Gram-Negative Bloodstream Infections in Hemodialysis Outpatient Centers

In the United States, more than
450,000 patients receive hemodialysis in approximately 6500 outpatient centers.
Patients receiving maintenance dialysis are at high risk for morbidity and
mortality. In 2014, the Centers for Disease Control and Prevention (CDC) received
29,516 reports of bloodstream infections among hemodialysis outpatients.

The most common cause of bloodstream
infections in hemodialysis patients is Gram-positive organisms; bloodstream
infections due to Gram-negative organisms are less common. However, there have
been reports of outbreaks associated with Gram-negative organisms in outpatient
hemodialysis facilities attributed to water sources, such as contaminated
reprocessed dialyzers, improper handling of medications, hemodialysis equipment,
and dialysate. Infections associated with water reservoirs have also been
reported.

Shannon A. Novosad, MD, MPH, and colleagues conducted matched
case-control investigations at three outpatient hemodialysis facilities to
examine an outbreak of Gram-negative bloodstream infections. Results of the
investigations were reported in the American Journal of Kidney Diseases
[2019;74(5):610-619].

Through an August 2016 review of
routine surveillance data reported to the National Healthcare Safety Network,
the CDC detected a cluster of five bloodstream infections caused by Serratia
marcescens in an outpatient hemodialysis facility (Facility A). In
subsequent consultations with state health departments, two additional
outbreaks caused by similar Gram-negative organisms were identified at
facilities owned by the same company (Facility B and Facility C). The most
commonly involved Gram-negative organisms were S marcescens, Pseudomonas
aeruginosa, and Enterobacter cloacae.

The investigation defined a case as a
blood culture from which any Gram-negative bacteria was identified from a
patient who received hemodialysis at Facility A, B, or C from July 1, 2105, to
November 30, 2016. For more than one case in a single patient, there had to
have been 21 days between positive cultures.

To examine risk factors for becoming
a case, two 1:1-matched case-control investigations were performed at
Facilities A and B. The focus of the first investigation was patient-specific
risk factors such as age and comorbid conditions. Case-patients were matched
with randomly selected control patients who received hemodialysis at the same
facility and did not develop a Gram-negative bloodstream infection during the
study period.

The exposures of interest were
infection control practices, sources of water, dialyzer reuse, handling of
medication, dialysis circuit priming, findings of water and dialysate testing,
environmental reservoirs such as wall boxes, vascular access care practices,
pulsed-field gel electrophoresis, and whole-genome sequencing of bacterial
isolates. Outcomes of interest were cases defined by a positive blood culture
for any Gram-negative bacteria drawn from July 1, 2015, to November 30, 2016,
from patients who had received hemodialysis at Facility A, B, or C.

The three facilities were less than
20 miles apart and had between 12 and 36 dialysis stations. All three shared
corporate ownership and some products (medication, dialyzers, acid, and
bicarbonate) came from the same distributors. The same municipal water supply
was used by Facilities A and B; Facility C had a different supply. The three
facilities did not commonly share staff.

During the study period, there were
58 cases of bloodstream infections associated with Gram-negative organisms; the
infections occurred in 51 patients. Facilities A and B had the majority of
cases (n=52; 90%). In comparison, during the previous year, the three
facilities identified 12 Gram-negative bloodstream infections. The most
commonly identified Gram-negative organisms were S marcescens (n=21;
36%), P aeruginosa (n=12; 21%), and E cloacae (n=11; 19%).

Multiple Gram-negative organisms were
isolated in 16 cases (28%). Hospital admission was required in 48 cases (83%),
with median length of stay of 8 days. Fifty of the cases (86%) had central
venous catheter for dialysis access. There were no associations between
infections and individual staff members across or within facilities and no
association between a single dialysis machine and a majority of the infections.

Case patients and the matched
control-patients were similar in age, sex, and comorbid conditions. The
examination of patient-specific risk factors 
found a significant association between longer dialysis vintage and
lower odds of infection (matched odds ratio [mOR], 0.19; 95% confidence
interval [CI], 0.05-0.57). In session-specific analyses, there was a
significant association between using a CVC for dialysis access and increased
odds of bloodstream infection (mOR, 54.32; lower bound of the 95% CI, 12.19).
Receiving dialysis after the first shift and having more than three staff
members involved in care were more common among case-patients than
control-patients (mOR, 2.83; 95% CI, 1.07-8.78 and mOR, 3.75; 95% CI,
1.20-15.52, respectively).

The investigation identified
deficiencies in infection control at all three facilities, including inadequate
aseptic technique during CVC care and multiple missed hand hygiene
opportunities such as not changing gloves or not performing hand hygiene when
changing gloves. There were multiple lapses in the more than 20 separate
machine and station cleaning and disinfection processes, including not applying
disinfectant to all surfaces or applying inadequate amount of disinfectant.

At Facility A, staff reported
problems with wall boxes that emerged in early 2016 and peaked in summer 2016,
including clogging and regurgitation of fluid from the drain, odors, and insect
infestation. Staff were observed touching wall boxes and then going directly to
CVC or other patient care without performing hand hygiene. At all three
facilities, wall box basins were damp and often had visible pools of fluid,
foaming, and waste fluid backing out of the drain.

Forty-three environmental samples
from the three facilities underwent testing. Multiple environmental sources
were found to have Gram-negative bacteria, including tap water, sinks, and
surfaces. All wall boxes contained at least one of the three most common
pathogens. S marcescens isolated from wall boxes were closely related to
pulsed-field gel electrophoresis and whole-genome sequencing.

The investigators recommended
addressing the observed lapses in infection control, including improving
aseptic technique during AVC access, care, and maintenance; machine and station
cleaning and disinfection, and hand hygiene.

There were some limitations to the
investigation cited by the authors, including the limited number of patient
isolates available for testing, the inability to sample every wall box or water
source, and conducting the on-site testing after the peak of the infections.

“Providers should be aware that wall
boxes are a potential source of Gram-negative bloodstream infections in
dialysis settings,” the researchers said.

“Infections with Gram-negative
organisms commonly found in water-related biofilms should prompt investigation
into water and sources of waste fluid serving as potential reservoirs in the
healthcare environment. Infection prevention and control practices should be
regularly assessed and incorporated into routine quality improvement activities
in all healthcare settings to decrease the likelihood of pathogen transmission
from the environment to patients.”

Takeaway Points

1. Reports to the CKC in 2016 resulted
   in an investigation of an outbreak of Gram-negative bloodstream infections at
   three outpatient dialysis facilities; the investigations focused on patients
   who received dialysis at one of the three facilities from July 2015 to November
   2016.
2. During the study period, 58 cases of
   Gram-negative bloodstream infections occurred in 51 patients; of those, 48
   patients required hospitalization.
3. The outbreak was attributed to wall
   boxes, a previously unidentified source of contaminated fluid and biofilms in
   the area providing immediate patient care.