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Fever of Unknown Origin in a Tracheostomy- and VentilatorDependent 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 CRP (mg/dL) WBC (k/mm3) History of Present Illness 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 7/16/07 (10 m/o) 7/19/10 12/17/10 1/31/11 CRP (mg/dL) WBC (k/mm3) or Tmax (°C) Clinical and Laboratory Trends 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 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] • • • • “Administration,Inhalation”[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. 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