INTRODUCTION:  According to WHO, Adverse drug reaction is defined as ‘An unintended and noxious response to a drug, which occurs at doses normally used in man for the prophylaxis, diagnosis, or therapy of disease, or for the modifications of physiological function’. These adverse drug reactions (ADRs) may result in physical, mental, and functional impairment. ADRs are known to impact the morbidity and mortality of patients, significantly more so in the hospitalized patients, apart from adding to the financial burden to patients as well as to the community at large. Prompt detection, evaluation, reporting and monitoring of ADRs is essential to maintain effective and safe drug treatment. Antibiotics as antimicrobial agents (AMAs) are one of the most commonly prescribed drugs by physicians of various clinical specialities in many developed and developing countries.  These are also one of the most common groups of drugs which are misused as over-the-counter medication, self-medication and also irrationally prescribed leading to ADRs and microbial resistance. 

There are various classes of antibiotics such as sulphonamides, quinolones, penicillins, cephalosporins, aminoglycosides, macrolides, carbapenems, etc with different mechanisms of action and associated adverse effects.  It is estimated that half of the hospitalized patients are given AMAs either for treatment or prophylaxis and more than 70% of ICU patients receive AMAs with much of their use being empiric and majority of them receiving multiple agents together.  

ADRs reported from the clinical trials may not be elaborate and have several limitations since they are studied in a small population for limited duration and selectively recruited controlling heterogeneity. Age, gender, disease prevalence, ethnic origin, cultural practices, socioeconomic status, and many other drug related factors can influence and lead to varied ADR patterns necessitating post marketing evaluation. The incidence of ADRs varies widely among different studies from 0.15% to 30%.   In a study conducted by Geer et al, anti-infective agents including anti-tubercular drugs were responsible for 40.9% of ADRs.   An Australian study reported 25% of ADRs were related to antimicrobials of which ADRs to penicillins were most common followed by cephalosporins.  

Postmarketing drug safety monitoring through pharmacovigilance activities is being carried out in most of the healthcare centres. Mining of ADR reports and carrying out observational prospective or retrospective studies allow to understand a much wider range of ADR characteristics, providing valuable means for ADR detection, and if possible prevention, and thereby reducing healthcare costs.   Despite high incidence, ADRs are underreported in most parts of our country. This study is being proposed to evaluate the ADRs reported due to antibiotics prescribed in a tertiary care hospital, to understand their pattern and to know the class of antibiotics which lead to maximum ADRs.

RATIONALE:

Though the data on ADRs related to AMAs is available, only a handful of studies exist from the Indian hospitals exclusively analyzing the ADR trends and patterns related to antibiotics. Wide variations in ADRs may be expected from region to region because of different prescribing practices, availability of drugs, genetic and epidemiological variations in the population, disease conditions warranting combination of multiple antimicrobials together, or for longer duration, associated co-morbidities, varying immune status of the patients, apart from drug related factors. These above mentioned factors also make it challenging to assess the causality and attributability of adverse event to particular drugs. Undertaking studies on ADRs may provide useful information to promote antimicrobial stewardship and in reframing hospital and national antibiotic policy in the best interest of patient care and safety. Thus, this study is aimed to analyze regional data existing in a tertiary care teaching hospital retrospectively to understand the pattern, severity, causality, and preventability of ADRs due to antibiotics.

STUDY PROCEDURE:

This is a retrospective, observational study, and shall be conducted in the Department of Clinical Pharmacology & Therapeutics, NIMS, after obtaining NIEC approval. Waiver of consent is requested.

All the records of suspected ADRs reported due to antibiotics between January 2015 and October 2020 will be collected (suspected ADR forms) and will be used as main source for data collection. If required consultation with prescribing doctors and reference of patient case files will be done. All the data from these ADR reports will be recorded into excel sheet and evaluated.

The demographic details, medical history including history of allergy, if any, will be noted. Drug history, i.e., suspected medication, the route of administration, dosage, start date, stop date, indication, concomitant medication will be noted. Drug reaction history, onset, date of reaction, duration, seriousness, outcome, date of recovery will also be noted. Data regarding de-challenge, re-challenge, treatment for reaction, relevant laboratory abnormalities if any, will be recorded.

Data will be assessed for age and gender preponderance, the most common antibiotic causing ADRs, most common manifestations of ADRs, system organ class (SOC) involved due to ADRs as per MedDRA coding system, causality assessment using WHO UMC causality assessment, severity will be assessed using modified Hartwig and Siegel scale, preventability will be assessed using Schumock and Thornton scale. The suspected antibiotics prescribed will be categorised as Access, Watch and Reserve categories according to 2019 WHO AWaRe classification of antibiotics for evaluation and monitoring of use.