C.D.C. -
22 september 1995
Recommendations for Preventing the Spread of Vancomycin Resistance
Recommendations of the Hospital Infection Control Practices Advisory Committee
(HICPAC).
Content
SUMMARY
Since 1989, a rapid increase in the incidence of infection and colonization
with vancomycin-resistant enterococci (VRE) has been reported by U.S.
hospi-tals.
This increase poses important problems, including a) the lack of available
antimicrobial therapy for VRE infections, because most VRE are also resistant
to drugs previously used to treat such infections (e.g., aminoglycosides
and am-picillin), and b) the possibility that the vancomycin-resistant genes
present in VRE can be transferred to other gram-positive microorganisms
(e.g., Staphylococcus aureus ).
An increased risk for VRE infection and colonization has been associated
with previous vancomycin and/or multiantimicrobial therapy, severe underlying
dis-ease or immunosuppression, and intraabdominal surgery. Because enterococci
can be found in the normal gastrointestinal and female genital tracts, most
en-terococcal infections have been attributed to endogenous sources within
the individual patient. However, recent reports of outbreaks and endemic
infections caused by enterococci, including VRE, have indicated that
patient-to-patient
transmission of the microorganisms can occur either through direct contact
or through indirect contact via a) the hands of personnel or b) contaminated
pa-tient-care equipment or environmental surfaces.
This report presents recommendations of the Hospital Infection Control Practices
Advisory Committee for preventing and controlling the spread of vancomycin
resistance, with a special focus on VRE. Preventing and controlling the
spread of vancomycin resistance will require coordinated, concerted efforts
from all involved hospital departments and can be achieved only if each
of the following elements is addressed: a) prudent vancomycin use by clinicians,
b) education of hospital staff regarding the problem of vancomycin resistance,
c) early detection and prompt reporting of vancomycin resistance in enterococci
and other gram-positive microorganisms by the hospital microbiology labora-tory,
and d) immediate implementation of appropriate infection-control meas-ures
to prevent person-to-person transmission of VRE.
INTRODUCTION
>From 1989 through 1993, the percentage of nosocomial enterococcal infections
re-ported to CDC„200 beds) and university affiliation ( 1 ). Other
hospitals also have reported increased endemic rates and clusters of VRE
infection and coloni-zation ( 2 to 8 ). The actual increase in the incidence
of VRE in U.S. hospitals might be greater than reported because the fully
automated methods used in many clinical laboratories cannot consistently
detect vancomycin resistance, especially moderate vancomycin resistance
(as manifested in the VanB phenotype) ( 9 to11 ). Vancomycin resistance
in enterococci has coincided with the increasing incidence of high-level
enterococcal resistance to penicillin and aminoglycosides, thus present-ing
a challenge for physicians who treat patients who have infections caused
by these microorganisms ( 1,4 ). Treatment options are often limited to
combining antimicro-bials or experimental compounds that have unproven efficacy
( 12 to14 ).
The epidemiology of VRE has not been clarified; however, certain patient
popula-tions are at increased risk for VRE infection or colonization. These
populations include critically ill patients or those with severe underlying
disease or immunosuppression (e.g., patients in ICUs or in oncology or
transplant
wards); persons who have had an intraabdominal or cardio-thoracic surgical
procedure or an indwelling urinary or cen-tral venous catheter; and persons
who have had a prolonged hospital stay or received multiantimicrobial and/or
vancomycin therapy ( 2 - 8 ). Because enterococci are part of the normal
flora of the gastrointestinal and female genital tracts, most infections
with these microorganisms have been attributed to the patient
RECOMMENDATIONS
Each hospital -;through collaboration of its quality-improvement and
infection-control
programs; pharmacy and therapeutics committee; microbiology laboratory;
clinical departments; and nursing, administrative, and housekeeping
services‹
should develop a comprehensive, institution-specific, strategic plan to
detect, prevent, and control infection and colonization with VRE. The following
elements should be addressed in the plan.
PRUDENT VANCOMYCIN USE
Vancomycin use has been reported consistently as a risk factor for infection
and colonization with VRE ( 2,4,7,8,17 ) and may increase the possibility
of the emergence of vancomycin-resistant S. aureus (VRSA) and/or
vancomycin-resistant
S. epider-midis (VRSE). Therefore, all hospitals and other health-care delivery
services, even those at which VRE have never been detected, should
a) develop a comprehensive, antimicrobial-utilization plan to provide education
for their medical staff (including medical students who rotate their training
in different departments of the health-care facility),
b) oversee surgical prophylaxis, and
c) develop guidelines for the proper use of vancomycin (as applicable to
the institution). Guideline development should be part of the hospital
## Situations in which the use of vancomycin is appropriate or
acceptable:
- ‹ For treatment of serious infections caused by beta-lactam-resistant
gram-positive microorganisms. Vancomycin may be less rapidly bactericidal
than are beta-lactam agents for beta-lactam-susceptible staphylococci
( 23,24 ).
- ‹ For treatment of infections caused by gram-positive microorganisms
in patients who have serious allergies to beta-lactam antimicrobials.
- ‹ When antibiotic-associated colitis fails to respond to
metronidazole
therapy or is severe and potentially life-threatening.
- ‹ Prophylaxis, as recommended by the American Heart Association,
for endo-carditis following certain procedures in patients at high risk
for endocarditis ( 25).
- ‹ Prophylaxis for major surgical procedures involving implantation
of prosthetic materials or devices (e.g., cardiac and vascular procedures
[26 ] and total hip replacement) at institutions that have a high rate of
infections caused by MRSA or methicillin-resistant S. epidermidis. A single
dose of vancomycin adminis-tered immediately before surgery is sufficient
unless the procedure lasts >6 hours, in which case the dose should be
repeated. Prophylaxis should be dis-continued after a maximum of two doses
( 27-30 ).
## Situations in which the use of vancomycin should be discouraged:
- ‹ Routine surgical prophylaxis other than in a patient who has
a life-threatening allergy to beta-lactam antibiotics ( 28 ).
- ‹ Empiric antimicrobial therapy for a febrile neutropenic patient,
unless initial evi-dence indicates that the patient has an infection caused
by gram-positive microorganisms (e.g., at an inflamed exit site of Hickman
catheter) and the prevalence of infections caused by MRSA in the hospital
is substantial ( 31-37 ).
- ‹ Treatment in response to a single blood culture positive for
coagulase-negative staphylococcus, if other blood cultures taken during
the same time frame are negative (i.e., if contamination of the blood culture
is likely). Because contamina-tion of blood cultures with skin flora (e.g.,
S. epidermidis ) could result in inappropriate administration of vancomycin,
phlebotomists and other personnel who obtain blood cultures should be trained
to minimize microbial contamina-tion of specimens ( 38-40 ).
- ‹ Continued empiric use for presumed infections in patients whose
cultures are negative for beta-lactam-resistant gram-positive microorganisms
( 41 ).
- ‹ Systemic or local (e.g., antibiotic lock) prophylaxis for infection
or colonization of indwelling central or peripheral intravascular catheters
( 42-48 ).
- ‹ Selective decontamination of the digestive tract.
- ‹ Eradication of MRSA colonization ( 49,50 ).
- ‹ Primary treatment of antibiotic-associated colitis ( 51 ).
- ‹ Routine prophylaxis for very low-birthweight infants (i.e.,
infants who weigh <1,500 g [3 lbs 4 oz]) ( 52 ).
- ‹ Routine prophylaxis for patients on continuous ambulatory
peritoneal
dialysis or hemodialysis ( 48,53 ).
- ‹ Treatment (chosen for dosing convenience) of infections caused
by beta-lactam- sensitive gram-positive microorganisms in patients
who have renal failure ( 54-57 ).
- ‹ Use of vancomycin solution for topical application or irrigation.
## Enhancing compliance with recommendations:
- ‹ Although several techniques may be useful, further study is
required to deter-mine the most effective methods for influencing the
prescribing
practices of physicians ( 58-61 ).
- ‹ Key parameters of vancomycin use can be monitored through the
hospital
EDUCATION PROGRAMS
Continuing education programs for hospital staff (including attending and
consult-ing physicians, medical residents, and students[59];
pharmacy, nursing, and laboratory personnel[59]; and other direct
patient-care providers) should include information con-cerning the epidemiology
of VRE and the potential impact of this pathogen on the cost and outcome
of patient care. Because detection and containment of VRE require an aggressive
approach and high performance standards for hospital personnel, special
awareness and educational sessions might be indicated.
ROLE OF THE MICROBIOLOGY LABORATORY
in the Detection, Reporting, and Control of VRE
The microbiology laboratory is the first line of defense against the spread
of VRE in the hospital. The laboratory Identification of Enterococci
Presumptively
identify colonies on primary isolation plates as enterococci by using colonial
morphology, a Gram stain, and a pyrrolidonyl arylamidase (PYR) test.
Al-though identifying enterococci to the species level can help predict
certain resistance patterns (e.g., Enterococcus faecium is more resistant
to penicillin than is Enterococ-cus faecalis ) and may help determine the
epidemiologic relatedness of enterococcal isolates, such identification
is not routinely necessary if antimicrobial susceptibility testing is performed.
However, under special circumstances or as laboratory re-sources permit,
biochemical tests can be used to differentiate between various enterococcal
species. Although most commercially available identification systems adequately
differentiate E. faecalis from other species of enterococci, additional
tests for motility and pigment production are required to distinguish
Enterococcus
galli-narum (motile and nonpigmented) and Enterococcus casseliflavus (motile
and pigmented) from E. faecium (nonmotile and nonpigmented).
Tests for Antimicrobial Susceptibility Determine vancomycin resistance and
high-level resistance to penicillin (or am-picillin) and aminoglycosides
( 62 ) for enterococci isolated from blood, sterile body sites (with the
possible exception of urine), and other sites as clinically indicated.
Laboratories routinely may test wound and urine isolates for resistance
to vancomy-cin and penicillin or ampicillin if resources permit (see Screening
Procedures for Detecting VRE in Hospitals Where VRE Have Not Been Detected).
- ## Laboratories that use disk diffusion should incubate plates for
24 hours and read zones of inhibition by using transmitted light ( 62,63
).
- ## Minimum inhibitory concentrations can be determined by agar dilution,
agar gradi-ent dilution, broth macrodilution, or manual broth microdilution
( 62-64 ). These test systems should be incubated for 24 hours.
- ## The fully automated methods of testing enterococci for resistance
to vancomycin currently are unreliable ( 9-11 ).
When VRE Are Isolated From a Clinical Specimen
Confirm vancomycin resistance by repeating antimicrobial susceptibility
testing using any of the recommended methods (see Tests for Antimicrobial
Susceptibility), particularly if VRE isolates are unusual in the hospital,
OR streak 1 mL of standard in-oculum (0.5 McFarland) from an isolated colony
of enterococci onto brain heart infusion agar containing 6 mg/mL of vancomycin,
incubate the inoculated plate for 24 hours at 35 C (95 F), and consider
any growth indicative of vancomycin resistance ( 62,63,65 ). Immediately,
while performing confirmatory susceptibility tests, notify the patient
Hospital screening
Where VRE Have Not Been Detected
In some hospital microbiology laboratories, antimicrobial susceptibility
testing of enterococcal isolates from urine or nonsterile body sites (e.g.,
wounds) is not per-formed routinely; thus, identification of nosocomial
VRE colonization and infection in hospitalized patients may be delayed.
Therefore, in hospitals where VRE have not yet been detected, implementing
special measures can promote earlier detection of VRE.
Antimicrobial susceptibility survey.
Perform periodic susceptibility testing on an epidemiologic sample of
enterococcal
isolates recovered from all types of clinical specimens, especially from
high-risk patients (e.g., those in an ICU or in an oncology or transplant
ward). The optimal frequency of testing and number of isolates to be tested
will vary among hospitals, depending on the patient population and number
of cultures performed at the hospital.
Hospitals that process large numbers of culture specimens need to test only
a fraction (e.g., 10%) of enterococcal isolates every 1-2 months, whereas
hospitals processing fewer specimens might need to test all en-terococcal
isolates during the survey period. The hospital epidemiologist can help
design a suitable sampling strategy. Culture survey of stools or rectal
swabs. In tertiary medical centers and other hos-pitals that have many
critically
ill patients (e.g., ICU, oncology, and transplant patients) at high risk
for VRE infection or colonization, periodic culture surveys of stools or
rec-tal swabs of such patients can detect the presence of VRE.
Because most patients colonized with VRE have intestinal colonization with
this organism, fecal screening of patients is recommended even though VRE
infections have not been identified clini-cally ( 2,4,16 ). The frequency
and intensity of surveillance should be based on the size of the population
at risk and the specific hospital unit(s) involved. If VRE have been detected
in other health-care facilities in a hospital
HOSPITALS
Preventing and Controlling Nosocomial Transmission of VRE
Eradicating VRE from hospitals is most likely to succeed when VRE infection
or colonization is confined to a few patients on a single ward. After VRE
have become endemic on a ward or have spread to multiple wards or to the
community, eradication becomes difficult and costly. Aggressive
infection-control
measures and strict compli-ance by hospital personnel are required to limit
nosocomial spread of VRE. Control of VRE requires a collaborative,
institution-wide,
multidisciplinary effort. Therefore, the hospital
Preventing and Controlling VRE Transmission in All Hospitals
The following measures should be implemented by all hospitals, including
those in which VRE have been isolated infrequently or not at all, to prevent
and control trans-mission of VRE.
..- ## Notify appropriate hospital staff promptly when VRE are detected (see
When VRE Are Isolated From a Clinical Specimen).
- ## Inform clinical staff of the hospital
- ## Establish system(s) for monitoring appropriate process and outcome
measures (e.g., cumulative incidence or incidence density of VRE colonization,
rate of compli-ance with VRE isolation precautions and handwashing, interval
between VRE identification in the laboratory and implementation of isolation
precautions on the wards, and the percentage of previously colonized patients
admitted to the ward who are identified promptly and placed on isolation
precautions). Relay these data to the clinical, administrative, laboratory,
and support staff to reinforce ongoing education and control efforts ( 67
).
- ## Initiate the following isolation precautions to prevent
patient-to-patient
transmis-sion of VRE:
- ‹ Place VRE-infected or colonized patients in private rooms
or in the same room as other patients who have VRE ( 8 ).
- ‹ Wear gloves (clean, nonsterile gloves are adequate) when
entering the room of a VRE-infected or colonized patient because VRE can
extensively contaminate such an environment ( 3,8,16,17 ). When caring for
a patient, a change of gloves might be necessary after contact with material
that could contain high concen-trations of VRE (e.g., stool).
- ‹ Wear a gown (a clean, nonsterile gown is adequate) when entering
the room of a VRE-infected or colonized patient a) if substantial contact
with the patient or with environmental surfaces in the patient
- ‹ Remove gloves and gown before leaving the patient
- ‹ Ensure that after glove and gown removal and handwashing,
clothing and hands do not contact environmental surfaces in the patient
- ## Dedicate the use of noncritical items (e.g., a stethoscope,
sphygmomanometer,
or rectal thermometer) to a single patient or cohort of patients infected
or colonized with VRE ( 17 ). If such devices are to be used on other patients,
adequately clean and disinfect these devices first ( 78 ).
- ## Obtain a stool culture or rectal swab from roommates of patients
newly found to be infected or colonized with VRE to determine their colonization
status, and apply isolation precautions as necessary. Perform additional
screening of patients on the ward at the discretion of the infection-control
staff.
- ## Adopt a policy for deciding when patients infected or colonized
with VRE can be removed from isolation precautions. The optimal requirements
remain unknown; however, because VRE colonization can persist indefinitely
( 4 ), stringent criteria might be appropriate, such as VRE-negative results
on at least three consecutive occasions („1 week apart) for all cultures
from multiple body sites (including stool or rectal swab, perineal area,
axilla or umbilicus, and wound, Foley catheter, and/or colostomy sites,
if present).
- ## Because patients with VRE can remain colonized for long periods
after discharge from the hospital, establish a system for highlighting the
records of infected or colonized patients so they can be promptly identified
and placed on isolation precautions upon readmission to the hospital. This
information should be comput-erized so that placement of colonized patients
on isolation precautions will not be delayed because the patients
- ## Local and state health departments should be consulted when developing
a plan regarding the discharge of VRE-infected or colonized patients to
nursing homes, other hospitals, or home-health care. This plan should be
part of a larger strategy for handling patients who have resolving infections
and patients colonized with antimicrobial-resistant microorganisms.
Hospitals With Endemic VRE or Continued VRE Transmission
The following measures should be taken to prevent and control transmission
of VRE in hospitals that have endemic VRE or continued VRE transmission
despite imple-mentation of measures described in the preceding section (see
Preventing and Controlling VRE Transmission in All Hospitals).
- ## Focus control efforts initially on ICUs and other areas where the
VRE transmission rate is highest ( 4 ). Such areas can serve as reservoirs
for VRE, allowing VRE to spread to other wards when patients are well enough
to be transferred.
- ## Where feasible, cohort the staff who provide regular, ongoing care
to patients to minimize the movement/contact of health-care providers between
VRE-positive and VRE-negative patients ( 4,8 ).
- ## Hospital staff who are carriers of enterococci have been implicated
rarely in the transmission of this organism ( 8 ). However, in conjunction
with careful epidemiologic studies and upon the direction of the
infection-control
staff, examine personnel for chronic skin and nail problems and perform
hand and rectal swab cultures of these workers. Remove from the care of
VRE-negative patients those VRE-positive personnel linked epidemiologically
to VRE transmission until their carrier state has been eradicated.
- ## Because the results of several enterococcal outbreak investigations
suggest a po-tential role for the environment in the transmission of enterococci
( 3,8,16,17,79,80), institutions experiencing ongoing VRE transmission should
verify that the hospital has adequate procedures for the routine care, cleaning,
and disinfection of environ-mental surfaces (e.g., bed rails, bedside commodes,
carts, charts, doorknobs, and faucet handles) and that these procedures
are being followed by housekeeping per-sonnel. To verify the efficacy of
hospital policies and procedures, some hospitals might elect to perform
focused environmental cultures before and after cleaning rooms that house
patients who have VRE. All environmental culturing should be approved and
supervised by the infection-control program in collaboration with the clinical
laboratory ( 3,8,16,17,79,80 ).
- ## Consider sending representative VRE isolates to reference laboratories
for strain typing by pulsed field gel electrophoresis or other suitable
techniques to aid in de-fining reservoirs and patterns of transmission.
DETECTING AND REPORTING VRSA and VRSE
The microbiology laboratory has the primary responsibility for detecting
and re-porting the occurrence of VRSA or VRSE in the hospital. All clinical
isolates of S. aureus and S. epidermidis should be tested routinely, using
standard methods, for susceptibility to vancomycin ( 62 ).
If VRSA or VRSE is identified in a clinical specimen, confirm vancomycin
resistance by repeating antimicrobial susceptibility testing using standard
methods ( 62 ). Restreak the colony to ensure that the culture is pure.
The most common causes of false-positive VRSA reports are susceptibility
testing on mixed cultures and misidentifying VRE, Leuconostoc, S. haemolyticus,
or Pediococ-cus as VRSA ( 81,82 ). Immediately (i.e., while performing
confirmatory
testing) notify the hospital
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