Prevalence and Determinants of Antibiotic Related Adverse Drug Reactions in Kenya: Spontaneously Reported Cases at the Pharmacy and Poisons Board Database

Abstract

Introduction: Antibiotics are used for treatment and prophylaxis of various infectious conditions and are considered as safe drugs when used rationally. Like all other drugs, they also cause adverse drug reactions in various patient conditions and many studies reveal that the incidence of adverse drug reactions could be higher in case of antibiotics. Adverse drug reactions contribute significantly to morbidity and mortality globally. The impact of adverse reactions include their effect on patient adherence to treatment, treatment outcomes and the development of antimicrobial resistance. Some of the documented reactions due to antibiotics include gastrointestinal reactions, skin reactions and liver injury among others. In Kenya, the Pharmacy and Poisons Board (PPB) is mandated to carry out pharmacovigilance activities in the country. The national pharmacovigilance system was established in 2004. In 2010, Kenya became a member of the World Health Organization - Program for International Drug Monitoring (PIDM). Individual case safety reports are submitted by healthcare workers to the PPB voluntarily to alert the regulatory body of suspected adverse drug reactions. Objective: The main aim of this study was to describe the prevalence and characteristics including the type, severity and outcome of adverse drug reactions (ADRs) due to antibiotics from the spontaneous reporting database in Kenya from January 2010 to December 2015. Methodology: A retrospective cross sectional study was carried out at the Pharmacy and Poisons Board. Spontaneously reported individual case safety reports (ICSRs) submitted between January 2010 and December 2015 to the national database were reviewed. Universal sampling was used. A pre-designed data collection form adopted from the Suspected Adverse Drug Reaction Reporting Form was used to collect data. Information on the patients’ biodata, diagnosis, description of the ADR, details of the suspected drug, concomitant medicines used, severity of the reaction, outcome of the reaction and causality assessment was abstracted from the ICSRs. Data was obtained from both manually filed and computerized reports. Data analysis was conducted using Stata version 13. Results: A total of 550 ICSRs were analyzed. There were more females (60.0%) with ADRs due to antibiotics compared to males (36.6%). The median age of the cases was 34 [IQR 22.0-45.0] years. The most affected organ systems was the integumentary system (60.9%)

with skin rash (39.7%) as the most commonly reported ADR. The antibiotic classes reported to have caused the most ADRs were sulphonamides (34.69%) followed by anti-tuberculosis agents (16.2%). Cotrimoxazole was suspected to cause the majority (56%) of the ADRs. The severity assessment revealed that most of the reported ADRs were moderate (50.7%) and mild (31.9%) with 83.2% of the suspected drug being withdrawn. Complete recovery was reported in 28.5% of the cases while 42.5% were in the process of recovering at the time of reporting the ADR. Age was reported to be associated with the severity of the reported ADRs while HIV status and the severity of the reported ADR were associated with an increased risk of having an undesirable outcome or no recovery. Causality assessment was done which showed that 66.2% of the reactions were probable, and 18.3% were certain to have been caused by the suspected antibiotic. Conclusion: This study showed the high burden of antibiotic related morbidity and mortality in adults taking antibiotics. Due to the nature of the reported ADRs, majority of the cases required an intervention to manage them. Antibiotics were also suspected to have contributed to fatalities during the six year period (2010-2015). This study found that most of the reported ADRs affected the skin. Majority of the ADRs occurred in HIV positive patients taking cotrimoxazole as a prophylaxis for opportunistic infections. The HIV status of the patients and severity of the ADRs put the patients at risk of having undesirable outcomes, including no recovery. The findings emphasize the importance of monitoring all patients on antibiotics especially HIV positive patients as well as children and the elderly who experienced more severe ADRs.