Hand hygiene is the most important practice that
reduces the risk of transmission of microbes by contact, thereby
reducing nosocomial infections [1]. Although hand washing with plain
soap has been a time-honored practice, hand rubbing with alcohol-based
solutions ensures better compliance and greater reduction of bacterial
counts, as do iodophors [2-4]. The Centers for Disease Control (CDC)
recommended the use of alcohol-based hand rubs, based on available
evidence [5]. However, the CDC acknowledged that there are still several
lacunae in the evidence, and need for better trials.
There is a paucity of well-designed randomized,
cross-over trials in patient care settings, particularly so in the
setting of a Neonatal Intensive Care Unit (NICU). There are no such
studies directly comparing hand washing with plain soap, alcohol-based
hand rub and iodophors. We, therefore, conducted a trial with the aim of
comparing the efficacy of the three common methods.
Methods
It was a randomized, cross-over clinical trial with
blinded outcome measurement. The trial compared hand washing with plain
soap, alcohol hand-rub and povidone iodine hand scrub. It was performed
in a level III NICU of a tertiary care institute in Northern India.
Subjects were staff nurses working for 1 year or more in the NICU, and
willing to comply with the instructions related to hand hygiene. Nurses
with a history of iodine sensitivity were excluded. Subjects were
enrolled after informed written consent. The study was approved by the
Institutional Ethics Committee.
There were 14-day neutral periods for each subject
prior to each intervention. During the neutral periods, enrolled nurses
received detailed instructions regarding the correct use of the hand
hygiene measures. Elbow operated taps were used. To allow the natural
hand flora to establish, they were asked to use only non-antimicrobial
soaps both in the NICU and at home and elsewhere during the neutral
periods [6]. They were also provided a list of brand names of items that
they had to avoid during these periods- soaps, lotions, body washes,
shampoos and deodorants, with antimicrobial activity.
Randomization was done at the end of the first
neutral period. Serially numbered opaque and sealed envelopes were
opened as nurses were enrolled. Each envelope had a slip of paper
bearing the random sequence of the 3 hand-hygiene methods. The sequence
was generated online. The methods were:
(a) Soap: Hands washed with a plain
(i.e. non-antimicrobial) bar soap for 15 seconds and rinsed under
running tap water. Hands were dried with autoclaved hand wipes after
the hand wash. The bar soap was placed in a soap tray with drainage
system.
(b) Alcohol: Alcohol hand rub,
which comprised of 45% 2-propranol, 30% 1-propranol and 0.2% ethyl-hexadecyl-dimethyl-ammonium-ethylsulphate
(Sterilium, Raman and Weil Pvt Ltd., Mumbai, India). Two ml of the
solution was dispensed, smeared on the hands and allowed to dry.
(c) Povidone: Povidone-iodine hand
scrub with 0.5% w/v available iodine (Povicidal, Cadila
Pharma-ceuticals Ltd., Dhokla, India). Two ml of the solution was
applied, scrubbed for 15 seconds and rinsed under running tap water.
Hands were dried with autoclaved hand wipes after the procedure.
On the day of intervention, the nurse was allowed to
care for only one baby in the NICU. That baby’s blood culture reports of
the last 14 days were recorded and skin swab cultures were taken from
the baby’s dorsum of hand, umbilical stump and groin. Irrespective of
the allocated hand hygiene measure, two minutes of hand washing with
plain soap and water was done when the enrolled nurse entered the NICU
at the beginning of her shift. Following the mandatory 2-minute hand
wash, the nurse used only the allocated method of hand hygiene during
the rest of that shift; and was observed till she performed five
healthcare activities that required prior hand hygiene. These included
tube feeding, suctioning, recording vital parameters, measuring
abdominal girth, changing sheets, attaching probes, handling vascular
access, changing position, clothing baby, removing nappy and
handling incubators or ventilators. One minute before and one minute
after each hand hygiene procedure, the finger tips and palm of the
dominant hand were pressed against a sterile media plate [Standard
Methods Agar with Tween 80 and Lecithin (Catalogue No. M302, HiMedia
Labs, Mumbai, India)]. The plates were incubated under aerobic
conditions for 48 hrs and colonies counted. Bacterial contamination of
the hand was assessed in terms of colony forming unit count (CFU-C).
CFU-C was limited to 300 units, beyond which confluent growth occurred.
The microbiologist was blinded to the hand hygiene method used and the
identity of the subject. Enrolled nurses were asked to avoid tasks
involving direct contact with infected fluids, fecal matter or other
grossly soiled materials, because these tasks would have resulted in
much higher degree of hand contamination and necessitated hand washing
for 2 minutes. These tasks were performed by other nurses not involved
in the study. Nurses were asked to report adverse effects, if any, after
use of the prescribed hand hygiene measures; and to rate the most
convenient measure.
The primary outcome was mean post-hygiene CFU-C.
Secondary outcomes included absolute and percentage reduction of CFU-C,
and post-hygiene "low CFU-C" (arbitrarily taken as less than 50). In a
cross-over study, 35 subjects could identify an inter-group difference
in the mean post-hygiene CFU-C, which was 70% of the within-subject
standard deviation, with 80% power and a 5% level of two-sided -error.
Statistical analysis: Tests of normality
confirmed the skewed distribution of numerical data. Three-way
comparison of numerical variables was done by the Kruskall-Wallis test
and two-way by the Mann Whitney U test. The absolute decrease in CFU-C
was defined as difference between pre and post-hygiene CFU-C, while the
percent decrease was [pre-hygiene CFU-C – post-hygiene CFU-C]
x100/pre-hygiene CFU-C. Multivariate logistic regression was performed
with post-hygiene "low CFU-C" as the dependent variable and hand hygiene
measures, high pre-hygiene CFU-C (³ 300), neonatal surface colonization,
and neonatal sepsis status as predictor variables.
Results
A total of 36 female staff nurses were evaluated, of
which 35 were included, as one had iodine sensitivity (Fig. 1).
The age of the nurses ranged from 25 to 48 years. They were working in
the NICU for a mean duration of 7.1 years, ranging from 1 to 19 years.
The total number of patient care activities monitored
was 175 in each group. The pre-hygiene and post-hygiene measure sample
was 166 and 167, 164 and 167, and 162 and 162, respectively for Plain
soap, alcohal hand rub and povidone iodine group, respectively.
Thirty-three pre-hygiene and 29 post-hygiene plates were not readable
after incubation due to extraneous contamination of the plate; and were
excluded from analysis. The number of procedures for which both pre- and
post-hygiene CFU-C were available was 159, 161 and 153 in the Soap,
Alcohol and Povidone groups, respectively.
TABLE I Comparison of Baseline Characteristics in 3 Hand Hygiene Groups
|
Soap (n=35) |
Alcohol (n=35) |
Povidone (n=35) |
Pre-hygiene CFU-C*
|
Mean±SD |
158.7± 129 |
161.8± 122 |
145.4± 128 |
Median (IQR)
|
105 (31-300) |
150 (31-300) |
89 (25-300) |
Neonatal sepsis in last 14 days(%) |
12 (34.2) |
11 (31.4) |
11 (31.4) |
Neonatal skin colonization: any site(%) |
23 (65.7) |
16 (45.7) |
20 (57.1) |
Neonatal groin colonization(%) |
17 (48.6) |
22 (62.8) |
16 (45.7) |
Neonatal umbilicus colonization(%) |
19 (54.3) |
22 (62.8) |
24 (68.6) |
Neonatal hand colonization(%) |
26 (74.3) |
26 (74.3) |
23 (65.7) |
*Calculated with number of pre-hygiene plates as denominator:
166, 164 and 162 for soap, alcohol and povidone groups
respectively |
Baseline characteristics (not directly related to
participants) were comparable in all 3 groups (Table I).
Among the colonizers, gram-positive organisms predominated, constituting
70.1%. A total of 175 activities were monitored in each study group.
Patient-care activities were similar across groups (P=0.339).
Data regarding post-hygiene CFU-C are compared in Table II.
Pair-wise comparisons showed that Soap was significantly inferior to
both Alcohol and Povidone. A total of 41.9%, 36.5% and 38.3% pre-hygiene
plates were labeled as having CFU-C of 300 in Soap, Alcohol and Povidone
groups respectively, because colonies could not be discretely counted
beyond 300; and this proportion was not significantly different across
groups (P=0.5). For procedures where the pre-hygiene CFU-C was
above 300, there may have been an underestimation of the extent of
decline in the CFU-C. A repeated measure ANOVA was also performed to
compare the CFU-C before and after hand-hygiene measures. A significant
main effect due to type of hand-hygiene measure was observed. The
estimated marginal means of the 3 groups was significantly different,
being 138.1, 106.6 and 103.1 in Soap, Alcohol and Povidone groups
respectively (P=0.002). There was a significant decline in CFU-C,
the estimated marginal means being 156.8 before and 75.1 after any
hand-hygiene, respectively (P< 0.001). The ‘CFU-C x hand-hygiene
method’ interaction was significant (P<0.001).
TABLE II Comparison of Hand Colony Count Data after Use of Hand Hygiene Measure
Hand colony count |
Hand hygiene measure |
A Soap
|
B Alcohol
|
C Povidone |
|
N =167 |
N=167 |
N= 162 |
Post-hygiene
|
60#(10,300) |
8(0,60) |
10.5(0,100.5) |
Absolute decrease* |
15(0,103) |
100(15,235) |
40(1.5,159) |
Percent decrease* |
33.3(0,82) |
92(67,100) |
87(40,100) |
CFU-C < 50 (%)#
|
79(47.3) |
119 (71.3) |
116(71.6) |
No decrease orconfluent (%)* |
69 (43.4) |
15 (9.3)
|
28(18.3) |
# Median (1st, 3rd quartile); *Included only
hand hygiene procedures for which both pre- and post hand
hygiene colony counts were available: 159, 161 and 153 in groups
A, B and C respectively; 3-way and A vs B P value was <0.001 for
all measures and for A vs C comparison for all measures except
percent decreas (P=0.04); All B rs C comparisons showed P.0.05
except last; #post-hygiene.
|
The proportions of plates with post-hygiene "low
CFU-C" was similar following use of Alcohol and Povidone, but
significantly lower following use of Soap (47.3%). Despite use of a
hand-hygiene measure, for some procedures there was either no decrease
in the CFU-C or failure to decrease below 300. The proportion of such
plates was significantly higher in the Soap versus the other groups; and
was also significantly higher when the Povidone group was compared with
Alcohol (P=0.02).
On multivariate logistic regression for post-hygiene
"low colony CFU-C" as the dependent variable, the use of Alcohol,
Povidone and high pre-hygiene CFU-C (³ 300) were independently
associated with post-hygiene "low CFU-C" (Table III).
TABLE III Multi-variate Logistic Regression for Predicting “Low Post-hygiene CFU-C”
Predictor |
Adjusted OR |
95% CI |
P value |
Alcohol hand rub |
3.2 |
1.9–5.4 |
< 0.001 |
Povidone-iodine
|
3.1 |
1.8–5.3 |
< 0.001 |
High pre-hygiene CFU-C |
0.18 |
0.1–0.3 |
< 0.001 |
Surface colonization |
1.1 |
0.7–1.7 |
0.78 |
Neonatal sepsis |
0.7 |
0.4–0.1 |
0.11 |
All the staff nurses reported that the use of Alcohol
hand rub was the most convenient measure. There were no reports of any
adverse effects (including contact dermatitis, rash or dryness) due to
any of the interventions during the study.
Discussion
This study showed that in the setting of an NICU,
hand washing with plain soap is inferior to alcohol hand rub and
povidone iodine hand scrub; and between the two, alcohol hand rub is
slightly superior to povidone-iodine.
Although the superiority of alcohol-based hand rubs
has been documented previously [8], there were methodological
limitations in many previous studies. There are 21 studies tabulated in
CDC-MMWR-2002, regarding comparison of hand hygiene measures in terms of
mean reduction of hand colony counts, out of which 13 were performed on
artificially contaminated hands of volunteers and only 8 were on
existing hand flora. Of the 8 studies on existing hand flora, only 4
studies were conducted in patient care settings- one in a Neonatal Unit;
one in adult ICU, and two in adult wards [8,10].
An important strength of the current study was that
the hand hygiene measures were evaluated during actual use in a NICU
setting by an RCT with cross-over design. This eliminated selection bias
and increased the power of the study. While the intervention could not
be blinded for practical reasons, the outcome measurement was blinded. A
minimum period of 1 year of working in the NICU environment provided an
opportunity for the hand flora of all nurses to stabilize, and also to
ensure that the enrolled nurses were equally familiar with NICU
routines.
Webster, et al. [11] reported on a crossover
trial in a neonatal care setting. However, the sample size was small (n=8)
and the hygiene agents used were different: Chlorhexidine gluconate 4%,
glycol-poly-siloxane gel and a bland liquid soap. Larson, et al.
[12] conducted a clinical trial with a crossover design to compare the
effect of an antiseptic hand wash and an alcohol hand sanitizer to
determine the effect on nosocomial infection rates, skin condition and
microbial counts on the hands of nurses working in NICUs. Unlike our
study, individual users did not cross over; instead the products were
used for 11 months in the NICU in random order. No significant
differences were found in infection rates and in microbial colonization
rates. The authors concluded that assessing the impact of a single
intervention on infection rates was fraught with problems.
The study in an adult ICU was an RCT with crossover
design that compared plain liquid soap and alcohol. The mean reduction
in the number of colony-forming units with hand washing was 49.6% for
soap and water and 88.2% for alcohol (P<0.001) [10]. One of the
studies conducted in a surgical ward assessed the relative effectiveness
of a number of preparations, including alcohol and hand washing with a
bar soap; and found lower density of Staphylococcus aureus after
alcohol use [13]. Another study in a ward evaluated the immediate and
residual efficacy of five surgical hand scrub products and concluded
that Chlorhexidine was the most suitable one [14].
The main advantages of volunteer studies are that
they are easier to organize, activities can be timed to calculate
residual activity and the glove juice technique (rather than agar) can
be used. However, their biggest drawback is that they do not resemble
real-life clinical situations.
Unlike many other studies, a 14-day "neutral" period
was used between measures in this study, based on a previous observation
[9]. During this period subjects avoided use of any anti-microbial hand
hygiene product; thus allowing the natural resident flora of the
subjects’ hands to stabilize, and serving as a washout period for
residual effects.
Since one cannot expect CFU-C to decline to zero
after the use of a hand hygiene measure, one has to accept CFU-C below a
certain cut-off value as being acceptably low. An exhaustive literature
search did not yield any data about what constitutes an acceptably low
hand CFU-C. Hence less than 50 CFU-C was taken arbitrarily as "low
CFU-C". This is a clinically important outcome because what ultimately
matters to the patient is not the degree of reduction from baseline, but
whether the actual CFU-C after using a hand hygiene measure is low or
not. This also overcomes the limitation of dealing with confluent growth
on the culture plate.
An alarming observation was the increase in CFU-C (or
post-hygiene CFU-C remaining above 300) in a few cases. This observation
was most frequently made after using Soap, followed by Povidone followed
by Alcohol. In this study, the hand hygiene products were not cultured
to check whether they were harboring bacteria. In the case of Soap, the
presence of bacteria in the product may be explained; since it was a
non-antimicrobial bar soap with which multiple users had a direct
contact.
The study was not without its limitations. The types
of organisms on the hands, the proportion of pathogenic organisms and
their quantification were outside the scope of this study. The outcomes
that were meaningful to the patients i.e. reduction in sepsis,
were not addressed in this study. Bacterial contamination was assessed
by taking agar handprints. Glove juice technique was not used, which
might be more effective in recovering the whole bacterial burden of the
hands [15]. The design of this study, which was planned not to interfere
with regular activities, did not allow using glove juice technique.
There were no adverse effects reported by nurses in
our study. A study comparing 6 alcohol-based hand gels showed that none
of them altered trans-epidermal water loss or caused irritation. Gels
with higher glycerine content and 70% ethanol were preferred [16].
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