Empirical Antibiotics Study on Pneumonia in Intensive Care Unit

Yeni Farida, Katarina Puspita and Zahra Yusvida

Department of Pharmacy, Faculty of Mathematics and Science, Universitas Sebelas Maret, Ir.Sutami Street No. 36A

Kentingan, Surakarta, Central Java, Indonesia

Keywords: Bacterial culture, Empiric antibiotics, Intensive care unit, Pneumonia

Abstract: Microorganisms and inflammatory cells are present in the air sacs of the lungs in most pneumonia patients,

preventing their lungs from functioning normally. The main treatment for pneumonia is antibiotics

supported by physiotherapy. This study aimed to determine the pattern of empirical antibiotic use and

bacterial etiology (sputum culture test) of ICU patients at a government hospital in Madiun, West Java. This

descriptive research used retrospective data collected from January to December 2016. The samples were

purposively selected based on specific inclusion criteria (i.e., patients diagnosed with pneumonia who

received antibiotic therapy and had information on their bacterial culture data). The study examined the

medical records of 77 subjects who were mostly aged 0-5 years old (67.5%). Acinetobacter baumannii was

the most commonly isolated organism (42.1%), followed by Klebsiella pneumonia and Pseudomonas

aeruginosa (15.79%). Meropenem was mostly used as a single antibiotic in pediatrics (24%), while

ceftriaxone was most common in adult (16.22%). The most widely used combinations of antibiotics were

ampicillin and gentamycin for pediatrics ICU patient (20%) and meropenem and metronidazole for adult

patients (13.51%). Acinetobacter baumannii was completely resistant to Ampicillin-sulbactam and partially

resistant to other beta-lactam antibiotics. Both Pseudomonas aeruginosa and Klebsiella pneumonia were

completely resistant to Ampicillin and Ampicillin-sulbactam.

1 INTRODUCTION

Pneumonia is one of the common infections that

require hospitalization and is considered one of the top

causes of death, especially in developing countries.

Basic health research in Indonesia claims that

pneumonia is the second leading cause of death after

diarrhea (Indonesian Health Ministry, 2013). The

mortality rate of hospitalized pneumonia patient is

15.5-24.8 % (Firmansyah et al., 2015). Furthermore,

the mortality rate for intensive care unit (ICU) patients

with pneumonia remains high, approximately 15-50 %

(Li et al., 2016). Ventilator-associated pneumonia

(VAP) is the most frequent infection in patients

admitted to ICU (Chawla, 2008). Most deaths in

pneumonia are attributable to VAP.

Empiric antibiotic therapy is highly recommended

to begin soon after the diagnosis, which is within 6

hours, to reduce the mortality and morbidity rate

(Harris et al., 2017). Ideally, antibiotic therapy can

cure pneumonia patients without causing

complications or contributing to the development of

antibiotic resistance (Stralin, 2008). IT requires proper

antibiotic choice based on sputum bacterial sensitivity

culture test. The bacterial etiology pattern of

pneumonia differs from one region to another. The

selection of antibiotics has to be based on the profile of

the local bacterial etiology and antibiotic susceptibility

(Hsueh et al., 2011).

In this study, we determined the pattern of

empirical antibiotic use and bacterial etiology based on

sputum culture test.

2 MATERIALS AND METHOD

2.1 Study Design

The retrospective study was designed by collecting

data from patients’ medical record. The data included

patient characteristics, empirical antibiotics use,

bacterial culture information, and antibiotics

susceptibility test data.

Farida, Y., Puspita, K. and Yusvida, Z.

Empirical Antibiotics Study on Pneumonia in Intensive Care Unit.

DOI: 10.5220/0008239200480053

In Proceedings of the 1st Muhammadiyah International Conference on Health and Pharmaceutical Development (MICH-PhD 2018), pages 48-53

ISBN: 978-989-758-349-0

2.2 Patient and Setting

This study focused on ICU patients at a government

hospital in Madiun, West Java starting from January

until December 2016. Patients admitted to ICU during

this period, who recieved antibiotic therapy for at least

three days, and had bacterial culture data were eligible

as samples in this study.

2.3 Data Analysis

The patient profile was analyzed descriptively by

calculating the percentage of sex, age, length of stay

(LOS), and the type of antibiotics use. The antibiotics

use was grouped into two, namely single-use and

combination. The percentage of each type of

antibiotics use was calculated. Bacterial etiology and

the pattern of antibiotics resistance were identified

from the bacterial culture data.

3 RESULTS AND DISCUSSION

3.1 Patient Characteristic

This study involved 77 patients, including neonates,

infants, toddlers, adults, and geriatrics. The age range

of the patients was from 1 day old to 72 years old. No

patients from the age range of child and adolescent

were identified in this study. The distribution of

patient age and gender is presented in Table 1.

The highest frequency of pneumonia cases was

found in the age range of <5 years old. Other studies

state that the incidence of pneumonia is dominant in

population aged younger than 5 years old and older

than 65 years old (Eida et al., 2015; Rozenbaum et al.,

2015). However, in this study, the proportion of

geriatric patients admitted to ICU is relatively small.

The results of this study are in line with a study in the

Philipines, a neighboring country of Indonesia, which

claims that the majority of pneumonia episodes occurs

in children aged < 2 years old (Kosai et al., 2015).

Table 1 also shows that the incidence of

pneumonia is similar in male and female patients. In

adult or geriatric patients, the incidence of pneumonia

in both sexes is nearly similar. While many studies

believe that gender contributed contributes to the risk

factor of pneumonia differently (Falagas et al., 2007;

Rozenbaum et al., 2015), another study reveals that

mortality rate among pneumonia patients doesn not

differ in gender (Gannon et al., 2004). On the contrary,

this study affirmed that either male or female had the

same chance of contracting pneumonia. Nevertheless,

compared with the other studies, this research had a

limited number of samples.

There are any risk factors related to pneumonia.

Besides age and sex, the other factors that contribute to

the incidence of pneumonia are chronic comorbidities,

exposure to cigarette smoke, alcohol abuse,

malnutrition, conditions that promote pulmonary

aspiration or inhibit coughing, and exposure to

contaminated respiratory equipment. Unfortunately,

this study could not evaluate these factors due to the

lack of retrospective data.

The length of stay of the patients in the ICU ranged

from 1 to 26 days. shows that most of the patients are

hospitalized in the ICU for 0-7 days. The average

lenght of stay is 8.5 days in pediatric patients and 9.5

days in adult and geriatric patients. It is substantially

shorter than the result of a study in the Netherlands

(i.e., 15.2 days) (Rozenbaum et al., 2015).

3.2 The Bacterial Etiology and Antibiotic

Susceptibility Test

The obstacles in this study lie in the limited bacterial

culture data due to financial problem. Bacterial culture

was not performed in all patients (19 out of 77

patients). Gram-negative bacteria were the dominant

pathogen that caused pneumonia in this study. Gram-

positive usually cause community-acquired pneumonia

(CAP), while gram-negative bacteria are behind

Table 1: The characteristics of the patients observed in this

study

Patient

(N= 77)

Age

Gende

(%)

Male Female

Neonates

0 – 1 month

(

n=17

)

7 10 22.08

Infants

1 month –

2years

(

n=33

)

17 16 42.96

Todlers

2–5 years

(n=2)

2 - 2.60

Adults

18–64 years

(n=18)

12 13 32.57

Geriatrics

≥ 65 years

(

n=7

)

4 3 9.09

Table 2: The length of stay in the intensive care unit (ICU)

Length

of Stay

(days)

Frequency (N=77)

Total

Pediatric Adult Geriatric

0 – 7 29 4 4 37

8 – 14 16 8 3 27

15 – 21 4 3 - 7

≥ 21 3 3 - 6

Empirical Antibiotics Study on Pneumonia in Intensive Care Unit

hospital-acquired pneumonia (HAP) (Cukic and

Hadzic, 2016). Based on the microbiological

observation results, the most bacterial etiologic agents

in ICU patients were Acinetobacter baumannii

(42.11%), followed by Klebsiella pneumonia and

Pseudomonas aeruginosa (15.79%). This result is in

line with a study in Thailand and India (Chawla,

2008). A study in the United States also confirms that

Pseudomonas aeruginosa and Klebsiella pneumonia

are two of the three major microorganisms that cause

HAP. The etiological bacteria in the observed patients

are listed in Table 3.

Acinetobacter baumannii has high survivability

and can form colonies outside the human body

(Uwingabiye, 2017). It is discovered as the main

nosocomial pathogen, that causes severe infections in

patients treated in (ICUs) (Sileem et al., 2017). A

study in Poland reveals that Acinetobacter baumannii

is the most frequent pathogen of VAP (53.3%)

(Duszynska et al., 2018).

Based on Figure 1, the isolated bacteria in ICU

patients are resistanr to nearly all beta-lactam

antibiotics. This study found that Acinetobacter

baumannii was completely resistant to Ampicillin-

sulbactam and partially resistant to other beta-lactam

antibiotics. Both Pseudomonas aeruginosa and

Klebsiella pneumonia were completely resistant to

Ampicillin and Ampicillin-sulbactam. However,

several cephalosporine antibiotics were not effective

for treating the infections caused by Pseudomonas

aeruginosa and Klebsiella pneumonia.

Aside from being resistance to beta-lactam

antibiotics, the pathogens had developed the ability to

adapt to Cotrimoxazole and Ciprofloxacin, except for

Acinetobacter baumannii. Because Pseudomonas

aeruginosa and Klebsiella pneumonia are highly

resistant to gentamycin, this antibiotic is not preferable

for treating their infections.

Multiple drug-resistant pathogens have increased in

hospitalized pneumonia, especially in the ICU

(Cilloniz et al., 2016). The bacteria that causes HAP

are more difficult to overcome due to its high

resistance level to several antibiotics.

Table 3: The bacterial etiology in ICU

Bacterial

type

Bacterial species

freq.

Gram-

negative

(N = 17)

Acinetobacter baumannii 8 42.11

Klebsiella pneumonia 3 15.79

Pseudomonas aeruginosa 3 15.79

Pasteurella pneumotropic 1 5.26

Pseudomonas

oryzibabitans

1 5.26

Stenotrophomonas

maltophilia

1 5.26

Gram-

positive

(N = 2)

Staphylococcus aureus

(MRSA)

1 5.26

Staphylococcus aureus 1 5.26

Figure 2: The pattern of bacterial resistance to other

antibiotics

Figure 1: The pattern of bacterial resistance to beta-lactam

antibiotics

MICH-PhD 2018 - 1st Muhammadiyah International Conference on Health and Pharmaceutical Development

3.3 Empirical Antibiotics Use

Antibiotics are the major therapy in infection cases

like pneumonia. The selection of appropriate

antibiotics can increase the success rate of therapy and

reduce the risk of death. A quick and precise

administration of empirical antibiotics can

immediately fix common symptoms of pneumonia,

such as fever and rapid breathing or tachypnea (Hazir

et al., 2013).

The antibiotic use of the patients in this study

presented in Tables 4 and 5. The mostly used single

antibiotics in pediatric case are cefotaxime, while

ceftriaxone is commonly prescribed to adult and

geriatric patients. Cefotaxime is the most preferred

antibiotics because of it is as effective as ampicillin-

sulbactam to treat pneumonia (Puspitasari et al., 2014).

Cefotaxim and ceftriaxone, the third generation of

cephalosporine, are a broad-spectrum antibiotic.

Patients with severe pneumonia should be treated with

broad-spectrum antibiotics before the etiologic

bacterial agent is detected (Stralin, 2008).

Nevertheless, a study confirms that there are no

differences in patient outcomes between the narrow-

spectrum and the broad-spectrum antibiotic treatment

(Williams et al., 2013).

Based on Tables 4 and 5, Ampicillin-gentamycin is

dominantly used in pediatric cases. In line with this

study, (Lodha et.al., 2013) suggest the combination

of ampicillin-gentamycin for pediatric inpatient with

severe and very severe pneumonia. When combined

with ampicillin, gentamycin produces a potent

bactericidal effect. It increases the drug uptake by the

inhibition of bacterial cell wall synthesis. Penicillin

alters the structure of the cell wall, allowing

gentamycin to penetrate easier into the bacteria

(Katzung, 2014).

Meropenem is an empirical antibiotic for severe

infection both in adult and pediatric patients (Baldwin

et al., 2008). Based on Table 5, the combination of

meropenem and metronidazole is the most prescribed

antibiotics in adult and geriatric patients. It is expected

to achieve broader therapeutic targets and optimum

ffects. Because these drugs work through the

mechanism of inhibiting protozoan DNA synthesis, it

Table 4: The empirical antibiotic use in pediatric patients

Types of

antibiotic

use

Antibiotics

Number

of use

(

N=47

)

Single

Cefotaxime 10 21.28

70.21

Mero

enem 7 14.90

Gentam

cin 5 10.64

Ceftazidime 3 6.38

Metronidazole 2 4.26

Cefixime 2 4.26

Cefazoline 1 2.13

Ceftriaxone 1 2.13

Ami

acin 1 2.13

Ampicillin 1 2.13

Combina-

tion

Ampicillin +

Gentam

cin

5 10.64

29.79

Meropenem +

Gentamycin

3 6.38

Meropenem +

Amikacin +

Metronidazole

1 2.13

Meropenem +

Ampicillin

1 2.13

Table 5: The empirical antibiotics use in adult and geriatric

patients

Types of

antibiotic

use

Antibiotics

Number

of use

(N=42)

(%)

Single

Ceftriaxone 9 21.43

69.05

Mero

ene

5 11.90

Cefotaxi

e 4 9.52

Ceftazidime 3 7.14

Gentamycin 2 4.76

Cefixime 2 4.76

Cotrimoxazole 1 2.38

Clindam

cin 1 2.38

Cefadroxil 1 2.38

Ampicillin/

Sulbacta

1 2.38

Combinat

ion

Meropenem +

Metronidazole

3 7.14

30.95

Ceftriaxone +

Metronidazole

2 4.76

Gentamycin +

Ceftriaxone

1 2.38

Gentamycin +

Mero

ene

1 2.38

Cefotaxime +

Gentamycin

1 2.38

Clindamycin +

Levofloxacin

1 2.38

Meropenem +

Metronidazole

1 2.38

Ceftriaxone +

Levofloxacin

1 2.38

Cefixime +

Metronidazole

1 2.38

Meropenem +

Metronidazole

+ Gentamycin

1 2.38

Empirical Antibiotics Study on Pneumonia in Intensive Care Unit

results in cell death (Fauziyah et al., 2011).

Meropenem is more effective than cefotaxime for

P.aeruginosa and isolated anaerobes. It is effective to

treat nosocomial infections (Mehtar et al., 1997). In

this study, a patient infected with Pseudomonas

aeroginosa and Acinetobacter baumannii recieved

meropenem as an empirical antibiotic.

The selection of antibiotics according to the

bacterial etiology can optimize the therapeutic effects

and reduce the risk of resistance. Unfortunately, this

study could not analyze the suitability of the empirical

antibiotic to deal with certain isolated bacteria because

the bacterial culture was not performed to all patients.

4 CONCLUSIONS

In this study, Acinetobacter baumannii was the most

common isolated organism (42,11%), followed by

Klebsiella pneumonia and Pseudomonas aeruginosa

(15.79%). Meropenem was the most used single

antibiotic in pediatric cases (24%), while ceftriaxone

was most commonly prescribed adult patients

(16.22%). The most widely used combination of

antibiotics was ampicillin and gentamycin for pediatric

ICU patients (20%), and meropenem and

metronidazole in adult patients (13.51%). This study

also found that Acinetobacter baumannii was

completely resistant to Ampicillin-sulbactam and

partially resistant to the other beta-lactam antibiotics.

Both Pseudomonas aeruginosa and Klebsiella

pneumonia were completely resistant to Ampicillin

and Ampicillin-sulbactam.

ACKNOWLEDGMENTS

The authors would like to thank the Fundamental

Grant, Universitas Sebelas Maret in 2018 for their

financial assiatance.

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Empirical Antibiotics Study on Pneumonia in Intensive Care Unit