Bacterial and Antibiotics Sensitivity Patterns among Pneumonia Patients at Sanglah Hospital Denpasar, Bali

(1)

ORIGINAL ARTICLE

Bacterial and Antibiotics Sensitivity Patterns among Pneumonia Patients at Sanglah Hospital Denpasar, Bali

Kadek Suryawan^∗, Ida Sri Iswari^∗∗, N.M Adi Tarini^∗∗, N.N.D Fatmawati^∗∗and N.S Budayanti^∗∗,1

∗Clinical Microbiology Specialist Medical Education Program, Faculty of Medicine Udayana University/Sanglah Hospital Denpasar.,^∗∗Department of Clinical Microbiology, Sanglah Hospital, Denpasar, Indonesia.

ABSTRACT Objective:To determine the differences in bacterial and antibiotic sensitivity patterns among Community- Acquired Pneumonia (CAP) and Hospital-Acquired Pneumonia (HAP) patients at the Sanglah Hospital Denpasar, Bali. Materials and Methods: This study is a cross-sectional retrospective study conducted at Clinical Microbiology Installation of Sanglah Hospital from 1 January-31 March 2019. Sputum specimens were obtained from patients diagnosed with pneumonia. Eighty-seven samples had been consecutively selected and fulfilled the inclusion and exclusion criteria.

Results:The mean age of patients undergoing sputum culture was 54.66 years old, with most of them were male. Sputum specimens were taken, on average, after the 3rd day of treatment and patients had received antibiotic therapy (82.6%) which was dominated by combined antibiotic therapy. Cefoperazone with Levofloxacin was the most commonly used antibiotic therapy (36%). Of the bacteria isolated from patients’ sputum, 96.6% were Gram Negative bacteria and 56.3%

were resistant to multiple antibiotics. Gram-Negative bacteria were sensitive to Amikacin (91.5%) and Meropenem (80.5%) while Gram-Positive bacteria were sensitive to Vancomycin (100%) and Linezolid (100%). Pseudomonas aeruginosa (27.6%), Klebsiella pneumoniae (26.4%), Acinetobacter baumannii (20.7%) and Escherichia coli (12.6%) were isolated from the patients’ sputum. The types of isolated bacteria showed no significant difference between CAP and HAP patients (p> 0.05). Multi-drug resistant (MDR) bacteria were commonly found in HAP patients (66.0%) (p = 0.034). MDR Pseudomonas aeruginosa had a significant difference between those who were isolated from CAP and HAP (p=0.036).

Amikacin and meropenem showed≥80% sensitivity in both CAP and HAP patients (p>0.05).Conclusion:The type of bacteria and antibiotic sensitivity found in CAP and HAP patients treated at Sanglah Hospital Denpasar showed no significant difference. The difference was only found in the MDR Pseudomonas aeruginosa. A sampling of specimens is expected to be done on the first day of treatment and the selection of empirical antibiotic therapy needs to refer to the hospital germ pattern.

KEYWORDSpneumonia, bacterial patterns, antibiotic sensitivity patterns, MDR

First Received: December 05, 2019 Accepted: January 02, 2020

Manuscript Associate Editor: Ivan Inkov (BG)

1Department of Clinical Microbiology, Sanglah Hospital, Denpasar, Indonesia.; Email:

[email protected]

Introduction

Lower respiratory tract infections are a significant problem in the health sector in both developed and developing countries.

The World Health Organization (WHO) reports lower respiratory infections as the most common cause of death in the world with an estimate of 3.5 million deaths per year.[1] The commonly occurred infection of the lower respiratory tract is pneumonia. Pneumonia is an infectious disease that affects the lung parenchymal tissue causing lung tissue consolida- tion and diffusion disorders.[2] Pneumonia, acquired by the

(2)

place, is divided into two categories: communities pneumonia (community-acquired pneumonia, CAP) and nosocomial pneumonia (Hospital-acquired pneumonia, HAP).[3]

CAP is one of the leading causes of death in the world and become the 6th largest in the United States.[4] In the United Kingdom, it is reported that every year there are 0.5-1% of the to- tal adult population suffering from CAP and 22-42% need to get treatment in a hospital with a mortality rate between 5-14%.[3]

In Indonesia, the Household Health Survey in 2001 recorded 34 deaths from pneumonia and respiratory tract infections af- fecting as many as 34 per 100,000 population in men and 28 per 100,000 population in women.[5] Meanwhile, according to the Basic Health Research in 2013, pneumonia ranks 9th (2.7%) out of 10 leading causes of death in Indonesia.[6]

Pneumonia patients need to get the proper attention and treatment, particularly in patients with advanced age (≥65 years old). Enforcement of a definitive case of pneumonia as early as possible by performing blood or sputum culture is expected to reduce morbidity and mortality.[7] In the microbiological examination, especially with sputum specimens, it is essential to consider the quality of these sputum specimens because it will significantly affect the results of analysis and interpretation of results.[8] With good quality sputum specimens, the likelihood of finding pathogenic germs is higher than that of poor sputum quality.[9]

Sanglah Hospital, as a tertiary referral hospital with facilities of microbiological laboratory, noted that the sputum culture is the third-highest examination after blood and urine cultures.[10]

Several types of bacteria cause pneumonia in CAP and HAP patients such as Streptococcus pneumoniae, Gram-Negative bacteria, atypical bacteria and others.[2] The differences in the types of bacteria isolated from CAP and HAP patients cause different treatment strategies.[3]

To differentiate between the causative agent of infection or simply as colonization or contamination, the interpretation from a clinical microbiology specialist is necessary.[11] The record of antibiotic sensitivity patterns from the prior isolated bacteria can be used as epherical therapy before the culture from the patient can be confirmed.[12] The accuracy of the germ pattern and the results of antibiotic sensitivity tests will help the clinicians to provide wise empirical therapy. Based on that, we wanted to do some research to find out the pattern of germs and results of the antibiotic sensitivity test of isolates from patients with pneumonia as well as to determine whether there are differences in bacterial and antibiotic sensitivity patterns of bacteria found in CAP and HAP patients at Sanglah Hospital, so it can be used as a reference by clinicians in providing empirical therapy.

Materials and Methods

The study was a cross-sectional retrospective analytic conducted at the Clinical Microbiology Installation of Sanglah Hospital in Denpasar, Bali for three months from January 1 to March 31, 2019. Data were taken from electronic medical records, sheets of sputum culture examination requests originating from patients with suspected pneumonia and the results of bacterial identification and bacterial sensitivity tests using Vitek 2 Compact (Biomereux, France).

The Kirby Bauwer diffusion method was used to test the sensitivity of Cefuroxime, Cefoperazone, Cefoperazone-Sulbactam and Levofloxacin, while Dilution method using Vitek 2 Compact (Biomereux, France) was used to test the sensitivity of other antibiotics. Consecutive sampling method was carried out on

Table 1The characteristics of patients

Sample Characteristics Number (%) (N = 87) Age

Average

<54 years old

≥54 years old

54, 66 ±13,91 years old 49,4 (43)

50,6 (44) Gender

Males Females

66,7 (58) 33,3 (29) Type of Pneumonia

CAP HAP

Mechanical (ventilated) Non-mechanical

42,5 (37) 57,5 (50) 12,6 (11) 44,8 (39) Comorbidities

Kidney illness Heard disease Stroke Malignancy Myastenia gravis Diabetes mellitus Chronic Obstructive Pulmonary Disease (COPD) Brain and nerve trauma AIDS

Pancytopenia Unknown

3,4 (3) 3,4 (3) 1,1 (1) 2,2 (2) 2,2 (2) 1,1 (1) 1,1 (1) 2,2 (2) 1,1 (1) 1,1 (1) 80,5 (70)

Antibiotic therapy Without antibiotic therapy With antibiotic therapy Monotherapy

Levofloxacin Ceftriaxone Cefoperazone Meropenem Azithromycin

Cefoperason sulbactam Cotrimoxazole

Combined therapy

Cefoperazone + Levofloxacin Cefoperazone-sulbactam + Levofloxacin

13,8 (12) 86,2 (75) 28,0 (21/75) 5,3 (4/75) 4,0 (3/75) 8,0 (6/75) 5,3 (4/75) 1,3 (1/75) 2,7 92/75) 1,3 (1/75) 72,0 (54/75) 36,0 (27/75) 9,3 (7/75)

(3)

Table 1. (continued) Ceftriaxone + Levofloxacin Cefoperazone + Azithromycin Ceftriaxone + Azithromycin Ceftriaxone + Gentamycin Ciprofloxacin + Gentamycin Ceftriaxone + Metronidazole Ceftriaxone + Ampicillin sulba Cefoperazone + Cotrimoxazole Cefepime + Amikacin

Meropenem + Amikacin

1,3 (1/75) 2,7 (2/75) 2,7 (2/75) 1,3 (1/75) 1,3 (1/75) 8,0 (6/75) 2,7 (2/75) 1,3 91/75) 2,7 (2/75) 2,7 (2/75) Specimen collection time after antibiotic

administration Average day

<3rd day

≥3rd day

3,5 hari 29,9 (26) 70,1 (61)

Bacterial Group Gram Positive Staphylococcus aureus Streptococccus Parasanguinis Enterococcus faecalis Gram Negative Enterobactericeae Klebsiella pneumoniae E. coli

Proteus mirabilis Enterobacter cloacae Shigella sonnei Non Enterobactericeae Pseudomonas aeruginosa Acinetobacter baumannii Stenotrophomonas Maltophilia Burkholderia cepacia

100,0 (87) 3,4 (3) 1,1 (1) 1,1 (1) 1,1 (1) 96,6 (84) 47,6 (40) 26,4 (23) 12,6 (11) 3,4 (3) 2,3 (2) 1,1 (1) 52,4 (44) 27,6 (24) 20,7 (18) 1,1 (1) 1,1 (1) Antibiotic resistance bacteria

Multi Drug Resistant Organisms (MDRO) Non MDRO

100,0 (87) 56,3 (49) 43,7 (38)

samples that had met the inclusion and exclusion criteria. The inclusion criteria were that sputum specimen that came from patients hospitalized at Sanglah Hospital Denpasar and sputum culture examinations were carried out in the period January - March 2019, sputum specimens were from adults (>18 years old), were equipped with sheets microbiological examination with precise written diagnosis of infection and empirical antibiotic treatment. Besides, bacteria identification must show a probability level of≥85% with consistent antibiotic sensitivity results.

The antibiotic inhibition zone was measured for the Kirby Bauwer method, which was then compared to the standard inhibition zone for each type of bacteria contained in the Clinical Laboratory Standard Institute (CLSI). The exclusion criteria include sputum culture results without germ growth, showed growth of 3 or more types of germs (normal flora) or fungal growth. Besides, the antibiotic sensitivity test results were un- able to be displayed by Vitek 2 Compact (Biomereux, France).

Data analysis was performed using the Chi-square test or the Fisher Exact Test. All data analyzes were performed using SPSS software for windows version 23. A value of p <0.05 was used as the significance level; the precision value was determined by a 95% confidence interval value. The study had obtained Ethical Clearance approval from the Ethics Commission and Research of Faculty of Medicine, University of Udayana, Sanglah Hospital (No. 1622 / UN14.2.2.VII.14 / LP / 2019).

Results

This study was conducted on 87 samples that met the inclusion criteria. Samples were obtained from pneumonia patients who divided into two groups, namely CAP (42.5%) and HAP (57.5%) with an average age of 54.66 ± 13.91 years (range of patients aged 24-93 years), while about 50.4% were patients aged≥54 years and 66.7% of them were male. The most comorbid diseases in this study were kidney and heart disease (3.4%). On average, the specimens were taken after three days of hospitalization and had received antibiotics (86.2%) in the form of combination antibiotics (72%) commonly a combination of Ceftriaxone Lev- ofloxacin (36%). Culture identification of the sputum specimens showed that 3.4% and 96.6% of the isolates were Gram Positive and Gram Negative, respectively. Isolated Gram-Positive bacteria were Staphylococcus aureus, Streptococcus parasanguinis and Enterococcus faecalis (1.1% respectively). Meanwhile, isolated Gram-Negative bacteria consisted of Pseudomonas aeruginosa (27.6%), Klebsiella pneumoniae (26.4%), Acinetobacter baumannii (20.7%), Escherichia coli (12.6%) and other Gram- Negative bacteria such as Proteus mirabilis (3.4%), Enterobac- ter cloacae (2.3%), Stenothropomonas malthopilia, Shigella spp.

And Burkholderia cepasia (1.1% respectively). Non- Enterobac- teriaceae were Gram-Negative bacteria caused most of the pneumonia cases (52.4%). Among all of the isolated bacteria, 56.3%

were resistant to more than two classes of antibiotics or Multi- Drug Resistant (MDR) bacteria. (Table 1)

Klebsiella pneumoniae were highly sensitive to Meropenem (100%) and Amikacin (96%). Antibiotics that have been commonly used to treat pneumonia were Cefoperazone (17%), Cefoperazone-Sulbactam (77%), Ciprofloxacin, Lev- ofloxacin (39%) with a sensitivity level of <80%. E.coli sensitivity has remained high against Meropenem, Tigecycline, Piperacillin Tazobactam and Amikacin (100%). Amikacin (83%) and Cefepime (91%) have remained effective against Pseu- domonas aeruginosa. Acinetobacter baumannii showed a

(4)

Table 2.Differences in Bacterial Patterns of Sputum Isolates in Pneumonia Patients

Pneumonia Cases (%) Significance

Types of Bacteria CAP (N=37) HAP (N=50) (p<0,05)

K.pneumoniae 21,6 (8) 30,0(15) 0,381

E.coli 16,7 (6) 12,0 (6) 0,538

P.aeruginosa 24,3 (9) 28,0 (14) 0,701

A.baumannii 24,3 (9) 18,0 (9) 0,472

P.mirabilis 2,7 (1) 4,0 (2) 1,000^∗

E. cloacae 2,7 (1) 2,0 (1) 1,000^∗

S.maltophilia 2,7 (1) 0 0,425^∗

Shigella sonnei 0 2,0 (1) 1,000^∗

B.cepacia 0 2,0 (1) 1,000^∗

S.aureus 0 2,0 (1) 1,000^∗

S.parasanguinis 2,7 (1) 0 0,425^∗

E.facalis 2,7 (1) 0 0,425^∗

Pathogenic MDRO 43,2 (16) 66,0 (33) 0,034

K.pneumoniae 62,5(5/8) 66,7 (10/15) 1,000

E.coli 83,3 (5/6) 100,0 (6/6) 1,000

P.aeruginosa 22,2 (2/9) 71,4 (10/14) 0,036

A.baumannii 44,4 (4/9) 77,8 (7/9) 0,335

Proteus mirabilis 0 50,0 (1/2) 1,000

good level of sensitivity only to Amikacin (89%) and Trimetho- prim/Sulfamethoxazole (89%). Other Gram-Negative bacteria such as Proteus mirabilis, Enterobacter cloacae, Shigella spp. and Burkholderia cepache have remained sensitive to Meropenem, Levofloxacin, Amikacin and Cepepime, while Stenotrop homonas maltophilhe were only sensitive to Trimetho- prim/Sulfamethoxazole and Levofloxacin. All Gram-Positive bacteria have remained sensitive to Vancomycin (100%) and Linezolid (100%).

Gram-Negative bacteria were commonly found from both CAP and HAP patients (94.6% and 98%, respectively). Almost 60% of CAP cases caused by Non-Enterobacteriaceae, whereas in the HAP cases, Enterobacteriaceae and Non-Enterobacteriaceae equally showed as the cause of the disease (50%). The types of bacteria that cause CAP cases were Pseudomonas aeruginosa (24.3%), Acinetobacter baumannii (24.3%), Klebsiella pneumoniae (21.6%) and E. coli (16.7%) which almost 46% of the bacteria were MDR. Whereas, HAP cases were caused by Klebsiella pneumoniae (30.0%), Pseudomonas aeruginosa (28.0%), Acineto- bacter baumannii (18.0%) and E. coli (12.0%) which 64,0% were MDR bacteria. The type of bacteria isolated from the patient’s sputum specimens showed no significant difference between CAP patients and HAP (p> 0.05). However, there was a significant difference between MDR isolated from CAP and HAP which were isolated more in HAP patients than in CAP patients (0<0.05). (Table 2)

Although not showing a significant difference (p>0.05), Amikacin and Meropenem were antibiotic with of≥80% sensitivity in both patients with CAP and HAP. In general, antibiotic

sensitivity patterns showed no significant difference between CAP patients and HAP (p> 0.05). (Table 3)

Discussion

Pneumonia is an infection of the lung parenchymal tissue that can be caused by bacteria, viruses, fungi and parasites. Pneumo- nia can be distinguished based on the place of infection, namely CAP and HAP. Pneumonia often occurs in infants and children decreasing in young and adult ages and then increasing in patients of advanced age.[13] In this study, patients suffering from pneumonia were found at an average age of 54.45 years. This data is following the results of research conducted in 2011 at Ko- rean Hospital which found that there were more cases of pneumonia in the older age group. This condition occurs because the risk factors are more prevalent in older age groups such as comorbid diseases and decreased quality of the body’s immune system compared to in younger age groups so that the likelihood of HAP and CAP is higher in old age.[14] Most of the CAP and HAP patients were male (62.2% and 70.0%). The same condition was also found in pneumonia patients in Korean hospitals (65.7%

and 60.0%) and Egyptian hospitals (92.5% and 65.3%).[14,15]

This is probably due to risk factors including smoking and comorbid diseases such as COPD, diabetes mellitus, kidney and heart disease and alcohol use which more common in men than women.[16.17] However, in developing countries, the risk of pneumonia is almost similar between men and women. A study conducted in South America in 2017 showed that the incidence of CAP was more common in women (53.6%).[13] The condition varies found in several studies in various countries confirms that

(5)

Table 3.Differences in Antibiotic Sensitivity Patterns in Pneumonia Patients

Pneumonia Cases (%) Significance

CAP HAP (p<0,05)

Types of Antibiotics

Ampicillin 5,9 (1/17) 0 0,405^∗

Ampicillin Sulbactam 36,0 (9/25) 22,9 (8/35) 0,265

Gentamicin 52,9(18/34) 47,6 (20/42) 0,645

Amikacin 91,2 (31/34) 91,7 (44/48) 0,618

Aztreonam 16,0 (4/25) 15,4 (6/39) 1,000^∗

Cefazoline 0(0/34) 2,0 (1/49) 1,000^∗

Cefuroxime 8,6 (3/35) 8,3 (4/48) 1,000^∗

Cefotaxime 100 (1/1) 0 NA

Ceftriaxone 24,0 (6/25) 14,3 (5/35) 0,338

Ceftazidime 41,2 (14/34) 42,6 (20/47) 0,901

Cefoperazone 14,3 (5/35) 20,8 (10/48) 0,444

Cefoperazone Sulbactam 60,0 (15/25) 50,0 (15/30) 0,458

Cepefime 55,9 (19/34) 53,1 (26/49) 0,800

Ciprofloxacin 28,6(10/35) 26,5 (13/48) 0,836

Levofloxacin 37,1 (13/35) 31,3 (15/48) 0,575

Meropenem 79,4 (27/34) 81,3 (39/48) 0,836

Tigecycline 54,3 (19/35) 40,8 (20/49) 0,222

Trimethoprim/Sulfamethoxazole 48,0 (12/25) 37,1 (13/35) 0,400

Piperacillin Tazobactam 65,7 (23/35) 51,0 (25/49) 0,180

Erythromycin 0 (0/2) 100,0 (1/1) 0,333^∗

Vancomycin 100,0 (2/2) 100,0 (1/1) NA

Linezolid 100,0 (2/2) 100,0 (1/1) NA

sex is not a risk factor for pneumonia.[18]

Empirical therapy is the initial therapy before the causative pathogen bacteria is known. In the case of CAP and HAP, empirical therapy divided into monotherapy and combination therapy of antibiotics. Selection of empirical treatment follows the lo- cal germ patterns or national/international if the patterns are not available.[12] Antibiotics used for empirical therapy can be broad-spectrum for Gram-Positive, Gram-Negative, anaerobic and atypical bacteria. In the case of CAP and HAP therapy, the choice of empirical therapy is also based on the severity of the patient showed on a CURB score of 65 or Pneumonia Severity Index ( PSI ).[7] The recommendation from the Infec- tious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) for CAP patients who are hospitalized in non- intensive care rooms include single Fluoroq quinolones, β-lactam (3rd Generation Cephalosporins and Carbapenem) and Macrolide orβ-lactam and Fluoroquinolone.[12,19] In this study, the use of combination antibiotic therapy (72.0%) was more than that of antibiotic monotherapy. This study is consistent with studies conducted at type A hospitals which found that combination therapy is more widely used than single therapy (93.1%

vs 6.9%).[19] This may be because cases handled in tertiary hos-

pitals are cases with a high severity according to CURB score of 65 or PSI and are referral cases from secondary hospitals that have received prior antibiotic therapy.

The fact that the CAP with HAP cases is generally different. In CAP patients, the causative bacteria are Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Legionella spp and less by Gram-Negative bacteria. Mean- while, HAP cases are mostly caused by Gram-Negative in both with or without MDR.[7,20] In this study, the bacteria which are agents in both CAP and HAP are predominantly caused by Gram-Negative bacteria. Most cases of CAP were caused by Pseudomonas aeruginosa and Acinetobacter baumannii followed by Klebsiella pneumoniae, E. coli and one case each was caused by Stenotrophomonas maltophilia, Proteus mirabilis and Enterobacter cloacae. This result is following research conducted by Cilonz C et al. 2019. Gram-Positive bacteria that caused CAP are Enterococcus faecalis and Streptococcus parasanguinis. The HAP cases were mostly caused by Klebsiella pneumoniae followed by Pseudomonas aeruginosa, Acinetobacter baumannii, E. coli, Proteus mirabilis, Shigella sonnei, Burkholderia cepacia, Enterobacter cloacae and Gram-Positive bacteria such as Staphylococcus aureus. The four main types of bacteria isolated

(6)

in the HAP cases are following the study of Khalil et al., 2013 in the Egyptian military hospital showing that Klebsiella pneumoniae (23.1%) followed by Pseudomonas aeruginosa (17.3%), E.coli (11.5%) and Acinetobacter baumannii (7.7%) were isolated from HAP cases.[15] Likewise, the study of Eun Ju Jeon, et al., 2011 isolated Klebsiella pneumoniae (26.7%) and Pseudomonas aeruginosa (26.7%) from the HAP cases.[14] There are differences for CAP cases because the most common isolated bacteria were Streptococcus pneumoniae (36.4%), Staphylococcus aureus (7%), Pseudomonas aeruginosa (2.1%) and E.coli (1.6%).[15] Likewise, with the results of a study at Korea in 2011 were Streptococ- cus pneumoniae (33.3%) was the leading cause of CAP cases.

There are similarities from this study with research conducted at Sanglah Hospital, such as the isolation of the bacteria Klebsiella pneumoniae (20.6%) and Pseudomonas aeruginosa (6.3%) after Streptococcus pneumoniae as the causative agent for CAP.[14]

Isolation of Gram-Negative bacteria as the leading cause of CAP in this study is probably due to a history of prior antibiotics use either during outpatient or even inpatient at the secondary hospital, especially on the use of antibiotics such as Macrolide, Chepalosporins and group of Fluoroquinolone which remains sensitive against Streptococcus pneumoniae. Besides, the po- tential to be colonized by bacteria that common in a hospital, especially Gram-Negative bacteria such as Pseudomonas spp., Acinetobacter spp., Stenotrophomonas spp., Enterobacteriaceae spp. Which are MDR is significantly high as the sputum specimens are collected on day 3 and 4 after administration of antibiotic treatment at the hospital. Besides, failing on isolation of Streptococcus pneumonia, Haemophilus influenzae and other atypical bacteria from sputum specimens in CAP patients can be caused by not using selective media for bacterial growth such as the use of blood media added with Gentamicin to increase the growth of Streptococcus pneumonia and inhibit the growth of other bacteria, not adding factors V and X to brown media to improve the growth of Haemophilus influenzae and not hav- ing molecular examination to identify Mycoplasma pneumonia, Legionella spp. and other atypical bacteria.[20,21] This is re- lated to limited resources available in the clinical microbiology laboratory at Sanglah Hospital.

Infection by MDR bacteria occurs in both CAP and HAP cases with a higher incidence was found in HAP cases (66.0%).

The results of this study are consistent with research by Eun Ju Jeon, et al., 2011 who found MDR bacteria in HAP patients were higher than CAP (56.7% vs 14.3%). [14] Also, following the study of Horie H, et al., 2018 that found MDR Gram Negatives (Pseudomonas aeruginosa, Enterobacteriaceae, and Methicillin- Resistant Staphylococcus aureus (MRSA) in HAP cases.[23]In HAP patients with a history of previous comorbidities and administration of empirical antibiotic therapy over a longer period often causes selective pressure. It will cause sensitive pathogenic bacteria and normal flora functioning as a natural immune system die and the remaining is only those bacteria with resistant genes that can spread these resistant genes through plasmids to other bacteria.[7] This will cause multiplication of resistant bacteria without competition with normal flora in the patient’s body or change the normal flora of the body into resistant bacteria and possibly spread the nature of resistance horizontally both utilizing conjugation and transformation.[21,22] In this study, MDR Pseudomonas aeruginosa were significantly different from CAP and HAP patients. Pseudomonas aeruginosa is a bacterium with many mechanisms to become resistant to antibiotics. Its abilities such as improving efflux antibiotic goes into the cell,

changing the target of the drug, forming biofilms, resizing porin on the outer membrane or changing the membrane permeabil- ity and producing carbapenemase lead to resistance of many types of antibiotics such as Cephalosporins (3rd and 4th gen- erations), Meropenem, Fluoroquinolone, Aminoglycoside and Macrolide.[21.22]

The bacteria isolated in this study are mostly MDR bacteria.

Antibiotics with high sensitivity for CAP and HAP cases are Amikacin and Meropenem. There is no significant difference between the types of antibiotics that are still sensitive to the treatment between CAP and HAP cases. However, the use of those antibiotics must be limited (restriction) and considered a last re- sort.[24] Resistance to those antibiotics will cause hardly treated infectious diseases which can increase morbidity, mortality and patient expenses in medical care.

This study has some limitations including no record of patients’ referral and prior patients’ antibiotic treatment before inpatient at Sanglah Hospital, especially for CAP patients. Those data will help to identify the effect of prior antibiotic treatment to types of isolated bacteria in CAP patients. Further study with a bigger sample size is needed to validate the prior study.

Conclusion

Gram-Negative bacteria with MDR such as Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii and E.coli are commonly found in both CAP and HAP patients at Sanglah Hospital, Denpasar. Meropenem and Amikacin are antibiotics with≥80% sensitivity. There are no differences in the types of bacteria that cause CAP and HAP in patients treated at Sanglah Hospital. However, there are differences in bacteria that are MDR, for instance, Pseudomonas aeruginosa. There is no significant difference in antibiotic sensitivity patterns between isolates that came from CAP and HAP patients. Collecting time of sputum specimens should be carried out on the first day of patient admission followed with proper collection method. The provision of selective media to grow bacteria that are specific to CAP cases needs to be done as well as the improvement on selecting empirical antibiotic therapy that refers to the hospital germ pattern for wiser antibiotic therapy.

Acknowledgement

We want to thank the Director of Sanglah Hospital and Head of Clinical Microbiology Laboratory Installation for permission to conduct the study Clinical Microbiology Laboratory at Sanglah Hospital; Colleges of Clinical Microbiology Specialist Medical Education Program 1 who provided input for the improvement of this study and all analysts Clinical Microbiology Installation at Sanglah Hospital who assisted in working on samples sputum culture. Thank I Dewa Gde Sathya Deva for the contribution on preparing the manuscript.

Disclosure Statement

There were no financial support or relationships between the authors and any organization or professional bodies that could pose any conflict of interests.

Competing Interests

Written informed consent obtained from the patient for publica- tion of this case report and any accompanying images.

(7)

References

1. World Health Organization. Global action plan for preven- tion and control of pneumonia. (2009)

2. Rachel L. Chin, Bradley W. Frazee. Emergency Manage- ment of Infectious Diseases. Second edition. New York.

(2018)

3. National Institute for Health and Care Excellences. Pneumo- nia in Adults: diagnosis and management. (2014) Clinical guideline.nice.org.uk/guidance/cg191

4. Wunderink RG, Watever GW.Community-acquired pneumonia. N Engl J Med. (2014) 370:543-51.

5. Priyanti ZS, Erlina B, Arifin N, Sardikin G, Fathiyah I, Heidy A, Diah H.. Pneumonia Komuniti. Pedoman Diagnosis dan Penatalaksaan di Indonesia. Perhimpunan Dokter Paru Indonesia. (2014)

6. Kementerian Kesehatan Republi Indonesia. Riset Kese- hatan Dasar. (2013)

7. Schlossberg D. Clinical Infection Disease.2nd ed. Cam- bridge University Press ; (2015). p. 205-32

8. Procop, Gary W. Koneman’s color atlas and textbook of diagnostic microbiology. Seventh edition. Philadelphia:

Wolters Kluwer Health; (2017)

9. Budayanti NS, Suryawan K, Iswari IS, Sukrama DM.

The Quality of Sputum Spesimenn as a Predictor of Isolated Bacteria From Patients With Lower Respira- tory Tract Infection at a Tertiary Refferal Hospital, Den- pasar, Bali-Indonesia.Front.Med. (2019) 6:64. Doi:10.3389 /fmed.2019.00064

10. Instalasi Mikrobiologi Klinik Rumah Sakit Sanglah Den- pasar. Laporan Tahunan Hasil Pemeriksaan Mikrobiologi Tahun 2018

11. Lindawati Alimsardjono, Priyo Budi Purwono, Pepy Dwi Endraswari, Deby Kusumaningrum, Ni Made Mertani- asih.Buku Ajar Pemeriksaan Mikrobiologi pada Penyakit Infeksi.Edisi 1. Jakarta. (2015).p. 83-103

12. Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community- acquired pneumonia in adults. Clin Infect Dis. (2007) 44:

Suppl. 2, S27–S72.

13. Lopardo GD, Fridman D, Raimondo E, et al. Incidence rate of community acquired pneumonia in adults: a population- based prospective active surveillance study in three cities in South America. BMJ Open. (2018) 8:e019439. DOI:10.1136/

BMJ open-2017-019439

14. Eun Ju Jeon, Sung-Gun Cho, Jong Wook Shin, Jae Yeol Kim, In Won Park, Byoung Whui Choi, et al. The Difference in Clinical Presentations between Healthcare-Associated and Community-Acquired Pneumonia in University-Affiliated Hospital in Korea.Yonsei Med J . (2011) 52(2):282-87. DOI 10.3349/ymj.2011.52.2.282

15. Khalil MH, Al-Hameed Farghal ADA, Shehata HM.

Pattern of community and hospital acquired pneumonia in Egyptian military hospitals. Egyptian Jour- nal of Chest Diseases and Tuberculosis. (2013) 62, 9–16.http://dx.doi.org/10.1016/j.ejcdt.2013.01.003 16. H. El-gazzar. Value of tracheal aspiration in the diagnosis

of bacterial infection in mechanically ventilated patients, Msc Thesis, Chest Department, Minufiya University. (2006) 17. G. Prod’hom, P. Leuenberger, J. Koerfer, et al. Nosocomial pneumonia in mechanically ventilated patients receiving antacid, ranitidine, or sucralfate as prophylaxis for stress ulcer: a randomized controlled trial, Ann. Intern. Med.

(2004) 12;653–662

18. Torres A, Peeterman WE, Viegi G, Blasi F. Risk Factor for Community Acquired Pneumonia in Adult in Europe : Lit- erature Review. Thorax (2013) 68 : 1057-1065

19. Sari IP, Nuryastuti T, Asdie RH, Pratama A, Estriningsih E.

Perbandingan pola Terapi antibiotik pada CAP di Rumah Sakit Tipe A dan B. Jurnal Manajemen dan Pelayanan Far- masi. (2017) Volume 7 Nomor 4. H : 168-74

20. Cilonz C, Dominedo C, Torres. Multidrug Resisten Gram-Negatif Bacteria In Community Acquired Pneumo- nia.Critical Care ,(2019) 23 : 79. P 1-9.

21. Mahon Connie R., Donald C.Lehman. Text Book Of Diag- nostic Microbiology.Edition : 6. Elseiver Saunder. (2019) 22. Tille PM.Bailey & Scott’s Diagnostic Microbiology. Ed

23. Horie H, Ito I, Konishi S, Yamamoto Y, Yamamoto Y, Uchida T, et al. Isolation of ESBL-producing Bacteria from Spu- tum in Community-acquired Pneumonia or Healthcare- associated Pneumonia Does Not Indicate the Need for An- tibiotics with Activity against This Class. Intern Med. (2018) 57: 487-495. DOI: 10.2169/internalmedicine

24. Antibiotic Expert Groups. Therapeutic guideline :antibiotic.Version 15. Melbourne : Therapeutic Guideline Lim- ited.(2014) p 1-12