A strain of Streptococcus pneumoniae that is resistant to all antibiotics approved to treat acute otitis media in children has been identified as an otopathogen, according to the findings of a study.
The multidrug-resistant serotype 19A strain is not included in the pneumococcal 7-valent conjugate vaccine (PCV-7), reported Dr. Michael E. Pichichero and Dr. Janet R. Casey, from the University of Rochester Medical Center and Legacy Pediatrics, a private practice involved in the study (JAMA 2007;298:1772–8).
Children with the serotype 19A strain “represented a small subset of those in our practice, but the results are worrisome, especially since there are no new antibiotics in the pipeline for ear infections in children,” said Dr. Pichichero in a statement.
“While it appears that the overall decrease in invasive pneumococcal disease still outweighs the increase in serotype 19A, it is clear that surveillance needs to continue for this important pathogen, both for strain type and antibiotic resistance,” commented Dr. Elizabeth Bancroft, from the Los Angeles County Department of Public Health, in an editorial in the same issue of the journal (JAMA 2007;298:1803–4).
The prospective study included 212 children from the authors' clinic who underwent tympanocentesis for acute otitis media (AOM) during one of three respiratory seasons: September 2003-June 2004, September 2004-June 2005, and September 2005-June 2006. All children had been previously immunized with the PCV-7 vaccine.
From the tympanocentesis procedures, a pathogen was identified in 162 cases: nontypable Haemophilus influenzae (n = 94); S. pneumoniae (n = 59); and other (n = 9). Serotyping of the 59 S. pneumoniae pathogens revealed 9 that belonged to serotype 19A, which is resistant to all antibiotics approved by the Food and Drug Administration for the treatment of AOM in children.
Infections caused by the serotype 19A strain “continued to produce symptoms and signs of AOM until aggressive therapy was provided—either surgery or levofloxacin, an antibiotic unapproved for children,” the authors noted.
While the incidence was the same, with two cases each in the 2003–2004 and 2004–2005 seasons, it increased to five cases in the 2005–2006 season. None of the first four cases was treated with effective antibiotics “because we did not perform antibiotic susceptibility testing (or serotyping) contemporaneously as we did in 2005–2006,” they wrote. The first four cases were referred to an otolaryngologist for tympanostomy tube insertion, “and all continued with drainage from their tubes for 1–4 weeks despite use of antibiotic otic drops.”
The five cases from the 2005–2006 season all recovered fully after treatment with levofloxacin.
“Our approach has been to use levofloxacin only for children in whom we have performed tympanocentesis and isolated a 19A serotype organism that is susceptible only to that drug,” according to the authors. But, they cautioned that “this information is shared with concern that some providers and the public will interpret this finding as an indication to begin using levofloxacin or other fluoroquinolones in difficult-to-treat cases of AOM, sinusitis, or other pneumococcal infections. This could lead to disastrous results.” The authors suggested that “an expanded pneumococcal conjugate vaccine to include additional serotypes may be needed sooner than previously thought,” noting that U.S. trials are underway of a vaccine containing 13 serotypes, including 19A.
“In the near future” more primary care providers may need to become trained to perform tympanocentesis in order to avoid the excessive use of fluoroquinolones in children.
While S. pneumoniae serotype 19A carries direct implications for children's health, its existence and treatment also has important implications for adults, said Dr. Keith Klugman, professor of infectious diseases at Emory University in Atlanta. “Strains that circulate among children are an important source of pneumococcal infections in adults,” he said. The fact that this new strain requires fluoroquinolone treatment in children, poses a potential threat to adults.
Both Dr. Pichichero and Dr. Carey report that they have received support for otitis media trials from Ortho-McNeil, maker of levofloxacin, and that they have received compensation for consulting, speaking, and conducting clinical trials of antibiotics and vaccines from multiple companies, including Wyeth, which has a 13-valent pneumococcal conjugate vaccine in phase III trials.
The results are worrisome since there are no new antibiotics in the pipeline for ear infections in children. DR. PICHICHERO