Impact of single room design on the spread of multi-drug resistant bacteria in an intensive care unit
Halaby et al. Antimicrobial Resistance and Infection Control
Impact of single room design on the spread of multi-drug resistant bacteria in an intensive care unit
Teysir Halaby 0
Nashwan al Naiemi 0 1 2
Bert Beishuizen 4
Roel Verkooijen 0
José A. Ferreira 3
Rob Klont 0 4
Christina vandenbroucke-Grauls 2
0 Laboratory for Medical Microbiology and Public Health , Boerhaavelaan 59, 7555, BB, Hengelo , The Netherlands
1 Medical Microbiology and Infection Control , Ziekenhuisgroep Twente, Almelo , The Netherlands
2 Department of Medical Microbiology & Infection Control, VU University Medical Center , Amsterdam , The Netherlands
3 Department of Statistics, Informatics and Modelling, National Institute for Public Health and the Environment, RIVM , Bilthoven , The Netherlands
4 Department of intensive care, Medisch Spectrum Twente , Enschede , The Netherlands
Background: Cross-transmission of nosocomial pathogens occurs frequently in intensive care units (ICU). The aim of this study was to investigate whether the introduction of a single room policy resulted in a decrease in transmission of multidrug-resistant (MDR) bacteria in an ICU. Methods: We performed a retrospective study covering two periods: between January 2002 and April 2009 (oldICU) and between May 2009 and March 2013 (new-ICU, single-room). These periods were compared with respect to the occurrence of representative MDR Gram-negative bacteria. Routine microbiological screening, was performed on all patients on admission to the ICU and then twice a week. Multi-drug resistance was defined according to a national guideline. The first isolates per patient that met the MDR-criteria, detected during the ICU admission were included in the analysis. To investigate the clonality, isolates were genotyped by DiversiLab (bioMérieux, France) or Amplified Fragment Length Polymorphism (AFLP). To guarantee the comparability of the two periods, the 'before' and 'after' periods were chosen such that they were approximately identical with respect to the following factors: number of admissions, number of beds, bed occupancy rate, per year and month. Results: Despite infection prevention efforts, high prevalence of MRD bacteria continue to occur in the original facility. A marked and sustained decrease in the prevalence of MDR-GN bacteria was observed after the migration to the new ICU, while there appear to be no significant changes in the other variables including bed occupancy and numbers of patient admissions. Conclusion: Single room ICU design contributes significantly to the reduction of cross transmission of MRDbacteria.
Cross-transmission of nosocomial pathogens has been
shown to occur frequently in intensive care units (ICU)
]. It may be promoted by several factors including
environmental source [
], invasive procedures, and
]. Bacterial cross-transmissions account for a
significant part of ICU-acquired infections [
majority of which are associated with Gram-negative (GN)
]. GN-infections in turn lead to
substantial morbidity, mortality and costs [
aimed at reducing the spread of nosocomial pathogens
include contact precautions and isolation of patients,
especially when multi-drug resistant (MDR) organisms are
] and hand hygiene [
], which has been
considered the most important control measures [
Despite evidence that transmission of pathogens by way of
health care workers’ hands is a major cause of
nosocomial infections [
], compliance with policies and
procedures for infection control has been uniformly poor [
Nursing patients in single-patient rooms can improve
hand washing compliance and facilitate cleaning and
decontamination and thereby contribute to infection
In this retrospective study we describe the long-term
persistence and transmission of MDR-GN organisms in
an ICU despite extensive infection control precautions.
We present evidence for the role of the single room
design of the new facility to which the ward was eventually
moved in their control.
The study covered two periods: a first period between
January 2002 and April 2009 (old-ICU) and a second
between May 2009 and March 2013 (new-ICU,
singleroom). In the first period patients were nursed in an
ICU with 21 beds: five in single ventilated rooms and
with ante-room, four in two double rooms without
anterooms, and 12 in an open bay (Fig. 1). The total number
of beds in use was 18, since a maximum of nine out of
the 12 open bay beds was used for admissions at any
This ICU was closed on two occasions: from January
through May 2003 because of an ongoing outbreak with
ESBL-producing Klebsiella pnumoniae (ESBL-Kp) which
started in 2001 [
], and between January and March
2008 because of an outbreak with multi-drug resistant
Acinetobacter baumannii (MDR-Ab). Because of these
outbreaks and because there was evidence of persistent
colonization and spread of other MDR-GN among
patients in the ICU despite extensive infection control
efforts, it was ultimately decided to transfer the ICU in
May 2009 to a newly built ICU, which consisted of a
two-floor unit, each with 9 single rooms with controlled
ventilation and ante-room (Fig. 2). The two floors were
identical regarding treatment facilities and casemix.
Initially only 16 beds were used. In January 2011 the
number beds in use was increased to 18. Only new patients
were admitted to the new ICU and no patients we
transferred from the old ICU during migration.
Routine microbiological screening started in February
2002 and continued through the whole study period.
Screening was performed on all patients on admission to
the ICU and then twice a week. Screening was done by
culture of throat and rectal-swab specimens and, in
intubated patients, of tracheal fluid samples. When clinically
indicated, samples were also obtained from relevant
body sites, such as wounds. MDR-GN strains were
stored at −70 °C.
From January 2002 until April 2010, species
identification was routinely performed by classical
biochemical methods and the API 20E system. Antimicrobial
susceptibility testing was performed by the agar
dilution method according to the National Committee
on Clinical Laboratory Standards (NCCLS), now
called Clinical and Laboratory Standards Institute
]. From April 2010 on, the Vitek 2
Advanced Expert System (bioMérieux, France) was used
to identify strains, to determine antimicrobial
susceptibility using the EUCAST breakpoints [
], and to
perform phenotypic screening for ESBL. ESBL
confirmation was performed by the double disk synergy
test with cefotaxime and/or ceftazidime, and
clavulanic acid [
Before the outbreak, infection control measures in the
ICU were implemented according to a national guideline
]. Infection prevention measures were mainly based
on the so-called “work island” principle, which means
contact precautions in the area surrounding the
ventilated patient bed, including cleaning and disinfection
and hand hygiene before entering and by leaving the
When an increase in the number of patients colonized
with ESBL-Kp was noticed in August 2001, an outbreak
management team was formed, including an infection
control nurse, an ICU medical officer, a consultant
microbiologist, and an ICU nurse. Infection control
practices were reinforced, including labelling and
isolation of ESBL-Kp-positive patients in the single-patient
rooms, cohort nursing of ESBL-Kp-colonised patients to
the two-bedded rooms when more patients were found
colonized, and disinfection of hospital equipment and
high-touch surfaces. Since the outbreak remained
uncontrolled despite these measures (Fig. 3), an intensified
infection control programme was started. This included
from September 2002, the use of a ‘short stay’
fourbedded unit outside the ICU area for patients expected
to be admitted to the ICU for fewer than 72 h. Secondly,
from October 2002 onwards, patients admitted to the
ICU received selective decontamination of the digestive
tract (SDD). The aim of the SDD treatment in this
setting was to reduce colonization of the digestive tract
with resistant bacteria [
]. SDD was given as topical
mixture of nonabsorbable antibiotics including
tobramycin, colistin and Amphotericin B (respective doses:
80, 100, and 500 mg), applied on the buccal mucosa and
as a suspension administered via a nasogastric tube in
the gastrointestinal tract, four times a day [
Finally, the ICU was temporarily closed from January
through May 2003 for thorough cleaning and
disinfection, during which period patients were admitted to a
temporary, 16-bed ICU. The same infection control
policy from the closed ICU was continued. No new patients
with ESBL-Kp were detected during this period, until
one week before moving the ICU back to the main
location. After the ICU was moved back to the main
location, an increase in the incidence of ESBL-Kp positive
patients was noted (Fig. 3). In 2005 a decrease in the
incidence was observed; however, the outbreak remained
uncontrolled. In 2007, it was concluded that radical
facility changes in design and infection control policy were
needed for optimal infection control practices.
Shortterm changes that followed within the following year
included SDD discontinuation (April 2007), the
appointment of additional infection control practitioners, and
the promotion of a high level of compliance with
infection control measures.
Between January and March 2008 the ward was closed
due to an outbreak with MDR-Ab. Rigorous infection
control measures were implemented including the grouping of
MDR-Ab-positive patients in single rooms with controlled
ventilation, education of staff, enforcement of hand hygiene
and surface decontamination. In addition, the ward was
temporarily closed for new admissions. After all beds
became available through discharges, the unit including
equipment was decontaminated with vaporized hydrogen
peroxide (VHP), according to manufacturer’s instructions
(Infection Control BV, Eemnes, the Netherlands).
Shortterm changes were implemented, including the reduction
of the number of beds to 16, and the unit was re-opened
on April the 3rd 2008. In April 2009 the ICU was
moved to a semi-permanent (http://www.cadolto.com/en/
products/healthcare_buildings/hospitals) single-room unit
(Fig. 2). Nurse-to-patient ratio (0,66) did not change. The
same infection control protocols were maintained. In the
single-room unit, a hand washing sink was located in each
ante-room and an alcohol-based hand rub dispenser in
each ante-room and at the bedside.
Retrospective microbiological analysis
In 2014, a retrospective study was undertaken on
existing laboratory databases to collect data on the
occurrence of MDR-GN, including ESBL-Kp,
Citrobacter spp., Proteus spp., Enterobacter spp., Serratia
spp., Morganella spp., Pseudomonas spp. and
Acinetobacter spp. Multi-drug resistance among
Gramnegative bacteria was defined according to a national
guideline (Table 1) [
MDR multi-drug resistant
a Proteus, Morganella, Serratia, Citrobacter, Enterobacter spp.
A: presence of ESBL production or resistance against this antibacterial agent or group is sufficient to define the microorganism as being MDR
B: resistance against 2 antibacterial agents or against at least 2 of the indicated groups is required to define the microorganism as being MDR
C: resistance against 3 antibacterial agents or against antimicrobial agents from at least 3 of the indicated groups is required to define the microorganism as
The first isolates per patient, that met the
MDRcriteria, detected during the ICU admission were
included in the analysis.
Since the dilutions values of antimicrobial agents
that were tested in the agar dilution method were
available in the Laboratory Information System (LIS),
it was possible to compensate for the change from
CLSI to EUCAST by retrospectively redefining the
breakpoints of the tested isolates to meet the
MDRcriteria. During the whole study period, ESBL
identification was performed on K. pneumonia, K. oxytoca
and bacteriemic P. mirabilis isolates that screened
]. Bacteriemic P. mirabilis isolates were
not detected [
], hence, no ESBL confirmation was
performed. So, from the ESBL-positive
Enterobacteriaceae only K. pneumonia isolates were included in the
analysis. The other Enterobacteriaceae were included
not as whether or not carrying ESBL but when
meeting the HRMO criteria.
Clonality of stored ESBL-Kp isolates obtained between
2002 and 2007 was retrospectively investigated by
DiversiLab (bioMérieux, France) [
]. Available data from
typing of Enterobacter, Acinetobacter, P. aeruginosa,
Citorbacter freundii, E. coli and ESBL-Kp isolates
obtained after 2007, prospectively investigated by
DiversiLab or AFLP [
], were also included in this study.
Frequency distribution of the MDR Gram-negative
bacteria that were used for genotyping is shown in Fig. 4.
Our objective was to investigate whether the
introduction of a single room policy resulted in a decrease in the
number of transmissions of MDR within the ICU. For
this purpose we compared a period before the
introduction of the policy and a period following it with respect
to the occurrence of representative MDR isolates of the
species Citrobacter, Enterobacter, Morganella, Proteus,
Serratia and Pseudomonas. To guarantee the
comparability of the two periods, the ‘before’ and ‘after’ periods
were chosen such that they were approximately identical
with respect to the following factors: number of
admissions, number of beds, bed occupancy rate, per year and
month (the average length of stay per month can be
dispensed with since it is determined by the average
number of admissions and the occupancy rate). A data set
derived from the NICE database (National Intensive
Care Evaluation, https://www.stichting-nice.nl) was
combined with the laboratory data and upon examination of
the monthly figures related to numbers of admissions,
number of beds and bed occupancy it was decided to
compare the periods from April 2008 to April 2009 and
from May 2009 to December 2010, during the whole
length of which the number of beds was kept at 16, as
the ‘before’ and ‘after’ periods for the main part of the
analysis. A third period (a second ‘after’ period) from
January 2011 to March 2012, in which the capacity of
the ICU was increased to 18 beds, was used for
The two periods were compared with respect to a
single variable (e.g. number of transmissions of a given
bacterium or bed occupancy) by a permutation test with
month as a ‘block factor’ based on a so-called sum
]. This is the sum, over the available months, of
the monthly differences in the average values of the
variable in the two periods. The blocking by month should
correct for eventual seasonal patterns in the number of
Fig. 4 Frequency distribution of the MDR Gram negative bacteria that were used for genotyping
transmissions. In order to compare the two periods with
respect to the transmissions of the six different species
simultaneously we used a generalization of the
permutation test based on the sum of the six sum statistics
corresponding to the six bacteria. The rationale for using
this test was the “principle of coherence” [
]: if the
intervention does have a positive (or at least
nonnegative) effect then that effect consists of a decrease (or
at least non-increase) in the number of all the bacteria.
All the tests were two-sided. Despite several tests being
carried out, no multiple testing corrections are presented
because, by the nature of the data and of the hypotheses
tested, the p-values are either unequivocally large or
unequivocally small. Statistical analyses were carried out
with programs written in R [
], which may be obtained
from the authors upon request.
The numbers of patients carrying MDR-Citrobacter spp.,
Proteus spp., Enterobacter spp., Serratia spp., Morganella
spp. and Pseudomonas spp. and ESBL-Kp are shown in
ESBL-Producing K. pneumoniae
Between January 2002 and March 2013, 225 patients
with ESBL-Kp were identified (Fig. 3). Typing of 163
isolates (one isolate per patient) by REP-PCR revealed that
the majority was clonally related. Of these isolates 121,
obtained between January 2002 and July 2007, were
found to be identical [
], while 42 appeared unrelated
to the major clone. Typing of 10 out of the 17 ESBL-Kp
isolates obtained between March 2008 and April 2009
(after disinfection of the old ICU with VHP and before
the move to the new ICU), showed no clonal relation of
these isolates to the outbreak strain. However, two
clusters of strains were identified: one of two strains
(isolated on 3/11/2008 and 11/12/2008), and the other of
three strains (isolated on 18/12/2008, 29/12/2008 and 3/
1/2009). The remaining five isolates had different
In October 2007, a patient known to harbour MDR-Ab
was transferred from a Turkish hospital to the ICU and
was directly placed in a separate room in strict isolation.
During his admission, which lasted three weeks, and
after discharge, no spread of the MDR-Ab was seen,
until early in January 2008, when two patients were
found to carry a strain of MDR-Ab. The patients were
placed in separate rooms with controlled ventilation in
strict isolation. During the following two weeks,
MDRAb was detected in three more patients. Genotyping
showed clonal relationship between strains from the five
patients, one strain from the index patient and seven
from the ICU environment. The unit was closed in the
third week of January and re-opened in March 2008.
Other MDR-gram negative organisms
Between March 2008 and April 2009, 46 patients
carrying MDR E. cloacae were identified. Typing of 23
isolates obtained between April and August 2008, with
] revealed two clusters: one of 7 and one
of 13 strains. The remaining three strains had different
After the old ICU was reopened in March 2008, cross
transmission of new microorganisms re-emerged and
persisted as evidenced by genotyping of ESBL-Kp
(unrelated to the major clone) and MDR E. cloacae (Fig. 5).
New ICU period
After the migration to the new ICU, a marked decrease
in the prevalence of MDR-GN was observed (Fig. 6).
Available data from typing of Enterobacter,
Acinetobacter, P. aeruginosa, C. freundii, E. coli and ESBL-Kp
isolates obtained after the migration showed no
transmission (Fig. 7).
The test comparing the ‘before’ (April 2008 to April
2009) and ‘after’ (May 2009 to December 2010) periods
regarding the numbers of transmissions of the six
bacteria jointly yielded a p-value of 0.001. With respect to
the number of admissions, the comparison between the
‘before’ and ‘after’ periods and between the ‘after’ period
and the second ‘after’ period (January 2011 to March
2012) no significant changes were observed (p-values of
0.17, and 0.34).
With respect to bed occupancy, testing for differences
between the ‘before’ and ‘after’ periods yields a p-value
of 0.99. In contrast, there was evidence for a difference
between the ‘after’ period and the second ‘after’ period
(increase in the capacity of the ICU from 16 to 18 beds),
with a p-value of 0.007.
Comparing the ‘before’ and ‘after’ periods with regard
to each species one at a time, p-values of 0.0015, 0.0005,
0.37, 0.99, 0.25, and 0.39 for Citrobacter, Enterobacter,
Morganella, Proteus, Serratia and Pseudomonas,
respectively, were found.
Our results provided strong evidence that the single
room policy as an infection control strategy has
contributed significantly to the control of cross transmission of
resistant pathogens in the ICU.
In this study we analysed the history of an ICU which
was affected by a protracted clustered occurrence of
MDR bacteria despite extensive infection control
precautions. Control was ultimately achieved by closing the
ward and moving it into a new single room designed
Despite combined interventions, including education
to improve adherence to hand hygiene practices, use of
contact precautions, isolation of ESBL-Kp positive
patients and temporary ward closure in early 2003, the
colonization by endemic ESBL-Kp, as evidenced by
genotyping with DiversiLab, and by other MDR-Gram
negative bacteria was observed soon after the unit was
re-opened. Educational meetings were held and hand
hygiene was emphasized on several occasions. Recorded
observations about hand hygiene performance, and
adherence to hygiene protocols were not part of the
experimental design, hence could not be described during
the study period. Even if lack of adherence to hand
washing protocols alone may not explain the failure to
halt transmission [
], breaches in hand hygiene may
have promoted it [
Although the importance of colonization pressure in
transmission of MDR-GN bacteria has not fully been
], our data suggest that the increased
number of colonized patients has contributed to the
persistence of MDR-bacteria. Not only was the
proportion of colonized patients high, patients were also
colonized with multiple MDR-GN bacteria. Selection
of these bacteria may have been facilitated by the
start and the prolonged use of SDD. Prior to the
introduction of SDD, most ESBL-Kp isolates were
resistant to tobramycin, and upon exposure to colistin,
heteroresistant subpopulations may have been selected
for. In addition, the proportion of tobramycin
resistance among pathogens intrinsically resistant to
colistin (Proteus, Morganella, and Serratia spp.) increased
under the use of SDD, and decreased after stopping
]. Abundant carriage of these MDR-bacteria
under SDD, i.e. colonization pressure [
] may have
enhanced the risk of their spread and acquisition.
Although temporary ward closure has been shown to
control ESBL-Kp outbreaks adequately [
], in our case
the ESBL-Kp outbreak persisted after closure of the ICU
early in 2003. The reason for this is not clear; no
common environmental source was identified, and cultures
obtained from the hands of nursing and medical staff
performed on one occasion were negative. After the
second ward closure and decontamination with HPV early
in 2008, clonal spread of the ESBL-Kp or MDR-Ab was
not observed again. However, transmission and
persistence of new MDR-GN bacteria after the ward was
reopened continued to occur, as evidenced by typing of
ESBL-Kp and E. cloacae strains.
Single-bed room design has been shown beneficial
in reducing contact transmission and acquisition of
resistant bacteria in several studies [
]. It enables
the separation of patients upon admission and
prevents transmission from unrecognized carriers of
pathogens. By design, single rooms are furnished with
a conveniently located sink in each, provided by
sufficient and accessible alcohol-based hand-rub
dispensers. Affecting staff behavior by single-room
design has in one study been found a possible
element that contributed to higher hand hygiene
compliance, compared to an open plan ICU [
Another study showing a substantial reduction in
transmission of some microorganisms after converting the
ICU to private rooms, has attributed the observed
reduction to better hand hygiene by hospital staff,
rather than to the move to a new and uncontaminated
]. The results from our study
supports these findings. Although adherence to hand
hygiene practice was not measured, ending of
crosstransmission occurred only after the move to the new
ICU (Fig. 6).
In this study, after the move to the single room unit, a
clear and sustained decrease in the prevalence of the
MDR-GN bacteria was observed, except for MDR-P.
aeruginosa which, however, could not be explained by
cross transmission since the genotyping of five isolates
between July and October 2009 revealed no similarities.
Statistical analysis testing for differences between the
periods before and after the move to the single room unit
showed good evidence that the single room policy was
very effective in controlling the cross transmission of the
MDR bacteria in this ICU.
Protracted clustered occurrence of MDR bacteria in an
ICU despite extensive infection control precautions,
including temporary ward closure on two occasions, was
ended only by the transformation of the unit into a
single-room unit. Single room ICU design significantly
contributed to the reduction of cross transmission of
Availability of data and materials
Please contact author for data requests.
Conception and design of the study: TH, NN, CG. Acquisition of data: AB, RK,
TH. Analysis and interpretation of data: RV, JF. Drafting and revising the
manuscript: all authors. Final approval of the manuscript: all authors.
Ethics approval and consent to participate
The study was subjected to an ethical review by the “Medisch Ethische
Toetsingscommissie Twente (METC)”, Medical School Twente, PoB 50,000,
7500 KA Enschede, the Netherlands. The study was judged as not meeting
the criteria for an assessment by a medical ethical committee according to
the Dutch low, with the ID number: METC/17247.hal.
Consent for publication
Not applicable. The study was judged as not meeting the criteria for an
assessment by a medical ethical committee according to the Dutch low,
with the ID number: METC/17247.hal.
The authors declare that they have no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in
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