Adverse Drug Reactions Related with Antibiotic Medicines in Malawi: A Retrospective Analysis of Prevalence and Associated Factors.

Objective: We aimed to assess the occurrence and characteristics of antibiotic-associated adverse drug reactions (ADRs) in Malawi. Methods: We retrospectively reviewed 304 patient records from medical wards in three hospitals in Southern Malawi. A global trigger tool was applied for the detection of suspected ADRs, and we used the Naranjo scale, the World Health Organization classification and the Schumock and Thornton scale for causality, seriousness and preventability assessment respectively. ADRs were also further characterized according to anatomical systems. Statistical analysis was done in STATA 14.1. The Chi-square test was used to determine the association between categorical variables and logistic regression analysis was used to measure the strength of the association between various independent variables and the occurrence of ADRs. Results: Suspected ADRs were detected in 24% (73/304) of patients, of which 1.4% were definite, 15.1% were probable and 83.6% were possible ADRs. Most of the sADRs were gastrointestinal events (42.5%), followed by: musculoskeletal (26.3%); cardiovascular (16.3%); central nervous system (13.8%; and urinary events (1.3%). About 27% of the sADRs were serious events such as convulsions. The geriatric age group (≥65 years) was more likely to experience sADRs as compared to the younger age group, with an adjusted odds ratio (aOR) of 4.53, 95% CI (2.21-9.28), P<0.001. Patients taking more than one antibiotic medicine had a higher risk of developing sADRs as compared to patients who were administered one type of antibiotic medicine, aOR 2.14, 95% CI (1.18-3.90), p < 0.012. A long hospital stay of >3days was associated with a higher risk of sADRs with aOR of 5.11, 95% CI (2.47-10.55), p < 0.001 than those who stayed ≤ 3 days in the hospital. Conclusion: We found a higher prevalence of serious sADRs associated with antibiotic medicines than reported elsewhere. This may, among others, contribute to high patient mortality, poor treatment adherence, antibiotic resistance and increased cost of care.

What is already known and why we did the study? Most health care workers and patients are less likely to voluntarily report suspected adverse drug reactions in low- and middle-income countries such as Malawi.Studies have revealed a high usage of antibiotic medicines in Malawi, but there is limited data on the associated adverse drug reactions. What did we do? We assessed the occurrence and characteristics of ADRs associated with antibiotics. What are the new findings? We found a higher prevalence (24%) of adverse drug reactions associated with antibiotic therapy than reported elsewhere using the global trigger tool.About 27.4% of the events were serious ADRs such as convulsions, arrhythmia and hypotension.We observed a higher rate of convulsions which could be a potential safety signal. What do the new findings imply? The high prevalence of serious ADRs leads to complicated treatment strategies and contribute to patient mortality, poor treatment adherence and antibiotic resistance.ADR risk factors need to be considered when prescribing and monitoring patients on antibiotic therapy.

Temperature variations in pharmaceutical storage facilities and knowledge, attitudes, and practices of personnel on proper storage conditions for medicines in southern Malawi.

Objective: We assessed the temperature variations in pharmacies and medicine storage areas in southern Malawi and conducted a knowledge, attitude and practices survey for personnel who manage medicine stores in various health facilities. Methods: This was a longitudinal study design that used installed Tempmate® thermometers in 27 selected health facilities to record temperatures every 15 min for a period of 9 months. In addition, a questionnaire was used to assess the knowledge, attitude, and practices regarding good pharmaceutical storage. Observations were also made on the storage structures of the facilities and compared with the mean kinetic temperature. Results: Storage temperature ranged from 13.8°C to 42°C with mean kinetic temperature (MKT) being 25.3°C (95% CI 24.4-26.2°C). Mean temperature for public facilities was lower (23.8°C) than the faith-based facilities (25.2°C) and private facilities (26.6°C). In terms of level of health care, lower temperatures were recorded in facilities offering tertiary level of care as compared to secondary and primary care facilities, p < 0.001. For the type of storage facilities, storage-in-a-box unit (SIAB) presented lower temperatures than ordinary storage areas (non-SIAB), p < 0.001. Majority of health workers (69%) had good knowledge on proper storage conditions. Air conditioners and thermometers were available in 88.4 and 76.9% of the facilities, respectively. However, few facilities utilized the air conditioners due to electricity problems. About 46.15% of the participants were able to correctly record temperatures (at least twice a day) for the storage facilities, 23.07% did not properly record while 30.77% of the personnel did not keep temperature records at all. Limited storage space was among the challenges that facilities encounter to maintain proper storage conditions. Conclusion: Despite having the necessary knowledge on proper storage conditions, the pharmacy personnel failed to adhere to good pharmaceutical storage practices due to resource limitations. There is a need for stakeholder interventions such as increasing budget allocation to address the challenges faced by the health facilities.

Effect of antibiotic medicines availability on adherence to standard treatment guidelines among hospitalized adult patients in southern Malawi.

BACKGROUND: Antibiotic resistance is a global public health problem. High and inappropriate use of antibiotic therapy exacerbate the risk of antibiotic resistance. We assessed the effect of availability of antibiotic medicines on adherence to standard treatment guidelines among hospitalized adult patients in Southern Malawi. METHODS: A cross-sectional study was done to assess the availability of 16 antibiotics among the first-line recommended treatments for common bacterial infections in Malawi. Data for up to six-month duration was extracted from stock card records in Machinga and Nsanje District Hospitals and Zomba Central Hospital. This was complemented by a retrospective review of 322 patient management files from medical wards to assess adherence to the Malawi Standard Treatment Guidelines (MSTG). Investigators abstracted data such as patient demographics, diagnoses, and prescribed therapy using a data collection form that resulted in analyzing 304 patient files. Data was entered into Microsoft excel and analyzed using STATA 14.1. Point availability, stock-out duration and adherence to treatment guidelines were presented in terms of frequencies and percentages. Chi-square test or Fisher's exact test was applied to assess the association between variables and adherence to treatment guidelines. RESULTS: Point availability of antibiotics was 81.5%, 87.7%, and 42.8% for Zomba Central, Machinga and Nsanje District Hospitals respectively. Over a period of six months, 12.5% of antibiotic medicines were stocked out for at least one day at Zomba (Median stock out days = 0, (IQR 0-0 days), while 64.3% were stocked out at Machinga (Median stock out days = 21, IQR 0-31 days) and 85.7% were stocked out at Nsanje District Hospital (Median stock out days = 66.5, IQR 18-113 days). Overall, adherence to MSTG was 79.6%, (95% CI, 73.3-84.9%). By facilities, adherence to guidelines at Zomba Central Hospital was 95.9% (95% CI, 89.7-98.9%) while at Nsanje and Machinga District Hospitals was 73.2% (95% CI, 59.7-84.2%) and 54.2% (95% CI, 39.2-68.6%) respectively. Adherence to treatment guidelines was associated with health facility, presence of laboratory test results, antibiotic spectrum, and WHO-AWaRe category of the medicine, p<0.005. Adherence was lower for antibiotics that were stocked out than antibiotics that were not stocked out during the study period (63.8%, 95% CI 48.5-77.3% vs 84.4%, 95% CI 77.7-89.8%), p< 0.002. CONCLUSION: We found unstable availability of antibiotic medicines in hospitals which might contribute to the sub-optimal adherence to standard treatment guidelines. This is a setback to efforts aimed at curbing antibiotic resistance in Malawi.

Burden of and factors associated with poor quality antibiotic, antimalarial, antihypertensive and antidiabetic medicines in Malawi.

OBJECTIVE: To assess the prevalence and factors associated with substandard and falsified (SF) medicines among antibiotic, antimalarial, antihypertensive and antidiabetic medicines in Malawi. METHODS: We conducted a cross-sectional study in 23 public, faith-based and private health facilities in Zomba, Machinga and Nsanje districts. We analyzed oral medicine samples of commonly used medicines among antibiotics, antimalarial, antihypertensive and antidiabetics in accordance with Malawi Essential Medicines List and local treatment guidelines. These medicines were subjected to visual inspection for any defects and screening for the content of active pharmaceutical ingredient and disintegration of dosage units. Samples that failed during screening and at least 10% of those that passed were subjected to pharmacopeia assay and dissolution test for confirmation. We used thin layer chromatography and disintegration test methods provided in the Global Pharma Health Fund minilab® for the screening purposes. We conducted confirmatory test using High-Performance Liquid Chromatography (HPLC) or ultra-violet/visible spectrophotometer and dissolution. RESULTS: Of the 293 medicine samples collected, 14.3% were SF medicines. Among the SF medicines were 12.5% of Amlodipine (1/8), 19.2% of Amoxicillin (5/26), 72.2% of Atenolol (8/11), 21.2% of Ciprofloxacin (7/33), 14.3% of Enalapril (1/7), 44.4% of Flucloxacillin (4/9), and 35.7% of sulfadoxine/ pyrimethamine (10/28). Medicine quality was associated with therapeutic medicine class, stated origin of manufacturer, primary packaging material and geographical location. Antimalarial and antidiabetic medicines were of better quality as compared to antibiotics, odds ratio OR 4.2 (95% CI 1.7-9.49), p < 0.002 and OR 5.6 (95% CI 1.21-26.09), p < 0.028 respectively. In terms of stated country of origin, the prevalence of SF medicines was 30% (15/50), 33% (9/27), 26.7% (4/15) and 6.6% (8/122) for medicines stated to be manufactured in Malawi, China, Kenya and India respectively. CONCLUSION: This study presents the first findings on the assessment of quality of medicines since the establishment of the national pharmacovigilance center in 2019 in Malawi. It is revealed that the problem of SF medicines is not improving and hence the need for further strengthening of quality assurance systems in Malawi.