Risk Factors Associated with Ventilator-associated Pneumonia

Incidence in the Intensive Care Unit at Haji Adam Malik

General Hospital, Medan, Indonesia

Miranda

, Achsanuddin Hanafie

, Rina Yunita

Tropical Medicine Program Faculty Medicine, Universitas Sumatera Utara, Jl Dr. Mansur No 5 Medan 20155,

Departement of Anesthesiology and Intensive Therapy, Haji Adam Malik General Hospital, Medan, Indonesia.

Departement of Mycrobiology, Faculty of Medicine, Universitas Sumatera Utara, Medan Indonesia.

Keywords: Ventilator-Associated Pneumonia, pneumonia, nosocomial, risk factors, Indonesia

Abstract: Ventilator-associated pneumonia (VAP) is defined as nosocomial pneumonia that occurs 48 hours after

using mechanical ventilation. The primary objective of this study is to investigate the risk factors associated

with the incidence of VAP. The secondary objective is to identify the pattern of bacterial sensitivity in

confirmed VAP cases. A retrospective study was conducted in the intensive care unit at Haji Adam Malik

General Hospital, Medan. Data of 60 patients with and without VAP diagnosis between March 2017 and

October 2018 were evaluated. The most common cause of infection was Klebsiella pneumonia (36.7%),

with 90.9% were sensitive to Amikacin. Majority of patients were (76.6%, 46/60) aged < 60 years, used

ventilator longer than 5 days (68.3%, 41/60) and with the smoking habit (53.5%, 32/60). We found no

association between age, duration of ventilator and smoking habit with the increased incidence of VAP.

Further study with a larger sample size may be needed to find the associations.

1 INTRODUCTION

Ventilator Associated pneumonia (VAP) is defined

as pneumonia occurring 48 hours after the initiation

of endotracheal intubation and mechanical

ventilation (MV)

(PDPI, 2003; Goel E et al., 2012;

Widyaningsih R and Buntaran L, 2012; Hezati M E

et al., 2015). The use of endotracheal tube increased

the risk of infectious agents to gain direct access to

the lower respiratory tract leading to pneumonia

(Kalanuria A et al., 2014).

VAP is classified into

early onset (<5 days) and late onset (≥5 days). Early

onset is usually caused by sensitive pathogens, while

late onset is due to multidrug resistance microbial

(Sedwick M B et al., 2012)

Clinical assessment,

physical examination and radiographic images

incorporated in the clinical pulmonary infection

scoring (CPIS) is the most common tool used to

predict the occurrence of VAP.

A systematic review of 51 prospective

randomized trial described the incidence of VAP

was 22,8% (Yunita R and Rondhianto W,2015), and

86% of all cases were due to nosocomial infections

(Wahyuning Tyas et al., 2013). VAP was associated

with increased morbidity and mortality, prolonged

hospital stay and patient cost (Koenig S M and

truwit J D, 2006). The incidences of VAP in other

countries varied from 9% to 27% (Chawla, 2008)

while there are no definite incidence rates reported

from Indonesia. High mortality ranging from 24% to

50% has been associated with the presence of

antimicrobial resistance particularly in cases of

Pseudomonas aeruginosa, Acinetobacter baumanii,

Klebsiella, and Enterobacter spp. The wide use of

antimicrobials, the presence of comorbidity and

prolonged used of mechanical ventilator facilitated

the development of antimicrobial resistance

(Resende M et al.,2013). Studies have reported

factors including prior intravenous antibiotic use

within the previous 90 days, septic shock at time of

VAP diagnosis, acute respiratory distress syndrome

(ARDS) preceding VAP, hospitalization > 5 days

prior to the occurrence of VAP, and acute renal

replacement therapy prior to VAP onset to be the

main factors associated with VAP.

There are several risk factors affecting the

development of VAP. Some of these risk factors

may have already been presented at admission to the

Intensive Care Unit (ICU), such as advanced age,

Miranda, ., Hanaﬁe, A. and Yunita, R.

Risk Factors Associated with Ventilator-associated Pneumonia Incidence in the Intensive Care Unit at Haji Adam Malik General Hospital, Medan, Indonesia.

DOI: 10.5220/0009863902370242

In Proceedings of the 2nd International Conference on Tropical Medicine and Infectious Disease (ICTROMI 2019), pages 237-242

ISBN: 978-989-758-469-5

237

presence of respiratory or cardiovascular system

disease, organ failure, burns, trauma, acute

respiratory distress syndrome (ARDS), gastric

colonization, sinusitis, high volume gastric

aspiration, and seasonal change (Ziyaettin K R I et

al., 2018) . Age is one of the main factors

influencing the VAP events. Susanti et al. described

that the older the age of the patients treating by a

ventilator, the greater the risk to develop VAP. This

is because the age older than 60 years old has a

greater risk of suffering pneumonia in the use of a

mechanical ventilator in the ICU and there is a

decrease in the body’s immune function (Susanti E

et al., 2013)

Another factor influencing VAP events is the

duration of mechanical ventilator used. Mechanical

ventilation is a machine to perform some or all of

the work of breathing and an essential aspect of

critical patient care (Clare M V and Dacvecc H K,

2005). Therefore, identification of risk factors

associated with VAP is needed to implement

preventive measures and to reduce mortality as the

outcome of VAP. In this study, we aimed to evaluate

the association between risk factors and the

incidence of VAP among intensive care unit patients

in Haji Adam Malik General Hospital in Medan,

Indonesia.

2 METHODS

Data from 60 ICU patients admitted at Haji Adam

Malik Hospital between March 2017 and October

2018 was collected (see table 1). CPIS form was

used to assess risk factors and information on VAP.

VAP diagnosis was made by the ICU doctors based

on the following criteria: at least two of the

following points, fever of ≥ 38°C, leukocytosis of

10.000/mm

or more, and purulent respiratory

secretions; with chest radiograph showing new,

persistent pulmonary

infiltrates. The diagnosis was

confirmed by sputum culture at the microbiology

laboratory (see table 2).

Inclusion criteria were patients aged more than

18 years old and intubated and mechanically

ventilated for more than 48 hours. Exclusion criteria

included patients with underlying diseases

(tuberculosis, malignancy, chronic obstructive

pulmonary diseases, and pneumonia).

The study was reviewed and approved by the

ethics committee at the Faculty of Medicine,

Universitas Sumatera Utara.

Table 1: Demographic characteristics of research subjects

in ICU

Characteristics n = 60 (%)

Gender, n (%)

Male 35 (58.3)

Female 25 (41.7)

Age (years)

<60 46 (76.7)

≥60 14 (23.3)

Duration of ventilator used

(days)

> 5 41 (68.3)

≤ 5 19 (31.7)

Education level,

Primary school 12 (20.0)

Junior high school 7 (11.7)

High school 38 (63.3)

University 3 (5.0)

Occupation

Private sectors 28 (46.7)

Midwife 16 (26.7)

Farmer 6 (10.0)

Trader 3 (5.0)

Fisherman 2 (3.3)

Government officers 2 (3.3)

Student 2 (3.3)

Retired 1 (1.7)

Smoking habits

Yes 32 (53.3)

No 28 (46.7)

Table 2 : Clinical Pulmonary Infection Score (CPIS)

Component

Score

Temperature (

C) 36,5 - 38,4

38,5 - 38,9

<36 and >39

Blood Leukocytes

(/mm

)

4000-11000

< 4000 atau > 11000

> 500 cells band

Tracheal

secretions

None

Few or non purulent

Purulent

Oxygenation PaO

/FiO

mmHg

>120 or ARDS

< 240 and absence

of ARDS

Chest radiograph No, infiltrate

Patchy or diffuse

infiltrate

Localized infiltrate

ICTROMI 2019 - The 2nd International Conference on Tropical Medicine and Infectious Disease

238

3 RESULTS

Sixty patients were enrolled in the study. Of those,

30 was patients diagnosed with VAP and 30 was not

identified as VAP cases. Baseline characteristics are

shown in Table 1. Thirty-five patients (58.3%) was

male, and 46 (76.7%) aged younger than 60 years

old. The duration of mechanical ventilation use

longer than 5 days occurred in 41 patients (68.3%).

None of the risk factors assessed in this study

increased the risk of VAP incidence in the ICU

(Table 3); being male (OR 1.115, 95% CI 0.364-

3.628, P=0.793), aged > 60 years old (OR 0.688,

95% CI 0.168-2.695, P=0.542), ventilator used

longer than 5 days (OR 1.592, 95% CI 0.465-5.573,

P=0.405), and had smoking habit (OR 1).

Furt

hermore, 30 patients confirmed with VAP

had bacterial growth in culture (See table 4) with

Klebsiella pneumonia (N=11) as the most common

organism, followed by Acinetobacter baumannii

(N=8) and Pseudomonas aeruginosa (N= 4).

Sensitivity test showed amikacin to be sensitive to

K. pneumonia infection (90.9%).

The evaluation of sensitivity and antibiotic

resistance on the pathogens are described in Table 5.

Nine antibiotics were still sensitive against P.

aeruginosa

including ceftazidime, amikacin,

ceftriaxone, meropenem, ertapenem, cefazoline,

cefixime, ciprofloxacin, and a

ztreonam. While there

were 14 antibiotics that were highly resistant to P.

aeruginosa.

Sensitivity analysis on K

. pneumoniae showed

12 antibiotics were still sensitive including

amikacin, ertapenem, meropenem, gentamycin,

ciprofloxacin, cefoperazone/sulbactam, ceftazidime,

amoxicillin/ clavulanic acid, levofloxacin,

tetracycline, tigecycline, and polymixin B. Fourteen

antibiotics showed resistance to K. pneumoniae (see

table 5).

The analysis also showed that amikacin,

ertapenem, meropenem, polymixin B, ceftazidime,

ciprofloxacin and piperacillin/tazobactam to be

sensitive to A. baumannii (see table 5)

Table 3: Relationship between risk factors with VAP in the ICU at Haji Adam Malik General Hospital, Medan, Indonesia

Variables

VAP

(95% CI)

Cases

(n=30)

Controls

(n=30)

Age, (Year)

≥ 60 6 (20.0) 8 (16.7) 0.688

(0.168-2.695)

0,542

< 60 24 (80.0) 22 (73.3)

Duration of ventilator used, (days)

> 5 22 (73.3) 7 (63.3) 1.592

(0.465-5.573)

0,405

≤ 5 8 (26.7) 3 (36.7)

Smoking habits

Yes 16 (53.3) 16 (53.3) 1

(0.322-3.109)

1,000

No 14 (46.7) 14 (46.7)

Table 4: Bacterial profile of patients diagnosed with VAP

Bacterial isolated N %

Klebsiella pneumonia 11 36,7

Acinetobacter baumanii 8 26,7

Pseudomonas aeruginosa 4 13,3

Staphylococcus aureus 3 10.0

Enterobacter cloacae 2 6,7

Elizabethkinqia meni 1 3,3

Raoultella ornithine 1 3,3

Total 30 100,0

Risk Factors Associated with Ventilator-associated Pneumonia Incidence in the Intensive Care Unit at Haji Adam Malik General Hospital,

Medan, Indonesia

239

Table 5: Antibiotic sensitivity and resistance to bacteria caused VAP in ICU Haji Adam Malik General hospital

Antibiotic

S I R S I R S I R

Amikasin 90,9 9,1 0 75 0 25 50 0 50

Ampicillin 0 54,5 45,5 0 87,5 12,5 0 100 0

Ampicillin/Sulbaktam 0 54,5 0 0 87,5 12,5 0 100 0

Cefazolin 0 36,4 63,6 0 50 50 25 25 50

Cefixim 0 45,5 54,5 0 75 25 25 75 0

Ceftazidime 9,1 36,4 0 12,5 12,5 75 100 0 0

Ceftriaxone 0 27,3 72,7 0 25 75 50 50 0

Ertapenem 81,8 0 18,2 25 12,5 62,5 50 0 50

Meropenem 81,8 0 18,2 25 12,5 62,5 50 0 50

Ciprofloxacin 27,3 0 18,2 12,5 62,5 25 25 75 0

Erithromycin 0 100 0 0 100 0 0 100 0

Gentamycin 36,4 45,5 18,2 0 100 0 0 75 25

Lefofloxacin 9,1 81,8 9,1 0 87,5 12,5 0 100 0

Netilmicin 0 90,9 9,1 0 100 0 0 100 0

Tetracycline 9,1 81,8 9,1 0 100 0 0 50 50

Vancomycin 0 100 0 0 100 0 0 100 0

Trimthoprime/Sulfamethoxazole 0 90,9 9,1 0 87,5 12,5 0 50 50

Aztreonam 0 90,9 9,1 0 100 0 25 75 0

Fosfomycin 0 100 0 0 100 0 0 100 0

Amoxicillin/Clavulanic Acid 9,1 90,9 0 0 100 0 0 100 0

Polymixin B 9,1 90,9 0 25 75 0 0 100 0

Linezolid 0 100 0 0 100 0 0 100 0

Tigecycline 9,1 90,9 0 0 100 0 0 100 0

Cefotaxime 0 63,6 36,4 0 37,5 62,5 0 100 0

Cefuroxime 0 90,9 9,1 0 87,5 12,5 0 100 0

Cotrimoxazole 0 100 0 0 100 0 0 100 0

Cefoperazone/Sulbactam 18,2 81,8 0 0 100 0 0 100 0

Nitrofurantoin 0 81,8 18,2 0 100 0 0 75 25

Piperacillin/Tazobactam 0 90,9 9,1 12,5 87,5 0 0 75 25

Clindamycin 0 100 0 0 100 0 0 100 0

KP Klebsiella pneumoniae, AB Acinetobacter baumanii, PA Pseudomonas aeruginosa, S sensitive, I intermediate,

R resistance

4 DISCUSSIONS

VAP has been associated with mortality, and this

study evaluated the risk factors associated with the

incidence of VAP in order to implement preventive

measures in order to reduce mortality in ICU

patients.

In this study, we found age not to be a risk factor

for VAP in contrast to other studies. This can be

explained by the age distribution among our

patients. The majority of patients hospitalized in the

ICU were aged less than 60 years old with the most

common diagnosis of post-craniotomy with a history

of traffic accidents. Similar results were shown in

studies from Kurdistan Iran which described the

majority of patients exposed to VAP was younger

than 60 years old, as also in a study reported in

Indonesia (Riatsa A et al., 2013).

VAP has also been reported to likely occur in the

first week of mechanical ventilation due to the

interaction of more risk factors at the beginning of

admission (Putri Y and Budiono, 2014). However, in

this study, the length of ventilator use was not

significantly associated with the development of

VAP. Neither the longer use of a ventilator (>5

days), as determined to be the cutoff for longer use

of a ventilator, nor shorter us increased the risk of

VAP. This is also supported by the results of a study

from the ICU of Dr. Kariadi General Hospital

Semarang Indonesia (Santoso B, 2015).

In addition, we also did not find a significant

association between smoking habit and the incidence

of VAP, similar to the findings in other studies

ICTROMI 2019 - The 2nd International Conference on Tropical Medicine and Infectious Disease

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(Santoso B, 2015; Maria YS, 2011; Othman HA et

al, 2017).

This retrospective study had several limitations.

First, this study was conducted in a single medical

center and there may have been patient selection

bias. Second, this study was a retrospective survey,

which not only resulted in incomplete data for some

patients. Third, the disproportion of the samples in

the collecting stage. This disproportion may result in

different findings from others, including age,

duration of ventilator used and smoking habits.

VAP remains an important nosocomial infection

especially among the critically ill patients admitted

to the ICU in our setting. Further study involving

more detailed risk factors, diagnosis at admission,

and presence of high-risk microorganisms need to be

conducted to determine the risk factor for this event.

5 CONCLUSIONS

1 The risk factor that has no significant related

with VAP infection in ICU patient at Haji

Adam Malik General hospital Medan are age

(OR= 0.688, 95% CI 0.168-2.695, P=0.542)

2 There was no significant association between

duration of ventilator used with VAP incidence

but the duration of ventilator used more than 5

days are more 1.592 at risk for VAP than ≤ 5

days OR 0.592, 95% CI 0.465-5.573, P=0.405)

3 There was no significant association between

smoking habits with VAP incidence. The risk

value cannot be assessed because the group of

cases exposed and the control group exposed to

the same number. (OR=1, 95% CI 0.322-3.109,

P=1,000)

4 There are seven bacteria cause VAP found in

this study: Klebsiella pneumonia, Acinetobacter

baumanii, Pseudomonas aeruginosa,

Staphylococcus aureus, Enterobacter cloacae,

Elizabethkinqia meni, and Staphylococcus

aureus.

5 The results of sensitivity test for K.pneumoniae,

Amikacin, Ertapenem, Meropenem,

Gentamycin,

Ciprofloxacin,Cefoperazone/Sulbactam,

Ceftazidime Amoxycillin/Clavulanic acid,

Levofloxacin, Tetracycline, Tigecycline and

Polymixin B. The results of sensitivity test for

A.baumanii Amikacin, Ertapenem,

Meropenem, Polymixin B, Ceftazidime,

Ciprofloxacin, and Piperacillin/Tazobactam.

The results of a sensitivity test for P.aeruginosa

Ceftazidime, Amikacin, Ceftriaxone,

Meropenem, Ertapenem, Cefazoline, Cefixime,

Ciprofloxacin, and Aztreonam.

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