The Rationality of Antibiotic use Based on Qualitative Parameters in Community-acquired Pneumonia Therapy at General Hospital, Indonesia

Rosaria Ika Pratiwi¹, Agung Endro Nugroho²*, Ika Puspitasari², Tri Murti Andayani²

¹Doctoral Program in Pharmaceutical Sciences, Faculty of Pharmacy,

Universitas Gadjah Mada, Yogyakarta, Indonesia.

²Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy,

Universitas Gadjah Mada, Yogyakarta, Indonesia.

ABSTRACT:

The use of antibiotics in Community-acquired pneumonia (CAP) patients, apart from being empiric therapy, is also a definitive therapy by the results of antibiotic sensitivity tests on bacteria, so it needs to be evaluated so that the use of antibiotics becomes more rational. This study aims to determine the rationality of antibiotic use based on qualitative parameters and analyze factors that correlate with the clinical outcomes of CAP patients. This study enrolled 94 adult patients diagnosed with CAP based on inclusion and exclusion criteria. CAP patients are hospitalized in the non-VIP ward at Dr. Sardjito General Hospital, Yogyakarta, Indonesia, from September to November 2022. Qualitative evaluation of antibiotics using Gyssens categories. Assessment of antibiotic use in CAP patients based on therapy guidelines and the Carmeli Score. Factors that correlated with the clinical outcomes of CAP patients were analyzed using the bivariate and univariate tests. Empirical antibiotics assessment shows that there was the inappropriate use of antibiotics for indications (0.82%), inappropriate use of antibiotics because there are other safer antibiotics (0.82%), inappropriate use of antibiotics because there are other more effective antibiotics (8.20%), the use of antibiotics was too short (14.75%), the use of antibiotics was too long (0.82%), the use of antibiotics was not in the right dose (4.92%), the timing of antibiotics administration was inappropriate (1.64%), while the appropriate use of antibiotics was 68.03%. Definitive antibiotics assessment shows that there was the inappropriate use of antibiotics for indications (4.81%), inappropriate use of antibiotics because there were other antibiotics with a narrow spectrum (0.96%), inappropriate use of antibiotics because there are other more effective antibiotics (8.65%), the use of antibiotics was too short (20.19%), the interval of antibiotic administration was inappropriate (0.96%), the use of the antibiotics was not in the right dose (7.69%), and the timing of antibiotic administration was inappropriate (2, 89%), while the appropriate use of antibiotics was 53.85%. Factors that correlate with clinical outcomes in CAP patients are BUN levels and CAP severity. The rationality of using antibiotics for empiric therapy was 68.03% and definitive therapy was 53.85%, the most inappropriate use occurred when giving antibiotics for too short a time (20.19%). BUN levels and severity of CAP correlate with clinical outcomes in CAP.

INTRODUCTION:

Community-acquired pneumonia (CAP) is a major cause of morbidity that often requires hospitalization and is a cause of death¹. This disease is one of the infectious diseases that can affect the population every year because it is a cause of mortality throughout the world². The incidence of CAP increases in the elderly and the highest mortality occurs in patients with risk factors such as stroke³. heart disease, lung disease⁴, smoking⁵, and other comorbidities⁶. CAP patients aged >65 years are hospitalized at a 10-fold increase compared to younger patients⁷. The increase in the incidence of CAP in the elderly population is due to decreased physiological function, the immune system, and the presence of accumulated chronic diseases that make elderly patients more susceptible to infection⁸.

CAP patients require hospitalization, empiric antibiotics are chosen as the initial treatment because the cause of the pathogen is unknown⁹. Appropriate administration of antibiotics has been shown to reduce mortality¹⁰. Antibiotic therapy is one of the main approaches for the treatment of infections, but it is necessary to be aware of the irrational use of antibiotics¹¹ which has a detrimental effect¹². The irrational use of antibiotics is one of the predisposing factors for resistance¹³, so efforts are needed to optimize the available drugs¹⁴. Since 1967, antibiotic resistance has increased, not only for beta-lactam¹⁵ but also for penicillin, fluoroquinolone, and macrolide¹⁶. This inappropriate use of antibiotics has an impact on the rapid emergence of bacterial resistance¹⁷ such as MDR (Multidrug-Resistant) bacteria in the community¹⁸, antibiotic toxicity, and prolongs the duration of patient hospitalization¹⁹.

Empirical treatment of CAP is recommended to reduce mortality²⁰ before the results of bacterial sensitivity cultures are available²¹. Routine sensitivity testing of bacteria is essential to reduce the crisis of antibiotic resistance²². The sensitivity test can provide information in decision-making so that it will impact more adequate patient care²³, avoid excessive use of antibiotics²⁴, and improve patient clinical outcomes²⁵. The use of antibiotics in CAP patients is not only therapy but use needs to be controlled with intensive monitoring for excessive use of antibiotics. The evaluation of antibiotic use qualitative using the Gyssens method, the administration is not only empirical but also definitive according to the bacterial antibiotic sensitivity testing.  This result test needs to be accompanied with the recommendation of selected antibiotics after considering the clinical relevance of the patient²⁶.

The study conducted by the Emerging Infections Program at selected hospitals in 10 states (California, Colorado, Connecticut, Georgia, Maryland, Minnesota, New Mexico, New York, Oregon, and Tennessee) showed that there was inappropriate use of antibiotics in CAP patients of 79.5%. This occurs because treatment in CAP patients is too long (59.2%)²⁷. A similar study in two tertiary hospitals in Malaysia showed that inaccurate use of empirical antibiotics occurred when antibiotics were given with incorrect duration, the spectrum was too narrow, and antimicrobials were not indicated²⁸. A study at the Dreifaltigkeits-Krankenhaus in Wesseling, a primary care hospital, reported that patients received antimicrobial treatment that was considered not optimal (73%), inadequate treatment (27%), and overtreatment (46%). Excessive antimicrobial treatment occurred more frequently in mild (55%) and moderate (49%) CAP than in severe CAP (0%)²⁹.

The study was conducted at Dr. Sardjito, General Hospital, Yogyakarta, Indonesia. This study aims to determine the rationality of antibiotic use based on qualitative parameters and analyze factors that correlate with the clinical outcomes of CAP patients.

MATERIALS AND METHODS:

Materials:

This study used the data of CAP patients admitted in the non-VIP ward of Dr. Sardjito General Hospital, Yogyakarta, Indonesia, from September to November 2022. 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. This study complies with the institutional and ethical standards of the research committee of Dr. Sardjito General Hospital, Yogyakarta, Indonesia.

Methods:

Study Design:

Descriptive observational study using a prospective cohort design.

Data Collection:

The inclusion criteria for this study were patients aged 18 years and over, diagnosed with CAP based on pneumonia-specific chest x-ray results and/or clinical assessment, received empiric and/or definitive oral or parenteral antibiotic therapy, bacterial culture, antibiotic sensitivity test, and had medical record data. complete. The exclusion criteria for this study were if there was no growth of cultured bacteria, the patient was discharged from the hospital at his request, and there was a change in diagnosis during the therapy period.

The rationality of using empiric and definitive antibiotics in CAP patients is assessed from the completeness of the patient's identity (medical record number, age, date of birth, gender, body weight, date of admission and discharge from hospital, and length of stay), diagnosis, radiological assessment, clinical assessment. and laboratory results, antibiotic name, dosage, duration of use, and clinical results. Assessment of antibiotic use in CAP patients based on therapy guidelines and the Carmeli Score, classifies patients into three main classes based on the following assessments: score 1 if there is no history of contact with health care system during the last 6 months, no history of antibiotic use during the last 6 months, young patient and no comorbidities; score 2 if there is a history of contact with health care system for the last 6 months, non-invasive procedures, no history of antibiotic use for the last 6 months, elderly patient and some comorbidities; score 3 if there is a history of contact with healthcare system over the past 6 months, invasive procedures, immunodepression and immunosuppression patients³⁰.

Qualitative evaluation of the rationality of antibiotic use was assessed based on Gyssen's categories. The parameters used in the Gyssens category include completeness of patient data, accuracy of antibiotic indications, accuracy of antibiotic choice, accuracy of administration time, the accuracy of administration route, the accuracy of administration interval, the accuracy of dose, and accuracy of administration timing. The quality of antibiotic use in CAP patients through the Gyssens category is assessed by trained clinicians and/or antimicrobial resistance control teams.

The use of antibiotics has VI assessment categories in the Gyssens flowchart. Category VI if patient data is incomplete so antibiotics cannot be assessed. Category V if there is no indication for administration of antibiotics. Category IVd if the choice of antibiotic is not appropriate because there are other narrow spectrum antibiotics. Category IVc if the choice of antibiotic is not appropriate because there are other antibiotics that are cheaper. Category IVb if the choice of antibiotics is not appropriate because other antibiotics are safer. Category IVa if the choice of antibiotics is not appropriate because other antibiotics are more effective. Category IIIb if the use of antibiotics is too short. Category IIIa if the use of antibiotics is too long. Category IIc if the route of antibiotic administration is not appropriate. Category IIb if the antibiotic administration interval is not appropriate. Category IIa if the dosage of antibiotics is not appropriate. Category I if the timing of antibiotics is not appropriate. category 0 if the use of antibiotics is appropriate and rational.

Observation of Clinical Outcome:

Clinical outcomes are considered "improvement" if one or more clinical assessment parameters are met, including respiratory rate ≤30/minute, normal temperature 36-38 C, heart rate ≤125 beats/minute, normal blood pressure ≥90 mmHg or diastolic ≥60 mmHg, no tightness or chest pain, radiological assessment results did not show pleural effusion, infiltration and consolidation, and the patient was discharged from the hospital with the doctor's permission. Clinical results are considered "worsen" if one or more clinical assessment parameters are met, including respiratory rate >30/minute, temperature >38 C, heart rate >125 beats/minute, systolic blood pressure <90 mmHg or diastolic <60 mmHg, feel short of breath and pain, radiological assessment results still show pleural effusion, infiltration and consolidation, use of a ventilator, and the patient dies.

Data Analysis:

The rationality of empirical and definitive antibiotic use based on qualitative parameters was analyzed descriptively using Gyssens categories. Factors that correlated with the clinical outcomes of CAP patients were analyzed using the chi-square test bivariate analysis and logistic regression test multivariate analysis.

RESULT:

Characteristics of CAP Patients:

This study enrolled 94 adult patients diagnosed with CAP based on inclusion and exclusion criteria. CAP patients are hospitalized in the non-VIP ward at Dr. Sardjito General Hospital, Yogyakarta, Indonesia, from September to November 2022. Correlation between CAP patient variables include demographic data on age and sex, laboratory data includes platelet, leucocytes, haematocrit, and BUN, data on CAP severity, data on length of stay, use of antibiotics, route of antibiotic administration, and comorbidities with clinical outcome, and the correlation between empiric and definitive antibiotic therapy with clinical outcome, through bivariate analysis, are shown in (Table 1).

Table 1. Correlation Between CAP patient variables with Clinical Outcome

Table 2. Assessment of Empiric Antibiotic Use in Adult CAP Patients

Use of Empiric and Definitive Antibiotics:

The empirical antibiotics assessment based on the Gyssens method shows that antibiotic use is inappropriate in category V (0.82%), category IVb (0.82%), category IVa (8.20%), category IIIb (14.75%), category IIIa (0.82%), category IIa (4.92%), and category I (1.64%), while appropriate use is category 0 (68.03%) (Table 2). 

The definitive antibiotics assessment based on the Gyssens method shows that antibiotic use is inappropriate in category V (4.81%), category IVd (0.96%), category IVa (8.65%), category IIIb (20.19%), category IIb (0.96%). ), category IIa (7.69%), and category I (2.89%), while appropriate use is category 0 (53.85%) (Table 3).

Table 3. Assessment of Definitive Antibiotic Use in Adult CAP Patients

The assessment of the severity of CAP in this study used the Pneumonia Severity Index (PSI) system which is based on risk factors. One component of the PSI assessment is radiology results showing pleural effusion in the lungs of CAP patients. A pleural effusion is a buildup of fluid between the layers of tissue that line the lungs and chest cavity. It can occur by itself or be caused by disease in the surrounding parenchyma such as infection, malignancy, or inflammatory conditions (Figure 1).

Figure 1. Pleural Effusion in the Lungs of CAP Patients From the Results of Radiological Assessment. The A arrow shows the normal width of the lung in the cavity. The arrow B shows fluid layering in the left pleural cavity. 

The factors that correlate with clinical outcomes in CAP include BUN levels and severity of CAP, through multivariate analysis, shown in (Table 4). 

Table 4. Multivariate Logistic Regression Analysis of Factors Correlated with Clinical Outcome Community-acquired Pneumonia

Variables

Bivariate

Multivariate

P

OR

95% CI

P

95% CI

0.010 

3.793 

1.319-10.910 

0.064 

0.943-8.636 

0.001 

6.092

1.863-19.920 

0.009 

1.484-16.743 

DISCUSSION:

Category V is no indication for administration of antibiotics. This patient has been treated with azithromycin tablets, as a recommendation for CAP therapy because macrolides provide a broader antibacterial spectrum and are effective against pathogens in patients with comorbidities³¹. One study showed that there was no significant difference in the use of macrolide therapy with fluoroquinolones in terms of clinical stability³² so the administration of levofloxacin infusion was not an appropriate indication.

For the definitive antibiotics category V, levofloxacin infusion is not an appropriate indication because this patient has received cefoperazone injection and ceftriaxone injection which are sensitive to bacteria that cause infection based on culture results. Levofloxacin tablets are also not an appropriate indication, this is because the patient has received levofloxacin infusion therapy. The two drugs have the same active substance, it's just that the dosage form is different. Ciprofloxacin infusion therapy is not anappropriate indication because this patient has received ceftazidim injection which are sensitive to bacteria that cause infection based on culture results. Meropenem injection is not an appropriate indication, because meropenem is used to treat Pseudomonas aeruginosa, while the patient's culture results show the growth of pathogens Klebsiella pneumonia (ESBL) and Staphylococcus aureus (MRSA). Therefore the use of ciprofloxacin infusion and meropenem injection is not the right indication when used as definitive therapy.

The definitive antibiotic in category IVd is levofloxacin infusion, because levofloxacin is a broad-spectrum fluoroquinolone antibiotic against Gram-positive and Gram-negative bacteria. This patient has a diagnosis of CAP, pulmonary TB, and pleural effusion, so there are other antibiotic options such as penicillin and aminoglycosides which have a narrow spectrum and are also sensitive to bacteria based on culture result³³.

Category IVb empirical antibiotics in this study were azithromycin tablets. Azithromycin orally is the antibiotic of choice for the short-term treatment of CAP, but safety needs to be considered. In a randomized trial study, a double-blind, noninferiority study comparing azithromycin with levofloxacin, the clinical cure rate for azithromycin was 93.7% while for levofloxacin was 89.7%. Treatment side effects were reported in 19.9% ​​of subjects receiving azithromycin and 12.3% of subjects receiving levofloxacin (𝑃 = 0.032). Most side effects are of mild to moderate severity, diarrhea being the most common occur with the use of azithromycin so it needs to be considered³⁴ .

Category IVa empirical antibiotics were ceftriaxone injection, levofloxacin infusion, ceftazidime injection, cefoperazone injection, and azithromycin tablets are less effective when used as monotherapy. A study showed that empiric therapy with a combination of beta-lactams and macrolides is an effective and appropriate treatment option for patients with mild CAP because it increases the survival of CAP patients at risk of bacteremia³⁵. In patients with severe CAP hospitalization, it is more effective to use a combination therapy of beta-lactams and macrolides because macrolides are immunomodulators that contribute as anti-inflammatories and reduce mucus secretion, or combination therapy of beta-lactams and fluoroquinolones³⁶.

The definitive antibiotic category IVa, the use of ciprofloxacin tablets and ceftriaxone injections is not appropriate because there are other antibiotics that are more effective. The culture results showed the growth of Pseudomonas aeruginosa bacteria. Even though this antibiotic is sensitive, there are still other antibiotics that are more effective and sensitive, including ceftazidime, cefepime, and meropenem. A study proves that until now ceftazidime is considered the most effective antibiotic among cephalosporins for the treatment of pneumonia caused by strains of Pseudomonas aeruginosa. Another antibiotic from the cephalosporin group that is effective against Pseudomonas aeruginosa is cefepime which is the choice³⁷.

The use of ampicillin sulbactam injection, ciprofloxacin infusion, ciprofloxacin tablets, and levofloxacin infusion in CAP patients is not appropriate. Bacterial culture in CAP patients shows the growth of ESBL (Extended-Spectrum Beta-Lactamase) Klebsiella pneumoniae and ESBL Escherichia coli bacteria which are also sensitive to carbapenem antibiotics. A study of bacteremic pneumonia caused by extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae suggested that carbapenems have been considered the drug of choice for the effective treatment of ESBL-producing infections. However, the administration of carbapenems as a treatment for infections caused by ESBL organisms should be considered for critically ill patients with multiple risk factors³⁸. The use of amoxicillin tablets is inappropriate because other antibiotics are more effective. The use of amoxicillin tablets is inappropriate because other antibiotics are more effective. The culture results of CAP patients showed the growth of Enterococcus faecalis bacteria which were sensitive to the antibiotics amoxicillin, ampicillin-sulbactam, carbapenems, and vancomycin. Although amoxicillin is sensitive, the antibiotic vancomycin was more effective, because the patient had a high severity of CAP and was hospitalized in intensive care. A study showed that pneumonia patients infected with Enterococcus faecalis could be controlled with vancomycin³⁹.

The use of moxifloxacin infusion was inappropriate because culture results showed growth of Enterobacter cloacae in CAP patients who were also sensitive to meropenem, amikacin, cefepime, aztreonam, and ceftazidime. A review reported that enzymatic resistance to fluoroquinolones has been associated with mutated alleles of enzymatic resistance. Carbapenems are the most potent agents for the treatment of infections, and the fourth generation cephalosporin cefepime can also maintain its activity against Enterobacter cloacae infections⁴⁰. The use of azithromycin tablets is inappropriate because there are other antibiotics that are more effective. The patient's culture results showed the growth of Staphylococcus haemolyticus bacteria which were sensitive to clindamycin, vancomycin, gentamicin and linezolide. A case report proves that successful management of a patient with Staphylococcus haemolyticus bacteremia was achieved by administering intravenous vancomycin, and linezolid which achieved a high level of penetration into the serum⁴¹.

The empirical and definitive antibiotics category IIIb in this study, were given to CAP patients for 2 to 4 days. According to the CAP therapy guidelines, the duration of antibiotic use in CAP patients for 5 to 7 days³⁶.

Category IIIa empirical antibiotics in this study were moxifloxacin tablets. CAP patients were given moxifloxacin tablets for 10 days since the patient was admitted to the hospital, had no risk factors for MRSA (Methicillin-Resistant Staphylococcus aureus) or Pseudomonas aeruginosa and had no complications of meningitis, endocarditis or other severe infections. The American Thoracic Society and The Infectious Diseases Society of America (ATS/IDSA) Guideline 2019 recommends the duration of antibiotic use in CAP patients for 5-7 days³⁶.

The definitive antibiotic category IIb in this study was ceftazidime injection because CAP patients are given ceftazidime injections every 12 hours. CAP therapy guidelines recommend a ceftazidime administration interval in CAP patients of every 8 hours³⁶.

Category IIa empirical antibiotics in this study were ceftazidime injections, cefixime tablets, and co-trimoxazole tablets. Ceftazidime injection is given to CAP patients at a dose of 2g/12 hours and 1 g/8 hours. These CAP patients have severe pneumonia and comorbid sepsis and require an increase in the therapeutic dose so that the initial dose is ceftazidime 2 g/8 hours on the first day of treatment^36,42. In this study, cefixime tablets were given to CAP patients as empiric therapy at a dose of 100g/12 hours. Cefixime is effective as an oral treatment for community-acquired pneumonia in adult patients when given at a dose of 400mg/12 hours⁴³. Cefixime has been used by several countries as a first-line drug for the treatment of community-acquired infections because of its widespread use spectrum activity against all Gram-negative, and Gram-positive pathogens, and atypical organisms⁴⁴. Co-trimoxazole tablets were given to CAP patients with comorbidities Human Immunodeficiency Virus (HIV) in this study at a dose of 480mg/12 hours. The North Bristol NHS empirical guidelines recommend that CAP patients with moderate to high severity be treated using co-trimoxazole at a dose of 960mg/12 hours⁴⁵. Co-trimoxazole is also used as prophylaxis in HIV patients to prevent the spread of infection due to HIV⁴⁶.

Definitive antibiotics category IIa were co-trimoxazole tablets, meropenem injection, ciprofloxacin tablets, ciprofloxacin infusion, ampicillin-sulbactam injection, and ceftazidime injection. The use of co-trimoxazole tablets in adult CAP patients with comorbid bronchiectasis disease and HIV, given a dose of 480 mg/12 hours after the patient's culture results are known. Based on therapeutic guidelines, the dose of co-trimoxazole for CAP therapy is 960 mg/12 hours (45) and used as prophylaxis in patients with comorbid HIV (46). In this study, CAP patients were given meropenem injection ata dose of 1g/12 hours. The culture results showed that meropenem was sensitive to pathogens, but the dose used was not appropriate. Based on therapeutic guidelines, the recommended dose of meropenem is 1 g/8 hours (36). Ciprofloxacin tablets are used as definitive therapy for CAP patients with a dose of 750 mg/12 hours. Ciprofloxacin infusion was also used in CAP patients with Pseudomonas aeruginosa culture in this study, the dose given is 200mg/12 hours. According to pneumonia treatment guidelines, the dose of ciprofloxacin as CAP therapy is 400mg/12 hours, so in this study giving ciprofloxacin is not appropriate⁴⁷.

Ampicillin-sulbactam injection is given as definitive therapy in CAP patients at a dose of 1.5g/12 hours. The therapy guideline of CAP recommends administering an

intravenous dose of ampicillin-sulbactam of 1.5 - 3g/ 6 hours³⁶. A multicenter study showed excellent clinical results and bacteriological response in the treatment of CAP and can be well tolerated in moderate to severe of CAP severity in adult patients when administered at a dose of 1.5 - 3g/ 6 hours⁴⁸. Therefore, administering intravenous ampicillin-sulbactam at a dose of 1.5g/12 hours is considered inappropriate. Ceftazidime injection in this study was given at a dose of 1g/8 hours for CAP patients, with culture results Pseudomonas aeruginosa and several other pathogens. According to the therapy guideline of CAP, the administration of ceftazidime injection for CAP therapy is a dose of 2g/8hours, especially in patients infected with Pseudomonas aeruginosa, so it is considered that the antibiotic dose is not appropriate³⁶.  

Category I empirical antibiotics in this study were ceftriaxone injection and azithromycin tablet. Ceftriaxone injection is prescribed twice daily³⁶, but the drug is administered to CAP patients inconsistently at the same time of 8 a.m. and 8 p.m. Azithromycin tablets were prescribed once daily³⁶, but were given to patients inconsistently at the same time of 8 am. The use of these two drugs is considered inappropriate because they are not consistently administered to patients at the same time.

Category I definitive antibiotics are ampicillin-sulbactam injection, ceftazidime injection, and ceftriaxone injection. Ampicillin-sulbactam injection was prescribed once daily because the CAP patient had comorbid chronic kidney disease⁴⁹ for 8 days, but was given to the patient inconsistently at the same time for 8 days. Ceftazidime injection is prescribed three times daily³⁶, but this drug is administered to CAP patients inconsistently at the same times of 8a.m., 4p.m., and 12 p.m. Ceftriaxone injection was prescribed twice daily³⁶, but the drug was administered to patients inconsistently at the same times of 8 a.m. and 8 p.m.

Antibiotics are included in category 0 if the use of antibiotics is appropriate and rational. In this study, the use of empirical antibiotics and definitive antibiotics was mostly rational if assessed qualitatively using the Gyssens method. Rationality of antibiotic therapy begins with an accurate diagnosis and administration of the correct antibiotic, the correct route, effective dose, optimal interval, and appropriate period. CAP patients also receive antibiotics in oral dosage forms because the patient has improved clinically and continues with outpatient treatment, so the antibiotic is switched from parenteral dosage form to oral dosage form. Antibiotic management aims to improve therapeutic outcomes and antibiotic sensitivity, as well as reduce side effects⁵⁰. The use of antibiotics according to guidelines contributes to reducing the length of hospital stay in patients with severe CAP⁵¹. Most antibiotic therapy guidelines recommend that treatment be based on disease severity and prognostic risk score⁵².

There is an increase in antimicrobial resistance over time, complicating therapy, and detrimental to patient care⁵³. Therefore, strict policies are needed in administering antibiotics to reduce the occurrence of resistance⁵⁴. In this study, most antibiotics were administered to CAP patients intravenously compared to the oral route. These findings are by previous studies on respiratory tract infections⁵⁵. Unnecessary use of antibiotics can encourage the development of resistance which would eliminate the antibacterial efficacy of most cell wall inhibitors⁵⁶. The availability of over-the-counter antibiotics without a prescription is the main reason for the irrational use of antibiotics⁵⁷.

In general, all classes of antibiotics used in the treatment of pneumonia are resistant, to overcome this resistance, a combination of antibiotics is used in prescribing and/or increasing the dose of antibiotics⁵⁸. Antibiotic resistance is a major challenge for medical personnel and pharmacists in the treatment of infectious diseases⁵⁹. The increasing number of bacterial strains that are becoming resistant to antibiotic compounds is currently problematic for the scientific world⁶⁰. A study found that despite the development of bacterial strains that are difficult to treat, there are still several antibiotics available that are able to dominate infections with a good percentage of success⁶¹. Inappropriate use of antibiotics influences the development of antibiotic resistance. Therefore, treating CAP infection with appropriate treatment guidelines is mandatory for doctors⁶².

In this study, the variables that correlated with the clinical outcome of CAP patients were BUN levels (p < 0.05) and CAP severity (p < 0.05) based on the results of statistical analysis. In CAP patients there is infection which can lead to sepsis and a systemic inflammatory response that can impact worse clinical outcomes⁶³. Patients experiencing decreased and increased BUN levels are associated with poor outcomes because they are more susceptible to receiving treatment in the ICU (Intensive Care Unit). CAP patients experience dehydration so urea reabsorption increases in the kidneys. Therefore, high BUN levels indicate a decrease in renal perfusion due to dehydration⁶⁴. The severity of CAP can be seen from the score at the start of the assessment. This study uses the Pneumonia Severity Index (PSI) which is designed to identify low and high risk for management of patients receiving outpatient or inpatient treatment. All scores correlated well with mortality and risk of complications, are simple and easy-to-use criteria to apply in clinical practice⁶⁵. The limitation of this study is that specimens were taken for antibiotic sensitivity culture after CAP patients received antibiotics so that it can influence the type of bacteria that grows, and influence antibiotic sensitivity.

CONCLUSION:

The rationality of antibiotic use based on qualitative parameters for empiric therapy was 68.03% and definitive therapy was 53.85%, the most inappropriate use occurred in giving antibiotics for too short a time (20.19%). Factors that correlate with clinical outcomes in CAP patients are BUN levels and CAP severity.

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 Committee section, Pulmonary Medical Staff Group, Internal Medicine Resident, and the Medical Records section of Dr. Sardjito General Hospital, Yogyakarta, Indonesia, for their support of this study.

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