Final Edits2.grand rounds 08-13 Chiraag.pptx

Final Edits2.grand rounds 08-13 Chiraag.pptx

1. Grand Rounds 08/13/24 Trinity Health Ann Arbor Chiraag Gupta, PGY IV

2. Patient Presentation 70 yo female presenting with Chest Pain, SOB, chills Symptom onset 1 day prior to presentation Chest pain described as: Tightness, diffuse distribution, pleuritic, improved w/ positional changes (resolved after O2 + acetaminophen) SOB (resolved) associated w/ “little cough”, scant production, pink-tinged sputum, no overt hemoptysis, sore throat present x2 days w/o dysphagia ROS: Decreased appetite x1 week w/o weight change, terrible taste, insomnia, chills evening prior to presentation, generalized weakness x2 days No fevers, no diaphoresis, no N/V, no rashes/wounds, no urinary symptoms, stable BMs

3. History PMHx: Ulcerative Colitis on infliximab therapy (last dose 5 days prior to presentation), provoked DVT s/p 3 mos on eliquis , seasonal allergies not on therapy Recent hospitalization 10 day stay, discharged 2 weeks prior to presentation - failed outpatient therapy for UC flare, treatment w/ infliximab x2 + methylprednisolone, discharged on prednisone taper, flex sig x2 showing improvement, CRP elevated at time of dc 2.7, TB quantiferon 1 month prior to presentation indeterminate (prior to initiation of infliximab) Home medications - ASA 81 mg qD , IV infliximab 100 mg qmonthly , 2 month prednisone taper FHx - father w/ CVA, mother w/ CAD and MI Allergies - environmental Social Hx - lives at home w/ husband, no pets at home, annual travel to Italy, ambulates w/o assistance, retired previously worked as a paraprofessional in elementary school Never smoker, no EtOH use, no recreational drugs

4. Physical exam VS: 38.8 C, 131 bpm → fluids → 80-90, 24 breaths/min, 110/54, 93% on RA → 89% → 2L NC Gen - AxO x3. NADHead - normocephalic, atraumatic Eyes - PERRLA, EOMI, no conjunctival infection Mouth - no dental caries, dentition maintained Neck - oral mucosa pink and moist, no pharyngeal erythema, no lymphadenopathy Chest – coarse crackles noted CVS - RRR, normal S1/S2, peripheral pulses strong bilaterallyAbdomen - soft non-tender, no organomegaly, audible BSEXT – non-pitting edema Skin - no rashes, wounds Neuro - strength and sensation intact x4 extremities, speech/cognition WNL Psych - appropriate affect

5. Work-up ECG - sinus tachycardia w/o ischemic changes WBC 11.8; N - 85.7, L - 11.7, M - 2.2, E - 0.0, B - 0.1 1+ Dohle bodies Hgb 11.8, Hct 32.8, MCV 88.9 1+ elliptocytes No schistocytes Plt 171 Na - 133, K - 3.3, Cl - 95, Ca - 8.3, Mg - 1.5 CO2 - 27, Cr - 0.8, GFR - 79 AST - 24. ALT - 25, ALP - 78, TB - 1.1, Alb - 3.2, Procalcitonin 3.24 Lactate 2.1 → 1.3, Troponin 57 → 51, UA trace protein, 1+ blood, +Ve leukocytes, 0-2 WBC, 0-2 RBC, 1-5 squamous cells, 1-5 transitional epithelial cells

6. Imaging on presentation CXR - masslike opacification LUL 7.8 x 6.8 cm, R. lung clear CT C/A/P w/ contrast - large masslike opacity LUL extending from L. anterior superior perihilar region, abutting pleural space along anterolateral L. chest wall, 8.0 x 6.6 cm small L. pleural effusion mild dependent L-sided atelectasis R. lung unremarkable single prominent L. aortopulmonary LN measuring 0.8 x 0.9 cm, not pathologically enlarged scattered colonic diverticulosis w/o diverticulitis Started on IV vancomycin and IV cefepime

7. Summary 70 yo American retired female w/ annual travel to Italy, on infliximab infusions (w/ indeterminate quantiferon prior to initiation) and prolonged prednisone taper after recent hospitalization w/ pleuritic C/P, cough w/ scant hemoptysis, SOB w/ hypoxia, decreased appetite, chills, insomnia, generalized weakness and imaging showing large LUL mass-like opacification What is your differential? What would you like to do?

8. Differential: TB, lung abscess, fungal , atypical bacterial, nocardia MRSA swab negative → vancomycin stopped, continued on IV cefepime 2g q8, with addition of metronidazole Respiratory Molecular Panel - negative AFB stain negative, MTB PCR x2 negative , TB quantiferon gold indeterminate x 2 Strep pneumo urine Ag negative Legionella urine Ag negative Serum Beta-glucan negative, 35 (day 2) Serum Aspergillus antigen negative Resp Cx normal upper respiratory flora Blood Cx x3 negative D4 of abx therapy - Clinical picture persisted, patient feeling subjectively worse, fevers worsening, negative Cx data → bronchoscopy w/ BAL and bx Antibiotics transitioned to bactrim 10 mg/kg BID + Zosyn 4.5 gm

9. AFB stain GMS stain

10. BAL Pathology weak AFB positive rods Silver staining (Gomori’s silver methanamine) positive organisms Pneumocystis jirovecii molecular study positive BAL fungal-B-glucan 345 (day 6) and BAL Aspergillus antigen negative What is the diagnosis?

11. Summary: Legionella urine antigen test negative ; Lgeionella PCR positive ; legionella culture positive AFB positive organisms and PCP noted on BAL, Diagnosis? Legionella PCR positive Resp Culture: growth of legionella started on azithromycin

12. Legionella micdadei

13. Legionella, but not the usual suspect Legionella micdadei , first described in 1979 (Pittsburgh pneumonia agent) Aerobic gram - ve bacteria found in water/soil, first isolated by Joseph E. McDade in 1980 AKA Tatlockia micdadei and L. pittsburgensis Most common legionella species causing infection after pneumophila - 9% Often presents in immunocompromised patients Weakly AFB positive (unique to Legionella), Cavitary disease reported → has been confused for MTB/NTB prior to identification Presents as legionella + ve on PCR but not associated w/ typical serotypes Difficult to Cx or identify Poor uptake on standard gram staining - miss the gram - ve organism Cx on BCYE rather than standard commercial medium Radiography - nodular infiltrates w/ tendency to cavitate and enlarge

14. Pittsburgh Pneumonia Agent (PPA) Another New Pneumonia, Pandora’s Box Reopened? Vol. 301, No. 18 NEJM 1979 8 IC patients presented with PNA in 1979 in Pittsburgh, weakly acid-fast GN organism isolated from lung tissue, with no distinct feature of the clinical PNA; but all patients had recent corticosteroids; 5 of 8 died. Cultivated on egg embryo, but did not grow on Legionella pneumophila culture media; sulfamethoxazole, rifampin, erythromycin activity shown on invitro cultures (Cell-wall active agents and aminoglycosides not effective) 6 of 8 renal transplant patients; all considered hospital-associated; all patients developed PNA within 3 weeks of CS therapy Survivors treated with sulfamethoxazole Concurrently a case series noted in Virginia among 5 patients with high IFA titers to PPA (4 of 5 renal transplant patients)

15. An outbreak of legionella micdadei pneumonia in transplant patients: Evaluation, Molecular Epidemiology, and Control. Knirsch et al, 2000 The American Journal of Medicine Evidence of in-patient outbreak in post-transplant patients prompting retrospective analysis of presentations of nosocomial pna in transplant patients where no pathogen identified 38 renal and cardiac transplant patients w/ culture-negative nosocomial pna , 12 in the initial outbreak w/ evidence of L. micdadei pna + 7 more in later cluster Several water sources identified - heated water recirculation loop → thermal disinfection + hyperchlorination, routine Cx testing for Legionella in all pna patients

16. Pontiac Fever due to Legionella micdadei from a Whirlpool Spa: Possible role of bacterial endotoxin. Fields et al. 2001. Journal of Infectious Disease 1998 - illness cluster Wisconsin - 12 hotel guests (38 families) exposed to whirlpool spa and swimming pool, confirmed w/ serology Isolated from pool filter and spa-water after heat enrichment Cases not immunocompromised Live legionella isolated, not precluding presence of dead organisms, potential for non-viable legionella or cellular components causing illness - water from spa contained more endotoxin than samples obtained at other sites Implicated in >3 outbreaks prior

17. Legionella micdadei : A forgotten etiology of growing cavitary nodules: A case report and literature review. Lachant et al, 2015, Case Reports in Pulmonology 31 yo female w/ PMHx of ulcerative colitis and primary sclerosing cholangitis w/ fevers, chills, SOB, dry cough - 2 months on immunosuppressive tx for autoimmune hepatitis (prednisone 40 mg qD , azathioprine 50 mg qD ) Chest CT: small b/l cavitary nodules, continuing to enlarge despite abx therapy vancomycin and meropenem, amphotericin added concern for fungal etiology Bronch + BAL, CT guided bx, clinical deteriorating, enlarging nodules Cx from bx positive for Legionella → levofloxacin, samples sent to health department → L. micdadei

18. Legionella urine antigen testing Allows for early dx of atypical infection → timely abx therapy Typically allows for detection at time of presentation CAP guidelines include tx for atypical infections ELISA for detecting L. pneumophila serogroup 1 Potential ability to cross-react w/ other L. pneumophila serogroups or other Legionella species Specificity > 99%, sensitivity 70-100% Advantages - ease of collection, ability to obtain large volume of specimen for concentration, ability to detect antigen after abx, obtain results quickly Unable to qualify relapse or re-infection d/t persistence of antigen excretion

19. Take home points Important to consider as part of differential when immunocompromised patient presents w/ pulmonary nodule (or cavitary, AFB+) and sxs consistent w/ infection Understand the shortfalls of LPUAT, - ve result potentially to be re-evaluated given clinical context and should not be relied upon exclusively Consideration of further evaluation in outbreak situations w/ environmental risk factors and appropriate clinical context

20. Patient outcome Oxygen weaned to RA, no O2 requirements on walk test, symptoms resolved, returned to subjective baseline health Discharged home to complete 2 week course of azithromycin No recurrence or hospitalizations since

21. Thank you!

22. References Case Records of the Massachusetts General Hospital (Case 27–1976).  N Engl J Med  295:34–42, 1976 Case Records of the Massachusetts General Hospital (Case 42–1978).  N Engl J Med  299:939–946, 1978 Dionne, M., Hatchette, T., & Forward, K. (2003). Clinical utility of a legionella pneumophila urinary antigen test in a large University Teaching Hospital. Canadian Journal of Infectious Diseases and Medical Microbiology , 14 (2), 85–88. https://doi.org/10.1155/2003/642159 Fields, B. S., Haupt, T., Davis, J. P., Arduino, M. J., Miller, P. H., & Butler, J. C. (2001). Pontiac fever due to legionella micdadei from a whirlpool spa: Possible role of bacterial endotoxin. The Journal of Infectious Diseases , 184 (10), 1289–1292. https://doi.org/10.1086/324211 Kashuba, A. D. M., & Ballow, C. H. (1996). Legionella urinary antigen testing: Potential impact on diagnosis and antibiotic therapy. Diagnostic Microbiology and Infectious Disease , 24 (3), 129–139. https://doi.org/10.1016/0732-8893(96)00010-7 Knirsch, C. A., Jakob, K., Schoonmaker, D., Kiehlbauch, J. A., Wong, S. J., Della-Latta, P., Whittier, S., Layton, M., & Scully, B. (2000). An outbreak of legionella micdadei pneumonia in transplant patients: Evaluation, Molecular Epidemiology, and Control. The American Journal of Medicine , 108 (4), 290–295. https://doi.org/10.1016/s0002-9343(99)00459-3 Lachant, D., & Prasad, P. (2015). legionella micdadei : A forgotten etiology of growing cavitary nodules: A case report and literature review. Case Reports in Pulmonology , 2015 , 1–3. https://doi.org/10.1155/2015/535012 Pasculle AW, Myerowitz RL, Rinaldo CR Jr: New bacterial agent of pneumonia isolated from renal-transplant recipients.  Lancet  2:58–61, 1979 Richard L. Myerowitz, M.D., A. William Pasculle, Sc.D., John N. Dowling, M.D., George J. Pazin, M.D., Sr. Marion Puerzer, M.S., Robert B. Yee, Ph.D., Charles R. Rinaldo, Jr., Ph.D., and Thomas R. Hakala, M.D. Opportunistic Lung Infection Due to “Pittsburgh Pneumonia Agent”, N Engl J Med 1979;301:953-958, DOI: 10.1056/NEJM1979110130118 Waldron, P. R., Martin, B. A., & Ho, D. Y. (2015). Mistaken identity: legionella micdadei appearing as acid‐fast bacilli on lung biopsy of a hematopoietic stem cell transplant patient. Transplant Infectious Disease , 17 (1), 89–93. https://doi.org/10.1111/tid.12334