Results
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 development time of VAP, no difference in the patient's age, gender, underlying diseases, causes of mechanical ventilation, a history of antibiotic medication and hospitalization in preceding 90 days, and mortality was found between the two groups. The time interval from mechanical ventilation to the occurrence of VAP was shown to be median 4 days (IQR, 4~5 days) and median 10 days (IQR, 7~15 days) in the early and late 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 different bacteria were cultured simultaneously in 12 patients (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 development time, S. aureus was first identified, and subsequently A. baumanii was identified in three patients. S. aureus, and subsequently Stenotrophomonas maltophilia, A. baumanii and subsequently P. aeruginosa, K. pneumoniae and subsequently P. aeruginosa were identified 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 identified 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%), respectively, for the late VAP group. There were no difference 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, respectively.
As for the drug-resistant pathogens among the isolated bacteria, all S. aureus belonged to methicillin resistance S. aureus (MRSA). Sixty nine percent (22/32) of A. baumanii was imipenem-resistant. No difference in the imipenem-resistant A. baumanii was found between 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) positivity rate of 67% (4/6). Two pathogens identified from the early VAP group were all negative for ESBL, whereas four pathogens identified from the late VAP group were all positive for ESBL.
Discussion
In this study, S. aureus was shown to be the most common causative pathogen of VAP at ICU, and A. baumanii, P. aeruginosa, S. maltophilia, K. pneumonia, and Serratia marcescens followed S. aureus in that order. No difference in the causative pathogens was found between 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 provided to patients with VAP
18. Thus, before the identification of causative pathogens, antibiotic selection is performed to target causative pathogens mainly identified in the corresponding region. However, most studies on causative pathogens have been conducted in western countries, and few studies have been conducted in Korea. According to the SENTRY antimicrobial 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, followed by
P. aeruginosa (21%),
Enterobacter species (9%), and
Acinetobacter species (4.4%) in that order
11. 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 nosocomial pneumonia in Korea, and
Acinetobacter species (16%),
P. aeruginosa (14%), and
K. pneumoniae (9%) followed
S. aureus in that order
17. Although this was different from the result of foreign studies, it was similar to the result of this study. Thus, in Korea, causative pathogens of VAP are likely to occur at the aforementioned frequency.
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 specificity
19. However, as bronchoscopy 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 divided into the definite, probable, and possible pathogens, followed by comparative analysis to investigate their role as causative pathogens of VAP
17. In the case of the definite pathogens with the highest possibility of being causative pathogens,
S. aureus was the most common causative pathogen, and
A. baumanii and
P. aeruginosa followed
S. aureus in that order, which was similar to the overall result. Thus, these pathogens are likely 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 bacteria 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 intubation, multidrug-resistant bacteria such as
P. aeruginosa,
A. baumanii, and MRSA are main causative pathogens
10,15. 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 previous studies, and might be associated with a local increase in drug-resistant bacteria. The recent study on nosocomial pneumonia in Asia including Korea also reported that
Acinetobacter species,
P. aeruginosa,
S. aureus, and
K. pneumoniae were the most common pathogens identified from both early and late nosocomial pneumonia
17. Thus, it could be possible that VAP that occur in Korea are antibiotic resistant pneumonia although 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 hospitalization (40%). Thus, drug-resistant bacteria might have been identified from the early VAP group.
The recent study on the causative pathogens of nosocomial 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 antibiotics
11,17. In particular, the imipenem-resistance rate of
Acinetobacter 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 imipenem-resistance rate of
Acinetobacter species in Korea due to only a small specimen number of 29 Korean cases in this study
17. 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. baumanii was reported to be 51%
20, and the carbapenem-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 causative pathogens of VAP may vary depending on country, region, and hospital. If information on the causative pathogens of VAP is available, it could increase the possibility of appropriate antibiotic therapy, thereby reducing the mortality and improving the prognosis. In summary, this study was conducted to investigate the causative pathogens of VAP in a tertiary referral hospital. As a result, S. aureus and A. baumanii were shown to be the most common and second commonest causative pathogens of VAP, respectively.