Hospital length of stay has steadily decreased over the past 30 years¹ and increasingly complex medical care is provided after discharge through home health and skilled nursing facilities. In turn, adverse events related to hospitalization, including hospital-associated infection, may increasingly present after discharge and result in readmission.^2–5 The costs and sequelae of hospital readmission have made it a target for hospital quality indicators and value based purchasing. ^6,7 Currently, the Centers for Medicare and Medicaid Services reports hospitals’ rates of readmission following treatment for myocardial infarction, congestive heart failure and pneumonia, prompting a national focus on preventing readmission.⁸ However, readmission rates for other important conditions, such as hospital-associated infections (HAIs), are not well studied despite national and state requirements for reporting hospital-specific rates of HAIs.^9–12

Clostridium difficile infection (CDI) is a common cause of diarrhea in healthcare settings and may be an important source of hospital readmissions.^13–15 Hospital-associated C. difficile acquisition may not be evident until after hospital discharge, especially since the average hospital length of stay is 3–5 days and acquisition may initially be asymptomatic.^1,16 In addition, risk factors related to medical care, such as predisposing antibiotics, may require time to deplete the normal intestinal flora and allow C. difficile to flourish and produce symptoms. The exact incubation period for CDI is unknown, but three studies found the incubation period to be less than 1 week.^22,23 However, several studies have found patients may be at an increased risk for developing CDI up to 3 months after hospital discharge.^18–21 One recent study found that among patients who developed CDI within 100 days post-discharge, 89% of patients developed CDI in the first 60 days and 85% occurred in the first month.¹⁷ To account for the range of incubation period, national guidance considers CDI occurring within 4 weeks of hospitalization as hospital-associated, and CDI occurring within 4–12 weeks of a hospitalization as potentially hospital-associated.^22,23

Concerns about CDI have been increasing in the US. Hospitals’ incidence of CDI has been rising in the past decade. This has been associated with the emergence of a new epidemic strain, BI/NAP1/027, that produces 20-fold more toxin than other strains and is associated with high rates of colectomy and death.^24–28 In fact, there is evidence in some hospitals that CDI prevalence may have surpassed that of methicillin-resistant Staphylococcus aureus (MRSA).²⁹ With continued pressure to reduce hospital length-of-stay, the frequency of post-discharge CDI (PD-CDI) and the opportunity for prevention may be increasing as well.

In response to rising CDI incidence, the Centers for Disease Control and Prevention (CDC) and the Society for Healthcare Epidemiology of America (SHEA) have recommended surveillance of HA-CDI rates.^9,10 In addition, reporting of CDI rates has been legislated or is under legislative consideration in several states.^30,31 Despite national guidance that post-discharge CDI events occurring within 4 weeks should be considered hospital associated and events between 4–12 weeks of discharge could potentially be hospital-associated, hospitals performing CDI surveillance often do not track PD-CDI events. However, tracking post-discharge events may facilitate efforts to prevent readmissions and may be helpful for reporting hospital-specific CDI incidence. Moreover, patients requiring readmission for PD-CDI may not return to the original facility, suggesting that the incidence of HA-CDI may be significantly underestimated if PD-CDI events are not uniformly identified among hospitals.¹⁴

We sought to identify CDI cases occurring at all hospitals in a large California county (population 3 million). We assessed the frequency of admission for new-onset CDI after a recent hospitalization, and the impact of including PD-CDI events resulting in readmission on hospital-specific CDI incidence.

C. difficile disease is a major cause of healthcare-associated infection and morbidity. Due to the known delay in presentation following antibiotic exposure, national guidelines consider cases up to 12 weeks following hospital discharge as potentially healthcare-associated and possibly preventable. Nevertheless, the majority of hospitals do not track post-discharge cases, and the impact of post-discharge cases has remained largely unknown. Remarkably, we found that PD-CDI cases within 12 weeks after hospital discharge accounted for the majority of HA-CDI and led to a 2-fold increase in HA-CDI incidence across hospitals in a large metropolitan county. This finding illustrates the need to expand prevention and education strategies to include the post-discharge period and thereby reduce the frequency of PD-CDI events.

Inclusion of post-discharge CDI events substantially altered hospital-specific CDI incidence, but the impact varied widely by hospital. For example, PD-CDI cases accounted for all HA-CDI cases in one hospital and none of the cases in another. This suggests that tracking PD-CDI events may impact the validity of inter-facility comparisons, since hospitals are affected differentially by including or excluding PD-CDI. These discrepancies could be magnified if some, but not all, hospitals track PD-CDI. When we ranked hospitals by HO-CDI incidence, half the hospitals captured in the quartile with the highest HO-CDI incidence changed when PD-CDI was included. In fact, one hospital changed from the best quartile to the worst quartile when PD-CDI cases were captured. In addition, since 75% of patients with PD-CDI returned to the same hospital for readmission, hospitals may be able to track most PD-CDI cases by performing post-discharge surveillance for PD-CDI cases that readmit to their own facility. Additional notification of PD-CDI cases back to transferring or recently discharging hospitals may also improve accuracy of CDI rates.

For prevention, patient characteristics may be utilized to identify populations at elevated risk for post-discharge CDI. We found that risk factors for HO-CDI and PD-CDI were often the same, including increasing age, higher length of stay, and overall poor health, including diabetes, cancer, and AIDS. In addition, prevention may be targeted at patients with specific primary admission diagnoses such as septicemia, post-operative infection, and pneumonia. These primary admission diagnoses all represent conditions likely to be treated with antibiotics, the main risk factor for CDI. The immediate post-discharge period should be considered an extension of the risk of CDI that begins during a hospital stay. This heightens the importance of educating high risk patients prior to hospital discharge about the potential for post-discharge diarrhea and of identifying prophylactic solutions to prevent disease in the high risk patient population.

In addition, we found that white and non-Hispanic patients had a higher risk of PD-CDI. While we did not evaluate reasons for this difference, racial and ethnic disparities, including access to healthcare, have been well-documented and may be magnified in the outpatient arena.^35–36 Differences in access to outpatient care are likely to impact antibiotic use in these groups, and their subsequent risk of PD-CDI. In addition, male gender was associated with lower risk of PD-CDI but not with HO-CDI. This difference may not be due to an increased post-discharge risk for women but may instead reflect men’s reduced tendency to seek care and therefore be hospitalized for PD-CDI.^37–39 More research is needed to understand the reasons for differential risk in these groups in order to develop effective prevention strategies for the post-discharge setting.

Our study has several limitations. We did not capture PD-CDI cases treated in the outpatient setting, which may have led to an underestimate of PD-CDI incidence. Nevertheless, the focus on PD-CDI associated with re-hospitalization ensured capture of the most serious cases. While errors present in administrative data may lead to an under or over estimation of CDI incidence, this California dataset is notable for containing present on admission codes that indicate hospital vs. community disease onset. These codes have been well established in California hospitals for over a decade and have been validated for select diseases such as community-acquired pneumonia and acute myocardial infarction.⁴⁰ We also minimized the chances that a code represented a history of CDI only versus active disease by limiting diagnoses to the first 3 coded positions. Another limitation is that we did not account for certain known risk factors (such as antibiotic use) that were unavailable in administrative data. However, we included primary admission diagnoses that are frequently treated with antibiotics. Finally, we attributed a PD-CDI event to the most recent hospitalization within 12 weeks. This definition does not account for multiple hospital exposures during that period or for intervening nursing home admissions, which may also contribute to CDI acquisition.⁴¹ Further, since the incubation period for CDI is unknown, some cases occurring within our 12 week window may be due to exposures in the community, including outpatient antibiotic use, household pets, and contamination of food.^42–43 Nonetheless, over half of PD-CDI cases detected in this study occurred within the first 4 weeks after discharge, a time window that is accepted by national guidance to most likely reflect healthcare associated CDI events.

In summary, tracking PD-CDI cases doubled the incidence of HA-CDI in a large county. Since the majority of hospitals do not track PD-CDI cases, the frequency and impact of PD-CDI may be widely underestimated, resulting in missed opportunities to prevent readmissions. Importantly for public reporting purposes, including PD-CDI affected individual hospitals differently, leading to substantial changes in hospital rankings by CDI incidence. Uniform tracking of PD-CDI events would allow more accurate estimates of overall CDI incidence and more equitable hospital-to-hospital comparisons. We found that the vast majority of cases can be captured if hospitals track PD-CDI cases that return to the same facility. We also identified several patient characteristics that were associated with PD-CDI, suggesting that preventative strategies may effectively focus upon specific patient groups. Targeted education and prevention for CDI may become increasingly important to help hospitals lower their readmission rates.