1 Introduction

It is anticipated that COPD will be the third most common cause of death worldwide by 2030, following heart disease and stroke [1]. Chronic Obstructive Pulmonary Disease is a progressive lung disease that is characterized by chronic respiratory symptoms (shortness of breath, cough, sputum production) due to airway abnormalities, including chronic bronchitis, emphysema, and sustained gradual airflow limitation [2]. The primary cause of COPD is exposure to cigarette smoke, whether through active or passive smoking [3]. Research findings indicate that the majority of COPD patients are male, with the highest prevalence occurring in the age group of \(\geq\) 60 years [3, 4]. Inadequate management and evaluation of drug use are contributing factors to the rise in mortality rates among patients with pulmonary obstruction [5]. The rational use of drugs must satisfy several criteria, including the selection of the appropriate drug, appropriate indication, dosage, route of administration, and patient. The irrational use of medication in COPD patients can result in inappropriate treatment, which ultimately exacerbates the condition, increases the severity of COPD, reduces the quality of life, and increases the risk of death [5]. Antibiotics are among the therapeutic interventions administered to patients with COPD.

The use of antibiotics in COPD therapy is only recommended for patients who have a bacterial infection and exhibit at least two of the following three symptoms: increased dyspnoea, increased sputum volume, and increased sputum purulence (change in sputum color). The risk of therapy failure and the global threat to public health, particularly in the context of bacterial resistance to antibiotics, can be elevated by the inappropriate use of antibiotics in COPD patients [4, 6]. The rational use of antibiotics in COPD patients is supported by prior research, which includes six types of antibiotics: ceftriaxone, azithromycin, cefixime, cefadroxil, levofloxacin, and cefazolin [4]. The implementation of the Antimicrobial Resistance Control Program (PPRA) in healthcare facilities, particularly hospitals, is crucial. It is imperative to conduct routine reporting on antimicrobial sensitivity patterns to assess the sensitivity levels of the local population [7]. An antibiogram is a report that delineates the general pattern of antibiotic sensitivity of isolates that have been tested by clinical microbiology laboratories [8]. Previous research on the antibiogram profile of pneumonia patients at RS Akademik UGM and ISPA patients at Puskesmas Jetis Yogyakarta revealed that the results were more favorable for gram-negative bacteria [8, 9]. The absence of data regarding COPD in Makassar is a compelling justification for the necessity of conducting this research. The findings may later serve as a clinical reference for the appropriate use of antibiotics and DDD values for patients in Makassar.

2 Research method

The research was conducted using a cross-sectional method and retrospective data collection based on medical records and analysed descriptively. The sampling technique used was purposive sampling. The population of this study consists of data from patients with Chronic Obstructive Pulmonary Disease who received antibiotic therapy, as well as the antibiogram profile data of COPD patients at Labuang Baji Hospital Makassar. The sample for this study was determined based on inclusion and exclusion criteria. Inclusion criteria are essential elements that must be present in the research, while exclusion criteria are populations that cause subjects not to meet the inclusion criteria, thus not included in the study [6]. The inclusion criteria for patients with Chronic Obstructive Pulmonary Disease receiving antibiotic therapy, patients with Chronic Obstructive Pulmonary Disease aged \(>\)18 years, patients with Chronic Obstructive Pulmonary Disease with complete medical records, and patients with Chronic Obstructive Pulmonary Disease treated from January to December 2024. Exclusion criteria are patients with Chronic Obstructive Pulmonary Disease who have a history of antibiotic allergy. The statistical analysis used is multivariate testing, and antibiotic usage data is analysed quantitatively using the Defined Daily Dose (DDD) method. The research procedure was conducted by collecting all medical record notes of Chronic Obstructive Pulmonary Disease patients, which included name, age, gender, length of hospitalisation, name of antibiotics, dosage, therapy frequency, name of bacteria, type of bacteria, DDD value, and clinical parameters including (initial leukocytes, final leukocytes, initial pulse, final pulse, initial temperature, final temperature, as well as initial respiratory rate and final respiratory rate) at RSUD Labuang Baji Makassar according to the inclusion and exclusion criteria.

3 Result

Data were collected from 149 patients who satisfied the inclusion criteria for this study. The characteristics of COPD patients at Labuang Baji Hospital, Makassar, are categorized according to gender, age, and length of hospital stay.

The prevalence of Chronic Obstructive Pulmonary Disease (COPD) is higher in men than in women, primarily due to the male smoking lifestyle. However, the current prevalence of COPD is nearly identical between men and women, a phenomenon associated with the increasing number of female smokers [10, 11]. Patient distribution by gender and duration of admission among COPD patients at Labuang Baji Hospital, Makassar (Table 1).

According to gender, the proportion of male patients is 50.3%, which is higher than the proportion of female patients (49.7%). The results obtained are consistent with those of previous studies, in which the number of male patients was greater than that of female patients [11, 12]. Smoking habits in Indonesia are likely to increase annually. Consequently, the risk of developing COPD is on the rise.

This is followed by the age-based distribution of COPD patients at RSUD Labuang Baji Makassar. Age is one of the risk factors that affect the prevalence of COPD. The likelihood of a decline in lung function capacity increases as an individual’s age increases, rendering them more susceptible to lung diseases. This susceptibility is further exacerbated by poor habits [13].

Table 1 indicates that the majority of hospitalized Chronic Obstructive Pulmonary Disease patients were admitted for 3–7 days, totaling 142 patients (95.3%), while those hospitalized for 7 days or more amounted to 7 patients (4.7%). The findings align with prior studies indicating that a greater number of patients were hospitalized for 3–5 days [14, 15]. The extension of hospitalization duration for COPD patients indirectly indicates a deceleration in the recovery process for those receiving inpatient treatment [16]. Multiple factors can influence the length of hospitalization, including smoking behaviors and the existence of comorbidities. Consequently, the prompt management of comorbidities and the cessation of smoking significantly contribute to reducing the length of hospital stays [15].

Antibiotics are administered to COPD patients during exacerbations. Exacerbations in chronic obstructive pulmonary disease are precipitated by viruses or bacteria. In patients experiencing exacerbations, the prioritization of empirical antibiotic administration is emphasized [11]. The Guidelines for the Diagnosis and Management of COPD indicate that empirical antibiotics suitable for patients experiencing acute COPD exacerbation include aminopenicillins with or without clavulanic acid, macrolides, tetracyclines, or quinolones [10]. Antibiotics should be administered for 5 to 7 days, as prolonged use may elevate the risk of antimicrobial resistance and lead to various complications.

The choice of antibiotics must consider the potential for bacterial resistance, particularly in the case of gram-negative bacteria. This study examines the characteristics of antibiotic utilization, encompassing both monotherapy and combination therapy regimens, which include cephalosporins (cefadroxil, cefixime, ceftriaxone, cefotaxime), macrolides (azithromycin), fluoroquinolones (ciprofloxacin, levofloxacin), tetracyclines (doxycycline), quinolones (moxifloxacin), lincosamides (clindamycin), and sulfonamides (cotrimoxazole).

Table 2 illustrates the distribution of antibiotic treatment for COPD patients at RSUD Labuang Baji Makassar in 2024. It indicates that there are 20 categories of antibiotic therapies, classified into two regimens: single or combination. The predominant therapeutic regimen employed is the combination antibiotic ceftriaxone + cefixime, utilized by 59 patients (39.6%), followed by the monotherapies azithromycin and cefixime (12.8%).

Ceftriaxone is extensively utilized as empirical therapy due to its broad-spectrum antibiotic properties, which are effective against gram-positive, gram-negative, and anaerobic bacteria [17, 18]. Third-generation cephalosporin antibiotics, including ceftriaxone and cefixime, exhibit enhanced efficacy against gram-negative bacteria compared to second-generation cephalosporins [4].

Azithromycin is administered to patients experiencing acute exacerbations of COPD caused by bacterial infections. The findings indicated that azithromycin was used as monotherapy in 12.8% of cases. This aligns with previous studies on antibiotic utilization in COPD patients, which found azithromycin used as a sole antibiotic in 21% of cases. Azithromycin is a macrolide antibiotic known for its antibacterial properties, as well as its immunomodulatory and anti-inflammatory effects. It is recognized for reducing the incidence of exacerbations in individuals with chronic obstructive pulmonary disease.

A statistical analysis was conducted to evaluate the therapeutic efficacy of antibiotics administered to COPD patients at Labuang Baji Hospital, Makassar, in 2024. This evaluation was based on the comparison of vital sign parameters, including initial and final leukocyte counts, pulse rates, body temperatures, and respiratory rates. The multivariate test analysis revealed a correlation between the type of antibiotic used and clinical outcomes. The results of this analysis are presented in Table 3, which summarizes the associations between antibiotic therapy regimens and clinical parameters.

The analysis revealed significant alterations in all measured clinical parameters—specifically leukocyte count, pulse rate, body temperature, and respiratory rate—before and after the intervention. The increase in leukocyte count from 20,572 to 25,946 indicates the body’s immune response to infection. This may reflect the efficacy of the therapy in stimulating the immune system or serve as an indicator of the recovery process. The average values of the initial and final leukocyte counts show a significant rise. These findings align with research conducted at RSIJ Sukapura, which reported that 88.6% of the samples exhibited elevated leukocyte levels. Additional studies also suggest that elevated leukocyte levels are significantly associated with the severity of COPD [19, 20].

Comorbidities in COPD patients are a known risk factor for elevated leukocyte counts. The development of COPD is closely linked to systemic oxidative stress mechanisms and elevated plasma levels of pro-inflammatory cytokines, including C-Reactive Protein (CRP), Interleukin-6 (IL-6), fibrinogen, Tumour Necrosis Factor (TNF), and leukocytosis [21, 22].

A notable reduction in pulse rate was observed, decreasing from 20.895 to 14.876. Pulse rate can serve as an indicator of lung function and may predict mortality risk in COPD patients during acute exacerbations [12]. An elevated resting pulse rate, independent of physical activity, correlates with increased mortality risk [23]. Body temperature and respiratory rate are also important indicators in chronic obstructive pulmonary disease. Common symptoms of COPD include dyspnoea and elevated respiratory rate. Body temperature serves as an indicator of coexisting infections, such as pneumonia or pulmonary tuberculosis, which often accompany COPD [12]. These trends suggest a general improvement in the patient’s clinical condition.

The statistical test results yielded a p-value \(<\) 0.001 for all measured parameters, indicating a highly significant difference between pre- and post-intervention values. This confirms that the administered therapy regimen was substantially effective.

The distribution of patients by the type of infecting bacteria in COPD cases at Labuang Baji Hospital is shown in Table 4.

The antibiogram provides insights into the bacterial patterns associated with chronic obstructive pulmonary disease (COPD), based on culture results obtained from hospital microbiology laboratory analyses. According to diagnostic guidelines for COPD, several bacterial pathogens are commonly implicated, including Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, and Haemophilus parainfluenzae. In severe cases of acute exacerbation, antibiotic-resistant bacteria such as Pseudomonas aeruginosa and other gram-negative organisms may also be present.

This study identified six bacterial species from culture examinations: Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli, and Staphylococcus haemolyticus. Among them, Pseudomonas aeruginosa was the most prevalent, with a frequency of 21.5%. This finding aligns with prior studies showing that COPD patients experiencing severe exacerbations are frequently infected by Pseudomonas aeruginosa.

As shown in Table 5, the total Length of Stay (LOS) for the 149 COPD patients was 744 days. The LOS is used in the computation of the Defined Daily Dose (DDD), which represents the assumed average maintenance dose per day for a drug used for its main indication in adults. The DDD value provides a standardised metric for evaluating drug consumption and facilitates international comparisons [24].

This study analysed 11 antibiotics prescribed to COPD patients at Labuang Baji Hospital in 2024. The highest DDD/100 patient-days were observed for ceftriaxone (58.9) and cefixime (56.2), followed by azithromycin (40.3), cotrimoxazole (9.0), doxycycline (41.9), ciprofloxacin (5.4), levofloxacin and cefadroxil (2.3), cefotaxime (1.7), clindamycin (1.3), and moxifloxacin (0.8).

4 Discussion

The antibiotics exhibiting the highest Defined Daily Dose (DDD) values belong to the Cephalosporin class, specifically ceftriaxone (58.9 g) and cefixime (56.2 g). This elevated value signifies that both antibiotics are the most extensively utilized. Cephalosporin antibiotics are the most frequently utilised as empirical therapy for patients with chronic obstructive pulmonary disease. A separate study indicates that ceftriaxone and cefixime, categorised as third-generation cephalosporins, have demonstrated efficacy against microorganisms responsible for exacerbations in patients with chronic obstructive pulmonary disease (COPD) [4, 25]. The extensive utilisation of ceftriaxone and cefixime is attributable to multiple factors, which indicates that the cephalosporin class is applicable as a treatment for chronic obstructive pulmonary disease (COPD). The third highest DDD/100 patient days value is attributed to azithromycin, recorded at 40.3 grammes. Macrolide antibiotics, including azithromycin, are advised for COPD patients experiencing acute exacerbations. Macrolides possess antibacterial, immunomodulatory, and anti-inflammatory properties, and their administration decreases the incidence of exacerbation events in patients with COPD [5]. The antibiotics with a low Defined Daily Dose value comprise cotrimoxazole (9.0 g), doxycycline (4.2 g), ciprofloxacin (4.0 g), levofloxacin and cefadroxil (2.3 g), cefotaxime (1.7 g), clindamycin (1.5 g), and moxifloxacin (0.8 g). The Defined Daily Dose (DDD) value indicates the extent of antibiotic usage; a lower DDD value correlates with a diminished probability of resistance [26]. The research findings reveal that the low DDD value signifies the limited prescription of medication for patients with chronic obstructive pulmonary disease at Labuang Baji Hospital.

The World Health Organization states that antibiotic usage should be reduced in infection management. An increase in the total DDD/100 patient days value may signify elevated antibiotic consumption and potentially indicate irrational drug utilization. If the DDD/100 patient days value declines, it signifies more regulated antibiotic usage and is likely aligned with the principles of rational use [27].

5 Conclusion

This study concludes that the most frequently utilized antibiotics are a combination of ceftriaxone and cefixime, both of which are third-generation cephalosporins, along with azithromycin as a monotherapy. Statistical analysis confirms the effectiveness of these treatments in managing chronic obstructive pulmonary disease (COPD).

The predominant bacterium identified was Pseudomonas aeruginosa, classified as gram-negative. The analysis of Defined Daily Dose (DDD) per 100 patient-days shows that ceftriaxone has the highest value, reflecting its broad-spectrum efficacy, while cefixime is notably effective against gram-negative bacteria.

Acknowledgment

The authors express their gratitude to Universitas Muslim Indonesia for supporting this research, and to Labuang Baji Hospital Makassar for facilitating the data collection and clinical collaboration.