| 1. |
- Do, Nga T. T., et al.
(author)
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Community-based antibiotic access and use in six low-income and middle-income countries: a mixed-method approach
- 2021
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In: The Lancet Global Health. - : Elsevier. - 2214-109X. ; 9:5, s. e610-e619
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Journal article (peer-reviewed)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.
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| 2. |
- Afari-Asiedu, Samuel, et al.
(author)
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Determinants of Inappropriate Antibiotics Use in Rural Central Ghana Using a Mixed Methods Approach
- 2020
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In: Frontiers In Public Health. - : Frontiers Media SA. - 2296-2565. ; 8
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Journal article (peer-reviewed)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.
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| 3. |
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| 4. |
- Laxminarayan, Ramanan, et al.
(author)
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Antibiotic resistance-the need for global solutions
- 2013
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In: The Lancet - Infectious diseases. - 1473-3099 .- 1474-4457. ; 13:12, s. 1057-1098
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Journal article (peer-reviewed)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.
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| 5. |
- Phu, Vu Dinh, et al.
(author)
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Ventilator-associated respiratory infection in a resource-restricted setting: impact and etiology
- 2017
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In: Journal of Intensive Care. - : BioMed Central (BMC). - 2052-0492. ; 5
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Journal article (peer-reviewed)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.
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| 6. |
- Ruth, Mike Marvin, et al.
(author)
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A bedaquiline/clofazimine combination regimen might add activity to the treatment of clinically relevant non-tuberculous mycobacteria
- 2019
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In: Journal of Antimicrobial Chemotherapy. - : OXFORD UNIV PRESS. - 0305-7453 .- 1460-2091. ; 74:4, s. 935-943
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Journal article (peer-reviewed)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.
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| 7. |
- Ruth, Mike Marvin, et al.
(author)
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Auranofin Activity Exposes Thioredoxin Reductase as a Viable Drug Target in Mycobacterium abscessus
- 2019
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In: Antimicrobial Agents and Chemotherapy. - 0066-4804 .- 1098-6596. ; 63:9
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Journal article (peer-reviewed)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.
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| 8. |
- Ruth, Mike Marvin, et al.
(author)
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Is there a role for tedizolid in the treatment of non-tuberculous mycobacterial disease?
- 2020
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In: Journal of Antimicrobial Chemotherapy. - : OXFORD UNIV PRESS. - 0305-7453 .- 1460-2091. ; 75:3, s. 609-617
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Journal article (peer-reviewed)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.
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| 9. |
- Sonawane, Vidhisha V., et al.
(author)
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An In Vitro Perspective on What Individual Antimicrobials Add to Mycobacterium avium Complex Therapies
- 2021
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In: Antimicrobial Agents and Chemotherapy. - : American Society for Microbiology. - 0066-4804 .- 1098-6596. ; 65:8
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Journal article (peer-reviewed)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.
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| 10. |
- Tien Viet Dung, Vu, et al.
(author)
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Antimicrobial susceptibility testing and antibiotic consumption results from 16 hospitals in Viet Nam: The VINARES project 2012-2013
- 2019
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In: Journal of Global Antimicrobial Resistance. - : ELSEVIER SCI LTD. - 2213-7165 .- 2213-7173. ; 18, s. 269-278
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Journal article (peer-reviewed)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.
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