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