Discussion
MLVA type 4-5-7-2 was a dominant stain of M. pneumoniae in many
countries in Asia, Europe, America .14-17 Our results
showed a similar result in Henan province of China. The relationship
between MLVA types and macrolide-resistant mutation was also shown in
our study. MLVA types have no relationship with macrolide-resistant
mutation.
The relationship between MLVA types and macrolide resistance mutation
have been reported before. In 2015, Xue et al. reported that increasing
MRMP in China was linked to the increase of M. pneumoniae strains
typed 4-5-7-2,18 and the similar finding was also
reported in Hongkong and Japan.19, 20 However, MLVA
type 4-5-7-2 is not always related to macrolide-resistance mutation. For
example, 4-5-7-2 was also the predominant type in the United States of
America, European, Australia, and Thailand,21-24 where
the prevalence rate of MRMP was low. The percentage of MRMP among MLVA
typed 4-5-7-2 may change with time. In Japan, the percentage of A2063G
mutation in M. pneumonia strains typed 4-5-7-2 was only 0.9% between
2004 and 2010, but increased rapidly to 83.8% between 2011 and
2014.19
In this study, the A2063G mutation was the primary mutation, accounting
for 100%, no other mutations such as 2064 or 2617 were found. Beside
this, our study found mixed infection of wild strain and mutation strain
in one sample. Several mixed infections were reported as case reports
before.25-27 In these reports, patients were first
infected by the macrolide-sensitive M. pneumoniae . After a period
of treatment (usually longer than a week), the macrolide-resistance
mutation on 23s rRNA was found. However, whether these patients had
received macrolide antibiotics before specimen collection was difficult
to confirm. So, these patients might have developed macrolide resistance
during treatment, or mixed strains might have infected them before
specimen collection. More research is needed to do in this area.
Macrolides were the first line pharmaceutics for children with M.
pneumoniae infection. Some mutations(A2063 and A2064)are associated
with high-level resistance to macrolides,7 widespread
use of macrolides for M. pneumoniae with these mutations is not
only useless but also dangerous to induce more MRMP. Delayed usage of
appropriate antibiotics against MRMP is responsible for poor clinical
response and prolonged clinical course.28As a result,
severe CAP caused by MRMP will increase. To break this vicious circle,
reasonable usage of antibody is important not only in treating the
patient but also in preventing further increase of MRMP.
There was a limitation in our study. All samples were from one center in
one year. The results of this study should be interpreted cautiously due
to possible selection bias.
In conclusion, this is the first study about MLVA profile and its
correlation with macrolide resistance in pediatric patients in Henan
province. In 2020, M. pneumoniae was responsible for 9.8%
pediatric patients with CAP. Macrolide resistance genes was detected in
96% strains in Henan province in 2020. All the MRMP strains carried
A2063G mutation (100%). The most common type was 4-5-7-2 ,followed by
3-4-6-2. MRMP was independent to MLVA types.