A 37-year-old man with a chronic cough

THE PATIENT BEGINS TREATMENT

2. Which treatment is most appropriate for this patient?

• Posaconazole (Noxafil)
• Caspofungin (Cancidas) and surgery
• Fluconazole
• Voriconazole (Vfend) and surgery
• Amphotericin B

Solitary pulmonary cavities tend to be asymptomatic and do not require treatment, even if coccidioidal infection is microbiologically confirmed.

However, if there is pain, hemoptysis, or bacterial superinfection, antifungal therapy may result in improvement but not closure of the cavity.¹⁸ Therefore, in all cases of symptomatic coccidioidal pulmonary cavities, surgical resection is the only definitive treatment.

Coccidioidal cavities may rupture and cause pyopneumothorax, but this is an infrequent complication, and antifungal therapy combined with surgical decortication is the treatment of choice.¹⁸

Commonly prescribed antifungals include fluconazole and amphotericin B, the latter usually reserved for patients with significant hypoxia or rapid clinical deterioration.¹⁸ At this time, there are not enough clinical data to show that voriconazole or posaconazole is effective, and thus neither is approved for the treatment of coccidioidomycosis. Likewise, there have been no human trials of the efficacy of caspofungin against Coccidioides infection, although it has been shown to be active in mouse models.¹⁸

Our patient was started on oral fluconazole and observed for clinical improvement or, conversely, for signs of dissemination. After 2 days, he had markedly improved, and within 1 week he was almost back to his baseline level of health. Testing for all other infectious etiologies was unrevealing, and he was removed from negative pressure isolation.

However, as we mentioned above, his CD4 count was 5 cells/μL. We discussed the issue with the patient, and he said he was willing to comply with his treatment for both his Coccidioides and his HIV infection. After much deliberation, he said he was also willing to start and comply with prophylactic treatment for opportunistic infections.

PREVENTING OPPORTUNISTIC INFECTIONS IN HIV PATIENTS

3. Which of the following prophylactic regimens is most appropriate for this patient?

• Trimethoprim-sulfamethoxazole, atovaquone (Mepron), and azithromycin
• Trimethoprim-sulfamethoxazole and azithromycin
• Pentamidine (Nebupent), dapsone, and clarithromycin (Biaxin)
• Dapsone and clarithromycin
• Trimethoprim-sulfamethoxazole by itself

According to guidelines for the prevention of opportunistic diseases in patients with HIV, he needs primary prophylaxis against the following organisms: P jirovecii, Toxoplasma gondii, and Mycobacterium avium complex.¹

The CD4 count dictates the appropriate time to start therapy. If the count is lower than 200 cells/μL or if the patient has oropharyngeal candidiasis regardless of the CD4 count, trimethoprim-sulfamethoxazole is indicated to prevent P jirovecii pneumonia. In those who cannot tolerate trimethoprim-sulfamethoxazole or who are allergic to it, dapsone, pentamidine, or atovaquone can be substituted.¹

In patients seropositive for T gondii, a CD4 count lower than 100/μL indicates the need for prophylaxis.¹ Prophylactic measures are similar to those for Pneumocystis. However, if the patient cannot tolerate trimethoprim-sulfamethoxazole, the recommended alternative is dapsone-pyrimethamine with leucovorin, which is also effective against Pneumocystis.¹

Finally, if the CD4 count is lower than 50 cells/μL, prophylaxis against M avium complex is mandatory, with either azithromycin weekly or clarithromycin daily.¹

Given our patient’s degree of immunosuppression, trimethoprim-sulfamethoxazole plus azithromycin is his most appropriate option.

Trimethoprim-sulfamethoxazole and azithromycin were added to his antimicrobial regimen before he was discharged. Two weeks later, he noted no side effects from any of the medications, he had no new symptoms, he was feeling well, and his cough had improved greatly. He did not have any signs of dissemination of his coccidioidal infection, and we concluded that the primary and only infection was located in the lungs.

DISSEMINATED COCCIDIOIDOMYCOSIS

4. Which of the following extrapulmonary sites is Coccidioides least likely to infect?

• Brain
• Skin
• Meninges
• Lymph nodes
• Bones
• Joints

Extrapulmonary coccidioidomycosis can involve almost any site. However, the most common sites of dissemination are the skin, lymph nodes, bones, and joints.¹⁴ The least likely site is the brain.

Central nervous system involvement

In the central nervous system, involvement is typically with the meninges, rather than frank involvement of the brain parenchyma.^18,28,29 Although patients with HIV or those who are otherwise severely immunocompromised are at higher risk for coccidioidal meningitis, it is rare even in this population.^30,31 Meningitis most commonly presents as headache, vomiting, meningismus, confusion, or diplopia.^32,33

If neurologic findings are absent, experts do not generally recommend lumbar puncture because the incidence of meningeal involvement is low. When cerebrospinal fluid is obtained in an active case of coccidioidal meningitis, fluid analysis typically finds elevated protein, low glucose, and lymphocytic pleocytosis.^1,32

Meningeal enhancement on CT or magnetic resonance imaging is common.³⁴ The diagnosis is established by culture or serologic testing of cerebrospinal fluid (IgM titer, IgG titer, immunodiffusion, or complement fixation).¹⁴

Of note, cerebral infarction and hydrocephalus are feared complications and pose a serious risk of death in any patient.^32,35 In these cases, treatment with antifungals is lifelong, regardless of immune system status.¹⁸

Skin involvement

Skin involvement is variable, consisting of nodules, verrucae, abscesses, or ulcerations.^15,16 Hemorrhage from the skin is relatively common.³⁶ From the skin, the infection can spread to the lymph nodes, leading to regional lymphadenopathy.^14,15 Nodes can ulcerate, drain, or even become necrotic.

Bone and joint involvement

Once integrity of the blood vessels is disrupted, Coccidioides can spread via the blood to the bones or joints,^14,15 causing osteomyelitis, septic arthritis, or synovitis. Subcutaneous abscesses or sinus tracts may subsequently develop.^14,15