurrent otitis media or failing other antibiotic therapy.

This study analyzes the in vitro activities of levofloxacin and other commonly used antimicrobials against middle ear fluid, nasopharyngeal, and oropharyngeal pathogens obtained from children with otitis media at risk of having a resistant pathogen. Levofloxacin proved to be very active against these pathogens and had intermediate activity against Streptococcus pyogenes.

Emergence of penicillin-nonsusceptible Streptococcus pneumoniae clones expressing serotypes not present in the antipneumococcal conjugate vaccine.

BACKGROUND: Penicillin-nonsusceptible Streptococcus pneumoniae isolates are confined mainly to a few serogroups. Capsular transformation may serve as a mechanism for spreading antibiotic resistance to new serotypes. METHODS: Antibiogram and molecular typing, by pulsed-field gel electrophoresis (PFGE), were performed on 46 nasopharyngeal and middle ear fluid (MEF) isolates expressing serotype 11A, 45 MEF isolates expressing serotype 15B/C (recovered during 1998-2003 from Israeli children <5 years old), and 57 MEF isolates expressing serotype 19F (recovered during 1998-2001 from Costa Rican children <7.5 years old). RESULTS: PFGE patterns showed that 49 (86%) of 57 serotype 19F isolates and 19 (41%) of 46 serotype 15B/C isolates were closely related. The vast majority of these isolates (80% of serotype 19F and 100% of serotype 15B/C isolates) were nonsusceptible to penicillin. Multilocus sequence typing (MLST) data show that the serotype 15B/C isolates belonged to the ST346 cluster, whereas the serotype 19F isolates were a single-locus variant of ST346. For serotype 11A isolates, PFGE patterns and MLST analysis showed that 8 (80%) of the 10 penicillin-nonsusceptible isolates belonged to a single clone--namely, ST156--which was identical to the international Spain9V-3 clone. CONCLUSIONS: Penicillin-nonsusceptible pneumococcal clones of serotypes not related to those included in the 11-valent conjugate vaccines may derive from capsular transformation of vaccine-related serotypes. Of particular concern was the detection of serotype 11A variants of the successful international Spain9V-3 clone. This phenomenon, although seemingly rare at present, can have implications for the long-term effectiveness of the conjugate vaccines.

Single dose azithromycin for the treatment of uncomplicated otitis media.

Three clinical trials have examined the efficacy and safety of single dose azithromycin (30 mg/kg) in children with uncomplicated acute otitis media (AOM). In the first trial, a small pilot study, the clinical and microbiologic efficacy of single dose azithromycin was comparable with that of 3-day azithromycin or single dose ceftriaxone. A second, non-comparative trial confirmed the clinical and microbiologic efficacy of the single dose regimen. The third study, a large double blind, double dummy trial, demonstrated comparable clinical success rates between single dose azithromycin and 10-day standard amoxicillin/clavulanate. The incidence of drug-related adverse events in patients treated with single dose azithromycin was low in all three trials and similar to rates that have been reported for other antimicrobial agents used for the treatment of patients with AOM. In the amoxicillin/clavulanate trial, compliance with single dose azithromycin was significantly better than with the amoxicillin/clavulanate regimen (P < 0.001). We conclude that a single dose of azithromycin (30 mg/kg) is safe and effective for the treatment of uncomplicated AOM in children.

Microbiology of otitis media in Costa Rican children, 1999 through 2001.

BACKGROUND: Because of the increasing number of resistant middle ear pathogens and the impact of the new conjugate Streptococcus pneumoniae vaccine, an active surveillance of the microbiology and susceptibility pattern of middle ear pathogens is required. OBJECTIVE: To study the microbiology and susceptibility pattern of middle ear pathogens obtained from Costa Rican children with acute otitis media (AOM), recurrent otitis media (ROM) and therapeutic failure otitis media (FOM). METHODS: Between 1999 and 2001 middle ear fluid (MEF) was collected from 276 Costa Rican patients. S. pneumoniae serotyping and pulsed field gel electrophoresis analysis was done on available strains. RESULTS: Among the total study population, 102 were AOM patients, 98 were ROM patients and 76 were FOM patients. Overall S. pneumoniae (88 strains) was the most common pathogen isolated followed by Haemophilus influenzae (41 strains) and Streptococcus pyogenes (10 strains). H. influenzae was the most common agent in FOM patients (P = 0.015). Beta-lactamase production was observed in 3 of 41 (7%) H. influenzae strains and 3 of 3 (100%) Moraxella catarrhalis strains. Penicillin-nonsusceptible S. pneumoniae strains were more common in FOM (64%) and ROM (63%) patients than in AOM (42%) patients (P = 0.05). S. pneumoniae serotype 19F was the most prevalent serotype, mainly within one distinct clone. CONCLUSIONS: Overall S. pneumoniae serotype 19F was the most common isolate from the middle ear fluid of Costa Rican children. Beta-lactamase-negative H. influenzae was the most prevalent in the subpopulation of patients with FOM. S. pyogenes was the third most common isolate and M. catarrhalis was uncommon.

A pilot study of single-dose azithromycin versus three-day azithromycin or single-dose ceftriaxone for uncomplicated acute otitis media in children.

BACKGROUND: The pharmacokinetic profile of azithromycin supports its use as single-dose therapy for uncomplicated acute otitis media (AOM) in children. OBJECTIVE: This study was designed to (1) compare the safety of single-dose oral azithromycin, 3 daily doses of oral azithromycin, and a single dose of intramuscular ceftriaxone for the treatment of uncomplicated AOM in children, and (2) provide preliminary efficacy data to support initiation of a larger, comparative trial of single-dose azithromycin for the treatment of uncomplicated acute otitis media in children. METHODS: In this single-center pilot study, children with uncomplicated AOM were randomly assigned to receive single-dose oral azithromycin (30 mg/kg), 3-day oral azithromycin (10 mg/kg once daily), or single-dose intramuscular ceftriaxone (50 mg/kg). Tympanocentesis was performed before administration of the first dose, and clinical response was assessed on days 14-15 and 28-30. RESULTS: Between September 1995 and May 1997, 198 children (mean age, 2.5 years) were enrolled. All of the patients were evaluable for the safety and clinical intent-to-treat (ITT) analyses, and 98 were evaluable for the microbiologic ITT analysis. On day 14-15, rates of clinical success (cure or improvement) for the 3 treatment groups were: 62/64 (97%) for single-dose azithromycin, 60/63 (95%) for 3-day azithromycin, and 61/62 (98%) for single-dose ceftriaxone. On day 28-30, the corresponding clinical success rates were 61/65 (94%), 61/66 (92%), and 62/64 (97%). For the 98 microbiologically evaluable patients, clinical success rates at day 14-15 were 28/30 (93%) for single-dose azithromycin, 31/35 (89%) for 3-day azithromycin, and 33/33 (100%) for single-dose ceftriaxone. On day 28-30, the corresponding clinical success rates were 27/30 (90%), 30/35 (86%), and 32/33 (97%). Treatment-related adverse event rates for single-dose azithromycin, 3-day azithromycin, and single-dose ceftriaxone were 10.6%, 9.1%, and 9.1%, respectively. CONCLUSION: In this pilot study comparing single-dose azithromycin, 3-day azithromycin, and single-dose ceftriaxone for the treatment of uncomplicated AOM in children, no differences were detected among the 3 regimens.