According to our knowledge, this is the first study that compares antibiotic prescribing practices for selected infectious diagnoses over a ten years period in two Indian private-sector hospitals. In the NTH, prescribing of antibiotics for all indications, including antibiotics specifically for cellulitis, pneumonia, peritonitis and sepsis diagnoses, increased from 2008 to 2017. In the TH, although antibiotic prescribing practices did not change during the study period, antibiotic prescribing for cellulitis, pneumonia and peritonitis increased and decreased for sepsis. Between 2008 and 2017, prescribing of access, watch and FDC of antibiotics rose in the NTH, and prescribing of watch, reserve and FDCs increased in the TH.
In this study, we analysed adherence to various international recommendations for antibiotic prescribing: the WHO’s recommendations for empirical antibiotic treatment for cellulitis and pneumonia, the recommendations for empirical antibiotic treatment from the ‘Surviving sepsis campaign’ for sepsis and the recommendations of the World Society of Emergency Surgery for peritonitis [15, 18, 19]. Adherence to these international guidelines increased in the TH compared to the NTH during the study period, especially prescribing of antibiotics for peritonitis and pneumonia.
Guidelines on empirical antibiotic treatment are often based on whether an infection is healthcare associated or community acquired. As both bacterial flora and susceptibility patterns vary worldwide, the following factors are important to consider while selecting the most appropriate antibiotic: the bacterium most likely to be the cause of the infection, patient's clinical status, allergies to specific antibiotics and current or previous antibiotic resistance and responses to antibiotic treatment [1, 18, 19]. In this study, most of the patients did not have cultures sent for analysis, as the use of microbiological analyses was limited at both hospitals. The lack of microbiological analyses makes it difficult to comment on the rationale underlying the antibiotic prescription practices in the hospitals. However, prescribing of broad-spectrum antibiotics in both hospitals was high, which is in line with previous reports on prescribing of broad-spectrum antibiotics in Indian hospitals [12, 20]. As all the patients in the NTH paid for the treatment they received, the patients might have put pressure on their physicians to prescribe broad-spectrum antibiotics. In a qualitative study including 36 Indian doctors, Kotwani et al. reported that doctors faced demands from their patients to prescribe ‘strong’ antibiotics and that they sometimes prescribed antibiotics because they did not have time to debate with patients due to time constraints in busy health care facilities [21]. The aforementioned factors, as well as the desire to avoid re-consultation, might have contributed to the prescribing of broad-spectrum antibiotics in the hospitals in the present study.
In the NTH, the FDCs of antibiotics (J01R) were commonly prescribed to all patients, including those with cellulitis, peritonitis, pneumonia and sepsis. In contrast, the FDCs were less frequently prescribed in the TH. Prescribing of the FDCs for all indications increased in the TH during the study period but decreased for diagnoses of pneumonia and sepsis. Prescribing FDCs of antibiotics is not recommended, as they have been shown to drive antibiotic resistance, a common consequence of unnecessarily prescribed antibiotics, often in incorrect doses [22]. Appropriate prescribing of antibiotics requires that the dose be tailored for the individual patient, which is often not possible while prescribing the FDCs. A few FDCs that includes unapproved formulations, are known to be widely used in India [23-26]. In March 2016, the Indian Government banned around 330 FDCs of drugs, of which 63 (19%) were FDCs of antibiotics [27]. However, there are still more than 118 FDCs of antibiotics available in the Indian market [27]. The presence of medical representatives and lack of local prescribing guidelines may have contributed to the higher prescribing of FDCs of antibiotics in the NTH as compared with that in the TH, where medical representatives are forbidden, and mainly generic medicines are procured by the management. Previous research demonstrated that pressure from pharmaceutical companies influence physicians’ prescribing practices in India [28].
Regardless of the country or setting, access antibiotics should primarily be used to save, whereas watch and reserve antibiotics should be used only for specific and limited indications in critically ill patients or patients with infections caused by bacteria with known antibiotic resistance [17]. In both hospitals, reserve antibiotics comprised less than 1% of the total antibiotics prescribed. In the TH, access antibiotics were most commonly prescribed (61% of antibiotics prescribed), followed by watch antibiotics (29%). However, in the NTH, access and watch antibiotics were prescribed in equal numbers (40% each). These results indicated that watch antibiotics accounted for a higher proportion of antibiotics prescribed in the NTH than in the TH. Furthermore, in the TH, prescribing of watch and reserve antibiotics for cellulitis or peritonitis increased in both hospitals during the study period, whereas prescribing of these antibiotics for sepsis decreased.
The relatively low incidence of some infectious diseases, such as infective endocarditis, among admissions to the NTH and the TH may be explained by underdiagnosing, which is a major problem in hospitals, as described in a previous study on infective endocarditis in India [29]. In many health care facilities in LMICs, microbiological tests and imaging methods are seldom used due to a lack of access to these diagnostic methods or a lack of time and money [8, 21]. In only a small number of cases in the present study, samples were sent for microbiological analyses, despite such analyses being readily available in both hospitals. Patient- and prescriber-related factors have been put forward to explain why culture tests are not routinely performed in the hospitals [12, 21, 30]. Patient-related factors include patients not being able to afford the tests or prefer to stay for short periods to pay less at the NTH. Prescriber-related factors might include doctors not having the time to wait for lab results due to overcrowding in the hospitals or an additional factor may be monetary driven, that doctors are paid for the number of patients they admit to the hospital so they might be wishing to see as many patients as possible in a given period [12, 21, 30]. Routine use of diagnostic methods, such as microbiological analysis and imaging methods, for patients with suspected infections might contribute to better management of and guidance on antibiotic treatment for infectious diseases to reduce antibiotic overuse.
Methodological considerations
Strengths and limitations
A strength of this study is the data collection design. The hospitals included in this study lacked computerized medial record systems, and the data were collected manually, using the same method over a long period of time. As data collection and data entry in the registry were performed manually, there was a risk of missing data. To minimize this risk, the staff who completed the forms and data entry were trained at regular intervals. Another strength of this study was that the same form was used for data collection at both hospitals, which enabled comparisons of antibiotic prescribing between the hospitals. A limitation was that none of the hospitals used microbiological analysis (cultures) consistently. Consequently, most of the diagnoses were based on clinical suspicion. As almost all antibiotic prescribing was empirical, it was not possible to assess whether the antibiotics were rationally prescribed. However, by applying the WHO’s antibiotic categories of access, watch and reserve, as well as existing guidelines on empirical prescribing for each diagnosis, the appropriateness of antibiotic prescribing practices in both hospitals could be assessed. Finally, this study included only adult patients. The reasons for this were two-fold: First, the ‘defined daily dose’ system is based on adult patients. Thus, antibiotic use among paediatric patients cannot be evaluated using the defined daily dose system. Second, the recommendations used to assess rationality in antibiotic prescribing in this study were for adults only.