Discussion

V&P therapy carries more than double the risk of

AKI as V&C with NNH = 5.9

Incidence of AKI in both groups is similar to that in

previously published literature

Multivariate analyses did not find other risk

factors to be contributing to this AKI risk

AKI occurs early in therapy course, particularly

with V&P

Trend towards greater need for dialysis in V&P

group and earlier resolution compared to V&C

Sick patients merit broad spectrum therapy and

AKI risk may be acceptable, however ~20-30% of

study patients did not meet sepsis criteria

Mechanism of injury from concomitant V&P is not

known. Possibilities include tubular injury or

decreased renal excretion of creatinine

Evaluate AKI incidence from cefepime and

piperacillin monotherapy

Characterize the mechanism and severity of AKI

from these concomitant antibiotics

Define AKI outcomes, such as need for renal

replacement therapy, time to resolution of AKI and

risk of recurrent injury with repeat antimicrobial

therapy

Develop strategies to optimize the choice and

timing of broad spectrum empiric antibiotics to

minimize AKI risk and thereby reduce morbidity

from AKI

Future Directions

Save the Beans!

Acute Kidney Injury During Vancomycin Therapy with Piperacillin-Tazobactam versus Cefepime

Sheetal Gandotra MD1, Mindee Sue Hite PharmD2, John Kevin Hix MD3, Maryrose Laguio-Vila MD4 1Department of Internal Medicine, 2Department of Pharmacy, 3Deparment of Nephrology, 4Department of Infectious Disease, Rochester General Hospital, Rochester New York

Introduction

Vancomycin and piperacillin-tazobactam are

among the most commonly used inpatient

antibiotics nationwide

A known adverse event of vancomycin is

AKI, with a reported incidence of ~5% in

current literature

Per drug manufacturer Pfizer, approximate

AKI risk from piperacillin-tazobactam is ~2%,

however published literature estimates an

incidence of 5% or greater

AKI increases morbidity, mortality, and

prolongs hospitalization

Abstracts at Society of Critical Care

Medicine in 2011 showed AKI risk

significantly increased with addition of

piperacillin-tazobactam to vancomycin

(18.6% vs 4.9%, p <0.001)1,2

Retrospective chart review by Gomes et al.

found the incidence of AKI is significantly

higher with vancomycin when combined with

piperacillin-tazobactam (V&P) than with

cefepime (V&C), 34.8% vs 12.5%

(p<0.0001)3

The results were preserved in a matched

cohort3

Should we reconsider antibiotic practices at

Rochester General Hospital?

Evaluate incidence of AKI from combination

therapy with V&P versus V&C

Determine incidence of AKI from

concomitant use of other nephrotoxic agents

during antibiotic therapy

Identify other risk factors for AKI in the

setting of antibiotic therapy with vancomycin

and a beta-lactam

Objective

Retrospective chart review

Single center, community hospital

January 1 - March 7, 2014

Extended to August 30, 2014 for V&C group

due to less frequent use

AKI defined by AKIN criteria

For 80% power to detect at least 15%

difference in AKI incidence between groups,

predicted need for 43 patients per group

Methods

Inclusion Criteria Exclusion Criteria

• Inpatient

• Age ≥ 18

• Antibiotic (abx) therapy

for >48h

• Combination started

within 48h of each other

• SCr within 24h of abx

initiation

• Received study abx in

prior 7 days

• Renal replacement

therapy

• SCr ≥ 1.5x baseline or

calculated CrCl

<30mL/min within 24h of

abx

• Incomplete medical

record

• Pregnancy

180 courses reviewed

69 (38%) met exclusion criteria:

28 – SCr >1.5 x baseline

25 – Combination <48 hrs

6 – Received study Abx w/i

previous seven days

3 – CrCl <30 mL/min

2 – Abx started >48 hrs apart

2 – Renal Replacement Therapy

2 – Pip-Tazo alone

1 – Incomplete medical record

111 Courses Included

• 174 patients

• 109 patients

Results

Fig 1a: V&P group

292 courses reviewed

226 (77%) met exclusion criteria:

72 – Cefepime alone

55 – Received study Abx w/i

previous seven days

50 – Combination <48 hrs

19 – SCr >1.5 x baseline

17 – Renal Replacement

Therapy

9 – Abx started >48 hrs apart

2 – CrCl <30 mL/min

1 – No SCr w/i 24 hrs of Abx

1 – Age <18 years

66 Courses Included

• 281 patients

• 65 patients

Fig 1b: V&C group

Description V & P

(n = 109)

V & C

(n = 65) p value

Age, yrs mean ± SD 66.8 ± 14.9 65.2 ± 14.4 0.494

Male, n (%) 56 (51) 35 (54) 0.752

BMI, kg/m2, median

(IQR)

28.1

(23.4-34.4)

28.2

(23.7-34.9) 0.732

LOS, median days (IQR) 9 (6-15) 8 (5.5-14.5) 0.984

Combination therapy,

median days (IQR) 3 (2-5) 4 (3-6) 0.051

Charlson Comorbidity

Index, median (IQR) 7 (4-9) 6 (4-8) 0.066

Table 1: Demographics

0

0.2

0.4

0.6

0.8

1

Baseline Antibiotic Initiation

Se

rum

Cre

atin

ine

, m

g/d

L

Vanco & Pip-Tazo Vanco & Cefepime

Fig 3: Serum Creatinine by Group

0

20

40

60

80

100

Non-ICU ICU ED

Pe

rce

nta

ge

of

pa

tie

nts

p=0.01

Fig 5: Admission Unit

0 10 20 30 40 50

HIV/AIDS

CKD

Liver Disease

PVD

CHF

CVD

MI

COPD

DM

Malignancy

Percentage of Patients

p=0.014

Fig 2: Comorbid Conditions

0 5 10 15 20 25 30 35 40

Amphotericin

NSAIDS

Acyclovir

Chemotherapy

ACEI/ARB

Aminoglycoside

Contrast

Percentage of Patients

p = 0.008

p = 0.001

p = 0.028

Fig 4: Concomitant Nephrotoxin Use

0

20

40

60

80

100

None Sepsis Severe

Sepsis

Septic

Shock

Pe

rce

nta

ge

of

Pa

tie

nts

Fig 6: Sepsis Classification

0

10

20

30

40

Vanco & Pip-Tazo Vanco & Cefepime

32

15

Pe

rce

nta

ge

of

Pa

tie

nts

p = 0.011

OR = 2.13

NNH = 5.9

Fig 1: PRIMARY OUTCOME - AKI Incidence

0

20

40

60

80

100

Resolved at Discharge Dialysis Required

36

8 10 0

Pe

rce

nta

ge

of P

atie

nts

p=0.584

p=0.143

Fig 7: AKI Outcomes

V & P V & C p value

Days to AKI,

median (IQR) 3 (2-5) 6.5 (3-10) 0.028

Total days of AKI,

median (IQR) 5 (3-12.5) 3 (3-25.5) 0.378

Vancomycin Level V & P V & C p value

Median (IQR) 14.5

(10.4-16.9)

13.6 (10.3-16.2)

0.521

Maximum, median

(IQR) 16.3

(10.8-20.5)

14.4 (11.2-19.3)

0.320

Table 2: Time to AKI and Duration

Table 3: Vancomycin Levels

0

20

40

60

80

100

None Sepsis Severe

Sepsis

Septic

ShockP

erc

en

tag

e o

f P

atie

nts

Fig 6: Sepsis Classification

0

20

40

60

80

100

1 2 3

Perc

enta

ge o

f Pati

ents

STAGE OF AKI

Fig 8: AKI Severity by AKIN Criteria

AKI incidence is significantly higher in patients

receiving concomitant V&P compared to V&C

(32% vs 15%, p.011)

Antimicrobial choices must be carefully selected

especially when alternative, potentially less toxic

therapy is available

AKI risk appears to be conferred by the

combination of V&P without significant

contribution from other renal injury risk factors

and nephrotoxins

Conclusions

1. Hellwig T, Hammerquist R, Loecker JS, et al. Retrospective evaluation of the incidence of vancomycin

and/or piperacillin-tazobactam induced acute renal failure (Abstract). Crit Care Med 2011; 39(Suppl. 12):

79.

2. Burgess LD & Drew RH. Comparison of the incidence of Vancomycin-induced nephrotoxicity in hospitalized

patients with and without concomitant piperacillin-tazobactam. Pharmacotherapy 2014;34(7):670-676.

3. Gomes DM, Smotherman C, et al. Comparison of acute kidney injury during treatment with vancomycin in

combination with piperacillin-tazobactam or cefepime. Pharmacotherapy 2014;34(7):662-669).

References