Tetracycline Treatment of Mycoplasma Infections in Children

Abstract & Commentary

By Dean L. Winslow, MD, FACP, FIDSA, Chairman, Department of Medicine, Santa Clara Valley, Medical Center; Clinical Professor, Stanford University School of Medicine, is Associate Editor for Infectious Disease Alert.

Dr. Winslow is a consultant for Siemens Diagnostic

Synopsis: 258 Japanese children were diagnosed with M. pneumoniae-associated pneumonia during 2011. Of the 202 isolates obtained from cultures of NP swabs 87% were shown to be macrolide-resistant. Minocycline (MIN) or doxycycline (DOX) appeared to be more effective than tosufloxacin (TFX) when used for treatment in these patients.

Source: Okada T, et al. Rapid effectiveness of minocycline or doxycycline against macrolide-resistant Mycoplasma pneumoniae infection in a 2011 outbreak among Japanese children. CID 2012;55:1642-9.

A large outbreak of community acquired pneumonia due to macrolide-resistant M. pneumoniae (MRMP) occurred in Japan in 2011 and mainly affected school-age children. 258 of these cases (diagnosed by chest radiography, real-time PCR and antibody titers) were extensively studied. Of the RT-PCR positive nasopharyngeal samples, Mycoplasma was isolated in liquid culture in 202 cases. Antimicrobial susceptibility testing was done by broth microdilution and the 23S ribosomal RNA gene was sequenced. 26 isolates were shown to be macrolide-susceptible and 176 were macrolide-resistant. Of the patients infected with macrolide-resistant isolates, 79% were treated with MIN or DOX and 9% were treated with TFX. 31% of patients treated with macrolides defervesced within 24 hours of initiation of treatment, whereas 58% of patients treated with MIN, 81% of patients treated with DOX and only 31% of patients treated with TFX became afebrile within 24 hours. In a small subset of patients studied with serial quantitative RT-PCR both MIN and DOX were significantly more effective than TFX in decreasing numbers of M. pneumoniae DNA copies by 3 days after initiation of treatment.

Commentary

M. pneumoniae is an important cause of community-acquired pneumonia (CAP) in both children and adults and may account for 15-30% of hospitalizations for CAP in children.1 While Mycoplasma is commonly thought to cause mainly a mild “walking pneumonia,” the fact is that severe and fatal cases of pneumonia due to Mycoplasma are often seen and in many cases result from the expression of a recently-described novel community-acquired respiratory distress syndrome (CARDS) toxin which can cause a picture consistent with bronchiolitis obliterans with organizing pneumonia (BOOP).2,3 Of great concern is the fact that macrolide resistance in Mycoplasma is now present world-wide with as high as 90% prevalence of MRMP in China and Japan,4 and about 8% in the U.S. with some areas of the U.S. showing higher rates.5 While the study reported here is rather small and retrospective it suggests that MIN and DOX are safe and effective in children with MRMP infections and probably superior to fluoroquinolones in vivo despite similar in vitro activity. Tetracyclines are generally not given to children less than 7 years of age due to the concern for these agents causing staining of permanent teeth. However most of the dental staining seen in children treated with tetracyclines during the 1950’s and early 1960’s was a result of the use of older tetracyclines, not newer tetracyclines such as MIN or DOX. The degree of teeth discoloration seen with tetracyclines is felt to be a function of these compounds acting as chelating agents binding to divalent cations (Calcium and Magnesium) and MIN and DOX are both relatively weak chelating agents compared to the older drugs. Due to the increasing incidence of severe infections due to MRMP expect to see more frequent and appropriate use of the newer tetracyclines in children in the future.

References

  1. Tsolia MN, et al. Etiology of community-acquired pneumonia in hospitalized school-age children: evidence for high prevalence of viral infections. CID 2004; 39: 681-6.
  2. Kannan TR, et al. Fatal outcomes in family transmission of Mycoplasma pneumoniae. CID 2012; 54: 225-31.
  3. Kannan TR, et al. ADP-ribosylating and vacuolating cytotoxin of Mycoplasma pneumoniae represents unique virulence determinants among bacterial pathogens. Proc Natl Acad Sci USA 2006;103:6724-9.
  4. Liu Y, et al. Characterization of macrolide resistance in Mycoplasma pneumoniae isolated from children in Shanghai, China. Diagn Microbiol Infect Dis 2010; 67: 355-8.
  5. Yamada M, et al. Rising rates of macrolide-resistant Mycoplasma pneumoniae in the central United States. Ped Infect Dis Journal 2012: 31: 409-11.