ASSESSMENT OF ANTIBIOTICS ASSOCIATED ADVERSE DRUG REACTIONS: A RETROSPECTIVE OBSERVATIONAL STUDY AT A TERTIARY CARE HOSPITAL

INTRODUCTION: According to WHO, Adverse drug reaction is defined as ‘An unintended andnoxious response to a drug, which occurs at doses normally used in man for theprophylaxis, diagnosis, or therapy of disease, or for the modifications ofphysiological function’. These adverse drug reactions (ADRs) mayresult in physical, mental, and functional impairment. ADRs are known to impactthe morbidity and mortality of patients, significantly more so in the hospitalizedpatients, apart from adding to the financial burden to patients as well as tothe community at large. Prompt detection, evaluation, reporting and monitoringof ADRs is essential to maintain effective and safe drug treatment. Antibioticsas antimicrobial agents (AMAs) are one of the most commonly prescribed drugs byphysicians of various clinical specialities in many developed and developingcountries.  These are also one of the most common groups of drugswhich are misused as over-the-counter medication, self-medication and alsoirrationally prescribed leading to ADRs and microbial resistance.

There arevarious classes of antibiotics such as sulphonamides, quinolones, penicillins,cephalosporins, aminoglycosides, macrolides, carbapenems, etc with differentmechanisms of action and associated adverse effects.  It isestimated that half of the hospitalized patients are given AMAs either fortreatment or prophylaxis and more than 70% of ICU patients receive AMAs withmuch of their use being empiric and majority of them receiving multiple agentstogether.

ADRsreported from the clinical trials may not be elaborate and have severallimitations since they are studied in a small population for limited durationand selectively recruited controlling heterogeneity. Age, gender, diseaseprevalence, ethnic origin, cultural practices, socioeconomic status, and manyother drug related factors can influence and lead to varied ADR patternsnecessitating post marketing evaluation. The incidence of ADRs varies widelyamong different studies from 0.15% to 30%.   In a study conducted byGeer et al, anti-infective agents including anti-tubercular drugs wereresponsible for 40.9% of ADRs.   An Australian study reported 25% ofADRs were related to antimicrobials of which ADRs to penicillins were mostcommon followed by cephalosporins.

Postmarketingdrug safety monitoring through pharmacovigilance activities is being carriedout in most of the healthcare centres. Mining of ADR reports and carrying outobservational prospective or retrospective studies allow to understand a muchwider 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. Thisstudy is being proposed to evaluate the ADRs reported due to antibioticsprescribed in a tertiary care hospital, to understand their pattern and to knowthe class of antibiotics which lead to maximum ADRs.

RATIONALE:

Though the data on ADRs related to AMAsis available, only a handful of studies exist from the Indian hospitals exclusivelyanalyzing the ADR trends and patterns related to antibiotics. Wide variationsin ADRs may be expected from region to region because of different prescribingpractices, availability of drugs, genetic and epidemiological variations in thepopulation, disease conditions warranting combination of multipleantimicrobials together, or for longer duration, associated co-morbidities,varying immune status of the patients, apart from drug related factors. Theseabove mentioned factors also make it challenging to assess the causality and attributabilityof adverse event to particular drugs. Undertaking studies on ADRs may provideuseful information to promote antimicrobial stewardship and in reframinghospital and national antibiotic policy in the best interest of patient careand safety. Thus, this study is aimed to analyze regional data existing in atertiary care teaching hospital retrospectively to understand the pattern, severity,causality, and preventability of ADRs due to antibiotics.

STUDY PROCEDURE:

This is aretrospective, observational study, and shall be conducted in the Department ofClinical Pharmacology & Therapeutics, NIMS, after obtaining NIEC approval. Waiverof consent is requested.

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

Thedemographic details, medical history including history of allergy, if any, willbe noted. Drug history, i.e., suspected medication, the route ofadministration, dosage, start date, stop date, indication, concomitant medicationwill be noted. Drug reaction history, onset, date of reaction, duration,seriousness, outcome, date of recovery will also be noted. Data regardingde-challenge, re-challenge, treatment for reaction, relevant laboratoryabnormalities if any, will be recorded.

Data willbe assessed for age and gender preponderance, the most common antibioticcausing ADRs, most common manifestations of ADRs, system organ class (SOC) involveddue to ADRs as per MedDRA coding system, causality assessment using WHO UMC causalityassessment, severity will be assessed using modified Hartwig and Siegel scale,preventability will be assessed using Schumock and Thornton scale. Thesuspected antibiotics prescribed will be categorised as Access, Watch and Reservecategories according to 2019 WHO AWaRe classification of antibiotics forevaluation and monitoring of use.