Multidrug-resistant Mycoplasma genitalium infections in Europe

Abstract

In Japan and Australia, multidrug-resistant Mycoplasma genitalium infections are reported with increasing frequency. Although macrolide-resistant M. genitalium strains are common in Europe and North America, fluoroquinolone-resistant strains are still exceptional. However, an increase of multidrug-resistant M. genitalium in Europe and America is to be expected. The aim of this paper is to increase awareness on the rising number of multidrug-resistant M. genitalium strains. Here, one of the first cases of infection with a genetically proven multidrug-resistant M. genitalium strain in Europe is described. The patient was a native Dutch 47-year-old male patient with urethritis. Mycoplasma genitalium was detected, but treatment failed with azithromycin, doxycycline and moxifloxacin. A urogenital sample was used to determine the sequence of the 23S rRNA, gyrA, gyrB and parC genes. The sample contained an A2059G single nucleotide polymorphism (SNP) in the 23S rRNA gene and an SNP in the parC gene, resulting in an amino acid change of Ser83 → Ile, explaining both azithromycin and moxifloxacin treatment failure. The SNPs associated with resistance were probably generated de novo, as a link with high-prevalence areas was not established. It is, thus, predictable that there is going to be an increase of multidrug-resistant M. genitalium strains in Europe. As treatment options for multidrug-resistant M. genitalium are limited, the treatment of M. genitalium infections needs to be carefully considered in order to limit the rapid increase of resistance to macrolides and fluoroquinolones.

Genetic Variation inMycoplasma genitalium

“…Some strong and consistent associations between the presence of 23S rRNA gene mutations and azithromycin treatment failure, as well as between the presence of type II topoisomerase gene mutations and fluoroquinolone treatment failure have been reported around the world [54][55][56]58].…”

“…Unfortunately, certain MG pathogens have become resistant to the primary azithromycin treatment. Some fluoroquinolones have revealed to be highly active against azithromycin-resistant MG [53][54][55][56][57], yet cases of moxifloxacin treatment failures have been reported recently in Japan, Australia, and some other developed countries in Europe [55][56][57]. Because of the current lack of a specific treatment strategy for macrolideresistant and fluoroquinolone-resistant MG, multi-drugs resistant MG infections will likely become a major problem in the near future [54].…”

“…In addition to inhibiting growing amino acid chains, macrolide antibiotics may also inhibit peptidyl transferase through the ribosomal elongation mechanism [63,64]. Some nucleotide sites in the 23S rRNA areas have hot spots that are critical in determining the azithromycin resistance of MG; mutational changes in these hot spots inhibit macrolide binding, which leads to the development of macrolide resistant infections [54][55][56][57]. Anagrius et al [66] reported that the prevalence of macrolide resistant MG has been increasing in a Swedish STD clinic, and the mutation rates in the 23S rRNA regions are as follows; wild type (A2058A and A2059A type-59%), A2058G (23%), A2058T (2%), A2059G (13%), and insufficient results (3%).…”

The rates of mutations associated with macrolide resistance in Mycoplasma genitalium among patients with non-gonococcal sexually transmitted infections in Smolensk and Tula

“…Несмотря на различия в тактике назначения макролидов в разных странах, проблемы, возникающие с их использованием, остаются: за последние годы наблюдается снижение эффективности препаратов данной группы во всем мире [14][15][16]. В зарубежных статьях неоднократно упоминалось о случаях безрезультатного лечения макролидами [17,21,22]. Клинический неуспех терапии джозамицином у пациентов с НГУ, вызванными M. genitalium, также был описан и в российских публикациях [18][19][20].…”

Spread of multidrug resistance among Ureaplasma serovars, Tunisia

“…Such a situation, could lead to the emergence of multidrug-resistant (MDR) strains, defined as those resistant to at least one agent in three or more antimicrobial classes [15], thus considerably restricting the treatment options. MDR Mycoplasma strains have been recently reported, particularly in Mycoplasma genitalium [16], while such findings are still relatively scarce in ureaplasmas [6].…”