1. Incidence of Clostridium difficile infections related to the administration of broad-spectrum antibiotics and proton pump inhibitors By: Jacob A. Foret, Dr. Amanda Eymard DNS, RN, CNE, Mrs. Jeanne Hamner, RN, MSN Nicholls State University Thibodaux, LA

2. Clostridium difficile.25 μ m

3. Let’s Talk About C. difficile. What is Clostridium difficile ? What is Clostridium difficile ? Gram positive bacteria Gram positive bacteria Infection rates in hospitals Infection rates in hospitals 337,000 infected annually 337,000 infected annually 14,000 deaths annually 14,000 deaths annually How is it spread? How is it spread? Fecal to oral route from bacterial spores Fecal to oral route from bacterial spores Patients are placed on contact precautions Patients are placed on contact precautions

4. Let’s Talk About C. difficile. Where can C. difficile normally live? Where can C. difficile normally live? Digestive tract of any human or on surfaces inactivated for two weeks. Digestive tract of any human or on surfaces inactivated for two weeks. What kills on C. difficile surfaces or people’s hands? What kills on C. difficile surfaces or people’s hands? Surfaces – bleach Surfaces – bleach People’s hands– only soap and water People’s hands– only soap and water Alcohol gels do not kill C. difficile Alcohol gels do not kill C. difficile What does that mean for you? What does that mean for you? Anyone can potentially have a colonization without symptoms. Anyone can potentially have a colonization without symptoms.

5. Let’s Talk About C. difficile. What are complications to an infection? What are complications to an infection? DEATH, subtotal colectomy, electrolyte depletion, or metabolic acidosis DEATH, subtotal colectomy, electrolyte depletion, or metabolic acidosis How does death occur? How does death occur? Severe dehydration from uncontrollable diarrhea Severe dehydration from uncontrollable diarrhea Financial Impact Financial Impact 1 billion dollars annually absorbed by health care agencies 1 billion dollars annually absorbed by health care agencies

6. Known Contributors Broad-spectrum antibiotics and proton pump inhibitors are known contributors to a patient contacting C. difficile in the hospital because of the mechanism of action of the medications.

7. Broad-Spectrum Antibiotics Intended Purpose Intended Purpose Destroy harmful bacteria that cause disease in humans Destroy harmful bacteria that cause disease in humans Actual Effects Actual Effects Destroy harmful bacteria and also the natural flora Destroy harmful bacteria and also the natural flora Relation to C. difficile Relation to C. difficile The natural flora helps protect against C. difficile by keeping a healthy, natural balance. The natural flora helps protect against C. difficile by keeping a healthy, natural balance.

8. Broad-Spectrum Antibiotics BSA

9. Proton-Pump Inhibitors What are proton-pump inhibitors? What are proton-pump inhibitors? A class of medications that inhibits the production of hydrochloric acid of the stomach through blocking proton pumps. A class of medications that inhibits the production of hydrochloric acid of the stomach through blocking proton pumps. How does this relate to C. difficile ? How does this relate to C. difficile ? Raising the pH of gastric contents can lower the body’s primary GI defense mechanism against C. difficile. Raising the pH of gastric contents can lower the body’s primary GI defense mechanism against C. difficile.

10. Let’s Talk About You and Me How does this affect you and me? How does this affect you and me? How many of you have ever been prescribed a broad-spectrum antibiotic for a cold or upper respiratory infection? How many of you have ever been prescribed a broad-spectrum antibiotic for a cold or upper respiratory infection? How many of you have taken a drug to lower the amount of acid in your stomach? How many of you have taken a drug to lower the amount of acid in your stomach? Or, how many of you know someone that fits into the two criteria above? Or, how many of you know someone that fits into the two criteria above? Criteria met? Criteria met? Have a higher potential to contract C. difficile Have a higher potential to contract C. difficile

12. Why Do Research? Purpose Purpose Determine if a single BSA or PPI or a combination of BSAs and a PPIs occur more frequently in patients with a positive C. difficile lab culture during hospital admission Determine if a single BSA or PPI or a combination of BSAs and a PPIs occur more frequently in patients with a positive C. difficile lab culture during hospital admission Goal Goal Raise awareness in healthcare systems that medication administration plays a vital role in patients contracting C. difficile infections Raise awareness in healthcare systems that medication administration plays a vital role in patients contracting C. difficile infections Share results with local healthcare organizations regarding correlation between BSAs and PPIs and the incidence of C. difficile infections Share results with local healthcare organizations regarding correlation between BSAs and PPIs and the incidence of C. difficile infections

13. Methodology Design Design Retrospective chart review of patient data relevant to the diagnosis of C. difficile that was retrieved from two hospitals Retrospective chart review of patient data relevant to the diagnosis of C. difficile that was retrieved from two hospitals Sample Sample Convenience sampling was utilized Convenience sampling was utilized Inclusion Criteria Inclusion Criteria Infection Control Nurse and MedMined® Infection Control Nurse and MedMined® T3 Power Analysis T3 Power Analysis

14. Methodology Data Data Demographics and medications administered during hospital stay Demographics and medications administered during hospital stay Data Analysis Data Analysis Descriptive statistics, ANOVA, Chi-square, and linear regression were utilized in the program of SPSS (v.19) Descriptive statistics, ANOVA, Chi-square, and linear regression were utilized in the program of SPSS (v.19) Multiple cross tabulations were also conducted to illustrate combination therapy Multiple cross tabulations were also conducted to illustrate combination therapy

15. Descriptive Statistics The average age of patients was 64.52 with a standard deviation of 17.78 The average age of patients was 64.52 with a standard deviation of 17.78 65.1% of patients were female and 34.9% were male 65.1% of patients were female and 34.9% were male The average number of days a BSA was administered was 11.24 with a standard deviation of 11.16 The average number of days a BSA was administered was 11.24 with a standard deviation of 11.16 The average number of days a PPI was administered was 10.47 days with a standard deviation of 11.13 The average number of days a PPI was administered was 10.47 days with a standard deviation of 11.13

16. Results

17. Results Vancomycin and Piperacillin/tazobactam (Zosyn) in combination occurred in 15 out of 80 cases in which more than one BSA was administered to a patient. Most Frequent Two BSA Combinations BSA #1 BSA #2# of Cases ZosynVancomycin15 VancomycinCipro5 LevaquinFlagyl4 LevaquinZosyn4 FlagylCipro4 FlagylZosyn3 FlagylVancomycin3 ZosynGaramycin2 ZosynCipro2 ZosynCilastatin2 ZosynRocephin2 VancomycinGaramycin2 VancomycinCeftriaxone2 VancomycinAzactam2 VancomycinClindamycin2

18. Results 57 patients were administered a PPI. Pantoprozole (Protonix) was the most frequent PPI administered in singularity with 47 cases.

19. A cross-tabulation was performed that measured how many occurrences a PPI was administered in combination with a BSA. Total ABX*PPI Crosstabulation PPI Total ProtonixPrilosecZantac Levaquin64010 Flagyl91010 Zosyn143017 Doxycycline0101 Rocephin2103 Tygacil0101 Merrem0101 Vancomycin142117 Garamycin1001 Cipro5005 Ancef1001 Cilastatin1001 Ertapenem1001 Ceftriaxone6006 Avelox1214 Trimeth- Sulfamethoxazol e 2002 Azactam1012 Cefuroxime1001 Clindamycin1001 Total6616385

20. Results A cross-tabulation was performed that measured how many occurrences two BSAs were administered in combination with a PPI. Crosstabulation ABX*PPI ProtonixPrilosecZantac ZosynVancomycin15710 Vancomyci nCipro5100 LevaquinFlagyl4210 LevaquinZosyn4100 FlagylCipro4200 FlagylZosyn3300 FlagylVancomycin3200 ZosynGaramycin2100 ZosynCipro2000 ZosynCilastatin2100 ZosynRocephin2200 Vancomyci nGaramycin2100 Vancomyci nCeftriaxone2200 Vancomyci nAzactam211 Vancomyci nClindamycin2100 Totals542721

21. Results Patients who received no BSAs and PPIs stayed an average of 5.18 days and patients who received both stayed an average of 16.69. Descriptive Statistics for Each Group Dependent Variable: TotalDays RecABXRecPPIMean Std. Deviation N No 5.183.20617 Yes6.715.56714 Total5.874.41831 Yes No8.296.10921 Yes16.6913.90642 Total13.8912.48563 Total No6.895.20338 Yes14.213.05756 Total11.2411.16194

22. Results Chi-square analysis was conducted on patients who received either a BSA or PPI. 45.3% of the patients in the study received both a PPI and BSA. Pearson regression was conducted showing a p = 0.04. RecABX*RecPPI Crosstabulation RecPPITotal NoYes RecABX No Count 17 14 31 % of Total17.9%14.7%32.6% Yes Count 21 43 64 % of Total22.1%45.3%67.4% Total Count 38 57 95 % of Total40.0%60.0%100.0% Chi-Square Tests Valuedf Asymp. Sig. (2- sided) Exact Sig. (2- sided) Exact Sig. (1- sided) Pearson Chi- Square4.22210.04 N of Valid Cases95

23. Limitations BSA administration in the study was not uniform, but more patients received BSAs and PPIs in combination than patients with single BSA administration. BSA administration in the study was not uniform, but more patients received BSAs and PPIs in combination than patients with single BSA administration. The study included data from patients who were admitted for the primary diagnosis of C. difficile. Home medication lists were not performed on some of these patients resulting in no BSA or PPI data. The study included data from patients who were admitted for the primary diagnosis of C. difficile. Home medication lists were not performed on some of these patients resulting in no BSA or PPI data. Retrospective chart review was performed by a single researcher. Retrospective chart review was performed by a single researcher.

24. Conclusions Conclusions Conclusions Piperacillin/tazobactam (Zosyn) was administered more frequently than any other BSA, in combination with other BSAs, and in combination with PPIs. Piperacillin/tazobactam (Zosyn) was administered more frequently than any other BSA, in combination with other BSAs, and in combination with PPIs. Pantoprazole (Protonix) accounted for the majority of PPI usage in the hospital. Pantoprazole (Protonix) accounted for the majority of PPI usage in the hospital. The administration of BSAs and PPIs together correlate with a patient having a positive C. difficile lab result in the hospital. The administration of BSAs and PPIs together correlate with a patient having a positive C. difficile lab result in the hospital. Future Studies Future Studies The study should be expanded to additional facilities to include a broader sample of prescribers. A control group should be utilized to support BSAs and PPIs in combination have the potential to cause C. difficile. The study should be expanded to additional facilities to include a broader sample of prescribers. A control group should be utilized to support BSAs and PPIs in combination have the potential to cause C. difficile.

25. What Does It Really Mean? Home Implications Home Implications Prescribers need to possibly be more conservative with prescribing BSAs and PPIs, especially in combination. Prescribers need to possibly be more conservative with prescribing BSAs and PPIs, especially in combination. Contributors to a patient contracting C. difficile have been identified but are still currently being prescribed to patient. Contributors to a patient contracting C. difficile have been identified but are still currently being prescribed to patient. Implications for practice Implications for practice

27. Acknowledgements

28. Acknowledgements cont.

29. Questions???