CYCH Ped case 20190131

1. Case conference
Presenter: FM R1盧敬文
Supervisor: VS郭馨璟
2019.1.31

2. • 4-year-6-month-old boy
• Growth: Body weight: 17.2 kg ( 15-50th percentile)
• Body height: 103 cm ( 15-50th percentile)

3. OPD: fever, vomiting for 2 days, cough
PE: injected throat and tonsils
Check hemogram, CRP and flu test
Zithromax 5 CC QD
20190102

4. OPD: fever, vomiting for 2 days, cough
PE: injected throat and tonsils
Check hemogram, CRP and flu test
Zithromax 5 CC QD
20190102
20190104
OPD: fever for 5 days up to 39℃, cough progressed
PE: injected throat and tonsils, chest: breathing sound: coarse
CXR
admission

5. • Patchy confluent opacification
in bilateral lower lung fields,
consider bronchopneumonia.
• No cardiomegaly.
• The diaphragm, mediastinum,
and major airway are all
unremarkable.
• The thoracic cage is
unremarkable.
• Rotatory asymmetry of
thoracolumbar spine.

6. 2019-1-04
Influenza A+B Negative
S. pneumoniae Ag Negative
M. pneumoniae Ab 1:40x
(Negative)
2019-1-07
M. pneumoniae Ab 1:1280x
(positive)
M. pneumoniae IgM positive
(2mg/kg/dose bid)
Productive cough was still noted during hospitalization.

7. OPD: fever, vomiting for 2 days, cough
PE: injected throat and tonsils
Check hemogram, CRP and flu test
Zithromax 5 CC QD
20190102
20190104
OPD: fever for 5 days up to 39℃, cough progressed
PE: injected throat and tonsils, chest: breathing sound: coarse
CXR
admission
20190115
OPD: cough occasionally
PE: NOT injected throat and tonsils, chest: breathing sound: clear
CXR

10. 1. Introduction to M. pneumoniae
• the smallest self-replicating bacteria
• lacks a cell wall
• causing about 10–40% of all CAP in children and young adolescents.
• Common chest X-ray patterns:
bronchopneumonia, plate-like atelectasis, nodular infiltration, and hilar adenopathy.
• Early administration of macrolides can shorten the duration of
symptoms(?)

11. macrolide resistance M. pneumoniae(MRMP)
• may promote refractory M. pneumoniae pneumonia in some patients.
• Alternative options: tetracyclines or fluoroquinolones
• not recommended as a first-line antibiotic choice
• age-related contraindications
• Macrolide, tetracyclines
act on the bacterial ribosome and inhibit protein synthesis
• Fluoroquinolones
inhibit DNA replication

12. 2. Mechanism for MRMP
• point mutations in the
peptidyl transferase loop of
23S rRNA
• A2063G or A2064G mutation at
the domain V of 23S rRNA
 MIC50 of erythromycin is 10,000
times higher (16 μg/mL)
• lack a cell wall and are intrinsically
resistant(beta-lactams)

13. 2.1 what contributes to the increase
• The role of antibiotic pressure
• highest in areas where M. pneumoniae infections are prevalent in children
and macrolides are widely used.
• reduction of macrolides through antibiotic stewardship may be crucial

14. 3. Global prevalence
• M. pneumoniae containing transitions in the 23S rRNA gene has been
reported worldwide since 2000.

15. 4.1 clinical clue
• between macrolide-resistant vs. susceptible cases
 did NOT show a difference
• symptoms including fever, cough, oxygen requirement, use of mechanical ventilator
along with laboratory, and also radiographic findings
• do not respond to treatment with macrolides or worsen despite the
treatment
 testing for macrolide resistance

16. 4.2 more severe infection?
• stimulation of a higher host immune response:
• cytokines interleukin (IL)-8 and IL-18
• related to the severity
• Acquisition of resistance
• NOT more virulent
• but make treatment more difficult

17. 4.3 are macrolide effective to MRMP?
• Prolonged:
fever, cough, and duration of hospitalization and treatment period after initiation of macrolides
• But no apparent treatment failures or serious illness
• mild and self-limiting nature of the infection
 macrolide resistance might not have a great impact(?)

18. 4.4 determinant of clinical course?
• fever duration determined by:
• radiologic findings,
• not by the presence of macrolide resistance.
1. presence of extrapulmonary signs,
2. homogeneous lobar consolidation,
3. parapneumonic effusion
 prolonged fever

19. 4.5 tetracyclines effective?
• Defervescence within 48 h:
 minocycline > macrolide
• Decrease DNA load within 48 h:
clinical and microbial: minocycline > macrolides
4.6 fluoroquinolones effective?
• Therapeutic efficacy have been reported in adolescents and adults
infected with MRMP

20. 4.7 safety issues using tetracycline and FQ in children
• Tetracyclines
• Contraindicated in pregnancy and children under 8 y/o
• short cycles with limited courses
(less than 6 courses, 6 days per course)
 negligible tooth discoloration in children < 5 y/o
• doxycycline binds calcium lesser
• Fluoroquinolones
• not licensed in children
• concerns regarding musculoskeletal adverse events.
adverse reactions:
gastrointestinal disturbances,
esophagitis, photosensitivity,
tooth discoloration
in children

21. 5. Choice of antimicrobials
• a more comprehensive approach must be established
• in most studies clinical response did not differ between children
randomized to a macrolide group
• there is insufficient evidence to draw any specific conclusions about the
efficacy of antibiotics for this condition in children.
• The use of antibiotics for M. pneumoniae LRTI has to be individualised and
balanced with possible adverse events associated with antibiotic use.

22. • due to safety concerns regarding tetracyclines and fluoroquinolones,
• the choice to turn to an alternative is not straightforward even in areas where
there is a high resistance to macrolide.
• The dilemma has been encountered
• Japanese guidelines which recommended macrolides as the first choice even
though the resistance rate was over 80%
• refractory pneumonia
alternative agents may be required

24. • 258 children with M. penumoniae- associated pneumonia
• Dx by CXR, real-time PCR, antibody titer
• Btw Jan and Dec 2011
• 176/202 were MRMP

25. • Minocycline or DOX (n = 125) or TFX or levofloxacin(n = 15) was used
for definitive treatment of MRMP patients.
• Minocycline or DOX was significantly more effective than TFX (P ≤ .05)
• achieving defervescence within 24 hours
• decreasing numbers of M. pneumoniae DNA copies 3 days after initiation.

26. almost 90%

27. • The advantage of MIN: relatively high blood concentration (2.3 μg/mL
after giving 4 mg/kg) and to a very long half-life (10 hours).

28. • Rapidly increasing macrolide resistance
• frequent initial prescription of macrolides to school-aged patients with M.
pneumoniae infection.
• account for 30% of all prescribed oral antibiotics in Japan.
• Macrolide did not decrease bacterial numbers in the nasopharynx,
and prolonged coughing caused further spread of MRMP.

29. Twice-daily dosage
MIN 4 mg/kg/day
DOX 4 mg/kg/day
TFX 12 mg/kg/day

30. Thank you for your attention.