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Mupirocin vs. Gentamicin in
the Prevention of PD-related
Infections
Mary Elliot
Nov. 23, 2010
1
Outline
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Objectives
Overview of case
DRPs
Background on peritoneal dialysis and peritonitis
Clinical question
Literature Review
Recommendation and monitoring plan
2
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
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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
The Man of the Hour
Vitals
BP = 125/58; Pulse = 58
Social Hx
Lives 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.
Father died at the age of 77 from kidney
failure
Mother died at 78, cause unknown
1 of 6 children, no others have renal disease
No known drug allergies
Family Hx
Allergies
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The Man of the Hour
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
6
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
7
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
Pregabalin
150 mg po BID
Colchicine
0.6 mg po daily,
available during
flare-ups
Gout
Uremol 10
Apply TID prn
Dry, irritated skin
Neuropathic pain
8
Pertinent Lab Values
• Anemia
Hgb
Ferritin
TSAT
109 (110-120)
690 (200 – 800)
24% ( > 20%)
• Mineral bone disease
PTH
Ca
Alb
25.4 (<80)
2.4 (2.1 – 2.55) 39
PO4
1.7 (0.8 – 1.8)
• Electrolytes and other values of interest
WBC
Plt
Na
K
LDL
HDL
Ratio
TG
9.5
130
127
4.3
2.2
1.2
3.8
2.5
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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
http://solacedme.com/Renal.aspx
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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
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.
Perit Dial Int. 2005 Mar-Apr;25(2):107-31
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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
I
C
O
In an 82 year man who is currently receiving
hemodialysis but is scheduled to be put back
on peritoneal dialysis is
gentamicin
as compared to mupirocin
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
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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
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
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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
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
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
• 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 clinic
Exclusion: 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
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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. 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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p = 0.75
p = 0.22
p = 0.45
Adv Perit Dial. 2009;25:56-9.
29
p = 0.07
p = 0.08
p = 0.83
Adv Perit Dial. 2009;25:56-9.
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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.
• 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%)
•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
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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 exitsite 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
Nurse,
pharmacist,
physician
On each clinic
visit
Absence of
uremic symptoms
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
months
Hgb, PO4, Ca
monthly
Parameters within
targets
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Thank-you!
Questions?
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