January 1996
NEW YORK—The emergence of resistant strains of pneumococcus is forcing physicians to reconsider standard treatments for infections with this pathogen, according to Eugene D. Shapiro, MD.
Pneumococcus is the most common cause of meningitis and serious invasive bacterial infections in children. It also causes as much as 50% of all episodes of otitis media.
Shapiro, who is Professor of Pediatrics and of Epidemiology at Yale University School of Medicine, New Haven, Conn., explained that risk factors for colonization and for infection with resistant strains include extremes of age (the very old and the very young), attendance at day care, recent hospitalization, and recent use of any antibiotics, particularly beta-lactam antibiotics.
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Ninety different serotypes of pneumococcus are now recognized. Almost all the resistant strains are serotypes 6, 14, 19, 23, and 9. "Unfortunately, these strains also are the ones that commonly cause infection," Shapiro reported here at the Eighth Annual Infectious-Diseases in Children Symposium.
High level pneumococcal resistance was not recognized in the United States before 1987. In 1994, however, a nationwide multicenter pneumococcal surveillance study in children who had bacteremia, meningitis, pneumonia, or septic arthritis showed that the overall prevalence for intermediate and highly resistant strains was 15%.
This study showed that the extent of the resistance varied a great deal by location. For example, in Colorado, resistance was at 35%; whereas in North Carolina, it was 0%. In addition, ceftriaxone resistance overall was 4%, varying from 0% to as much as 20%.
"This [situation] is only going to get worse," Shapiro said. "There is no question that we have seen the tip of the iceberg; the problem of resistant strains can only increase."
Shapiro reported that a new rapid test to assess susceptibility to penicillin and other antimicrobial agents, called the E-test, is available and is very useful. "It is inexpensive, rapid, and gives you a quantitative estimate of the MIC right away," he said.
Pneumococcal resistance to penicillin is based on altered penicillin-binding proteins, not on the production of beta-lactamase. "Thus, it makes no sense to give amoxicillin/clavulanate, for resistant strains," Shapiro said. Other beta-lactam antimicrobial agents have varying degrees of efficacy for resistant strains.
Resistant strains make reconsideration of standard treatment essential in certain instances, for example, in children with meningitis. Beta-lactam antimicrobial drugs diffuse poorly into the cerebrospinal fluid; hence, children with possible bacterial meningitis should be treated with vancomycin plus a third-generation cephalosporin, either cefotaxime or ceftriaxone, until the results of the antimicrobial susceptibility test become available. When these results come back, adjust your treatment accordingly. If the strain is susceptible, stop vancomycin and substitute penicillin, Shapiro advised.
If the patient received dexa- methasone, consider rifampin in addition to vancomycin. Rifampin has better diffusion into the cerebrospinal fluid (CSF). Because vancomycin does not diffuse into the CSF very well, steroids also may decrease its effectiveness.
"If a resistant strain is isolated from the CSF (some would say in everybody with pneumococcal meningitis), you should repeat the lumbar puncture to document that the CSF was sterilized," Shapiro said.
For other infections such as pneumonia, bacteremia, and otitis media, penicillin or amoxicillin usually is still fairly effective because of the relatively high concentrations achieved with routine treatment. Shapiro said if a patient is not severely ill, he recommends using penicillin.
If a patient is severely ill, however, he recommends using vancomycin pending susceptibility testing of the isolate. He explained, "If a resistant organism is isolated, you could consider alternative agents. For example, if you know that otitis media was caused by a resistant organism, you might consider clindamycin."
Clearly, prevention is the answer to these problems, Shapiro concluded.
Polyvalent protein- polysaccharide conjugate pneumococcal vaccines are being developed with the goal of routine universal immunization of infants. Unfortunately, he noted, these vaccines probably won't become available until the turn of the century.
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