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 cystic fibrosis (CF), a genetic disorder affecting the respiratory, digestive, and reproductive systems, given the history of persistent pneumonia, pleural effusion, and granuloma formation with Burkholderia cepacia infection, which is a common pathogen in CF patients. The diagnosis is supported by the presence of Burkholderia cepacia, a bacterium commonly found in CF patients, as stated in Summary Statement 50 1. Treatment should include targeted antibiotics based on susceptibility testing, such as intravenous tobramycin, ceftazidime, or both, as mentioned in Summary Statement 51 1.

Key points to consider in the management of this patient include:

• The patient's persistent fever and pneumonia despite empiric antibiotic therapy suggest a complex infection, possibly related to an underlying condition like CF.
• The presence of granuloma formation and Burkholderia cepacia infection supports the diagnosis of CF, as these are common findings in CF patients, as noted in Summary Statement 50 1.
• The patient's history of perirectal abscess at a young age may also be related to CF, as patients with CF are at increased risk of developing gastrointestinal complications.
• Definitive diagnosis of CF can be made using the Gibson-Cooke sweat test or quantitative pilocarpine iontophoresis, as stated in the provided evidence 1.
• Long-term management of CF includes aggressive pulmonary therapy, pancreatic enzyme replacement, and nutritional support, as well as regular monitoring for complications such as bronchiectasis and malnutrition.

The underlying pathophysiology of CF involves defects in the CF transmembrane conductance regulator (CFTR) gene, leading to abnormal chloride ion transport and increased viscosity of exocrine secretions, particularly in the airway and gastrointestinal tract, as explained in the provided evidence 1. This results in recurrent respiratory infections, pancreatic insufficiency, and other complications. Given the high suspicion of CF, further testing, including sweat testing and genetic analysis, should be pursued to confirm the diagnosis and guide management.

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 spp. The ceftazidime drug label indicates that it is effective against Pseudomonas aeruginosa and other Pseudomonas spp. However, Burkholderia (Pseudomonas) cepacia is not explicitly mentioned in the label as being susceptible to ceftazidime. Therefore, no conclusion can be drawn about the effectiveness of ceftazidime against Burkholderia (Pseudomonas) cepacia 2.

From the Research

Treatment Options for Burkholderia cepacia Infections

The patient's condition, characterized by persistent fever after empiric antibiotic therapy and the growth of Burkholderia cepacia in biopsy cultures, necessitates a review of effective treatment options.

• The use of ceftazidime, meropenem, and penicillins (mainly piperacillin) has been considered as alternative options for BCC infections, according to in vitro antimicrobial susceptibility patterns and clinical results 3.
• In vitro susceptibility testing has shown that ceftazidime-avibactam and ceftolozane-tazobactam have activity against BCC strains, with 81% and 63% of strains being susceptible, respectively 4.
• However, standard antimicrobial susceptibility testing methods have poor predictive value for clinical outcomes in BCC infections, highlighting the need for more clinically relevant testing approaches 5.
• The evaluation of antimicrobial susceptibility testing methods for BCC isolates has shown that broth microdilution (BMD) and MicroScan WalkAway have limited reproducibility and accuracy, with only meropenem meeting acceptance criteria for BMD 6.

Considerations for Initial Antimicrobial Management

Given the severity of the patient's condition and the potential for sepsis, initial antimicrobial management should prioritize broad-spectrum therapy.

• Immediate, empiric, broad-spectrum therapy is necessary for severe sepsis and/or shock, but this approach should be accompanied by a commitment to de-escalation and antimicrobial stewardship 7.
• The use of biomarkers such as procalcitonin can provide decision support for antibiotic use and guide duration of therapy.
• Consideration of newer antimicrobial agents may be necessary due to the potential involvement of drug-resistant pathogens.