A 30-month-old boy is admitted to the hospital due to a 3-day history of fever, cough, and dyspnea. He has a history of recurrent infections, including 4 episodes of cervical lymphadenitis that responded slowly to treatment with clindamycin. Temperature is 38.2 C (100.8 F), blood pressure is 90/60 mm Hg, pulse is 100/min, and respirations are 30/min. The anterior cervical lymph nodes are palpated bilaterally with several firm, 1- to 1.5-cm nodes that are nontender, nonfluctuant, and without overlying erythema. Breath sounds are diminished at the left lower lung base. The abdomen is soft, nontender, and nondistended without hepatosplenomegaly. A chest x-ray reveals a patchy infiltrate in the left lower lobe and a moderately sized pleural effusion. A chest tube is placed, and cloudy fluid is obtained. Laboratory results are as follows: Microscopy of pleural fluid shows numerous, intact gram-negative rods within neutrophils; cultures ultimately grow Burkholderia cepacia. The patient's condition improves with appropriate treatment. Which of the following is most appropriate for infection prophylaxis for this patient?
A)Azithromycin and palivizumab
B)Granulocyte colony-stimulating factor
C)Intravenous immunoglobulin
D)Trimethoprim-sulfamethoxazole and itraconazole

Question

A 30-month-old boy is admitted to the hospital due to a 3-day history of fever, cough, and dyspnea.  He has a history of recurrent infections, including 4 episodes of cervical lymphadenitis that responded slowly to treatment with clindamycin.  Temperature is 38.2 C (100.8 F), blood pressure is 90/60 mm Hg, pulse is 100/min, and respirations are 30/min.  The anterior cervical lymph nodes are palpated bilaterally with several firm, 1- to 1.5-cm nodes that are nontender, nonfluctuant, and without overlying erythema.  Breath sounds are diminished at the left lower lung base.  The abdomen is soft, nontender, and nondistended without hepatosplenomegaly.  A chest x-ray reveals a patchy infiltrate in the left lower lobe and a moderately sized pleural effusion.  A chest tube is placed, and cloudy fluid is obtained.  Laboratory results are as follows:  Microscopy of pleural fluid shows numerous, intact gram-negative rods within neutrophils; cultures ultimately grow Burkholderia cepacia.  The patient's condition improves with appropriate treatment.  Which of the following is most appropriate for infection prophylaxis for this patient?
A)Azithromycin and palivizumab 
B)Granulocyte colony-stimulating factor 
C)Intravenous immunoglobulin 
D)Trimethoprim-sulfamethoxazole and itraconazole

Quizplus · Accepted Answer

Explanation: 11ec2b69_c0da_1190_8f63_61f1259d629e_MD0005_00 This patient with a history of recurrent infections has evidence of intact organisms within neutrophils, suggestive of impaired neutrophilic intracellular killing. The most likely cause is chronic granulomatous disease (CGD), an X-linked immunodeficiency in which a defect in NADPH oxidase prevents the neutrophil respiratory burst and superoxide formation. These reactive oxygen species (ROS) normally lead to the activation of lysosomal proteases involved in pathogen destruction; however, in CGD, organisms are engulfed by phagocytes but cannot be destroyed within phagolysosomes. Although neutrophils are defective, absolute count is normal or elevated with infection, as seen in this patient. Patients with CGD are predisposed to recurrent infections by catalase-positive bacteria and fungi (Staphylococcus aureus, Burkholderia cepacia, Serratia, Nocardia, Aspergillus); these organisms can degrade their own hydrogen peroxide, making it unavailable for use by the defective neutrophils that cannot produce ROS. Infections most commonly involve the skin (eg, abscess), lymph nodes (eg, adenitis), and lungs (eg, pneumonia) and are often difficult to treat, requiring prolonged courses of antibiotics. In addition to treatment of active infection, prophylactic antibiotic (ie, trimethoprim-sulfamethoxazole) and antifungal (ie, itraconazole) therapies are required to decrease the risk for life-threatening infections by the most common organisms. In severe cases, immunomodulatory therapy with interferon gamma may also be considered. (Choice A) Azithromycin and palivizumab are sometimes used in patients with cystic fibrosis (CF) to help prevent lung infection due to mycobacteria and respiratory syncytial virus, respectively. Unlike in this patient, intact organisms within neutrophils would not be seen with CF. Moreover, recurrent infection (including with B cepacia) is typically limited to the sinopulmonary tract, and this patient's recurrent lymphadenitis makes CF less likely. In CGD, mycobacterial infections are less common and do not warrant prophylaxis; patients are not at high risk for viral infections. (Choice B) Granulocyte colony-stimulating factor is used to enhance neutrophil production in patients with neutropenia (eg, autoimmune, chemotherapy-induced), which is not present in this patient. (Choice C) Intravenous immunoglobulin repletes immunoglobulins in patients with low levels, such as in X-linked agammaglobulinemia. Immunoglobulin deficiency typically presents with recurrent sinopulmonary infections by encapsulated bacteria due to lack of opsonizing IgG and mucosal IgA. This patient's lymphadenitis and Burkholderia infection make CGD more likely, and immunoglobulin levels are normal in CGD. Educational objective: Chronic granulomatous disease presents with recurrent infections by catalase-positive organisms (eg, Burkholderia cepacia) due to impaired neutrophilic intracellular killing. Prophylactic trimethoprim-sulfamethoxazole and itraconazole are indicated to prevent high-risk infections. References: Chronic granulomatous disease. (http://www.ncbi.nlm.nih.gov/pubmed/29630223)

A 30-Month-Old Boy Is Admitted to the Hospital Due to a 3-Day