Severe Clostridium Difficile Infection in Children
Severe Clostridium Difficile Infection in Children
Background: The incidence and severity of Clostridium difficile infection(CDI) is increasing among adults; however, little is known about the epidemiology of CDI among children.
Methods: We conducted a nested case-control study to identify the risk factors for and a prospective cohort study to determine the outcomes associated with severe CDI at 2 children's hospitals. Severe CDI was defined as CDI and at least 1 complication or ≥2 laboratory or clinical indicators consistent with severe disease. Studied outcomes included relapse, treatment failure, and CDI-related complications. Isolates were tested to determine North American pulsed-field gel electrophoresis type 1 lineage.
Results: We analyzed 82 patients with CDI, of whom 48 had severe disease. Median age in years was 5.93 (1.78 –12.16) and 1.83 (0.67– 8.1) in subjects with severe and nonsevere CDI, respectively (P = 0.012). All patients with malignancy and CDI had severe disease. Nine subjects (11%) had North American pulsed-field gel electrophoresis type 1 isolates. Risk factors for severe disease included age (adjusted odds ratio [95% confidence interval]: 1.12 [1.02, 1.24]) and receipt of 3 antibiotic classes in the 30 days before infection (3.95 [1.19, 13.11]). If infants less than 1 year of age were excluded, only receipt of 3 antibiotic classes remained significantly associated with severe disease. Neither the rate of relapse nor treatment failure differed significantly between patients with severe and nonsevere CDI. There was 1 death.
Conclusions: Increasing age and exposure to multiple antibiotic classes were risk factors for severe CDI. Although most patients studied had severe disease, complications were infrequent. Relapse rates were similar to those reported in adults.
Clostridium difficile is the most common cause of healthcareassociated diarrhea in the United States, with significant associated morbidity, mortality, and healthcare costs. The clinical presentation of C. difficile infection (CDI) varies widely, ranging from self-limited diarrhea to toxic megacolon or death. Recently, the rate and severity of CDI have been increasing among adults. Much of this changing epidemiology has been attributed to the emergence of a hypervirulent strain of C. difficile, referred to as the North American pulsed-field gel electrophoresis type 1, or NAP1, strain.
The epidemiology of CDI among children has not been well characterized. However, recent studies have shown a rise in CDI among children in both community and hospital settings. Traditionally, C. difficile was believed to cause less significant disease among children than adults, although severe CDI in children has been reported. Furthermore, the hypervirulent NAP1 strain has also been identified among children. Still, the epidemiology of severe CDI in children remains undefined.
Previous antimicrobial use is accepted as the single most important risk factor for CDI, and nearly all antimicrobials have been associated with the development of CDI. Additional risk factors for severe CDI and poor outcomes reported in adults include the following host factors: advanced age, severity of underlying illness, and impaired immune status. Other risk factors, notably fluoroquinolone use and gastric acid suppression, have garnered recent attention. There are few epidemiologic studies evaluating risk factors for CDI in pediatric patients. We performed a prospective cohort study to determine the outcomes and a nested case-control study to determine the risk factors associated with severe CDI among hospitalized pediatric patients.
Abstract and Introduction
Abstract
Background: The incidence and severity of Clostridium difficile infection(CDI) is increasing among adults; however, little is known about the epidemiology of CDI among children.
Methods: We conducted a nested case-control study to identify the risk factors for and a prospective cohort study to determine the outcomes associated with severe CDI at 2 children's hospitals. Severe CDI was defined as CDI and at least 1 complication or ≥2 laboratory or clinical indicators consistent with severe disease. Studied outcomes included relapse, treatment failure, and CDI-related complications. Isolates were tested to determine North American pulsed-field gel electrophoresis type 1 lineage.
Results: We analyzed 82 patients with CDI, of whom 48 had severe disease. Median age in years was 5.93 (1.78 –12.16) and 1.83 (0.67– 8.1) in subjects with severe and nonsevere CDI, respectively (P = 0.012). All patients with malignancy and CDI had severe disease. Nine subjects (11%) had North American pulsed-field gel electrophoresis type 1 isolates. Risk factors for severe disease included age (adjusted odds ratio [95% confidence interval]: 1.12 [1.02, 1.24]) and receipt of 3 antibiotic classes in the 30 days before infection (3.95 [1.19, 13.11]). If infants less than 1 year of age were excluded, only receipt of 3 antibiotic classes remained significantly associated with severe disease. Neither the rate of relapse nor treatment failure differed significantly between patients with severe and nonsevere CDI. There was 1 death.
Conclusions: Increasing age and exposure to multiple antibiotic classes were risk factors for severe CDI. Although most patients studied had severe disease, complications were infrequent. Relapse rates were similar to those reported in adults.
Introduction
Clostridium difficile is the most common cause of healthcareassociated diarrhea in the United States, with significant associated morbidity, mortality, and healthcare costs. The clinical presentation of C. difficile infection (CDI) varies widely, ranging from self-limited diarrhea to toxic megacolon or death. Recently, the rate and severity of CDI have been increasing among adults. Much of this changing epidemiology has been attributed to the emergence of a hypervirulent strain of C. difficile, referred to as the North American pulsed-field gel electrophoresis type 1, or NAP1, strain.
The epidemiology of CDI among children has not been well characterized. However, recent studies have shown a rise in CDI among children in both community and hospital settings. Traditionally, C. difficile was believed to cause less significant disease among children than adults, although severe CDI in children has been reported. Furthermore, the hypervirulent NAP1 strain has also been identified among children. Still, the epidemiology of severe CDI in children remains undefined.
Previous antimicrobial use is accepted as the single most important risk factor for CDI, and nearly all antimicrobials have been associated with the development of CDI. Additional risk factors for severe CDI and poor outcomes reported in adults include the following host factors: advanced age, severity of underlying illness, and impaired immune status. Other risk factors, notably fluoroquinolone use and gastric acid suppression, have garnered recent attention. There are few epidemiologic studies evaluating risk factors for CDI in pediatric patients. We performed a prospective cohort study to determine the outcomes and a nested case-control study to determine the risk factors associated with severe CDI among hospitalized pediatric patients.
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