Tuberc Respir Dis 2012;73:32-37
CopyrightⒸ2012. The Korean Academy of Tuberculosis and Respiratory Diseases. All rights reserved.
Bacterial Pathogens of Ventilator Associated Pneumonia in a Tertiary
Su Young Chi, M.D., Tae Ok Kim, M.D., Chan Woo Park, M.D., Jin Yeong Yu, M.D., Boram Lee, M.D., Ho
Sung Lee, M.D., Yu Il Kim, M.D., Sung Chul Lim, M.D., Yong Soo Kwon, M.D.
Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
Background:Background: This study evaluates the bacterial pathogens of Ventilator-associated pneumonia (VAP) in a tertiary
Methods: Methods: A total of 109 bacterial pathogens from 91 adult patients with VAP, who were admitted to the medical
intensive care unit from January 2008 to December 2009, were examined. Clinical characteristics, bacterial
pathogens, and resistance profiles were analyzed.
Results:Results: Staphylococcus aureus (44%) was the most frequently isolated. Acinetobacter baumanii (30%), Pseudo-
monas aeruginosa (12%), Stenotrophomonas maltophilia (7%), Klebsiella pneumoniae (6%), and Serratia marcescens
(2%) were isolated from the transtracheal aspirates or bronchoalveolar lavage in patients with VAP. There was
no significant difference of bacterial pathogens between early and late onset VAP. All isolated S. aureus were
methicillin resistant S. aureus; the imipenem resistance rate of A. baumanii was 69%.
Conclusion:Conclusion: The two most frequent pathogens of VAP were S. aureus and A. baumanii. There were no pathogenic
differences between early and late onset VAP.
Key Words:Key Words: Pneumonia, Ventilator Associated; Staphylococcus aureus ; Acinetobacter baumanii
Address for correspondence: Yong Soo Kwon, M.D.
Department of Internal Medicine, Chonnam National Uni-
versity Medical School, 42, Jebong-ro, Dong-gu, Gwangju
Phone: 82-62-220-6575, Fax: 82-62-225-8578
Received: Mar. 21, 2012
Revised: Apr. 6, 2012
Accepted: May 30, 2012
CC It is identical to the Creative Commons Attribution Non-Commercial
Ventilator associated pneumonia (VAP) occurs 48
hours after intubation and mechanical ventilation. It is
a common infectious disease that is found in intensive
care unit (ICU), which occurs in 8∼38% of patients
who underwent mechanical ventilation1. The incidence
of pneumonia has been known to be higher in ICU pa-
tients than in general ward patients, and even 3∼
10-fold higher in patients who underwent mechanical
ventilation2-9. In addition, the mortality of VAP has been
reported to be 24~76%, which is higher than those of
other hospital acquired infections10.
Common causative pathogens of VAP include Gram-
negative bacteria such as Pseudomonas aeruginosa,
Escherichia coli, Klebsiella pneumoniae, and Acineto-
bacter species, and Gram-positive bacteria such as
Staphylococcus aureus9-14. As the type of causative
pathogens and the rate of drug-resistant pathogens may
vary depending on region and hospital, data of micro-
bial surveillance are required for each region. As most
studies on causative pathogen, however, have been
conducted in western counties, domestic data are
insufficient. Accordingly, this study was conducted to
investigate the bacterial pathogens of VAP in a domestic
tertiary referral hospital.
Materials and Methods
This study was conducted on 104 patients who sat-
Tuberculosis and Respiratory Diseases Vol. 73. No. 1, Jul. 2012
isfied the diagnostic criteria of VAP via the retrospective
analysis of their medical records and diagnostic results
among 713 patients who underwent intubation and me-
chanical ventilation in the ICU of the department of in-
ternal medicine, Chonnam National University Hospital
from January 1st, 2008 to December 31st, 2009. Thirteen
patients who had unknown causative pathogens were
excluded among the 104 patients.
Pneumonia was diagnosed by chest radiograph and
clinical and laboratory findings. If the patients, who had
a new pulmonary infiltration, satisfied 2 or more con-
ditions among the cases of body temperature 38.3oC or
higher, purulent bronchial secretions, and a leukopenia
or leukocytosis (＜4,000 or ＞11,000 mm3), they were
diagnosed with pneumonia15. The patient's age, gender,
a history of antibiotic therapy before hospitalization, a
history of hospitalization in other hospitals, concurrent
diseases, causes of mechanical ventilation, causative
pathogens, antibiotic resistances, and mortality were ret-
rospectively examined. The subjects were divided into
two groups according to the development time of VAP:
early VAP group where VAP occurred within 5 days af-
ter mechanical ventilation and late VAP group where
VAP occurred 5 days or later after mechanical ventila-
tion. A comparative analysis was conducted between
the two groups10,15.
2. Microbiologic analysis
Specimens were collected from all patients with the
suspected pneumonia via transtracheal aspirate (TTA) or
bronchoalveolar lavage (BAL) before antibiotic admin-
istration, followed by qualitative or quantitative culture.
In the cases of deterioration via a chest radiograph, per-
sistent fever, or worsening of PaO2/FiO2 rate even after
antibiotic administration, antibiotics were changed.
Specimens were again collected from the patients via
TTA or BAL before antibiotic change, followed by
culturing. VITEK device (Vitek-120; Biomerieux, St.
Louis, MO, USA) was used for culturing, and antibiotic
susceptibility test was conducted in accordance with the
National Committee for Clinical Laboratory Standard
The isolated bacteria were classified into causative
pathogens according to the followings17: 1) definite
pathogen: if bacteria from the blood culture and those
from TTA or BAL specimens are identical; 2) probable
pathogen: if qualitative culture has 105 colony-forming
unit (CFU)/mL or more in TTA specimens or 104
CFU/mL or more in BAL specimens; 3) possible patho-
gen: if bacteria are cultured from the TTA specimen via
a qualitative culturing method.
3. Statistical analysis
Median and interquartile range (IQR) were used for
continuous variables, whereas frequency and percentile
were used for the remaining variables. Pearson's Chi-
square test or Fisher's exact test was conducted for pa-
tient's age, concurrent diseases, causes of mechanical
ventilation, and a history of antibiotic medication in pre-
ceding 90 days, a history of hospitalization, and causa-
tive pathogens of VAP. Mann-Whitney U test was con-
ducted for the patient's age and interval from mechan-
ical ventilation to the development of VAP. If p＜0.05,
it was considered statistically significant.
1. Clinical features of the patients
The median age of the patients was 69 years (IQR,
56∼77 years). The male patients accounted for 68% of
the total subjects. VAP occurred median 7 days (IQR,
5∼13 days) after mechanical ventilation. Pulmonary
diseases were the most common cause of mechanical
ventilation, which accounted for 42%. The in-hospital
mortality was 40%. When the patients were divided into
the early and late VAP groups according to the develop-
ment time of VAP, no difference in the patient's age,
gender, underlying diseases, causes of mechanical ven-
tilation, a history of antibiotic medication and hospital-
ization in preceding 90 days, and mortality was found
between the two groups. The time interval from me-
chanical ventilation to the occurrence of VAP was
shown to be median 4 days (IQR, 4∼5 days) and me-
dian 10 days (IQR, 7∼15 days) in the early and late
SY Chi et al: Pathogens of ventilator associated pneumonia
Table 1. Baseline characteristics of patients with VAP depending on development time
Variables Total (n=91) Early VAP (n=26)Late VAP (n=65)p-value
Chronic lung disease
Chronic renal disease
Chronic liver disease
Cause of mechanical ventilation
Sepsis other than pneumonia
Antibiotics therapy in the preceding 90 days
Hospitalization for 2 or more days in the preceding 90 days
43 (66) 0.623
Values are presented as the median (first quartile∼third quartile) or number (%).
VAP: ventilator-associated pneumonia; DM: diabetes mellitus.
VAP groups, respectively (Table 1).
2. Causative pathogens of VAP
A total of 109 bacteria were identified from 91
patients. Two or more bacteria were identified from 18
patients, and no difference was found between the early
and late VAP groups (3/26 vs. 15/65, p=0.257). Among
the 18 patients who had two or more bacteria, the dif-
ferent bacteria were cultured simultaneously in 12 pa-
tients (67%), and time-dependent changes were shown
in six patients (33%). No difference was found between
the early and late VAP groups (p=1.000). As for the
changes in bacterial identification according to develop-
ment time, S. aureus was first identified, and sub-
sequently A. baumanii was identified in three patients.
S. aureus, and subsequently Stenotrophomonas malto-
philia, A. baumanii and subsequently P. aeruginosa, K.
pneumoniae and subsequently P. aeruginosa were iden-
tified in one patient, respectively.
The most commonly identified bacteria was shown to
be S. aureus, which accounted for 44%. A. baumanii,
P. aeruginosa, S. maltophilia, K. pneumoniae, and
Serratia marcescens followed S. aureus in that order.
However, no difference in the frequency of the identi-
fied bacteria was found according to the onset time of
VAP (Table 2).
One hundred nine causative pathogens were divided
into the definite, probable, and possible pathogens: 5
(19%), 0 (0%), and 21 (81%), respectively, for the early
VAP group, and 7 (11%), 11 (17%), 47 (72%), re-
spectively, for the late VAP group. There were no differ-
ence between the late VAP group and the early VAP
group (p=0.061). Among 12 cases of definite pathogen,
S. aureus (6 cases, 50%) was the most commonly found,
and A. baumanii, and P. aeruginosa were identified in
two cases, respectively, and K. pneumoniae, and S.
maltophilia were shown in identified in one case,
As for the drug-resistant pathogens among the iso-
lated bacteria, all S. aureus belonged to methicillin re-
sistance S. aureus (MRSA). Sixty nine percent (22/32)
of A. baumanii was imipenem-resistant. No difference
Tuberculosis and Respiratory Diseases Vol. 73. No. 1, Jul. 2012
Table 2. Organisms isolated from patients with VAP depending on development time
Organisms Total (n=109) Early VAP (n=29) Late VAP (n=79) p-value
Values are presented as the number (%).
VAP: ventilator-associated pneumonia; MRSA: methicillin resistance Staphylococcus aureus.
in the imipenem-resistant A. baumanii was found be-
tween the early and late VAP groups (73% [8/11] vs.
67% [14/21], p=1.000). K. pneumoniae was shown to
have an extended spectrum beta-lactamase (ESBL) pos-
itivity rate of 67% (4/6). Two pathogens identified from
the early VAP group were all negative for ESBL, where-
as four pathogens identified from the late VAP group
were all positive for ESBL.
In this study, S. aureus was shown to be the most
common causative pathogen of VAP at ICU, and A. bau-
manii, P. aeruginosa, S. maltophilia, K. pneumonia, and
Serratia marcescens followed S. aureus in that order. No
difference in the causative pathogens was found be-
tween the early and late VAP groups according to the
development time of VAP.
VAP is one of serious complications that occur at
ICU. As its causative pathogens are antibiotic resistant
in many cases, it is difficult to select appropriate
antibiotics. In addition, the mortality has been reported
to increase if an early antibiotic treatment is not pro-
vided to patients with VAP18. Thus, before the identi-
fication of causative pathogens, antibiotic selection is
performed to target causative pathogens mainly identi-
fied in the corresponding region. However, most stud-
ies on causative pathogens have been conducted in
western countries, and few studies have been con-
ducted in Korea. According to the SENTRY anti-
microbial surveillance program operated in US, Europe,
and South America, P. aeruginosa (27%) is the most
common causative pathogen taken all regions together,
and S. aureus (20%), and Acinetobacter species (14%)
follow P. aeruginosa in that order. In the US, S. aureus
(32%) is the most common causative pathogen, fol-
lowed by P. aeruginosa (21%), Enterobacter species
(9%), and Acinetobacter species (4.4%) in that order11.
Meanwhile, according to a recent study on the causative
pathogens of nosocomial pneumonia in Asia, S. aureus
(27%) was the most common causative pathogen of no-
socomial pneumonia in Korea, and Acinetobacter spe-
cies (16%), P. aeruginosa (14%), and K. pneumoniae
(9%) followed S. aureus in that order17. Although this
was different from the result of foreign studies, it was
similar to the result of this study. Thus, in Korea, causa-
tive pathogens of VAP are likely to occur at the afore-
It is uneasy to conduct the microbiological diagnose
of VAP. A quantitative culture test of lower airway
specimens via bronchoscopy has been reported to have
high sensitivity and specificity19. However, as broncho-
scopy has not been conducted in all patients in this
study, the pathogens, which were identified according
to the method of the recent study on the causative
pathogen of nosocomial pneumonia in Asia, were div-
ided into the definite, probable, and possible patho-
gens, followed by comparative analysis to investigate
their role as causative pathogens of VAP17. In the case
of the definite pathogens with the highest possibility of
being causative pathogens, S. aureus was the most com-
mon causative pathogen, and A. baumanii and P. aeru-
SY Chi et al: Pathogens of ventilator associated pneumonia
ginosa followed S. aureus in that order, which was sim-
ilar to the overall result. Thus, these pathogens are like-
ly to be the main causative pathogens of VAP.
Causative pathogens of VAP has been known to vary
depending on the development time of VAP. In the case
of early VAP that occurs within 5 days after mechanical
ventilation following intubation, antibiotic sensitive bac-
teria such as S. aureus, Streptococcus pneumoniae, and
Haemophilus influenzae are main causative pathogens.
Meanwhile, in the case of late VAP that occur 5 days
or later after mechanical ventilation following in-
tubation, multidrug-resistant bacteria such as P. aerugi-
nosa, A. baumanii, and MRSA are main causative patho-
gens10,15. In this study, no difference in the causative
pathogens was found between the early and late VAP
groups. This was inconsistent with the results of pre-
vious studies, and might be associated with a local in-
crease in drug-resistant bacteria. The recent study on
nosocomial pneumonia in Asia including Korea also re-
ported that Acinetobacter species, P. aeruginosa, S. aur-
eus, and K. pneumoniae were the most common patho-
gens identified from both early and late nosocomial
pneumonia17. Thus, it could be possible that VAP that
occur in Korea are antibiotic resistant pneumonia al-
though they belong to early VAP. However, the result
of this study might be attributable to the fact that most
patients of this study had a previous history of antibiotic
medication (78%) and some had of recent hospital-
ization (40%). Thus, drug-resistant bacteria might have
been identified from the early VAP group.
The recent study on the causative pathogens of noso-
comial pneumonia in Asia reported that A. baumanii,
the second commonest causative pathogen of VAP in
this study, more commonly occurred compare to US or
Europe, and that it was resistant to many antibiotics11,17.
In particular, the imipenem-resistance rate of Acineto-
bacter species was more than 80% in Thailand,
Malaysia, and India, and 28% in Korea. Although the
overall imipenem-resistance rate was reported to be
high in Asia, the rate was relatively low in Korea.
However, this rate could not represent general imipe-
nem-resistance rate of Acinetobacter species in Korea
due to only a small specimen number of 29 Korean cas-
es in this study17. The Korean Nationwide Surveillance
of Antimicrobial Resistance (KONSAR) was shown to
have the largest subject number. According to the
KONSAR where drug susceptibility test was conducted
in 24 hospitals, the imipenem-resistance rate of A. bau-
manii was reported to be 51%20, and the carbape-
nem-resistance rate of A. baumanii identified in the ICU
of a university hospital was reported to be 53%
(26/49)21. In this study, the imipenem-resistance rate
was shown to be 69%. Thus, the imipenem-resistance
rate of A. baumanii is expected to be high in Korea.
VAP is a fatal disease with a high mortality. The caus-
ative pathogens of VAP may vary depending on coun-
try, region, and hospital. If information on the causative
pathogens of VAP is available, it could increase the pos-
sibility of appropriate antibiotic therapy, thereby re-
ducing the mortality and improving the prognosis. In
summary, this study was conducted to investigate the
causative pathogens of VAP in a tertiary referral hos-
pital. As a result, S. aureus and A. baumanii were
shown to be the most common and second commonest
causative pathogens of VAP, respectively.
This study was supported by a grant (CRI11004-1) of
the Chonnam National University Hospital Research
Institute of Clinical Medicine.
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