Vancomycin Prescribing Practices in Hospitalized Chronic
Hemodialysis Patients
Kevin Green, MD, Gerald Schulman, MD, David W. Haas, MD,
William Schaffner, MD, and Erika M.C. D’Agata, MD, MPH
● To determine the prevalence of and indications for vancomycin administration among hospitalized chronic
hemodialysis patients, we performed a 3-month prospective cohort study at a tertiary care center. Modified
guidelines for vancomycin use from the Hospital Infections Control Practices Advisory Committee of the Centers
for Disease Control and Prevention were used. Vancomycin was administered during 56 of 144 admissions (39%)
requiring chronic hemodialysis compared with 336 of 7,212 admissions (5%) not requiring hemodialysis (relative
risk, 11; 95% confidence interval, 8 to 15; P F 0.001). Among chronic hemodialysis patients, vancomycin use was
judged appropriate for 131 of the 164 vancomycin doses (80%). The most common appropriate indication was
empiric therapy in a febrile patient before culture or susceptibility results. Of 32 infections identified in patients who
received empiric vancomycin, 15 infections (47%) were caused by ␤-lactam–resistant pathogens. Among the 33
doses (20%) judged inappropriate, continued therapy for a presumed infection despite failure to identify a
␤-lactam–resistant pathogen was the most common indication. Although vancomycin administration was frequent
among hospitalized chronic hemodialysis patients, its use was justified in the majority of cases. Efforts should
focus on limiting vancomycin administration for treating infections caused by ␤-lactam–sensitive pathogens.
娀 2000 by the National Kidney Foundation, Inc.
INDEX WORDS: Vancomycin; enterococcus; hemodialysis; hospital; chronic; antibiotic.
T
HE INCIDENCE of infections caused by
vancomycin-resistant enterococci (VRE) is
increasing in the dialysis population. In 1995,
11% of the hemodialysis centers in the United
States reported at least one patient colonized or
infected with VRE. By 1996, the number of
centers reporting VRE had doubled to 21%.1
Because identified risk factors for VRE colonization and/or infection include severity of underlying illness, frequent hospitalizations, and antibiotic exposure, particularly to vancomycin,2-5 the
increase in VRE cases among dialysis patients
was inevitable.
Vancomycin exposure is a potentially modifiable risk factor for VRE acquisition. To determine the indications for vancomycin administration, we performed a cohort study among
hospitalized patients requiring chronic hemodialysis. We sought to identify the frequency and
From the Department of Medicine, Divisions of Infectious
Diseases and Nephrology, and the Departments of Microbiology and Immunology and Preventive Medicine, Vanderbilt
University School of Medicine, Nashville, TN.
Received April 30, 1999; accepted in revised form August
10, 1999.
Address reprint requests to Erika M.C. D’Agata, MD,
Vanderbilt University Medical Center, Division of Infectious
Diseases, Medical Center North A-3310, 21st and Garland
St, Nashville, TN 37232. E-mail: erika.d’agata@mcmail.
vanderbilt.edu
娀 2000 by the National Kidney Foundation, Inc.
0272-6386/00/3501-0011$3.00/0
64
reasons for inappropriate administration of vancomycin based on modified guidelines of the
Hospital Infections Control Practices Advisory
Committee (HICPAC) of the Centers for Disease
Control and Prevention.6
METHODS
Vanderbilt University Medical Center (Nashville, TN) is a
663-bed tertiary care hospital. Approximately 14,000 patients are admitted per year, of whom an average of 400
(3%) require chronic hemodialysis.
From August 8 through November 11, 1998, a prospective
cohort study was performed on all patients admitted to
Vanderbilt University Medical Center who required chronic
hemodialysis. Approval for this study was obtained from the
institutional review board. A computerized pharmacy database was used to obtain information on vancomycin exposure for all patients admitted to the medical center.
Chronic hemodialysis was defined as dialysis initiated
before the current hospitalization. Medical records for patients receiving chronic hemodialysis were reviewed for
demographic and clinical data.
Indications for vancomycin use were classified as appropriate or inappropriate based on modified HICPAC criteria.6
Because of a high proportion of methicillin-resistant Staphylococcus aureus isolates (37%) at our institution and frequent infections caused by coagulase-negative staphylococci among the dialysis population, we modified the
HICPAC criteria to include as appropriate the empiric administration of a single dose of vancomycin in a febrile chronic
hemodialysis patient pending culture results or pending
susceptibility data if gram-positive cocci in clusters were
identified. Subsequent vancomycin doses administered to
the same patient were considered inappropriate if a ␤-lactam–
resistant gram-positive pathogen was not identified, per
HICPAC guidelines. Infections were classified according to
American Journal of Kidney Diseases, Vol 35, No 1 (January), 2000: pp 64-68
VANCOMYCIN USE IN DIALYSIS PATIENTS
65
Centers for Disease Control and HICPAC criteria.7,8 Pathogen identification and antimicrobial susceptibility testing
were performed following guidelines of the National Committee for Clinical Laboratory Standards.9
Differences in vancomycin exposure among hemodialysis
patients compared with nonhemodialysis patients were assessed using the chi-squared test. P of 0.05 or less was
considered statistically significant (Stata Statistical Software, College Station, TX).
RESULTS
Vancomycin Administration
During the 3-month study period, there were
7,356 hospital admissions. One hundred three
patients required chronic hemodialysis during
144 admissions. Demographic and clinical data
are listed in Table 1. Chronic hemodialysis patients received at least one dose of vancomycin
during 56 of these admissions (39%). The mean
number of doses received per patient was 2.9
(range, 1 to 10 doses), and the average dose of
vancomycin administered was 0.85 g (median, 1
g; range, 0.25 to 2.25 g). For those patients who
received at least two doses, the average interval
between doses was 6 days (median, 3 days;
range, 1 to 21 days). Among patients not requiring chronic hemodialysis, at least one dose of
vancomycin was administered during 336 of
7,212 admissions (5%). Thus, patients requiring
chronic hemodialysis received vancomycin significantly more often than those not requiring
hemodialysis (relative risk, 11; 95% confidence
interval, 8 to 15; P ⬍ 0.001).
Table 1. Demographic and Clinical Data of
Hospitalized Chronic Hemodialysis Patients
Patient Characteristics
Age (y)
Sex (M:F)
Race
White
Black
Hispanic
Underlying kidney disease
Hypertension
Diabetes mellitus
Connective tissue disease
Cyclosporine nephrotoxicity
Other
Mean length of hospital stay (d)
No. of Patients
(n ⫽ 103)
56 ⫾ 18
51:52
55 (53)
46 (45)
2 (2)
47 (46)
41 (40)
5 (5)
4 (4)
6 (6)
8 (1-75)
NOTE. Values expressed as mean ⫾ SD, number (percent), or number (range).
Table 2. Indications for Vancomycin Use Among
Chronic Hemodialysis Patients
Indications
No. of
Doses
(n ⫽ 164)
Appropriate
Empiric therapy for a febrile patient on hemodialysis pending culture/susceptibility data* 73 (45)
Treatment of ␤-lactam–resistant organisms
51 (31)
␤-Lactam allergy
5 (3)
Surgical prophylaxis in patient with a prosthesis
2 (1)
Endocarditis prophylaxis in high-risk patient
0 (0)
Treatment of antibiotic-associated colitis if
severe or after failure of metronidazole
therapy
0 (0)
Total
131 (80)
Inappropriate
Continued therapy despite negative cultures
for ␤-lactam–resistant organisms†
23 (14)
Routine surgical prophylaxis
4 (2)
Single positive blood culture for coagulasenegative staphylococci
1 (1)
Empiric treatment for febrile patients with
neutropenia unless evidence of gram-positive infection and prevalence of MRSA is
substantial
0 (0)
Prophylaxis for indwelling or peripheral intravascular catheters‡
5 (3)
Selective decontamination of digestive tract
0 (0)
Eradication of MRSA colonization
0 (0)
Primary treatment of antibiotic-associated
colitis
0 (0)
Routine prophylaxis of low-birth-weight
infants
0 (0)
Topical application
0 (0)
Total
33 (20)
NOTE. Values expressed as number (percent).
Abbreviation: MRSA, methicillin-resistant Staphylococcus aureus.
*Not included in HICPAC guidelines.
†Includes HICPAC guideline: treatment of ␤-lactam–
sensitive organisms in patients with renal failure.
‡Includes HICPAC guideline: routine prophylaxis for dialysis patients.
Indications for Vancomycin Administration
Administration was judged appropriate for 131
of the 164 vancomycin doses (80%; Table 2).
Seventy-three doses (median, 1 dose; range, 1 to
3 doses) were administered as empiric therapy to
42 febrile patients. Thirty-two infections were
subsequently identified in 30 of these patients.
Vancomycin was required for optimal therapy in
15 infections (47%). The types of infections and
pathogens are listed in Table 3. Of the 26 doses
66
GREEN ET AL
Table 3. Type of Infections and Pathogens Among 30 Febrile Chronic Hemodialysis Patients Prescribed
Empiric Vancomycin
Type of Infection
Pathogen
Total
(n ⫽ 32)
Bacteremia
(n ⫽ 17)
Local Catheter
(n ⫽ 5)
Intra-Abdominal
(n ⫽ 5)
Other
(n ⫽ 5)
Methicillin-resistant Staphylococcus aureus*
Coagulase-negative Staphylococcus spp*
Methicillin-susceptible S aureus
Enterobacter cloacae
Candida spp
Pseudomonas aeruginosa
Diphtheroids†
Other†
8
6
4
3
3
1
1
6
5
4
2
1
0
1
0
3
1
2
1
0
0
0
1
0
2
0
1
0
1
0
0
1
0
0
0
2
2
0
0
2
*Vancomycin required for optimal therapy.
†Two infections or less per species.
administered as empiric therapy in which an
infection was not identified, cultures were not
obtained before five doses among five patients,
and cultures were subsequently negative after a
total of 21 doses among seven patients.
Administration of vancomycin was judged inappropriate for 33 of the doses (20%; Table 2).
Twenty-three doses were administered to nine
patients for continued therapy of a presumed
infection despite failure to identify a ␤-lactam–
resistant gram-positive pathogen. Pathogens identified from cultures before administering 21 of
these doses were as follows: ␤-lactam–susceptible gram-positive organisms (11 doses), Enterobacter cloacae (4 doses), Pseudomonas aeruginosa (2 doses), VRE (2 doses), Streptococcus
spp (1 dose), and Candida spp (1 dose). Pathogens were not identified before two vancomycin
doses administered to two patients. Although
these patients met the criteria for inappropriate
vancomycin administration, one patient received
vancomycin for a presumed tunneled-catheter
infection in view of erythema and tenderness at
the catheter site; cultures of the wound site were
negative. The second patient received vancomycin for a community-acquired pneumonia with
negative sputum cultures.
DISCUSSION
This study demonstrates that hospitalized
chronic hemodialysis patients receive vancomycin significantly more often than other hospitalized patients. Furthermore, 80% of vancomycin
doses administered to chronic hemodialysis patients were judged appropriate.
Since the publication of the HICPAC guidelines for appropriate vancomycin use, several
studies have addressed physician compliance with
these recommendations among the general hospital population, with appropriate administration
ranging from 21% to 59%.10-15 In the present
study, appropriate administration of vancomycin
was considerably more frequent and reflects the
use of modified guidelines. In view of the high
rate of ␤-lactam–resistant gram-positive pathogens in the dialysis population, empiric therapy
for febrile patients or for patients with positive
cultures for gram-positive cocci in clusters, pending susceptibility data, was considered an appropriate use of vancomycin. This modification was
clearly appropriate because 47% of infections in
patients who received vancomycin empirically
were caused by ␤-lactam–resistant gram-positive pathogens, two thirds of which were implicated in blood-stream infections. If this modification was not included, only 35% of vancomycin
doses would have been considered appropriate
based on strict interpretation of HICPAC guidelines.
Vancomycin use was judged inappropriate for
20% of doses, the majority of which were administered for treatment of ␤-lactam–sensitive grampositive pathogens. This percentage may be
greater in outpatient hemodialysis centers in
which the convenience of longer dosing intervals
of vancomycin may prevail. Regardless of the
VANCOMYCIN USE IN DIALYSIS PATIENTS
setting, vancomycin should not be used to treat
infections caused by ␤-lactam–sensitive grampositive pathogens for several reasons. First, it is
important to reduce the overall vancomycin exposure to minimize the incidence of VRE, which
are major causes of morbidity and mortality. Of
possibly greater concern is the recent emergence
of S aureus with decreased susceptibility to vancomycin. Since 1996, four patients with S aureus
with reduced susceptibility to vancomycin have
been reported, three of whom were receiving
dialysis therapy and had received prolonged
courses of vancomycin.16-18 Thus, the judicious
use of vancomycin in dialysis patients cannot be
overemphasized. Second, vancomycin is not the
preferred antimicrobial agent for treating infections caused by ␤-lactam–sensitive gram-positive organisms because several studies have
shown that vancomycin is less efficacious than
␤-lactam antibiotics against ␤-lactam–susceptible staphylococci.19-22
The HICPAC guidelines provide a framework
to assist physicians in deciding when to prescribe
vancomycin. These guidelines, however, require
prudent interpretation and modification based on
the individual clinical situation. In the present
study, two doses of vancomycin were administered to patients who had negative culture results
and thus did not meet the HICPAC criteria for
appropriate vancomycin administration. Both patients, however, had evidence of active infection.
Because cultures may fail to identify the causative pathogen,23 administration of vancomycin
is not always inappropriate in these cases.
In summary, the present study shows that
vancomycin use is frequent among hospitalized
chronic hemodialysis patients and that its use is
justified in the large majority of cases. Nevertheless, ongoing efforts to limit vancomycin exposure in the chronic hemodialysis population is of
utmost importance, especially in patients who do
not require empiric antimicrobial therapy.
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