A 5-year-old boy is undergoing a partial hepatectomy to treat a poorly draining liver abscess. He has a history of recurrent skin abscesses. Cultures from his liver abscess are growing Staphylococcus aureus, which is sensitive to the current antibiotic regimen, but the abscess has failed to improve. Genetic analysis reveals an inactivating mutation affecting a neutrophil oxidase enzyme. This patient most likely has an increased risk of infection with which of the following organisms?

Question

A 5-year-old boy is undergoing a partial hepatectomy to treat a poorly draining liver abscess.  He has a history of recurrent skin abscesses.  Cultures from his liver abscess are growing Staphylococcus aureus, which is sensitive to the current antibiotic regimen, but the abscess has failed to improve.  Genetic analysis reveals an inactivating mutation affecting a neutrophil oxidase enzyme.  This patient most likely has an increased risk of infection with which of the following organisms?

Quizplus · Accepted Answer

11ec160b_3a71_2e78_9249_635b431e5d09_MD0001_00 This patient with a mutation in the neutrophil oxidase enzyme has chronic granulomatous disease (CGD), a condition that results in recurrent bacterial and fungal infections due to impaired intracellular killing by phagocytes. CGD is caused by a genetic defect in the NADPH oxidase complex. NADPH oxidase normally functions to transfer an electron from NADPH to oxygen, resulting in the production of superoxide (O₂^•−) and other reactive oxygen species such as hydroxyl radicals (HO^•) and hydrogen peroxide (H₂O₂). These oxidants activate granule proteases (eg, elastase, cathepsin G) that destroy engulfed pathogens and also have direct microbicidal activity. Most microorganisms produce H₂O₂ as a waste product of metabolism, which can help activate microbicidal peptides within defective neutrophils in patients with CGD. However, some pathogens also produce catalase, which can destroy their own metabolically produced H₂O₂. As a result, the bacteria and fungi responsible for infections in CGD are usually catalase-positive organisms, particularly the following: (Choices B and E) Catalase-negative organisms (eg, Enterococcus faecalis, Streptococcus pyogenes) cannot prevent the accumulation of H₂O₂ within phagosomes, a process that allows the phagocytes to generate potent microbicidal agents (eg, hypochlorite) and activate granule proteases even when host O₂^•− production is impaired. (Choices C and D) Patients with CGD are at increased risk of bacterial and fungal infections, not parasitic (Giardia lamblia) or viral (herpes simplex virus type 1) infections. Educational objective: Chronic granulomatous disease (CGD) results from defective NADPH oxidase. Normally, this enzyme participates in the respiratory burst pathway to produce reactive oxygen species critical in intracellular pathogen killing. Patients with CGD develop recurrent bacterial and fungal infections predominantly caused by 5 catalase-positive organisms: Staphylococcus aureus, Burkholderia cepacia, Serratia marcescens, Nocardia, and Aspergillus. __________ References: Chronic granulomatous disease. (http://www.ncbi.nlm.nih.gov/pubmed/29630223)

A 5-Year-Old Boy Is Undergoing a Partial Hepatectomy to Treat