Ijccm 19 14
Ijccm 19 14
Background: The increased morbidity and mortality associated with nosocomial infections Access this article online
Website: www.ijccm.org
in the intensive care unit (ICU) is a matter of serious concern today. Aims: To determine
DOI: 10.4103/0972-5229.148633
the incidence of nosocomial infections acquired in the ICU, their risk factors, the causative
Quick Response Code:
pathogens and the outcome in a tertiary care teaching hospital. Materials and Methods:
This was a prospective observational study conducted in a 12 bedded combined medical
and surgical ICU of a medical college hospital. The study group comprised 242 patients
admitted for more than 48 h in the ICU. Data were collected regarding severity of the
illness, primary reason for ICU admission, presence of risk factors, presence of infection,
infecting agent, length of ICU and hospital stay, and survival status and logistic regression
analysis was done. Results: The nosocomial infection rate was 11.98% (95% confidence
interval 7.89–16.07%). Pneumonia was the most frequently detected infection (62.07%),
followed by urinary tract infections and central venous catheter associated bloodstream
infections. Prior antimicrobial therapy, urinary catheterization and length of ICU stay
were found to be statistically significant risk factors associated with nosocomial infection.
Nosocomial infection resulted in a statistically significant increase in length of ICU and
hospital stay, but not in mortality. Conclusion: Nosocomial infections increase morbidity
of hospitalized patients. These findings can be utilized for planning nosocomial infection
surveillance program in our setting.
Keywords: Intensive care unit, morbidity, mortality, nosocomial infection, risk factors
From:
Department of Anaesthesiology and Critical Care Medicine, R. G. Kar Medical
In our setting that of a busy ICU in a tertiary care
College and Hospital, 2Department of Pharmacology, Institute of Post Graduate teaching hospital in the public sector, survey of
Medical Education and Research, Kolkata, West Bengal, 1Department of
Medical Research, Breach Candy Hospital, Mumbai, Maharashtra, India
nosocomial infection has not been carried out in the
recent past. The objectives of the present study were to
Correspondence:
Dr. Sugata Dasgupta, 1, Kshudiram Bose Sarani, Kolkata - 700 004,
determine the incidence of nosocomial infection, identify
West Bengal, India. E-mail: [email protected] possible risk factors for these infections, to clarify the
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Indian Journal of Critical Care Medicine January 2015 Vol 19 Issue 1
distribution of the causative pathogens and to evaluate from where the patient was transferred to the ICU,
the outcome of the infected patients in terms of length cause of ICU admission and the APACHE II score
of ICU and hospital stay and mortality. during the first 24 h of admission to the ICU. The
following factors were recorded as present (at any time
Materials and Methods during the ICU stay) or absent in a particular patient
before the development of ICU acquired infection:
After approval from the Institutional Ethics Committee,
Underlying disease, comorbidity, central venous
we conducted this prospective observational study in the
catheterization, pulmonary arterial catheterization,
12 bed combined medical and surgical ICU of a tertiary
invasive arterial catheterization, peripheral venous
care medical college hospital between January 1 and
catheterization, urinary catheterization, endotracheal
June 30, 2012.
intubation, re-intubation, tracheostomy, nasogastric tube
insertion, mechanical ventilation, surgical procedure,
Out of the total of 455 patients admitted to the ICU
prior antimicrobial therapy, antacid and stress ulcer
during the 6-month study period, 242 patients staying
prophylaxis therapy, sedative-analgesic therapy,
for more than 48 h in the ICU were included in the study.
vasopressor therapy, parenteral nutrition, enteral
All patients were monitored daily for the development of
nutrition, horizontal body position with head at <30°,
infection during their ICU stay and during the 72 h after
discharge from the ICU. Patients who were re-admitted blood transfusion, hypoalbuminemia, diabetes mellitus,
72 h after discharge from the ICU were regarded as chronic renal failure, chronic alcoholism, malnutrition
new admissions. Patients with infection at the time of and immunocompromise.
admission were included in the noninfected group for
the purpose of analysis. However, such patients were For statistical analysis, the APACHE II scoring was
included in the group with ICU-acquired infection when grouped into two classes of ≥13 and <13 taking the
they developed a new infection at a different anatomical median value for APACHE score as the cut-off. For the
site during the ICU stay. determination of the incidence of nosocomial infection,
infections rates were expressed as a percentage. Also,
All 242 patients in the study group were also infection rates were calculated per 1000 patient-days
followed-up till hospital discharge to acquire data on or per 1000 device days (for specific device associated
length of hospital stay and outcome in terms of mortality. infections) according to the CDC recommended
Information on each patient was recorded on a structured formulas.
case report form.
For classification of the different causative pathogens
To assess the severity of illness on the 1 day in the ICU,
st associated with nosocomial infections, all the
the Acute Physiology and Chronic Health Evaluation microorganisms isolated on culture from each of the
II (APACHE II) score[5] was used. The patients were patients with confirmed infection according to the CDC
classified into seven groups according to the primary definitions were recorded and their relative frequency
reason for ICU admission – cardiovascular, respiratory, of isolation were determined as percentage.[6,7] Bacterial
neurological, renal, metabolic, gastrointestinal and isolates were identified by Gram-stain, cultures on
surgical. Decision on infection or colonization was routine media (e.g. Blood agar, MacConkey agar)
based on laboratory and clinical evidence. Nosocomial and where necessary, selective media and specific
infections were diagnosed according to the standard biochemical tests following standard protocols. [8,9]
definition of the (United States centers for disease Fungal isolates were identified by cultures on Sabouraud
control and prevention [CDC]). [6,7] Antimicrobial dextrose agar, and Sabouraud dextrose chloramphenicol
therapy was administered to the patients as necessary agar media followed by Gram-stain, lactophenol cotton
and cultures were requisitioned when infection was blue mount and germ tube testing following standard
suspected. Patients were always sampled for microbial protocols.[10] For assessing outcome, each patient was
culture before starting a new antimicrobial. Appropriate followed-up till ICU and hospital discharge or death.
essential investigations were regularly performed as Length of ICU stay and hospital stay were recorded as
needed. the number of days from admission to discharge from
the ICU and hospital respectively. The length of ICU and
For the determination of risk factors associated with hospital stay in patients with and without nosocomial
ICU acquired nosocomial infection, the following infections and also the ICU and hospital mortality rates
putative risk factors were recorded: Age, gender, site in patients in both groups were statistically compared.
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Indian Journal of Critical Care Medicine January 2015 Vol 19 Issue 1
Data have been summarized by routine descriptive Upon comparison of putative risk factors of nosocomial
statistics. 95% confidence interval (CI) values have infection by univariate analysis [Table 1], prior
been calculated for key variables. Numerical variables
have been compared between groups by Student’s Table 1: Comparison of putative risk factors for nosocomial
independent samples t-test when normally distributed infections by univariate analysis
or by Mann–Whitney U-test when otherwise. Fisher’s Factors Infected Uninfected P
exact test has been employed for intergroup comparison (n=29) (n=213)
of independent proportions. Univariate analysis has Age (years)
been two-tailed, and P < 0.05 has been considered Range 38-92 10-95 0.069
Mean±SD 70.9±12.51 66.6±14.24
statistically significant. All variables returning P < 0.1 Sex
on univariate analysis were entered into a logistic Male 21 (72.4) 139 (65.3) 0.534
regression model of risk factors for nosocomial Female 8 (27.6) 74 (34.7)
Length of ICU stay (days)
infection. Univariate and adjusted odds ratios (ORs) Range 7-41 3-41 <0.001
from the logistic regression analysis have been reported. Mean±SD 17.28±8.59 5.8±4.72
SPSS Statistics version 17 (Illinois, Chicago: SPSS Inc., Median (IQR) 15 (11.5-23.5) 4 (3-7)
Length of hospital stay (days)
2008) software was employed for statistical analysis. Range 7-120 4-65 <0.001
Mean±SD 32.17±23.06 12.74±11.42
Median (IQR) 25 (18.0-39.5) 8 (6-16)
Results Transferred from
Data were collected from 242 patients accounting for Emergency room 14 (48.3) 138 (64.8) 0.171
Operation theater 4 (13.8) 32 (15.0)
a total of 1736 patient days. Ward 10 (34.5) 37 (17.4)
Others 1 (3.4) 6 (2.8)
Intensive care unit acquired nosocomial infections were Antimicrobial therapy 20 (69.0) 6 (2.8) <0.001
Antacid 27 (93.1) 131 (61.5) 0.001
detected in 29 patients (11.98%; 95% CI: 7.89–16.07%). Sedatives 13 (44.8) 65 (30.5) 0.140
These 29 patients developed one type of nosocomial Vasopressors 11 (37.9) 52 (24.4) 0.174
infection each. The most frequently diagnosed Parental nutrition 2 (6.9) 10 (4.7) 0.642
Enteral nutrition 28 (96.6) 188 (88.3) 0.332
nosocomial infection was nosocomial pneumonia. Body position
Combining both ventilator associated pneumonia (VAP) Supine 5 (17.2) 46 (21.6) 0.808
and non-VAP, nosocomial pneumonia was found in Semi recumbent 24 (82.8) 167 (78.4)
Hypoalbuminemia 16 (55.2) 46 (21.6) <0.001
18 (62.07%; 95% CI: 44.41–79.73%) of the 29 infected Diabetes mellitus 14 (48.3) 90 (42.3) 0.555
patients. Taken separately, VAP was diagnosed in Chronic renal failure 4 (13.8) 30 (14.1) 1.000
10 (34.48%) and nonventilator associated nosocomial Chronic alcoholism 1 (3.4) 5 (2.3) 0.539
Malnutrition 9 (31.0) 14 (6.6) <0.001
pneumonia was diagnosed in 8 (27.59%) of the infected Immunocompromised 7 (24.1) 41 (19.2) 0.619
patients. Urinary tract infection was diagnosed in Central venous catheter 28 (96.6) 179 (84.0) 0.091
8 (27.59%) out of the 29 infections and central venous Peripheral venous line 25 (86.2) 191 (89.7) 0.529
Arterial line 25 (86.2) 145 (68.1) 0.052
catheter related blood stream infection was detected
Pulmonary artery catheter 1 (3.4) 2 (0.9) 0.319
in 3 (10.34%) patients. Hence, when judged separately, Urinary catheter 28 (96.6) 156 (73.2) 0.004
VAP was the commonest ICU acquired infection Endotracheal intubation 16 (55.2) 46 (21.6) <0.001
detected. Re-intubation 3 (10.34) 1 (0.5) 0.006
Tracheostomy 7 (24.1) 2 (0.9) <0.001
Nasogastric tube 23 (79.3) 112 (52.6) 0.009
On the calculation of the infection rate per 1000 patient’s Mechanical ventilator 18 (62.1) 42 (19.7) <0.001
Surgery 3 (10.34) 32 (15.0) 0.778
days or per 1000 device days, the following values were APACHE II score
obtained: ≤13 4 (13.8) 125 (58.7) <0.001
• Overall nosocomial infection rate = 16.71/1000 patient >13 25 (86.2) 88 (41.3)
Main reason for ICU admission
days Cardiovascular 11 (37.9) 97 (45.5) 0.411
• Nosocomial pneumonia rate (both VAP and Respiratory 10 (34.5) 48 (22.5)
Surgical 3 (10.34) 32 (15.0)
non-VAP) =10.37/1000 patient days Neurological 4 (13.8) 13 (6.1)
• VAP rate = 26.6/1000 ventilator days Gastrointestinal 1 (3.4) 12 (5.6)
Metabolic - 7 (3.3)
• Non-VAP rate = 4.61/1000 patient days Renal - 4 (1.9)
• Urinary tract infection = 7.44/1000 catheter days Infection at admission 23 (79.3) 154 (72.3) 0.508
• Central venous catheter associated bloodstream Percentage values denote within group percentage. Statistically significant associations are
in bold. APACHE: Acute Physiology and Chronic Health Evaluation; ICU: Intensive care
infection rate = 2.46/1000 central venous catheter days. unit; IQR: Interquartile range (i.e., 25th-75th percentile range); SD: Standard deviation
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Indian Journal of Critical Care Medicine January 2015 Vol 19 Issue 1
antimicrobial therapy, antacid use, hypoalbuminemia, hospital stay, in terms of mortality, between the two
malnutrition, urinary catheterization, endotracheal groups. There was no statistically significant difference
intubation, re-intubation, tracheostomy, placement between the hospital mortality rates among the patients
of nasogastric tube, mechanical ventilation, APACHE with and without nosocomial infection (P = 0.181).
II score >13 and length of ICU stay were found to be There was a trend toward greater mortality in the ICU
statistically significant. The logistic regression model in patients with nosocomial infection than in patients
tested a large number of predictors for possible without (17.2% vs. 6.6%), although this did not reach
association with the outcome of nosocomial infection statistical significance (P = 0.060).
as shown in Table 2. Out of these, prior antimicrobial
therapy, urinary catheterization and length of ICU stay Discussion
were found to be statistically significant risk factors
The prevention of ICU acquired infections demands
for nosocomial infection by multivariate analysis.
knowledge of the infection rates and of the sources, the
The model fit was good with a Nagelkerke R2 value
pathogens involved as well as the common risk factors for
of 0.754, indicating that over 75% of the variability
infection. The incidence of nosocomial infections varies
in the model could be explained by the predictors
according to the setting, that is, the type of hospital or
selected. However, the limited sample size has ICU, the patient population and the precise definition
resulted in relatively large 95% CI of adjusted ORs of and surveillance techniques used to identify a nosocomial
the individual predictors. infection.[11] A large cohort multicentric international
study has reported at least one ICU acquired infection in
Table 3 summarizes the distribution of pathogens 18.9% of patients, with an incidence ranging from 2.3%
responsible for the nosocomial infection cases in this to 49.2% across the centers.[12] In a 1-day point prevalence
study, categorized by site of infection. A total of 40 study involving 1265 ICU s from 76 countries (extended
pathogens were isolated on culture and accounted for prevalence of infection in intensive care [EPIC II] study),
the nosocomial infections in 29 patients. Some infections 51% patients were found to have nosocomial infection.
were polymicrobial. Gram-negative Enterobacteriaceae However, the rates of infections varied considerably
were the most frequently isolated pathogens (n = 15; according to the country, with Greece and Portugal
37.5%) closely followed by Pseudomonas species (n = 14; having the highest and Switzerland and Germany and
35%, Pseudomonas aeruginosa = 13, Burkholderia the Netherlands having the lowest infection rates.[13] Other
cepacia = 1). studies[14,15] have reported incidence rates between 9% and
37%, depending largely on the populations studied. Crude
Regarding outcome, the length of total hospital and infection rates might not be representative of the overall
ICU stays have been depicted and compared in Table 1. problem since they do not take into account the patients’
Table 4 compares the outcome of ICU stay and total intrinsic risk of infection or extrinsic risks associated
Table 2: Results of univariate and multivariate (logistic regression) analysis of potential risk factors for nosocomial infections
in the intensive care environment
Parameter P value from OR from 95% CI of P value from AOR 95% CI for
univariate analysis univariate analysis univariate OR logistic regression AOR
Age 0.069 - - 0.683 0.99 0.93-1.05
Prior antimicrobial use <0.001 76.67 24.75-237.48 <0.001 409.67 29.99-5594.76
Antacid use <0.001 8.45 1.96-36.50 0.574 0.51 0.05-5.41
Hypoalbuminemia <0.001 4.47 2.00-9.96 0.260 2.83 0.46-17.28
Malnutrition <0.001 6.40 2.46-16.63 0.667 1.63 0.18-15.05
Central venous line 0.091 5.32 0.70-40.44 0.742 1.75 0.06-48.07
Arterial line 0.052 2.93 0.98-8.76 0.176 0.24 0.03-1.90
Urinary catheterization 0.004 10.23 1.36-76.98 0.041 42.00 1.18-1501.35
Endotracheal intubation <0.001 4.47 2.00-9.96 0.157 0.11 0.01-2.38
Reintubation 0.006 24.46 2.45-244.01 0.620 0.39 0.01-15.81
Tracheostomy <0.001 33.57 6.56-171.68 0.301 0.16 0.01-5.30
Nasogastric intubation 0.009 3.46 1.35-8.83 0.169 0.24 0.03-1.85
Mechanical ventilation <0.001 6.66 2.93-15.17 0.118 9.03 0.57-141.92
Surgery 0.778 0.65 0.19-2.29 0.565 2.13 0.16-28.12
Days in ICU <0.001 - - 0.005 1.25 1.07-1.46
Days in hospital <0.001 - - 0.856 1.01 0.95-1.07
APACHE II score 0.001 - - 0.323 1.10 0.91-1.32
Parameters returning P < 0.1 on univariate analysis were included in logistic regression analysis; Statistically significant associations are in bold. APACHE: Acute Physiology and
Chronic Health Evaluation; CI: Confidence interval; OR: Odds ratio; AOR: Adjusted odds ratio; ICU: Intensive care unit
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Indian Journal of Critical Care Medicine January 2015 Vol 19 Issue 1
Table 3: Distribution of causative micro-organisms of antibiotic protocols, infection control practice and local
nosocomial infections by site ecology and resistance patterns.[20] Although recent
Pathogen n (%) Total years have seen swings in the pathogen pattern toward
(%) Gram-positive bacterial infections, [21,22] still, most
Pneumonia VAP UTI BSI
(nonVAP) studies report that more than half of the nosocomial
Pseudomonas aeruginosa 5 (45.5) 6 (46.2) 1 (7.7) 1 (33.3) 13 (32.50) infections occurring in the ICU are due to Gram-negative
Escherichia coli - 2 (15.4) 4 (30.8) 1 (33.3) 7 (17.50) bacteria.[13,19] In our study too, the most commonly
Candida spp. 2 (18.2) 1 (7.7) 3 (23.1) - 6 (15.00) isolated organisms were Gram-negative Enterobacteriaceae
Klebsiella pneumoniae 2 (18.2) 2 (15.4) 1 (7.7) - 5 (12.50)
Enterococcus spp. - 1 (7.7) 2 (15.4) - 3 (7.50) followed closely by Pseudomonas species. The detection
Acinetobacter spp. - - 2 (15.4) - 2 (5.00) of Candida species in 15% of the isolates in the present
Burkholderia cepacia 1 (9.1) - - - 1 (2.50) study is also consistent to some extent with the studies
Coagulase negative - - - 1 (33.3) 1 (2.50)
staphylococci of Pittet and Wenzel[23] and Edgeworth et al.,[24] who
Enterobacter spp. - 1 (7.7) - 1 (2.50) have reported that fungal pathogens are also becoming
Stenotrophomonas spp. 1 (9.1) - - - 1 (2.50) increasingly common among patients with nosocomial
Total 11 13 13 3 40
bloodstream infections.
Percentage values denote column percentage. UTI: Urinary tract infection;
VAP: Ventilator associated pneumonia; BSI: Bloodstream infection
Intensive care unit acquired infections have been
Table 4: ICU stay and hospital stay outcome compared
reported to be associated with increased length of ICU
and hospital stays.[25] Correa and Pittet[26] reported an
Infected (n=29) Uninfected (n=213) P
additional cost of about $3.5 billion/year due to ICU
ICU outcome
Alive 24 (82.8) 199 (93.4) 0.060 acquired infections. The findings in the present study
Expired 5 (17.2) 14 (6.6) are corroborative. Crude mortality rates associated with
Hospital outcome nosocomial infection vary from 12% to 80%, dependent
Alive 24 (82.8) 194 (91.1) 0.181
on the population studied and the definitions used.[20]
Expired 5 (17.2) 19 (8.9)
Percentage values denote within group percentage. The P value is from intergroup
Whereas some studies do report increased mortality
comparison by Fisher’s exact test. ICU: Intensive care unit associated with nosocomial infections, [27,28] other
studies, like those of Rello et al.,[29] have not shown
with exposure to medical interventions.[16] The findings higher mortality, emphasizing the problems in defining
in our study were found to be closer to the lower range cause-effect relationship in these individuals. In the study
of incidence rates reported in the other studies referred by Rosenthal et al.,[30] crude mortality rate for patients
above. This difference in findings is not necessarily related with device associated infections ranged from 35.2% (for
to better quality of care, since many other factors may be central venous catheter associated blood stream
responsible including difference in the criteria for patient infection) to 44.9% (for VAP). In the present study there
selection, the case mix, ICU type, length of stay, rate of was a trend, but no statistically significant difference in
device utilization and discharge criteria.[17,18] The patients ICU mortality rate in the patients with compared to those
from a single institution can present with different risk of without nosocomial infection despite a significantly
infection in the context of differing case mix, severity of greater proportion of infection patients falling in the
illness and utilization rates of invasive devices.[19] higher APACHE II category. A probable explanation for
the lack of difference could be a variation in the baseline
In the EPIC II study,[13] the most frequently reported severity of illness mentioned before and described by
sites for ICU acquired infections were the lungs (64%), Vincent.[20] Another factor that may have prevented
abdominal (19%), and blood stream (15%). Data from the trend from becoming statistically significant is the
the United States National Nosocomial infections relatively small number of deaths in both arms observed
surveillance system showed that the nosocomial over the 6-month study period. A longer study may have
pneumonia accounted for 31% of all nosocomial produced more deaths leading to the observed difference
infections followed by urinary tract infections and blood becoming statistically significant.
stream infections.[19] The site distribution of nosocomial
infections in this study broadly conforms to the findings Although there is a plethora of studies detailing the
of earlier and larger studies mentioned above. risk factors for various type of nosocomial infections in
various groups of patients, more commonly identified
The precise pattern of causative organisms, whether risk factors can be divided into four groups: (a) Those
bacterial or fungal, varies across countries and between related to underlying health impairment; (b) those
ICUs according to patient case mix, site of infection, related to the acute disease process; (c) those related to
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Indian Journal of Critical Care Medicine January 2015 Vol 19 Issue 1
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Source of Support: Nil, Conflict of Interest: None declared.
et al. Device-associated nosocomial infections in 55 intensive care units
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