Treatment of Recurrent/Nonresponsive Acute Otitis Media
Treatment of Recurrent/Nonresponsive Acute Otitis Media
Background: Gatifloxacin is an 8-methoxyfluoroquinolone with good activity against respiratory pathogens.
Objectives: To document the bacteriologic and clinical efficacy of gatifloxacin in recurrent/nonresponsive acute otitis media (AOM).
Methods: One hundred sixty patients 6 to 48 months of age with recurrent/nonresponsive AOM received gatifloxacin suspension (10 mg/kg once daily for 10 days). Recurrent AOM was defined as ≥3 AOM episodes during the previous 6 months or ≥4 AOM episodes during the previous 12 months. Nonresponsive AOM was defined as AOM occurring ≤14 days after completing antibiotic treatment or not improving after ≥48 h of therapy. Middle ear fluid (MEF) obtained by tympanocentesis pretreatment (Day 1) and 3 to 5 days after initiation of treatment (Days 4 to 6) was cultured. Additional MEF cultures were obtained if clinical failure or recurrence of AOM occurred. Bacteriologic failure was defined by culture-positive MEF during treatment. Patients were followed until Days 22 to 28. Susceptibility was determined by broth microdilution.
Results: One hundred twenty-eight (80%) patients completed treatment, and 32 discontinued the study prematurely (adverse events, 17; lost to follow-up, 10; consent withdrawal, 3; and laboratory abnormalities, 2). From 89 patients (median age, 1 year; median number of prior AOM episodes, 4; range, 0 to 12), 121 pathogens were recovered: Haemophilus influenzae, 74 (61%); Streptococcus pneumoniae, 36 (30%); Moraxella catarrhalis, 9 (7%); and Streptococcus pyogenes, 2 (2%). The 36 S. pneumoniae isolates were susceptible to gatifloxacin (MIC50 0.25 µg/ml); 26 of 36 (72%) were penicillin-nonsusceptible (15 fully resistant). All 74 H. influenzae isolates were susceptible to gatifloxacin (MIC ≤ 0.03 mg/ml). Fourteen of 74 (19%) and 9 of 9 (100%) H. influenzae and M. catarrhalis isolates, respectively, produced beta-lactamase. Bacteriologic eradication was achieved for 118 of 121 (98%) pathogens: 74 of 74 H. influenzae; 34 of 36 (94%) S. pneumoniae; 9 of 9 M. catarrhalis; and 1 of 2 S. pyogenes. Clinical improvement/cure at end of treatment was seen in 103 of 114 (90%) clinically evaluable patients. Clinical recurrence of AOM after completion of therapy occurred in 31 patients. Of the 27 recurrent AOM cases in which tympanocentesis was performed, there were 16 (59%) new infections, 4 (15%) culture-negative results and only 7 (26%) true bacteriologic relapses. Adverse events were recorded in 21 of 160 (13%) patients: vomiting, 16; diarrhea, 3; maculopapular rash, 2. No articular adverse events were recorded.
Conclusion: Gatifloxacin is efficacious and safe for the treatment of recurrent/nonresponsive AOM.
Recurrent acute otitis media (AOM) is a common illness of childhood occurring during the first year of life in ~20 to 30% of the pediatric population. It is characterized by three or more AOM episodes in a 6-month period or four or more episodes in a 12-month period. These "otitis-prone" children may spend ≥7 months with middle ear effusion after AOM in the first year of life alone. Recurrent AOM should be distinguished from persistent or nonresponsive AOM, which is characterized by persistence of signs and symptoms of middle ear infection after 48 to 72 h of antibiotic therapy.
The pathogens causing recurrent or nonresponsive AOM are not different from those causing uncomplicated AOM, but a higher prevalence of antibiotic-resistant Streptococcus pneumoniae and beta-lactamase-producing Haemophilus influenzae was found among AOM patients recently treated with antibiotics than in nontreated patients.
The Centers for Disease Control Drug Resistant Streptococcus pneumoniae Working Group recommended that antibiotic drugs used for recurrent and/or nonresponsive AOM should be effective against drug-resistant S. pneumoniae and against beta-lactamase-producing H. influenzae. These recommendations were mainly made on the basis of the results of several studies supporting the choice of amoxicillin/clavulanate (high dose, 80 to 90 mg/kg/day amoxicillin), cefuroxime axetil (30 mg/kg/day) and ceftriaxone (50 mg/kg/day im for 3 days) as second line therapy for AOM. Of these only the ceftriaxone regimen was studied in a double tympanocentesis study in the specific group of patients with nonresponsive AOM and showed a 97 and 100% eradication rate of penicillin-nonsusceptible S. pneumoniae and H. influenzae, respectively, if administered for 3 successive days.
The new fluoroquinolone antibiotics have activity against the three major AOM pathogens (S. pneumoniae, H. influenzae and Moraxella catarrhalis) and might represent an alternative therapy for this disease, if safety can be assured. The purpose of our clinical trial was to study the bacteriologic and clinical efficacy of a newer fluoroquinolone, gatifloxacin, for the treatment of recurrent/nonresponsive AOM in infants and children and to document the incidence and nature of adverse events in infants and children receiving this drug.
Background: Gatifloxacin is an 8-methoxyfluoroquinolone with good activity against respiratory pathogens.
Objectives: To document the bacteriologic and clinical efficacy of gatifloxacin in recurrent/nonresponsive acute otitis media (AOM).
Methods: One hundred sixty patients 6 to 48 months of age with recurrent/nonresponsive AOM received gatifloxacin suspension (10 mg/kg once daily for 10 days). Recurrent AOM was defined as ≥3 AOM episodes during the previous 6 months or ≥4 AOM episodes during the previous 12 months. Nonresponsive AOM was defined as AOM occurring ≤14 days after completing antibiotic treatment or not improving after ≥48 h of therapy. Middle ear fluid (MEF) obtained by tympanocentesis pretreatment (Day 1) and 3 to 5 days after initiation of treatment (Days 4 to 6) was cultured. Additional MEF cultures were obtained if clinical failure or recurrence of AOM occurred. Bacteriologic failure was defined by culture-positive MEF during treatment. Patients were followed until Days 22 to 28. Susceptibility was determined by broth microdilution.
Results: One hundred twenty-eight (80%) patients completed treatment, and 32 discontinued the study prematurely (adverse events, 17; lost to follow-up, 10; consent withdrawal, 3; and laboratory abnormalities, 2). From 89 patients (median age, 1 year; median number of prior AOM episodes, 4; range, 0 to 12), 121 pathogens were recovered: Haemophilus influenzae, 74 (61%); Streptococcus pneumoniae, 36 (30%); Moraxella catarrhalis, 9 (7%); and Streptococcus pyogenes, 2 (2%). The 36 S. pneumoniae isolates were susceptible to gatifloxacin (MIC50 0.25 µg/ml); 26 of 36 (72%) were penicillin-nonsusceptible (15 fully resistant). All 74 H. influenzae isolates were susceptible to gatifloxacin (MIC ≤ 0.03 mg/ml). Fourteen of 74 (19%) and 9 of 9 (100%) H. influenzae and M. catarrhalis isolates, respectively, produced beta-lactamase. Bacteriologic eradication was achieved for 118 of 121 (98%) pathogens: 74 of 74 H. influenzae; 34 of 36 (94%) S. pneumoniae; 9 of 9 M. catarrhalis; and 1 of 2 S. pyogenes. Clinical improvement/cure at end of treatment was seen in 103 of 114 (90%) clinically evaluable patients. Clinical recurrence of AOM after completion of therapy occurred in 31 patients. Of the 27 recurrent AOM cases in which tympanocentesis was performed, there were 16 (59%) new infections, 4 (15%) culture-negative results and only 7 (26%) true bacteriologic relapses. Adverse events were recorded in 21 of 160 (13%) patients: vomiting, 16; diarrhea, 3; maculopapular rash, 2. No articular adverse events were recorded.
Conclusion: Gatifloxacin is efficacious and safe for the treatment of recurrent/nonresponsive AOM.
Recurrent acute otitis media (AOM) is a common illness of childhood occurring during the first year of life in ~20 to 30% of the pediatric population. It is characterized by three or more AOM episodes in a 6-month period or four or more episodes in a 12-month period. These "otitis-prone" children may spend ≥7 months with middle ear effusion after AOM in the first year of life alone. Recurrent AOM should be distinguished from persistent or nonresponsive AOM, which is characterized by persistence of signs and symptoms of middle ear infection after 48 to 72 h of antibiotic therapy.
The pathogens causing recurrent or nonresponsive AOM are not different from those causing uncomplicated AOM, but a higher prevalence of antibiotic-resistant Streptococcus pneumoniae and beta-lactamase-producing Haemophilus influenzae was found among AOM patients recently treated with antibiotics than in nontreated patients.
The Centers for Disease Control Drug Resistant Streptococcus pneumoniae Working Group recommended that antibiotic drugs used for recurrent and/or nonresponsive AOM should be effective against drug-resistant S. pneumoniae and against beta-lactamase-producing H. influenzae. These recommendations were mainly made on the basis of the results of several studies supporting the choice of amoxicillin/clavulanate (high dose, 80 to 90 mg/kg/day amoxicillin), cefuroxime axetil (30 mg/kg/day) and ceftriaxone (50 mg/kg/day im for 3 days) as second line therapy for AOM. Of these only the ceftriaxone regimen was studied in a double tympanocentesis study in the specific group of patients with nonresponsive AOM and showed a 97 and 100% eradication rate of penicillin-nonsusceptible S. pneumoniae and H. influenzae, respectively, if administered for 3 successive days.
The new fluoroquinolone antibiotics have activity against the three major AOM pathogens (S. pneumoniae, H. influenzae and Moraxella catarrhalis) and might represent an alternative therapy for this disease, if safety can be assured. The purpose of our clinical trial was to study the bacteriologic and clinical efficacy of a newer fluoroquinolone, gatifloxacin, for the treatment of recurrent/nonresponsive AOM in infants and children and to document the incidence and nature of adverse events in infants and children receiving this drug.
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