128 AJTCCM VOL. 30 NO. 3 2024
CORRESPONDENCE: CASE REPORT
To the editor: Mycoplasma pneumoniae is one of the leading causes of
community-acquired pneumonia in school-aged children and young
adults. Although it is self-limiting, M. pneumoniae pneumonia (MPP)
can lead to serious complications, with 25% of patients experiencing
prolonged fever, worsening symptoms and deteriorating radiological
ndings despite appropriate macrolide therapy for ≥7 days.[1]
Macrolide resistance of M. pneumoniae (MRMP) is a potential
cause of refractory MPP (RMPP). Dierences in clinical features and
severity between MRMP and macrolide-sensitive M. pneumoniae
infections are unclear, but studies show longer fever duration, a
more severe clinical course and an increased risk of intensive care
unit (ICU) admission in MRMP.[2] Recent childhood pneumonia
outbreaks in northern China may be due to post-pandemic
changes in endemic respiratory infections, similar to US and
European outbreaks in 2022. Epidemiological evidence suggests
that re-emerging infections by organisms such as respiratory
syncytial virus, influenza viruses and M. pneumoniae are the
cause.[3] Non-pharmaceutical interventions signicantly reduced
M. pneumoniae transmission during the COVID-19 pandemic to
1.69% between 2020 and 2021, compared with a global incidence
of 8.61% between 2017 and 2020. A resurgence of M. pneumoniae
in an unexposed population during the pandemic may result in an
increase in severe disease.
We present the case of a young child with severe MPP (SMPP) who
required paediatric ICU care and did not respond to azithromycin.
e parents gave consent for the publication of the case report.
A 5-year-old HIV-negative boy presented with a history of fever,
persistent cough and tachypnoea for 8 days. He had completed a
course of oral amoxicillin/clavulanate with no improvement. He had
previously been well, with no contact with tuberculosis or signicant
travel history. On examination, he had a fever and reduced air entry in
the right lower lobe (RLL) area. A chest radiograph (CXR) conrmed
RLL airspace disease and obscuration of the right hemidiaphragm
(Fig.1A). Because the fever persisted, the CXR was repeated aer
3 days, confirming worsening consolidation and a small pleural
eusion (Fig.1B). M. pneumoniae was conrmed on nasopharyngeal
aspirate by polymerase chain reaction (PCR) on day 8. No other
viruses or bacteria were identied. e C-reactive protein (CRP)
level remained low (Table1), but persistent swinging fever of 40˚C
was present. On day 5 of treatment with intravenous cefuroxime and
oral azithromycin, the boy developed respiratory distress requiring
escalation to high-ow nasal cannula respiratory support. e follow-
up CXR demonstrated an expansile RLL pneumonia, significant
eusion with mediastinal shi to the le, and parenchymal disease in
the le lower lobe (Fig.1C).
An ultrasound scan conrmed a large uncomplicated eusion with
underlying RLL consolidation (Fig.1D). Pleural uid was drained,
yielding 800 mL. A post-contrast computed tomography (CT) scan
also showed parenchymal airspace consolidation of the RLL with a
bulging anterior margin, as well as le-sided airspace consolidation
and a le-sided eusion (Fig.1E - H).
On day 8, the CXR showed improvement in the eusion size, but there
was residual parenchymal airspace disease in the RLL (Fig.1I). PCR
testing for M. pneumoniae was positive in the pleural uid on the
Biore FilmArray Pneumonia Panel (BioFire PN; BioMérieux, France)
(Table1). In view of the persistent symptoms, radiological features
of severe disease and no response to azithromycin, the therapy was
changed to doxycycline to treat presumptive resistant mycoplasma.
Oral prednisone was added owing to prolonged symptoms and high
ferritin levels (213 µg/L). e fever improved aer 48 hours. e
pigtail catheter was removed aer 5 days.
e treating clinicians were informed that there were three other
microbiologically conrmed MPP cases at the patient’s school, two
children of the same age and an adult. ey were all eectively treated
at home with azithromycin.
A CXR on day 15 and aer completion of 10 days of doxycycline
demonstrated marked improvement of both the eusion and the
parenchymal airspace disease (Fig.1J).
MPP in South African children may be on the rise, but lack of access
to serological and molecular testing in the public sector may mean
that there is a paucity of data.
MPP, or ‘walking pneumonia’, is a benign, self-limiting disease
characterised by subacute fever, cough, asthma-like symptoms and
dyspnoea. Some children cannot be eectively treated with 7 days
of macrolides, leading to RMPP.[4] RMPP is dened as no signicant
improvement, worsening lung disease or complications. Patients
have longer fever duration, longer hospitalisation, and a higher
incidence of extrapulmonary complications. Radiological ndings
include lobar consolidation, lobar atelectasis, pleural eusions and
bronchopneumonia.[5]
Expansile pneumonia, as was seen in the case reported here, is not
a common presentation. CT scans have shown that the incidence of
lung consolidation and pleural eusion was higher in MRMP than in
non-resistant MPP.[6]
Serum ferritin levels have been reported as an indicator of the
severity of MPP and have been used in making the decision whether
to add corticosteroid therapy.[7]
D-dimer results predict severe disease, SMPP with D-dimer levels
>0.308 mg/L being associated with more complications such as pleural
eusion and myocardial and liver damage. In our case, the D-dimer
level was 3.41 mg/L.[8]
SMPP patients have a higher prevalence of sputum plugs than
patients with non-severe MPP. ese plugs are caused by bronchial
inammation and ciliary abnormalities, which can result in increased
mucus production and decreased mucus clearance, leading to sputum
plug formation.
MPP patients requiring ICU care have higher white blood cell
counts, CRP levels and alanine transaminase than those who are less
severely ill, and are more likely to have underlying illnesses and pleural
eusion.[9] Studies indicate that 71 - 88% of macrolide-sensitive MPP
patients are free of fever within 48 hours of starting treatment. In
macrolide-resistant MPP patients, fever remains in 52 - 73% and
Severe Mycoplasma pneumoniae infection in a young child:
Anemerging increase in incidence?
AJTCCM VOL. 30 NO. 3 2024 129
CORRESPONDENCE: CASE REPORT
30% for more than 48 and 72 hours, respectively. Tetracyclines and
uoroquinolones can be considered for patients who do not respond
to macrolides, but the minimum inhibitory concentrations of
azithromycin oen exceed 64 mg/mL.[10]
Okada et al.[11] reported that fever subsides within 72 hours
of switching to tetracyclines (doxycycline or minocycline) or
uoroquinolones in nearly all patients with macrolide-resistant MPP.
Doxycycline and other tetracyclines are contraindicated in children
aged <8 years owing to permanent tooth discoloration and enamel
degradation. Studies show that doxycycline is less likely to cause
enamel staining because it binds to calcium less readily. e American
Academy of Pediatrics now recommends use of doxycycline for short
periods.[12,13]
When combined with macrolide treatment in SMPP, prednisolone
signicantly reduces fever, dyspnoea and hypoxaemia, accelerates
radiological improvement, and reduces serum ferritin and lactate
dehydrogenase levels.[14]
The incidence of MPP has been increasing globally during the
post-COVID-19 pandemic period.[15] e reasons for the increase
are unknown, but may be related to the fact that large sectors of
the population were not exposed during the pandemic. Our case
demonstrates that MPP can present as severe disease needing ICU
admission, as well as the possibility that patients with RMPP may
require doxycycline and corticosteroids.
P Goussard, PhD
Department of Paediatrics and Child Health, Faculty of Medicine and Health
Sciences, Stellenbosch University and Tygerberg Hospital, Cape Town, South Africa
pgouss@sun.ac.za
H Rabie, PhD
Department of Paediatrics and Child Health, Faculty of Medicine
and Health Sciences, Stellenbosch University and Tygerberg Hospital,
CapeTown, South Africa
Fig 1. (A) Day 1. Frontal plain CXR demonstrating airspace disease in the RLL (star) resulting in obscuration of the right hemidiaphragm.
(B)Day 3. Frontal plain CXR demonstrating progression of the RLL airspace disease (star) and development of a lamellar effusion
(blackarrow) tracking also into the minor fissure. (C) Day 5. Frontal plain CXR demonstrating further expansion of the RLL airspace
process (star) with a convex superior border (white arrow), in keeping with an expansile pneumonia, and enlargement of the right effusion
(black arrow), now tracking over the apex of the lung. There is also some loss of clarity of the left hemidiaphragm in keeping with developing
parenchymal disease in the left lower lobe. (D) Ultrasound scan after day 5. Longitudinal ultrasound scan of the right chest demonstrating
a large simple effusion (star) and the underlying consolidated lung (arrow). (E and F) Post ICD CT scan demonstrating sequential images of
a post-contrast scan of the chest on soft-tissue windows, confirming the appropriate intrathoracic location of the thoracic drain (longwhite
arrow in E) and parenchymal airspace consolidation of the RLL (stars in E and F), with normal vascular enhancement but showing a
bulging anterior margin (black arrow in F), as well as left-sided airspace consolidation and a left-sided effusion (short white arrow inE).
(G and H) Axial sequential images of the same CTscan on lung windows, demonstrating areas of localised air trapping (white stars) in
addition to the multifocal airspace disease. (I) Day 8 post ICD. Frontal CXR demonstrating a right thoracic pigtail drain in situ (arrow),
with marked improvement in the size of the effusion but with residual parenchymal airspace disease in the RLL (star). (J) Day 15. Frontal
CXR demonstrating marked improvement of both the effusion and the parenchymal airspace disease, with only a small residual area of
parenchymal density on the RLL and reappearance of the hemidiaphragms bilaterally. (CXR = chest radiograph; RLL = right lower lobe;
ICD = intercostal chest drain; CT = computed tomography.)
130 AJTCCM VOL. 30 NO. 3 2024
CORRESPONDENCE: CASE REPORT
L Frigati, PhD
Department of Paediatrics and Child Health, Faculty of Medicine
and Health Sciences, Stellenbosch University and Tygerberg Hospital,
CapeTown, South Africa
A Gie, PhD
Department of Paediatrics and Child Health, Faculty of Medicine
and Health Sciences, Stellenbosch University and Tygerberg Hospital,
CapeTown, South Africa
S Irusen, Cert Nephrology (SA) Paed
Department of Paediatrics and Child Health, Faculty of Medicine
and Health Sciences, Stellenbosch University and Tygerberg Hospital,
CapeTown, South Africa
C Jacobs, FC Paed (SA)
Department of Paediatrics and Child Health, Faculty of Medicine
and Health Sciences, Stellenbosch University and Tygerberg Hospital,
CapeTown, South Africa
S Venkatakrishna, MBBS
Department of Pediatric Radiology, Children’s Hospital of
Philadelphia, Penn., USA
S Andronikou, PhD
Department of Pediatric Radiology, Children’s Hospital of
Philadelphia, Penn., USA; Department of Radiology, Perelman
School of Medicine, University of Pennsylvania, Philadelphia,
Penn.,USA
1. Tamura A, Matsubara K, Tanaka T, Nigami H, Yura K, Fukaya T. Methylprednisolone
pulse therapy for refractory Mycoplasma pneumoniae pneumonia in children. J Infect
2008;57(3):223-228. https://doi.org/10.1016/j.jinf.2008.06.012
2. Lanata MM, Wang H, Everhart K, Moore-Clingenpeel M, Ramilo O, Leber A.
Macrolide-resistant Mycoplasma pneumoniae infections in children, Ohio, USA.
Emerg Infect Dis 2021;27(6):1588-1597. https://doi.org/10.3201/eid2706.203206
3. Parums DV. Editorial: Outbreaks of post-pandemic childhood pneumonia and the
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https://doi.org/10.12659/MSM.943312
Table1. Laboratory results
Patient’s result Reference range
Complete blood count
WBC count (× 109/L) 10.8 6 - 16
Neutrophils (× 109/L) 7.34 2.4 - 7.50
Lymphocytes (× 109/L) 1.37 2.3 - 8.0
MCV (fL) 89.5 75 - 87
MCH (pg) 114 24 - 30
MCHC (g/dL) 127 31 -3 7
Serum biomarkers
Serum ferritin (µg/L) 213 4 - 67
CRP (mg/L) 6 <10
LDH (U/L) 688 110 - 295
D-dimers (mg/L) 3.41 0.00 - 0.25
Bilirubin (μmol/ L) 6 5-21
Troponin (ng/L) <3 Abnormal >100
Pleural aspirate analysis
Pleural uid protein (g/dL) 37 <1.5
Pleural uid LDH (U/L) 1 406 n/a
Pleural uid ADA (U/L) 24.7 4.8 - 38
Pleural uid cell counts
Neutrophils (%) 7 0 - 2
Lymphocytes (%) 89 2 - 11
PCR tests
SARS-CoV-2 antigen Negative n/a
Xpert MTB/RIF Negative n/a
Mycoplasma pneumoniae PCR Positive n/a
Viral PCR Negative n/a
Bacterial PCR Negative n/a
Malignant cytology Negative n/a
WBC = white blood cell; MCV = mean corpuscular volume; MCH = mean corpuscular haemoglobin; MCHC = mean corpuscular haemoglobin concentration ; CRP = C-reactive protein;
LDH = lactate dehydrogenase; n/a = not applicable; ADA = adenosine deaminase; PCR = polymerase chain reaction.
AJTCCM VOL. 30 NO. 3 2024 131
CORRESPONDENCE: CASE REPORT
4. Akashi Y, Hayashi D, Suzuki H, etal. Clinical features and seasonal variations in
the prevalence of macrolide-resistant Mycoplasma pneumoniae. J Gen Fam Med
2018;19(6):191-197. https://doi.org/10.1002/jgf2.201
5. Zhao J, Ji X, Wang Y, Wang X. Clinical role of serum interleukin-17A in the prediction
of refractory Mycoplasma pneumoniae pneumonia in children. Infect Drug Resist
2020;13:835-843. https://doi.org/10.2147/IDR.S240034
6. Choi YJ, Chung EH, Lee E, etal. Clinical characteristics of macrolide-refractory
Mycoplasma pneumoniae pneumonia in Korean children: A multicenter retrospective
study. J Clin Med 2022;11(2):306. https://doi.org/10.3390/jcm11020306
7. Kawamata R, Yokoyama K, Sato M, etal. Utility of serum ferritin and lactate
dehydrogenase as surrogate markers for steroid therapy for Mycoplasma pneumoniae
pneumonia. J Infect Chemother 2015;21(11):783-789. https://doi.org/10.1016/j.
jiac.2015.07.009
8. Qiu J, Ge J, Cao L. D-dimer: The risk factor of children’s severe Mycoplasma
pneumoniae pneumonia. Front Pediatr 2022;10:828437. https://doi.org/10.3389/
fped.2022.828437
9. Lee KL, Lee CM, Yang TL, etal. Severe Mycoplasma pneumoniae pneumonia requiring
intensive care in children, 2010-2019. J Formos Med Assoc 2021;120(1 Pt 1):281-291.
https://doi.org/10.1016/j.jfma.2020.08.018
10. Morozumi M, Takahashi T, Ubukata K. Macrolide-resistant Mycoplasma pneumoniae:
Characteristics of isolates and clinical aspects of community-acquired pneumonia.
J Infect Chemother 2010;16(2):78-86. https://doi.org/10.1007/s10156-009-0021-4
11. Okada T, Morozumi M, Tajima T, et al. Rapid effectiveness of minocycline or
doxycycline against macrolide-resistant Mycoplasma pneumoniae infection in a 2011
outbreak among Japanese children. Clin Infect Dis 2012;55(12):1642-1649. https://
doi.org/10.1093/cid/cis784
12. Kimberlin DW, ed., Barnett ED, Lyneld R, Sawyer MH, assoc. eds.Red Book: 2021-
2024 Report of the Committee on Infectious Diseases. 32nd ed. Itasca, Ill.: American
Academy of Pediatrics, 2021.
13. Todd SR, Dahlgren FS, Traeger MS, etal. No visible dental staining in children
treated with doxycycline for suspected Rocky Mountain spotted fever. J Pediatr
2015;166(5):1246-1251. https://doi.org/10.1016/j.jpeds.2015.02.015
14. Luo Z, Luo J, Liu E, etal. Effects of prednisolone on refractory Mycoplasma
pneumoniae pneumonia in children. Pediatr Pulmonol 2014;49(4):377-380. https://
doi.org/10.1002/ppul.22752
15. Meyer Sauteur PM, Chalker VJ, Berger C, Nir-Paz R, Beeton ML; ESGMAC and the
ESGMAC-MyCOVID study group. Mycoplasma pneumoniae beyond the COVID-19
pandemic: Where is it? Lancet Microbe 2022;3(12):e897. https://doi.org/10.1016/
S2666-5247(22)00190-2
Received 2 April 2024. Accepted 20 June 2024. Published 11 October 2024.
Afr J Thoracic Crit Care Med 2024;30(3):e2036. https://doi.
org/10.7196/AJTCCM.2024.v30i3.2036
