Hostname: page-component-7b7567c8c-tnzcf Total loading time: 0 Render date: 2026-11-12T09:36:04.533Z Has data issue: false hasContentIssue false
  • English
  • Français

Antibiotic Overuse is a Major Risk Factor for Clostridium difficile Infection in Surgical Patients

Published online by Cambridge University Press:  31 July 2017

James T. Bernatz,
Nasia Safdar,
Scott Hetzel and
Paul A. Anderson
James T. Bernatz*
Affiliation:
Department of Orthopedics and Rehabilitative Medicine; University of Wisconsin School of Medicine & Public Health, Madison, Wisconsin
Nasia Safdar
Affiliation:
Department of Medicine, Division of Infectious Disease, University of Wisconsin School of Medicine & Public Health, Madison, WisconsinWilliam S. Middleton Memorial Veterans Hospital, Madison, Wisconsin
Scott Hetzel
Affiliation:
Department of Biostatistics and Medical Informatics, University of Wisconsin–Madison, Madison, Wisconsin.
Paul A. Anderson
Affiliation:
Department of Orthopedics and Rehabilitative Medicine; University of Wisconsin School of Medicine & Public Health, Madison, Wisconsin
*
Address correspondence to James Bernatz, MD, UW Medical Foundation Centennial Buildingm 1685 Highland Avenue, 6th Floor, Madison, WI 53705-2281 (jbernatz@wisc.edu).
Rights & Permissions [Opens in a new window]

Abstract

Clostridium difficile infection (CDI) is associated with increased cost, morbidity, and mortality in postoperative patients. Variable rates of postoperative CDI are reported among 4 surgical specialties during the 30-month study period. Risk factors for CDI include antibiotic use, increased ASA score, and increased admissions in the past year.

Infect Control Hosp Epidemiol 2017;38:1254–1257

Information

Type
Concise Communications
Information
Infection Control & Hospital Epidemiology , Volume 38 , Issue 10 , October 2017, pp. 1254 - 1257
Copyright
© 2017 by The Society for Healthcare Epidemiology of America. All rights reserved 

Clostridium difficile infection (CDI) following surgical procedures is associated with morbidity, mortality, and cost. Length of stay is increased by 1 week if surgery is complicated by a CDI, and mortality has been reported as high as 35% in trauma surgery patients.Reference Maltenfort, Rasouli, Morrison and Parvizi 1 , Reference Sharma, Bomireddy and Phillips 2 Cost of care more than doubles if the postoperative patient contracts CDI.Reference Maltenfort, Rasouli, Morrison and Parvizi 1 Therefore, it is essential to reduce the risk of CDI in surgical patients.

Previous studies have reported CDI rates for individual specialties or after specific procedures with small sample sizes.Reference Maltenfort, Rasouli, Morrison and Parvizi 1 , Reference Damle, Cherng and Flahive 3 – Reference Krapohl, Morris and Cai 7 To our knowledge, there have been no reports of CDI across multiple surgical specialties. Differences across surgical specialties could be due to overall health of the patient population, complexity of surgery, perioperative antibiotic selection, pre- and postoperative exposure to additional antibiotics, or many other factors. The aims of our study were to determine the incidence of postoperative CDI across four surgical specialties (orthopedic surgery, neurosurgery, trauma surgery, and general surgery) and to examine risk factors for CDI.

METHODS

This study was conducted at a 592-bed tertiary-care academic center, and we were granted an exemption by the institutional review board. Using the hospital’s quality improvement database, all admissions to 4 hospital units (ie, orthopedic surgery, neurosurgery, trauma surgery, and general surgery) from January 2014 to July 2016 were reviewed. Patients who underwent an inpatient surgical procedure were included. Exclusion criteria included a documented CDI in the 2 months prior to admission or within 72 hours of admission. A case patient was defined as a patient who underwent an inpatient surgical procedure and subsequently developed healthcare-associated CDI (HA-CDI), defined as a positive PCR for C. difficile toxin gene recorded more than 72 hours after admission and within 12 weeks of discharge. Controls were patients selected from the same group of patients who underwent an inpatient surgical procedure but did not develop HA-CDI. The electronic medical record was used for data extraction. Variables of interest were extracted by a single author.

Statistical Methods

Control patients were matched in triplicate based on age, sex, and admitting department. If more than 3 controls fit the matching criteria for a case, then 3 were chosen at random.

Data analysis included summarizing the cases with means (±standard deviation [SD]) for normally distributed continuous variables, medians (with interquartile range [IQR]) for nonnormally distributed continuous variables, and frequency (%) for categorical variables. Associations between collected data and subject group were first assessed with univariable mixed-effect logistic regression (MELR) models with matched pair number as a random effect followed by multivariable MELR analyses with a priori defined covariates of body mass index (BMI), American Society of Anesthesiologists (ASA) classification, and antibiotic use in the previous 6 months. A P value≤.05 was considered significant. R version 3.3 software (R Foundation for Statistical Computing, Vienna, Austria) was used for statistical analyses.

RESULTS

Incidence

Over the 30-month study period, there were 11,310 admissions to the 4 included hospital units during which the patient had an inpatient operation. In 52 cases, the patient had a positive C. difficile polymerase chain reaction (PCR) test recorded more than 72 hours after admission and within 12 weeks of discharge. The incidence rate of hospital-acquired CDI was 0.80 cases per 1,000 patient days. Comparing specialties, trauma surgery had the highest rate of CDI at 9.5 cases per 1,000 admissions (Table 1).

TABLE 1

Incidence of Clostridium difficile infection (CDI) by Hospital Unit

NOTE. OR, odds ratio; CI, confidence interval.

a Cases per 1,000 admissions.

Risk Factor Analysis

From univariable analysis, the following variables were associated with statistically significant increased odds of CDI: number of admissions in past year (OR, 2.25; P<.001), ASA classification of 4–5 versus 1–2 (OR, 10.45; P<.001), antibiotic use in the previous 6 months (OR, 2.80; P=.002), proton pump inhibitor or H2 receptor blocker use in the previous 6 months (OR, 2.14; P=.026), antibiotics continued more than 24 hours postoperatively (OR, 5.44; P<.001), and nonperioperative antibiotics (OR, 3.59; P<.001) (Table 2).

TABLE 2

Risk Assessment of Subject and Procedure Characteristics and OutcomesFootnote a

NOTE. SD, standard deviation; IQR, interquartile ratio; OR, odds ratio; CI, confidence interval; BMI, body mass index, CCI, Charlson comorbidity index, ASA, American Society of Anesthesiologists; CKD, chronic kidney disease; PPI, proton pump inhibitor; SNF, skilled nursing facility.

a Data reported as mean (SD), median (IQR) or OR (95% CI).

b Multivariable analysis controls for BMI, ASA classification, and previous antibiotic use in the past 6 months.

c ASA classification: 1, a normal healthy patient; 2, a patient with mild systemic disease; 3, a patient with severe systemic disease; 4, a patient with severe systemic disease that is a constant threat to life; 5, a moribund patient who is not expected to survive without the operation.

Controlling for BMI, ASA classification, and antibiotic use in the previous 6 months, the following variables were associated with statistically significant increased odds of CDI by multivariable analysis: number of admissions in past year (OR, 2.33; P=.001), ASA class of 4–5 versus 1–2 (OR, 15.39; P<.001), antibiotic use in the previous 6 months (OR, 3.74; P<.001), antibiotics continued more than 24 hours postoperatively (OR, 3.38; P=.026), and nonperioperative antibiotics (OR, 2.20; P=.038).

Outcomes

Length of stay during the postoperative admission was significantly increased on univariable analysis (OR, 1.16; P<.001) as well as multivariable analysis (OR, 1.14; P<.001) (Table 2). Length of stay was evaluated as a continuous variable, and for every additional admission in the previous year, odds of CDI increased by 14%. Discharge to skilled nursing facility versus home was also more likely for patients with CDI on univariable analysis (OR, 2.61; P=.020).

DISCUSSION

Our study examined incidence of and risk factors for CDI across multiple surgical specialties in one tertiary-care center. We found rates 4–5 times higher in the trauma and general surgery units than in the orthopedic and neurosurgery units. This variability may be attributable to differences in patient factors such as overall health, antibiotic use, or healthcare setting exposure as well as surgical factors (eg, intra-abdominal trauma surgeries versus orthopedic joint surgeries).

We found that having an ASA class of 4 or 5 increases the odds of CDI 15-fold compared to an ASA class of 1 or 2. This suggests that the complexity of a patient’s illness may increase the risk of CDI. Interestingly, the complexity of the surgery itself, as represented by operative time and blood loss, does not correlate with increased odds of CDI.

If the perioperative antibiotic is continued more than 24 hours after surgery, outside of the perioperative window, the odds of CDI increase 3.34-fold. This finding has been reported previously and highlights the importance of minimizing antibiotic use to only the perioperative period if possible.Reference Shah, Pass, Cox, Lanham and Arnold 8 Use of antibiotics while in the hospital other than the perioperative antibiotic was also associated with 2.2 times greater odds of CDI. Antibiotic exposure as long as 6 months prior to surgery increases the odds of CDI more than 3-fold. Although the surgeon cannot change the fact that their patient received antibiotics, it should alert him or her to the fact that the patient may be at higher risk for postoperative CDI.

Previous studies have shown a correlation between CDI and hospital admission in the previous 3 months.Reference Zacharioudakis, Zervou, Pliakos, Ziakas and Mylonakis 9 Our study reports that this association extends to 12 months. We found that the number of hospital admissions in the past year increases the odds of CDI by 133% for each admission. Given the extensive environmental contamination with C. difficile in healthcare settings, this is a biologically plausible finding.

This study has several limitations. First, the hospital database only tracks patients within the hospital system. Therefore, CDI diagnoses, admissions, and medications from other facilities were not tracked. This study has a relatively small sample size of 52 cases, which limits the power of our statistical analysis. Further, this case-control study is subject to the limitations of all case-control studies.Reference Lewallen and Courtright 10

In conclusion, we found a variable incidence of CDI among surgical specialties at a single tertiary-care hospital. Our analysis suggests that higher ASA class, pre- or postoperative antibiotic use (outside of the perioperative period), and more admissions in the past year are associated with increased odds of CDI. Future studies should examine antibiotic stewardship efforts in the surgical population for reducing CDI.

ACKNOWLEDGMENTS

Financial support. None reported.

Conflicts of interest. All authors report no conflicts of interest relevant to this article.

References

REFERENCES

1. Maltenfort, MG, Rasouli, MR, Morrison, TA, Parvizi, J. Clostridium difficile colitis in patients undergoing lower-extremity arthroplasty: rare infection with major impact. Clin Orthop Relat Res 2013;471:3178–3185.Google Scholar
2. Sharma, P, Bomireddy, R, Phillips, S. Clostridium difficile-associated diarrhoea after internal fixation of intertrochanteric femoral fractures. Eur J Clin Microbiol Infect Dis 2003;22:615–618.Google Scholar
3. Damle, RN, Cherng, NB, Flahive, JM, et al. Clostridium difficile infection after colorectal surgery: a rare but costly complication. J Gastrointest Surg 2014;18:1804–1811.Google Scholar
4. Dasenbrock, HH, Bartolozzi, AR, Gormley, WB, Frerichs, KU, Aziz-Sultan, MA, Du, R. Clostridium difficile infection after subarachnoid hemorrhage: a nationwide analysis. Neurosurgery 2016;78:412–420.Google Scholar
5. Egorova, NN, Siracuse, JJ, McKinsey, JF, Nowygrod, R. Trend, risk factors, and costs of Clostridium difficile infections in vascular surgery. Ann Vasc Surg 2015;29:792–800.Google Scholar
6. Guzman, JZ, Skovrlj, B, Rothenberg, ES, et al. The burden of Clostridium difficile after cervical spine surgery. Global Spine J 2016;6:314–321.Google Scholar
7. Krapohl, GL, Morris, AM, Cai, S, et al. Preoperative risk factors for postoperative Clostridium difficile infection in colectomy patients. Am J Surg 2013;205:343–347; discussion 347–348.CrossRefGoogle ScholarPubMed
8. Shah, K, Pass, LA, Cox, M, Lanham, M, Arnold, FW. Evaluating contemporary antibiotics as a risk factor for Clostridium difficile infection in surgical trauma patients. J Trauma Acute Care Surg 2012;72:691–695.CrossRefGoogle ScholarPubMed
9. Zacharioudakis, IM, Zervou, FN, Pliakos, EE, Ziakas, PD, Mylonakis, E. Colonization with toxinogenic C. difficile upon hospital admission, and risk of infection: a systematic review and meta-analysis. Am J Gastroenterol 2015;110:381–390; quiz 391.Google Scholar
10. Lewallen, S, Courtright, P. Epidemiology in practice: case-control studies. Community Eye Health 1998;11:57–58.Google ScholarPubMed
Figure 0

TABLE 1Incidence of Clostridium difficile infection (CDI) by Hospital Unit

Figure 1

TABLE 2Risk Assessment of Subject and Procedure Characteristics and Outcomesa