Patrick J. Scoble, PharmD

 infection (CDI) has become one of the most common hospital-acquired infections (HAI) in the United States, affecting nearly 500,000 people annually.

 Hospitalizations due to CDI alone increased by 339% over the period of 2000-2014 in the United States, and impose a significant burden on the health care system.

Hospitalized patients developing CDI have a longer length of hospital stay (LOS),

 and in acute care facilities, approximately $6.3 billion is spent on CDI annually.4 Risk factors for CDI include previous antibiotic exposure, patient age greater than 65 years, and hospitalization or stay in long-term care facilities.

Other risk factors include having pre-existing, inflammatory bowel disease, undergoing gastrointestinal surgeries, having undergone solid organ transplantation, pre-existing chronic kidney diseases, and concomitant immunosuppressant drug therapy.

Although CDI has been associated with health care exposure, there has been a stark rise in the number of CDI cases in the community. A population-based surveillance study performed through the CDC’s Emerging Infections Program (EIP) was done to measure the burden of CDI in the population, characterize 

 strains associated with disease, and to monitor trends in disease over time.

EIP data revealed that from 2011-2017, the number of cases of CDI overall remained stable number while there was a 14.4% increase in the community-setting CDI cohort. Although the estimated burden of CDI among health care-associated infections (HAI) declined a similar pattern over the same 7-year period, this decline was not observed among community-acquired infections, which contributed to nearly 50% of the burden of CDI in 2017.

The added risk of recurrent CDI infections (rCDI) increases the overall burden of disease. Data from the Healthcare Cost and Utilization Project in the United States over a 15-year period showed a steady increase in the number of hospitalizations associated with CDI, reaching nearly 350,000 hospitalizations in 2008.

The proportion of patients diagnosed with complicated CDI over a 15-year period (i.e. having active disease with the concomitant development of megacolon, intestinal perforation, need for colectomy, or vasopressor support) increased from 7.1% to 18.2%, while 30-day mortality, specifically, rose from 4.7% to a staggering 13.8% during this same period.

In the ICU setting, mortality rates increase more than 3 times—with the mortality rate directly from CDI being 5%, mortality secondary to CDI complications ranges between 15% and 25%, and the overall mortality in ICU setting is approximately 34%.

CDI also carries a higher risk of hospital readmission, with as many as 30% of patients within 30 days of initial discharge.

 Disease recurrence with rCDI is especially problematic and is increasing disproportionately relative to initial episodes. 

Between 2001 and 2012, rCDI increased by 189%, independent of known CDI risk factors.

 Of these first recurrences, a subset of >30% will recur a second time, and of these second recurrences, a further 40%-60% will subsequently recur with CDI again. rCDI is associated with worse health outcomes and longer hospitalization LOS, resulting in a demonstrable, financial burden in which the gap between hospital costs and drug reimbursements are most pronounced with rCDI.

Seen and Unseen Financial Cost and Economic Burden of CDI

From an economic perspective, CDI has a staggering financial impact on the US health care system, as well on the patients infected. Some of the known, contributory factors to the extraordinary burden, are those direct costs associated with hospitalization and the treatment of secondary complications as they arise (which include surgical costs, prolonged LOS, and requiring intensive care).

Development of rCDI only worsens this burden. Lesser-considered, indirect, patient costs of CDI include productivity loss because of absenteeism (missed days of work) and secondary, economic costs incurred through burden placed on caregivers. From 2002-2016, the annual cost of CDI in the United States increased from $1.3 billion

 Several studies have determined both the total and attributable cost of CDI per case (

Additionally, it has been found that the burden of CDI adds up to 20 hospital days/patient, with additional expenditures exceeding $1 billion per year.

 A meta-analysis of 45 studies, performed in the United States over a 16-year period reported the attributable, CDI costs to range from $8911 to $30,049 in hospitalized patients.

A systematic review of studies in patients between 1986 and 2013 found that not only was CDI among the top 5 most-expensive health care-associated infections (HAIs) in the United States, but it also accounted for 15.4% of all HAIs.

 However, these studies were limited in that the focus was on hospitalization and drug costs, while excluding indirect expenses.

What needs to be considered include the cost of treatment of serious complications due to CDI cases requiring surgery and postoperative care, follow-up, outpatient care, as well as the need for decontamination, isolation, and rigorous hygiene within the hospitals. The median cost of an individual case of CDI increases by 1.4–1.5 times when societal costs are considered in addition to direct hospital costs, further illustrating the overall economic burden of CDI.

The standard of care for CDI has shifted from metronidazole and vancomycin towards fidaxomicin, fecal microbiota transplantation, and when appropriate, the use of bezlotoxumab.

 While being more expensive from a drug cost perspective, these emerging therapies have shown to be more efficacious in preventing recurrences, thereby proving to be more beneficial forms of therapy from a pharmacoeconomic perspective. The cost efficacy of various treatment regimens in the management of either the initial or recurrent CDI has been examined 

It is important to note that some studies have examined individual treatments, whereas others not only evaluated treatment strategies, but also the appropriate use of novel therapeutic options. It is imperative to be mindful that the cost efficacy is incumbent upon not only the direct costs of the treatment used, but also the relative efficacy in reducing recurrent disease-related morbidity and mortality.

Unrecognized Administrative Cost Implications of CDI

As stated earlier, CDI is one of the most common HAIs and comes within the US government’s Hospital Acquired Condition (HAC) reduction program. This program encourages hospitals to improve patient safety and reduce the number of conditions patients experience from their time in hospital. This program applies to most general acute care hospitals. There are some exemptions, such as critical access hospitals and rehabilitation units, among others. The HAC Reduction Program covers many types of events, including HAI, such as CDI.

The impact of a hospital’s Medicare reimbursement from CMS is directly attributed to their HAC score. The overall Medicare program can reduce the total payment by 1% if a hospital has a total HAC score greater than 75th percentile of all total HAC scores. Although the calculation process is multi-factorial, the impact occurs with each DRG claimed. The payments apply to all fee-for-service discharges.

One of the components included in the calculation of HAC Reduction Program is the Standardized Infection Ratio (SIR), which is calculated by formula published by the National Healthcare Safety Network (NHSN). SIR is a summary measure used to track HAI at a national, state, or local level over time. The SIR adjusts for various facility and/or patient-level factors that contribute to HAI risk within each facility. The SIR is currently calculated in NHSN for a variety of HAI types, including CDI.

Using this system, it is possible to compare a hospital with itself over time to determine whether infection reduction is occurring and to what degree.

 Finally, another measure used in the determination of the impact of CDI is the in-patient rehabilitation facility quality reporting program which is enforced by the IMPACT Act of 2014. The identification of hospital-onset CDI is included in these data submissions.

Other programs relating to 30-day readmissions can also play a part in the overall assessment of health care performance. Thus, it is evident that CDI has an impact on reimbursement of Medicare fees. If a hospital does not achieve certain standards such as reduction in the incidence of CDI, calculated by various formulae, the implications can be financially important. It is therefore important to employ management approaches which can help reduce the recurrence of CDI.

In summary, CDI is a significant condition in terms of morbidity, mortality, and health care economics. The various cost analyses usually do not include the likely negative impact of CDI on the total hospital reimbursement to a hospital. One percent of an annual fee payment can mount up, CDI and its recurrences are financially significant, and appropriate management can contribute to the overall financial status of an institution.

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