What is the diagnosis for a 2-year-old boy with persistent fever, bilateral focal pneumonia, and granuloma formation, with cultures growing Burkholderia (Pseudomonas) cepacia?

From the Guidelines

This patient likely has chronic granulomatous disease (CGD) and should be treated with targeted antibiotics, including trimethoprim-sulfamethoxazole, and possibly additional agents like ceftazidime, meropenem, or ciprofloxacin for B. cepacia, as recommended by the Infectious Diseases Society of America guidelines 1. The clinical presentation strongly supports this diagnosis: a young boy with history of perirectal abscess (a common manifestation of CGD), persistent pneumonia unresponsive to standard antibiotics, granuloma formation on biopsy, and infection with Burkholderia cepacia, which is a catalase-positive organism typically pathogenic only in immunocompromised hosts. Key points to consider in the management of this patient include:

• Targeted antibiotic therapy based on susceptibility testing, with consideration of trimethoprim-sulfamethoxazole, ceftazidime, meropenem, or ciprofloxacin for B. cepacia, as suggested by the guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia 1.
• Long-term management with prophylactic trimethoprim-sulfamethoxazole (5 mg/kg/day of the trimethoprim component divided twice daily) and itraconazole (5 mg/kg/day) to prevent bacterial and fungal infections.
• Consideration of interferon-gamma (50 μg/m² subcutaneously three times weekly) to reduce infection frequency.
• Definitive diagnosis requires neutrophil function testing, such as dihydrorhodamine (DHR) flow cytometry or nitroblue tetrazolium (NBT) test, and genetic testing to identify the specific mutation, with X-linked being most common.
• Hematopoietic stem cell transplantation is potentially curative and should be considered, especially for patients with severe disease manifestations.

From the FDA Drug Label

FORTAZ is indicated for the treatment of patients with infections caused by susceptible strains of the designated organisms in the following diseases: 1. Lower Respiratory Tract Infections, including pneumonia, caused by Pseudomonas aeruginosa and other Pseudomonas spp. The patient has bilateral focal pneumonia caused by Burkholderia (Pseudomonas) cepacia, which is a type of Pseudomonas. The drug ceftazidime is indicated for the treatment of Lower Respiratory Tract Infections, including pneumonia, caused by Pseudomonas aeruginosa and other Pseudomonas spp. However, Burkholderia (Pseudomonas) cepacia is not explicitly mentioned in the drug label as a susceptible organism. Therefore, no conclusion can be drawn about the effectiveness of ceftazidime for this specific patient 2.

From the Research

Treatment Options for Burkholderia cepacia Infections

• The patient has been diagnosed with Burkholderia cepacia complex (BCC) infection, which is a group of pathogens that can cause severe infections in people with cystic fibrosis, chronic granulomatous disease, and immunocompromised patients 3.
• The treatment options for BCC infections are limited due to high levels of resistance to many antimicrobial agents, but ceftazidime, meropenem, and penicillins, mainly piperacillin, may be considered as alternative options 3.
• A study found that trimethoprim-sulfamethoxazole had the highest susceptibility rate (83%) against BCC isolates, followed by ceftazidime/avibactam (78%) 4.
• Another study found that 81% of BCC strains were susceptible to ceftazidime-avibactam, and 63% were susceptible to ceftolozane-tazobactam 5.

Management and Outcomes of BCC Infections

• A retrospective study found that the management and outcomes of BCC bacteremia in patients without cystic fibrosis were mostly hospital-acquired and central venous catheter-related 6.
• The study found that early removal of the catheter is crucial in the treatment of catheter-related BCC bacteremia, and delayed removal was associated with a higher rate of persistent bacteremia and lower rate of clinical response 6.
• The 14-day, 30-day, and in-hospital mortality rates for BCC bacteremia were 19.4%, 23.1%, and 31.0%, respectively, and female sex, liver cirrhosis, septic shock, and catheter-related infection were independent risk factors for 30-day mortality 6.

Antibiotic Susceptibility and Resistance

• A study found that there were major discrepancies between standard susceptibility results and activity in artificial sputum medium, and some antibiotics showed minimal activity despite low minimal inhibitory concentrations 7.
• The study found that tobramycin was more active in high-density growth conditions than in standard time-kill assays, and ceftazidime showed minimal activity in all time-kill assays despite low minimal inhibitory concentrations 7.
• Another study found that the majority of BCC isolates carried blaPenA (98%) and blaAmpC (86%) resistance genes, and aztreonam in combination with ceftazidime/avibactam had no synergistic effect in BCC isolates 4.