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Kensho Iwanaga, MDFellow, Pediatric Pulmonology03.23.11
Fever of Unknown Origin in a Tracheostomy- and Ventilator-Dependent Child
History of Present Illness
• 4 y/o girl with tracheostomy and nighttime ventilator dependence for BPD and UAO with acute respiratory distress• Nasal congestion and decreased activity x24 hours• Fever to 103 °F overnight• Unable to come off the ventilator this morning• Low-grade fevers and greenish drainage from the
tracheostomy stoma site for the last 5 months
History of Present IllnessW
BC
(k/
mm
3 ) CR
P (m
g/d
L)
Augm
entin
(clin
ic)
Cipro
(telep
hone
)
Augm
entin
(adm
it)
Augm
entin
(PCP)
Ceftin/TOBI(clinic)
Past Medical History
• 25-5/7 weeks gestational prematurity• Moderate-severe BPD• Tracheostomy for severe subglottic stenosis• Oral aversion with G-tube dependence• Baseline respiratory support
• Day: HME + 0.5 L/min oxygen• Night: Ventilator + 1 L/min oxygen• IMV 12, PIP 20, PS 6 above PEEP 6
Past Medical History
• Medications• Flovent 44 mcg 2 puffs bid• Albuterol 4 puffs q4h prn cough/wheeze• TobraDex topical prn stoma irritation• Ibuprofen prn fever
• All: Sulfa, latex• FH: Negative• SH: Lives with parents, developing well• EH: Negative
Physical Examination
• VS: 36.7 155 30 117/66 98% on 1.5L• Gen: Well appearing.• EENT: Mild conjunctival injection. TMs normal. Clear
rhinorrhea. OP clear.• Neck: No cervical adenopathy• Resp: RR 28-30 with 1+ inspiratory work. Symmetric
chest excursion. Diffusely coarse inspiratory BS without wheezes or crackles. No prolongation of expiration.
• CV: Sinus tachycardia. Good pulses.
Physical Examination
• Stoma:• 1-2 mm margin of erythema• 3 mm granulation at 7:30 position• 4 mm area of denudation at 3:30 position• Mild-moderate thick greenish drainage• No fluctuance, hematoma
Admission Labs
• CBG 7.46/36; serum HCO3 26
• WBC 26.1• CRP 6.2• Viral FA negative• Tracheal aspirate
• Gram stain: Few PMNs• Culture: Pa, MSSA
12/17/10
7/19/107/16/07 (10 m/o)
1/31/11
Clinical and Laboratory Trends
CR
P (m
g/d
L)
WB
C (
k/m
m3 )
or
Tm
ax (
°C)
ceftaz+gent pip/tazo linezolid+cipro
metronidazole 2/9-2/24
Friday 4:00 PM Call
• Abundant growth of AFB within 48 hours on a fungal plate
→ Mycobacterium abscessus
Never Saw That One Coming…
• M. abscessus an unusual disease-causing pathogen in this population• Uncommon cause of tracheitis• Tracheostomy nor BPD not considered a siginficant risk factor
• Colonization versus infection?• Circumstances surrounding recovery of this pathogen• Clinical symptoms• Radiographic disease
2007 ATS/IDSA Diagnostic Criteria
Microbiological Findings
• 3/2/11: Tracheostomy stoma site and a tracheal aspirate both positive
• 3/9/11: BAL fluid positive
Rapidly Growing Mycobacteria (RGM)
• Subgroup of nontuberculous mycobacteria (NTM)• Visible growth on solid media within 7 days
• Ubiquitous environmental organism• Southern coastal states• Water, soil, biofilm
M. abscessus Epidemiology
• RGM-specific incidence not definitively known• Isolation: 1.51/100,000• Disease: 0.39/100,000
• Most common clinical disorders due to RGM• Skin/soft tissue infections• Chronic lung disease (bronchiectasis, nodules, cavitations)
• M. abscessus• Most common respiratory pathogen among RGM• Third most common respiratory pathogen among all NTM
Risk Factors For M. abscessus Pulmonary Disease
• Caucasian women, >60 years old, thin, nonsmoker• Prior TB infection/treatment• Gastroesophageal motility disorders• Cystic fibrosis• Alpha 1 antitrypsin deficiency
M. abscessus Treatment
• In vitro resistance to multiple antibiotics
• Typical regimen• IV amikacin +• IV imipenem or cefoxitin +• PO clarithromycin
• Newer agents• Linezolid• Tigecycline• Telithromycin
Our Patient
• Admitted 3/21/11 to initiate antimicrobial therapy• Inhaled amikacin• IV tigecycline• GT clarithromycin
Summary and Considerations
• Fevers of unknown origin in a 4 year old trach/vent child• Stoma drainage, supplemental oxygen need, radiographic
findings• “Reassuring” serial clinical examinations of the stoma• Serendipitous isolation of M. abscessus
• Now that we’ve started therapy…• Monitoring?• Duration?• Immune work-up?
Take Home Points For My Fellow Fellows
1. M. abscessus is a member of rapidly growing (≤7 days) mycobacteria
2. Neither tracheostomy nor BPD are well-documented risk factors for M. abscessus
3. 2007 ATS/IDSA guidelines• Clinical symptoms• Radiographic findings• Confirmatory cultures
• ≥2 sputum from different samples or• ≥1 bronchial or• lung biopsy (granuloma/AFB + a positive culture)
Thank You!
References
1. Griffith DE et al. Am J Respir Crit Care Med. 2007;175:367-416.
2. Colombo RE et al. Semin Respir Crit Care Med. 2008;29:577-88.
3. Daley CL et al. Clin Chest Med. 2002;23:623-32.
4. Griffith DE. Curr Opin Infect Dis. 2010;23:185-90.
5. Nash KA et al. Antimicrob Agents Chemother. 2009;53:1367-76.
6. Esteban J et al. Eur J Clin Microbiol Infect Dis. 2008;27:951-7.
Cryptic Resistance
• Macrolide antimicrobial agents act by binding to the 50S ribosomal subunit and inhibiting peptide synthesis.
• Erythromycin methylase (erm) genes code for methylases that impair binding of macrolides to ribosomes
• Inducible erm41 is the primary mechanism of acquired clinically significant macrolide resistance for some mycobacteria, especially RGM
• All isolates of M. abscessus, M. fortuitum and several other RGM, but not M. chelonae, contain an inducible erm gene
• If an M. fortuitum or M. abscessus isolate is exposed to macrolide, the erm gene activity is induced with subsequent in-vivo macrolide resistance which may not be accompanied by a change in the in-vitro MIC
Nash KA et al. Antimicrob Agents Chemother. 2009;53:1367-76.
Literature Search
• ("Tracheitis"[Mesh] OR "Tracheostomy"[Mesh]) AND "Mycobacteria, Atypical"[Mesh]• Kasai S et al. [A case of bronchial ulcer due to infection by Mycobacterium abscessus].
Nihon Kokyuki Gakkai Zasshi. 2004;42:919-23. Japanese.• Levashev IuN et al. [Circular resection of the upper trachea for concomitant postintubation
cicatricial stenosis and mycobacterial lesion]. Probl Tuberk Bolezn Legk. 2003;10:61-3. Russian.
• Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 33-1996. A 55-year-old man with a long-term tracheostomy and acid-fast bacilli in peristomal granulations. N Engl J Med. 1996;335:1303-7.
• “Administration,Inhalation”[Mesh] AND "Mycobacteria, Atypical"[Mesh]• Wang BY et al. Atypical mycobacteriosis of the larynx: an unusual clinical presentation
secondary to steroids inhalation. Ann Diagn Pathol. 2008;12(6):426-9.
• "Bronchopulmonary Dysplasia"[Mesh] AND "Mycobacteria, Atypical"[Mesh]• No items found