2016 Infectious Diseases Society

of America (IDSA) Clinical Practice

Guideline for the Treatment of

Coccidioidomycosis

Miki Watanabe MD

Hospitalist/ID

UC Irvine medical center

Coccidioidomycosis

• Coccidioides immitis

• Coccidioides posadasii

Distribution

Arthroconidia<->Spherule

Sx

• CAP

• Dermatologic syndromes

• Rheumatologic syndromes

CAP

California: Kaiser Permanente Southern

California retrospectively reviewed all

CAP cases in 2011

Only 2, 023 (5.7%) of 35,567 CAP patients

tested for cocci

Among patients tested, 19% were positive

Dermatologic syndromes

• Erythema nodosum

• Erythema multiforme

• Toxic erythema

• Papule

• Nodules

• Gummas

• Pustular acneiform lesions

• Ulcerated and verrucous plaque

• Abscesses and fistulae

Rheumatologic syndromes

Arthralgias of multiple joints

- generally symmetrical

- distal lower extremities

- never associated with detectable joint

effusions.

As with CAP, these syndromes should be

evaluated for coccidioidal disease

Incubation period 1 week to 4 weeks

CAP, dermatologic syndromes, or

rheumatologic syndromes

- endemic exposure in1–2 months

->think coccidioidomycosis as a possible

etiology.

Hematogenous spread

Can take weeks to several months

Let’s Review the Guideline

Case

24 M healthy male visiting from Arizona came to ER presenting cough x 3 days. T 37.9, BP 110/80, HR 70, RR 16, SpO2 94 RA. CXR RML small infiltration. WBC 10,000. Cr 0.8. Lactate 1.0. HIV(-). CTRX+Azithro started. Dr Barns in ER checked coccidioid titer that was positive. Over night, he felt OK. No fever. Cough not getting worse. What is the recommended treatment for this cocci PNA by IDSA?

1- Fluconazole 400mg po daily

2- Fluconazole 200mg po daily

3- Itraconazole 400mg po daily

4- Education and close follow up

5- Amph B iv

6- Lumber puncture

In Which Patients With Newly Diagnosed,

Uncomplicated Coccidioidal Pneumonia Should

Antifungal Drug Therapy Be Started?

Recommendations

Patient education, close observation, and supportive measures for mild or nondebilitating symptoms, or who have substantially improved or resolved their clinical illness by the time of diagnosis (strong, low).

Start antifungal treatment for patients with

- debilitating illness (strong, low).

- extensive pulmonary involvement, with concur

- diabetes

- otherwise frail because of age or comorbidities

- Some experts would also include African or Filipino ancestry as indications for treatment (strong, low).

- Primary choice: azole antifungal (eg, fluconazole) at a daily dose of ≥400 mg (strong, low).

Lumbar Puncture

Only in patients with unusual, worsening,

or persistent headache, with altered

mental status, unexplained nausea or

vomiting, or new focal neurologic deficit

after adequate imaging of the central

nervous system (CNS) (strong, moderate).

Follow up plan for Newly Diagnosed,

Uncomplicated Coccidioidal Pneumonia,

- Subjective symptoms: fatigue, cough

- History and physical

- CXR

- Titer

- Needs 2 yrs follow up

Case

24 M healthy male visiting from Arizona came to ER presenting cough x 3 days. T 37.9, BP 110/80, HR 70, RR 16, SpO2 94 RA. CXR RML small infiltration. WBC 10,000. Cr 0.8. Lactate 1.0. HIV(-). CTRX+Azithro started. Dr Barns in ER checked coccidioid titer that was positive. Over night, he felt OK. No fever. Cough not getting worse. What is the recommended treatment for this cocci PNA by IDSA?

1- Fluconazole 400mg po daily

2- Fluconazole 200mg po daily

3- Itraconazole 400mg po daily

4- Education and close follow up

5- Amph B iv

6- Lumber puncture

Case

55M with HTN presented with chronic cough with hemoptysis and fatigue x 1 months. VSS. CT chest showed a 3cm lung nodule. PET scan was not suggestive for malignancy. HIV(-). Coccidial titer was elevated.

What is the recommendation by IDSA for this case?

1- Close observation

2- L-AmphB

3- Lung biopsy

4- Fluconazole

5- VATS

Primary Pulmonary Coccidioidomycosis With an

Asymptomatic Pulmonary Nodule, and No Overt

Immunosuppressing

Asymptomatic

• no antifungal treatment (strong, very low).

Symptomatic Chronic Cavitary

Coccidioidal Pneumonia

Antifungal Treatment fluconazole or itraconazole (strong, moderate).

Surgical options - persistently symptomatic on antifungal

treatment.

- when cavities have been present for more than 2 years and if symptoms recur whenever antifungal treatment is stopped (strong, very low).

Case

55M with HTN presented with chronic cough with hemoptysis and fatigue x 1 months. VSS. CT chest showed a 3cm lung nodule. PET scan was not suggestive for malignancy. HIV(-). Coccidial titer was elevated.

What is the recommendation by IDSA for this case?

1- Close observation

2- L-AmphB

3- Lung biopsy

4- Fluconazole

5- VATS

Case

The same 55M with symptomatic coccidioid pulmonary cavity now on fluconazole, came to ER for chest pain x 1day. CT chest showed ruptured cavity. LFTs were elevated ALT/AST 1000/1500. Tbil 1.1. What is the treatment choice now.

1. Increase fluconazole to 800mg po daily

2. Urgent CTS consult for procedure + fluconazole 800mg po daily

3. Urgent CTS consult for procedure + L-amphB

4. Consult CTS for chest tube only

If ruptured…

For patients with ruptured coccidioidal cavity,

- Prompt decortication and resection of the cavity (strong, very low) if possible.

- If the pleural space is massively contaminated, decortications combined with prolonged chest tube drainage may be more appropriate (weak, very low).

- Oral azole therapy is recommended.

- Amph B recommended for patients who do not tolerate oral azole therapy or patients whose disease requires 2 or more surgical procedures for control (strong, very low).

Case

The same 55M with symptomatic coccidioid pulmonary cavity now on fluconazole, came to ER for chest pain x 1day. CT chest showed ruptured cavity. LFTs were elevated ALT/AST 1000/1500. Tbil 1.1. What is the treatment choice now.

1. Increase fluconazole to 800mg po daily

2. Urgent CTS consult for procedure + fluconazole 800mg po daily

3. Urgent CTS consult for procedure + L-amphB

4. Consult CTS for chest tube only

Intermission

Pretty in Pink( GNR)

What is the gram negative rod that can

cause culture negative endocarditis that

has the longest name?

Answer:

Aggregatibacter actinomycetemcomitans

Case

24 healthy M came to urgent care clinic for 1cm supra-clavicular mass for a month. No pain. No fever, chills. No joint pain.Labs wnl. HIV(-). CXR(-). Cocci IgG+IgM elevated.

What is the recommended management by IDSA for this case.

1- Close observation

2- L-Amph B

3- Excisional biopsy

4- Fluconazole po

Extrapulmonary Soft Tissue

Coccidioidomycosis without

osteomyelitis

• Antifungal therapy in all cases of extrapulmonary

soft tissue coccidioidomycosis (strong,

moderate).

• Azoles(fluconazole or itraconazole)for first-line

therapy of (strong, moderate).

• AmB in cases of azole failure, particularly in

coccidioidal synovitis (strong, moderate).

Case

24 healthy M came to urgent care clinic for 1cm supraclaviclar mass for a month. No pain. No fever, chills. No joint pain.Labs wnl. HIV(-). CXR(-). Cocci IgG+IgM elevated.

What is the recommended management by IDSA for this case.

1- Close observation

2- L-Amph B

3- Exicisional biopsy

4- Fluconazole po

Case

55M from Bakersfield, CA with PMH of uncontrolled DM presented with chronic back pain, and night sweat. 1 wk ago he started having L leg numbness/weakness. HIV(-). No headache. Cocci serology elevated. MRI showed extensive T-, L vertrebral osteomyelitis with L nerve root compression.

What is the recommended management for this case by IDSA .

1- Fluconazole and PT/OT

2- Fluconazole and Neurosurgery consult

3- L-AmphB and Neurosurgery consult

4- Voriconazole and Neurosurgery consult

Bone and/or Joint

Coccidioidomycosis

• Azole therapy for bone and joint

coccidioidomycosis, unless the patient has

extensive or limb-threatening skeletal or

vertebral disease causing imminent cord

compromise (strong, low).

• For severe osseous disease, we

recommend AmB as initial therapy, with

eventual change to azole therapy for the

long term (strong, low).

Vertebral Coccidioidal infection

• Recommend surgical consultation for all patients

with vertebral coccidioidal infection to assist in assessing the need for surgical intervention (strong, low).

• Surgical procedures are recommended in addition to antifungal drugs for patients with bony lesions that produce spinal instability, spinal cord or nerve root compression, or significant sequestered paraspinal abscess (strong, low).

• Recommend that surgical consultation be obtained periodically during the course of medical treatment (strong, low).

Case

55M from Bakersfield, CA with PMH of uncontrolled DM presented with chronic back pain, and night sweat. 1 wk ago he started having L leg numbness/weakness. HIV(-). No headache. Cocci serology elevated. MRI showed extensive T-, L vertrebral osteomyelitis with L nerve root compression.

What is the recommended management for this case by IDSA ?

1- Fluconazole and PT/OT

2- Fluconazole and Neurosurgery consult

3- L-AmphB and Neurosurgery consult

4- Voriconazole and Neurosurgery consult

Intermission

What is the name of the Australian scientist

Who discovered H. pylori?

Answer:Barry Marshall

Case

32M healthy male from Arizona came to ER presenting worsening

headache. He developed dry cough 3 weeks ago without dyspnea.

Fever 38.9 HR 98, RR 18, SPO2 99 RA. CXR RML opacity. HCT no

acute abnormality. CSF WBC 800, Dif Lymph 85% Protein 70,

Glucose 25. Coccidioid titer elevated. CSF culture grew cocci. What

is the recommended management for this case by IDSA?

1- L-Amph

2- Fluconazole

3- Neurosurgery consult

4- L-Amph+flucytosin

Coccidioid meningitis

What Is the Primary Treatment?

Fluconazole 400–1200 mg orally daily

No head to head data to suggest other regimen’s

superiority

Case

32M healthy male from Arizona came to ER presenting worsening

headache. He developed dry cough 3 weeks ago without dyspnea.

Fever 38.9 HR 98, RR 18, SPO2 99 RA. CXR RML opacity. HCT no

acute abnormality. CSF WBC 800, Dif Lymph 85% Protein 70,

Glucose 25. Coccidioid titer elevated. CSF culture grew cocci. What

is the recommended management for this case by IDSA?

1- L-Amph

2- Fluconazole

3- Neurosurgery consult

4- L-Amph+flucytosin

Case

The same 32 M with cocci meningitis improving on fluconazole . He came back to internal medicine clinic 3 months later. He said he feels great and now back to job. He asked you when he can stop fluconazole. You say he should:

1- Continue at least 6 months

2- Continue at least 12months

3- Continue for life

4- He can stop fluconazole now with close follow up

For Patients With CM Who Improve or Become

Asymptomatic on Initial Therapy, When Can

Treatment be Stopped?

For CM, we recommend azole treatment for

life (strong, moderate).

- High relapse rate

Case

The same 32 M with cocci meningitis improving on fluconazole . He came back to internal medicine clinic 3 months later. He said he feels great and now back to job. He asked you when he can stop fluconazole. You say he should:

1- Continue at least 6 months

2- Continue at least 12months

3- Continue for life

4- He can stop now with close follow up

Case

46M from Mexico who was recently diagnosed cocci meningitis started on fluconazole 400mg po daily 4 week ago at OSH . He came to ER complaining persistent headache. Outside record reviewed: cocci (+) from CSF culture. HCT wnl. LP was repeated: opening pressure not elevated. CSF culture cocci(+). Cocci titer was the same. What is the recommended management by IDSA?

1- Intrathecal L Amph B

2- Increase fluconazole dosage

3- Repeat daily LP

4- NS consult for shunt

In Patients With CM Who Do Not Have a

Satisfactory Response to Initial Antifungal

Therapy, What Modifications Can Be

Considered?

• higher doses are a first option (strong, moderate). Alternative options are to change therapy to another orally administered azole, or to initiate intrathecal AmB therapy.

• IV Amph B has now shown as effective

• increased ICP at the time of diagnosis, we recommend medical therapy and repeated lumbar punctures as initial management (strong, low).

Case

46M from Mexico who was recently diagnosed cocci meningitis started on fluconazole 400mg po daily 4 week ago at OSH . He came to ER complaining persistent headache. Outside record reviewed: cocci (+) from CSF culture. HCT wnl. LP was repeated: opening pressure not elevated. CSF culture cocci(+). Cocci titer was the same. What is the recommended management by IDSA?

1- Intrathecal L Amph B

2- Increase fluconazole dosage

3- Repeat daily LP

4- NS consult for shunt

Case

60F with ESRD s/p renal transplant 5 yrs ago on immunosuppressant moved from NY to Riverside 5 months ago came to ER for worsening dyspnea x 10days. 5 days ago, she was diagnosed as Valley fever with cocci titer(+)on fluconazole 400mg daliy. In ER, she wasfebrile and hypoxic. CXR bilateral ground glass. What is the antibiotic choice of this case by IDSA.

1- L amph B

2- L amph B and flucyutosin

3- Fluconazole 1200mg po daily

4- Fluconazole + L amph B

5- consult ID

Transplant Recipients With Active Coccidioidomycosis, Which Initial

Treatment Strategy Is Preferred: Oral Azole or Intravenous AmB?

Recommendations

- For transplant recipients with acute or chronic pulmonary coccidioidomycosis who are clinically stable and have normal renal function, we recommend initiating treatment with fluconazole 400 mg daily or the equivalent dose based upon renal function (strong, low).

- For the treatment of patients with very severe and/or rapidly progressing acute pulmonary or disseminated coccidioidomycosis, we recommend the use of AmB until the patient has stabilized, followed by fluconazole (strong, low).

- For transplant recipients with extrapulmonary coccidioidomycosis, we recommend the same treatment as for non–transplant recipients (strong, very low).

Case

60F with ESRD s/p renal transplant 5 yrs ago on immunosuppressant moved from NY to Riverside 5 months ago came to ER for worsening dyspnea x 10days. 5 days ago, she was diagnosed as Valley fever with cocci titer(+)on fluconazole 400mg daliy. In ER, febrile and hypoxic. CXR bilateral ground glass. What is the antibiotic choice of this case by IDSA.

1- L amph B

2- L amph B and flucyutosin

3- Fluconazole 1200mg po daily

4- Fluconazole + L amph B

5- Consult ID

In Such Patients, Should Antirejection Treatment Be

Modified or Continued Without Change?

For transplant recipients with severe or

rapidly progressing coccidioidomycosis,

we recommend reduction of

immunosuppression (without risking graft-

vs-host disease or organ rejection,

respectively, whenever possible) until the

infection has begun to improve (strong,

very low).

Coccidioidomycosis

• Close observation for healthy mild CAP

• Main treatment option is azoles

- When to use L-Amph

- When to call specialists, surgery

• If not sure, consult ID

Bugbowl 2nd round

What is the name of spirochete that is

transmitted by ixodes scapularis, that

does not have any cross-reaction to the

serum test of Lyme disease, and that

causes relapsing fever without rash?

Answer: Borrelia miyamotoi

Final Jeopardy

What is the Plasmodium that was

mistaken as P vivax in South America but

now known to be a novel spieces?

Answer:Plasmodium simium

Questions?

• What Is the Best Way to Manage Coccidioidomycosis in Patients Infected With HIV?

• Recommendations

• 45. Antifungal prophylaxis is not recommended to prevent coccidioidomycosis in patients infected with HIV living in coccidioidal-endemic regions (strong, moderate).

• 46. Antifungal therapy is recommended for all patients with HIV infection with clinical evidence of coccidioidomycosis and a peripheral blood CD4+ T-lymphocyte count <250 cells/µL (strong, moderate).

• 47. Antifungal therapy should be continued as long as the peripheral CD4+ T-lymphocyte count remains <250 cells/µL (strong, low).

• 48. For patients with peripheral CD4+ T-lymphocyte counts ≥250 cells/µL, clinical management of coccidioidomycosis should occur in the same manner as for patients without HIV infection, including discontinuing antifungal therapy in appropriate situations (strong, moderate).

• 49. Within coccidioidal-endemic regions, patients should receive yearly serologic screening and chest radiography for coccidioidomycosis (strong, low).

• 50. Outside coccidioidal-endemic regions, serologic screening is not recommended (strong, moderate).

• 51. Although data are lacking, pediatric patients with HIV infection and coccidioidomycosis should be managed in a manner similar to adult patients (strong, very low).

• 52. Initiation of potent antiretroviral therapy (ART) should not be delayed because of the concern about coccidioidal immune reconstitution inflammatory syndrome (strong, low).

• What Is the Best Way to Manage Coccidioidomycosis in Patients Infected With HIV?

• RECOMMENDATIONS FOR PREEMPTIVE STRATEGIES FOR COCCIDIOIDOMYCOSIS IN SPECIAL AT-RISK POPULATIONS

• XXVI. For Organ Transplant Recipients Without Active Coccidioidomycosis, Which Primary Prevention Strategy Is Preferred: Observation or Oral Azole?

• Recommendation

• 53. For all patients undergoing organ transplantation in the endemic area without active coccidioidomycosis, we recommend the use of an oral azole (eg, fluconazole 200 mg) for 6–12 months (strong, low).

• XXVII. For Recipients of Biological Response Modifiers Without Active Coccidioidomycosis, Which Primary Prevention Strategy Is Preferred: Observation or Prophylactic Antifungal Therapy?

• Recommendation

• 54. For patients in the endemic area, we recommend screening with Coccidioides serology prior to initiation of biologic response modifier therapy, as well as regular clinical follow-up for new signs and symptoms (strong, very low). We do not recommend regular serologic screening or antifungal prophylaxis in asymptomatic patients taking biologic response modifiers (BRMs) (strong, very low).

Case

44 healthy M from San Joaquin Valley came to ER for L knee pain. IVDU(-). HIV(-). Joint aspirate grew cocci. Cocci IgM(+). IgG(-). What is the recommended management for this case by IDSA?

1- Fluconazole

2- L-Amph

3- Surgical drainage + L amph

4- Observation