Author Proof

About the Authors

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Samuel L Aitken

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Dhara N Shah

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Kevin W Garey

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© 2013 Future Medicine www.futuremedicine.com

Chapter

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Economic burden of Clostridium difficile infection Samuel L Aitken, Dhara N Shah & Kevin W Garey

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Clostridium difficile infection (CDI) is an increasingly prevalent cause of morbidity and mortality worldwide. The increasing burden of CDI has led to substantial rises in the costs associated with the care of patients with CDI. Variations in the patient populations being studied lead to significant heterogeneity in assessments of the economic burden; however, it is clear that CDI contributes significantly to overall healthcare costs. Novel preventative strategies and new treatment options may reduce the economic burden of CDI.

doi:10.2217/EBO.13.185

© 2013 Future Medicine

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Aitken, Shah & Garey Clostridium difficile infection (CDI) is the leading cause of infectious diarrhea among hospitalized inpatients [1], with an estimated 284,875 cases per year in the USA [2]. Between 1993 and 2005, the incidence of CDI rose threefold in the USA, from 25 to 76.9 cases per 10,000 hospital discharges with a 1–2.5% attributable mortality rate. During the same time frame, mortality due to C. difficile was nearly sixfold more common in Britain. The increased incidence and mortality rates have been attributed to the emergence of the epidemic BI/NAP1/027 strain in the early 2000s [3]. Adding to the growing initial burden of disease, recurrence occurs in roughly one quarter of patients, with recurrence causing a substantial increase in the risk of subsequent recurrences [4]. The economic impact of disease is significant, with the total cost to the US healthcare system placed between US$750 million and US$3.2 billion per year [5–7]. New treatment options, such as fidaxomicin and fecal transplantation, may lead to increased cure rates and decreased recurrences compared with current standard-of-care therapies; however, their role in the economics of CDI remains to be elucidated [8–10]. This chapter aims to summarize the current understanding of the economic impact of CDI from a global perspective.

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Clostridium difficile infection (CDI) recurrence is a substantial clinical problem, occurring in approximately onequarter of all patients with an episode of CDI. The economic impact of a CDI recurrence has not been well studied, but may be assumed to be associated with a minimum cost of US$15,000.

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Attributable costs Several single-center studies have attempted to determine the directly attributable costs of an initial episode of CDI to the total cost of hospitalization. It is clear that additional costs are primarily driven by an increased hospital length of stay and associated boarding fees, rather than additional laboratory or pharmacy costs [11–13]. See Figure 1 for an estimate of the attributable cost of CDI in different countries.

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Wilcox et al. conducted a prospective case–control study of patients with CDI during a 7-month span in England [11]. In addition to identifying over GB£4000 in CDI-attributable costs for each case, a more in-depth analysis found that boarding costs accounted for roughly 94% of these charges. Vonberg et al. performed a retrospective case–control analysis at a tertiarycare center in Germany to determine attributable costs of CDI [12]. In their analysis, a case of CDI was associated with an increase of €7147; however, daily hospital costs were similar between the cases and control groups, at €1110 and The directly attributable costs of CDI are largely €1034, respectively. The substantial due to increases in hospital length of stay, with increase in total hospital costs despite additional laboratory and pharmacy costs accounting for a small fraction of the total additional costs similar daily charges is explained by a incurred.

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Economic burden of Clostridium difficile infection Figure 1. Estimated attributable cost by study country. 12,000

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Attributable cost (US$)

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4000

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Germany

All costs are converted to 2012 US$. Data adapted from [7,11–13].

Northern Ireland

USA

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median 8-day increase in length of stay. Al-Eidan et al. determined an increase in total costs of GB£2691 for patients with CDI in Northern Ireland, with pharmacy and laboratory costs accounting for only GB£177 of these costs [13]. These additional total costs probably represent an overestimate, as their analysis extrapolated costs from an increased length of stay of 13 days, and failed to adjust for clinical variables that may have contributed. In the largest single-center study of the economic impact of CDI to date, Dubberke et al. evaluated the attributable costs of CDI among 24,691 hospitalized patients at a tertiary-care center in St Louis (MO, USA) [7]. During the index hospitalization, hospitalized patients with CDI were found to have an excess cost of US$3240 based on a propensity-matched case– control analysis and US$2454 with a linear-regression methodology. These increased costs were durable when extended to 180 days from the index case, with attributable costs due to inpatient care rising to US$7179 and US$5042 using case–control and linear-regression methodologies, respectively. When the specific cost was analyzed by center (e.g., pharmacy, laboratory or respiratory therapy), patients with CDI had significantly higher total cost in each center compared with patients without CDI. Unfortunately, the contribution of CDI to each of those cost centers was not provided. Kyne et al. performed a prospective cohort study in order to determine the attributable cost of CDI at a tertiary-care hospital in Boston (MA, USA),


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Aitken, Shah & Garey as well as to provide an estimate for total cost to the US healthcare system [6]. After adjusting for numerous potential demographic and clinical confounders, the authors estimated that a hospital course that was complicated by CDI was associated with an additional US$3669, with a mean total-hospitalization cost of US$4657. By using nationwide hospital admission data, the attributable annual cost to the US healthcare system of CDI was estimated at over US$1.1 billion – it is important to note that the data used to generate this estimate do not include outpatient cost data or information or subsequent readmissions due to CDI, and is therefore probably a substantial underestimate of the true financial burden of CDI.

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The total individual costs associated with CDI vary widely based on the specific study population and method of statistical analysis, but in general, are higher among patients who die in hospital and among those with specific comorbid conditions.

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Total costs A number of studies have attempted to estimate the total costs of a CDI case using a number of different administrative databases. The cost estimates provided by these models are heterogeneous and are somewhat difficult to reconcile, as each study utilizes unique study populations and methods of case matching or adjustment for confounding variables. However, these studies do provide valuable insight into the economic burden of CDI and allow for rough estimation of the total cost of disease. Table 1 provides a summary of the estimated annual total cost of CDI in the USA.

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O’Brien et al. performed a retrospective analysis of acute-care hospitals in Massachusetts (USA) between 1993 and 2003 in order to estimate the economic burden of CDI for an individual patient and the US healthcare system [14]. Cases of CDI were identified on the basis of the presence of the International Classification of Diseases, Ninth Edition (ICD-9) code corresponding with CDI and then classified as primary (i.e., CDI was the main discharge diagnosis for that admission) or secondary cases. CDI cases were then further stratified based on hospital-onset healthcare facility- or community-acquired status. Primary cases of CDI were associated with a mean total cost of US$10,212, with costs for patients who died in hospital (US$26,507) substantially higher than those who survived to discharge (US$9434). Secondary cases had a mean total cost of US$29,946, with an attributable cost of US$13,675, or 46% of the total inpatient costs. For this analysis, the authors attributed the additional costs of CDI to an average 2.9-day increase in the length of stay. By extrapolating costs to the US healthcare system, the annual economic burden of CDI was estimated at US$3.2 billion.

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Economic burden of Clostridium difficile infection Table 1. Estimated cost to the USA per year. Study population

Estimated cost (US$ billion)

Dubberke et al. (2008)

Single center, St Louis (MO, USA). Inpatients only (extended to 180-day total costs)

0.897–1.3

[7]

Ghantoji et al. (2010)

Systematic literature review. All peerreviewed studies reporting economic data

0.433–0.797

[5]

Kyne et al. (2002)

Single center (MA, USA). Inpatients only

1.1

[6]

Lipp et al. (2012)

Select acute-care hospitals (NY, USA). Inpatients only

0.792

McGlone et al.

Economic simulation. Estimates incorporate multiple economic perspectives

0.496–0.796

O’Brien et al. (2007)

Acute-care hospitals (MA, USA). Inpatients only

3.2

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Study (year)

Ref.

[18]

[14]

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To provide a national perspective on the burden of CDI, Stewart and Hollenbeak reviewed the Nationwide Inpatient Sample (NIS) for the year 2007 [15]. The NIS provides discharge-level information on a representative 20% sample of inpatients in the USA, and is the largest publically available, all-payer database for this information. Using a propensity score casematched design, CDI cases were found to have a mean total hospital cost of US$23,344 compared with US$14,918 for those without CDI. CDI cases were again found to have a longer length of stay than those without, with a mean length of stay of 13 days for CDI cases versus 7.9 days for controls. Numerous comorbid conditions, including congestive heart failure, cardiopulmonary disease, valvular heart disease and coagulopathy, were found to further increase costs among patients with CDI. Interestingly, and somewhat counterintuitively, patients with chronic renal failure and diabetes and CDI experienced lower total hospitalization costs than matched cases without CDI.

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Li and Stewart performed a similar analysis using data from the Pennsylvania Health Care Cost Containment Council database from 2005 to 2008 [16]. Cases were again identified using the ICD-9 code for CDI and matched using a propensity score case-matched design. CDI cases had a mean US$22,094 in total costs, compared with US$10,865 in the non-CDI cohort. The mean cost for a CDI case rose 9% between 2005 and 2008, while the costs for those without CDI remained roughly static. The nature of the database also allowed the authors to analyze costs based on the size, hospital teaching status and location of the hospital for each CDI case. These detailed analyses revealed that mean total costs for a CDI case were far lower in


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Aitken, Shah & Garey small, rural (US$24,465); large, rural (US$22,068); and urban, nonteaching hospitals (US$25,239) in comparison with urban teaching hospitals (US$37,100). The data utilized were insufficient to allow for a more in-depth analysis of this information to determine if differences in a patient’s clinical status between these hospital categories contributed to these large discrepancies.

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Pakyz et al. performed a retrospective, case–control study of 45 hospitals in the University Health Consortium database, using data from 2002 to 2007 [17]. Cases were identified as having an ICD-9 code for CDI as well as receiving either oral vancomycin or metronidazole for at least 4 days during the hospitalization. Control patients were matched by diagnosis-related group code, quarter and year of discharge, and age. Using a multivariate linear-regression analysis, mean costs of hospitalization for a patient with CDI were US$55,769 compared with US$28,069 for those without. This increase in costs corresponded with a near doubling in length of stay for cases compared with controls (21.1 vs 10.0 days, respectively). The authors also compared total costs for cases on the basis of anti-CDI antibiotics received, and found that mean total costs were highest for those treated with metronidazole following oral vancomycin (US$82,792), while those treated with oral vancomycin alone had the lowest total costs (US$29,260). Information on whether the more costly capsule formulation of oral vancomycin was utilized instead of the more common compounded liquid formulation was not provided.

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Lipp et al. utilized data from the Statewide Planning and Research Cooperative System database in order to determine the costs associated with hospital-acquired CDI across New York state (USA) [18]. Cases were identified on the basis of ICD-9 code corresponding to CDI, as well as having a modifier indicating that the condition was not present on admission to the hospital; however, no specific time frame for the development of CDI during the hospitalization was available through the database. Through generalized linear regression modeling, CDI was associated with nearly US$29,000 in additional charges and an increase in length of stay of almost 12 days. Based on these estimates, the estimated total annual cost of CDI to New York state (USA) was roughly US$55 million, and in the USA, US$792 million. These additional costs were associated with an estimated additional 209,000 inpatient hospital days per year nationwide. A wide-ranging analysis of gastrointestinal disorders, utilizing multiple public and private databases, was conducted by Peery et al. in order to place the burden of CDI within the context of other gastroenterological complaints [19]. Based on the analysis of the NIS, CDI was found to be the

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Economic burden of Clostridium difficile infection

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Total costs to the US healthcare system have tenth most frequent gastrointestinalbeen estimated between US$750 million and related principal discharge diagnosis, with US$3.2 billion. These costs are probably an data from the US CDC’s National Vital underestimate, as they do not include many of the Statistics System showing CDI as the ninth costs associated with outpatient care, long-term leading cause of death among gastro follow-up costs or indirect nonmedical costs. intestinal disease. The impact of CDI on health-related quality of life was assessed using the 2010 US National Health and Wellness Survey, which provides information on health-related quality of life and work/activity impairment through the use of an annual, online, cross-sectional survey [19]. CDI was associated with the highest work-impairment score of all gastrointestinal disorders analyzed along with the third highest impairment of daily activities, ranking behind only chronic liver disease and chronic constipation. However, the economic impact of these lost wages has not been assessed. Using additional information from the NIS, total annual costs to the US healthcare system were estimated at roughly US$1.1 billion; however, this estimate includes only inpatient costs, and does not assess the contribution of decreased quality of life or outpatient burden of CDI.

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In the only study to date that assessed both the inpatient and outpatient burden of CDI, Kuntz et al. performed a retrospective cohort study of members of the Kaiser Permanente Colorado and Northwest healthcare plans between 2005 and 2008 [20]. Outpatient cases of CDI were identified on the basis of ICD-9 code or positive C. difficile toxin test along with a prescription for either metronidazole or vancomycin, while inpatient cases were identified on the basis of ICD-9 code alone. A total of 56% of all cases in this study were identified as outpatients. Mean total outpatient costs during the 180-day study period were US$859.40, and in contrast to inpatient costs, the cost of the anti-CDI drugs made up a substantial portion of these costs (US$424.30). This figure is inclusive of all costs associated with a patient’s care during the study time frame, including follow-up visits, laboratory testing, and telephone follow-up. Total inpatient costs were similar to those identified by other authors, at US$10,708.40. During the time period of analysis, only metronidazole and vancomycin were used as treatment for CDI. These data indicate that other estimates of the total annual national cost of CDI are probably significant underestimates, as these analyses have failed to identify the nearly 50% of cases that are identified and treated solely on an outpatient basis [20].

Special populations Other investigators have examined the impact of CDI in specific subpopulations, allowing for determination of whether the burden of


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Aitken, Shah & Garey disease falls disproportionately on specific groups of patients. See Figure 2 for a summary of the excess costs of CDI in select populations with CDI.

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Two studies have used the NIS to examine the effects of CDI on inpatient costs for patients with solid organ transplants (SOTs). The first analysis, conducted by Pant et al., identified recipients of liver, kidney, heart or lung transplants as well as patients with CDI by utilizing ICD-9 codes [21]. Total charges, rather than cost, were assessed and compared between patients with SOTs, patients with CDI and patients with both. Median total charges were highest in the SOT group, with CDI at US$53,808, compared with US$37,917 in the CDI-alone group and US$31,488 in the SOT-alone group. It is not clear from the data what the reason for admission for the non-CDI SOT patients was; therefore, comparison of these charge estimates is difficult to decipher. Ali et al. conducted a similar analysis, analyzing the impact of CDI on patients with liver transplants [22]. In patients with both liver transplant and CDI, median overall hospital charges were US$143,000 compared with US$73,000 for those without. Charges were also further divided by patients who survived to discharge versus those who did not, with charges substantially higher in the CDI population in both the survivor Figure 2. Estimated excess cost and length of stay increase for select populations. 100,000

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14 12 10

80,000 70,000 60,000 50,000 40,000

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8

90,000

6

30,000

Mechanical ventilation

Irritable bowel disease

Overall

Trauma

0

Medical intensive care

10,000

0

Liver transplant

20,000

2

Surgical inpatients

4

Excess cost (2012 US$)

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A

Excess length of stay (days)

18

In this figure, the red line represents the excess length of stay and bars represent the increase in costs attributable to Clostridium difficile infection. All values are converted to 2012 US$. Adapted from [15,22–27].

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Economic burden of Clostridium difficile infection group (US$129,000 vs US$69,000) and nonsurvivor groups (US$393,000 vs US$206,000). The dramatic differences in total charges accrued in these two analyses despite using the same data set raise questions about how the specific analyses were conducted, and the failure to convert charge to cost data prevents these data from being compared with those found in the general population.

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Two studies have evaluated the costs associated with CDI among patients in intensive care units (ICUs). The first, conducted by Lawrence et al., was a retrospective cohort review of patients in a 19-bed medical ICU over a 30-month span [23]. Patients with CDI were found to have significantly longer median ICU and total hospital stays versus those without (6.1 and 24.5 compared with 3.0 and 10.1, respectively) as well as significantly higher median ICU and total hospital costs (US$11,353 and US$45,910 vs US$6,028 and US$18,620, respectively). A second study, performed by Zilberberg et al., examined the impact of CDI on a nationwide cohort of patients receiving prolonged, acute mechanical ventilation [24]. All patients with ICD-9 codes for either prolonged, acute mechanical ventilation or CDI were identified through the 2005 NIS, with a propensity score-based model used to adjust for confounding variables. After adjustment for comorbid conditions, demographics, and hospital and admission characteristics, CDI was found to result in a median hospital length-of-stay increase of 6.1 days and US$10,355 in additional costs.

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Ananthakrishnan et al. utilized the NIS data from 2003 to examine the impact of CDI in patients with coexisting inflammatory bowel disease (IBD) [25]. All patients in the data set with ICD-9 codes corresponding with CDI, and either Crohn’s disease or ulcerative colitis were identified; patients with Crohn’s disease or ulcerative colitis and no CDI served as a comparator group. Patients with CDI were found to have an overall length-of-stay increase of approximately 3 days, with a concomitant increase in hospital charges of US$13,652. This analysis was unable to adjust for severity of the underlying IBD, and patients with both CDI and IBD were more likely to have elevated Charlson comorbidity scores, introducing the possibility of a selection bias in the underlying estimates.

Three studies have explored the economic impact of CDI in surgical patients. Zerey et al. reviewed the NIS from 1999 to 2003, using ICD-9 codes to identify patients who had undergone a wide variety of surgical procedures and were diagnosed with CDI [26]. After controlling for type of surgical procedure and a number of potential postoperative complications, patients with CDI were found to have a total length of stay that was 16 days longer with an additional US$77,483 in additional hospital charges. Of note,


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Aitken, Shah & Garey

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the median charges for patients with CDI varied widely between procedure types, ranging from US$23,349 for an appendectomy to US$100,845 for Heller myotomy, indicating that the overall cost estimate cannot be applied universally across all surgical types. Glance et al. also utilized the NIS to study the economic impact of CDI, but restricted their analysis to trauma patients from 2005 to 2006 [27]. Patients with CDI had a median 10-day difference in hospital length of stay and US$20,445 in costs, although these estimates were not adjusted for confounders. As in the general surgery population, patients with CDI had highly variable total costs, ranging from US$21,276 for a low fall to US$90,691 for a pedestrian trauma. Kim et al. utilized the NIS from 2001 through to 2008 to investigate the burden of CDI in patients undergoing a radical cystectomy for bladder cancer [28]. Using similar methods of adjustment as Zerey et al., CDI was associated with a 9-day increase in median length of stay and an additional US$8,340,806 in attributable costs for the total population studied [26].

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The cost of CDI recurrence Although many of the previously mentioned studies, particularly those studying large, administrative databases, have potentially included recurrent CDI in their cost estimates, the economic impact of recurrent CDI has been explicitly evaluated in only two studies. McFarland et al. utilized data obtained as part of a USA-based prospective, placebocontrolled, randomized trial that evaluated treatment options for recurrent CDI [29]. Direct costs of the medical care provided, including outpatient items (e.g., antibiotics, clinic costs and laboratory testing) as well as inpatient costs (e.g., daily charges, physician fees and procedural costs) were evaluated. Indirect medical costs, such as patient travel time or lost work days, were not included in the analysis. The total costs of lifetime medical care for the 209 patients enrolled in the trial were calculated at US$2,292,856, or an average of US$10,970 per patient. When evaluated by treatment episode (i.e., initial or subsequent episodes), the cost of recurrent disease was found to be substantially higher for recurrences (US$3103) compared with the initial episode (US$1914). The authors attributed this difference to the shorter duration of antibiotic therapy utilized in the treatment of an initial episode of CDI.

Miller et al. conducted a prospective, multicenter study to assess the outcomes associated with nosocomial CDI in Canadian hospitals in 1997 [30]. Patients were enrolled if a laboratory test was positive for C. difficile toxin and met the case definition of CDI on the basis of the Society for Healthcare Epidemiology of America’s definition of nosocomial acquisition. A total of 269 patients met the criteria for inclusion in the study, of whom

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Economic burden of Clostridium difficile infection 19 (7%) were readmitted within 30 days for management of CDI. The mean length of stay associated with these readmissions was 13.6 days per case. The authors calculated a total cost of CAN$128,200 to each hospital per year, assuming a 7% admission rate for CDI and incorporating estimated minimum daily bed rates and the cost of antibiotic therapy.

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Despite the paucity of data evaluating costs for recurrent CDI, inference can be made on the basis of surveillance data that estimates the rate of recurrence as well as the frequency of rehospitalization for recurrences. O’Brien et al. noted a 13% admission rate within 1 year following their index admission, of which 32% again received a primary diagnosis of CDI [14]. These readmissions were associated with a mean 15-day hospital length of stay. These data are similar to that of Miller et al., both in terms of total rehospitalizations for CDI and length of stay, allowing for a reasonable estimate of a range to aid in making a gross cost estimate of recurrent CDI [30]. By comparison, Kuntz et al. noted a 21.6% readmission rate for CDI within 180 days of their index case, substantially higher than what had previously been reported [20]. These readmissions were associated with a 15-day length of stay, remarkably similar to the results of both O’Brien et al. and Miller et al. Based on these similarities, an approximation of the cost of a readmission for CDI in the USA by using average daily costs provided by the US Census Bureau [101]. Conservatively, assuming a daily cost of US$1853 and a total hospital stay of 15 days, the estimated minimum cost of a readmission for CDI is US$27,795. It is important to note that this estimate does not account for the likelihood of increased severity of disease with a recurrence [31], nor the no-longer negligible cost of drugs such as fidaxomicin, which may be more likely to be used in the setting of a disease recurrence [10].

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Conclusion Comparison of the costs of CDI is difficult due to the substantial heterogeneity of the studies on the topic, with in-study population and methods of cost calculation leading to an enormous range of estimates of total cost. Despite these limitations, two key conclusions can be drawn from these studies: first, that C. difficile dramatically increases total cost of hospitalization and second, that this cost is directly related to an increased length of stay. Regardless of the population studied, data sources utilized, or the country in which the study was performed, these conclusions hold true. Further study is needed to determine the exact economic burden of CDI on outpatients, as well as the impact of recurrent CDI and its relation to the total cost of CDI. Table 2 provides a summary of the characteristics of the studies that have evaluated the economics of CDI.


13

14

A

Retrospective, USA, hospital nationwide

Ali et al. (2012)

24,691 hospital Primary 41.31 nonsurgical admission: inpatients US$8394 versus 5940 Inpatient costs 52.97 over 180 days: US$14,560 versus 9518

of

US$5042‡

US$2454‡

US$11,000‡

Attrib utable LOS (days)

NA

NA

7 versus 4 3‡

17.8 NR versus 7.7

16.9 13 versus 3.9

Total LOS† versus controls† (days)

CDAD: xxx; CDN: xxx; CDI: Clostridium difficile infection; HMO: xxx; IBD: Irritable bowel syndrome; ICU: xxx; LOS: xxx; NA: xxx; NR: xxx; SOT: xxx.

MO, USA

Dubberke et al. (2008)

45.11

44,400 CDI IBD patients patients with with or or without IBD without CDI: US$19,548 versus 13,471

Retrospective cohort, hospital

NR

NR

Attributable or incremental costs

P ro

Inpatients 95.89 with or without CDAD: US$143,000 versus 73,000

GB£3675.3

Change in costs versus controls (%)

Ananthakrishnan Retrospective, USA, et al. (2008) hospital nationwide

193,174 inpatients with liver transplant ation, with or without CDAD

87 hospital inpatients

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Retrospective, Northern hospital Ireland

Al-Eidan et al. (2000)

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Study design, Location economic perspective

Study (year) Sample Total costs characteristic, (vs controls setting where applicable)†

Table 2. Characteristics of the studies that have evaluated the economics of Clostridium difficile.

[7]

[25]

[22]

[13]

Ref.



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A


Prospective, hospital

Kyne et al. (2002)

Inpatients 53.8 with or without CDAD: US$10,489 versus 6820

NA

US$3,669‡

of

NR

P ro Inpatients with CDAD: US$10,708.40 Outpatients with CDAD: US$859.40


NR



10.2 3.6‡ versus 6.6

NR

17 versus NR 8

16 versus NR 6




3067 HMO members

Retrospective, CO and payer Northwest (USA)

Kuntz et al. (2012)

MA, USA

10,856 inpatients undergoing radical cystectomy with or without CDAD

Kim et al. (2012) Retrospective, USA, hospital nationwide



ho r 155,891 trauma patients with or without CDAD


Glance et al. (2011)

Sample Total costs characteristic, (vs controls setting where applicable)†


Study (year)


[6]

[28]

[27]

Ref.


15

16

A

78,273 inpatients

4,853,800 inpatients

Retrospective, PA, USA hospital

Lipp et al. (2012) Retrospective, NY, USA hospital

NR

NA

Inpatients 68.56 with or without CDAD: US$10,931 versus 6485

of

US$29,000

NA

12

NA

14.4

24.5 versus 10.1

US$27,290


6.1 versus 3.1 3


US$5325


P ro

CDAD patients 88.34 versus nonCDAD patients ICU stay only: US$11,353 versus 6028 CDAD patients 146.56 versus nonCDAD patients entire hospitalization US$45,910 versus 18,620



1835 ICU patients

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Li et al. (2011)

USA

ut

Retrospective cohort, hospital

Lawrence et al. (2007)



Study (year)


[18]

[23]

Ref.



ut

A



Pakyz et al. (2011) 30,071 inpatients

NR


NA


Primary NA admission: US$10,212 CDI-secondary diagnosis: US$29,946

CDI primary diagnosis: US$12,456 (CDN)

of

NA

US$13,675

NA

NA

21.1 versus 10.0

15.7

6.4

13.6

NR

8.8

NR


NA

2.9

NA

NA

NA



MA, USA

3692 patients inpatient data with recurrence evaluation

Retrospective cohort, payer

O’Brien et al. (2007)

NA


P ro


Canada

Laboratorybased prevalence, hospital

Miller et al. (2002)

ho r


209 patients Primary with recurrent episode: CDI US$1914 Recurrent episodes: US$3103 Primary plus recurrent: US$10,970


McFarland et al. Prospective USA, (1999) cohort, patient nationwide

Study (year)


[17]

[14]

[30]

[29]

Ref.


17

18

A



Prospective case–control, hospital

Prospective case–control, hospital

Peery et al. (2012)

Stewart et al. (2011)

Vonberg et al. (2008)

Wilcox et al. (1996) 142 geriatric inpatients

45 inpatients

82,414 inpatients

49,198 inpatients with SOT with or without CDAD NA

Inpatients with or without CDI: €33,840 versus 18,981

NA

78.28


NR

N/A

NR


of

£4107

€7147

P ro

Inpatients with CDAD: US$6774




46.5 versus 25.2

21.3

27 versus 7 20

13 versus NA 7.9

5

9 versus 4 NR



UK

Germany


ho r

ut

Pant et al. (2012) Retrospective, USA, hospital nationwide


Study (year)


[11]

[12]

[15]

[19]

[21]

Ref.



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A



Zilberberg et al. (2009) 64,910 inpatients undergoing prolonged acute mechanical ventilation with or without CDAD

8113 surgical inpatients

of

US$10,355

US$77,483‡ (total attributable charges)


P ro

266.67


Surgical inpatients with or without CDI: US$63,184 versus 17,232



25 versus 6.1 17

18 versus 16‡ 4




Zerey et al. (2007)


ho r


Study (year)


[24]

[26]

Ref.


19


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When viewed from any perspective, the total cost of C. difficile is substantial. For an individual patient with CDI, overall hospital costs may range from approximately US$10,000 to over US$50,000 – of which, US$2500 to nearly US$5000 may be directly attributable to the disease. For certain specific populations, such as surgical inpatients with CDI, cost estimates may increase to over US$100,000 per episode. Placed in the context of the overall healthcare system the costs are staggering. In the USA, reasonable estimates place the total cost of CDI at US$3.2 billion per year (see Figure 3 for cost estimates in other countries). Novel therapeutic strategies and preventive measures will hopefully decrease this substantial burden.

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Financial & competing interests disclosure KW Garey and DN Shah have ongoing research support from Merck, Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Summary.

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The economic impact of disease is significant, with the total cost to the US healthcare system placed between US$750 million and US$3.2 billion per year. Additional costs are primarily driven by an increased hospital length of stay and associated boarding fees, rather than additional laboratory or pharmacy costs. Hospitalized patients with Clostridium difficile infection (CDI) have excess costs of at least US$2500–3000 compared with patients without CDI. CDI is associated with an estimated additional 209,000 inpatient hospital days per year in the USA. CDI is the tenth most frequent gastrointestinal-related discharge diagnosis, and is the ninth leading cause of death among gastrointestinal disorders.

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