Constancy of distribution of serogroups of invasive pneumococcal isolates among children: experience during 4 decades.

Serogroups of pneumococci that caused bacteremia or meningitis in children were examined from 1981 through 1998 at Boston City Hospital/Boston Medical Center. There were 410 episodes of pneumococcal bacteremia (13--36 cases per year), of which 14 occurred in human immunodeficiency virus (HIV)--infected children and 9 occurred in children with sickle-cell disease. The 7 most common serogroups were 14 (30.7% of isolates), 19 (11.7%), 6 (11%), 18 (10.7%), 9 (7.6%), 23 (7.3%), and 4 (5.6%). The rate of episodes due to serogroups 4, 6, 9, 14, 18, 19, and 23 ranged from 80% to 91.9% during the study period. The rate of episodes due to serogroups 4, 6, 14, 18, 19, and 23 was 84.6% among patients with HIV infection, 100% among patients with sickle-cell disease, and 94.1% among the 18 patients for whom cultures of CSF specimens revealed pneumococcal meningitis. The results demonstrate that type 14 was the dominant pneumococcal serogroup responsible for invasive disease throughout the 18-year study period and that serogroup distribution overall remained constant. A comparison of these findings with historical pediatric data from our institution showed serogroup stability dating back to 1957.

In vitro and in vivo antimicrobial activity of topical ofloxacin and other ototopical agents.

BACKGROUND: Ototopical agents are extensively used for otitis externa (OE), acute otitis media identified by otorrhea in patients who have tympanostomy tubes (AOM-TT) and chronic suppurative otitis media (CSOM). The quinolones have particular value as ototopical agents because of the broad spectrum of antibacterial activity of importance in otic diseases and the high concentrations of antibacterial activity at the site of infection. METHODS: A survey of literature on in vitro activity and microbiologic efficacy in clinical trials of quinolone otic products for OE, AOM-TT and CSOM. RESULTS: OE: Floxin otic and Cortisporin TC otic suspension were equally effective in eradicating the three major pathogens Pseudomonas aeruginosa, Proteus mirabilis and Staphylococcus aureus. CSOM: Ofloxacin otic was effective in an open label trial in uniform eradication of S. aureus, P. aeruginosa, Proteus mirabilis and Enterobacter spp. AOM-TT: Ofloxacin otic and amoxicillin/clavulanate (by mouth) were equivalent clinically; rates of eradication of initial pathogens were similar for Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, but ofloxacin otic was superior in eradication of S. aureus and P. aeruginosa CONCLUSIONS: In each of the studies of OE, CSOM and AOM-TT, ofloxacin otic solution was effective in eradicating the bacterial pathogen from the site of infection: equivalent to Cortisporin for children with OE; superior to amoxicillin/clavulanate for patients with AOM-TT who had acute drainage; and effective in eradicating bacterial pathogens from the external canal of patients with CSOM.

Management of otitis media: 2000 and beyond.

BACKGROUND: In the next few years what will alter our modes of diagnosis, choice of therapies and strategies for prevention of acute otitis media (AOM)? These issues, as well as whether antibiotic resistance will continue to threaten the efficacy of currently available antimicrobial agents, whether industry and academia will be able to respond to bacterial resistance with effective new antimicrobial drugs and whether the pneumococcal conjugate vaccine will substantially reduce the incidence of AOM provide a basis for discussing the problems and possible solutions related to AOM. ANTIMICROBIAL DRUGS: Bacteria and viruses will continue to find ways to survive the activity of currently available antimicrobial drugs. Among the new antibacterial drugs under consideration are ketolides, oxazolodinones and quinolones. Guidelines stress limiting usage of antimicrobial agents to diseases that are likely caused by bacterial pathogens. Antiviral drugs are now available against influenza virus and respiratory syncytial virus infections. DIAGNOSIS: Tympanometry and/or acoustic reflectometry are adjunctive techniques for assisting in the diagnosis of middle ear effusion in children whose otoscopic examination is ambiguous. Laser myringotomy has been used in several hundred children; however, there are no published studies of randomized trials. NEW VACCINES: Investigators have evaluated the safety and efficacy of a heptavalent pneumococcal polysaccharide vaccine conjugated with CRM197 (a diphtheria toxin mutant). The results showed a reduction in the overall burden of severe and recurrent AOM. Respiratory syncytial virus is the viral pathogen most frequently associated with AOM. For this reason safe and effective viral vaccines are needed to complement the efficacy of bacterial vaccines for prevention of AOM. CONCLUSIONS: Parents influence decisions by pediatricians to use antimicrobial agents and should be informed about the appropriate usage of antibiotics. Educators and public health officials must find techniques to distinguish WebSites that provide information of value from those that are not credible. Of paramount importance is the development of techniques to increase the accuracy of clinical and microbiologic diagnosis. Finally there is a need for studies of appropriate scientific design that can assess the efficacy and safety of alternative therapies.

Projected cost-effectiveness of pneumococcal conjugate vaccination of healthy infants and young children.

CONTEXT: Pneumococcal conjugate vaccine for infants has recently been found effective against meningitis, bacteremia, pneumonia, and otitis media. OBJECTIVE: To evaluate the projected health and economic impact of pneumococcal conjugate vaccination of healthy US infants and young children. DESIGN: Cost-effectiveness analysis based on data from the Northern California Kaiser Permanente randomized trial and other published and unpublished sources. SETTING AND PATIENTS: A hypothetical US birth cohort of 3.8 million infants. INTERVENTIONS: Hypothetical comparisons of routine vaccination of healthy infants, requiring 4 doses of pneumococcal conjugate vaccine (at 2, 4, 6, and 12-15 months), and catch-up vaccination of children aged 2 to 4.9 years requiring 1 dose, with children receiving no intervention. MAIN OUTCOME MEASURES: Cost per life-year saved and cost per episode of meningitis, bacteremia, pneumonia, and otitis media prevented. RESULTS: Vaccination of healthy infants would prevent more than 12000 cases of meningitis and bacteremia, 53000 cases of pneumonia, 1 million episodes of otitis media, and 116 deaths due to pneumococcal infection. Before accounting for vaccine costs, the vaccination program would save $342 million in medical and $415 million in work-loss and other costs from averted pneumococcal disease. Vaccination of healthy infants would result in net savings for society if the vaccine cost less than $46 per dose, and net savings for the health care payer if the vaccine cost less than $18 per dose. At the manufacturer's list price of $58 per dose, infant vaccination would cost society $80000 per life-year saved or $160 per otitis media episode prevented (other estimated costs would be $3200 per pneumonia case prevented, $15000 for bacteremia, and $280000 for meningitis). The cost-effectiveness of an additional program to administer 1 dose of vaccine to children aged 2 to 4.9 years would vary depending on the children's ages, relative risks of pneumococcal disease, and vaccine cost. CONCLUSIONS: Pneumococcal conjugate vaccination of healthy US infants has the potential to be cost-effective. To achieve cost savings, its cost would need to be lower than the manufacturer's list price. In addition to tangible costs, the vaccine should be appraised based on the less tangible value of preventing mortality and morbidity from pneumococcal disease.

The burden of otitis media.

Otitis media is the most frequent reason that children go to the doctor for illness. In developing countries, where children have limited access to medical care, suppurative complications of otitis media (OM) are frequent and permanent hearing loss results. In developed countries, the most common morbidity of OM is conductive hearing loss due to middle ear effusion. Infants with severe and recurrent OM and persistent middle ear effusion are at risk for problems in behavior and development of speech, language and cognitive abilities. Parent stress is frequent. The cost of otitis media is large (>$5 billion in the United States). Selection and spread of multi-drug resistant bacterial pathogens arising from extensive use of antimicrobial agents for OM is a problem for management of all diseases due to the pathogens. The incidence and severity of OM may diminish with introduction of new bacterial and viral vaccines.

Management of acute otitis media in an era of increasing antibiotic resistance.

Development of resistance to available antimicrobial agents has been identified in every decade since the introduction of the sulfonamides in the 1930s. Current concerns for management of acute otitis media (AOM) are multi-drug resistant Streptococcus pneumoniae and beta-lactamase producing Haemophilus influenzae and Moraxella catarrhalis. In the USA, amoxicillin remains the drug for choice for AOM. Increasing the current dose to 80 mg/kg/day in two doses provides increased concentrations of drug in serum and middle ear fluid and captures additional resistant strains of S. pneumoniae. For children who fail initial therapy with amoxicillin an expert panel convened by the Centers for Disease Control and Prevention suggested amoxicillin-clavulanate, cefuroxime axetil or intramuscular ceftriaxone. To protect the therapeutic advantage of antimicrobial agents used for AOM, it is important to promote judicious use of antimicrobial agents and avoid uses if it is likely that viral infections are the likely cause of the disease, to implement programs for parent education and to increase the accuracy of diagnosis of AOM. Conjugate polysaccharide pneumococcal vaccines are currently in clinical trial; early results indicate protective levels of antibody can be achieved with a three dosage schedule beginning at 2 months of age. Finally, alternative medicine remedies may be of value for some infectious diseases including AOM; garlic extract is bactericidal for the major bacterial pathogens of AOM but is heat- and acid-labile and loose activity when cooked or taken by mouth.

Immune response to pneumococcal conjugate and polysaccharide vaccines in otitis-prone and otitis-free children.

We compared responses to pneumococcal conjugate and polysaccharide vaccines in 48 otitis-free and 64 otitis-prone children. Pre- and postimmunization concentrations of antibodies to pneumococcal serotypes 6B, 14, 19F, and 23F were measured by enzyme-linked immunosorbent assay. Postimmunization mean concentrations of antibodies to all four serotypes were significantly higher for children receiving conjugate vaccine than for those receiving polysaccharide vaccine; the difference in responses was primarily due to a better response to conjugate vaccine in the otitis-prone group. Significantly higher postimmunization concentrations of antibodies to all four serotypes and to one of the four serotypes were found in otitis-prone children and otitis-free children who received conjugate vaccine, respectively. Pneumococcal conjugate vaccine has the potential to reduce the incidence of disease due to vaccine serotypes, even among children with recurrent otitis media.