What is the likely diagnosis for a 4-month-old boy with persistent fever, cough, and shortness of breath, who has multifocal pneumonia with cavitation and cultures positive for Nocardia, a filamentous, gram-positive rod, suggesting immunodeficiency?

From the Guidelines

This infant likely has chronic granulomatous disease (CGD), a primary immunodeficiency characterized by defective neutrophil function, and should be treated with trimethoprim-sulfamethoxazole for the Nocardia infection and considered for hematopoietic stem cell transplantation. The presentation of recurrent infections (cervical lymphadenitis at 2 months, now pneumonia), failure to respond to conventional antibiotics, and infection with an opportunistic pathogen like Nocardia strongly suggests CGD, as noted in the practice parameter for the diagnosis and management of primary immunodeficiency 1. This condition results from mutations in genes encoding components of the NADPH oxidase complex, preventing phagocytes from generating reactive oxygen species needed to kill certain pathogens.

Key Considerations

• Treatment should include trimethoprim-sulfamethoxazole for the Nocardia infection, typically at 8-10 mg/kg/day (based on trimethoprim component) divided twice daily for at least 6-12 months, as suggested by guidelines for the diagnosis and management of skin and soft tissue infections 1.
• Long-term prophylaxis with trimethoprim-sulfamethoxazole (5 mg/kg/day of trimethoprim component) and itraconazole (5 mg/kg/day) is recommended to prevent future infections.
• Interferon-gamma (50 μg/m² subcutaneously three times weekly) may also be beneficial.
• Definitive diagnosis requires neutrophil function testing such as dihydrorhodamine (DHR) flow cytometry or nitroblue tetrazolium (NBT) test.
• Genetic testing should be performed to identify the specific mutation.
• Hematopoietic stem cell transplantation represents the only curative option and should be considered, especially for patients with severe disease manifestations.

Management of Pneumonia

The management of community-acquired pneumonia in infants and children older than 3 months of age should follow clinical practice guidelines by the pediatric infectious diseases society and the infectious diseases society of America 1. These guidelines emphasize the importance of assessing the severity of illness, using tools such as pulse oximetry, and considering the need for hospitalization based on factors such as respiratory distress, hypoxemia, and comorbid conditions.

Prognosis and Quality of Life

The prognosis and quality of life for patients with CGD can be significantly improved with appropriate treatment and management, including long-term prophylaxis and consideration of hematopoietic stem cell transplantation. Early diagnosis and intervention are critical to preventing recurrent infections and reducing the risk of complications.

From the FDA Drug Label

At least 90 percent of the following bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for imipenem against isolates of similar genus or organism group. However, the efficacy of imipenem in treating clinical infections due to these bacteria has not been established in adequate and well-controlled clinical trials Aerobic bacteria Gram-positive bacteria Bacillus spp. Listeria monocytogenes Nocardia spp. Staphylococcus saprophyticus Group C streptococci Group G streptococci Viridans group streptococci

The patient has been diagnosed with Nocardia infection. According to the drug label, imipenem has been shown to have in vitro activity against Nocardia spp. However, the efficacy of imipenem in treating clinical infections due to Nocardia has not been established in adequate and well-controlled clinical trials 2 2. Therefore, the use of imipenem for the treatment of Nocardia infection is not supported by the FDA drug label.

From the Research

Nocardia Infection Treatment

• The patient is diagnosed with Nocardia infection, which is a type of bacterial infection that can cause pneumonia and other diseases 3, 4.
• Trimethoprim-sulfamethoxazole (TMP-SMX) is a commonly used antibiotic combination for treating Nocardia infections, including pulmonary and disseminated nocardiosis 3, 4, 5.
• TMP-SMX works by inhibiting the growth of bacteria, including Nocardia, by blocking the synthesis of folic acid, which is essential for bacterial growth 6.

Immunodeficiency Suspected

• The patient's history of recurrent infections, including cervical lymphadenitis and Nocardia infection, suggests that the patient may have an underlying immunodeficiency 3, 4.
• Immunodeficiency can increase the risk of developing opportunistic infections, such as Nocardia infection, and can make it more difficult to treat these infections 3, 4.

Treatment Options

• TMP-SMX is the drug of choice for treating Nocardia infections, and it is often used in combination with other antibiotics to treat severe or disseminated infections 4, 5.
• The patient's treatment should be guided by the results of culture and susceptibility testing to ensure that the most effective antibiotic regimen is used 3, 4, 5.
• Other antibiotics, such as amikacin and imipenem, may also be effective against Nocardia infections, but TMP-SMX is generally considered the first-line treatment 3, 4.