US Centers for Disease Control
Outbreaks of bacterial Gram negative bloodstream infections
traced to probable contamination of hemodialysis machines
Morbid Mortal Weekly Rep
(Jan) 47:No. 03 1998
Canada, 1995; United States, 1997; and Israel, 1997
During 1996, approximately 236,000 persons received
hemodialysis in the United States; of these, an estimated 183,000
(78%) received chronic hemodialysis (1). Patients who receive
chronic hemodialysis are at increased risk for bloodstream
infections (BSIs) because of the need for repeated vascular access.
Reported BSI rates for hemodialysis patients have ranged from 8.4
to 16.8 episodes per 100 patient-years (2), and BSI has been
identified as the cause of death in 6%-18% of hemodialysis patients
(2). Outbreaks of BSIs in hemodialysis units usually have been
caused by inadequate disinfection of 1) water treatment or
distribution systems (3,4) and 2) reprocessed dialyzers (5-8). This
report summarizes the investigations of three clusters of
gram-negative bacterial BSIs at hemodialysis centers in Canada, the
United States, and Israel. The findings indicate that all three
outbreaks probably resulted from contamination of the waste drain
ports in the same model of hemodialysis machine.
From June 17 through November 15, 1995, nine adult patients at
an ambulatory hemodialysis center in Montreal, Canada, had
Enterobacter cloacae BSIs. All patients at the hemodialysis center
were dialyzed on COBE[Registered] Centrysystem 3* (CS3,
GAMBRO[Registered] HealthcareTM, Lakewood, Colorado) hemodialysis
machines. Each CS3 had a Centry[Registered] Waste Handling Option
(WHOTM), which is a waste port designed to dispose of the saline
used to flush a dialyzer before the machine is used for a patient
(Figure 1). The WHO waste drain line employs two one-way valves to
prevent drain line waste from refluxing into the WHO. The
investigation indicated that at least one of the two one-way valves
in the WHO waste drain lines of seven of 11 machines were
incompetent,** potentially allowing drain backflow and
contamination of dialysis lines in contact with the WHO port.
An epidemiologic investigation demonstrated that case-patients
(i.e., the nine patients at the hemodialysis center who had
Enterobacter cloacae BSIs) were more likely than control-patients
to have received dialysis on a machine that had at least one
incompetent valve on the WHO waste drain line (all seven
case-dialysis sessions versus 145 [53%] of 272 control-dialysis
sessions; odds ratio: undefined; p=0.02). Case- and
control-patients were otherwise similar in demographic
characteristics, underlying renal disease, type of vascular access,
and dialyzer type. Enterobacter cloacae isolated from all nine
infected patients and from the WHOs of 10 of 11 dialysis machines
were identical when examined by pulsed field-gel electrophoresis
From December 5, 1996, through January 25, 1997, a total of 10
adult patients at an ambulatory hemodialysis center in Maryland had
gram-negative bacterial BSIs. Six BSIs were caused by Enterobacter
cloacae, four by Pseudomonas aeruginosa, and two by
coli; two were polymicrobial BSIs. All patients at the hemodialysis
center were dialyzed on CS3 hemodialysis machines that had WHOs.
Results of a cohort study of all patients receiving dialysis at the
center during the 2-month epidemic period indicated that the risk
for gram-negative BSI was associated with exposure to any of three
particular dialysis machines (seven BSIs in 20 patients who were
exposed to one or more of the three machines versus three BSIs in
64 patients who were exposed to the other machines; relative
risk=7.5; 95% confidence interval=2.1-26.2). Incompetent valves on
WHO waste drain lines were present in eight of 26 dialysis machines
and in two of the three implicated machines. Enterobacter cloacae
was recovered from the WHOs of 14 of 26 machines, and P. aeruginosa
was recovered from seven of 26. PFGE patterns of available
Enterobacter cloacae isolates from the dialysis machines and from
three patients were identical; none of the P. aeruginosa isolates
obtained from patients were available for PFGE testing.
From February 9 through September 19, 1997, eight adult
patients at an ambulatory hemodialysis center in Jerusalem, Israel,
had gram-negative bacterial BSIs. BSIs in four patients were caused
by Escherichia coli, three by P. aeruginosa, two by
cloacae, and one by Stenotrophomonas maltophilia; two patients
polymicrobial BSIs. All patients at the hemodialysis center were
dialyzed on CS3 hemodialysis machines that had WHOs. All eight
patients who had BSIs had been dialyzed on three of 13 dialysis
machines. Backflow was observed in the WHOs of the three implicated
dialysis machines, and cultures obtained from the WHOs of six of 13
machines were positive for gram-negative organisms. Five of the
eight patients, including all four with Escherichia coli BSIs, had
been dialyzed on one machine that subsequently was culture-positive
for Escherichia coli and P. aeruginosa. Both patients with
Enterobacter cloacae BSIs had been dialyzed on a second machine
that was culture-positive for Enterobacter cloacae and P.
aeruginosa. Escherichia coli isolates obtained from three
and the WHO of the implicated machine were identical by PFGE.
Daily quality-control testing of WHOs as specified by the
manufacturer had not been performed at any of the three
hemodialysis centers. The manufacturer specifies that preventive
maintenance of the valves in the WHO waste drain line includes
replacement of the two valves after every 2000 hours of use.
However, personnel at the three hemodialysis centers were aware of
the need to change only one valve in the WHO waste drain line, and
personnel at two centers did not know a second WHO valve existed;
schematic diagrams provided by the manufacturer to these two
hemodialysis centers identified only one of the two valves. At one
center, experimentally bending and twisting the main drain line of
a machine that had incompetent valves in the WHO waste drain line
demonstrated the ease with which backflow can occur in the WHO.
In one hemodialysis center, the outbreak was controlled after
high-level WHO disinfection (i.e., disinfecting dialysis machines
with formaldehyde on two occasions and increasing the dwell time
for routine weekly machine disinfection). In the other two centers,
the outbreaks were terminated by discontinuing use of the WHO. All
three hemodialysis centers discontinued using the WHOs.
In June 1997, GAMBRO Healthcare sent a Medical Device Safety
Alert letter to all hemodialysis centers of record that use the
CS3. This letter informed users of the need to ensure proper
functioning of the WHO and outlined procedures for proper
disinfection and maintenance of the equipment.
C Frenette, MD, M Delorme, H˘pital Charles LeMoyne,
Quebec; J Hockin, Health Canada, Ottawa, Ontario, Canada. FG
Grillo, MD, T Killar, SJ Boyer, Maryland; DM Dwyer, MD, State
Epidemiologist, Maryland Dept of Health & Mental Hygiene. C Block,
MBBCh, R Backenroth, MD, M Shapiro, MD, Hadassah Univ Hospital,
Jerusalem; B Lev, MD, Associate Director General, Israel Ministry
of Health. Hospital Infections Program, National Center for
Infectious Diseases; and EIS Officers, CDC.
Bacterial BSI is a potentially severe complication
associated with hemodialysis vascular access. In the United States,
complications associated with vascular access represent one of the
most common sources of morbidity among patients undergoing
end-stage renal dialysis, with associated costs exceeding an
estimated $1 billion per year (9). This report links three
outbreaks of gram-negative bacterial BSIs to a unique design
feature of the CS3 hemodialysis machine. The results of these
outbreak investigations demonstrated that the WHO, if not properly
maintained and disinfected, may be a source of bacterial
contamination leading to BSIs in hemodialysis patients. Because
waste backflow can occur with incompetent valves and WHO
contamination can occur easily, the design of the WHO creates a
mechanism for possible cross-contamination of the patient dialysis
In addition to the problems associated with the WHO feature,
insufficient training of hemodialysis personnel about the design
and proper handling and maintenance of WHOs might contribute to
transmission of BSIs to hemodialysis patients. In June 1996, GAMBRO
Healthcare and CDC surveyed 595 U.S. dialysis centers that use CS3
machines to characterize the methods used to clean and disinfect
the dialysis machines and to characterize quality-control
procedures (GAMBRO Healthcare and CDC, unpublished data). The
survey indicated that personnel at most (87%) of the responding
dialysis centers reported weekly disinfection of their dialysis
machines as specified by COBE guidelines, although most (62%) were
not disinfecting dialysate and bicarbonate sampling ports as often
as recommended. Of the 290 centers that reported using the WHO,
only 42 (14%) performed the recommended daily quality-control
assessment of the WHO valves to determine whether drain reflux was
occurring. Of the 137 centers responding to the question "If fluid
can be aspirated from the WHO, what is done?," 112 (82%) indicated
the need for replacing WHO valves or taking the machine off-line
This report underscores the importance of surveillance and
infection control in the ambulatory health-care setting. The
detection of these outbreaks and identification of the likely cause
was aided by the brief time-frame during which multiple infections
were identified. The limited availability of data about infection
rates in ambulatory dialysis centers impedes the identification of
small or prolonged low-level outbreaks. Because of the lack of such
data, inappropriate infection-control or maintenance practices that
were identified in the GAMBRO Healthcare/CDC survey could not be
linked to adverse patient outcomes at the dialysis centers
Outbreaks of gram-negative bacterial BSIs in hemodialysis
patients that appear to be associated with use of the WHO should be
reported to state health departments and to CDC's Hospital
Infections Program, National Center for Infectious Diseases;
telephone (404) 639-6413.
1. Health Care Financing Administration. ESRD Facility Survey data,
1996. Washington, DC: US Department of Health and Human Services,
Health Care Financing Administration, 1997.
2. Kessler M, Hoen B, Mayeux D, Hestin D, Fontenaille C. Bacteremia
in patients on chronic hemodialysis: a multicenter prospective
survey. Nephron 1993;64:95-100.
3. Favero MS, Petersen NJ, Boyer KM, Carson LA, Bond WW. Microbial
contamination of renal dialysis systems and associated health
risks. Trans Am Soc Artif Intern Organs 1974;20A:175A-183A.
4. CDC. Pyrogenic reactions and gram-negative bacteremia in
patients in a hemodialysis center. Atlanta: US Department of Health
and Human Services, CDC, 1991; epidemic investigation report no.
5. Beck-Sague CM, Jarvis WR, Bland LA, Arduino MJ, Aguero SM,
Verosic G. Outbreak of gram-negative bacteremia and pyrogenic
reactions in a hemodialysis center. Am J Nephrol 1990; 10:397-403.
6. Bolan G, Reingold AL, Carson LA, et al. Infections with
Mycobacterium chelonei in patients receiving dialysis and using
processed hemodialyzers. J Infect Dis 1985;152:1013-9.
7. Lowry PW, Beck-Sague CM, Bland LA, et al. Mycobacterium chelonae
infection among patients receiving high-flux dialysis in a
hemodialysis clinic in California. J Infect Dis 1990;161:85-90.
8. Flaherty JP, Garcia-Houchins S, Chudy R, Arnow PM. An outbreak
of gram-negative bacteremia traced to contaminated O-rings in
reprocessed dialyzers. Ann Intern Med 1993;119:1072-8.
9. Feldman HI, Kobrin S, Wasserstein A. Hemodialysis vascular
access morbidity. J Am Soc Nephrol 1996;7:523-35.
* Use of trade names and commercial sources is for identification
only and does not imply endorsement by CDC or the U.S. Department
of Health and Human Services.
** The manufacturer recommends daily testing of the competency of
WHO valves by filling a 30 cc syringe with water, injecting the
contents into the WHO drain port, and attempting to draw back fluid
from the WHO. Competent valves should prevent backflow.
(Full text from the MMWR)