Evaluation of antibiotic use and analysis of ciprofloxacin and gentamicin residue in fish samples from farms in Lagos, Nigeria.

Antibiotic use in aquaculture for increase yield has been established over time; however, consumption of such fish may lead to inadvertent intake of sub therapeutic doses of antibiotics. Therefore, this study aimed to investigate the extent of antibiotic use in fish farming and ciprofloxacin and gentamicin residues in fish that are consumed in Lagos, Nigeria. It was conducted in two parts: a survey of 60 fish producers to assess their use of antibiotics and an analysis of ciprofloxacin and gentamicin residues in fish organs using high-performance liquid chromatography (HPLC). The survey found that twenty-nine (48%) of the farms used antibiotics, with oxytetracycline being the most common (20%), followed by ciprofloxacin (15%); gentamicin (5%); neomycin (8.33%); and probiotics (13%). HPLC analysis of fish liver and fillet samples showed that Lagos Island had the lowest residual ciprofloxacin dose (0.3014ug/g), while Lagos mainland had the greatest residual ciprofloxacin dosage (113.78765ug/g). The mean gentamicin residue in flesh of fish from farms in Lagos Island LGA was 0.37ug/g while that obtained for liver of fish samples from Surulere LGA was 2.12ug/g). The largest (5.3240ug/g) and lowest (0.2661ug/g) residual gentamicin antibiotic concentrations were found in fishes harvested from farms located in Surulere and Lagos Island, respectively. The residue levels were within the permitted range set by the WHO, but continuous regulatory surveillance is necessary to prevent antimicrobial resistance spread and improved food safety. The study has revealed that fish produced in the study area contained residues of the commonly used antibiotics hence farmers should be encouraged to consult veterinarians in cases of disease treatment for judicious use of antibiotics while self-medication and purchase of antibiotics from vendors should be discouraged.

'Prospective audit with intervention and feedback' as a core antimicrobial stewardship strategy in the paediatrics department of a Nigerian tertiary hospital.

Introduction: Inappropriate use of antibiotics for childhood illnesses, especially for non-bacterial infections, contributes to the development of antimicrobial resistance (AMR). Globally, implementation of antimicrobial stewardship programme (ASP) in all healthcare institutions is a strategic intervention to improve the appropriate use of antibiotics, reduce antimicrobial consumption and tackle AMR. The aim of this study was to evaluate the effect of prospective audit with intervention and feedback as an antimicrobial stewardship strategy on antimicrobial use, evaluate prescribers' response to recommendations and determine the rate of AMR in the Paediatrics Department of the Lagos University Teaching Hospital, Nigeria. Materials and Methods: This was an implementation study of the paediatrics Antimicrobial Stewardship Programme (ASP) over a period of 6 months. It was initiated with a point prevalence survey (PPS) to describe the antimicrobial prescribing patterns and followed by prospective audit with interventions and feedback using an antimicrobial checklist and the existing antimicrobial guidelines in the Paediatrics Department. Results: The antibiotic prescribing prevalence was high (79.9%) at baseline PPS with 139 patients on admission, of which 111 (79.9%) were treated with 202 antibiotic therapies. Over the 6 months of study, 582 patients on 1146 antimicrobial therapies were audited. Compliance with departmental guidelines was 58.1% of the total 1146 prescriptions audited (n = 666), making the antimicrobial prescription inappropriate in 41.9% (n = 480) of therapies. The most recommended intervention for inappropriateness was 'change antibiotics' 48.8% (n = 234), followed by 'stop antibiotics' 26% (n = 125), 'reduce the number of antibiotics' 19.6% (n = 194) and 'de-escalate' 2.4% (n = 11). Agreement with ASP interventions occurred in 193 (40.2%) cases, and the least agreed intervention was 'stop antibiotics' (n = 40, 32%). However, there was a steady increase in compliance rates with ASP interventions over the 6 months of period study, which was statically significant (χ2: 30.005; P = 0.001). Conclusion: ASP prospective audit with intervention and feedback was of significant benefit in improving compliance with antimicrobial guidelines, thereby improving antimicrobial therapy in the Paediatrics Department of LUTH, Nigeria.

Evaluation of cardiotoxicity and other adverse effects associated with concomitant administration of artemether/lumefantrine and atazanavir/ritonavir-based antiretroviral regimen in patients living with HIV.

The interplay of artemether-lumefantrine (AL) and atazanavir-ritonavir (ATVr) with Cytochrome P (CYP) 3A4 isoenzyme and QTc-interval may spawn clinically significant drug interactions when administered concomitantly. Cardiotoxicity and other adverse effects associated with interaction between AL and ATVr were evaluated in patients with HIV infection and malaria comorbidity. In a two-arm parallel study design, six doses of AL 80/480 mg were administered to 20 participants [control-arm (n = 10) and ATVr-arm (n = 10)], having uncomplicated Falciparum malaria, at intervals of 0, 8, 24, 36, 48 and 60 h respectively. Participants in the control arm took only AL while those in ATVr-arm took both AL and ATVr-based ART regimen. Electrocardiography, adverse events monitoring and blood tests were carried out for each of them at pre and post doses of AL. Data obtained were analyzed. QTc-interval was significantly increased in the ATVr-arm (0.4079 ± 0.008 to 0.4215 ± 0.007 s, p = 0.008) but not in the control-arm (0.4016 ± 0.018 to 0.4024 ± 0.014 s, p = 0.962). All values were, however, within normal range [0.36 - 0.44 / 0.46 s (male/female)]. General body weakness and chest pain were new adverse events reported, at post-dose of AL, in the ATVr-arm but not in the control-arm. There was no significant change (p > 0.05) in the plasma levels of creatinine, alanine aminotransferase, aspartate aminotransferase and hemoglobin at post-dose compared to pre-dose of AL in both arms of study. Concomitant administration of artemether-lumefantrine with atazanavir-ritonavir-based regimen is potentially cardiotoxic but not associated with clinically significant renal, blood nor liver toxicities. They must be used with caution.

Evaluation of the effects of atazanavir-ritonavir on the pharmacokinetics of lumefantrine in patients living with HIV in Lagos University Teaching Hospital, South-Western Nigeria.

PURPOSE: Atazanavir-ritonavir (ATVr)-based antiretroviral therapy and artemether-lumefantrine (AL) are commonly used drugs for the treatment of human immune deficiency virus (HIV) infection and malaria respectively. However, interaction of both drugs, with Cytochrome P 3A4 (CYP 3A4) isoenzyme, may spawn clinically significant pharmacokinetic interactions. This study evaluated the effects of atazanavir-ritonavir on the pharmacokinetics of lumefantrine. METHOD: In a case-control study, twenty participants having Plasmodium falciparum malaria were recruited and divided into two groups (ATVr-arm, n=10; and control-arm, n= 10). All the participants were administered six oral doses of AL 80-480 mg (Coartem). Thereafter, their blood samples were collected at different time intervals over seven days. The concentration of lumefantrine in each sample was quantified with high-performance liquid chromatography (HPLC) and used to determine its pharmacokinetic parameters which were compared between the test and control groups. RESULTS: ATVr increased the mean day 7 concentration of lumefantrine (ATVr 3847.09 ± 893.35 ng/mL, control 1374.53 ± 265.55 ng/mL, p = 0.016) and the area under its plasma concentration-time curve (ATVr 670529.57 ± 157172.93 ng.h/mL, control 447976.28 ± 80886.99 ng.h/mL, p = 0.224) by 179.88 % and 49.68 %, respectively, but decreased its mean maximum plasma drug concentration (Cmax) (ATVr 13725.70 ± 2658.44 ng/mL, control 15380.48 ± 2332.62 ng/mL, p = 0.645) by 10.76 %. CONCLUSION: ATVr increased drug exposure and day 7 plasma concentration of lumefantrine. AL is therefore considered effective for the treatment of malaria in patients taking ATVr-based regimen. However, the safety associated with the interaction requires further elucidation. TRIAL REGISTRATION: Clin ClinicalTrials.gov Identifier: NCT04531072, August 27, 2020. "Retrospectively registered".

Low prevalence of isoniazid preventive therapy uptake among HIV-infected patients attending tertiary health facility in Lagos, Southwest Nigeria.

INTRODUCTION: the burden of HIV and tuberculosis co-infection is a global public health challenge. Despite the benefit of isoniazid preventive therapy (IPT) in reducing the rate of co-infection, the uptake is generally limited in developing countries. This study aimed to determine the prevalence of IPT use and the factors affecting the uptake among HIV-infected patients attending our Teaching Hospital. METHODS: this cross-sectional survey involved 300 HIV-infected individuals attending the AIDS prevention initiatives in Nigeria clinic of the Lagos University Teaching Hospital. A self-designed and well-structured questionnaire was used to document the demographic data, patients' exposure to tuberculosis, and IPT uptake. Clinical data of eligible patients were also extracted from their case notes. The main outcome measure was the prevalence of IPT use and non-use. RESULTS: out of the respondents evaluated, (72.7%, n = 218) were females. Tuberculosis was the predominant comorbidity (15.7%, n = 47) and majority (53.0%, n = 159) had a CD4 count of < 500 cells/ml. Overall prevalence of IPT uptake was very low (7.1%, n = 18) among HIV-infected patients. Major factors affecting uptake were lack of awareness of benefit (44.4%, n = 8) and lack of fear of contracting tuberculosis (22.2%, n = 4). However, lack of awareness of IPT benefit was the only independent factor associated with poor IPT uptake (adjusted odds 1168.75, 95% confidence interval: 85.05-16060.33; p = 0.001). CONCLUSION: isoniazid preventive therapy uptake was found to be very low in this study. Increased awareness and policy implementation of IPT by the healthcare provider is necessary.

High Risk of Drug-drug interactions among Hospitalized Patients with kidney Diseases at a Nigerian Teaching Hospital: A Call for Action.

BACKGROUND: Potential drug-drug interactions (DDIs) are increasingly common in clinical practice, especially among individuals with chronic conditions, such as chronic kidney dysfunction. However, data relating to DDIs among chronically ill patients are limited in Nigeria. We, therefore, investigated the prevalence and pattern of DDIs among patients with kidney diseases on admission at a tertiary hospital in Lagos, Nigeria. MATERIALS AND METHODS: This was a prospective observational study involving 61 adults with kidney diseases and on admission in medical wards of the study center, over a 3-month period. Data extractions were with a purposefully designed pro forma to extract relevant data on demographic, clinical, and dosing regimens of the prescribed drugs for individual patients. Potential DDIs were identified, and their severity was rated using the MICROMEDEX® software database (IBM® Watson-Truven Health Analytics), which is available online with limited access. RESULTS: Of the 61 patients evaluated, majority were males (34; 55.7%), were elderly (26; 42.6%), and had chronic kidney disease Stage 3 (40; 65.5%). The most common cause of kidney disease was hypertension (20; 32.8%). Out of the 542 prescriptions received by the patients, potential DDI was observed in 508 (93.7%) prescriptions. Clinically significant drug interactions (CSDIs) were detected in 486 (85.7%) prescriptions. Pharmacodynamic DDIs (466; 91.7%) were the most common. Pill burden exceeding 25 pills/day was present in nine (14.8%) patients. The severities of the potential DDIs were major (135; 24.9%), moderate (333; 61.4%), and minor (38; 7.1%). Only two different potential DDIs were rated X (contraindicated). CONCLUSION: Exposure to drugs with potential DDIs was very common among patients with kidney diseases. Most of the CSDIs observed were of major severity. The use of DDI checker before prescribing drugs for individuals with kidney diseases could avert clinically significant interactions.

Protective but Non-Synergistic Effects of Nigella Sativa and Vitamin E against Cisplatin-Induced Renal Toxicity and Oxidative Stress in Wistar Rats.

BACKGROUND: Cisplatin is an anti-cancer drug that causes nephrotoxicity and oxidative stress. Extracts of Nigella sativa is nephroprotective. Vitamin E is also a potent antioxidant. This study sought to determine a possible synergistic effect of administering the two agents prior to cisplatin use on nephrotoxicity and oxidative stress. METHODS: 48 male Wistar rats were randomly divided into 6 groups of 8 rats each. Group I served as the control. Group II received cisplatin without any treatment for 6 days. Groups III, IV, V and VI received 100 mg/kg Nigella sativa (NS), 200 mg/kg NS, 100 mg/kg Vitamin E and 200 mg/kg NS+100 mg/kg Vitamin E respectively for 5 days prior to 6 days administration of cisplatin. On the last day of the experiment, all the animals were sacrificed and serum samples collected for analysis. RESULTS: Cisplatin administration caused a significant increase in creatinine level (p<0.01), urea level (p<0.01), sodium concentration and malondialdehyde level (p<0.001). Pre-administration with NS caused a significant reduction in creatinine level (p<0.001), urea level (p<0.001), sodium concentration (p<0.001) and malondialdehyde (p<0.01) level. Pre-administration with vitamin E caused a significant reduction in creatinine level (p<0.001), urea level (p<0.01), sodium concentration (p<0.001) and malondialdehyde level. They both also caused a significant increase in superoxide dismutase, reduced glutathione and catalase (CAT) levels. The combination of NS and vitamin E however did not show significant synergistic effects. CONCLUSION: These results suggest that even though pre-administration of the two agents protect against renal toxicity and oxidative stress, the effects are however not collaborative.