Editorial commentary: infections due to macrolide-resistant Mycoplasma pneumoniae: now what?

In this issue of Clinical Infectious Diseases, Okada et al describe the first large outbreak of macrolide-resistant Mycoplasma pneumoniae infections in Japan [1]. Furthermore, they provide the first data describing the responses of a large number of these cases to treatment with several nonmacrolide antibiotics. The significance of macrolide resistance in M. pneumoniae has become much more apparent in the past decade; it has become widespread in Japan and China and is now spreading through Europe and North America. Reports of macrolide resistance during 2008–2010 include rates of >40% in Japan, 80%– 90% in China, and 3%–10% in Europe and the United States [2]. Mycoplasma pneumoniae infections occur both endemically and epidemically worldwide, especially in children and young adults. A substantial increase in incidence was reported in 2010 and 2011 in several countries in Northern Europe [3, 4] and in Israel [5]. The outbreak reported in Israel was shown to be polyclonal by multilocus variablenumber analysis (MLVA). A similar epidemic was described in Japan in 2011. The P1 adhesin-based genotyping method used in the study, which differentiated the strains into only 2 types, identified a type 1 M. pneumoniae surge [1]. However, that typing method was not discriminant enough to determine whether the epidemic was polyclonal. Interestingly, the epidemics of M. pneumoniae in 2010–2011 in Denmark, Sweden, and Norway were associated with the high consumption of macrolides and an increase in macrolide prescriptions [3]. However, to date, this does not seem to have affected levels of macrolide resistance in M. pneumoniae, which remain low in these countries [6]. In contrast, in Japan [1], the authors linked the increase in macrolide-resistant M. pneumoniae (up to 87% of the 202 isolates in the 2011 surge) to extensive macrolide use (30% of oral prescribed antibiotics) and observed a parallel rise in macrolide resistance in other respiratory pathogens, apparently as a result of antibiotic selective pressure in children. M. pneumoniae is susceptible to macrolides and related antibiotics, the tetracyclines and fluoroquinolones [2]. Macrolides have generally been the treatment of choice for pneumonia, especially in children, because they are the most potent treatments for this disease, and fluoroquinolones and tetracyclines are contraindicated in all children and in children <8 years of age, respectively. The presence of macrolide-resistant M. pneumoniae may lead to treatment failure, which translates into more febrile days and a longer duration of persistent cough than are observed in patients with macrolide-susceptible isolates. Furthermore, children with macrolide-resistant M. pneumoniae required therapeutic switching because of either persistent symptoms or unresolved or worsening chest radiographic abnormalities. Several sporadic cases of infections with macrolide-resistant M. pneumoniae requiring the change of macrolides to either tetracyclines (minocycline or doxycycline) or fluoroquinolones (levofloxacin or ciprofloxacin) have been described; some of these cases were associated with severe symptoms such as life-threatening pneumonia [7] or Stevens-Johnson syndrome [8]. The control of macrolide-resistant M. pneumoniae infections has become a major therapeutic challenge in Asia with resistance rates exceeding 80% in both Japan and China in 2011 [1, 9]. In contrast to Europe and the United States, minocycline and tosufloxacin, a fluoroquinolone agent, have been approved in Japan for pediatric use to treat macrolide-resistant M. pneumoniae infections Received 27 August 2012; accepted 30 August 2012; electronically published 12 September 2012. Correspondence: Cécile Bébéar, MD, PhD, USC/EA 3671 Infections humaines à mycoplasmes et chlamydiae, Université Bordeaux Segalen, 146 rue Léo Saignat 33076 Bordeaux cedex, France (cecile.bebear@u-bordeaux2.fr). Clinical Infectious Diseases 2012;55(12):1650–1 © The Author 2012. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. permissions@oup.com. DOI: 10.1093/cid/cis791