INTRODUCTION:

Community-acquired pneumonia (CAP) is among the top ten causes of death in the world¹. One of the bacteria that causes respiratory tract infections is Klebsiella pneumoniae². Other pathogens that cause CAP are Streptococcus pneumoniae, Haemophilus influenza, and Moraxella catarrhalis³. A study in Saudi Arabia reported that the irrational use of antibiotics in intensive care units and over-the-counter antimicrobials by community pharmacies has resulted in the emergence of multi-drug resistant organisms (MDRO)⁴. The emergence of MDRO in human clinical pathogenic bacteria in the last decades has become worrying⁵. Investigations in the USA show that methicillin-resistant Staphylococcus aureus (MRSA) trends vary by region, while the frequency of Pseudomonas aeruginosa has increased since 2005-2019⁶. A study conducted in Sudan, Africa, showed that the frequency of extended-spectrum β-lactamase (ESBL) producers in CAP patients was relatively high, and most of the Staphylococcus aureus isolated were found to be resistant to Methicillin⁷.

Bacteria that cause community-acquired infections, especially pathogens resistant to various antibiotics, are a dangerous warning⁸. An increase in bacterial strains resistant to antibiotics will facilitate genetic changes in bacteria, resulting in the emergence of superbacteria resistant to various antibiotics⁹. Currently, antibiotics have an important role in the treatment of various infections, but antibiotic resistance has also become a major problem in health worldwide¹⁰.Unnecessary use of antibiotics causes antibiotic prescribing patterns to be inappropriate, both in quantity and choice of medication¹¹, so it becomes a challenge for medical personnel in treating infectious diseases¹². A study in India reported that Pseudomonas aeruginosa was the most resistant bacteria to all antibiotics, followed by Staphylococcus aureus, and Klebsiella pneumoniae, which showed different resistance patterns to antibiotics¹³. Pseudomonas aeruginosa is the most dangerous microorganism with high morbidity and mortality rates due to the rapid spread of antimicrobial resistance¹⁴. A study in Ethiopia reported indications of inappropriate use of antibiotics in hospitals and showed that many pathogens that cause infections are resistant to antibiotics that are often used in hospitals¹⁵.

The results of another study also reported that patients diagnosed with CAP had a high mortality rate in Bucharest, Romania, with microbiological analysis revealing the presence of several strains of Acinetobacter baumannii, Klebsiella sp., Escherichia coli, Staphylococcus aureus, and Pseudomonas sp. which is highly resistant to commonly prescribed antibiotics¹⁶.

Antimicrobial susceptibility patterns were developed by exploiting microbiology laboratory data available at the hospital¹⁷. Specimen culture and the use of antimicrobial susceptibility patterns can help clinicians identify organisms and select antibiotics¹⁸. Diagnosing the bacteria that cause CAP is a challenge because the lungs as a site of infection are not easily accessible to obtain samples without contamination of upper respiratory tract secretions¹⁹. Although it is difficult to obtain specimens without contaminants, culture, and local antimicrobial susceptibility testing need to be carried out periodically to reduce resistance levels and better manage CAP²⁰. This study aims to determine the etiological profile of community-acquired pneumonia in adult inpatients and antimicrobial susceptibility patterns at the Dr. Sardjito General Hospital, Yogyakarta, Indonesia.

MATERIALS AND METHODS:

Materials:

This study protocol was reviewed and approved by the Research Ethics Committee of the Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, approval number KE/FK/1026/EC/2022, and complies with the institutional and ethical standards of the research committee of Dr. Sardjito General Hospital, Yogyakarta, Indonesia. This study used the data of CAP patients admitted to the non-VIP ward of Dr. Sardjito General Hospital, Yogyakarta, Indonesia, from September 2022 to May 2023.

Methods:

Study Design:

A prospective cohort study was conducted in the non-VIP adult ward at Dr. Sardjito General Hospital.

Study Participants:

Includes 222 adult patients clinically or radiologically diagnosed with CAP, hospitalized in the adult ward unit, cardiovascular center unit, cardiovascular care unit (CVCU), intensive care unit (ICU), medical high care unit (MHCU), medical intensive care unit (MICU), intermediate care (IMC), high care unit (HCU), surgical intensive care unit (SICU), and surgical high care unit (SHCU), have a complete history of past illnesses, early symptoms of the disease, disease progression, and demographic details were collected from patients.

Inclusion Criteria:

Patients aged 18 years and over who were diagnosed with CAP based on pneumonia-specific chest x-ray results or clinical assessment, received empiric and definitive antibiotic therapy, bacterial culture using sputum specimens with a leukocyte count of >25 PMN per low field, antibiotic sensitivity testing, and had complete medical record data.

Exclusion Criteria:

If there is no growth of cultured bacteria, growth of bacterial flora, growth of fungal, the patient is discharged from the hospital at his request, and there is a change in diagnosis during the therapy period.

Sample Collection:

Sputum:

The sputum samples obtained were collected in a sterile container. Patients are instructed to gargle with water when they wake up in the morning and collect sputum after coughing into a sterile container given to the patient. The patient's sputum is collected only once in the morning.

Induced sputum collection: Performed in patients with difficulty expelling sputum, using 3% hypertonic saline in a nebulizer¹⁹.

Sample Processing:

All samples collected were processed at the Microbiology Laboratory of Dr. Sardjito General Hospital in less than 2 hours. Samples containing a large amount of saliva are rejected by the laboratory. All sputum samples were mucopurulent and subjected to Gram staining and culture.

Gram staining:

Ziehl-Neelsen staining was performed for screening for acid-fast bacilli and to look for the presence of epithelial cells and bacteria. The presence of <10 squamous epithelial cells (SECs) per low-power field (LPF) and >25 polymorphonuclear leukocytes (PMNs) per low-power field, or >10 polymorphonuclear leukocytes (PMNs) per oil immersion field (OIF), shows the validity of the sputum specimen. Quality samples having >10 microorganisms with the same morphotype in OIF were considered significant. The presence of multiple morphologies of microorganisms for which the dominant morphotype is not identified is considered a polymicrobial flora. If the sputum sample shows less than the number of cells mentioned above, bacterial culture is not continued because it indicates oropharyngeal contamination²¹.

Culture:

The obtained isolates were stored at −70°C in Trypticase-glycerol soy broth, subcultured on Columbia agar with 5% sheep blood, and incubated for 24 h at 35°C before testing²².

Inoculum preparation:

For the assay, inoculums of respective bacteria were prepared in the suspension by emulsifying the bacterial isolate in a 0.45% salt solution to the equivalent of a 0.5 McFarland turbidity standard. This suspension was also used for identification on the VITEK-2 instrument. The bacterial identification procedure was carried out by the manufacturer's recommendations²².

Antimicrobial Susceptibility Testing:

Identification of bacterial strains in this study used the VITEK-2 instrument which can perform automatic screening as an antimicrobial susceptibility test (AST). Vitex 2 consists of a fluorimetric test panel (ID-GPC) that works by detecting changes in pH to identify the presence of aminopeptidase and -osidase. The card on the test panel is filled automatically by a vacuum device, and sealed, then inserted into the VITEK 2 reader incubator (bacteria incubation process at 35.5°C). Kinetic fluorescence measurements were carried out every 15 minutes. The data on the ID-GPC test panel interprets the results automatically. Antimicrobial susceptibility results were interpreted according to Clinic and Laboratory Standards Institute (CLSI) standards. Results were reported as sensitive if ≥70%, intermediate if 40-69%, or resistance if <40%. All used cards are automatically thrown into the trash²².

RESULT:

A total of 879 patients were diagnosed with pneumonia, there were 293 patients according to specimen validity. Only 222 patients with pathogenic bacterial growth were included in this study. Patient enrollment is shown in (Figure 1).

Figure 1. Patient enrollment. CAP patients were excluded because the patients sputum can’t be collected and not according to the specimen validity, and the culture results shows bacterial flora and fungal

Characteristics of CAP Patients:

This study enrolled 222 adult patients diagnosed with CAP based on inclusion and exclusion criteria. Patient characteristics including age, sex, and distribution of CAP patients according to wards/intensive and non-intensive units are shown in (Table 1). CAP patients are mostly male, aged 18–59 years, and most patients receive treatment in non-intensive wards.

Table 1. Characteristics of CAP Patients

Frequency

Percent

Age (in years)

18 – 59

≥60

136

61.3

38.7

Sex

Male

Female

138

62.2

37.8

Wards

Intensive

Non-intensive

159

28.4

71.6

In this study, from 222 CAP patients, culture results were obtained as much 236 isolates of pathogenic bacteria which were suspected to be the clinical cause of CAP, with details of 208 patients each producing one strain of pathogenic bacteria (n=208 isolates), and 14 patients each producing two strains of pathogenic bacteria (n=28 isolates). Classification of resistant bacteria in CAP patients, extended-spectrum β-lactamase (ESBL), methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant coagulase-negative Staphylococci (MR-CoNS), multidrug-resistant organisms (MDRO), and extensively drug-resistant organism (XDRO), are shown in (Table 2).

Table 2. Classification of Resistant Bacteria in CAP Patients

Classification of Resistant Bacteria	Frequency	Percent
ESBL	30	12.7
MRSA	2	0.9
MR-CoNS	10	4.2
MDRO	8	3.4
XDRO	9	3.8
Not resistant	177	75
Total	236	100

ESBL : Extended Spectrum β-Lactamase

MRSA : Methicillin-Resistant Staphylococcus aureus

MR-CoNS: Methicillin-Resistant Coagulase-negative Staphylococci

MDRO : Multi-Drug Resistant Organisms

XDRO : Extensive Drug Resistance. Organisms

Gram-Positive Antimicrobial Susceptibility Patterns:

Pathogenic Gram-positive bacteria suspected to be the cause of CAP in this study are Coagulase-negative Staphylococci, Enterococcus faecalis/ faecium, Kocuria kristinae, Streptococcus sp., Staphylococcus epidermidis, Staphylococcus aureus, and Streptococcus mitis. Among the antibiotics tested on Gram-positive isolates, linezolid (83.3-100%) and vancomycin (75-100%) showed the highest sensitivity against almost all strains of bacterial isolates tested. Imipenem and levofloxacin had lower sensitivity to the number of bacterial isolate strains tested, but still has a sensitivity of 71.4-100%, are shown in (Table 3).

Table 3. Gram-Positive Antimicrobial Susceptibility Patterns

Antibiotics	Coagulase Negative Staphylococci (n=9)		Enterococcus faecalis/ faecium (n=8)		Kocuria kristinae (n=7)		Streptococcus sp. (n=7)		Staphylococcus epidermidis (n=5)		Staphylococcus aureus (n=4)		Streptococcus mitis (n=3)
Antibiotics	%S	n	%S	n	%S	n	%S	n	%S	n	%S	n	%S	n
Amikacin	-	-	-	-	-	-	50	2	-	-	-	-	0	3
Amoxicillin	0	2	100	7	-	-	-	-	0	2	0	1	-	-
Amoxicillin/ Clavulanic Acid	25	4	100	4	-	-	-	-	0	2	-	-	-	-
Ampicillin	-	-	100	7	-	-	100	2	-	-	-	-	100	3
Ampicillin/ Sulbactam	25	8	100	8	-	-	100	4	0	5	0	3	100	1
Azithromycin	22.2	9	-	-	75	4	57.1	7	0	5	75	4	100	2
Carbenicillin	0	1	-	-	-	-	-	-	0	2	-	-	-	-
Cefadroxil	0	6	-	-	-	-	-	-	0	4	0	1	-	-
Cefamandole	33.3	3	-	-	-	-	-	-	0	3	100	1	-	-
Cefazolin	66.7	3	-	-	-	-	-	-	0	3	100	1	-	-
Cefepime	0	6	0	1	100	5	100	2	0	3	33.3	3	100	1
Cefixime	0	1	-	-	-	-	-	-	0	3	0	1	-	-
Cefotaxime	22.2	9	0	1	-	-	100	2	0	5	50	4	33.3	3
Cefoxitin	0	7	-	-	-	-	66.7	6	0	4	0	2	100	1
Cefpirome	0	1	-	-	-	-	-	-	0	2	-	-	-	-
Ceftazidime	14.3	7	0	1	66.7	6	83.3	6	0	3	50	4	50	2
Ceftizoxime	14.3	7	-	-	-	-	-	-	0	4	33.3	3	-	-
Ceftriaxone	40	5	-	-	-	-	25	4	0	5	66.7	3	33.3	3
Cefuroxime	12.5	8	-	-	-	-	100	4	0	5	33.3	3	66.7	3
Cephalexin	0	1	-	-	-	-	-	-	0	3	-	-	-	-
Cephalothin	50	2	-	-	-	-	-	-	0	2	-	-	-	-
Chloramphenicol	-	-	-	-	85.7	7	100	7	-	-	-	-	100	2
Ciprofloxacin	12.5	8	71.4	7	50	6	66.7	3	0	4	50	4	33.3	3
Clindamycin	50	8	-	-	66.7	3	80	5	40	5	75	4	66.7	3
Cloxacillin	-	-	-	-	-	-	-	-	0	2	0	1	-	-
Doxycycline	-	-	-	-	66.7	3	0	1	-	-	-	-	50	2
Erythromycin	0	7	0	8	0	5	33.3	3	0	4	66.7	3	100	1
Flucloxacillin	-	-	-	-	-	-	-	-	0	2	-	-	-	-
Gentamicin	75	8	-	-	20	5	75	4	40	5	66.7	3	-	-
Imipenem	0	4	100	6	-	-	100	2	0	2	100	1	100	1
Kanamycin	-	-	-	-	-	-	0	2	-	-	-	-	100	1
Levofloxacin	25	8	71.4	7	100	2	100	2	0	4	66.7	3	100	2
Linezolid	100	7	83.3	6	-	-	-	-	100	5	100	3	100	1
Meropenem	20	5	-	-	100	1	-	-	0	5	0	3	-	-
Moxifloxacin	0	6	-	-	60	5	50	2	0	3	0	1	100	1
Nafcillin	-	-	-	-	-	-	-	-	0	2	-	-	-	-
Ofloxacin	-	-	-	-	60	5	80	5	-	-	-	-	100	2
Oxacillin	12.5	8	-	-	0	7	100	7	0	5	33.3	3	100	3
Penicillin G	0	7	66.7	6	0	6	-	-	0	5	33.3	3	50	2
Piperacillin	-	-	-	-	-	-	-	-	0	2	-	-	-	-
Piperacillin/ Tazobactam	0	1	100	1	-	-	-	-	0	2	0	1	-	-
Quinupristin/ Dalfopristin	100	2	0	2	-	-	-	-	100	1	-	-	-	-
Tetracycline	44.4	9	50	8	66.7	3	0	5	100	4	50	2	0	2
Ticarcillin/ Clavulanic Acid	0	1	-	-	-	-	-	-	0	2	0	1	-	-
Tigecycline	100	1	-	-	-	-	100	1	100	2	-	-	0	1
Trimethoprim	-	-	-	-	33.3	3	25	4	-	-	-	-	100	2
Trimethoprim/ Sulfamethoxazole	50	6	-	-	100	1	66.7	3	33.3	3	50	2	-	-
Vancomycin	87.5	8	100	5	-	-	-	-	100	5	75	4	100	1

Table 4. Gram-Negative Antimicrobial Susceptibility Patterns

Antibiotics	*Klebsiella pneumoniae (n=61)*		*Acinetobacter baumannii (n=41)*		*Pseudomonas aeruginosa (n=33)*		*Enterobacter cloacae (n=20)*		*Escherichia coli (n=13)*		*Stenotrophomonas maltophilia (n=6)*		*Serratia marcescens (n=5)*
Antibiotics	%S	n	% S	n	% S	n	% S	n	%S	n	%S	n	%S	n
Amikacin	98.1	52	83.8	37	87.5	32	100	15	100	10	66.7	3	50	4
Ampicillin	0	61	0	7	0	5	0	20	15.4	13	0	4	0	5
Ampicillin/ Sulbactam	54.1	61	63.4	41	0	4	0	19	33.3	12	0	3	20	5
Amoxicillin/ Clavulanic acid	0	2	0	4	0	3	0	1	0	1	0	1	0	1
Azithromycin	44.4	9	66.7	3	50	2	40	5	-	-	100	1	-	-
Aztreonam	33.3	30	0	5	57.6	33	72.2	18	12.5	8	0	3	25	4
Cefadroxil	0	2	0	3	0	3	0	1	0	1	0	1	0	1
Cefazolin	0	4	0	36	0	28	0	19	-	-	0	3	0	5
Cefepime	71.1	38	59	39	69.2	26	90.9	11	42.9	7	0	2	50	2
Cefixime	-	-	0	5	0	4	-	-	-	-	0	1	0	1
Cefoperazone	20	5	0	9	0	4	100	3	0	3	0	1	-	-
Cefotaxime	25	4	0	8	0	4	0	1	0	1	0	5	50	2
Cefoxitin	75	4	0	8	0	5	0	1	-	-	0	4	0	1
Ceftazidime	55.8	52	51.4	37	75	32	68.8	16	38.5	13	50	2	40	5
Ceftriaxone	50.9	57	23.1	39	14.3	14	63.2	19	23.1	13	0	4	25	4
Cefuroxime	0	3	0	7	0	4	100	1	0	1	0	3	50	2
Cephalothin	0	1	-	-	-	-	0	1	0	1	0	1	-	-
Chloramphenicol	66.7	3	0	8	0	4	100	1	0	1	50	4	50	2
Colistin	100	1	100	5	100	4	-	-	100	1	-	-	-	-
Ciprofloxacin	52.6	57	55	40	75.8	33	83.3	18	16.7	12	80	5	40	5
Doripenem	100	1	0	1	-	-	-	-	-	-	100	1	-	-
Ertapenem	91.7	36	0	4	0	5	90.9	11	90	10	25	4	100	2
Fosfomycin	0	1	0	8	0	4	-	-	100	1	50	2	50	2
Gentamicin	72.4	59	62.5	40	85.7	28	100	19	33.3	12	100	5	25	4
Imipenem	100	2	0	5	25	4	0	1	-	-	0	3	-	-
Kanamycin	0	1	0	3	0	3	-	-	-	-	0	1	100	1
Levofloxacin	57.1	7	12.5	8	14.3	7	100	4	0	5	100	4	0	1
Meropenem	98.1	54	63.4	41	81.8	33	100	19	90.9	11	0	5	80	5
Moxifloxacin	33.3	3	0	1	-	-	0	1	-	-	-	-	-	-
Netilmicin	100	1	0	4	0	4	-	-	-	-	100	1	100	1
Ofloxacin	-	-	0	1	-	-	-	-	-	-	-	-	-	-
Piperacillin/ Tazobactam	54.5	22	20	15	78.3	23	91.7	12	80	5	100	1	50	2
Tetracycline	0	2	12.5	8	0	3	100	1	0	1	0	4	50	2
Tigecycline	77.8	9	71.4	28	0	30	66.7	3	100	5	100	1	100	2
Tobramycin	0	3	12.5	8	0	5	0	1	-	-	100	5	50	2
Trimethoprim	25	4	0	6	0	3	100	1	0	1	50	2	0	2
Trimethoprim/ Sulfamethoxazole	64.9	57	69.2	39	10	10	87.5	16	38.5	13	100	5	60	5

Gram-Negative Antimicrobial Susceptibility Patterns:

Pathogenic Gram-negative bacteria suspected to be the cause of CAP in this study are Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter cloacae, Escherichia coli, Stenotrophomonas maltophilia, and Serratia marcescens. Among the antibiotics tested on Gram-negative isolates, amikacin (83.8-100%), meropenem (80-100%), and tigecycline (71.4-100%) showed the highest sensitivity against almost all strains of bacterial isolates tested. Colistin, ertapenem, and gentamicin had lower sensitivity to the number of bacterial isolate strains tested, but still had a sensitivity of 74.6-100% are shown in (Table 4).

DISCUSSION:

Of the 236 isolates of pathogenic bacteria in community-acquired pneumonia patients analyzed, there were 30 isolates (12.71%) of Klebsiella pneumoniae and Escherichia coli as ESBL producers. A similar study was conducted in Chiangrai Prachanukroh Hospital, Thailand, reported that out of 384,001 bacterial isolates from pneumonia patients, Klebsiella pneumoniae and Escherichia coli species as ESBL producers, 6,403 isolates (1.67%)²³. The same study was also conducted at Sree Gokulam Medical College and Research Foundation, Venjaramoodu, Thiruvananthapuram, Kerala, India reported that out of a total of 120 pneumonia cases there were Klebsiella pneumoniae and Escherichia coli species as ESBL producers in 10 isolates (8.33%)²⁴. Klebsiella pneumoniae and Escherichia coli were identified based on colony morphology and biochemical characteristics, then confirmed by the VITEK 2 system identification²⁵. Isolates showing reduced susceptibility to β-Lactam antibiotics were considered ESBL producers²⁶. In vitro, resistance to ceftazidime or aztreonam is used as a phenotypic marker of ESBL, including amino-penicillin combinations, β-lactamase inhibitor ampicillin sulbactam, piperacillin/tazobactam¹³, and cephalosporins (cefotaxime, and ceftriaxone). The test was considered positive when an increase in any inhibition zone of the marker and ceftazidime/clavulanic acid or cefotaxime/ clavulanic acid²⁷. The highest frequency of pathogenic bacterial infections in this study were ESBL producers Klebsiella pneumoniae and Escherichia coli in patients with CAP. Klebsiella pneumoniae bacteria are mostly found in sputum, and these ESBL-producing strains are highly resistant to several antimicrobial agents, especially carbapenems and aminoglycosides. Escherichia coli strains are very widely distributed, and some special types of Beta-Lactamases also hydrolyze broad-spectrum cephalosporins²³.

The MRSA-positive isolates in this study were 2 (0.85%) out of 236 isolates of CAP pathogenic bacteria. This number is greater than a multicenter study conducted at hospitals in Chicago, Illinois, and hospitals in Nashville, Tennessee. This study reported that 15 isolates (0.66%) of pathogenic bacteria were positive for MRSA from 2259 bacterial isolates from CAP patients²⁸. A study at Barcelona Hospital, Spain also reported regarding the discovery of MRSA bacteria that there were 34 isolates (2%) of MRSA-positive pathogenic bacteria from 1548 bacterial isolates from CAP patients²⁹. MRSA bacteria in CAP patients can be detected using methicillin or oxacillin by the Clinical and Laboratory Standards Institute (CLSI) guidelines for Antimicrobial Susceptibility Testing (AST)¹⁵. MRSA develops not only as a nosocomial infection but also outside hospitals. Mec A is a gene transpeptidase that most frequently mediates methicillin resistance on Staphylococcus aureus³⁰.

Based on the culture results, there were 8 isolates (3.39%) of MDRO bacteria from a total of 236 isolates of pathogenic bacteria from CAP patients. Most patients with MDRO culture results have complications from other diseases, such as sepsis, Hodgkin lymphoma, ulcers, hepatitis, congestive heart failure, and kidney disease, so they receive a lot of medication. This MDRO case also occurred at Arba Minch General Hospital, Arba Minch town, Ethiopia, based on studies that had been carried out, it was found that 15 isolates (68.18%) had MDRO from a total of 22 isolates from infected patients³¹. A study conducted at Bukavu General Hospital, Democratic Republic of the Congo reported that 35 isolates (31.25%) of bacteria were MDRO out of 112 total isolates analysed³². MDRO cases that occur in many hospitals have the potential to cause the widespread prevalence of infectious diseases and outbreaks. The development of bacterial resistance to various antibiotics is a major crisis because it limits the choice of antibiotics for the treatment of infections³⁰. MDRO can occur through enzymatic inactivation of drugs by degradation (hydrolysis) or by transfer of chemical groups of acetyl, phosphoryl, and adenyl groups³³, so that the bacteria are not susceptible to at least one antimicrobial in three or more antimicrobial groups³⁴.

XDRO-positive isolates were identified in 9(3.81%) of the 236 isolates of CAP pathogenic bacteria. This number is almost the same as a study conducted in King Saud University Medical City (KSUMC) Hospital, Riyadh, Saudi Arabia, reported that there were 8 isolates (3.52%) of XDRO bacteria from a total of 227 cultures identified³⁵. Another study related to XDRO was also conducted at Jawaharlal Nehru Medical College and Hospital, India, reporting that there were 146 isolates (13.77%) of Gram-positive and Gram-negative bacteria identified by XDRO out of a total of 1,060 bacterial isolates³⁶. There is an XDRO strain in our study because Dr. Sardjito General Hospital is a referral hospital for patient care in Yogyakarta and parts of Central Java, so before patients come to Dr. Sardjito General Hospital has received antibiotics from general practitioners or other hospitals, which are often in inappropriate doses. Enterobacteriaceae isolates were considered XDRO if they were resistant to five or six of the six antimicrobial groups. Isolate Acinetobacter spp. or Pseudomonas aeruginosa is considered XDRO if it is resistant to all of five groups of antimicrobials³⁷. The most common pathogens that cause moderate to severe pneumonia and potentially be MDRO/XDRO are Pseudomonas spp., Acinetobacter spp., and Klebsiella spp.³⁴ as was the case in this study.

After the culture test, 10 isolates (4.24%) of MR-CoNS bacteria were found from a total of 236 bacteria identified. Another similar study conducted at Osaka City University Hospital, Japan reported that 70 isolates (0.50%) of MR-CoNS bacteria were found from a total of 13.941 isolates analysed³⁸. A study related to MR-CoNS also conducted at a University Hospital, in India reported that there were 115 isolates (85.80%) of positive MR-CoNS bacteria from a total of 134 isolates analysed³⁹. Several studies have shown that infections in various countries are caused by strains of coagulase-negative staphylococci (CoNS) that are resistant to methicillin (MR-CoNS). CoNS are categorized in the Micrococcaceae family which is considered less virulent than Staphylococcus aureus. CoNS infection is associated with the use of existing health equipment in the community, immunocompromised patients, and frequency of equipment implantation patient during hospitalization⁴⁰. Various factors, such as biofilm production in CoNS strains, inappropriate antibiotic prescribing, and excessive use of antibiotics, cause CoNS bacteria to become resistant to antibiotics, this has resulted in several therapeutic problems in the health system⁴¹.

In Gram-positive bacteria, CoNS strains are susceptible to the antibiotics gentamicin, linezolid, quinupristin/dalfopristin, tigecycline, and vancomycin, with a susceptibility level of 75-100%, this is similar to another study conducted in the Department of Microbiology, B.P. Koirala Institute of Health Sciences, Dharan, Nepal⁴². CoNS that were resistant to methicillin (oxacillin) are Staphylococcus haemolyticus, Staphylococcus epidermidis, and Staphylococcus hominis, in line with the results of other study conducted at the Department of Microbiology, University Hospital, Uttar Pradesh, India, and in the Department of Microbiology, B.P. Koirala Institute of Health Sciences, Dharan, Nepal³⁹^,⁴². More than half of MR-CoNS patients were diagnosed with sepsis, chronic myeloid leukemia, lung adenocarcinoma, breast cancer, non-small cell lung cancer, and non-Hodgkin's lymphoma. Increased risk of CoNS bacteremia in patients with malignancy possibly related to chemotherapy side effects, mucosal and skin abnormalities, and catheter infections³⁸. Staphylococcus epidermidis bacteria had a very high susceptibility to the antibiotics linezolid, tigecycline, and vancomycin with a susceptibility level of 100%, this is similar to another study at the Chinese People's Liberation Army General Hospital (PLAGH), Beijing, China⁴³.

Staphylococcus aureus is only susceptible to azithromycin, cefamandole, cefazolin, clindamycin, imipenem, linezolid, and vancomycin, with a susceptibility level of 75-100%. Staphylococcus aureus is one of the main pathogens in hospitals and causes infectious diseases including mild to severe pneumonia has the attracted attention of the global medical community⁴⁴. Vancomycin is the first-line antibiotic choice for Staphylococcus aureus or MRSA bacteremia, if bacteremia occurs without complications, treatment is at least 14 days from the first negative blood or sputum culture, if complications occur then treatment is carried out for 4 to 6 weeks⁴⁵. Vancomycin has poor penetration of lung tissue, therefore there are other recommended antibiotic options such as linezolid or clindamycin⁴⁴. Linezolid has bacteriostatic action so that patients with MRSA infections treated with linezolid have good clinical outcomes⁴⁶. The Enterococcus faecalis/ faecium strain was susceptible to the penicillin group, imipenem, vancomycin, and linezolid with a susceptibility level of 83,3.-100%, widely used to treat systemic infections Enterococcus, including CAP and sepsis⁴⁷. The Streptococcus sp. strain was susceptible to the penicillin group, cephalosporin group, chloramphenicol, macrolide group, imipenem, fluoroquinolone group, aminoglycoside group, and tigecycline with a susceptibility level of 75-100%. Based on clinical studies, linezolid can be well tolerated by patients, and has a strong effect on most Gram-positive bacteria, but it is necessary to be aware of the potential side effects⁴⁸.

In Gram-negative bacteria, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter cloacae, and Escherichia coli are susceptible to amikacin (83,8-100%). Strains of Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli are susceptible to colistin (100%), The bacterial strains were susceptible to amikacin and colistin, in line with the results of other studies conducted across regions of Latin America (LATAM), Africa-Middle East (AfME), and Asia from 2016 - 2020⁴⁹. Strains susceptible to gentamicin (72,4-100%) are Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterobacter cloacae, and Stenotrophomonas maltophilia. This is different from another study which reported that gentamicin was susceptible to Pseudomonas species (93.4%), Escherichia coli (92.5%), and Klebsiella pneumonia (>85%)⁵⁰. Strains susceptible to the ciprofloxacin and levofloxacin (75.8-100%) are Pseudomonas aeruginosa, Enterobacter cloacae, and Stenotrophomonas maltophilia, this is similar to other studies on K. R.

hospital, Mysore, India⁵¹.

Strains of Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterobacter cloacae, Escherichia coli, and Serratia marcescens are susceptible to the meropenem (80-100%), imipenem is only susceptible to Klebsiella pneumonia (100%), and doripenem susceptible to Klebsiella pneumoniae and Stenotrophomonas maltophilia (100%). This is different from another study which reported that the carbapenem group was susceptible only to Klebsiella pneumonia and Pseudomonas aeruginosa⁵². Strains susceptible to piperacillin/ tazobactam (78.3-100%) are Pseudomonas aeruginosa, Enterobacter cloacae, Escherichia coli, and Stenotrophomonas maltophilia. This is different from another study which reported that the piperacillin/ tazobactam was susceptible only to Escherichia coli (82%)¹². Strains of Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli, Stenotrophomonas maltophilia, and Serratia marcescens are susceptible to the tigecycline (71.4-100%). This is different from another study which reported that the tigecycline was susceptible are Acinetobacter baumannii (95.3%), Escherichia coli (98.9%), Pseudomonas aeruginosa (98.3%), Enterobacter cloacae (96.1%)⁵⁰. Strains susceptible to trimethoprim/ sulfamethoxazole (87.5-100%) are Enterobacter cloacae and Stenotrophomonas maltophilia. This is different from another study which reported that the trimethoprim/ sulfamethoxazole was susceptible are Klebsiella pneumonia (86%), Acinetobacter baumannii (73%), Stenotrophomonas maltophilia (65%), and Enterobacter (100%)⁵³.

This study is useful for clinicians in determining empirical treatment for CAP patients in hospital. Through sputum culture, the organism causing the infection can be identified. The antimicrobial susceptibility patterns that have been compiled can be used as a guide in choosing the right antibiotic according to the patient's condition.

CONCLUSION:

The bacteria suspected to cause CAP are dominated by coagulase-negative Staphylococci which was susceptible to gentamicin, linezolid, quinupristin/dalfopristin, tigecycline, and vancomycin; Enterococcus faecalis/faecium which was susceptible to penicillin, fluoroquinolone, carbapenem, vancomycin, and linezolid; Streptococcus sp. which was susceptible to penicillin, cephalosporin, chloramphenicol, macrolide, imipenem, fluoroquinolone, and tigecycline; Klebsiella pneumoniae which is susceptible to aminoglycosides, second and fourth-generation cephalosporins, colistin, and tigecycline; Acinetobacter baumannii which is susceptible to amikacin, colistin, and tigecycline; Pseudomonas aeruginosa which is susceptible to aminoglycosides, third-generation cephalosporins, colistin, fluoroquinolones, carbapenems, and penicillins.

LIMITATIONS OF THE STUDY:

Antibiotic susceptibility testing of atypical bacteria was not performed and the virus-causing CAP was not explored in this study as a diagnostic approach to the disease. The lack of surveillance data is due to the difficulty in collecting sputum specimens that meet validity requirements, thereby limiting the detailed interpretation of the results.

CONFLICT OF INTEREST:

Authors declare that there are no conflict of interest.

ACKNOWLEDGMENTS:

The authors would like to thank the Head of Wards, the Medical Staff Group of Internal Medicine, The Microbiology Laboratory, and the Medical Records section of Dr. Sardjito General Hospital, Yogyakarta, Indonesia, for their support of this study.

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Received on 06.09.2024 Revised on 20.01.2025

Accepted on 25.03.2025 Published on 05.09.2025

Available online from September 08, 2025

Research J. Pharmacy and Technology. 2025;18(9):4313-4322.

DOI: 10.52711/0974-360X.2025.00619

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