Anaesth Intensive Care 2010; 38: 325-335

The role of admission surveillance cultures in patients

requiring prolonged mechanical ventilation in the intensive
care unit
M. Viviani*, H. K. F. van Saene†, F. Pisa‡, U. Lucangelo*, L. Silvestri§, E. Momesso*,
G. Berlot**
Department of Anaesthesia, Intensive Care and Emergency, Company University Hospital, Hospitals Meeting of Trieste, University
of Trieste, Cattinara Hospital, Italy

Summary
We undertook a prospective observational cohort study in intensive care unit (ICU) patients requiring mechanical
ventilation for four days or more to evaluate normal and abnormal bacterial carriage on admission detected by
surveillance cultures of throat and rectum. We assessed the importance of surveillance and diagnostic cultures for
the early detection of resistance to third generation cephalosporins employed as the parenteral component of the
selective decontamination of the digestive tract. Finally, we sought the risk factors of abnormal carriage on
admission to the ICU. During the 58-month study 621 patients were included: 186 patients (30%) carried
abnormal flora including methicillin-resistant Staphylococcus aureus (MRSA) and aerobic Gram negative bacilli
(AGNB) on admission to the ICU. Both MRSA and AGNB carriers were more commonly present in the hospital
group of patients than in patients referred from the community (P <0.001), although overgrowth was equally
present both in community and in hospital patients. The incidence of infections during ICU stay was higher in
abnormal (n=120, 64.5%) than in normal carriers (n=185, 42.5%) (P <0.0001), with an odds ratio of 2.46 (95%
confidence interval 1.72 to 3.51). Third generation cephalosporins covered ICU admission flora in 482 (78%)
of the studied population. AGNB resistant to cephalosporins and MRSA were detected in surveillance cultures
of 139 patients (22%), while the same resistant micro-organisms were identified only in 49 diagnostic samples
(7.9%). Parenteral cephalosporins were modified in patients with abnormal flora (P <0.0001). One hundred
and ninety-six patients received antibiotics before admission to the ICU and 42% carried AGNB resistant to
cephalosporins. Previous antibiotic use was the only risk factor for abnormal carriage in the multivariate analysis
(OR 3.5; 95% confidence interval 2.1 to 5.8). The knowledge of carriage on admission using surveillance cultures
may help intensivists to identify patients with abnormal carriage on admission and resistant bacterial strains at an
early stage even when diagnostic samples are negative. Third generation cephalosporins covered admission flora in
about 80% of the enrolled population and were modified in patients with abnormal flora who received antibiotic
therapy before ICU admission. Our finding of overgrowth present on admission may justify the immediate
administration of enteral antimicrobials.
Key Words: carriage, infection, intensive care, selective decontamination, antibiotic policy

* M.D., Anesthetist. Forty years ago Johanson et al1 introduced the

† M.D., Professor, Department of Medical Microbiology, University of
Liverpool, Liverpool, United Kingdom.
‡ M.D., Epidemiologist, Regional Health Agency of Friuli Venezia Giulia,
Section of Epidemiology, Udine.
§ M.D., Chief, Department of Anaesthesia and Intensive Care, Presidio
Hospital Gorizia.
** M.D., Chief Professor.
Address for correspondence: Dr Marino Viviani, Ospedali Riuniti di
Trieste, Ospedale di Cattinara - Dipartimento di Anestesia, Terapia Intensiva
ed Emergenza, Strada di Fiume 447, 34149 Trieste, Italy.
Accepted for publication on October 20, 2009.
Anaesthesia and Intensive Care, Vol. 38, No. 2, March 2010
concept that disease influences carriage of potential
pathogens in throat and gut. Individuals who are
in good health carry low level pathogens including
indigenous anaerobes, viridans streptococci,
enterococci, coagulase-negative staphylococci and
the six ‘community’ potential pathogens including
Streptococcus pneumoniae2, Haemophilus influenzae3,
Moraxella catarrhalis4, Escherichia coli5, Candida
species6 and methicillin sensitive Staphylococcus
326 M. Viviani, H. K. F. van Saene et al
aureus (MSSA)7 (normal flora). Carriage of the
‘hospital’ potential pathogens including aerobic
Gram-negative bacilli (AGNB)8 and methicillin-
resistant Staphylococcus aureus (MRSA) in the
oropharynx and gastrointestinal tract is considered
abnormal in healthy individuals and it is uncommon9.
Two studies in patients requiring treatment in
the intensive care unit (ICU) showed a correlation
between AGNB carriage on admission and the level
of illness severity10,11. This may be in part due to an
increased availability of AGNB receptor sites on
the digestive tract mucosa in illness12,13. One third of
ICU patients with an Acute Physiology and Chronic
Health Evaluation II score >15 were AGNB carriers.
This increased to 50% in a population with an Acute
Physiology and Chronic Health Evaluation II score
≥27. Severity of illness is thought to be the most
important factor in the conversion of the ‘normal’ to
the ‘abnormal’ carrier state.
Risk factors for abnormal carriage of both AGNB
and MRSA include chronic underlying disease, such
as diabetes, chronic obstructive pulmonary disease,
alcoholism, liver disease and antibiotic use14-18. In
general, most risk factors associated with abnormal
carriage on admission to the ICU reflect the illness
severity.
Some authors report that the abnormal carrier
state is not only a marker of illness but is a disease
on its own19,20, as overgrowth of AGNB in the gut has
been shown to cause immuno-paralysis. Hence the
detection of abnormal carriage on admission to the
ICU may identify a subset of patients at high risk of
infection and mortality.
Immediate appropriate antimicrobial therapy of
pneumonia and septicaemia has been recognised
to increase survival21,22. Several studies have shown
that when the initiation of appropriate antimicrobial
treatment is delayed, patients have adverse outcomes
and that the adverse prognostic implications of late
or inappropriate antimicrobial treatment cannot be
overcome by the correction of the initial empirical
antibiotic management23,24. Severe infections with
multi-resistant AGNB and MRSA can be the reason
for the admission to the ICU. These observations
have led to the immediate administration of empirical
broad-spectrum antibiotics to cover most pathogens.
For example, the combination of fluoroquinolones,
meropenem and vancomycin has been promoted
by some authors23,24. However, the overuse of
antimicrobial drugs is associated with the emergence
of multi-resistant bacteria25 even when antibiotic
guidelines are tailored to local flora. Selective
decontamination of the digestive tract (SDD) is an
antibiotic prophylaxis regimen to reduce serious
infections of lower airways and bloodstream in
patients requiring treatment in the intensive
care setting. SDD using parenteral and enteral
antimicrobials aims to control primary endogenous,
secondary endogenous and exogenous infections26,27.
A prospective observational study was
undertaken in patients requiring at least four days
of mechanical ventilation and receiving the full
SDD protocol to evaluate the following clinical
and microbiological endpoints. First, this study
was conducted to determine normal and abnormal
bacterial carriage and its level by surveillance
cultures collected on admission to the ICU.
Second, we assessed the importance of surveillance
and diagnostic cultures for the early detection
of resistance to third generation cephalosporins
employed as the parenteral component of SDD.
Finally, we sought the risk factors related to
abnormal carriage on admission to the ICU.
MATERIALS AND METHODS
Setting
The University Hospital of Trieste is a multi-
disciplinary, regional referral centre. The ICU is an
11-bed facility with an annual admission rate of about
600 patients; medical and surgical patients each
account for 45% of the population and 10% are
trauma. The overall mortality is 10% for all
admissions.
Patients
Patients aged over 18 years, admitted to the ICU
and expected to require at least four days of
mechanical ventilation were enrolled in the study.
Data were recorded from 1 March 2000 until 31
December 2004. Patients with severe immuno-
suppression (organ transplantation, neutropenia
<1×109/l, acquired immune deficiency syndrome)
were excluded because of the need for a different
parenteral antibiotic protocol on admission. Patients
without complete surveillance cultures due to
clinical reasons could not be analysed and were
also excluded. A third reason for exclusion was
prolonged extubation (greater than five days) during
the ICU treatment because of the discontinuation of
surveillance cultures and SDD protocol. The Hospital
Institutional Review Board waived the need for
informed consent, because of the epidemiological
nature of the study and absence of invasive
procedures.
Patients were classified into ‘community’ and
‘hospital’ groups. Patients admitted to the ICU from
home or the street, via the Department of Accident
and Emergency, were considered to belong to the
Anaesthesia and Intensive Care, Vol. 38, No. 2, March 2010
 Admission surveillace cultures in ICU
‘community’ group. Patients referred to the ICU
from the hospital ward, even if they stayed less than
one day, were included in the ‘hospital’ group.
Design and endpoints
The design was a prospective observational cohort
study on carriage detected by surveillance cultures28.
Surveillance samples of throat and rectum were
obtained on admission to the ICU and twice in a week
thereafter until extubation. A swab with a cotton
wool tip was rubbed over the tonsil area after
intubation. At the same time a rectal swab was
obtained. Only rectal swabs coloured by faeces were
considered valid. In addition, diagnostic cultures
were obtained from all patients showing signs of
inflammation or infection on admission to the unit.
The set of throat and rectal and diagnostic samples
were sent immediately to the department of clinical
microbiology where they were processed within one
hour.
Endpoints
1. Normal and abnormal carriage and overgrowth
on admission;
2. Surveillance compared with diagnostic cultures
to detect resistance to third generation
cephalosporins as the parenteral component of
SDD;
3. Analysis of risk factors for abnormal carriage
including age, Simplified Acute Physiology Score
(SAPS) II, diagnostic category, infection on
admission to the ICU and previous antibiotic
usage.
Definitions
Carriage on admission to the ICU was defined as
the patient condition in which the same potential
pathogen was isolated from the first two sets of
surveillance cultures in any concentration.
Normal carriage was defined as the presence
of ‘community’ potential pathogens including S.
pneumoniae, H. influenzae, M. catarrhalis, MSSA
and Candida species. The presence of E. coli was
considered normal in the rectal swab but abnormal
in the oropharyngeal swab if present in overgrowth29.
Abnormal carriage was defined as the isolation of
AGNB including Klebsiella, Enterobacter, Citrobacter,
Morganella, Proteus, Acinetobacter, Serratia,
Pseudomonas species and MRSA in throat and/or
rectum in any concentration.
Overgrowth was defined as the presence of ≥3+
(semi-quantitatively) or ≥105 (quantitatively) colony
forming units of abnormal bacteria/ml of saliva
and/or gram of faeces30.
Anaesthesia and Intensive Care, Vol. 38, No. 2, March 2010
327
The level of carriage, both normal and abnormal,
was expressed by the ‘carriage index’, defined as the
sum of all semi-quantitative growth densities isolated
from surveillance swabs, divided by the total number
of positive swabs collected31.
The diagnosis of infection included signs of local
and/or generalised inflammation, laboratory findings
and positive bacteriological diagnostic samples.
Pneumonia was diagnosed based on fever 38.5°C,
new pulmonary infiltrate on chest X-ray for more
than 48 hours, leukocytosis (white blood cells count
>12000 /ml) or leukopenia (white blood cells count
<4000 /ml), purulent tracheal aspirate with semi-
quantitative cultures at a threshold of ≥3+ colony
forming units. Tracheo-bronchitis was diagnosed
when all above signs were present but normal chest
radiography was found. Urinary tract infection was
defined as freshly voided catheter urine containing
105 colony forming units/ml and ≥5 leukocytes per
high-power-light microscope field. Bloodstream
infection was diagnosed in the presence of clinical
signs of generalised inflammation and one positive
blood culture. A second positive blood culture for
the same strain was required when the first blood
culture yielded low level pathogenic micro-organisms
(i.e. coagulase-negative staphylococci). Catheter-
related bloodstream infection was diagnosed
when the same potential pathogenic micro-organism
was cultured from the intravascular device and
from the blood samples. Wound infection was defined
by local signs of inflammation, purulent discharge
from the wound site with culture yielding ≥3+
and ≥++ leukocytes. The isolation of skin flora
was considered contamination. Intra-abdominal
infection covered either solid organ or peritoneal
cavity (localised or diffuse). Peritonitis was diagnosed
according to clinical conditions, ultrasound and/
or computed tomography scan and/or laparotomy
findings associated with microbiological positive
samples (micro-organism ≥3+ and leukocytes
≥++).
A patient diagnosed as infected in the first 48 hours
was considered infected on admission. Using the
criterion of carriage, infections were classified into
endogenous and exogenous. An exogenous infection
was caused by a potential pathogen not present in
the surveillance cultures. Endogenous infection
was due to a micro-organism carried by the patient
in throat and/or rectum. Primary endogenous were
infections caused by community (normal) or hospital
(abnormal) micro-organisms already carried by the
patient on admission to the ICU. Micro-organisms
acquired during the ICU stay but not present on
admission caused secondary endogenous infections32.
328 M. Viviani, H. K. F. van Saene et al
Patients were considered on antibiotic therapy
before admission to the ICU when antimicrobials
were administered for more than 24 hours.
Antibiotic policy
All patients studied received selective
decontamination of the digestive tract using enteral
and parenteral antimicrobials from admission until
extubation28. Half a gram of a paste containing
polymyxin E 2%, tobramycin 2% and amphotericin
B 2% was applied in the lower cheeks and 9 ml of
a suspension containing 100 mg of polymyxin E,
80 mg of tobramycin, 500 mg of amphotericin B
was administered through the nasogastric tube four
times daily. The combination of polymyxin and
tobramycin covers all AGNB including Proteus,
Morganella and Serratia species being the gap in the
spectrum of the polymyxins. Additionally, polymyxin
is active against Pseudomonas and Acinetobacter
resistant to beta-lactams, aminoglycosides,
fluoroquinolones, beta-lactam plus beta-lactamase
inhibitors and carbapenems.
A third generation cephalosporin was chosen as
the parenteral component of SDD. Patients who
belonged to the ‘community’ group received
cefotaxime (100 mg/kg/day via intravenous
continuous infusion for four days33) to cover
community respiratory pathogens such as S.
pneumoniae, H. influenzae, M. catarrhalis, MSSA.
Amongst the normal flora only Candida is naturally
resistant to cefotaxime. Ceftazidime (100 mg/kg/day
via intravenous continuous infusion for four days33)
was given to patients classified as belonging to the
hospital group because they were considered to be
exposed to abnormal AGNB such as P. aeruginosa.
Antimicrobials were administered according to
the hospital guidelines based on site of infection
and culture results. The parenteral antimicrobials
of SDD were continued after the fourth day when
patients were infected and the causative micro-
organisms were sensitive. Failure of the parenteral
component of SDD was defined as any change of
third generation cephalosporins following the results
of surveillance or diagnostic cultures and/or clinical
deterioration within 48 to 72 hours.
Microbiology
Surveillance samples of throat and rectal swabs
were processed qualitatively and semi-quantitatively,
to detect the level of carriage. Three solid media –
MacConkey, staphylococcal and yeast agar – were
inoculated using the four-quadrant method combined
with brain-heart infusion broth. Each swab was
streaked onto the three solid media, then the tip
was broken off into 5 ml of enrichment broth. The
MacConkey plate was examined after one night and
the staphylococcal and yeast plates after two nights.
In addition, if the enrichment broth was turbid after
one night’s incubation it was then inoculated onto
the three media. A semi-quantitative estimation was
made by grading growth density on a scale of 1+ to
5+34. Standard methods for identification, typing
and sensitivity patterns were used for all micro-
organisms.
To differentiate S. aureus from other species of
staphylococci, the laboratory used production of
DNAse (by a DNA agar-plate method) and a slide-
agglutination test to detect clumping factor and
protein A (Pastorex Staph Plus, Sanofi Diagnostics,
Marnes, France). If the results were inconclusive, a
tube-coagulase test with the NCTC 6571 strain as
a positive control was done and interpreted at four
and 24 hours. A coagulase-negative staphylococcus
was identified by a negative tube-coagulation test.
S. aureus isolates were tested for methicillin
susceptibility by subculturing the isolates onto
nutrient agar plus 5% salt (Oxoid, Basingstoke, UK)
with a strip containing 25 µg of methicillin. S. aureus
isolates growing up to the strip and subsequently
shown to have an MIC >256 g/ml on gradient plates
in the exponential antibiotic gradient test (E-test),
were confirmed to be MRSA. The breakpoints for
vancomycin resistance amongst enterococci was
16 µ/ml and 8 µ/ml for S. aureus with intermediate
sensitivity to vancomycin.
Database
The data collected included age, gender, illness
severity using SAPS II score, diagnostic category
(medical, surgical and trauma) on ICU admission.
Duration of previous hospital stay, antibiotic
treatment before ICU admission, normal and
abnormal carrier state on admission, length of ICU
stay, length of mechanical ventilation, incidence
of infection in ICU and ICU mortality were put
into the database (Excel for Windows®, Microsoft,
Redmond, USA).
In cases where an identical micro-organism was
carried at both oropharyngeal and rectal sites by the
same patient, that particular micro-organism was
counted once only.
Statistical analysis
Descriptive statistics were used to describe
demographics, health status and other variables
related to ICU admission, carrier state and
antibiotic usage. Nominal or categorical data were
tabulated in 2×2 or 2×k contingency tables. The
difference between proportions was tested using the
χ2 test with Satterthwaite approximation in case of
Anaesthesia and Intensive Care, Vol. 38, No. 2, March 2010
 Admission surveillace cultures in ICU 329

unequal variances. The difference between means interval (CI) by means of non-conditional logistic
was tested using the unpaired t-test for regression, univariate or multivariate. In the
independent samples. Two-tailed P values were multivariate model age, SAPS II score (four
reported. Non-normally distributed variables (i.e. categories: <30; 30 to 39; 40 to 49; >50), diagnostic
ICU stay) were log transformed. category on ICU admission (medical vs non medical)
To estimate the relative probability of abnormal and infection on ICU admission were included35.
carriage to prior use of antibiotics we calculated Analyses were performed using SAS software (SAS
the odds ratio (OR) and its 95% confidence Institute Inc., Cary, USA).
Table 1
General characteristics and abnormal carriage of the study population

Admission Community group Hospital group Total population

n n% n % P values n %
Patients 295 47.5 326 52.5 621 100
Gender
F 98 33 126 39 224 36
M 197 67 200 61 397 64
Age, y (mean ± SD) 52.5 (±20) 64.7 (±13.6) <0.0001 59 (±18)
SAPS II, (mean ± SD) 43.3 (±13.5) 44.4 (±13.6) 43.9 (±13.6)
Classification of patients
Medical 75 25 221 68 <0.0001 296 48
Surgical 52 18 92 21 144 23
Trauma 168 57 14 4 <0.0001 182 29
Previous antibiotic use 196 60
Length of hospital stay, (mean ± SD) – 12.1 (±15.8)
Length of ICU stay, (mean ± SD) 18.8 (±16.1) 19.4 (±18.4) 19.1 (±17.4)
Length of mechanical ventilation, 15.5 (±14.5) 16.9 (±16.8) 16.2 (±15.8)
(mean ± SD)
Overall infected patients 117 40 188 58 305 49
Patients infected on admission 20 6.7 117 35.8 <0.0001 137 22
Mortality 62 21 99 30 161 25.9
Abnormal carriage
Patients with AGNB 42 14.2 98 30.1 <0.0001 140 22.5
Patients with AGNB resistant to 3rd 16 5.4 56 17.2 <0.001 72 11.6
generation cephalosporins

AGNB isolates* Community group Hospital group Total population

n Res. n Res. n Res.
Escherichia coli§ 8 0 15 1 23 1
Klebsiella spp 8 0 14 7 22 7
Enterobacter spp 9 3 17 17 26 20
Citrobacter spp 1 0 1 1 2 1
Morganella spp 1 0 1 1 2 1
Proteus spp 7 2 11 4 18 6
Pseudomonas spp 10 9 52 36 62 45
Acinetobacter spp 3 3 3 2 6 5
Serratia spp – – 3 3 3 3
*There were more aerobic Gram negative bacilli (AGNB) obtained from surveillance cultures than the number of patients because some
patients carried more than one AGNB. § >3+ in oropharyneal swab. F=female, M=male, SAPS=Simplified Acute Physiology Score,
Res=number of isolates resistant to third generation cephalosporins, spp=species.
Anaesthesia and Intensive Care, Vol. 38, No. 2, March 2010
330 M. Viviani, H. K. F. van Saene et al

RESULTS patients, accounting for 11,693 patients’ days on

General characteristics and infection on admission to the ICU and 10,084 mechanical ventilation days,
the intensive care unit were analysed (Table 1). The mean age of the total
A total of 1926 patients were admitted to the population was 59 years and the mean SAPS II
unit between 1 March 2000 and 31 December was 43.9; 48% of the population was medical. Of
2004. Information was recorded on 656 severely ill the overall population, 326 (52.5%) patients were
patients admitted to the ICU. Thirty-five patients referred from the hospital ward and 196 (31.6%)
were not included in the analysis because they did received antibiotics before ICU admission. The
not fulfil the inclusion criteria due to incomplete mean length of stay on the hospital ward was 11.8
surveillance (n=18), prolonged extubation (n=11) (SD±15.5) days; the mean length of ICU stay
and immunosuppression (n=6). A total of 621 was 19.1 (SD±17.4) days in both community and
Table 2
Causative micro-organisms and number of patients with isolates resistant to third generation cephalosporins in 137 patients infected on
admission to the intensive care unit

Community group (n=295) Hospital group (n=326)

Potential pathogens 20 patients 8 patients infected with 117 patients 72 patients infected with
bacteria resistant to third bacteria resistant to third
generation cephalosporins generation cephalosporins
Normal flora
Streptococcus pneumoniae 6 0 6 0
Haemophilus influenzae – – 4 0
Escherichia coli 3 0 11 (2)§ 1
MSSA – – 4 4
Candida albicans – – 4 4
Total 9 0 29 9
Abnormal flora – –
Klebsiella spp 1 0 6 (1)§ 2
Enterobacter spp – – 4 (1)§ 3
Serratia spp – – 1 0
Acinetobacter spp 1 1 – –
Pseudomonas spp – – – –
aeruginosa 2 2 27 (10)§ 18
non aeruginosa 1 0 2 1
Non identified aerobic gram negative bacilli – – 3 0
MRSA 2 2 20 (4)§ 20
Total 7 5 63 44
Low level pathogens
Coagulase negative staphylococci 1 1 6 (1)§ 6
Enterococci 1 1 6 (1)§ 6
Anaerobes – – 3 3
Total 2 2 15 15
Legionella pneumophila – 3 3
Mycoplasma pneumoniae 1 1 – –
Cytomegalovirus – – 1 1
Total 1 1 4 4
Unknown 1 6
‘Resistant to third generation cephalosporins’ includes both intrinsic and acquired resistance to ceftazidime and cefotaxime.
MSSA=methicillin-sensitive Staphylococcus aureus, spp=species, MRSA=methicillin-resistant Staphylococcus aureus. The denominator in
this table are patients infected with the main pathogenic micro-organism (§) in case of polymicrobial infection.
Anaesthesia and Intensive Care, Vol. 38, No. 2, March 2010
 Admission surveillace cultures in ICU 331

hospital groups. About half of the total population Detection of overgrowth on admission to the intensive
was infected: 22% on admission and 27% during care unit
the treatment on ICU. Normal and abnormal flora were present in
The patients in the hospital group were overgrowth concentrations in both community and
significantly older (mean age 64.7, SD±13.6) hospital groups. Mean values of carriage indices of
compared with those referred from the community MSSA were 3.2 (±1 SD) and 3.3 (±1.01 SD) in the
(mean age 52.5, SD±20.2) (P <0.0001). There were community and in the hospital group, respectively.
significantly more medical admissions in the hospital E. coli was detected at mean index value of 3.6
group (n=221, 68%) compared to the community (±0.92 SD) in patients coming from the community
group (n=75, 25%) (P <0.0001). and 3.6 (±0.96 SD) in patients referred from the
Twenty (6.7%) patients belonging to the wards. Mean carriage indices of MRSA were 3.4
community group were infected on admission to the (±0.87 SD) and 3.5 (±0.88 SD) in the community
ICU compared with 117 (35.8%) patients belonging and hospital groups respectively. Finally, the mean
to the hospital group (P <0.001) (Table 2). A total of carriage indices of AGNB were 3.6 (±0.87 SD) in
70 patients (seven community, 63 hospital) were the community group and 3.5 (±0.88 SD) in the
infected with abnormal bacteria on admission to hospital group. In particular the indices of
the ICU. Remarkably, Pseudomonas species caused P. aeruginosa were 3.3 (±1.15 SD) and 3.5 (±0.9 SD)
infection in 24.8% of the hospital group. Table 2
Table 3
shows the micro-organisms causing infection
Characteristics of normal and abnormal carriers
diagnosed on admission in 137 patients and their
resistance to third generation cephalosporins. Normal Abnormal P value
n % n %
Normal and abnormal carriage on admission to the
Patients 435 70 186 30
intensive care unit.
Gender
Seventy percent (n=435) of the study population
F 153 35 71 38 ns
carried normal flora and 30% (n=186) abnormal
flora. A total of 283 patients (45.6%) carried yeasts. M 282 65 115 62 ns
There were significantly more hospital patients Age, y (mean ± SD) 56.9 (±18.9) 63.9 (±15) ns
who carried Candida species on admission to ICU SAPS II (mean ± SD) 43.1 (±13.4) 45.7 (±13.7) 0.03
(n=181, 55.5%) compared to the community Classification of patients
patients (n=102, 34.6%) (P <0.0001). A total of
medical 193 44.6 102 54.8 ns
51 (8.2%) patients carried MSSA, 25 and 26 in
the community and hospital groups, respectively. surgical 87 20.0 56 30.1 ns
Out of the total population, 67 (11%) patients trauma 154 35.4 28 15.1 ns
carried MRSA on admission. There were 62 (19%) Previous antibiotic use 154 35.4 28 15.1 ns
MRSA carriers in the hospital group compared Length of hospital stay, 8.5 (±12) 15.5 (±18.7) ns
to five (1.7%) in the community group (P <0.0001). (mean ± SD)
One hundred and forty (22%) patients had Length of ICU stay, 18.9 (±17.9) 19.7 (±16.1) ns
surveillance cultures positive for AGNB in their (mean ± SD)
admission flora (Table 1). There were significantly Length of mechanical 16 (±16.4) 16.8 (±14.4) ns
more AGNB carriers in the hospital group (n=98, ventilation, (mean ± SD)
30.1%) than in the community group (n=42, 14.2%) Overall infected patients 185 42.5 120 64.5 <0.0001
(P <0.0001) (Table 1). The three most common Patients infected on 70 16.0 67 36.0 <0.0001
AGNB isolated were P. aeruginosa, and E. coli in the admission in ICU
oropharynx, and Enterobacter species. Infection episodes
In the univariate analysis, patients who carried classified using CS
abnormal flora had a higher risk of infection, both primary endogenous 99 22.8* 85 45.6 § <0.0001
overall (OR 2.46; 95% CI 1.72 to 3.51) and on secondary endogenous 54 12.4* 18 9.7 § ns
admission to the intensive care (OR 2.9; 95% CI 2 exogenous 26 6* 14 7.5 §
to 4.4), compared to normal carriers. Primary endo-
ICU mortality 117 26.9 44 23.7 ns
genous infections were significantly more observed
in patients with abnormal flora on admission than The pathogenesis of six (*) and three (§) infections was not available
due to incomplete microbiological data. F=female, M=male,
in the normal flora group (45.6% vs 22.8%, SAPS II=Simplified Acute Physiology Score II, ICU=intensive
P <0.0001) (Table 3). care unit, CS=carrier state classification of infections.
Anaesthesia and Intensive Care, Vol. 38, No. 2, March 2010
332 M. Viviani, H. K. F. van Saene et al
respectively. Amongst patients who developed a
primary endogenous infection, overgrowth was
detected in 70 (70.8%) of the normal flora group
and in 71 (83.5%) of the abnormal flora group.
Surveillance samples versus diagnostic samples for the
detection of antimicrobial resistance to third generation
cephalosporins
Surveillance cultures on admission identified
139 (22%) patients with bacteria resistant to third
generation cephalosporins (cefotaxime and
ceftazidime) used as the parenteral component
of SDD. Seventy-two patients (16 community,
56 hospital) carried AGNB resistant to third
generation cephalosporins and 67 patients carried
MRSA intrinsically resistant to third generation
cephalosporins.
Diagnostic samples identified 49 (7.9%) patients
with bacteria resistant to third generation
cephalosporins (MRSA n=22, resistant AGNB
n=27).
The administration of third generation
cephalosporins was modified on clinical grounds in
two of the 70 patients who were normal carriers and
infected on admission to the ICU (2.9%) (Table 3).
In contrast, the abnormal carriers infected on
admission required changing 36 times in 67 patients
(53.7%) (P <0.0001).
Analysis of risk factors for abnormal carriage
Antibiotics were administered on the wards
before admission to the ICU in 196 (60%) patients
(Table 1) and 82 (41.8%) carried ceftazidime
resistant AGNB. The most common antimicrobials
employed were beta-lactams (63%), followed
by quinolones (11%), glycopeptides (8%) and
metronidazole (8%).
Abnormal carriage on admission to the ICU
was associated with previous antibiotic usage
(OR 3.24; 95% CI 2 to 5.26) and infection on
admission to the unit (OR 1.7; 95% CI 2 to 5.26)
at univariate analysis. The multivariate analysis
demonstrated that only previous antibiotic treatment
was associated with abnormal carriage (OR 3.5;
95% CI 2.1 to 5.8).
DISCUSSION
Four findings emerge from this prospective
observational cohort study including 621 severely ill
patients over approximately five years:
•• Thirty percent of the study population carried
abnormal flora on arrival to ICU; 22 and 11%
carried AGNB and MRSA, respectively. AGNB
and MRSA carriers were significantly more
present in the hospital group than in the
community group.
•• Overgrowth of both ‘normal’ and ‘abnormal’ flora
was present on admission; 70.8 and 83.5% of
the patients who had overgrowth of normal and
abnormal potential pathogens, respectively,
developed primary endogenous infections.
•• Bacteria resistant to third generation
cephalosporins used as the parenteral component
of SDD, including MRSA and AGNB, were
present in surveillance cultures to a higher extent
(threefold) than in the diagnostic samples.
•• Antibiotic usage before the admission to the
ICU was found to be a risk factor for abnormal
carriage.
The patients who were admitted to the ICU as
abnormal carriers belonged mainly to the population
referred to the unit from the wards (75%) (Table 3).
MRSA and AGNB carriers were significantly more
common in the hospital group. Although the hospital
group was significantly older and included more
medical patients, known to suffer from chronic
underlying diseases, than the community group,
the multivariate analysis failed to confirm illness
severity as a risk factor for abnormal carriage. Only
previous antibiotic usage was shown to promote
abnormal carriage in the multivariate analysis.
This study showed that the parenteral component
of SDD, i.e. cefotaxime or ceftazidime, was not
modified in the majority of patients admitted to the
ICU with normal flora and developing a subsequent
infectious episode. The immediate administration
of broad-spectrum antimicrobials on admission
has been shown to improve survival21,22 and recent
literature recommends a broad-spectrum antibiotic
combination, to cover multi-resistant AGNB and
MRSA in patients admitted from the hospital23,24.
Our study shows that only a subset of patients with
previous antimicrobial treatment requires broad-
spectrum antibiotics, as patients from the community
and without previous antibiotic treatment were
admitted to the ICU carrying normal flora.
Abnormal carriers of AGNB and MRSA had
overgrowth concentrations on ICU admission.
Overgrowth has been shown to be an independent
risk factor for both pneumonia and septicaemia36-39.
For example, once P. aeruginosa is present ≥105
in the oropharynx the chance that identical
Pseudomonas is isolated from the lower airways is
50%40. In a pancreatitis study gut overgrowth was
associated with infection of the necrotic tissue of
the pancreas37. There was a significant correlation
between overgrowth of MRSA in the surveillance
Anaesthesia and Intensive Care, Vol. 38, No. 2, March 2010
 Admission surveillace cultures in ICU
cultures and diagnostic samples positive for MRSA
in a recent epidemiological study38. Small intestinal
overgrowth is required for yeasts to translocate
through the gut mucosa lining into the gut-
associated lymphoid tissue and blood39. Our data
show that the subset of patients with overgrowth on
admission is at risk of primary endogenous infection
of internal organs. Control of overgrowth using
enteral polymyxin/tobramycin, and amphotericin B
or nystatin, with or without vancomycin, has been
shown to prevent colonisation and infection of
internal organs by potential pathogens37-39. A recent
meta-analysis of randomised controlled trials
confirms that a short course of a parenteral
antibiotic combined with enteral antimicrobials
significantly reduces pneumonia (OR 0.35; CI
0.29 to 0.41) and mortality (OR 0.78; CI 0.68 to
0.89)26. In our study cefotaxime or ceftazidime
were administered for four days as the parenteral
component of SDD. Additionally, the enteral
component of SDD was equally effective in both
normal and abnormal carriers as the incidence
of secondary endogenous infections was low, i.e.
12.4% and 9.7%, respectively.
In this study, 22% of the total population were
carriers of resistant bacteria in their throat and
gut admission flora, while 7.9% had diagnostic
cultures positive for resistant bacteria, showing that
surveillance swabs are more sensitive for the
identification of the abnormal and resistant micro-
organisms, especially when diagnostic samples are
negative. Our observation confirms the results of an
American study in which 18% of patients carried
resistant AGNB in their admission flora, while only
5% of patients had resistant AGNB in diagnostic
cultures18.
Previous antibiotic usage has been recognised to
promote abnormal carriage with resistant AGNB
and MRSA. Hence, ceftazidime, as the parenteral
component of SDD, may be less useful and may
require adjusting into more broad-spectrum
antibiotics, to cover resistant strains causing
infections on admission. Most SDD trials
employed cefotaxime; parenteral ceftazidime was
administered in two trials41,42 and fluoroquinolones
in three studies43-45. After finishing this study we
have decided to adjust the parenteral component of
SDD by replacing ceftazidime with imipenem plus
vancomycin only in patients who received
antimicrobials before admission to the ICU due
to the presence of MRSA and pseudomonal
resistance problems on the wards of our hospital.
The addition of enteral antibiotics cleared carriage
of resistant bacteria on our intensive care resulting
Anaesthesia and Intensive Care, Vol. 38, No. 2, March 2010
333
in the interesting observation that the wards of our
hospital have a higher resistance problem compared
with the ICU.
We acknowledge that the results of this study may
not be generalisable to different clinical settings, as
the microbial ecology of the community and wards
may be different from our cohort. However, this
study showed that the knowledge of the patient’s
carrier state on ICU admission is important for the
distinction between normal and abnormal carriage,
resistance at an early stage and subsequent
appropriate antibiotic therapy. Furthermore, the
knowledge of abnormal resistant carriage at an
early stage could be relevant for the application of
preventive strategies, i.e. the isolation of patients
carrying multi-resistant strains and high levels of
hygiene.
CONCLUSIONS
Our study shows that the knowledge of carriage
using surveillance cultures is useful to the intensivist
for three reasons. First, surveillance cultures allowed
identification of abnormal carriage and resistant
strains at an early stage, particularly when diagnostic
samples were negative. Second, third generation
cephalosporins used as the parenteral component
of SDD were effective in about 80% of the studied
population avoiding the immediate administration of
broad-spectrum antimicrobials. Systemic antibiotics
were modified mainly in the abnormal flora group
who received antibiotic therapy before ICU
admission. Third, our finding of overgrowth being
present on admission may justify the immediate
administration of enteral antibiotics as part of SDD.
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