Eradication by Ceftriaxone of Streptococcus pneumoniae Isolates with Increased Resistance to Penicillin in Cases of Acute Otitis Media

Abstract

This multicenter, noncomparative, nonrandomized study evaluated the clinical efficacy and safety of ceftriaxone for treating acute otitis media in children following clinical failure of oral antibiotic therapy. Middle-ear fluid samples were collected on day 0 and on day 3, 4, or 5 (day 3 to 5) and were used to test whether ceftriaxone therapy can eradicate Streptococcus pneumoniae isolates with increased resistance to penicillin (MIC ≥ 1 mg/liter). At the first visit, on day 0, middle-ear fluid was sampled for bacteriological testing by tympanocentesis or otorrhea pus suction. Patients were administered 50 mg of ceftriaxone/kg of body weight/day, injected intramuscularly once daily, for 3 days. A second sample was collected by tympanocentesis if a pneumococcus isolate for which the MIC of penicillin was ≥1 mg/liter was detected in the day-0 sample and if the middle-ear effusion persisted on day 3 to 5. This second sample was tested for bacterial eradication. One hundred eighty-six children aged 5 months to 5 years, 10 months, with acute otitis media clinical failure were enrolled and treated in this trial. On day 10 to 12, 145 (83.8%) of the 173 patients evaluable for clinical efficacy were clinically cured. Of the 59 patients infected by pneumococci, 36 had isolates for which the MICs of penicillin were ≥1 mg/liter. Of those patients, on day 10 to 12, 32 (88.9%) were clinically cured. Middle-ear fluid samples collected by day 3 to 5 following the onset of treatment with ceftriaxone were sterile for 24 of the 27 (88.9%) patients who were infected as of day 0 by pneumococci for which the MICs of penicillin were ≥1 mg/liter and who were evaluable for bacteriological eradication. On day 10 to 12, 81.4% of S. pneumoniae-infected children and 87.5% of Haemophilus influenzae-infected children were clinically cured. No discontinuation of treatment due to adverse events, particularly due to local reactions at the injection site, were reported. Only 11 adverse events which had doubtful, probable, or possible links with the study treatment were recorded. Both the bacteriologically assessed eradication of pneumococci for which the MICs of penicillin were ≥1 mg/liter and the clinical cure rates demonstrate that ceftriaxone is of value in the management of acute otitis media unresponsive to previous oral antibiotic therapy.

Controlled release of ciprofloxacin and ceftriaxone from a single ototopical administration of antibiotic-loaded polymer microspheres and thermoresponsive gel

“…A standard dose duration for AOM antibiotic prescriptions is 7–14 days [ 22 , 35 , 42 ], therefore microsphere release was tailored to last the full treatment duration. High initial antibiotic concentration followed by continuous presentation has been shown to be effective against non-responsive bacteria and biofilms, therefore this release pattern is desirable [ 39 – 41 , 43 , 67 ]. Ex vivo study of transtympanic permeability also indicates that antibiotic released from MS/gel system can permeate across the TM without the use of chemical permeation enhancers.…”

“…Additionally, several of the bacterial strains most common in OM, including Haemophilus influenzae and Streptococcus pneumoniae readily form biofilms, which may inhibit the effectiveness of antibiotic therapy [ 17 , 18 ]. Although less commonly used than other treatments, the current treatment when there is suspicion of resistance or low patient compliance is a three-day course of intramuscular ceftriaxone treatment, which has shown to be as effective as a two-week treatment course of amoxicillin and has proven effective in treatment of penicillin-resistant infections and persistent Streptococcus -based infections [ 39 – 43 ]. Therefore, to maximize efficacy of treatment, ciprofloxacin and ceftriaxone were chosen for encapsulation in the drug delivery system described herein.…”

Controversies in the Medical Management of Persistent and Recurrent Acute Otitis Media Recommendations of a Clinical Advisory Committee

“…The only published clinical trials of ceftriaxone for the treatment of persistent and recurrent AOM have administered 3 consecutive daily injections of ceftriaxone. 58 • 65 The DRSP therapeutic working group stated that 3 consecutive daily injections might be needed for persistent and recurrent AOM. 1 A 3day regimen would require 3 separate office visits and increase direct and indirect costs.…”

Antimicrobial Resistance in Gram-Positive Bacteria: The Myth of the MIC

“…For example, numerous publications could not establish a relationship between NCCLS standards and clinical outcome. [18][19][20] In other words, susceptible, intermediate, and even fully resistant isolates from infections such as pneumonia and otitis media respond clinically in the same fashion. For isolates from spinal fluid causing meningitis, however, the relationship to clinical outcome appears to be good.…”