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Mupirocin vs. Gentamicin in the Prevention of PD-related

Infections

Mary Elliot

Nov. 23, 2010

Outline

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

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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

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

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The Man of the Hour

Vitals BP = 125/58; Pulse = 58

Social Hx Lives with wife in Vancouver, has two childrenQuit smoking in 1985 after a 38 pack yr habitMinimal alcohol intakeImmigrated to Canada from China in 1952Retired in 1986 after owning a restaurant.

Family Hx Father died at the age of 77 from kidney failureMother died at 78, cause unknown1 of 6 children, no others have renal disease

Allergies No known drug allergies

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The Man of the Hour

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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

Current Medications

Medication Dosage Indication

Alfacalcidol 0.5 mcg po once daily

Secondary hyperparathyroidism

Darbepoetin 30 mcg IV once weekly

ESRD related anemia

Ferrous Fumarate 300 mg po once daily

Sevelamer 2400 mg TID with meals

Phosphate binder

Renavite 1 tablet daily Water-soluble (B&C) vitamin supplement

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Current Medications

Medication Dosage Indication

ASA 81 mg daily Cardiac and stroke prevention

Omeprazole 20 mg po once daily Reflux

Acetaminophen 325 mg po QID prn Neuropathic pain

Pregabalin 150 mg po BID

Colchicine 0.6 mg po daily, available during flare-ups

Gout

Uremol 10 Apply TID prn Dry, irritated skin

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Pertinent Lab Values

• Anemia

• Mineral bone disease

• Electrolytes and other values of interest

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Hgb Ferritin TSAT

109 (110-120) 690 (200 – 800) 24% ( > 20%)

PTH Ca Alb PO4

25.4 (<80) 2.4 (2.1 – 2.55) 39 1.7 (0.8 – 1.8)

WBC Plt Na K LDL HDL Ratio TG

9.5 130 127 4.3 2.2 1.2 3.8 2.5

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.

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Peritoneal Dialysis

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http://solacedme.com/Renal.aspx

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.

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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.

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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.

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Perit Dial Int. 2005 Mar-Apr;25(2):107-31

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.

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PICO

P In an 82 year man who is currently receiving hemodialysis but is scheduled to be put back on peritoneal dialysis is

I gentamicin

C as compared to mupirocin

O a safe and effective therapy for preventing PD-related infections.

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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

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

Design Randomized, 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.

Intervention Gentamicin (n = 67) vs. mupirocin ( n = 66) cream applied to peritoneal catheter site during routine exit site care.

Primary outcome P. aeruginosa and S. aureus catheter infection rates

Secondary Gram-negative and Gram-positive peritonitis.

Other outcomes Overall catheter infection and peritonitis rates, causative organisms, catheter removals as a result of infection, and time to first catheter infection

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J Am Soc Nephrol 2005;16:539-45

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

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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

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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

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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

Design Prospective

Patients(n = 95)

Inclusion: Adult PD patients in a Hong Kong outpatient clinicExclusion: active infection; exit site infection or peritonitis in previous 4 weeks; allergy to treatment; inability to apply drug or give consent.

Intervention Mupirocin ointment (n = 38) vs. Gentamicin cream (n = 43) applied around the exit site after their routine daily cleaning procedure.

Outcome No pre-specified outcomes were mentioned in the methodology. Episodes of infection and side effects were tracked during hospital admissions and clinic visits.

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

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

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

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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.

Design Retrospective chart review

Objective To 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.

Intervention Mupirocin (n = 50) vs. Gentamicin (n = 50)[23 gentamicin patients had previously been on mupirocin]

Outcomes Rates of ESI, peritonitis and the organism causing the infection.

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Adv Perit Dial. 2009;25:56-9.

p = 0.45

p = 0.75

p = 0.22

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Adv Perit Dial. 2009;25:56-9.

p = 0.07

p = 0.08

p = 0.83

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

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Comparison of gentamicin ointment to mupirocin ointment for prevention of peritoneal dialysis catheter-related

infections. VGH based study – Wu, Greanya, Shalansky

Design Observational sequential cohort

Objective Compare 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.

Intervention Mupirocin (n = 59) vs. Gentamicin (n = 14) ointment to catheter site

Primary outcome Length 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.

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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) 18 19

Total number of infections 34 5

Type of infection, n (%) ESI 8(24); P* 26(76) ESI 4(80); P* 1(20)

Gram-positive bacteria 14 (41%) 2 (40%)

Gram-negative bacteria 8 (24%) 0

Negative culture 8 (24%) 3 (60%)

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•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

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: $14.14 Gentamicin: $14.31

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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.

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Monitoring

Parameter Who Frequency End-point

Signs of infection (redness at exit-site, abdominal pain, cloudy dialysate, purulent drainage, fever)

Patient Daily No recurrent exit-site infection

Nurse On each clinic visit

Adverse effects (exit-site irritation and rash)

Patient Daily Absence of adverse effects

Uremia symptoms (itchy skin, insomnia)

Patient Daily Absence of uremic symptomsNurse,

pharmacist, physician

On each clinic visit

General ESRD associated parameters (Hgb 110-120; PO4 0.8-1.8; Ca 2.1-2.55; PTH 20-80)

Pharmacist and physician

PTH every 3 monthsHgb, PO4, Ca monthly

Parameters within targets

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Thank-you!

Questions?

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