- Research article
- Open Access
National age group trends in Clostridium difficile infection incidence and health outcomes in United States Community Hospitals
BMC Infectious Diseases volume 16, Article number: 682 (2016)
Prior studies have demonstrated an increase in Clostridium difficile infection (CDI) incidence in the United States (U.S.) in recent years, but trends among different age groups have not been evaluated. This study describes national CDI incidence by age group over a 10-year period and mortality and hospital length of stay (LOS) among patients with CDI.
This was a retrospective analysis of the U.S. National Hospital Discharge Surveys from 2001 to 2010. Eligible patients with an ICD-9-CM discharge diagnosis code for CDI (008.45) were stratified by age: <18 years (pediatrics), 18–64 years (adults), and ≥65 years (elderly adults). Data weights were used to derive national estimates. CDI incidence was calculated as CDI discharges/1000 total discharges. Mortality and LOS were compared between age groups using chi-square or Wilcoxon rank sum tests.
These data represent 2.3 million hospital discharges for CDI over the study period. CDI incidence was highest among elderly adults (11.6 CDI discharges/1000 total discharges), followed by adults (3.5 CDI discharges/1000 total discharges) and pediatrics (1.2 CDI discharges/1000 total discharges). The elderly also had higher rates of mortality (8.8%) compared to adults (3.1%) and pediatrics (1.4%) (p < 0.0001). In addition, median hospital LOS was highest in the elderly (8 days) compared to adults (7 days) and pediatrics (6 days) (p < 0.0001).
CDI incidence among patients hospitalized in U.S. hospitals differed based on age group between 2001 and 2010. CDI incidence, mortality, and hospital LOS were highest in the elderly adult population.
Clostridium difficile is the most prevalent pathogen among healthcare-associated infections and recognized by the Centers of Disease Control and Prevention (CDC) as one of the top three urgent threats to public health [1, 2]. C. difficile infection (CDI) often presents as diarrhea, but can result in more severe clinical manifestations like toxic megacolon, intestinal perforation, and sepsis. Additionally, CDI can result in death (approximately 29,000 deaths in 2011) , prolonged patient hospital stays [4–6], and a marked increase in the economic burden on the healthcare system with mean attributable costs ranging from $8,911 to $30,049 per patient .
CDI incidence nearly doubled in United States (U.S.) community hospitals between 2001 and 2010 . A similar report by the Agency for Healthcare Research and Quality (AHRQ) estimated that the number of hospitalizations due to CDI in the U.S. increased almost four times from 1993 to 2009 with the majority of cases affecting individuals 65 and older . Prior studies have affirmed that CDI disproportionately affects the elderly, likely due to immunosuppression from advanced age or chronic comorbidities, more health care exposures, and greater antibiotic use [10, 11]. Despite this, it is unknown if incidence trends differ among age groups [3, 12]. Furthermore, trends in CDI health outcomes have not been explored by age group.
The objectives of this study were to: 1) identify national CDI incidence trends by age group and 2) describe mortality and hospital length of stay (LOS) among CDI patients by age group over a 10-year period.
This study utilized data from the CDC’s National Hospital Discharge Surveys (NHDS) from 2001 to 2010. The NHDS survey design and variable definitions have been described previously . Several prior infectious diseases epidemiological studies, specifically evaluating healthcare-associated infections, have utilized NHDS data [8, 14, 15]. The UT Health Science Center San Antonio Institutional Review Board waived formal ethics approval and patient consent, as these data are publically available and do not contain any patient identifiers.
This was a retrospective analysis of patients discharged from U.S. hospitals from 2001 to 2010. Patients were included if they had any (principal or secondary) International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) discharge diagnosis code for CDI (008.45). The cohort was categorized into three age groups: pediatrics (<18 years), adults (18–64 years), and elderly adults (≥65 years).
Baseline patient demographics, as provided by the NHDS variable categories, were summarized using median (interquartile range) for continuous variables and counts (percentages) for categorical variables. Annual CDI incidence rates were calculated between 2001 and 2010 using CDI discharges in each age group as the numerator and total discharges in each age group as the denominator. Data weights were applied to derive national estimates. Patient mortality represented all-cause, in-hospital mortality and was identified by the “discharge status” variable of the NHDS. Hospital LOS was identified using the “days of care” variable of the NHDS.
CDI incidence was compared by age group using the z-score. Patient baseline characteristics, mortality, and hospital LOS were compared by age group using appropriate bivariable statistics (chi-square test for categorical variables and Wilcoxon rank sum test for continuous variables). JMP 10.0® (SAS Corp, Cary, NC) was used for all statistical comparisons.
Approximately 2.3 million CDI discharges over the study period were included for analysis. Table 1 describes the patients’ baseline demographics and hospital, payment, and admissions characteristics. Of these patients, 67.5% were elderly adults, 28.9% were adults, and 3.6% were pediatrics. The patient population was predominately female (58.7%) and White (85.6%), with a median (IQR) age of 74 (59–83) years. The median age for each group was as follows: pediatrics (6 years), adults (53 years), and elderly adults (80 years). Adult, elderly adult, and pediatric patients with CDI significantly differed with respect to patient sex, race, hospital size and ownership, principal payment source, and admission type and source (p < 0.0001 for all) (Table 1). The principal payment source was Medicare for 67% of patient discharges, as expected by the high proportion of elderly adult discharges in the study population. The primary admission source was through the emergency room for adults (60.3%) and elderly adults (59.8%); however; pediatric patients were more likely to be admitted by referral (39.2%).
CDI incidence by age group
Overall, CDI incidence significantly differed among age groups (p < 0.0001) (Table 2). CDI incidence was higher for elderly adults (11.6 CDI discharges/1000 total discharges), compared to adults (3.5 CDI discharges/1000 total discharges) and pediatric populations (1.2 CDI discharges/1000 total discharges). Elderly adults experienced the greatest change in CDI incidence over the study period (from 7.2 CDI discharges/1000 elderly adult discharges in 2001 to 13.7 CDI discharges/1000 elderly adult discharges in 2010) (Fig. 1). Among adults, CDI incidence increased over the study period, from 2.4 CDI/1000 adult discharges in 2001 to 4.3 CDI discharges/1000 adult discharges in 2010. CDI remained relatively unchanged among pediatrics over the study period (1.2 CDI/1000 pediatric discharges in 2001 and 2010).
Mortality and hospital LOS among patients with CDI by age group
The overall all-cause, in-hospital mortality was 6.9% and the median (IQR) hospital LOS was 8 (5–14) days. Mortality and hospital LOS significantly differed by age group (p < 0.0001 for each comparison). Mortality was higher for elderly adults (8.8%) as compared to adult (6.9%) and pediatric populations (3.1%) (p < 0.0001). Among those patients with CDI who died, the most common co-mortalities were septicemia (ICD-9-CM code 038.X; 35.7%), acute renal failure (ICD-9-CM code 584.X; 31.8%), pneumonia (ICD-9-CM codes 480–486.XX; 22.3%), and urinary tract infection (ICD-9-CM codes 599.0; 18.8%). Similar to mortality, median hospital LOS was longest for elderly adults (8 days), followed by adults (7 days), and pediatrics (6 days) (p < 0.0001). There were no differences between male and female elderly CDI patients for mortality (8.8% for both sexes) or median hospital LOS (8 days for both sexes).
Prior national epidemiological investigations demonstrated considerable increases in CDI incidence over the last decade [3, 15, 16]; however, this is the first study to document the national burden of CDI longitudinally among different age groups. This report identified a disproportionate rise in CDI incidence among elderly adults, with an estimated 61% rate of increase from 2001 to 2010. Notably, elderly adults also suffered significantly higher all-cause, in-hospital mortality and increased hospital LOS compared to adult and pediatric patients.
Several factors could contribute to the disparate CDI incidence increase and health outcomes among the elderly compared to other age groups. Advanced patient age has been previously linked to an increase risk for CDI development. This is likely attributed to innate and iatrogenic changes such as: immunosenescence , higher prevalence of comorbid illness , changes in the gut flora , more healthcare exposures (e.g., hospitalizations and long-term care facility residence), and exposure to antibiotics  and other medications (e.g., proton pump inhibitors [PPIs]) . In recent years, there has been an increase in the use of certain antibiotics, particularly among the elderly. Lee et al.  demonstrated an increase in overall antibiotic use in older adult patients by 30% and use of broad spectrum antibiotics in elderly adults by 68% from 2000 to 2010. Furthermore, two meta-analyses suggest that PPI use is associated with increased risk for CDI [22, 23]. Often, patients take PPIs inappropriately [24, 25]. Choudhry et al.  found that in a predominately elderly population (median age 76 years), more than half (53.4%) were prescribed a PPI without an appropriate indication. Furthermore, 7.9% were prescribed a PPI for unknown reasons. In addition, there has been a dramatic increase in the use of PPIs among outpatients in the U.S. A 2013 study by Rotman et al.  found that the use of PPIs more than doubled among outpatients in the U.S. between 2002 and 2009.
The poorer health outcomes among elderly patients with CDI could be due to several factors. First, the European and North American CDI guidelines report age over 65 years as a marker of severity [26, 27]. Severity of infection has been previously linked with increased patient mortality, as well as longer hospital LOS . Additionally, a prior study demonstrated an increased risk of severe infection and death due to the more pathogenic C. difficile strain, BI/NAP1/027 strain in elderly adults compared to younger populations .
Our study findings are important for several reasons. First, in 2001, elderly adults represented approximately 13% of the U.S. population. During our study period, there was an addition of approximately five million elderly adults to the U.S. population . By the year 2030, it is expected that elderly adults will grow to 19% of the total U.S. population. As the population ages, a greater proportion of Americans become high-risk for developing CDI. The incidence and health outcome trends elucidated in our study may help increase awareness of CDI, identify and protect high risk patients, and possibly reduce the occurrence of CDI in the hospital setting.
CDI incidence was highest among elderly adults at least 65 years of age, followed by adults and pediatric patients. The increase in CDI incidence among the elderly markedly outpaced that of the other two age group populations from 2001 to 2010. Additionally, elderly adults experienced higher all-cause, in-hospital mortality and longer hospitals stays as compared to adults and pediatrics patients.
This study has potential limitations. First, this study was retrospective and relied on administrative coding to identify CDI cases rather than positive laboratory identification of C. difficile, which could result in misclassification bias. Although the use of ICD-9-CM codes to identify CDI has relatively high specificity (99.7%) and sensitivity (78%), it cannot be considered equivalent to medical chart review or microbiological analysis . Importantly, our CDI case definition did not change over the study period; therefore, any coding error would persist throughout the study years and would have limited effects on CDI trends. Additionally, an initial CDI episode could not be discriminated from a recurrent CDI episode or readmission. Furthermore, there are factors that could have contributed to differences in CDI incidence and outcomes between age groups that we were not able to account for in our analyses including: antibiotic exposure, differences in CDI testing procedures, severity of comorbid illness, and C. difficile strain/ribotype. The exclusion of federal hospitals and long-term care hospitals in the NHDS and the lack of data after 2010 potentially limit the generalizability to those settings and may underestimate the burden of CDI in the U.S., particularly in recent years. Finally, the NHDS includes a large sample size, resulting in high study power. This limits the utility of p-values to establish differences among groups, as small variations are likely to be statistically significant.
Agency for Healthcare Research and Quality
Centers for Disease Control and Prevention
Clostridium difficile infection
Length of stay
National Hospital Discharge Survey
Proton pump inhibitor
Magill SS, Edwards JR, Bamberg W, Beldavs ZG, Dumyati G, Kainer MA, Lynfield R, Maloney M, McAllister-Hollod L, Nadle J, et al. Multistate point-prevalence survey of health care-associated infections. N Engl J Med. 2014;370(13):1198–208.
Centers for Disease Control and Prevention. Antibiotic resistant threats in the United States, 2013. Available at: http://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf. Accessed 6 Mar 2015.
Lessa FC, Mu Y, Bamberg WM, Beldavs ZG, Dumyati GK, Dunn JR, Farley MM, Holzbauer SM, Meek JI, Phipps EC, et al. Burden of Clostridium difficile infection in the United States. N Engl J Med. 2015;372(9):825–34.
Aitken SL, Joseph TB, Shah DN, Lasco TM, Palmer HR, DuPont HL, Xie Y, Garey KW. Healthcare resource utilization for recurrent Clostridium difficile infection in a large university hospital in Houston, Texas. PLoS ONE. 2014;9(7):e102848.
Sammons JS, Localio R, Xiao R, Coffin SE, Zaoutis T. Clostridium difficile infection is associated with increased risk of death and prolonged hospitalization in children. Clin Infect Dis. 2013;57(1):1–8.
Forster AJ, Taljaard M, Oake N, Wilson K, Roth V, van Walraven C. The effect of hospital-acquired infection with Clostridium difficile on length of stay in hospital. CMAJ. 2012;184(1):37–42.
Nanwa N, Kendzerska T, Krahn M, Kwong JC, Daneman N, Witteman W, Mittmann N, Cadarette SM, Rosella L, Sander B. The economic impact of Clostridium difficile infection: a systematic review. Am J Gastroenterol. 2015;110(4):511–9.
Reveles KR, Lee GC, Boyd NK, Frei CR. The rise in Clostridium difficile infection incidence among hospitalized adults in the United States: 2001–2010. Am J Infect Control. 2014;42(10):1028–32.
Lucado J, Gould C, Elixhauser A. Clostridium difficile infections (CDI) in hospital stays, 2009. HCUP Statistical Brief 124. January 2012. Rockville, MD: Agency for Healthcare Research and Quality. http://www.hcup-us.ahrq.gov/reports/statbriefs/sb124.pdf. Accessed 27 Dec 2015.
Islam J, Cohen J, Rajkumar C, Llewelyn MJ. Probiotics for the prevention and treatment of Clostridium difficile in older patients. Age Ageing. 2012;41(6):706–11.
Di Bella S, Capone A, Musso M, Giannella M, Tarasi A, Johnson E, Taglietti F, Campoli C, Petrosillo N. Clostridium difficile infection in the elderly. Infez Med. 2013;21(2):93–102.
Keller JM, Surawicz CM. Clostridium difficile infection in the elderly. Clin Geriatr Med. 2014;30(1):79–93.
Dennison C, Pokras R. Design and operation of the National Hospital Discharge Survey: 1988 redesign. Vital Health Stat 1. 2000;39:1–42.
Daniels KR, Frei CR. The United States’ progress toward eliminating catheter-related bloodstream infections: incidence, mortality, and hospital length of stay from 1996 to 2008. Am J Infect Control. 2013;41(2):118–21.
McDonald LC, Owings M, Jernigan DB. Clostridium difficile infection in patients discharged from US short-stay hospitals, 1996–2003. Emerg Infect Dis. 2006;12(3):409–15.
Zilberberg MD, Shorr AF, Kollef MH. Increase in adult Clostridium difficile-related hospitalizations and case-fatality rate, United States, 2000–2005. Emerg Infect Dis. 2008;14(6):929–31.
Biagi E, Nylund L, Candela M, Ostan R, Bucci L, Pini E, Nikkila J, Monti D, Satokari R, Franceschi C, et al. Through ageing, and beyond: gut microbiota and inflammatory status in seniors and centenarians. PLoS ONE. 2010;5(5):e10667.
Tartof SY, Yu KC, Wei R, Tseng HF, Jacobsen SJ, Rieg GK. Incidence of polymerase chain reaction-diagnosed Clostridium difficile in a large high-risk cohort, 2011–2012. Mayo Clin Proc. 2014;89(9):1229–38.
Owens Jr RC, Donskey CJ, Gaynes RP, Loo VG, Muto CA. Antimicrobial-associated risk factors for Clostridium difficile infection. Clin Infect Dis. 2008;46 Suppl 1:S19–31.
Seto CT, Jeraldo P, Orenstein R, Chia N, DiBaise JK. Prolonged use of a proton pump inhibitor reduces microbial diversity: implications for Clostridium difficile susceptibility. Microbiome. 2014;2:42.
Lee GC, Reveles KR, Attridge RT, Lawson KA, Mansi IA, Lewis 2nd JS, Frei CR. Outpatient antibiotic prescribing in the United States: 2000 to 2010. BMC Med. 2014;12:96.
Kwok CS, Arthur AK, Anibueze CI, Singh S, Cavallazzi R, Loke YK. Risk of Clostridium difficile infection with acid suppressing drugs and antibiotics: meta-analysis. Am J Gastroenterol. 2012;107(7):1011–9.
Janarthanan S, Ditah I, Adler DG, Ehrinpreis MN. Clostridium difficile-associated diarrhea and proton pump inhibitor therapy: a meta-analysis. Am J Gastroenterol. 2012;107(7):1001–10.
Rotman SR, Bishop TF. Proton pump inhibitor use in the U.S. ambulatory setting, 2002–2009. PLoS ONE. 2013;8(2):e56060.
Choudhry MN, Soran H, Ziglam HM. Overuse and inappropriate prescribing of proton pump inhibitors in patients with Clostridium difficile-associated disease. QJM. 2008;101(6):445–8.
Bauer MP, Kuijper EJ, van Dissel JT, European Society of Clinical M, Infectious D. European Society of Clinical Microbiology and Infectious Diseases (ESCMID): treatment guidance document for Clostridium difficile infection (CDI). Clin Microbiol Infect. 2009;15(12):1067–79.
Cohen SH, Gerding DN, Johnson S, Kelly CP, Loo VG, McDonald LC, Pepin J, Wilcox MH, Society for Healthcare Epidemiology of A, Infectious Diseases Society of A. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of America (SHEA) and the infectious diseases society of America (IDSA). Infect Control Hosp Epidemiol. 2010;31(5):431–55.
Kyne L, Hamel MB, Polavaram R, Kelly CP. Health care costs and mortality associated with nosocomial diarrhea due to Clostridium difficile. Clin Infect Dis. 2002;34(3):346–53.
Miller M, Gravel D, Mulvey M, Taylor G, Boyd D, Simor A, Gardam M, McGeer A, Hutchinson J, Moore D, et al. Health care-associated Clostridium difficile infection in Canada: patient age and infecting strain type are highly predictive of severe outcome and mortality. Clin Infect Dis. 2010;50(2):194–201.
Administration on Aging. Aging Statistics. Available at: http://www.aoa.gov/Aging_Statistics/. Accessed 19 Aug 2013.
Dubberke ER, Reske KA, McDonald LC, Fraser VJ. ICD-9 codes and surveillance for Clostridium difficile-associated disease. Emerg Infect Dis. 2006;12(10):1576–9.
No funding was provided for the conduct of this study. KRR is supported by The University of Texas at Austin and the University of Texas Health Science Center at San Antonio Older Americans Independence Center Career Development (KL2) Program (1P30AG044271-01A1).
Availability of data and materials
Data from this study are publically available from the Centers for Disease Control and Prevention (http://www.cdc.gov/nchs/nhds/nhds_questionnaires.htm).
All authors were involved in the study design, data interpretation, and drafting of the manuscript. Additionally, KR acquired the data and performed the statistical analyses. All authors read and approved the final manuscript.
The authors declare that they have no competing interests.
Consent for publication
The UT Health Science Center San Antonio Institutional Review Board waived formal ethics approval and patient consent.
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Cite this article
Pechal, A., Lin, K., Allen, S. et al. National age group trends in Clostridium difficile infection incidence and health outcomes in United States Community Hospitals. BMC Infect Dis 16, 682 (2016). https://doi.org/10.1186/s12879-016-2027-8
- Clostridium difficile infection
- Age group