1. 1 Mupirocin vs. Gentamicin in the Prevention of PD-related Infections Mary Elliot Nov. 23, 2010

2. Outline Objectives Overview of case DRPs Background on peritoneal dialysis and peritonitis Clinical question Literature Review Recommendation and monitoring plan 2

3. 3 Objectives Be able to describe the mechanism of peritoneal dialysis (PD) as related back to JW Know the 3 types of infections that can occur as complications during peritoneal dialysis Understand the current evidence behind choosing a prophylactic treatment for PD related infections and be able to apply this back to JW

4. The Man of the Hour ID JW, 82 year old Chinese male, 67 kg CC/HPI ESRD secondary to glomerulosclerosis Started on peritoneal dialysis December 2004 Admission to VGH Oct. 27/10 for catheter infection with gram positive cocci treated with vancomycin IV for 2 weeks as an outpatient. Was using gentamicin ointment prior to catheter removal. Peritoneal catheter removed as had recurrent exit site infections over past few months. Currently receiving hemodialysis as an outpatient at VGH Plan to assess reinsertion of the catheter late Nov 4

5. The Man of the Hour VitalsBP = 125/58; Pulse = 58 Social HxLives with wife in Vancouver, has two children Quit smoking in 1985 after a 38 pack yr habit Minimal alcohol intake Immigrated to Canada from China in 1952 Retired in 1986 after owning a restaurant. Family HxFather died at the age of 77 from kidney failure Mother died at 78, cause unknown 1 of 6 children, no others have renal disease AllergiesNo known drug allergies 5

6. The Man of the Hour 6 Past medical history Peritonitis July 2008 Hypertension x 15 years Abdominal aortic aneurysm repair in April 2006 Gout – no recent flare-ups Renal calculi 1990 Remote eczema Neuropathic pain Reflux BPH

7. Current Medications MedicationDosageIndication Alfacalcidol0.5 mcg po once daily Secondary hyperparathyroidism Darbepoetin30 mcg IV once weekly ESRD related anemia Ferrous Fumarate300 mg po once daily Sevelamer2400 mg TID with meals Phosphate binder Renavite1 tablet dailyWater-soluble (B&C) vitamin supplement 7

8. Current Medications MedicationDosageIndication ASA81 mg dailyCardiac and stroke prevention Omeprazole20 mg po once dailyReflux Acetaminophen325 mg po QID prnNeuropathic pain Pregabalin150 mg po BID Colchicine0.6 mg po daily, available during flare-ups Gout Uremol 10Apply TID prnDry, irritated skin 8

9. Pertinent Lab Values Anemia Mineral bone disease Electrolytes and other values of interest 9 HgbFerritinTSAT 109 (110-120)690 (200 – 800)24% ( > 20%) PTHCaAlbPO 4 25.4 (<80)2.4 (2.1 – 2.55)391.7 (0.8 – 1.8) WBCPltNaKLDLHDLRatioTG 9.51301274.32.21.23.82.5

10. DRPs 1.JW is at risk of developing a peritoneal dialysis related infection upon restarting PD and requires review of technique and assessment of prophylactic therapy 1.JW is at JW is at risk of increased drowsiness secondary to a recently increase in dose of pregabalin for the treatment of neuropathic pain and requires monitoring. 10

11. Peritoneal Dialysis A system where the peritoneal membrane acts as a filter. Plastic catheter is inserted into the peritoneal cavity and anchored into the subcutaneous tissue. A dialysis solution is infused into the peritoneal cavity and remains there for several hours. Solute transport occurs across the membrane until the solution is drained and replaced with fresh solution. 11

12. Peritoneal Dialysis 12 http://solacedme.com/Renal.aspx

13. Peritoneal Dialysis Various regimens available: –CAPD (continuous ambulatory PD) where multiple exchanges, generally 4, are performed daily with 2L at each exchange –APD (automated PD) where a mechanized cycler infuses and drains dialysate at night –CCPD (continuous cycling PD) involves using the cycler at night plus a daytime fill. Desirable for people who wish to keep a flexible, active lifestyle, to whom dialysis units are not easily accessible, or who cannot tolerate the fluid shifts and blood-pressure swings associated with hemodialysis. 13

14. Peritoneal Dialysis Complications –Exit site infections (ESI) Purulent drainage from exit site +/- erythema –Tunnel infections Erythema, edema, or tenderness over SQ pathway –Peritonitis Patients typically present with abdominal pain, fever, and cloudy dialysate solution. Most commonly caused by Staph aureus or Pseudomonas aeruginosa. 14

15. Peritonitis Prevention Proper technique for exit site care Flushing the line with dialysate prior to filling the abdomen reduces the risk of peritonitis from contamination. Antibiotic ointment to exit site daily after cleansing –Mupirocin: covers gram positive (S. Aureus) –Gentamicin: covers S. Aureus and gram negative (including pseudomonas) –Either of these therapies are recommended in the ISPD guidelines. 15 Perit Dial Int. 2005 Mar-Apr;25(2):107-31

16. Goals of Therapy Prevent recurrence of exit site infection and peritonitis in JW. Prevent complications of peritonitis in JW such as peritoneal membrane failure, hospitalization, and death. Avoid adverse effects such as exit site irritation and rash. 16

17. PICO PIn an 82 year man who is currently receiving hemodialysis but is scheduled to be put back on peritoneal dialysis is Igentamicin Cas compared to mupirocin Oa safe and effective therapy for preventing PD-related infections. 17

18. 18 Search Strategy Pubmed, Embase, Web of Science Search terms: mupirocin, gentamicin, peritonitis, peritoneal dialysis Limits: English, humans Results: 3 studies directly comparing mupirocin and gentamicin in PD patients. Local research

19. Randomized, Double-Blind Trial of Antibiotic Exit Site Cream for Prevention of Exit Site Infection in Peritoneal Dialysis Patients; Bernardini et al. J Am Soc Nephrol 2005;16:539-45 DesignRandomized, double-blind multi-centred Patients (n = 133) Inclusion: at least 18 y.o.; on PD; able to give informed consent; already enrolled in a registry permitting data collection. Exclusion: allergy to either cream, involvement in another study, or peritonitis or catheter infection either currently or in the last 30 days. InterventionGentamicin (n = 67) vs. mupirocin ( n = 66) cream applied to peritoneal catheter site during routine exit site care. Primary outcomeP. aeruginosa and S. aureus catheter infection rates SecondaryGram-negative and Gram-positive peritonitis. Other outcomesOverall catheter infection and peritonitis rates, causative organisms, catheter removals as a result of infection, and time to first catheter infection 19

20. 20 J Am Soc Nephrol 2005;16:539-45

21. Randomized, Double-Blind Trial of Antibiotic Exit Site Cream for Prevention of Exit Site Infection in Peritoneal Dialysis Patients; Bernardini et al. J Am Soc Nephrol 2005;16:539-45 21

22. Randomized, Double-Blind Trial of Antibiotic Exit Site Cream for Prevention of Exit Site Infection in Peritoneal Dialysis Patients; Bernardini et al. J Am Soc Nephrol 2005;16:539-45 22

23. Randomized, Double-Blind Trial of Antibiotic Exit Site Cream for Prevention of Exit Site Infection in Peritoneal Dialysis Patients; Bernardini et al. J Am Soc Nephrol 2005;16:539-45 Catheter removal rates similar between two groups Adverse effects: Exit site irritation, led to withdrawal in 7 patients of each arm. Conclusion: Gentamicin applied to exit site was highly effective in reducing P. aeruginosa infections and was as effective as mupirocin in preventing S. aureus infections. Comments: –Designed to look at exit site infection rates as opposed to peritonitis rates, however, still found a difference. –Stopped early 23

24. A PROSPECTIVE STUDY OF THE EFFICACY OF LOCAL APPLICATION OF GENTAMICIN VERSUS MUPIROCIN IN THE PREVENTION OF PERITONEAL DIALYSIS CATHETER-RELATED INFECTIONS. Chu et al. Pert Dial Int. 2008;28:505-8 DesignProspective Patients (n = 95) Inclusion: Adult PD patients in a Hong Kong outpatient clinic Exclusion: active infection; exit site infection or peritonitis in previous 4 weeks; allergy to treatment; inability to apply drug or give consent. InterventionMupirocin ointment (n = 38) vs. Gentamicin cream (n = 43) applied around the exit site after their routine daily cleaning procedure. OutcomeNo pre-specified outcomes were mentioned in the methodology. Episodes of infection and side effects were tracked during hospital admissions and clinic visits. 24

25. 25 Pent Dial Int. 2008 Sep-Oct:28(5);505-8

26. 26 Pent Dial Int. 2008 Sep-Oct:28(5);505-8

27. A PROSPECTIVE STUDY OF THE EFFICACY OF LOCAL APPLICATION OF GENTAMICIN VERSUS MUPIROCIN IN THE PREVENTION OF PERITONEAL DIALYSIS CATHETER-RELATED INFECTIONS. Chu et al. Pent Dial Int. 2008 Sep-Oct:28(5);505-8 Side effects notes were local irritation, itching, and rash Conclusions: –Peritonitis occurred at the same rates in both groups. –Gentamicin was not superior to mupirocin in the prevention of exit site infections –Catheter removal required in 1 x mup and 2 x gent Limitations: –Small sample size, single site –No mention of randomization or blinding –No power calculation performed –No parameters specified for diagnosis of infection 27

28. Comparison of Gentamicin and Mupirocin in the Prevention of Exit-Site Infection and Peritonitis in Peritoneal Dialysis. Mahaldar et al. Adv Perit Dial. 2009;25:56-9. DesignRetrospective chart review ObjectiveTo determine if the incidence of ESIs and peritonitis changed after a switch from mupirocin to gentamicin ointment. Patients (n = 100)18 years and older PD patients seen in outpatient clinic who had had their catheter for at least 3 months. InterventionMupirocin (n = 50) vs. Gentamicin (n = 50) [23 gentamicin patients had previously been on mupirocin] OutcomesRates of ESI, peritonitis and the organism causing the infection. 28

29. 29 Adv Perit Dial. 2009;25:56-9. p = 0.45 p = 0.75 p = 0.22

30. 30 Adv Perit Dial. 2009;25:56-9. p = 0.07 p = 0.08 p = 0.83

31. Comparison of Gentamicin and Mupirocin in the Prevention of Exit-Site Infection and Peritonitis in Peritoneal Dialysis. Mahaldar et al. Adv Perit Dial. 2009;25:56-9. Conclusion: No difference in rates of ESI between the two groups, with a non-statistically significant trend towards higher rates of peritonitis in gentamicin group. Limitations: –Small sample size and infection rate –Retrospective, therefore not controlled for other contributing factors such as aseptic exit-site care. –Inaccurate chart documentation may have led to over to under reporting of cases of infection. –Single site 31

32. Comparison of gentamicin ointment to mupirocin ointment for prevention of peritoneal dialysis catheter-related infections. VGH based study – Wu, Greanya, Shalansky DesignObservational sequential cohort ObjectiveCompare the efficacy of gentamicin and mupirocin in the prevention of catheter-related PD infections. Patients (n = 73)18 years +, new PD catheter, followed by outpt PD clinic. Exclusion: allergic to either ointment or experienced an episode of infection during the catheter healing process before the ointment was started. InterventionMupirocin (n = 59) vs. Gentamicin (n = 14) ointment to catheter site Primary outcomeLength of time to first infection (CES, tunnel, or peritonitis) Secondary outcome Catheter-related infection rates, incidence and types of infection, treatment regimens required, and outcomes of infections. 32

33. Comparison of gentamicin ointment to mupirocin ointment for prevention of peritoneal dialysis catheter-related infections. VGH based study – Wu, Greanya, Shalansky Mupirocin (n = 59)Gentamicin (n = 14) Patients with infections, n (%)18 (31)4 (29) Time to earliest infection (days)1819 Total number of infections345 Type of infection, n (%)ESI 8(24); P* 26(76)ESI 4(80); P* 1(20) Gram-positive bacteria14 (41%)2 (40%) Gram-negative bacteria8 (24%)0 Negative culture8 (24%)3 (60%) 33 Conclusion: Similar incidence in infection rate in gentamicin arm as mupirocin arm with less peritonitis and similar gram +ve infection rates. Limitations: Interim analysis with gentamicin arm incomplete. Mupirocin arm is retrospective therefore data could be missing or incomplete. * P = peritonitis

34. Summary Efficacy –Bernardini et al: Gentamicin arm showed a statistically significant lower rate in both exit site infections and peritonitis over the mupirocin arm. –No other study showed a statistically significant difference between the two groups. Safety –Side effects were minimal in both groups and included exit site irritation, itching, and rash Cost: –Mupirocin: $14.14Gentamicin: $14.31 34

35. Back to the Case JW has recently had his catheter removed secondary to recurrent exit site infections, for which cultures have grown gram positive cocci. Evidence shows gentamicin ointment prevents gram negative and gram positive infections. Once the catheter is reinserted recommend using gentamicin applied daily to exit site for prevention of PD related infections. 35

36. Monitoring ParameterWhoFrequencyEnd-point Signs of infection (redness at exit-site, abdominal pain, cloudy dialysate, purulent drainage, fever) PatientDailyNo recurrent exit- site infection NurseOn each clinic visit Adverse effects (exit-site irritation and rash) PatientDailyAbsence of adverse effects Uremia symptoms (itchy skin, insomnia) PatientDailyAbsence of uremic symptoms Nurse, pharmacist, physician On each clinic visit General ESRD associated parameters (Hgb 110-120; PO 4 0.8-1.8; Ca 2.1-2.55; PTH 20-80) Pharmacist and physician PTH every 3 months Hgb, PO 4, Ca monthly Parameters within targets 36

37. Thank-you! Questions? 37