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Infections in the 
Immunocompromised: 
the Wild West 
Jade Le, MD 
Assistant Professor, Infectious Diseases 
November 6, 2014
Wild Wild West… 
MD 
Bacteria 
Parasite 
Fungus 
MD 
Virus
Infections in the 
Immunocompromised 
Immune Deficit? 
Meds, GVHD, s/p splenectomy, s/p 
transplant, 
hypogammaglobulinemic, T cell 
deficiencies? 
Exposure 
community vs. nosocomial 
Prophylaxis: yes/no
Underlying Immune Defects 
Determines Risk of Infection 
Humoral 
• Encapsulated bacteria 
• S. Pneumo 
• H. Influenza 
• N. meningitidis 
• Capnocytophaga canimorsus 
• Bordetella holmesii 
• Parasites 
• Giardia 
• Cryptosporidia 
• Salmonella 
• Campylobacter 
Cell-mediated 
• Intracellular pathogens 
• Mycobacteria 
• Legionella 
• Listeria 
• Nocardia 
• Strongyloides 
• Fungi 
• Histoplasma 
• Cryptococcus 
• Candida 
• Molds: Aspergillus, Mucor 
• Pneumocystis 
• Viruses 
• Herpes viruses: CMV, EBV, HSV, VZV, 
HHV6
Levels of Immunosuppression & 
Risk of Infections 
High level 
• Primary combined 
immunodeficiency 
• Receiving cancer chemotherapy 
• Within 2 months after solid 
organ transplantation 
• HIV with CD4 <200 
• Daily corticosteroid therapy with 
dose ≥20mg or prednisone or 
equivalent for ≥ 14 days 
• Receiving certain biologic 
immune modulators- tumor 
necrosis factor-alpha (TNF-α) 
blocker or rituximab 
Low level 
• Asymptomatic HIV with CD4 ≥200 
• Lower daily dose of systemic 
corticosteroids 
• Methotrexate ≤0.4mg/kg/week; 
azathioprine ≤3mg/kg/day, or 6- 
mercaptopurine ≤1.5mg/kg/day 
Rubin et al, CID 2013: 1-57.
Biologics Affect Different Targets 
Salvana. Clin Micro Rev. 2009,22(2):274
Risk of Infection According to 
Biologic Agent 
INCREASED RISK (meta-analysis, RCT) 
Adalimumab, Infliximab, Certolizumab, Etanernept, Abatacept, 
Anakinra, Rilonacept, Efalizumab, Alemtuzumab, Y-ibritumomab, 
Rituximab, I-tositumomab, Gemtuzumab, Bevacizumab, Cetuximab, 
Panitumumab, Trastuzumab, Natalizumab 
PROBABLE RISK (post hoc phase III RCT) 
Alefacept, Basiliximab, Daclizumab, 
Muromonab 
POSSIBLE RISK (case reports) 
Abciximab 
Omalizumab, 
Palivizumab 
Salvana. Clin Micro Rev. 2009,22(2):274
Risk of Infection and 
Transplanted Organ 
Bacteremias Deep fungal infections 
Liver 
Lung, 
Heart-lung 
Kidney 
Lung, Heart-lung 
Liver 
Kidney 
Mortality rate from 
infections 
Lung, Heart-lung 
Liver 
Kidney
Graft-versus host disease and 
risk of infections 
Mucositis 
GVHD 
Functional 
hyposplenism 
Prophylactic 
immuno-suppressants 
Treatment with 
high-dose 
steroids or 
immuno-suppressants 
Altered 
humoral/cellular 
immunity 
GVHD is the most 
important cause 
of mortality after 
HCT
Exposures and Risk of 
Infection 
• Travel 
• Africa, SE Asia: Malaria 
• SE Asia: Penicillium 
marneffei, Burkholderia 
pseudomallei 
• Midwest: Blastomycosis, 
Histoplamosis 
• Southwest: 
Coccidioidomycosis 
• Gardening/Construction/ 
Pets/Well water 
• Aspergillus, molds 
• Nocardia 
• Capnocytophaga 
• Giardia 
• Cryptosporidium 
• Healthcare-acquired 
• C difficile 
• MRSA 
• Prior exposures – 
reactivation: 
• Toxoplasma 
• Chagas 
• CMV 
• VZV 
• Strongyloides 
• M. Tuberculosis 
• Donor-derived 
• WNV 
• Rabies
Donor-derived infections 
• Pyogenic bacteria 
• Trypanosoma cruzi 
• Hepatitis C virus 
• HIV 
• West Nile Virus 
• Lymphocytic choriomeningitis virus (LCMV) 
• Legionella 
• Histoplasma capsulatum 
• Candida spp. 
• Strongyloides stercoralis 
• Cryptococcus neoformans 
• Schistosoma spp. 
• Toxoplasma gondii 
• Mycobacterium tuberculosis 
• Rabies virus
Changing Timeline of Infection 
after Organ Transplantation 
Fishman JA. N Engl J Med 2007;357:2601-2614.
Post HSCT risk periods for 
infection
Case #1: 
• HPI: 41 HF with h/o Rheumatoid Arthritis on Enbrel 
 Humira x 4 years presents with: 
• 15 day h/o fever & intermittent headaches 
• Non-productive cough, night sweats 
• 9lb wt loss in 2-3 weeks 
• Labs: 2.0>--------<144 (77%PMNs) 
32.5 
• CSF: 100RBCs, 274 WBCs (94%L), glucose 14, 
protein 198
Case # 1: CT chest
Case # 1: MRI brain
Case #1: What is your 
diagnosis? 
• A) Pneumococcal meningitis 
• B) TB meningitis 
• C) Histoplasma meningoencephalitis 
• D) Nocardia pulmonary disease with brain 
abscess
Risk of TB Activation According to Level of 
Immune Compromise 
Risk of 
activation 
per year 
Normal host 0.1% 
Hemodialysis 1-2% 
Solid organ 
5-6% 
transplant 
HIV/AIDS 10% 
Positive TST in HIV = > 5mm
TUBERCULIN SKIN TEST RESULTS 
INTERPRETATION 
≥ 5mm ≥ 10mm ≥ 15mm 
HIV infection 
Close contact 
Abnormal CXR 
Immunosuppressed: 
TNF-alpha inhibitors, 
chemotherapy, 
organ transplant, 
glucocorticoid 
treatment 
Risk factors for reactivation: 
silicosis, HD, DM, malignancies 
(leukemia, lymphoma, 
head/neck/lung cancer), 
underweight, jejunoileal bypass, 
IVDA 
Children < 4 
Foreign born from high-risk 
countries 
Residents/employees in high-risk 
settings: prisons, jails, healthcare 
facilities, mycobacteriology labs, 
homeless shelters 
Healthy persons 
with low likelihood 
of true TB infection
TSTin3d.com 
TB risk 
calculator
Corticosteroids and TB 
≥15mg prednisone ≥1 month are at increased risk 
for TB reactivation (but exact risk unknown) 
Am J Respir Crit Care Med. 2000;161(4 Pt 2):S221 
• Arthritis Rheum. 2006;55(1):19 
Arthritis Rheum. 2006;55(1):19
IFX or ADA Associated with Increased Risk of TB 
compared to ETN 
Study Country Results demonstrating risk of active TB 
Brassard. CID. 2006 Canada ETN <<<< IFX (by 1.3x) 
Gomez-Reino. Arthritis 
Rheum. 2006 
Spain No diff btw the 3 groups risk active TB, but 
ETN <<<< IFX (by 2x) 
Tubach. Arthritis Rheum. 
2009 
France ETN SIR 1.8<<<IFX SIR 18.6<<< ADA SIR 29.3 
(SIR = standardized incidence ratio) 
Fonseca. Acta Reumatol 
Port. 2006 
Portugal ETN <<<< IFN or ADA (3-4x) 
Dixon. Ann Rheum Dis. 2010 UK ETN<<<<IFN or ADA (3-4x)
TB Risk Factors in Patients on TNF 
Antagonists 
Tubach et al. Arthritis & Rheum. 2009
TNF is Needed to Create 
Granulomas 
A)TNF from macrophage 
co-stimulates T cells 
B)TNF from T cells primes 
macrophages for 
mycobactericidal 
activity 
C)Macrophage and T cell 
TNF recruit monocytes 
and promote 
granuloma formation 
D)Anti-TNF results in 
granuloma breakdown 
an dissemination of TB 
Solovic et al. Eur Resp J. 2010
When to Screen for TB? 
• Prior to initiation of any immune suppressant: 
• Steroids > 10mg po q day 
• Methotrexate 
• Cyclosporine 
• Azathioprine 
• Leflunomide 
• Cyclophosphamide 
• Plus prior to initiation of any TNF antagonist 
• Yearly while on TNF antagonist in high TB endemic areas 
• Every 3 months while on TNF antagonist therapy for those 
who have completed treatment for TB (BTSSCC. Thorax. 2005) 
Fonseca et al. Acta Reumatol Port. 2006
When Is It Safe to Resume 
Biologics? 
Guidelines Latent TB Active TB 
France > 3 weeks of prophylaxis > 2 months after completion of TB treatment, 
but recommend prophylaxis while on TNF 
antagonists after completion of therapy 
Germany >1-2 months of prophylaxis 
Ireland As long as possible after starting 
prophylaxis 
On completion of TB treatment 
Portugal >1 month of prophylaxis > 2 months on TB treatment 
Spain 1 month, but may consider days after 
starting prophy 
Switzerland 1 month after completion of prophylaxis 
UK Abnl CXR  after completion of 
prophylaxis 
Nl CXR  start concurrently 
> 2 months on TB treatment 
USA Preferably complete prophylaxis Preferably complete TB treatment 
TBNET > 4 weeks after initiation of prophylaxis Preferably complete TB treatment 
Solovic. Eur Resp J. 2010, Doherty. J Am Acad Derm. 2008,
Case #2: 
Courtesy Bonnie Prokesch
Case #2: 
• 56 yo WM Veterinarian with fevers to 102-105, nightsweats, 
fatigue, 10lb weight loss x 2 months 
• No other localizing symptoms 
• Labs: 
• 14.6 
3.4>--------<69 (N 72%) ferritin 766
Case # 2: CT A/P 
Courtesy Bonnie Prokesch
Case #2 CT chest 
Courtesy Bonnie Prokesch
Case #2 H&E LN aspirate 
Courtesy Bonnie Prokesch
Case #2: GMS stain 
Courtesy Bonnie Prokesch
Case #2: What is your 
diagnosis? 
• A) Disseminated candidiasis 
• B) Blastomycosis 
• C) Mycobacterium avium intracellulare 
• D) Disseminated Histoplasmosis
Histoplasmosis capsulatum var. 
capsulatum 
www.mycology.adelaide.edu.au 
pathmicro.med.sc.edu/mycology 
Courtesy Francesca Lee
Histoplasma and 
Immunocompromised 
• Histoplasma – 
• Most commonly 
reported- “classic 
intracellular pathogen”- 
contained primarily by 
cell-mediated immunity 
• No data re prophylaxis 
or routine screening 
• Avoid high risk 
activities-construction, 
spelunking 
• Incidence of 
histoplasmosis 
• 18.78 per 100,000 
persons for infliximab 
• 2.65 per 100,000 
persons for etanercept 
Drugs 2009 Jul 30;69(11):1403-15.
Case #3 
• 24 year old WM with B-ALL s/p FLAG-IDA with prolonged 
neutropenia with neutropenic fevers and R sided pleuritic CP.
Case # 3: What is your 
diagnosis? 
• A) Nocardia 
• B) Pulmonary aspergillosis 
• C) Mycobacterium tuberculosis 
• D) Legionella
Aspergillus 
• Ubiquitous mold 
• Most common invasive 
fungal infection (48%) –25% 
survival per TRANSNET 
• Risk: chronic GVHD, older, 
construction, lymphopenia, 
CMV, respiratory virus, 
multiple myeloma 
• Diagnosis: fungal culture, 
galactomannan assay, PCR? 
• CXR/CT findings: “Halo 
sign”, air-crescent sign
Case # 3: CT chest after one 
month treatment
Invasive Aspergillosis in AML 
Patients 
Prolonged neutropenia is 
a risk factor for invasive 
aspergillosis 
No significant difference 
amongst L-AmB, Caspo, 
and Vori 
Pagano. Haematologica. 2010
Improved Survival in Voriconazole-treated 
Patients with Invasive Aspergillosis 
Herbrecht et al. NEJM.2002
Case #4 
• 45 year old HF with RA s/p MTX/Enbrel 2009, later diagnosed 
with ALL s/p HyperCVA 1A-4B with relapse s/p re-induction 
chemotherapy with prolonged neutropenia who has the 
following physical exam: 
Courtesy Miloni Shroff
Case #4 
Courtesy Miloni Shroff
Case # 4: What is your 
diagnosis? 
• Blood cultures + mold 
• Skin biopsy + narrow-branching fungal elements within vessel 
walls 
• A) Aspergillus 
• B) Mucormycosis 
• C) Fusarium 
• D) Nocardia
Case #4: Skin lesions during 
treatment 
Courtesy Miloni Shroff
Case #4: Skin lesions weeks 
into treatment 
Courtesy Miloni Shroff
Case #5 
• 36 year old HM with ALL, s/p induction chemotherapy with 
prolonged neutropenia (1 month) with L sided chest 
pain/upper back pain. + weight loss, no fevers, no SOB. 
Former construction worker in Florida (15-17 years prior to 
diagnosis of ALL). Had been on prophylactic micafungin. 
0.2>-----<11 ANC 100 
20.1
Case #5 CT chest
Case #5: What is your 
diagnosis? 
• Endobronchial biopsy of lung nodule – “…numerous fungal 
hyphae characterized by broad hyphal elements with thin 
membranes, irregular branching, non-parallel walls…”, non-septated, 
“…focal areas of vascular invasion 
• What is your diagnosis? 
• A) Aspergillus 
• B) Cryptococcus 
• C) Coccidioidomycosis 
• D) Zygomycosis
Non-AspergillusMolds 
• Zygomycetes (8%), Fusarium & Scedosporium (16%), 
Acremonium, Paecilomyces 
• Clinical: 
• 6% survival with Fusarium, 28% with Mucormycosis 
• Diagnosis: Fungal blood culture (Fusarium), tissue biopsy cultures 
• RX: 
• Aggressive surgical debridement 
• Liposomal ambisome (5mg/kg/day  10mg/kg/day?) 
• Combination with azole? 
• Reduce immune suppression 
• ? GCSF 
• Control blood glucose Silveira. Med Mycol. 2007 
Hosseini-Moghaddam. Sem Resp Crit Care Med. 2010
Breakthrough Zygomycetes on 
Prophylactic Voriconazole in 
HSCT 
Trifilio. Bone Marrow Transplant. 2007 
•71 allo HSCT 
•Voriconazole 200mg po bid 
•6 Candida, 4 Zygomyces (3 lung, 1 sinus)
Probability of Zygomycosis/Invasive Fungal 
Infections at 1 year After Voriconazole 
Initiation 
7% 18% 
Trifilio. Bone Marrow Transplant. 2007
Case #6 
• 45 year old Vietnamese female with metastatic high grade 
pontine glioma with metastasis to the spine with 
leptomeningeal dissemination undergoing chemo/XRT, DM2, 
on dexamethasone 4mg po tid since 1/2013 (now 11/2013) 
admitted with acute hypoxemic respiratory failure. 
• Exam: + moon facies, 85% O2 sat on RA, tachy 120s 
• Lungs with coarse crackles B 
• Labs: 
12.2 
1.4>---------<61 Fungitell > 500 LDH 579
Case # 6: CXR
Case # 6: CT chest
Case # 6: What is your 
diagnosis? 
• A) Streptococcal pneumonia 
• B) Legionella pneumonia 
• C) Pneumocystis pneumonia 
• D) Mycobacterium tuberculosis
Pneumocystis jiroveci Risk factors 
• Defects in cell-mediate immunity 
• Steroids (> 20mg/day 
prednisone for > 1 month) 
with immune suppressants, 
TNF antagonists, 
alemtuzumab, fludarabine, T-cell 
depleting agent 
• Heme malignancy (ALL) 
• SOT: lung-heart >>renal 
• HSCT 
• Rheumatologic d/o 
(pyomyositis/dermatomyositis 
, Wegener’s) 
• Solid tumors, esp.. CNS 
• Primary immunodeficiencies 
• Risk factors in patients 
with autoimmune 
inflammatory 
disorders, or on 
systemic steroids: 
• Lymphopenia (< 600 
cells/mm3) 
• Steroid dose > 15mg 
prednisolone or 
equivalent/day 
• CD4 count < 200 
cells/mm3 
Sowden. BMC Infect Dis. 2004,4:42 
Courtesy Francesca Lee
Pneumocystis Diagnostic Tests 
Indirect tests 
• High A-a gradient 
• Decreased DLCO (< 70%) 
• Elevated LDH (90%) 
• Elevated fungitell 
(13)-β-D-glucan 
• Sensitivity 90-100% 
• Specificity 88-96% 
Direct tests 
Sens Spec 
Bronch with 
BAL 
90-98% 
Induced 
sputum DFA 
100% 55-92% 
Endotracheal 
aspirate 
92% 
PCR 81-100% 86-100% 
Note: decreased sensitivity BAL 
(62%) in patients s/p aerosolized 
pentamidine
Beta-D-glucan and Diagnosis of 
Pneumocystis 
Sax. Clin Infect Dis. 2011 
Positive: Candida, Aspergillus, Pneumocystis, NOT 
Zygomycetes or Cryptococcus 
False positive: augmentin, zosyn, S. pneumo, 
Pseudomonas, IVIG, albumin, HD, mucositis
Prophylaxis for PJP in 
immunocompromised patients 
• Cochrane review 2007 of 11 
RCTs evaluating prophylaxis 
with TMP/SMX vs. placebo or 
other antibiotics with no PCP 
activity: 
• Adults with acute leukemia or 
solid organ transplant; children 
with acute leukemia 
• No increased rate of adverse 
events 
• Number needed to treat to 
prevent one episode of PCP = 15 
• ATS 2010 Fungal Infections 
Guideline 
• Prednisone dose ≥ 
20mg/day >1 month, 
especially if patient has T 
cell defects, or has other 
cytotoxic drugs or TNF-a 
inhibitors 
Green. Cochrane Database Syst Rev. 2007 Jul 18;(3):CD005590 
Am J Respir Crit Care Med Vol 183. pp 96–128, 2011 
Rahier et al, Journal of Crohn's and Colitis (2009), p1-46 
Courtesy Francesca Lee
Steroid Potency Comparison
TMP-SMX vs. Aerosolized 
Pentamidine vs. Dapsone 
TMP-SMX 
Dapsone, 
atovaquone 
Aerosolized 
pentamidine 
> > 
Best tolerated 
No toxo coverage 
Screen for tb 
•Most effective 
•Covers toxo, salmonella, 
listeria, nocardia, strep, 
staph 
Less toxo coverage 
Check G6PD
Aerosolized pentamidine 
Upper lobe infiltrates 38% 
pentamidine vs.. 7% no 
pentamidine 
Jules-Elysee. Ann Int Med. 1990 
Levine et al. Am Rev Respir Dis. 1991
Case #7 
• 60 year old HM with DM, s/p DDKT 2007, admitted with 
abdominal pain, found to have skin nodules: 
Courtesy Suresh Kachhdiya
Case #7: CT chest
Case #7 
• Biopsy of skin nodule shows suppurative granulomatous 
inflammation with yeast forms + by PAS/GMS stain, mostly 
with narrow bases. 
• Crypto Antigen 1:64 Creatinine 2.5 
• What would you do next? 
A) Start Ambisome + flucytosine 
B) Start Fluconazole + flucytosine 
C) Start Posaconazole 
D) Start Itraconazole
• Risk factor: T cell defect (i.e. AIDS, SOT) 
• Calcineurin inhibitors 
• Alemtuzumab, antithymocyte 
• Clinical: asymptomatic, acute 
respiratory distress, pneumonia, 53- 
72% with disseminated disease in SOT 
• Radiography: nodules, lobar infiltrates, 
pleural effusions, 
• Diagnosis: culture, crypto antigen in 
blood positive in 56-70% 
• Treatment: 
• Amphotericin and 5-FC for severe 
cases 
• Fluconazole for mild cases and for 
long term maintenance 
• Watch out for immune 
reconstitution inflammatory 
syndrome (5-11%) 
• Mortality in SOT 14% 
Singh. Am J Transplant. 2009
Case #7…but wait… 
• He had abdominal pain and difficulty swallowing… 
• s/p EGD  esophagitis and gastric ulcer & duodenal stricture 
• Path: + duodenitis with + H. pylori and cells with viral 
inclusions  CMV duodenitis (CMV PCR detectable only) 
• Eventually also diagnosed with: 
• Enterobacter bacteremia 
• Candida glabrata endocarditis 
• EBV + in CSF
Case #8 
• 53 year old WF with ileocolonic Crohn’s disease s/p small 
bowel resection on imuran x 10 years and prednisone 20mg 
daily admitted with fevers, chills, and abdominal pain, bloody 
diarrhea, shortness of breath. 
• Exam: febrile to 101.7, tachycardic 
• Abdomen tender in upper epigastric region, + bowel sounds, no 
rebound 
• Labs: 
10 
• 1.1>-------<182 (ANC 800) AST 98 ALT 43
Case # 8: CT A/P
Case # 8: CT chest
Case # 8: What is your 
diagnosis? 
• A) Legionella Pneumonia 
• B) Mycobacterium tuberculosis 
• C) CMV colitis and pneumonitis 
• D) Adenovirus pneumonia and enteritis
Case #8: Results 
• CMV PCR 413,000 
• CMV + BAL and + lung biopsy 
• CMV + immunostain on flex sig 
• Initiated on ganciclovir and cytopenias resolved 
and abdominal pain/diarrhea/hypoxia resolved. 
• Also + C difficile
Cytomegalovirus- 
“Big Bad Wolf of SOT” 
• Risk: GVHD, lymphopenia, D+/R- 
• Immunomodulatory 
• Superinfections: PJP, Aspergillus, GNR, Listeria, 
Candida 
• Clinical: 
• pneumonitis 
• enteritis 
• bone marrow suppression 
• retinitis (rare) 
• Diagnosis: CMV PCR 
• NOTE GI disease often occurs WITHOUT CMV 
viremia 
• Prevention: CMV-safe transfusions 
• Treatment: ganciclovir, valganciclovir, CMV 
immune globulin
CMV Spectrum of Disease 
Immunocompetent 
• Mononucleosis-like 
syndrome 
Congenital 
• Ventriculitis/E 
ncephalitis 
• Hepatospleno 
megaly 
HIV 
• Retinitis 
• Ventriculitis 
• Myelitis 
• Polyradiculopa 
thy 
• Colitis/Esopha 
gitis 
Transplant 
• CMV 
syndrome 
• Colitis/Esopha 
gitis 
• Pneumonitis 
• Hepatitis 
Courtesy of Jason Gillman, MD
CMV and Solid Organ Transplant: 
Serostatus and Risk of Reactivation 
Rubin RH. TID. 2001 Courtesy J. Gillman
Case #9 
• 69 year old WM s/p R lung transplant 2/2013 presents 4 
months later with respiratory distress and UGIB.
Case #9:What is your diagnosis 
• s/p EGD with this 
found on biopsy and 
in the BAL fluid. 
1) Ascaris 
2) Strongyloides 
3) Schistosomiasis 
4) Toxoplasmosis
Strongyloides hyperinfection 
syndrome 
• Strongyloides stercoralis – helminth with 
autoinfection possibility 
• Risk factors: defects in cell-mediated 
immunity 
• Steroids, Calcineurin inhibitors, TNF 
antagonists 
• SOT 
• HSCT 
• Burn victims, alcoholics, DM 
• Hypogammaglobulinemia 
• HTLV-1 co-infection 
• AIDS 
• Clinical: fever, dyspnea, wheezing, 
hemoptysis, cough, diarrhea, 
nausea/vomiting, gram negative sepsis 
Balagopal et al. Transplant Infect Dis. 2009
Screening for Strongyloides? 
• “Experts estimate that there are between 3-100 million infected 
persons worldwide” 
• US- 0-6.1% of persons sampled 
• Immigrants to US- 0-46.1% of persons sampled 
• Risk factors: contact with soil 
• Walking with bare feet 
• Contact with human waste or sewage 
• Occupations that increase contact with contaminated soil, such as 
farming and coal mining 
http://www.cdc.gov/parasites/strongyloides/epi.html 
• Consider screening with serologic testing in “at risk” patients 
• Immigrants from Central and South America 
• If positive, treat with ivermectin prior to immunosuppression 
Curr Opin Infect Dis 2012, 25:458–463
Case #10 
• 58 year old WM with AML 
s/p allo SCT c/b GVHD, 
admitted with SOB with 
pleuritic CP, L buttock mass 
x 6 weeks after scraping his 
bottom on a yucca plant, 
and R axillary nodule 
• Exam: Afebrile, 95% on RA 
• L buttock wound s/p I&D 
with minimal erythema 
• R axillary mobile soft, NT, 
subcutaneous nodule 
• R thigh with soft 
erythematous nontender 
nodule
Case # 10: CT chest
Case #10: CT pelvis
Case #10: What is your 
diagnosis? 
• Culture from I&D of buttock abscess, R thigh and R 
axillary nodules + gram positive branching filamentous 
rods. 
• A) Mycobacterium abscessus 
• B) Stenotrophomonas maltophilia 
• C) Scedosporium 
• D) Nocardia
Case #10: What should you do if you 
diagnose a patient with pulmonary 
nocardia? 
• A) Start oral bactrim prophylaxis 
• B) Get MRI brain 
• C) Order nocardia serum PCR assay 
• D) Place in airborne isolation
Case #10: MRI brain
Nocardia 
• Gram-positive filamentous 
branching 
• Risk (2/3 immunocompromised): 
HIV/AIDS, glucocorticoids, 
malignancy (Heme, BMT), SOT, 
COPD, CGD, TNF-alpha, ETOH, TB 
• Clinical: pneumonia, pulmonary 
nodules, brain abscess 
• 39% Lung only 
• 32% with > 2 sites (44% + CNS) 
• Prophylaxis: TMP-SMX 
• Treatment: TMP-SMX, Imipenem, 
Amikacin, Ceftriaxone, Linezolid, 
Moxifloxacin, Minocycline
Case # 11 
• 35 year old white female with relapsed Hodgkin’s lymphoma 
s/p auto SCT 2012 c/b GVHD of gut, skin, and lungs and h/o 
CMV colitis who was admitted with pleuritic R sided CP with 
shortness of breath 
• Exam: afebrile, O2 sat 88% on 2LPM O2, tachypneic, 
tachycardic 
• Moon facies, dyspneic, decreased BS R> L, stable GVHD skin rash 
• Labs: 
• 17.4>-------<133 LDH 286 fungitell 210 
• 36.2 
• Resp PCR panel + rhinovirus/enterovirus
Case # 11: CXR
Case # 11: CT chest
Case # 11: CT chest
Case # 11: What is your 
diagnosis? 
• A) Zygomycete 
• B) Pneumocystis 
• C) Nocardia 
• D) Legionella
Wild, Wild West… 
You never know what to expect….
Wild Wild West… 
“Always drink upstream 
from the herd…” 
- Will Rogers

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Infections in Immunocompromised Pts

  • 1. Infections in the Immunocompromised: the Wild West Jade Le, MD Assistant Professor, Infectious Diseases November 6, 2014
  • 2. Wild Wild West… MD Bacteria Parasite Fungus MD Virus
  • 3. Infections in the Immunocompromised Immune Deficit? Meds, GVHD, s/p splenectomy, s/p transplant, hypogammaglobulinemic, T cell deficiencies? Exposure community vs. nosocomial Prophylaxis: yes/no
  • 4. Underlying Immune Defects Determines Risk of Infection Humoral • Encapsulated bacteria • S. Pneumo • H. Influenza • N. meningitidis • Capnocytophaga canimorsus • Bordetella holmesii • Parasites • Giardia • Cryptosporidia • Salmonella • Campylobacter Cell-mediated • Intracellular pathogens • Mycobacteria • Legionella • Listeria • Nocardia • Strongyloides • Fungi • Histoplasma • Cryptococcus • Candida • Molds: Aspergillus, Mucor • Pneumocystis • Viruses • Herpes viruses: CMV, EBV, HSV, VZV, HHV6
  • 5. Levels of Immunosuppression & Risk of Infections High level • Primary combined immunodeficiency • Receiving cancer chemotherapy • Within 2 months after solid organ transplantation • HIV with CD4 <200 • Daily corticosteroid therapy with dose ≥20mg or prednisone or equivalent for ≥ 14 days • Receiving certain biologic immune modulators- tumor necrosis factor-alpha (TNF-α) blocker or rituximab Low level • Asymptomatic HIV with CD4 ≥200 • Lower daily dose of systemic corticosteroids • Methotrexate ≤0.4mg/kg/week; azathioprine ≤3mg/kg/day, or 6- mercaptopurine ≤1.5mg/kg/day Rubin et al, CID 2013: 1-57.
  • 6. Biologics Affect Different Targets Salvana. Clin Micro Rev. 2009,22(2):274
  • 7. Risk of Infection According to Biologic Agent INCREASED RISK (meta-analysis, RCT) Adalimumab, Infliximab, Certolizumab, Etanernept, Abatacept, Anakinra, Rilonacept, Efalizumab, Alemtuzumab, Y-ibritumomab, Rituximab, I-tositumomab, Gemtuzumab, Bevacizumab, Cetuximab, Panitumumab, Trastuzumab, Natalizumab PROBABLE RISK (post hoc phase III RCT) Alefacept, Basiliximab, Daclizumab, Muromonab POSSIBLE RISK (case reports) Abciximab Omalizumab, Palivizumab Salvana. Clin Micro Rev. 2009,22(2):274
  • 8. Risk of Infection and Transplanted Organ Bacteremias Deep fungal infections Liver Lung, Heart-lung Kidney Lung, Heart-lung Liver Kidney Mortality rate from infections Lung, Heart-lung Liver Kidney
  • 9. Graft-versus host disease and risk of infections Mucositis GVHD Functional hyposplenism Prophylactic immuno-suppressants Treatment with high-dose steroids or immuno-suppressants Altered humoral/cellular immunity GVHD is the most important cause of mortality after HCT
  • 10. Exposures and Risk of Infection • Travel • Africa, SE Asia: Malaria • SE Asia: Penicillium marneffei, Burkholderia pseudomallei • Midwest: Blastomycosis, Histoplamosis • Southwest: Coccidioidomycosis • Gardening/Construction/ Pets/Well water • Aspergillus, molds • Nocardia • Capnocytophaga • Giardia • Cryptosporidium • Healthcare-acquired • C difficile • MRSA • Prior exposures – reactivation: • Toxoplasma • Chagas • CMV • VZV • Strongyloides • M. Tuberculosis • Donor-derived • WNV • Rabies
  • 11. Donor-derived infections • Pyogenic bacteria • Trypanosoma cruzi • Hepatitis C virus • HIV • West Nile Virus • Lymphocytic choriomeningitis virus (LCMV) • Legionella • Histoplasma capsulatum • Candida spp. • Strongyloides stercoralis • Cryptococcus neoformans • Schistosoma spp. • Toxoplasma gondii • Mycobacterium tuberculosis • Rabies virus
  • 12. Changing Timeline of Infection after Organ Transplantation Fishman JA. N Engl J Med 2007;357:2601-2614.
  • 13. Post HSCT risk periods for infection
  • 14. Case #1: • HPI: 41 HF with h/o Rheumatoid Arthritis on Enbrel  Humira x 4 years presents with: • 15 day h/o fever & intermittent headaches • Non-productive cough, night sweats • 9lb wt loss in 2-3 weeks • Labs: 2.0>--------<144 (77%PMNs) 32.5 • CSF: 100RBCs, 274 WBCs (94%L), glucose 14, protein 198
  • 15. Case # 1: CT chest
  • 16. Case # 1: MRI brain
  • 17. Case #1: What is your diagnosis? • A) Pneumococcal meningitis • B) TB meningitis • C) Histoplasma meningoencephalitis • D) Nocardia pulmonary disease with brain abscess
  • 18. Risk of TB Activation According to Level of Immune Compromise Risk of activation per year Normal host 0.1% Hemodialysis 1-2% Solid organ 5-6% transplant HIV/AIDS 10% Positive TST in HIV = > 5mm
  • 19. TUBERCULIN SKIN TEST RESULTS INTERPRETATION ≥ 5mm ≥ 10mm ≥ 15mm HIV infection Close contact Abnormal CXR Immunosuppressed: TNF-alpha inhibitors, chemotherapy, organ transplant, glucocorticoid treatment Risk factors for reactivation: silicosis, HD, DM, malignancies (leukemia, lymphoma, head/neck/lung cancer), underweight, jejunoileal bypass, IVDA Children < 4 Foreign born from high-risk countries Residents/employees in high-risk settings: prisons, jails, healthcare facilities, mycobacteriology labs, homeless shelters Healthy persons with low likelihood of true TB infection
  • 20. TSTin3d.com TB risk calculator
  • 21.
  • 22. Corticosteroids and TB ≥15mg prednisone ≥1 month are at increased risk for TB reactivation (but exact risk unknown) Am J Respir Crit Care Med. 2000;161(4 Pt 2):S221 • Arthritis Rheum. 2006;55(1):19 Arthritis Rheum. 2006;55(1):19
  • 23. IFX or ADA Associated with Increased Risk of TB compared to ETN Study Country Results demonstrating risk of active TB Brassard. CID. 2006 Canada ETN <<<< IFX (by 1.3x) Gomez-Reino. Arthritis Rheum. 2006 Spain No diff btw the 3 groups risk active TB, but ETN <<<< IFX (by 2x) Tubach. Arthritis Rheum. 2009 France ETN SIR 1.8<<<IFX SIR 18.6<<< ADA SIR 29.3 (SIR = standardized incidence ratio) Fonseca. Acta Reumatol Port. 2006 Portugal ETN <<<< IFN or ADA (3-4x) Dixon. Ann Rheum Dis. 2010 UK ETN<<<<IFN or ADA (3-4x)
  • 24. TB Risk Factors in Patients on TNF Antagonists Tubach et al. Arthritis & Rheum. 2009
  • 25. TNF is Needed to Create Granulomas A)TNF from macrophage co-stimulates T cells B)TNF from T cells primes macrophages for mycobactericidal activity C)Macrophage and T cell TNF recruit monocytes and promote granuloma formation D)Anti-TNF results in granuloma breakdown an dissemination of TB Solovic et al. Eur Resp J. 2010
  • 26. When to Screen for TB? • Prior to initiation of any immune suppressant: • Steroids > 10mg po q day • Methotrexate • Cyclosporine • Azathioprine • Leflunomide • Cyclophosphamide • Plus prior to initiation of any TNF antagonist • Yearly while on TNF antagonist in high TB endemic areas • Every 3 months while on TNF antagonist therapy for those who have completed treatment for TB (BTSSCC. Thorax. 2005) Fonseca et al. Acta Reumatol Port. 2006
  • 27. When Is It Safe to Resume Biologics? Guidelines Latent TB Active TB France > 3 weeks of prophylaxis > 2 months after completion of TB treatment, but recommend prophylaxis while on TNF antagonists after completion of therapy Germany >1-2 months of prophylaxis Ireland As long as possible after starting prophylaxis On completion of TB treatment Portugal >1 month of prophylaxis > 2 months on TB treatment Spain 1 month, but may consider days after starting prophy Switzerland 1 month after completion of prophylaxis UK Abnl CXR  after completion of prophylaxis Nl CXR  start concurrently > 2 months on TB treatment USA Preferably complete prophylaxis Preferably complete TB treatment TBNET > 4 weeks after initiation of prophylaxis Preferably complete TB treatment Solovic. Eur Resp J. 2010, Doherty. J Am Acad Derm. 2008,
  • 28. Case #2: Courtesy Bonnie Prokesch
  • 29. Case #2: • 56 yo WM Veterinarian with fevers to 102-105, nightsweats, fatigue, 10lb weight loss x 2 months • No other localizing symptoms • Labs: • 14.6 3.4>--------<69 (N 72%) ferritin 766
  • 30. Case # 2: CT A/P Courtesy Bonnie Prokesch
  • 31. Case #2 CT chest Courtesy Bonnie Prokesch
  • 32. Case #2 H&E LN aspirate Courtesy Bonnie Prokesch
  • 33. Case #2: GMS stain Courtesy Bonnie Prokesch
  • 34. Case #2: What is your diagnosis? • A) Disseminated candidiasis • B) Blastomycosis • C) Mycobacterium avium intracellulare • D) Disseminated Histoplasmosis
  • 35. Histoplasmosis capsulatum var. capsulatum www.mycology.adelaide.edu.au pathmicro.med.sc.edu/mycology Courtesy Francesca Lee
  • 36. Histoplasma and Immunocompromised • Histoplasma – • Most commonly reported- “classic intracellular pathogen”- contained primarily by cell-mediated immunity • No data re prophylaxis or routine screening • Avoid high risk activities-construction, spelunking • Incidence of histoplasmosis • 18.78 per 100,000 persons for infliximab • 2.65 per 100,000 persons for etanercept Drugs 2009 Jul 30;69(11):1403-15.
  • 37. Case #3 • 24 year old WM with B-ALL s/p FLAG-IDA with prolonged neutropenia with neutropenic fevers and R sided pleuritic CP.
  • 38. Case # 3: What is your diagnosis? • A) Nocardia • B) Pulmonary aspergillosis • C) Mycobacterium tuberculosis • D) Legionella
  • 39. Aspergillus • Ubiquitous mold • Most common invasive fungal infection (48%) –25% survival per TRANSNET • Risk: chronic GVHD, older, construction, lymphopenia, CMV, respiratory virus, multiple myeloma • Diagnosis: fungal culture, galactomannan assay, PCR? • CXR/CT findings: “Halo sign”, air-crescent sign
  • 40. Case # 3: CT chest after one month treatment
  • 41. Invasive Aspergillosis in AML Patients Prolonged neutropenia is a risk factor for invasive aspergillosis No significant difference amongst L-AmB, Caspo, and Vori Pagano. Haematologica. 2010
  • 42. Improved Survival in Voriconazole-treated Patients with Invasive Aspergillosis Herbrecht et al. NEJM.2002
  • 43. Case #4 • 45 year old HF with RA s/p MTX/Enbrel 2009, later diagnosed with ALL s/p HyperCVA 1A-4B with relapse s/p re-induction chemotherapy with prolonged neutropenia who has the following physical exam: Courtesy Miloni Shroff
  • 44. Case #4 Courtesy Miloni Shroff
  • 45. Case # 4: What is your diagnosis? • Blood cultures + mold • Skin biopsy + narrow-branching fungal elements within vessel walls • A) Aspergillus • B) Mucormycosis • C) Fusarium • D) Nocardia
  • 46. Case #4: Skin lesions during treatment Courtesy Miloni Shroff
  • 47. Case #4: Skin lesions weeks into treatment Courtesy Miloni Shroff
  • 48. Case #5 • 36 year old HM with ALL, s/p induction chemotherapy with prolonged neutropenia (1 month) with L sided chest pain/upper back pain. + weight loss, no fevers, no SOB. Former construction worker in Florida (15-17 years prior to diagnosis of ALL). Had been on prophylactic micafungin. 0.2>-----<11 ANC 100 20.1
  • 49. Case #5 CT chest
  • 50. Case #5: What is your diagnosis? • Endobronchial biopsy of lung nodule – “…numerous fungal hyphae characterized by broad hyphal elements with thin membranes, irregular branching, non-parallel walls…”, non-septated, “…focal areas of vascular invasion • What is your diagnosis? • A) Aspergillus • B) Cryptococcus • C) Coccidioidomycosis • D) Zygomycosis
  • 51. Non-AspergillusMolds • Zygomycetes (8%), Fusarium & Scedosporium (16%), Acremonium, Paecilomyces • Clinical: • 6% survival with Fusarium, 28% with Mucormycosis • Diagnosis: Fungal blood culture (Fusarium), tissue biopsy cultures • RX: • Aggressive surgical debridement • Liposomal ambisome (5mg/kg/day  10mg/kg/day?) • Combination with azole? • Reduce immune suppression • ? GCSF • Control blood glucose Silveira. Med Mycol. 2007 Hosseini-Moghaddam. Sem Resp Crit Care Med. 2010
  • 52. Breakthrough Zygomycetes on Prophylactic Voriconazole in HSCT Trifilio. Bone Marrow Transplant. 2007 •71 allo HSCT •Voriconazole 200mg po bid •6 Candida, 4 Zygomyces (3 lung, 1 sinus)
  • 53. Probability of Zygomycosis/Invasive Fungal Infections at 1 year After Voriconazole Initiation 7% 18% Trifilio. Bone Marrow Transplant. 2007
  • 54. Case #6 • 45 year old Vietnamese female with metastatic high grade pontine glioma with metastasis to the spine with leptomeningeal dissemination undergoing chemo/XRT, DM2, on dexamethasone 4mg po tid since 1/2013 (now 11/2013) admitted with acute hypoxemic respiratory failure. • Exam: + moon facies, 85% O2 sat on RA, tachy 120s • Lungs with coarse crackles B • Labs: 12.2 1.4>---------<61 Fungitell > 500 LDH 579
  • 55. Case # 6: CXR
  • 56. Case # 6: CT chest
  • 57. Case # 6: What is your diagnosis? • A) Streptococcal pneumonia • B) Legionella pneumonia • C) Pneumocystis pneumonia • D) Mycobacterium tuberculosis
  • 58. Pneumocystis jiroveci Risk factors • Defects in cell-mediate immunity • Steroids (> 20mg/day prednisone for > 1 month) with immune suppressants, TNF antagonists, alemtuzumab, fludarabine, T-cell depleting agent • Heme malignancy (ALL) • SOT: lung-heart >>renal • HSCT • Rheumatologic d/o (pyomyositis/dermatomyositis , Wegener’s) • Solid tumors, esp.. CNS • Primary immunodeficiencies • Risk factors in patients with autoimmune inflammatory disorders, or on systemic steroids: • Lymphopenia (< 600 cells/mm3) • Steroid dose > 15mg prednisolone or equivalent/day • CD4 count < 200 cells/mm3 Sowden. BMC Infect Dis. 2004,4:42 Courtesy Francesca Lee
  • 59. Pneumocystis Diagnostic Tests Indirect tests • High A-a gradient • Decreased DLCO (< 70%) • Elevated LDH (90%) • Elevated fungitell (13)-β-D-glucan • Sensitivity 90-100% • Specificity 88-96% Direct tests Sens Spec Bronch with BAL 90-98% Induced sputum DFA 100% 55-92% Endotracheal aspirate 92% PCR 81-100% 86-100% Note: decreased sensitivity BAL (62%) in patients s/p aerosolized pentamidine
  • 60. Beta-D-glucan and Diagnosis of Pneumocystis Sax. Clin Infect Dis. 2011 Positive: Candida, Aspergillus, Pneumocystis, NOT Zygomycetes or Cryptococcus False positive: augmentin, zosyn, S. pneumo, Pseudomonas, IVIG, albumin, HD, mucositis
  • 61. Prophylaxis for PJP in immunocompromised patients • Cochrane review 2007 of 11 RCTs evaluating prophylaxis with TMP/SMX vs. placebo or other antibiotics with no PCP activity: • Adults with acute leukemia or solid organ transplant; children with acute leukemia • No increased rate of adverse events • Number needed to treat to prevent one episode of PCP = 15 • ATS 2010 Fungal Infections Guideline • Prednisone dose ≥ 20mg/day >1 month, especially if patient has T cell defects, or has other cytotoxic drugs or TNF-a inhibitors Green. Cochrane Database Syst Rev. 2007 Jul 18;(3):CD005590 Am J Respir Crit Care Med Vol 183. pp 96–128, 2011 Rahier et al, Journal of Crohn's and Colitis (2009), p1-46 Courtesy Francesca Lee
  • 63. TMP-SMX vs. Aerosolized Pentamidine vs. Dapsone TMP-SMX Dapsone, atovaquone Aerosolized pentamidine > > Best tolerated No toxo coverage Screen for tb •Most effective •Covers toxo, salmonella, listeria, nocardia, strep, staph Less toxo coverage Check G6PD
  • 64. Aerosolized pentamidine Upper lobe infiltrates 38% pentamidine vs.. 7% no pentamidine Jules-Elysee. Ann Int Med. 1990 Levine et al. Am Rev Respir Dis. 1991
  • 65. Case #7 • 60 year old HM with DM, s/p DDKT 2007, admitted with abdominal pain, found to have skin nodules: Courtesy Suresh Kachhdiya
  • 66. Case #7: CT chest
  • 67. Case #7 • Biopsy of skin nodule shows suppurative granulomatous inflammation with yeast forms + by PAS/GMS stain, mostly with narrow bases. • Crypto Antigen 1:64 Creatinine 2.5 • What would you do next? A) Start Ambisome + flucytosine B) Start Fluconazole + flucytosine C) Start Posaconazole D) Start Itraconazole
  • 68. • Risk factor: T cell defect (i.e. AIDS, SOT) • Calcineurin inhibitors • Alemtuzumab, antithymocyte • Clinical: asymptomatic, acute respiratory distress, pneumonia, 53- 72% with disseminated disease in SOT • Radiography: nodules, lobar infiltrates, pleural effusions, • Diagnosis: culture, crypto antigen in blood positive in 56-70% • Treatment: • Amphotericin and 5-FC for severe cases • Fluconazole for mild cases and for long term maintenance • Watch out for immune reconstitution inflammatory syndrome (5-11%) • Mortality in SOT 14% Singh. Am J Transplant. 2009
  • 69. Case #7…but wait… • He had abdominal pain and difficulty swallowing… • s/p EGD  esophagitis and gastric ulcer & duodenal stricture • Path: + duodenitis with + H. pylori and cells with viral inclusions  CMV duodenitis (CMV PCR detectable only) • Eventually also diagnosed with: • Enterobacter bacteremia • Candida glabrata endocarditis • EBV + in CSF
  • 70. Case #8 • 53 year old WF with ileocolonic Crohn’s disease s/p small bowel resection on imuran x 10 years and prednisone 20mg daily admitted with fevers, chills, and abdominal pain, bloody diarrhea, shortness of breath. • Exam: febrile to 101.7, tachycardic • Abdomen tender in upper epigastric region, + bowel sounds, no rebound • Labs: 10 • 1.1>-------<182 (ANC 800) AST 98 ALT 43
  • 71. Case # 8: CT A/P
  • 72. Case # 8: CT chest
  • 73. Case # 8: What is your diagnosis? • A) Legionella Pneumonia • B) Mycobacterium tuberculosis • C) CMV colitis and pneumonitis • D) Adenovirus pneumonia and enteritis
  • 74. Case #8: Results • CMV PCR 413,000 • CMV + BAL and + lung biopsy • CMV + immunostain on flex sig • Initiated on ganciclovir and cytopenias resolved and abdominal pain/diarrhea/hypoxia resolved. • Also + C difficile
  • 75. Cytomegalovirus- “Big Bad Wolf of SOT” • Risk: GVHD, lymphopenia, D+/R- • Immunomodulatory • Superinfections: PJP, Aspergillus, GNR, Listeria, Candida • Clinical: • pneumonitis • enteritis • bone marrow suppression • retinitis (rare) • Diagnosis: CMV PCR • NOTE GI disease often occurs WITHOUT CMV viremia • Prevention: CMV-safe transfusions • Treatment: ganciclovir, valganciclovir, CMV immune globulin
  • 76. CMV Spectrum of Disease Immunocompetent • Mononucleosis-like syndrome Congenital • Ventriculitis/E ncephalitis • Hepatospleno megaly HIV • Retinitis • Ventriculitis • Myelitis • Polyradiculopa thy • Colitis/Esopha gitis Transplant • CMV syndrome • Colitis/Esopha gitis • Pneumonitis • Hepatitis Courtesy of Jason Gillman, MD
  • 77. CMV and Solid Organ Transplant: Serostatus and Risk of Reactivation Rubin RH. TID. 2001 Courtesy J. Gillman
  • 78. Case #9 • 69 year old WM s/p R lung transplant 2/2013 presents 4 months later with respiratory distress and UGIB.
  • 79. Case #9:What is your diagnosis • s/p EGD with this found on biopsy and in the BAL fluid. 1) Ascaris 2) Strongyloides 3) Schistosomiasis 4) Toxoplasmosis
  • 80. Strongyloides hyperinfection syndrome • Strongyloides stercoralis – helminth with autoinfection possibility • Risk factors: defects in cell-mediated immunity • Steroids, Calcineurin inhibitors, TNF antagonists • SOT • HSCT • Burn victims, alcoholics, DM • Hypogammaglobulinemia • HTLV-1 co-infection • AIDS • Clinical: fever, dyspnea, wheezing, hemoptysis, cough, diarrhea, nausea/vomiting, gram negative sepsis Balagopal et al. Transplant Infect Dis. 2009
  • 81. Screening for Strongyloides? • “Experts estimate that there are between 3-100 million infected persons worldwide” • US- 0-6.1% of persons sampled • Immigrants to US- 0-46.1% of persons sampled • Risk factors: contact with soil • Walking with bare feet • Contact with human waste or sewage • Occupations that increase contact with contaminated soil, such as farming and coal mining http://www.cdc.gov/parasites/strongyloides/epi.html • Consider screening with serologic testing in “at risk” patients • Immigrants from Central and South America • If positive, treat with ivermectin prior to immunosuppression Curr Opin Infect Dis 2012, 25:458–463
  • 82. Case #10 • 58 year old WM with AML s/p allo SCT c/b GVHD, admitted with SOB with pleuritic CP, L buttock mass x 6 weeks after scraping his bottom on a yucca plant, and R axillary nodule • Exam: Afebrile, 95% on RA • L buttock wound s/p I&D with minimal erythema • R axillary mobile soft, NT, subcutaneous nodule • R thigh with soft erythematous nontender nodule
  • 83. Case # 10: CT chest
  • 84. Case #10: CT pelvis
  • 85. Case #10: What is your diagnosis? • Culture from I&D of buttock abscess, R thigh and R axillary nodules + gram positive branching filamentous rods. • A) Mycobacterium abscessus • B) Stenotrophomonas maltophilia • C) Scedosporium • D) Nocardia
  • 86. Case #10: What should you do if you diagnose a patient with pulmonary nocardia? • A) Start oral bactrim prophylaxis • B) Get MRI brain • C) Order nocardia serum PCR assay • D) Place in airborne isolation
  • 87. Case #10: MRI brain
  • 88. Nocardia • Gram-positive filamentous branching • Risk (2/3 immunocompromised): HIV/AIDS, glucocorticoids, malignancy (Heme, BMT), SOT, COPD, CGD, TNF-alpha, ETOH, TB • Clinical: pneumonia, pulmonary nodules, brain abscess • 39% Lung only • 32% with > 2 sites (44% + CNS) • Prophylaxis: TMP-SMX • Treatment: TMP-SMX, Imipenem, Amikacin, Ceftriaxone, Linezolid, Moxifloxacin, Minocycline
  • 89. Case # 11 • 35 year old white female with relapsed Hodgkin’s lymphoma s/p auto SCT 2012 c/b GVHD of gut, skin, and lungs and h/o CMV colitis who was admitted with pleuritic R sided CP with shortness of breath • Exam: afebrile, O2 sat 88% on 2LPM O2, tachypneic, tachycardic • Moon facies, dyspneic, decreased BS R> L, stable GVHD skin rash • Labs: • 17.4>-------<133 LDH 286 fungitell 210 • 36.2 • Resp PCR panel + rhinovirus/enterovirus
  • 90. Case # 11: CXR
  • 91. Case # 11: CT chest
  • 92. Case # 11: CT chest
  • 93. Case # 11: What is your diagnosis? • A) Zygomycete • B) Pneumocystis • C) Nocardia • D) Legionella
  • 94. Wild, Wild West… You never know what to expect….
  • 95. Wild Wild West… “Always drink upstream from the herd…” - Will Rogers