Purpose. To determine the timing of the emergence of macrolide-resistant mutations after macrolide treatment in individuals with Mycoplasma pneumoniae infections.
Methodology. Between October 2011 and December 2013, serial pharyngeal swab specimens were collected before and after macrolide treatment from 21 otherwise healthy children infected with M. pneumoniae without macrolide-resistant mutations. The copy numbers of a M. pneumoniae gene and the proportion of clones showing macrolide-resistance mutations were determined for each specimen.
Results. After macrolide treatment (10–15 mg kg−1 day−1 clarithromycin for 5–10 days or 10 mg kg−1 day−1 azithromycin for 3 days), fever resolved in 19 (90 %) of 21 children within 1 to 2 days, and the M. pneumoniae gene copy number decreased in all but one specimen in the second set of specimens relative to the number in the corresponding initial specimens. None of the second specimens, which were collected 2–4 days after initiation of macrolide treatment, showed mutations in the 23S rRNA gene. However, the proportion of mutant clones with A2063G and A2064G mutations in the specimens collected 7–24 days after initiation of treatment increased to 100 %. We identified a family in which three members had M. pneumoniae infections. The analysis of transmission in this household indicated that the M. pneumoniae harbouring a macrolide-resistant mutation that developed in the index patient after macrolide treatment was not transmitted to the family members.
Conclusion. A macrolide-resistant population might develop in individual patients up to 24 days after initiation of macrolide treatment. However, the decrease in M. pneumoniae load after macrolide administration effectively reduces interpersonal transmission.
YamazakiT, KenriT. Epidemiology of Mycoplasma pneumoniae infections in Japan and therapeutic strategies for macrolide-resistant M. pneumoniae. Front Microbiol2016; 7:693 [View Article][PubMed]
OkazakiN, NaritaM, YamadaS, IzumikawaK, UmetsuM et al. Characteristics of macrolide-resistant Mycoplasma pneumoniae strains isolated from patients and induced with erythromycin in vitro. Microbiol Immunol2001; 45:617–620 [View Article][PubMed]
PereyreS, GoretJ, BébéarC. Mycoplasma pneumoniae: current knowledge on macrolide resistance and treatment. Front Microbiol2016; 7:974 [View Article][PubMed]
UbukataK, MorozumiM, IwataS. Large epidemic of Mycoplasmal pneumonia caused by Mycoplasma pneumoniae strains highly resistant to macrolides among children in 2011. IASR2011; 32:337–339
SuzukiY, SetoJ, ItagakiT, AokiT, AbikoC et al. Gene mutations associated with macrolide-resistance and p1 gene typing of Mycoplasma pneumoniae Isolated in Yamagata, Japan, between 2004 and 2013. Kansenshogaku Zasshi2015; 89:16–22 [View Article][PubMed]
PereyreS, GuyotC, RenaudinH, CharronA, BébéarC et al.In vitro selection and characterization of resistance to macrolides and related antibiotics in Mycoplasma pneumoniae. Antimicrob Agents Chemother2004; 48:460–465 [View Article][PubMed]
OhyaH, SuzukiI, NaritaM, OkazakiN. In vitro development of macrolide-resistant Mycoplasma pneumoniae and transition mutation in 23Sr RNA of resistance strains. Jpn J Mycoplasmol2008; 35:47–52
ChironnaM, SallustioA, EspositoS, PerulliM, ChinellatoI et al. Emergence of macrolide-resistant strains during an outbreak of Mycoplasma pneumoniae infections in children. J Antimicrob Chemother2011; 66:734–737 [View Article][PubMed]
HantzS, GarnierF, PeuchantO, MenetreyC, CharronA et al. Multilocus variable-number tandem-repeat analysis-confirmed emergence of a macrolide resistance-associated mutation in Mycoplasma pneumoniae during macrolide therapy for interstitial pneumonia in an immunocompromised child. J Clin Microbiol2012; 50:3402–3405 [View Article][PubMed]
ItagakiT, SuzukiY, SetoJ, AbikoC, MizutaK et al. Two cases of macrolide resistance in Mycoplasma pneumoniae acquired during the treatment period. J Antimicrob Chemother2013; 68:724–725 [View Article][PubMed]
DumkeR, StolzS, JacobsE, JuretzekT. Molecular characterization of macrolide resistance of a Mycoplasma pneumoniae strain that developed during therapy of a patient with pneumonia. Int J Infect Dis2014; 29:197–199 [View Article][PubMed]
SuzukiY, ItagakiT, SetoJ, KanekoA, AbikoC et al. Community outbreak of macrolide-resistant Mycoplasma pneumoniae in Yamagata, Japan in 2009. Pediatr Infect Dis J2013; 32:237–240 [View Article][PubMed]
LevenM, UrsiD, van BeverH, QuintW, NiestersHG et al. Detection of Mycoplasma pneumoniae by two polymerase chain reactions and role of M. pneumoniae in acute respiratory tract infections in pediatric patients. J Infect Dis1996; 173:1445–1452 [View Article][PubMed]
SasakiT, KenriT, OkazakiN, IsekiM, YamashitaR et al. Epidemiological study of Mycoplasma pneumoniae infections in Japan based on PCR-restriction fragment length polymorphism of the P1 cytadhesin gene. J Clin Microbiol1996; 34:447–449[PubMed]
DégrangeS, CazanaveC, CharronA, RenaudinH, BébéarC et al. Development of multiple-locus variable-number tandem-repeat analysis for molecular typing of Mycoplasma pneumoniae. J Clin Microbiol2009; 47:914–923 [View Article][PubMed]
ChalkerVJ, PereyreS, DumkeR, WinchellJ, KhoslaP et al. International Mycoplasma pneumoniae typing study: interpretation of M. pneumoniae multilocus variable-number tandem-repeat analysis. New Microbes New Infect2015; 7:37–40 [View Article][PubMed]
SuzukiY, SetoJ, ShimotaiY, IkedaT, YahagiK et al. Development of an endpoint genotyping assay to detect the Mycoplasma pneumoniae 23S rRNA gene and distinguish the existence of macrolide resistance-associated mutations at position 2063. J Microbiol Methods2016; 131:130–134 [View Article][PubMed]
NilssonAC, BjörkmanP, PerssonK. Polymerase chain reaction is superior to serology for the diagnosis of acute Mycoplasma pneumoniae infection and reveals a high rate of persistent infection. BMC Microbiol2008; 8:93 [View Article][PubMed]
FoyHM. Infections caused by Mycoplasma pneumoniae and possible carrier state in different populations of patients. Clin Infect Dis1993; 17:S37–S46 [View Article][PubMed]