Infectious Diseases EmergenciesHenry F. Chambers, MD

• 34 y/o M, HIV+ since 1991. CD4 207 (nadir 156), VL 58K.

• 1 year ago +RPR of 1:128; Rx benzathine PCN weekly x 3.

• RPRs @ 3 mo: 1:128; @ 6 mo 1:64; @ 8 mo 1:64; currently 1:64.

• Asymptomatic until right sided Bell's Palsy• LP : OP 18, WBC 27 (97% lymphs), glucose

58, protein 59, RPR negative• Discharged to home on acyclovir

Case 1

What is the Best Course of Action?

1. Add prednisone to the acyclovir regimen, repeat LP2. Treat for neurosyphilis with benzathine penicillin 2.4

mU once weekly for 3 doses, then repeat LP3. Send CSF FTA-ABS and if this is positive treat for

neurosyphilis with benzathine penicillin 2.4 mU once weekly for 3 doses

4. Send CSF FTA-ABS and if this is positive treat for neurosyphilis with 14 days of high dose intraveneous pencillin

5. Treat for neurosyphilis with 14 days of high dose intravenous penicillin regardless of CSF FTA-ABS

What is the Best Course of Action?

1. Add prednisone to the acyclovir regimen, repeat LP2. Treat for neurosyphilis with benzathine penicillin 2.4

mU once weekly for 3 doses, then repeat LP3. Send CSF FTA-ABS and if this is positive treat for

neurosyphilis with benzathine penicillin 2.4 mU once weekly for 3 doses

4. Send CSF FTA-ABS and if this is positive treat for neurosyphilis with 14 days of high dose intraveneous pencillin

5. Treat for neurosyphilis with 14 days of high dose intravenous penicillin regardless of CSF FTA-ABS

• 45M with AIDS, MSM, marginally housed• ARV’s recently restarted, CD4 35 and VL 11K• H/o latent syphilis (never adequately treated),

HBV, HCV, active IVDU. • New onset blindness x1 day, affecting the

right eye.• Cough, SOB, fevers, and weakness x1week.• Decreased hearing from the right ear x3days.

Case 2VS: T 35.9, BP 94/62, HR 80, RR 18, 95% (6LFM)GEN: Moderate distress, ill-appearing. Cachectic.NECK: supple. COR: no murmurs.RESP: Crackles and egophony at R base. Using

accessory muscles.SKIN: no rashes. No peripheral manifestations of

endocarditis. No e/o abscesses or cellulitis.NEURO: AAOx4. Non-focal

Exam

CXR on admission

What is the Diagnosis? 1. MRSA endocarditis 2. Pneumococcal pneumonia & bacteremia 3. Neurosyphilis 4. Klebsiella pneumonia & bacteremia5. Pneumocystic pneumonia with ocular

involvement

What is the Diagnosis? 1. MRSA endocarditis 2. Pneumococcal pneumonia & bacteremia 3. Neurosyphilis 4. Klebsiella pneumonia & bacteremia5. Pneumocystic pneumonia with ocular

involvement

• 69 y/o Chinese male redness in left eye but w/o pain or vision loss

• Iritis and multifocal choroiditis• RPR – neg, • ACE level – wnl, • PPD – “positive” (unknown size), CXR

negative• HLA-B27-neg

Case 3More History

• PMH: none; MEDS: none• Travel history

– Lived in central and NE China for ~ 50 years– 1995: Harrisburg, PA for 1 year– 1996-98: Returned to China– 1998-99: Cincinnati, OH for 15 months– 1999 to present: Pleasanton, CA – Has driven to LA on 5-6 occasions

• Occupation history– Agriculture teacher – Chef in Chinese restaurant

• HIV risk factors: none • Enjoys gardening, he did go caving once in CA

Initial Exam• VS: AF, VSS• GEN: well appearing, pleasant, NAD• HEENT: oropharynx clear, minimal left

scleral/conjunctival injection, EOMI• Fundoscopic Exam: OS multifocal

choroidal lesions with scleral thickening• Remainder of exam: normal

Direct fundoscopic exam

Optic disc

Optic cup

Vein

Arterioles

FoveaMultifocal choroidal lesions

• Enhancement of the lateral aspect of the left sclera, lacrimal gland, and lateral rectus

• T2 enhancement within the left globe. • Lesion not amenable for biopsy• Concerning for ocular lymphoma

MRI Brain/Orbit

• CT scans to determine extent of disease and to find alternate site for biopsy– Necrotic lymph node in mediastinum between

left main bronchus and aorta– Calcified lymph node within mediastinum in

subcarinal space– Two calcified granulomas in left lung

• Bronchoscopy w/ Wang needle bx of LN– Areas of necrosis in bronchial tree at lingular/left

main take off, corresponding to node between LM and aorta

– FNA: budding yeast forms, likely c/w crypto vs. cocci vs. histo; does not have appearance of candida, and specimen is from within node itself

• On hospital day #3 (after 2 doses of Ambisome) ophtho felt that exam was improved from week prior

• Serology - serum CRAG – neg, HIV – neg, Urine histo antigen – neg, Histo CF Ab –neg, Cocci CF Ab – neg, Blasto Ab – neg

• Ambisome was discontinued• Patient discharged on voriconazole

1 week later….

• Eye exam: resolution of eye findings • F/u scans: resolution of eye findings,

decrease in uptake of mediastinal lymph node

• Microbiology lab reports positive results from lymph node culture

What Organism Had the Laboratory Isolated?

1. Blastomyces dermatitidis2. Histoplasma capsulatum3. Penicillium marneffei4. Sporothrix schenckii5. Coccidioides immitis6. None of the above

What Organism Had the Laboratory Isolated?

1. Blastomyces dermatitidis2. Histoplasma capsulatum3. Penicillium marneffei4. Sporothrix schenckii5. Coccidioides immitis6. None of the above

Tuberculous Chorioretinitis and Lymphademitis

• 1/3 samples from bronchoscopy positive for Mycobacterium tuberculosis

• Budding yeast on original path specimen upon review felt to be an artifact

• 56 y/o M w/ h/o HTN, hyperlipidemia • Complain of respiratory distress and

cough for 1 day. • T= 101.7, tachypenic into the 30s and O2

saturation 90% on 100% face mask

Case 4 Physical Exam

• VS: 101.7, 154, 24, 151/82, 90% on 100% FM

• GEN: altered MS, resp distress• Oral-clear, Neck-supple• Chest-Bilat scattered rhonchi• CV-tachycardic, regular• Abd-obese, NT• Ext-Symm ROM• Neuro-altered but alert, GCS=15

LABS

• WBC = 19.1, Hct =56, Platelets = 341• C02 – 19• Cr-3.2• 7.23/46/78

Which of Antimicrobial Regimen Would You Choose?

1. Ceftriaxone + doxycycline2. Levofloxacin 3. Ceftriaxone + azithromycin4. Vancomycin + piperacillin/tazobactam +

azithromycin5. Clindamycin + vancomycin +

piperacillin/tazobactam + levofloxacin

History

• Ceftriaxone/doxy administered• Patient admitted to the ICU • Patient intubated for worsening hypoxia• Vasopressors for refractory hypotension • Antibiotics changed to Vancomycin/Pip-

tazo/Azithromycin • Post-intubation CXR obtained (4 h after

admission)

• Extensive consolidation of much of the right lower lobe. Somewhat complex cavities are seen at the posterior medial mid right lower lobe.

• Right upper lobe surrounded by approximately 2 to 2-1/2 cm thickness of pleural fluid. Pleural fluid also present in the dependent right lower chest.

Diagnosis?

1. Community-associated MRSA pneumonia

2. Pneumococccal pneumonia3. Pseudomonas pneumonia 4. Streptococcus pyogenes pneumonia5. Klebsiella pneumonia 6. Legionella pneumophila pneumonia

Hospital course cont.• IR guided thoracentesis that evening had “3+

gm + cocci some in pairs” on gram stain

Hospital course cont.• 5 hours later the patient went into cardiac

arrest and then died.• Cultures from blood x 2, sputum, and

pleural fluid revealed gram + cocci.

Streptococcus pyogenes (GAS)

Case 5

• 35 yo Kenyan female, 38 wks gestation• Fevers for 2 days• Cough w/scant yellow-white sputum, sore

throat, myalgias• No SOB, CP, N/V/D, abd pain, HA

Physical Exam• VS: 37.5, 115/62, 76, 18 (98% on RA)• Gen: diaphoretic, NAD• HEENT: normal• Lungs: normal• CV: 1/6 systolic murmur• Abdomen: gravid uterus • Extremities: trace ankle edema • Neuro: non-focal• Late decelerations noted on fetal exam

Labs

INR 1.2DFA: influenza A and B, parainfluenza virus

1, 2, and 3, adenovirus, RSV all negativeCXR and EKG: not obtained

136

3.4

106

22

6

0.889

Hgb12

WBC12.2

Plt103

Hct34

(90% PMNs)

Hospital Course

• Admitted for induction of labor• Prior positive GBS culture → penicillin• Worsening fetal distress → OR for low

forceps delivery of a healthy 7# baby girl• The next day the patient c/o shaking chills,

but was afebrile and discharged home

Readmission

• Returns to ER the next day • Persistent fevers, chills, worsening SOB,

left sided chest pain, productive cough• No HA, N/V/D, abdominal pain, rash • VS: 35.1 117/70 95 20 (88% on RA)

Labs

133

3.6

103

17

19

1.089

Hgb11.5

WBC2.0

Plt147

Hct32(95%

PMNs)

Liver panel within normal limits

Additional History

• Traveled to Kenya while 5 months pregnant; worked with HIV+ pts in a TB clinic; went on safari but no animal contact

• No malaria ppx; noticed insect bites• Traveled to Idaho two months prior to visit

her brother is a vet who takes care of pregnant animals

Hospital Course

D 2-3

↑ hypoxia

Blood cx drawn

Antibiotics

D 1-2

Vanco added

DFA neg

Sputum: OF

ICU

Intubated for resp. failure

CXR: ↑RLL RLL consolidationconsolidation

CTX/Azithro

D 3-4

CTX/Azithro/Vanco

Hospital Course (cont.)

D 4-5New abx

BAL: mucopuruleucopurulent nt secretions secretions

D 4↑↑ consol.consol.Hydro PTXHydro PTXChest tube

Vanco/mero/levo

D 5-8

Persistent air Persistent air leak, 2 more leak, 2 more chest tubeschest tubes

Negative Lab Results• Multiple blood and sputum cx • Legionella cultures and antigen negative• Mycoplasma IgM negative (IgG positive)• HIV: antibody neg; viral load <75• Urine Histo Ag negative• Coccidioides serologies negative• Q fever serologies negative• AFB sputum x 3 negative• Malaria thick and thin neg x 3• CrAg neg• CMV shell vial cx from BAL neg final

Hospital Course (cont.)

D 8-10

ECMO

Flucon Flucon added added

D 9

FiO2 1.0FiO2 1.0Peep 8Peep 8

Thoracotomy for Thoracotomy for trach, debridement of trach, debridement of necrotic L lung, necrotic L lung, subtotal resection of subtotal resection of LUL & LLLLUL & LLL

Vanco/mero/levo/fluconazole

D 11

Which one of the following was found to be the cause of this infection?

1. Community-associated MRSA2. Rhodococcus equi3. Histoplasma duboisii4. Mycobacterium tuberculosis5. Streptococcus pyogenes6. Streptococcus pneumoniae

Pathology and Microbiology

• Pathology: necrotic and acutely inflamed lung parenchyma; no viable lung tissue– Acute necrotizing PNA

• OR specimens – Cultures: routine, AFB, fungal, legionella,

viral including CMV, HSV all negative – Viral DFA, AFB, and fungal stains negative

16S rRNA Real-Time PCR of Lung Tissue Nucleic Acid Extract

Will Probert, Microbial Diseases Lab, CDPH

Lung Tissue

Control

16S rRNA Gene Sequence

GenBank Database Search

Streptococcus pneumoniae/S. mitis Group

Pneumococcal Confirmation

• Pneumococcal-specific Real-time PCR– Targets Autolysin gene

• Molecular Serotyping– Multiplex PCRs target genetic differences in

enzymes that synthesize the various polysaccharide capsule

– Detects the 35 most prevalent serotypes

And the diagnosis…

S. pneumoniae necrotizing pneumoniaSerotype 19A

Case 6• 49 y/o F, AIDS, active IVDU, h/o crack use• H/o TCV endocarditis 1 year ago• 6 wks PTA admitted for RLE cellulitis, hypoxia

– CXR RLL consolidation . – Chest CT: necrotizing pneumonia– Treated with levofloxacin + clindamycin. – BAL for persistent hypoxia → positive for PCP– Treated with clinda/primaquine + steroids + ARVs

Prior CXR Prior CT Scan

Present Illness • 3-4 days of

– SOB, increasing DOE– Subjective fevers– Right-sided pleuritic chest pain– Cough productive of green sputum– Admitted for hypoxia

• Meds (compliance?)– Truvada, raltegravir, etraverine– Azithromycin, clinda, primiquine, fluconazole– Prednisone

Physical Exam

• VS: 37.3, 104/64, 111, Sat 80% RA • GENERAL: very thin, • CV: 2/6 SEM LLSB (old)• RESP: Decreased BS R side to mid-lung,

decreased tactile fremitus on R; L lung clear

Labs

ABG (Room Air): pH 7.41, pO2 50, pCO246

133

4.1

100

26

20

0.489

Hgb9.3

WBC11.8

Plt354

Hct27.4

HIV VL 5284, CD4 61 (nadir 34)

CXR: Opacification of R lower hemithorax

Hospital Course

• Sputum for AFB• Small amount of hemoptysis with 6 point

Hct drop → transfused • Worsening hypoxia → ICU, intubated• Linezolid + meropenem added to

clinda/primaquine

Case 12

Chest CT this Admission• Large inhomogeneous, loculated,

multiseptated R pleural effusion with multiple fluid levels

• Nodular areas of nondependent soft tissue attenuation, extensive mass effect with mediastinal shift to the left; compression of R pulmonary veins and R upper, middle, and lower lobe bronchi

• R lung is nearly completely collapsed.

Chest CT

Hospital Course

• Thoracentesis and pigtail catheter placement

• Pleural fluid– Bloody– RBC: 1.8 million – WBC1467, 80% PMNs– Protein 5.2, LDH 850, Glucose < 20– Gram-stain, cultures, and cytology negative

Hospital Course• Progressively worsening hypoxia, hypotension,

small amounts of hemoptysis• Chest tube output < 200 ml• Fevers to 38.5C, rising WBCs• Voriconazole added • Thoracotomy performed

– “Surface of the lung had numerous sites, consistent with ruptured abscess or necrotizing lung, with evidence of previous hemorrhage.”

– Post-op DX• Tension hemothorax• Necrotizing pneumonia

Final Diagnosis?

1. Rhodococcus equi lung abscess2. Mycobacterium tuberculosis3. Lymphoma4. Invasive aspergillosis5. Kaposi’s sarcoma6. Adenocarcinoma of the lung Adenocarcinoma of the lung

Case 7

• A 50 year old marginally housed man with a history of alcoholic cirrhosis

• 5 days of fever, headache, fatigue, cough, and dysuria

Past Medial History

• PMH: – EtOH cirrhosis– PPD positive s/p INH x 12 months while

incarcerated ~5 years ago• Meds: none• Allergies: none

Social History

• No tobacco or IDU. Prior heavy EtOH • Born in Mexico. Moved to US in 1974, last

trip to Mexico in 1982. No recent travel.• Currently unemployed but has worked in

landscaping, construction, as a mechanic

Other Exposures

• No pets but some friends with a parakeet• No queso fresco or unpasteurized milk

products • Sexually active only with his wife from

whom he is separated• Saw a dentist for a cleaning 2 wk prior to

onset of symptoms

Exam

• T 101.1 F, BP 80s/50s, HR 110 • GEN: ill appearing, tremulous• Poor dentition• CV: RRR, 1/6 SEM ULSB

Laboratory Data• WBC = 13, Hct = 26, Plt = 88• Creatinine = 0.9• Other labs:

– UA: >50 RBCs, otherwise normal– HIV negative

• Non-contrast head CT: negative• TTE: Mobile 2.1x1.7 cm aortic valve, with valve

ring abscess • 3 blood cultures negative (no prior antibiotics)

Hospital Course

• Initially treated with levofloxacin, then switched to ceftriaxone/ampicillin

• HD#10: new RLE weakness

Head CT

Multiple lesions in the brain c/w septic emboli with hemorrhagic conversion

Head CTA

Multiple small (~2mm) mycotic aneurysms

Hospital Course

• LP findings:– WBC 104 (78N, 18L, 4M), RBC 97, protein 356,

glucose 17– GS: many WBCs, no organisms (although initially

read as gram positive rods)– Cx: negative

• Persistent fevers: vancomycin and doxycycline added

• HD#15: acute loss of pedal pulses bilaterally

CT of Abd/pelvis

Splenic infarct Renal infarcts

CT Pelvis/legs

Final Diagnosis?

1. Hemophilus aphrophilus2. Brucella melitensis3. Abiotrophia defectiva4. Aspergillus fumigatus5. Chlamydia psittici6. Listeria monocytogenes

Gram Stain 100X

45 degree angle branching Septate hyhae

Embolus cultures

blood brain heart infusion flask potato flake agar

Case 2Aspergillus fumigatus