| 1. |
- Afari-Asiedu, Samuel, et al.
(författare)
-
Determinants of Inappropriate Antibiotics Use in Rural Central Ghana Using a Mixed Methods Approach
- 2020
-
Ingår i: Frontiers in Public Health. - : Frontiers Media SA. - 2296-2565. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The consequences of antibiotic resistance are projected to be most severe in low and middle income countries with high infectious disease burden. This study examined determinants of inappropriate antibiotic use at the community level in rural Ghana. Methods: An observational study involving qualitative and quantitative methods was conducted between July, 2016 and September, 2018 in Ghana. Two household surveys were conducted at two time points (2017 and 2018) among 1,100 randomly selected households over 1 year. The surveys focused on antibiotic use episodes in the past month. Four in-depth interviews and two focus group discussions were performed to further explain the survey results. Determinants of inappropriate antibiotic use were assessed using a mixed effect logistic regression analysis (multilevel analysis) to account for the clustered nature of data. We defined inappropriate antibiotic use as either use without prescription, not completing treatment course or non-adherence to instruction for use. Qualitative data were thematically analyzed. Results: A total of 1,100 households was enrolled in which antibiotics were used in 585 (53.2%) households in the month prior to the surveys. A total of 676 (21.2%) participants out of 3,193 members from the 585 reportedly used antibiotics for 761 episodes of illness. Out of the 761 antibiotic use episodes, 659 (86.6%) were used inappropriately. Paying for healthcare without health insurance (Odds Ratio (OR): 2.10, 95% CI: 1.1-7.4, p-value: 0.026), not seeking healthcare from health centers (OR: 2.4, 95% CI: 1.2-5.0, p-value: 0.018), or pharmacies (OR: 4.6, 95% CI: 1.7-13.0, p-value: 0.003) were significantly associated with inappropriate antibiotic use. Socio-demographic characteristics were not significantly associated with inappropriate antibiotic use. However, the qualitative study described the influence of cost of medicines on inappropriate antibiotic use. It also revealed that antibiotic users with low socioeconomic status purchased antibiotics in installments which, could facilitate inappropriate use. Conclusion: Inappropriate antibiotic use was high and influenced by out-of-pocket payment for healthcare, seeking healthcare outside health centers, pharmacies, and buying antibiotics in installments due to cost. To improve appropriate antibiotic use, there is the need for ministry of health and healthcare agencies in Ghana to enhance healthcare access and healthcare insurance, and to provide affordable antibiotics.
|
|
| 2. |
- Afari-Asiedu, Samuel, et al.
(författare)
-
To sell or not to sell; the differences between regulatory and community demands regarding access to antibiotics in rural Ghana
- 2018
-
Ingår i: Journal of Pharmaceutical Policy and Practice. - : BMC. - 2052-3211. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- Background: In Ghana, there is extensive over-the-counter dispensing of antibiotics, resulting in high levels of inappropriate use, and an increase in antibiotic resistance. Regulations prevent Licenced Chemical Sellers (LCS, Over-the-Counter Medicine Sellers) from selling antibiotics other than Cotrimoxazole. In practice, however, these sellers sell a variety of antibiotics. This paper aims to provide insight into the differences between regulatory and community demands on the sale of antibiotics, and to explore how these differences in demand could be resolved to facilitate safe and appropriate use of antibiotics in rural Ghana.Methods: A total of 32 in-depth interviews were conducted in the Kintampo North and South Districts in Ghana; 16 among antibiotic suppliers, predominantly LCS, and 16 among community members. Six focus group discussions were also conducted among 40 community members. Data were coded using Nvivo 10 and thematically analyzed in line with study objectives. The results are presented as narratives with quotes to illustrate the findings.Results: Generally, antibiotic suppliers were aware that regulations prevent LCS from selling antibiotics except Cotrimoxazole. However, LCS sell all types of antibiotics because of community demand, economic motivations of LCS, and the poor implementation of regulations that are intended to prevent them from selling these medications. Factors that influence community demand for antibiotics include previous knowledge of effectiveness of some antibiotics, delays in seeking care at health facilities, financial constraints, and distance to health facilities. LCS suggested that they should be trained and allowed to sell some types of antibiotics instead of being prevented completely from selling. Community members also suggested that Community-based Health Planning and Services (CHPS) compounds should be equipped to dispense antibiotics.Conclusion: The sale of antibiotics by LCS at the community level is influenced by both structural and individual contextual factors. There is a need to educate community members on the appropriate access and use of antibiotics in rural Ghana. In addition, rather than enforcing rules that go against practice, it may be more effective to regulate the sale of antibiotics by LCS and train them to make their dispensing more appropriate. CHPS compound could also be equipped to dispense some antibiotics to improve appropriate antibiotic access at the community level.
|
|
| 3. |
|
|
| 4. |
- Cambaco, Olga, et al.
(författare)
-
Community knowledge and practices regarding antibiotic use in rural Mozambique : where is the starting point for prevention of antibiotic resistance?
- 2020
-
Ingår i: BMC Public Health. - : BMC. - 1471-2458. ; 20:1
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundAntibiotic misuse and other types of unnecessary use of antibiotics can contribute to accelerate the process of antibiotic resistance, which is considered a global concern, mostly affecting low-and middle-income countries (LMICs). In Mozambique there is limited evidence on community knowledge and practices regarding antibiotics and antibiotic resistance. As part of the ABACUS project, this paper describes knowledge and practices of antibiotic use among the general population in the semi-rural district of Manhica to inform evidence-based communication intervention strategies for safer antibiotic use.MethodsThe study was conducted in Manhica, a semi-rural district of Southern Mozambique. Sixteen in-depth interviews and four focus group discussions (FGDs) were conducted with community members to explore lay knowledge and practices regarding antibiotics and awareness of antibiotic resistance. The qualitative data was analysed using a combination of content and thematic analysis. The SRQR guidelines for reporting qualitative studies was performed.ResultsAlthough participants did not hold any consistent knowledge of antibiotics, their visual recognition of amoxicillin (distinct red yellow capsule) was acceptable, but less so for different types and brands of antibiotics. The majority of participants were aware of the term 'antibiotic', yet the definition they gave was rarely backed by biomedical knowledge. Participants associated antibiotics with certain colours, shapes and health conditions. Participants reported common habits that may contribute to resistance: not buying the full course, self-medication, sharing medicines and interruption of treatment. Most had never heard of the term 'antibiotic resistance' but were familiar with the phenomenon. They often understood the term 'resistance' as treatment failure and likened 'resistance' to non-compliance, ineffective medication, disease resistance or to an inability of the physical body to respond to it.ConclusionThere is a broad understanding of the importance of medication compliance but not specifically of antibiotic resistance. In addition, there is a recognized gap between knowledge of responsible drug compliance and actual behaviour. Future qualitative research is required to further explore what determines this behaviour. The existing ability to visually identify amoxicillin by its distinct red and yellow appearance is informative for future awareness and behavioural change campaigns that may incorporate visual aids of antibiotics.
|
|
| 5. |
- Chowdhury, Moyukh, et al.
(författare)
-
Rural community perceptions of antibiotic access and understanding of antimicrobial resistance : qualitative evidence from the Health and Demographic Surveillance System site in Matlab, Bangladesh
- 2020
-
Ingår i: Global Health Action. - : Taylor & Francis. - 1654-9716 .- 1654-9880. ; 12:sup1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The use of large quantities of antimicrobial drugs for human health and agriculture is advancing the predominance of drug resistant pathogens in the environment. Antimicrobial resistance is now a major public health threat posing significant challenges for achieving the Sustainable Development Goals. In Bangladesh, where over one third of the population is below the poverty line, the achievement of safe and effective antibiotic medication use for human health is challenging.Objective: To explore factors and practices around access and use of antibiotics and understanding of antimicrobial resistance in rural communities in Bangladesh from a socio-cultural perspective.Methods: This qualitative study comprises the second phase of the multi-country ABACUS (Antibiotic Access and Use) project in Matlab, Bangladesh. Information was collected through six focus group discussions and 16 in-depth interviews. Informants were selected from ten villages in four geographic locations using the Health and Demographic Surveillance System database. The Access to Healthcare Framework guided the interpretation and framing of the findings in terms of individuals' abilities to: perceive, seek, reach, pay and engage with healthcare.Results: Village pharmacies were the preferred and trusted source of antibiotics for self-treatment. Cultural and religious beliefs informed the use of herbal and other complementary medicines. Advice on antibiotic use was also sourced from trusted friends and family members. Access to government-run facilities required travel on poorly maintained roads. Reports of structural corruption, stock-outs and patient safety risks eroded trust in the public sector. Some expressed a willingness to learn about antibiotic resistance.Conclusion: Antimicrobial resistance is both a health and development issue. Social and economic contexts shape medicine seeking, use and behaviours. Multi-sectoral action is needed to confront the underlying social, economic, cultural and political drivers that impact on the access and use of antibiotic medicines in Bangladesh.
|
|
| 6. |
|
|
| 7. |
- Do, Nga T. T., et al.
(författare)
-
Community-based antibiotic access and use in six low-income and middle-income countries: a mixed-method approach
- 2021
-
Ingår i: The Lancet Global Health. - : Elsevier. - 2214-109X. ; 9:5, s. e610-e619
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Antimicrobial misuse is common in low-income and middle-income countries (LMICs), and this practice is a driver of antibiotic resistance. We compared community-based antibiotic access and use practices across communities in LMICs to identify contextually specific targets for interventions to improve antibiotic use practices.Methods: We did quantitative and qualitative assessments of antibiotic access and use in six LMICs across Africa (Mozambique, Ghana, and South Africa) and Asia (Bangladesh, Vietnam, and Thailand) over a 2·5-year study period (July 1, 2016–Dec 31, 2018). We did quantitative assessments of community antibiotic access and use through supplier mapping, customer exit interviews, and household surveys. These quantitative assessments were triangulated with qualitative drug supplier and consumer interviews and discussions.Findings: Vietnam and Bangladesh had the largest proportions of non-licensed antibiotic dispensing points. For mild illness, drug stores were the most common point of contact when seeking antibiotics in most countries, except South Africa and Mozambique, where public facilities were most common. Self-medication with antibiotics was found to be widespread in Vietnam (55·2% of antibiotics dispensed without prescription), Bangladesh (45·7%), and Ghana (36·1%), but less so in Mozambique (8·0%), South Africa (1·2%), and Thailand (3·9%). Self-medication was considered to be less time consuming, cheaper, and overall, more convenient than accessing them through health-care facilities. Factors determining where treatment was sought often involved relevant policies, trust in the supplier and the drug, disease severity, and whether the antibiotic was intended for a child. Confusion regarding how to identify oral antibiotics was revealed in both Africa and Asia.Interpretation: Contextual complexities and differences between countries with different incomes, policy frameworks, and cultural norms were revealed. These contextual differences render a single strategy inadequate and instead necessitate context-tailored, integrated intervention packages to improve antibiotic use in LMICs as part of global efforts to combat antibiotic resistance.
|
|
| 8. |
- Laxminarayan, Ramanan, et al.
(författare)
-
Antibiotic resistance-the need for global solutions
- 2013
-
Ingår i: The Lancet - Infectious diseases. - 1473-3099 .- 1474-4457. ; 13:12, s. 1057-1098
-
Tidskriftsartikel (refereegranskat)abstract
- The causes of antibiotic resistance are complex and include human behaviour at many levels of society; the consequences affect everybody in the world. Similarities with climate change are evident. Many efforts have been made to describe the many different facets of antibiotic resistance and the interventions needed to meet the challenge. However, coordinated action is largely absent, especially at the political level, both nationally and internationally. Antibiotics paved the way for unprecedented medical and societal developments, and are today indispensible in all health systems. Achievements in modern medicine, such as major surgery, organ transplantation, treatment of preterm babies, and cancer chemotherapy, which we today take for granted, would not be possible without access to effective treatment for bacterial infections. Within just a few years, we might be faced with dire setbacks, medically, socially, and economically, unless real and unprecedented global coordinated actions are immediately taken. Here, we describe the global situation of antibiotic resistance, its major causes and consequences, and identify key areas in which action is urgently needed.
|
|
| 9. |
- Matin, Mohammad Abdul, et al.
(författare)
-
What influences antibiotic sales in rural Bangladesh? : A drug dispensers' perspective
- 2020
-
Ingår i: Journal of Pharmaceutical Policy and Practice. - : Springer Nature. - 2052-3211. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Antibiotic resistance poses a great threat to global health, especially in low- and middle-income countries with a high infectious disease burden and limited resources. In spite of regulations, antibiotics are sold in many settings as non-prescription medicines, resulting in inappropriate use and resistance.Objective: This study aimed to investigate the current status of access and use of antibiotics in rural Bangladesh, by exploring the perspectives and sales practices of antibiotic drug dispensers.Methods: We used a mixed methods approach (qualitative and quantitative). We mapped and characterized antibiotic purchasing and dispensing sites in the Matlab Health and Demographic Surveillance System catchment area. Furthermore, we investigated the volume of provision of systemic antibiotics in 10 drug outlets. We held 16 in-depth interviews with randomly selected antibiotics dispensers. Interviews explored factors associated with antibiotic selling. Responses were transcribed, coded for themes, and summarized. We used ATLAS.ti 5.2 for conducting a thematic analysis.Results: A total of 301 antibiotic dispensers were identified, of whom 92% (n = 278) were private and 8% (n = 23) public. 52% (n = 155) operated informally (i.e. without legal authorization). In order to promote and survive in their business, dispensers sell antibiotics for a range of conditions without a qualified physician's prescription. Factors that facilitate these inappropriate sales include lack of access to healthcare in the rural community, inadequate doctor: population ratio, limited dispenser knowledge, poor pharmacovigilance concerning safety of self medication, lack of enforcement of policies, financial benefits for both customers and dispensers, and high dependency on pharmaceutical companies' information.Conclusion: Dispensers in rural Bangladesh sell antibiotics inappropriately by ignoring existing national regulations. They operate the antibiotic sales without facing any legal barriers and primarily with a view to sustain their business, resulting in inappropriate sales of antibiotics to the rural community. The influence of the drug industry needs to be replaced with evidence-based, not commercially driven information. Awareness programs for antibiotic providers that promote understanding of antibiotics and antibiotic resistance through tailored interventions may be helpful in changing current antibiotic sales practices.
|
|
| 10. |
- Nguyen, Hong Hanh, et al.
(författare)
-
"I can make more from selling medicine when breaking the rules" : understanding the antibiotic supply network in a rural community in Viet Nam
- 2019
-
Ingår i: BMC Public Health. - : BioMed Central. - 1471-2458. ; 19:1
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: As in many other low and middle income countries (LIMCs), Vietnam has experienced a major growth in the pharmaceutical industry, with large numbers of pharmacies and drug stores, and increasing drug expenditure per capita over the past decade. Despite regulatory frameworks that have been introduced to control the dispensing and use of prescription-only drugs, including antibiotics, compliance has been reported to be strikingly low particularly in rural parts of Vietnam. This qualitative study aimed to understand antibiotic access and use practices in the community from both supplier and consumer perspectives in order to support the identification and development of future interventions.METHODS: This qualitative study was part of a project on community antibiotic access and use (ABACUS) in six LMICs. The focus was Ba Vi district of Hanoi capital city, where we conducted 16 indepth interviews (IDIs) with drug suppliers, and 16 IDIs and 6 focus group discussions (FGDs) with community members. Drug suppliers were sampled based on mapping of all informal and formal antibiotic purchase or dispensing points in the study area. Community members were identified through local networks and relationships with the field collaborators. All IDIs and FGDs were audio-taped, transcribed and analysed using content analysis.RESULTS: We identified a large number of antibiotic suppliers in the locality with widespread infringements of regulatory requirements. Established reciprocal relationships between suppliers and consumers in drug transactions were noted, as was the consumers' trust in the knowledge and services provided by the suppliers. In addition, antibiotic use has become a habitual choice in most illness conditions, driven by both suppliers and consumers.CONCLUSIONS: This study presents an analysis of the practices of antibiotic access and use in a rural Vietnamese setting. It highlights the interactions between antibiotic suppliers and consumers in the community and identifies possible targets for interventions.
|
|
| 11. |
- Phu, Vu Dinh, et al.
(författare)
-
Burden of Hospital Acquired Infections and Antimicrobial Use in Vietnamese Adult Intensive Care Units
- 2016
-
Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background Vietnam is a lower middle-income country with no national surveillance system for hospital-acquired infections (HAIs). We assessed the prevalence of hospital-acquired infections and antimicrobial use in adult intensive care units (ICUs) across Vietnam. Methods Monthly repeated point prevalence surveys were systematically conducted to assess HAI prevalence and antimicrobial use in 15 adult ICUs across Vietnam. Adults admitted to participating ICUs before 08: 00 a.m. on the survey day were included. Results Among 3287 patients enrolled, the HAI prevalence was 29.5% (965/3266 patients, 21 missing). Pneumonia accounted for 79.4% (804/1012) of HAIs Most HAIs (84.5% [855/1012]) were acquired in the survey hospital with 42.5% (363/855) acquired prior to ICU admission and 57.5% (492/855) developed during ICU admission. In multivariate analysis, the strongest risk factors for HAI acquired in ICU were: intubation (OR 2.76), urinary catheter (OR 2.12), no involvement of a family member in patient care (OR 1.94), and surgery after admission (OR 1.66). 726 bacterial isolates were cultured from 622/1012 HAIs, most frequently Acinetobacter baumannii (177/726 [24.4%]), Pseudomonas aeruginosa (100/726 [13.8%]), and Klebsiella pneumoniae (84/726 [11.6%]), with carbapenem resistance rates of 89.2%, 55.7%, and 14.9% respectively. Antimicrobials were prescribed for 84.8% (2787/ 3287) patients, with 73.7% of patients receiving two or more. The most common antimicrobial groups were third generation cephalosporins, fluoroquinolones, and carbapenems (20.1%, 19.4%, and 14.1% of total antimicrobials, respectively). Conclusion A high prevalence of HAIs was observed, mainly caused by Gram-negative bacteria with high carbapenem resistance rates. This in combination with a high rate of antimicrobial use illustrates the urgent need to improve rational antimicrobial use and infection control efforts.
|
|
| 12. |
- Phu, Vu Dinh, et al.
(författare)
-
Ventilator-associated respiratory infection in a resource-restricted setting: impact and etiology
- 2017
-
Ingår i: Journal of Intensive Care. - : BioMed Central (BMC). - 2052-0492. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- Ventilator-associated respiratory infection (VARI) is a significant problem in resource-restricted intensive care units (ICUs), but differences in casemix and etiology means VARI in resource-restricted ICUs may be different from that found in resource-rich units. Data from these settings are vital to plan preventative interventions and assess their cost-effectiveness, but few are available.
|
|
| 13. |
- Ruth, Mike Marvin, et al.
(författare)
-
A bedaquiline/clofazimine combination regimen might add activity to the treatment of clinically relevant non-tuberculous mycobacteria
- 2019
-
Ingår i: Journal of Antimicrobial Chemotherapy. - : OXFORD UNIV PRESS. - 0305-7453 .- 1460-2091. ; 74:4, s. 935-943
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Non-tuberculous mycobacteria (NTM) infections are hard to treat. New antimicrobial drugs and smarter combination regimens are needed.Objectives: Our aim was to determine the in vitro activity of bedaquiline against NTM and assess its synergy with established antimycobacterials.Methods: We determined MICs of bedaquiline for clinically relevant NTM species and Mycobacterium tuberculosis by broth microdilution for 30 isolates. Synergy testing was performed using the chequerboard method for 22 reference strains and clinical isolates of Mycobacterium abscessus (MAB) and Mycobacterium avium complex (MAC). Time-kill kinetics (TK) assays with resistance monitoring of bedaquiline alone and combined with clofazimine were performed for MAB CIP 104536 and M. avium ATCC 700898; bedaquiline/clarithromycin combinations were evaluated against M. avium ATCC 700898. Interactions were assessed for TK experiments based on Bliss independence.Results: Bedaquiline had modest activity against tested NTM, with MICs between <0.007and 1mg/L. Bedaquiline showed no interaction with tested drugs against MAB or MAC. Lowest mean fractional inhibitory concentration index (FICI) values were 0.79 with clofazimine for MAB and 0.97 with clofazimine and 0.82 with clarithromycin for MAC. In TK assays, bedaquiline showed a bacteriostatic effect. Clofazimine extended the bacteriostatic activity of bedaquiline against MAB and yielded a slight bactericidal effect against M. avium. The bedaquiline/clofazimine combination slowed emergence of bedaquiline resistance for M. avium but promoted it for MAB. Relative to Bliss independence, bedaquiline/clofazimine showed synergistic interaction over time for MAB and no interaction for M. avium and bedaquiline/clarithromycin showed antagonistic interaction for M. avium.Conclusions: Following these in vitro data, a bedaquiline/clofazimine combination might add activity to MAB and MAC treatment. The bedaquiline/clarithromycin combination might have lower activity compared with bedaquiline alone for MAC treatment.
|
|
| 14. |
- Ruth, Mike Marvin, et al.
(författare)
-
Auranofin Activity Exposes Thioredoxin Reductase as a Viable Drug Target in Mycobacterium abscessus
- 2019
-
Ingår i: Antimicrobial Agents and Chemotherapy. - 0066-4804 .- 1098-6596. ; 63:9
-
Tidskriftsartikel (refereegranskat)abstract
- Nontuberculous mycobacteria (NTM) are highly drug-resistant, opportunistic pathogens that can cause pulmonary disease. The outcomes of the currently recommended treatment regimens are poor, especially for Mycobacterium abscessus. New or repurposed drugs are direly needed. Auranofin, a gold-based antirheumatic agent, was investigated for Mycobacterium tuberculosis. Here, we test auranofin against NTM in vitro and ex vivo. We tested the susceptibility of 63 NTM isolates to auranofin using broth microdilution. Next, we assessed synergy between auranofin and antimycobacterial drugs using the checkerboard method and calculated the fractional inhibition concentration index (FICI). Using time-kill kinetics assays (TK), we assessed pharmacodynamics of auranofin alone and in combination with drug combinations showing the lowest FICIs for M. abscessus CIP 104536. A response surface analysis was used to assess synergistic interactions over time in TKs. Primary isolated macrophages were infected with M. abscessus and treated with auranofin. Finally, using KEGG Orthology, we looked for orthologues to auranofins drug target in M. tuberculosis. M. abscessus had the lowest auranofin MIC50 (2 mu g/ml) among the tested NTM. The lowest average FICIs were observed between auranofin and amikacin (0.45) and linezolid (0.50). Auranofin exhibited concentration-dependent killing of M. abscessus, with >1-log killing at concentrations of >2x MIC. Only amikacin was synergistic with auranofin according to Bliss independence. Auranofin could not lower the intracellular bacterial load in macrophages. Auranofin itself may not be feasible for M. abscessus treatment, but these data point toward a promising, unutilized drug target.
|
|
| 15. |
- Ruth, Mike Marvin, et al.
(författare)
-
Is there a role for tedizolid in the treatment of non-tuberculous mycobacterial disease?
- 2020
-
Ingår i: Journal of Antimicrobial Chemotherapy. - : OXFORD UNIV PRESS. - 0305-7453 .- 1460-2091. ; 75:3, s. 609-617
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Pulmonary infections caused by non-tuberculous mycobacteria (NTM) are hard to treat and have low cure rates despite intensive multidrug therapy.Objectives: To assess the feasibility of tedizolid, a new oxazolidinone, for the treatment of Mycobacterium avium and Mycobacterium abscessus.Methods: We determined MICs of tedizolid for 113 isolates of NTM. Synergy with key antimycobacterial drugs was assessed using the chequerboard method and calculation of the FIC index (FICI). We performed time-kill kinetics assays of tedizolid alone and combined with amikacin for M. abscessus and with ethambutol for M. avium. Human macrophages were infected with M. abscessus and M. avium and subsequently treated with tedizolid; intracellular and extracellular cfu were quantified over time.Results: NTM isolates generally had a lower MIC of tedizolid than of linezolid. FICIs were lowest between tedizolid and amikacin for M. abscessus (FICI = 0.75) and between tedizolid and ethambutol for M. avium (FICI = 0.72). Clarithromycin and tedizolid showed initial synergy, which was abrogated by erm(41)-induced macrolide resistance (FICI = 0.53). Tedizolid had a weak bacteriostatic effect on M. abscessus and combination with amikacin slightly prolonged its effect. Tedizolid had concentration-dependent activity against M. avium and its efficacy was enhanced by ethambutol. Both combinations had a concentration-dependent synergistic effect. Tedizolid could inhibit the intracellular bacterial population of both M. avium and M. abscessus.Conclusions: Tedizolid should be further investigated in pharmacodynamic studies and clinical trials for M. avium complex pulmonary disease. It is less active against M. abscessus, but still promising.
|
|
| 16. |
- Ruth, Mike Marvin, et al.
(författare)
-
Standard therapy of Mycobacterium avium complex pulmonary disease shows limited efficacy in an open source hollow fibre system that simulates human plasma and epithelial lining fluid pharmacokinetics
- 2022
-
Ingår i: Clinical Microbiology and Infection. - : Elsevier. - 1198-743X .- 1469-0691. ; 28:3, s. 448.e1-448.e7
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: Mycobacterium avium complex (MAC) bacteria can cause chronic pulmonary disease (PD). Current treatment regimens of azithromycin, ethambutol and rifampicin have culture conversion rates of around 65%. Dynamic, preclinical models to assess the efficacy of treatment regimens are important to guide clinical trial development. The hollow fibre system (HFS) has been applied but reports lack experimental details.Methods: We simulated the human pharmacokinetics of azithromycin, ethambutol and rifampicin both in plasma and epithelial lining fluid (ELF) in a HFS, exposing THP-1 cells infected with M. avium to the triple-drug regimen for 3 weeks. We accounted for drug-drug interactions and protein-binding and provide all laboratory protocols. We differentiated the effects on the intracellular and extracellular mycobacterial population.Results: The antibiotic concentrations in the HFS accurately reflected the time to peak concentration (T-max), the peak concentration (C-max) and half-life of azithromycin, rifampicin and ethambutol in plasma and ELF reported in literature. We find that plasma drug concentrations fail to hold the MAC bacterial load static (Delta Log10 CFU/ml(Control:Regimen) = 0.66 +/- 0.76 and 0.45 +/- 0.28 at 3 and 21 days); ELF concentrations do hold the bacterial load static for 3 days and inhibit bacterial growth for the duration of the experiment (Delta Log10 CFU/ml(Control:Regimen) = 1.1 +/- 0.1 and 1.64 +/- 0.59 at 3 and 21 days).Discussion: In our model, the current therapy against MAC is ineffective, even when accounting for antibiotic accumulation at the site of infection and intracellularly. New treatment regimens need to be developed and be compared with currently recommended regimens in dynamic models prior to clinical evaluation. With the publication of all protocols we aim to open this technology to new users.
|
|
| 17. |
- Sonawane, Vidhisha V., et al.
(författare)
-
An In Vitro Perspective on What Individual Antimicrobials Add to Mycobacterium avium Complex Therapies
- 2021
-
Ingår i: Antimicrobial Agents and Chemotherapy. - : American Society for Microbiology. - 0066-4804 .- 1098-6596. ; 65:8
-
Tidskriftsartikel (refereegranskat)abstract
- For Mycobacterium avium complex pulmonary disease (MAC-PD), current treatment regimens yield low cure rates. To obtain an evidence-based combination therapy, we assessed the in vitro activity of six drugs, namely, clarithromycin (CLR), rifampin (RIF), ethambutol (EMB), amikacin (AMK), clofazimine (CLO), and minocycline (MIN), alone and in combination, against Mycobacterium avium and studied the contributions of individual antibiotics to efficacy. The MICs of all antibiotics against M. avium ATCC 700898 were determined by broth microdilution. We performed kinetic time-kill assays of all single drugs and clinically relevant two-, three-, four-, and five-drug combinations against M. avium. Pharmacodynamic interactions of these combinations were assessed using area under the time-kill curve-derived effect size and Bliss independence. Adding a second drug yielded an average increase of the effect size (E) of 18.7% +/- 32.9%, although antagonism was seen in some combinations. Adding a third drug showed a smaller increase in effect size (112.2% +/- 11.5%). The RIF-CLO-CLR (E of 102 log(10) CFU/ml . day), RIF-AMK-CLR (E of 101 log(10) CFU/ml . day), and AMK-MIN-EMB (E of 97.8 log(10) CFU/ml . day) regimens proved more active than the recommended RIF-EMB-CLR regimen (E of 89.1 log(10) CFU/ml . day). The addition of a fourth drug had little impact on effect size (+14.54% +/- 3.08%). In vitro, several two- and three-drug regimens are as effective as the currently recommended regimen for MAC-PD. Adding a fourth drug to any regimen had little additional effect. In vitro, the most promising regimen would be RIF-AMK-macrolide or RIF-CLO-macrolide.
|
|
| 18. |
- Sunpuwan, Malee, et al.
(författare)
-
What is in the drug packet? : access and use of non-prescribed poly-pharmaceutical packs (Yaa Chud) in the community in Thailand
- 2019
-
Ingår i: BMC Public Health. - : BioMed Central. - 1471-2458. ; 19:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: ‘Yaa Chud’ is a non-prescribed poly-pharmaceutical pack containing several types of drugs, including antibiotics and steroids, which can be purchased over the counter in Thailand for self-medication. Although it is illegal, it is still available at some community outlets. This study aimed to understand access to and use of Yaa Chud at the community level in order to raise awareness on its usage and to provide policy recommendations to address the problem.Methods: This study employed qualitative methods, including in-depth interviews with 18 drug suppliers and 16 community members, and six focus group discussions. It included inventories from 17 drug suppliers. Data were collected in selected communities of the Kanchanaburi Demographic Surveillance System, located in the western region of Thailand.Thematic analysis was based upon the Health Services Utilization Model and conducted using the Open Code qualitative software program.Results: Overcrowding, long waiting times, and a perceived unwelcoming environment at public health-care service outlets were identified as factors that drive people into the private sector, where loose regulation of drug laws facilitates access and use of Yaa Chud. Migrants and older people were most likely to seek and use Yaa Chud, especially for mild illness. Availability, easy access through a user’s network, low cost, and perceived effectiveness were identified as factors that enable access and use of Yaa Chud.Conclusions: Though illegal in Thailand, Yaa Chud is likely to remain available for self-medication by community members, due to the persisting demand by the elderly and migrant workers. There is an urgent need to replace these mixed medications with better choices. Safer Yaa Chud may be a preferred, first-line health-care option, which could help reduce congestion in the formal health-care setting. At the same time, enforcement of regulatory compliance needs to be continued in order to stop the supply of unsafe Yaa Chud.
|
|
| 19. |
- Tien Viet Dung, Vu, et al.
(författare)
-
Antimicrobial susceptibility testing and antibiotic consumption results from 16 hospitals in Viet Nam: The VINARES project 2012-2013
- 2019
-
Ingår i: Journal of Global Antimicrobial Resistance. - : ELSEVIER SCI LTD. - 2213-7165 .- 2213-7173. ; 18, s. 269-278
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To establish a hospital-based surveillance network with national coverage for antimicrobial resistance (AMR) and antibiotic consumption in Viet Nam. Methods: A 16-hospital network (Viet Nam Resistance: VINARES) was established and consisted of national and provincial-level hospitals across the country. Antimicrobial susceptibility testing results from routine clinical diagnostic specimens and antibiotic consumption data in Defined Daily Dose per 1000 bed days (DDD/1000 patient-days) were prospectively collected and analysed between October 2012 and September 2013. Results: Data from a total of 24 732 de-duplicated clinical isolates were reported. The most common bacteria were: Escherichia coli (4437 isolates, 18%), Klebsiella spp. (3290 isolates, 13%) and Acinetobacter spp. (2895 isolates, 12%). The hospital average antibiotic consumption was 918 DDD/1000 patient-days. Third-generation cephalosporins were the most frequently used antibiotic class (223 DDD/1000 patient-days, 24%), followed by fluoroquinolones (151 DDD/1000 patient-days, 16%) and second-generation cephalosporins (112 DDD/1000 patient-days, 12%). Proportions of antibiotic resistance were high: 1098/1580 (69%) Staphylococcus aureus isolates were methicillin-resistant (MRSA); 115/344 isolates (33%) and 90/358 (25%) Streptococcus pneumoniae had reduced susceptibility to penicillin and ceftriaxone, respectively. A total of 180/2977 (6%) E. coli and 242/1526 (16%) Klebsiella pneumoniae were resistant to imipenem, respectively; 602/1826 (33%) Pseudomonas aeruginosa were resistant to ceftazidime and 578/1765 (33%) to imipenem. Of Acinetobacter spp. 1495/2138 (70%) were resistant to carbapenems and 2/333 (1%) to colistin. Conclusions: These data are valuable in providing a baseline for AMR among common bacterial pathogens in Vietnamese hospitals and to assess the impact of interventions. (C) 2019 The Authors. Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy.
|
|
| 20. |
- Watkins, Jocelyn Anstey, et al.
(författare)
-
Rural South African Community Perceptions of Antibiotic Access and Use : Qualitative Evidence from a Health and Demographic Surveillance System Site
- 2019
-
Ingår i: American Journal of Tropical Medicine and Hygiene. - : AMER SOC TROP MED & HYGIENE. - 0002-9637 .- 1476-1645. ; 100:6, s. 1378-1390
-
Tidskriftsartikel (refereegranskat)abstract
- Knowledge and practices of rural South African populations with regard to antibiotic access and use (ABACUS) remain understudied. By using the case of four villages in the north east of the country, our aim was to investigate popular notions and social practices related to antibiotics to inform patient-level social interventions for appropriate antibiotic use. To achieve this, we investigated where community members (village residents) were accessing and sourcing medication, and what they understood antibiotics and antibiotic resistance (ABR) to be. Embedded within the multicountry ABACUS project, this qualitative study uses interviews and focus group discussions. A sample of 60 community members was recruited from the Agincourt Health and Demographic Surveillance System, situated in Mpumalanga Province, from April to August, 2017. We used the five abilities of seek, reach, pay, perceive, and engage in access to healthcare as proposed by Levesque's "Access to Healthcare" framework. Respondents reported accessing antibiotics prescribed from legal sources: by nurses at the government primary healthcare clinics or by private doctors dispensed by private pharmacists. No account of the illegal purchasing of antibiotics was described. There was a mix of people who finished their prescription according to the instructions and those who did not. Some people kept antibiotics for future episodes of infection. The concept of "ABR" was understood by some community members when translated into related Xitsonga words because of knowledge tuberculosis and HIV/AIDS treatment regimens. Our findings indicate that regulation around the sale of antibiotics is enforced. Safer use of antibiotics and why resistance is necessary to understand need to be instilled. Therefore, context-specific educational campaigns, drawing on people's understandings of antibiotics and informed by the experiences of other diseases, may be an important and deployable means of promoting the safe use of antibiotics.
|
|
| 21. |
|
|
| 22. |
- Wertheim, Heiman, et al.
(författare)
-
Global survey of polymyxin use : A call for international guidelines
- 2013
-
Ingår i: JOURNAL OF GLOBAL ANTIMICROBIAL RESISTANCE. - : Elsevier BV. - 2213-7165. ; 1:3, s. 131-134
-
Tidskriftsartikel (refereegranskat)abstract
- Polymyxins (polymyxin B and colistin) are older bactericidal antibiotics that are increasingly used to treat infections caused by multidrug-resistant (MDR) Gram-negative bacteria. However, dosing and clinical use of these drugs vary widely. This survey was undertaken to reveal how polymyxins are used worldwide. Data were collected through a structured online questionnaire consisting of 24 questions regarding colistin usage patterns and indications as well as colistin dosage for adult patients. The questionnaire was disseminated in 2011 to relevant experts worldwide and was completed by 284 respondents from 56 different countries. Respondents from 11/56 countries (20%) had no access to colistin; 58/284 respondents (20.4%) reported that in 2010 they experienced that colistin was not available when needed. Formulations of polymyxins used were reported as: colistimethate sodium (48.6%); colistin sulfate (14.1%); both (1.4%); polymyxin B (1.4%); and unknown. Intravenous formulations were used by 84.2%, aerosolised or nebulised colistin by 44.4% and oral colistin for selective gut decontamination by 12.7%. Common indications for intravenous colistin were ventilator-associated pneumonia, sepsis and catheter-related infections with MDR Gram-negative bacteria. Only 21.2% of respondents used a colistin-loading dose, mainly in Europe and North America. This survey reveals that the majority of respondents use colistin and a few use polymyxin B. The survey results show that colistin is commonly underdosed. Clear guidance is needed on indications, dosing and antibiotic combinations to improve clinical outcomes and delay the emergence of resistance. Colistin should be considered a last-resort drug and its use should be controlled. International guidelines are urgently needed. (C) 2013 International Society for Chemotherapy of Infection and Cancer.
|
|
