Journal of Medical Sciences and Health

Unit of measurement Defined Daily Dose (DDD) 6

The Defined Daily Dose (DDD) represents the standard average maintenance dosage of a medication utilized in adults for its primary indication. For drugs with an existing Anatomical Therapeutic Chemical (ATC) code, a specific DDD has been allocated.

Number of DDDs = Total grams used / DDD values in grams

DDD/bed-day x 100 = Antimicrobial consumption index (ACI). The number obtained is the hospital's antibiotic consumption index for CAP. Quantifying antibiotic usage through the Antimicrobial Consumption Index (ACI) enables hospitals to compare their antibiotic consumption levels with those of other institutions, irrespective of variations in formulary composition, antibiotic potency, and hospital census 7. The collected data was statistically analyzed through SPSS version 27. Descriptive data were presented as percentages or the mean ± standard deviation.

Antibacterial agents used as empirical therapy

The empirical therapy most commonly prescribed for antibacterial treatment consisted of amoxicillin-clavulanic acid, administered to 73 (56.2%) patients, followed by levofloxacin for 33 (25.4%) patients, ceftriaxone for 16 (12.3%) patients, ofloxacin for 6 (4.6%) patients, and piperacillin-tazobactam for 2(1.5%) patients.

Distribution of Antibacterial agents as definitive therapy in CAP

As definitive therapy, the most frequently utilized antibacterial agents included levofloxacin, [prescribed for 33 (25.4%) patients, azithromycin for 9 (6.9%) patients, and vancomycin for 5 (3.8%) patients. Less commonly used agents included linezolid, cefoperazone, and moxifloxacin, each administered to 1 (0.8%) patients.

Antibacterial dose consumption

The highest antibiotics Consumption Index (ACI) value observed for empirical therapy was 14.4, attributed to amoxicillin-clavulanic acid, followed by azithromycin with an ACI of 12.6. In contrast for definitive therapy, levofloxacin exhibited the highest ACI of 14.8, followed by meropenem with an ACI of 13.0 (Table 1). A statistical comparison of empirical and definitive therapies regarding the antibiotic consumption index revealed a p-value less than 0.05. This indicates a statistically significant difference in antibiotics consumption between the two therapies. The difference was calculated using a paired Student’s t-test (Figure 3, Figure 4).

Microbial pathogens isolated

Five pathogens were isolated via sputum culture, with Streptococcus pneumoniae being the most prevalent, affecting 50 (38.4%) patients. Following this, K. pneumoniae was identified in 34 (26.1%) patients, Escherichia coli in 29 (22.3%) patients, Staphylococcus aureus in 12 (9.2%) patients, and Pseudomonas in 5 (3.8%) patients (Figure 2)

The pattern of combinational antimicrobials prescribed in CAP patients

In the management of Community-Acquired Pneumonia (CAP), the most commonly prescribed combinations of antimicrobials were amoxicillin-clavulanic acid in conjunction with azithromycin, accounting for 31 (43%) of cases in empirical and 14 (32.5%) in definitive therapy. Conversely, the least frequently utilized combination was amoxicillin-clavulanic acid combined with amikacin, constituting only 2.3% of cases. Overall, multiple antimicrobial prescriptions were observed in 115 cases (88.4%), Figure 5.

Duration of stay in hospital

The hospital stay duration ranged from a minimum of 3 days to a maximum of 12 days, with a mean duration of 7.35 ± 1.63 days. The mean duration of empirical therapy was 3.42 ± 0.80 days, while that of definitive therapy was 4.47 ± 0.87 days.

Prescribing indicators

The average number of drugs prescribed per prescription was 7.67 ± 2.17, with an average of 2.66 ± 1.89 antibiotics per prescription. Approximately 41 (32%) of drugs were prescribed using their generic names. On average, 89 (93.5%) of prescriptions included injections.

Community-acquired pneumonia is the predominant cause of hospital admissions among infectious diseases. Antimicrobial agents constitute the primary treatment approach empirically and upon confirmation of microbial pathogens. Nonetheless, their utilization has raised concerns due to instances of overuse and misuse, leading to adverse drug reactions, emergence of drug resistance, prolonged hospital stays, and escalated therapy costs 8. This study seeks to delineate the prevailing trends and extent of antibacterial utilization in patients diagnosed with Community-Acquired Pneumonia at Sarojini Naidu Medical College in Agra.

In this study, the highest proportion of cases (35.4%) fell within the age bracket of 61-70 years. The mean age of patients was recorded as 63.65 ± 11.54 years. Notably, approximately 72 cases were aged over 65 years, meeting one of the admission criteria for CAP patients. Studies conducted by Menon et al. and Shah et al. have consistently demonstrated that the highest incidence of Community-Acquired Pneumonia occurs in patients aged over 60 years 9, 10. The extremes of age are associated with lower immunity and an increased prevalence of predisposing risk factors, which contribute to multi-organ failure. This susceptibility to multi-organ failure is often attributed to the predisposition associated with old age.

The table shows different studies from other countries for comparison of CAP patients prescribing pattern of antibiotics along with microbial pathogen identified and adherence to the guidelines of that country.

The predominant approach to treatment in CAP largely relies on observational methods, emphasizing clinical and radiological diagnoses of the most prevalent causative pathogens. However, CAP remains a considerable public health concern. Therefore, it is imperative that antimicrobial treatment strategies be tailored to align with the distribution and prevalence of etiological pathogens within the population. Resistance trends at the local, national, and international levels, alongside prior exposure, must all be carefully weighed in antimicrobial decision-making. Additionally, the decision regarding hospitalization is guided by prognostic criteria, ensuring optimal management of patients with Community-Acquired Pneumonia. The results of this study reveal that amoxicillin-clavulanic acid combined with azithromycin (56.2%) and levofloxacin (25.4%) were the most commonly prescribed empirical therapy antibiotics. Interestingly, a study by Kotwani et al. conducted in Delhi over five years reported a similar trend, with two antimicrobials from the same drug class being prescribed to the majority of patients. Moreover, Nayar et al. found in their study a preference for the combination of beta-lactam and macrolide antibiotics, particularly ceftriaxone and azithromycin. These findings align closely with our study's observations regarding prescribed antibiotics 11, 12.

To compare the data with antimicrobial prescribing practices for patients with community-acquired pneumonia (CAP) in various countries, including those in Europe, Norway, and Malaysia. The studies found frequent non-adherence to national clinical practice guidelines, especially concerning empirical regimens in non-severe CAP, timely de-escalation to targeted therapy, transition to oral regimens, and overall therapy duration 13. There was a notable initiation and continuation of broad-spectrum antimicrobial therapy without a documented rationale. This was partly due to clinical improvement observed while on broad-spectrum regimens, even when microbiological tests did not confirm the necessity for such broad-spectrum coverage 14. These studies concluded that there is a need for better antimicrobial de-escalation strategies and continuous focus on improving microbiological diagnostics and adherence to guideline-recommended therapies. Table 2 shows the comparison of the studies from different countries.

Following the receipt of culture and sensitivity reports, definitive therapy was promptly initiated for targeted treatment based on the identified organism. It was noted that a significant number of cases of S. pneumoniae and K. pneumoniae exhibited resistance to first-line treatments, necessitating a shift to higher classes of antibiotics to which the organisms remained sensitive 13. Consequently, in this study, the most commonly prescribed drugs included levofloxacin (25.4%), ceftriaxone (19.2%), meropenem (13.8%), azithromycin (6.9%), amoxicillin-clavulanic acid, vancomycin, piperacillin-tazobactam, amikacin, clarithromycin, doxycycline, and cefoperazone. These findings align closely with those of the Kotwani et al. study, wherein cephalosporins followed by macrolides emerged as the most commonly prescribed antimicrobials, resembling the pattern observed in our study. Moreover, in the present study, antimicrobial agents were utilized empirically in 55.3% and as definitive therapy in 33.0% of patients, a pattern comparable to that reported in the Kotwani et al. study 11.

The total duration of antimicrobial therapy as definitive treatment for hospitalized patients in this study was 4.47 ± 0.87 days, while the overall length of hospital stay was 7.35 ± 1.63 days. Interestingly, these findings closely mirror those reported in studies conducted by Kotwani et al. and Nayar et al. 11, 12.

Indeed, the route of administration of antimicrobial agents (AMAs) is typically determined by several factors, including the site and severity of the infection 15, 16. In this study, a majority of antimicrobials were administered intravenously (76.2%), while medications such as clarithromycin, ofloxacin, and azithromycin were given orally (23.8%) as definitive therapy. A study by Cyriac et al. delves into the policy regarding changing the route of drug administration 17. In 72.3% of patients, a combination of antimicrobial agents (AMAs) was utilized. Amikacin was included in cases of gram-negative infections to enhance the synergistic prolongation of the post-antibiotic effect of beta-lactams. However, the concurrent use of ceftriaxone with amoxicillin-clavulanic acid and piperacillin with carbapenems may not be deemed rational, as there is no documented advantage with these combinations. In this study, the most frequently employed combinations included amoxicillin-clavulanic acid with either azithromycin or levofloxacin. A similar pattern of fixed-dose combination (FDC) prescription was observed in the study conducted by Mahajan et al. 18. Beta-lactam in combination with fluoroquinolones and macrolides was prescribed in 4.1% of patients. Additionally, fluoroquinolones paired with cephalosporins in 11% of patients were noted as being irrationally prescribed in empirical treatment.

In this study, the average number of drugs prescribed per patient was 7.67 ± 2.1, with an average of 2.66 ± 1.86 antibiotics per prescription. A critical indicator of prescription quality is the average number of medications per prescription. It is generally recommended to minimize this number as much as possible, as higher numbers often correlate with increased risks of drug interactions, bacterial resistance, and elevated hospital costs. Upon thorough screening of prescriptions, it was observed that mono-antibiotic prescriptions accounted for 35 (15.3%) instances, while poly-antibiotic therapy was prescribed in 195 (84.7%) cases. This presentation underscores the prevalence of poly-antibiotic prescriptions over mono-antibiotic therapy. Studies conducted by Mehrad et al. in 2015 and Bala et al. in 2009 demonstrated similar prescribing indicators 19, 20.

In our study, approximately 32% of drugs were prescribed using their generic names, with the majority of medications being prescribed by brand names. However, it is noteworthy that prescribing medications by their generic names can facilitate better inventory monitoring by the hospital pharmacy. A study conducted by Mittal et al. revealed a similar pattern of prescribing, highlighting the importance of this practice in optimizing healthcare management 21. The average number of prescriptions involving intravenous (IV) antimicrobials was 93.5%. Despite the feasibility of an oral route, the majority of inpatients receive IV antibiotics for an extended duration 22, 23.

Data on drug consumption was quantified in terms of fixed daily doses (DDD) per 100 bed days. Amoxicillin-clavulanic acid exhibited the highest value of 14.45 DDD per 100 bed days, indicating its status as the most commonly used broad-spectrum antibiotic, followed by azithromycin with a value of 12.6 DDD per 100 bed days in empirical therapy. In definitive therapy, the highest value was recorded for levofloxacin at 14.85 DDD per 100 bed days, followed by meropenem with a value of 13.0 DDD per 100 bed days. This pattern of drug utilization observed in our study aligns with findings reported by Ravi et al. in the Himalayan region of northern India and Charave et al. in Karnataka in 2020 24, 25. The consumption of antibiotics as definitive therapy was strongly correlated with the culture sensitivity report, with an overall DDD of 52.24 compared to 35.34 DDD/100 bed days for empirical therapy. This association can be attributed to the resistance observed against first-line drugs for CAP. Consequently, patients had to transition to higher-class antibiotics, resulting in increased consumption of DDD 26. The findings of this study were consistent with those of the study conducted by Naik et al., wherein patients in the medicine department exhibited increased consumption of antibiotics following the receipt of culture reports 27.