What are the recommended lab tests and treatment for a suspected Cocci infection?

Recommended Laboratory Testing for Suspected Coccidioidomycosis

For suspected coccidioidomycosis, order multiple complementary diagnostic tests simultaneously: serology (IgM and IgG antibodies via EIA with confirmatory immunodiffusion or complement fixation), urine and serum antigen testing, and respiratory culture from sputum or BAL—no single test is sufficient due to variable sensitivities. 1

Core Diagnostic Testing Strategy

Serological Testing (Primary Diagnostic Method)

• Order serology on all patients with suspected coccidioidomycosis, looking for IgM antibodies (appear 1-3 weeks after symptom onset) followed by IgG antibodies (appear 4-8 weeks later) 2
• Use initial EIA testing followed by confirmatory immunodiffusion (ID) or complement fixation (CF) testing 1
• Obtain quantitative CF testing and repeat approximately every 12 weeks during treatment to evaluate therapeutic response 2
• Be aware that serologic tests may be negative early in infection or persistently negative despite active disease, particularly in immunocompromised patients 1, 2

Antigen Testing

• Perform urinary and serum antigen testing, especially in immunocompromised patients (HIV with CD4+ <250 cells/µL, transplant recipients, those on high-dose corticosteroids ≥20 mg/day for ≥2 weeks, TNF inhibitor users) 1, 2
• Urine and serum antigen testing are complementary—some samples are positive in either serum or urine but not both 1
• Coccidioidal antigen testing via EIA is available at reference laboratories and is particularly helpful when antibody responses are blunted 2

Culture and Direct Visualization

• Order fungal culture from respiratory specimens (sputum, BAL, or other biopsy material) if the patient is severely ill or hospitalized 1, 2
• Coccidioides grows on routine blood agar and Sabouraud dextrose agar at 25-30°C, with mycelial growth visible as early as 4-5 days (hold cultures up to 6 weeks) 2
• Culture from any clinical site proves the diagnosis, though sensitivity is low 1
• Histopathology showing spherules or endospores is considered proven disease, even without positive culture 2

Blood Cultures

• Consider 2-4 sets of blood cultures if disseminated infection is suspected, though these are less commonly positive than respiratory cultures 2

Essential Baseline Workup

Imaging and Laboratory Studies

• Obtain chest radiograph in all patients—look for dense infiltrates (often upper lobe), hilar or mediastinal adenopathy 2
• Order complete blood count with differential, creatinine, electrolytes, hepatic transaminases, and total bilirubin 1

Risk Factor Documentation

• Document specific high-risk features: immunosuppression status, pregnancy (especially third trimester), African or Filipino ancestry, diabetes, cardiopulmonary comorbidities 2

Severity Assessment and Warning Signs

Markers Warranting Treatment

• Weight loss >10% 2
• Night sweats >3 weeks duration 2
• Infiltrates exceeding 50% of one lung or bilateral disease 2
• CF titers ≥1:16 (equivalent to 1/32 or higher) 2

Signs of Dissemination Requiring Immediate Evaluation

• Progressive headache or mental status changes 2
• New skin lesions (cutaneous involvement occurs in 15-67% of disseminated cases) 2
• Unexplained nausea or vomiting 2
• Focal neurologic deficits 2

Cerebrospinal Fluid Analysis

When to Perform Lumbar Puncture

• Obtain CSF sample from all patients with sustained headache, altered mental status, unexplained nausea/vomiting, or focal neurologic deficits 2

CSF Testing

• Order complement fixation test on CSF as the recommended method for suspected coccidioidal meningitis 2
• CSF typically shows low glucose, elevated protein, lymphocytic pleocytosis 2
• CF antibody is frequently detected in CSF, though culture is positive in <33% of cases 2

Critical Diagnostic Pitfalls to Avoid

Interpretation Errors

• Do not rely solely on CF antibody titers to diagnose disseminated disease—while higher titers correlate with dissemination in groups, individual variability is substantial and tissue diagnosis is usually required 2
• Do not rule out coccidioidomycosis based on negative serology alone—antibody tests may remain negative despite active infection, especially early or in immunosuppressed patients 1, 2
• Do not assume positive serology equals disseminated disease—any positive antibody test usually indicates recent or active infection, but tissue-destructive lesions require direct evidence 2

Special Population Considerations

• In HIV-infected patients with CD4+ counts <250 cells/µL, serologic tests are less frequently positive than in immunocompetent persons 2
• In immunosuppressed patients, maintain higher clinical suspicion as serologic responses may be blunted 2
• Cross-reactivity with other fungal infections can occur—interpret both positive and negative results in the context of symptomatology and radiological findings 1

Temporal Considerations

• Serological testing for coccidioidomycosis can wane over time and results might become negative after successful treatment of infection 1