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Microbes & Immunity Re-emergence of M. pneumoniae in the post-COVID-19 era

post-pandemic period compared to the pandemic period, middle-income countries has been largely improved during
although it remained below the pre-pandemic levels. It the COVID-19 pandemic, this PCR-based diagnostic is
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was speculated that this phenomenon was associated with still not widely available since it is too expensive and could
the unique and atypical characteristics of M. pneumoniae in not be covered by universal health insurance. Therefore,
comparison to other pathogens as previously mentioned. 6 in low- and middle-income countries, M. pneumoniae

The threat of M. pneumoniae transmission in the is not regularly detected in the clinical settings, but
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community has raised awareness of the government and only in a limited range of research-based settings. In a
health authorities globally, including Indonesia. At the multicenter, hospital-based study in Indonesia to examine
time of writing (December 2023), there were six cases the bacterial and viral etiologies of childhood community-
of M. pneumoniae reported by the Ministry of Health, acquired pneumoniae, only five samples from among 188
Indonesia, affecting children aged 3 – 12 years but without enrolled children were tested for M. pneumoniae. Based on
causing fatalities. The patients were hospitalized in October induced sputum PCR and serological tests, 5 (100%) and
and November 2023. The epidemics of M. pneumoniae 1 (20%) subjects were tested positive for M. pneumoniae,
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have posed serious challenges on accurate diagnosis and respectively.
treatment, particularly in the low- and middle-income For treatment, M. pneumoniae is naturally resistant
countries. Previously, M. pneumoniae infections were to all beta-lactam antibiotics because it has no cell wall.
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generally underreported or underdiagnosed health Macrolides, tetracyclines, and fluoroquinolones have
problems in the area. 14 constantly been the antibiotic of choices used to treat
1,19
Culturing M. pneumoniae from clinical specimens M. pneumoniae infections. However, the administration
is technically challenging. The culture needs specialized of tetracyclines and fluoroquinolones is generally not
media (modified Hayflick medium), supplemented with recommended in infants and young children due to their
horse serum (20%) that supplies cholesterol as a growth potential side effects. Thus, the physicians must carefully
stimulant, yeast extracts (15%), among others. However, weigh the risks and benefits. The protein synthesis
bacterial isolation may take up to 21 days due to its slow inhibitors belonging to the macrolide class are the first-
generation time as previously mentioned. In addition, choice antibiotics for pediatric M. pneumoniae infections
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polymerase chain reaction (PCR) technique is still since they offer better side effect profiles. However, its
needed to identify the isolated organism, commonly by extensive use for years has led to the increased frequency
1,15
targeting the P1 and 16S rRNA genes. Thus, culture- of macrolide-resistant M. pneumoniae (MRMP). In highly
based detection is not suitable for clinical settings and it is endemic settings, the frequency was reported to be more
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unavailable in the hospital and diagnostic laboratories. Due than 90%. In contrast, the frequency of MRMP was
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to these limitations, serological tests – regarded as the “gold relatively low in Europe. Notably, children infected with
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standard” – are recommended to diagnose M. pneumoniae MRMP developed significantly more severe diseases,
infections by detecting a four-fold increase of antibody underscoring its clinical relevance.
titers in paired acute and convalescent sera. However, this For other bacterial pathogens, antibiotic therapy can
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serological-based test is also not suitable for use in clinics be guided by automated antibiotic susceptibility testing
since it is very time-consuming and not valuable to guide (AST) systems. However, these systems are not applicable
the clinicians for prompt antibiotic therapy. The waiting to M. pneumoniae. To determine the minimum inhibitory
period for the convalescent phase to develop might also be concentrations, a (manual) laborious broth microdilution
too long for establishing the diagnosis. method is required, and thus, it is not feasible in daily
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At present, the diagnosis of M. pneumoniae is mainly settings. Consequently, detection of MRMP primarily
based on its direct detection from respiratory specimens depends on sequencing of resistance-associated mutations
(sputum, nasopharyngeal swabs, and bronchoalveolar (primarily the A2063G mutation) in the V domain of the
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lavage) by PCR. However, due to the very high sensitivity 23S rRNA gene. The recent development of next-generation
of PCR, it cannot be used to distinguish between sequencing technology could be helpful in clinical settings to
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colonization (carriage) and infection. M. pneumoniae detect MRMP, but its use is also limited due to its high cost.
is known to be present in the upper respiratory tracts of In conclusion, the recent upsurge of M. pneumoniae
healthy, asymptomatic children for months. Thus, a cases poses a significant challenge for prompt diagnosis and
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careful analysis is needed to interpret the PCR results to treatment, particularly for those in low- and middle-income
avoid overestimation of M. pneumoniae infections based countries. The data on M. pneumoniae epidemiology as well
on PCR diagnostic test. Although the laboratory capacity as its antimicrobial resistance profile in low- and middle-
of many clinical microbiology laboratories in the low- and income countries are generally not available. Therefore,

Volume 1 Issue 1 (2024) 122 doi: 10.36922/mi.3599