AIDS CLINICAL ROUNDSThe UC San Diego AntiViral Research Center sponsors weeklypresentations by infectious disease clinicia...
 DC is a 37yo with a h/o AIDS, (CD4= 6, VL = 527,104 1/11)  who presented with 1 mo h/o fever and cough     Cough p/o gr...
 Teeth have been falling out for the past 3 mo + weight loss – d/t poor dentition & anorexia ROS: Poor historian     N...
 PMHx: AIDS     PCP     Hepatitis C     Neurosyphilis     Thrombocytopenia – ITP vs myelosuppression d/t etoh     Pa...
 Meds: ARVs – can’t remember names – hasn’t been taking  them SHx:     Tob: 1PPD     Drugs: smokes meth – last used ~ ...
103 116              99/60 28 93% RA Cachetic Horrible dentition; white plaques c/w candida Coarse rhonchi heard throug...
Labs WBC 7.1     S86     B11    L1 H/H = 9.9/29.4      MCV = 84 Plt = 217 NA 129; K 3.4       BUN 7; Cr 0.59 AG = 5 A...
CXR
Hosp Course Started on Vanc/Zosyn, TMP/SMP Fluconazole 100mg for thrush Admitted to resp isolation Crag, Cocci, urine ...
Chest CT Multifocal consolidation predominantly in the upper lobes &  LLL. There are multiple areas of cavitation within...
Chest CT
Ddx?
Cavitary Lung Disease in HIV+ pts 3 studies – Spain, USA, Taiwan Cavity definition: a gas containing space within the lu...
Cavitary Lung disease in HIV+:             Spain 1998 78 cases of cavitation in 73 pts with HIV admitted from  1/89-12/94...
Cavitary Lung Dis in HIV+ pts              Spain ‘98 Pathogens:   Fungi – 15 cases (19%)     PCP (11), Crypto (2), Aspe...
Cavitary Lung Disease in HIV+ pts            USA ’01 Miami Reviewed chest CTs April ‘96 – March ‘98 25 patients 20 wit...
Cavitary Lung Disease in HIV+ Pts            USA ‘01 Pathogens:   Fungi - 4 cases (16%)      Candida (2), Aspergillus (...
Cavitary Lung Dis in HIV+ pts               Taiwan ‘09 Time Period June ‘94 – March ‘08 Open Cohort study 66 pts with 7...
Cavitary Lung Dis in HIV+ pts           Taiwan ‘09 81(!) pathogens found   Fungi - 34 cases (42%)     Penicillium marne...
Cavitary Lung Dis in HIV+ pts             Taiwan ‘09 15% were polymicrobial   Penicillium + PCP   Pseudomonas + MAC   ...
Updated Labs/Course AFB smear negative x 3 Modified AFB negative Crag, Cocci, histo negative Quantiferon negative Spu...
 Maintained on vanc (pip/tazo d/c’d after 3 days) Cough and SOB improve significantly Defervesces w/in 24 hours
MRSA Pneumonia Risk Factors
Bronch Procedure unremarkable BAL cultures:     Heavy MRSA     AFB smears/culture negative     Cytology negative for ...
Dx of invasive fungal infections Proven: fungal elements detected by histological analysis  or culture of tissue from dis...
Dx of invasive fungal infections Probable and possible depend on 3 criteria:   Host factors      Immunosuppression   C...
Galactomannan Galactomannan (GM) is a fungal antigen produced by  Aspergillus during its growth GM is a validated criter...
False + GM in serum & BAL Intubated pts who did not meet diagnostic criteria for IA  (proven, probable or possible)   73...
Really a false +? Pip/tazo seems to be no longer responsible for false-positive  results in Journal of Antimicrobial Chem...
(1-3) β-D-glucan A major component of the cell wall of most fungal species  except cryptococcus and zygomycetes Levels a...
β-D-glucan: False Positives Hemodialysis – cellulose membranes contain BG IVIG, albumin or other commercial blood compon...
Transbronchial biopsy Path   No Atypical or Malignant cells   Respiratory mucosa and alveolar tissue with acute and    ...
Comment
Comment
Cryptococcus & GM Glucuronoxylomannan in crypto   90% of capsular mass   Governs serotype   Prominent virulence factor...
GM in pts with Crypto &          Penicillium marneffei Tested serum samples from 48 HIV+ pts for GM   15 with penicillio...
Hosp course cont’d Serum Crag negative on 6/3 and 6/12 CSF Crag negative Serum GM negative 6 days after last dose of pi...
Post CXR
Serum Crag Latex particles covered with anti-cryptococcal globulin Latex reacts with the antigen, causing visible  agglu...
Serum Crag Sensitivity ranges from 83-97% in pts with cx+ disease Sensitivity = 82% in pulmonary disease Specificity ra...
Pulmonary Cryptococcosis 25-55% of cryptococcal meningitis has pulm involvement Clinical manifestations:   Asymptomatic...
Crypto Radiography: Non-AIDS Solitary or multiple pulmonary nodules – 60-80%   Size varies   Appearance varies: smooth ...
Crypto: Radiography - AIDS Diffuse interstitial infiltrates Ground glass opacities Lobar, often mass-like infiltrates ...
After the fact β-D glucan + at 88pg/ml (drawn 8 days after last dose of  Pip/tazo) 6/09 Crag 1:4 at San Ysidro CSF nega...
The End
An Unusual Case of Pneumonia
An Unusual Case of Pneumonia
An Unusual Case of Pneumonia
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An Unusual Case of Pneumonia

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Jennifer N. Blanchard, MD of UC San Diego Owen Clinic presents "An Unusual Case of Pneumonia"

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An Unusual Case of Pneumonia

  1. 1. AIDS CLINICAL ROUNDSThe UC San Diego AntiViral Research Center sponsors weeklypresentations by infectious disease clinicians, physicians andresearchers. The goal of these presentations is to provide the mostcurrent research, clinical practices and trends in HIV, HBV, HCV, TBand other infectious diseases of global significance.The slides from the AIDS Clinical Rounds presentation that you areabout to view are intended for the educational purposes of ouraudience. They may not be used for other purposes without thepresenter’s express permission.
  2. 2.  DC is a 37yo with a h/o AIDS, (CD4= 6, VL = 527,104 1/11) who presented with 1 mo h/o fever and cough  Cough p/o green and black sputum; occ hemoptysis  Pleuritic CP  Dyspnea  F/C/NS  All sx similar to admissions in 4/09 and 1/11  Bronch – silver stain negative, AFB negative. MTD PCR negative  Quantiferon, Crag, cocci, & histo negative  Responded as if CAP
  3. 3.  Teeth have been falling out for the past 3 mo + weight loss – d/t poor dentition & anorexia ROS: Poor historian  No HA or photophobia  Vision is “fair”  No odynophagia  No N/V/D  +Abd pain  Poor memory – fell out of care b/c he couldn’t remember to make appointments
  4. 4.  PMHx: AIDS  PCP  Hepatitis C  Neurosyphilis  Thrombocytopenia – ITP vs myelosuppression d/t etoh  Pancytopenia  BMbx 4/09 unremarkable  Alcohol abuse  Meth abuse  Non-compliance NKDA
  5. 5.  Meds: ARVs – can’t remember names – hasn’t been taking them SHx:  Tob: 1PPD  Drugs: smokes meth – last used ~ 2 weeks ago  No etoh  Not currently sexually active  Lives in Rosarito with his mom and step-father
  6. 6. 103 116 99/60 28 93% RA Cachetic Horrible dentition; white plaques c/w candida Coarse rhonchi heard throughout with ? Of rales at the L base No supraclavicular or axillary LAD Tachy but no M Soft, NT, ND, NABS; no HSM No rash
  7. 7. Labs WBC 7.1 S86 B11 L1 H/H = 9.9/29.4 MCV = 84 Plt = 217 NA 129; K 3.4 BUN 7; Cr 0.59 AG = 5 Alb = 2.6 SGOT/SGPT = 148/60 LDH = 232 7.52/29/122 on RA
  8. 8. CXR
  9. 9. Hosp Course Started on Vanc/Zosyn, TMP/SMP Fluconazole 100mg for thrush Admitted to resp isolation Crag, Cocci, urine histo sent  Of note, all previously negative 4/09 and 1/11;  CSF Crag negative 6/09
  10. 10. Chest CT Multifocal consolidation predominantly in the upper lobes & LLL. There are multiple areas of cavitation within the consolidation. The LUL consolidation may invade the anterior chest wall. There are multiple micronodules, some with tree-in-bud configuration Background of moderate centrilobular emphysema L pleural effusion Multiple enlarged mediastinal and hilar lymph nodes
  11. 11. Chest CT
  12. 12. Ddx?
  13. 13. Cavitary Lung Disease in HIV+ pts 3 studies – Spain, USA, Taiwan Cavity definition: a gas containing space within the lung surrounded by a wall of at least 1mm & >1cm Pts with bacterial causes had higher CD4 counts Pts with nonbacterial causes had lower CD4 counts Mycobacteria accounted for 25-30% of the disease at all sites No malignancies identified
  14. 14. Cavitary Lung disease in HIV+: Spain 1998 78 cases of cavitation in 73 pts with HIV admitted from 1/89-12/94  31 pts with unilobar cavity; 47 with multilobar  Multiple cavities in 40 cases and solitary in 38  7 cases (9%) d/t endocarditis  93% of pts were IDUs  Median CD4 = 30 (10-560)
  15. 15. Cavitary Lung Dis in HIV+ pts Spain ‘98 Pathogens:  Fungi – 15 cases (19%)  PCP (11), Crypto (2), Aspergillus (2)  Bacteria – 33 cases (42%)  Staph (14), Pseudomonas (13), Rohodococcus (6), anaerobes (5)  Salmonella (3), Strep pneumo (2), Strep milleri (1)  Mycobacteria 23 cases (30%)  TB (22), M. kansasii (1)
  16. 16. Cavitary Lung Disease in HIV+ pts USA ’01 Miami Reviewed chest CTs April ‘96 – March ‘98 25 patients 20 with definitive diagnoses Median CD4 = 106 (2-934) No comment on HIV risk factor
  17. 17. Cavitary Lung Disease in HIV+ Pts USA ‘01 Pathogens:  Fungi - 4 cases (16%)  Candida (2), Aspergillus (1), PCP (1)  Bacteria – 17 cases (68%)  Staph Aureus (5), Pseudomonas (5), Klebsiella (4), Nocardia (3),  Enterobacter (2), E. Coli (2), Rhodococcus (1)  Mycobacteria – 8 cases (32%)  TB (4), MAI (3), M. kansasii (1), M. fortuitum (1)  Viruses – 3 cases (12%)  CMV Polymicrobial in 17 pts (85%)
  18. 18. Cavitary Lung Dis in HIV+ pts Taiwan ‘09 Time Period June ‘94 – March ‘08 Open Cohort study 66 pts with 73 episodes of cavitary lung disease out of 1790 pts (3.7%)  Median CD4 = 25 (1-575)  95% had AIDS  10% IDUs  70% naïve to ARVs  1 case possibly d/t IRIS
  19. 19. Cavitary Lung Dis in HIV+ pts Taiwan ‘09 81(!) pathogens found  Fungi - 34 cases (42%)  Penicillium marneffei (19), Cryptococcus neoformans (11)  PCP (2), Aspergillus (2)  Bacteria - 24 cases (30%)  SA (7), Rhodococcus (6), Pseudomonas (4)  Strep Pneumo (3), Klebsiella (2), Nocardia (1)  Mycobacteria - 21 cases (26%)  TB (11), MAC (9), kansasii (1)  CMV 2%
  20. 20. Cavitary Lung Dis in HIV+ pts Taiwan ‘09 15% were polymicrobial  Penicillium + PCP  Pseudomonas + MAC  Pseudomonas + PCP Propensity to cavitate by bug  11/205 (5.4%) of TB  19/36 (53%) of P. marneffi  11/64 (17%) of crypto
  21. 21. Updated Labs/Course AFB smear negative x 3 Modified AFB negative Crag, Cocci, histo negative Quantiferon negative Sputum growing MRSA Blood cultures negative TTE: normal valves; no e/o vegetation
  22. 22.  Maintained on vanc (pip/tazo d/c’d after 3 days) Cough and SOB improve significantly Defervesces w/in 24 hours
  23. 23. MRSA Pneumonia Risk Factors
  24. 24. Bronch Procedure unremarkable BAL cultures:  Heavy MRSA  AFB smears/culture negative  Cytology negative for PCP  CMV Shell Vial culture negative  Aspergillus Galactomannan + Start vori?
  25. 25. Dx of invasive fungal infections Proven: fungal elements detected by histological analysis or culture of tissue from diseased tissue Probable - host factor & clinical criterion & mycological criterion Possible - host factor & clinical criterion but no mycological criteria
  26. 26. Dx of invasive fungal infections Probable and possible depend on 3 criteria:  Host factors  Immunosuppression  Clinical manifestations  Findings on imaging +/- exam findings  Mycological evidence  Direct test (cytology, direct microscopy or culture)  Indirect test (detection of antigen or cell wall constituents)  Aspergillus Galactomannan (GM) in blood, BAL or CSF  β-D-glucan in serum for diseases other than crypto or zygomycosis
  27. 27. Galactomannan Galactomannan (GM) is a fungal antigen produced by Aspergillus during its growth GM is a validated criterion for the diagnosis of probable invasive aspergillosis in immunocompromised pts Several studies have demonstrated false + serum GM in pts on pip/tazo in ‘03-’04  Pip/tazo itself has GM in it 1 study demonstrated false + GM in both serum and BAL
  28. 28. False + GM in serum & BAL Intubated pts who did not meet diagnostic criteria for IA (proven, probable or possible)  73 pts on at least 1 abx for at least 3 days  14 pts not on abx False + GM in serum:  Pip/Tazo, AMP/CLA  Cefipime, cefoperazone/sulbactam False + GM in BAL:  Pip/tazo, AMP/CLA  Ceftriaxone & cefipime
  29. 29. Really a false +? Pip/tazo seems to be no longer responsible for false-positive results in Journal of Antimicrobial Chemotherapy, 4/12 10/09-10/10  Pip/tazo manufactured by Pfizer  Tested serum from HSCT pts both off & on pip/tazo  25/1606 (1.6%) drawn in the absence of pip/tazo tested +  10/394 (2.5%) while on pip/tazo tested +  90 vials from 30 randomly selected batches tested negative UCSD uses pip/tazo manufactured by Baxter for Wyeth Studies suggest repeating test at least 5 days after last dose
  30. 30. (1-3) β-D-glucan A major component of the cell wall of most fungal species except cryptococcus and zygomycetes Levels are elevated in blood with systemic infections Consistently negative levels in pts with mucosal candidiasis but no systemic disease Sensitive marker of PCP More sensitive than GM in pts with invasive aspergillosis
  31. 31. β-D-glucan: False Positives Hemodialysis – cellulose membranes contain BG IVIG, albumin or other commercial blood components  BG is released from cellulose filters used during the manufacturing process Gauze used intraoperatively (see false + in the first 3 days after surgery) Antibiotics:  Pip/tazo  Cefazolin, SMP/TMZ, cefotaxime, cefepime, amp/sul – all + at reconstituted vial concentrations but not when diluted to usual plasma concentrations
  32. 32. Transbronchial biopsy Path  No Atypical or Malignant cells  Respiratory mucosa and alveolar tissue with acute and chronic inflammation, edema, and fibrosis, see comment
  33. 33. Comment
  34. 34. Comment
  35. 35. Cryptococcus & GM Glucuronoxylomannan in crypto  90% of capsular mass  Governs serotype  Prominent virulence factor Galactoxylomannan – the OTHER polysaccharide  7% of the capsular mass Galactoxylomannan cross reacts with GM assays
  36. 36. GM in pts with Crypto & Penicillium marneffei Tested serum samples from 48 HIV+ pts for GM  15 with penicilliosis – 73% had OD >0.5  22 with crypto – 14% had OD >0.5  11 w/o fungal infection – 9% had OD >0.5 No pts with aspergillus or on PIP/tazo or amox/clav GM strongly + for penicilliosis pts  OD range 0.16 - >20, median = 4.4 + for crypto  OD range 0.11-3.8; median 0.25
  37. 37. Hosp course cont’d Serum Crag negative on 6/3 and 6/12 CSF Crag negative Serum GM negative 6 days after last dose of pip/tazo Treated with fluconazole 400mg bid Treated with vanc for 6-8 weeks Lung biopsy by IR non-diagnostic; cx negative TEE negative
  38. 38. Post CXR
  39. 39. Serum Crag Latex particles covered with anti-cryptococcal globulin Latex reacts with the antigen, causing visible agglutination Pronase, a proteolytic enzyme, reduces the number of false + tests by eliminating nonspecific interference w/ globulins (such as RF and other immune complexes which could cause false +) False negative rarely reported (none since ‘96) False + with trichosporonosis
  40. 40. Serum Crag Sensitivity ranges from 83-97% in pts with cx+ disease Sensitivity = 82% in pulmonary disease Specificity ranges from 93-100% Animal studies:  Low titers or negative titers in pulmonary infection that has not disseminated  High titers seen in mice with pulmonary infection that has disseminated  Intratracheal administration of crypto did not result in measurable levels
  41. 41. Pulmonary Cryptococcosis 25-55% of cryptococcal meningitis has pulm involvement Clinical manifestations:  Asymptomatic colonization to severe pneumonia/resp failure  Typically:  Cough, dyspnea, hemoptysis, chest pain  Fever, weight loss, night sweats  Onset:  Weeks to months in immunocompetent  Subacute to rapidly progressive in immunocompromised
  42. 42. Crypto Radiography: Non-AIDS Solitary or multiple pulmonary nodules – 60-80%  Size varies  Appearance varies: smooth to spiculated  Peripheral predominance Focal or multifocal consolidation - 10-30%
  43. 43. Crypto: Radiography - AIDS Diffuse interstitial infiltrates Ground glass opacities Lobar, often mass-like infiltrates Pulmonary nodules; diffuse reticulonodular opacities Mediastinal and hilar lymphadenopathy Cavitation in only 10-15% of cases Infiltrates or effusion often ass’d with disseminated disease
  44. 44. After the fact β-D glucan + at 88pg/ml (drawn 8 days after last dose of Pip/tazo) 6/09 Crag 1:4 at San Ysidro CSF negative with nl chemistries & cell counts 7/09 treated with flucon 800mg qday 8/09 Crag 1:8; flucon decreased to 400mg qday Notes after that say Crag negative
  45. 45. The End

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