Fever of Unknown Origin in a Tracheostomy- and Ventilator-Dependent Child Kensho Iwanaga, MD Fellow, Pediatric Pulmonology 03.23.11
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 Illness WBC (k/mm3) CRP (mg/dL) Augmentin (admit) Augmentin (clinic) Augmentin (PCP) Cipro (telephone) 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.
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 Physical Examination
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
7/19/10 7/16/07 (10 m/o) 12/17/10 1/31/11
Clinical and Laboratory Trends CRP (mg/dL) WBC (k/mm3)orTmax (°C) metronidazole 2/9-2/24 ceftaz+gent pip/tazo linezolid+cipro
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
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 • M. abscessus is a member of rapidly growing (≤7 days) mycobacteria • Neither tracheostomy nor BPD are well-documented risk factors for M. abscessus • 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 • Griffith DE et al. Am J Respir Crit Care Med. 2007;175:367-416. • Colombo RE et al. Semin Respir Crit Care Med. 2008;29:577-88. • Daley CL et al. Clin Chest Med. 2002;23:623-32. • Griffith DE. Curr Opin Infect Dis. 2010;23:185-90. • Nash KA et al. Antimicrob Agents Chemother. 2009;53:1367-76. • 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