Multidrug-Resistant Infections in the Developing World.

Antimicrobials are essential in reducing morbidity and mortality from infectious diseases globally. However, due to the lack of effective surveillance measures and widespread overuse, there is an increasing threat to the effectiveness of antimicrobials. Although there is a global increase in antimicrobial resistance, low- and middle-income countries share a much higher burden. Antimicrobial stewardship efforts such as effective surveillance and reduction in overuse can help combat the increase in antimicrobial resistance.

Global access to existing and future antimicrobials and diagnostics: antimicrobial subscription and pooled procurement.

The COVID-19 pandemic has underlined the importance of an efficient and equitable supply of and access to essential health products. These factors are equally pertinent to the antimicrobial resistance pandemic, in which access to a portfolio of existing and pipeline antimicrobials plus complementary diagnostics is crucial. This Viewpoint focuses on market shaping in low-income and middle-income countries (LMICs), where the need for effective antimicrobials and complementary diagnostics is most acute. We propose the creation of a subscription and pooled procurement model that consolidates the growing demand for a portfolio of antimicrobials and diagnostics in LMICs. Anchored by regional market leaders, these pooling mechanisms would guarantee consistent private-sector and public-sector access in participating countries, while creating conditions for long-term best practice in stewardship. Supported by data from South Africa and India, this proposal sets out an innovative approach to tackle the antimicrobial resistance crisis in LMICs.

Effects of the cefazolin shortage on the sales, cost, and appropriate use of other antimicrobials.

BACKGROUND: Shortages of antimicrobials lead to treatment failures, increase medical costs, and accelerate the development of antimicrobial resistance. We evaluated the effects of the serious cefazolin shortage in 2019 in Japan on the sales, costs, and appropriate use of other antimicrobials. METHODS: We evaluated monthly defined daily doses/1000 inhabitants/day (DID) values of antimicrobial sales from January 2016 to December 2019 using wholesaler's sales databases. Using 2016-2018 sales data, we generated a prediction model of DID in 2019 under the assumption that the cefazolin shortage did not occur. We then compared the predicted DID and actual DID. Cefazolin, government-recommended alternatives, and government-not-recommended broad-spectrum alternatives were assessed. Antimicrobial groups according to the AWaRe classification were also assessed to evaluate the effect on appropriate antimicrobial use. In addition, we evaluated changes in costs between 9 months before and after the cefazolin shortage. RESULTS: DID values of total antimicrobials increased sharply 1 month before the decrease in cefazolin. Actual DIDs were higher than predicted DIDs for ceftriaxone, flomoxef, clindamycin, cefotiam, piperacillin/tazobactam, and meropenem. Actual DID values were higher than the predicted DID values in the Watch group. The costs of antimicrobials between pre- and post- cefazolin shortage were unchanged. CONCLUSION: The cefazolin shortage brought confusion to the antimicrobial market and led to a setback in the appropriate use of antimicrobials. Early recognition and structures for prompt reactions to antimicrobial shortages are needed. Moreover, development of a system to secure the supply of essential antimicrobials is required.

Income compensation options and partial budget analysis following a reduction of antimicrobial sales at the veterinary practice level.

Over the years, the excessive consumption of antimicrobials (AM) by animals and humans has become a major concern at the global level, and several studies have highlighted the link between antimicrobial use (AMU) and antimicrobial resistance. Previous studies showed that, in Switzerland, every calf in the fattening process received in average seven days of AM treatment, and mainly oral group treatments. Therefore, policies to reduce the consumption of AM among veal calves should be implemented and promoted to decrease AM pressure on the microbiome. This study aimed to assess how a potential loss of income due to a reduction of AM prescriptions and sales in the Swiss veal calves sector could potentially be compensated. Partial budget models at the veterinary practice level were built to evaluate the effect on the net profit of veterinary practices, following four different national policy interventions that aim to reduce AM prescriptions for veal calves. The best-case scenarios resulted in a positive net profit. The scenarios assuming complete loss of profit from AM sales resulted in very low or negative net profit. Therefore, without financial support (e.g. through the government or other entities), veterinarians are likely to find it difficult to fully compensate the economic losses. At the practice level, income compensation mechanisms require a fundamental change of the business model. New model should be largely independent of pharmaceutical sales and should promote paid counselling on herd health management.

Characterization of low-cost glycolipoprotein biosurfactant produced by Lactobacillus plantarum 60 FHE isolated from cheese samples using food wastes through response surface methodology and its potential as antimicrobial, antiviral, and anticancer activities.

Considering the need of new lactic acid bacteria (LAB) for the production of novel biosurfactant (BS) molecules, the current study brings out a new insight on the exploration of cheese samples for BS producers and process optimization for industrial applications. In view of this, Lactobacillus plantarum 60FHE, Lactobacillus paracasei 75FHE, and Lactobacillus paracasei 77FHE were selected as the most operative strains. The biosurfactants (BSs) described as glycolipoproteins via Fourier-transform infrared spectroscopy (FTIR) exhibited antimicrobial activity against the food-borne pathogens. L. plantarum 60FHE BS showed an anticancer activity against colon carcinoma cells and had a week antiviral activity against Hepatitis A virus. Furthermore, glycolipoprotein production was enhanced by 1.42-fold through the development of an optimized process using central composite design (CCD). Emulsifying activities were stable after 60-min incubation from 4 to 120 °C, at pH 2-12, and after the addition of NaCl (2-14%). Characterization by nuclear magnetic resonance spectroscopy (1H NMR) revealed that BS produced from strain 60FHE was glycolipoprotein. L. plantarum produced mixed BSs determined by Liquid Chromatography/Mass Spectrometry (LC-MS). Thus, indicating that BS was applied as a microbial food prevention and biomedical. Also, L. plantarum 60FHE BS was achieved with the use of statistical optimization on inexpensive food wastes.

Value assessment of antimicrobials and the implications for development, access, and funding of effective treatments: Australian stakeholder perspective.

BACKGROUND: The frameworks used by Health Technology Assessment (HTA) agencies for value assessment of medicines aim to optimize healthcare resource allocation. However, they may not be effective at capturing the value of antimicrobial drugs. OBJECTIVES: To analyze stakeholder perceptions regarding how antimicrobials are assessed for value for reimbursement purposes and how the Australian HTA framework accommodates the unique attributes of antimicrobials in cost-effectiveness evaluation. METHODS: Eighteen individuals representing the pharmaceutical industry or policy-makers were interviewed. Interviews were transcribed verbatim, coded, and thematically analyzed. RESULTS: Key emergent themes were that reimbursement decision-making should consider the antibiotic spectrum when assessing value, risk of shortages, the impact of procurement processes on low-priced comparators, and the need for methodological transparency when antimicrobials are incorporated into the economic evaluation of other treatments. CONCLUSIONS: Participants agreed that the current HTA framework for antimicrobial value assessment is inadequate to properly inform funding decisions, as the contemporary definition of cost-effectiveness fails to explicitly incorporate the risk of future resistance. Policy-makers were uncertain about how to incorporate future resistance into economic evaluations without a systematic method to capture costs avoided due to good stewardship. Lacking financial reward for the benefits of narrower-spectrum antimicrobials, companies will likely focus on developing broad-spectrum agents with wider potential use. The perceived risks of shortages have influenced the funding of generic antimicrobials in Australia, with policy-makers suggesting a willingness to pay more for assured supply. Although antibiotics often underpin the effectiveness of other medicines, it is unclear how this is incorporated into economic models.

Antimicrobial-impregnated central venous catheters for preventing neonatal bloodstream infection: the PREVAIL RCT.

BACKGROUND: Clinical trials show that antimicrobial-impregnated central venous catheters reduce catheter-related bloodstream infection in adults and children receiving intensive care, but there is insufficient evidence for use in newborn babies. OBJECTIVES: The objectives were (1) to determine clinical effectiveness by conducting a randomised controlled trial comparing antimicrobial-impregnated peripherally inserted central venous catheters with standard peripherally inserted central venous catheters for reducing bloodstream or cerebrospinal fluid infections (referred to as bloodstream infections); (2) to conduct an economic evaluation of the costs, cost-effectiveness and value of conducting additional research; and (3) to conduct a generalisability analysis of trial findings to neonatal care in the NHS. DESIGN: Three separate studies were undertaken, each addressing one of the three objectives. (1) This was a multicentre, open-label, pragmatic randomised controlled trial; (2) an analysis was undertaken of hospital care costs, lifetime cost-effectiveness and value of information from an NHS perspective; and (3) this was a retrospective cohort study of bloodstream infection rates in neonatal units in England. SETTING: The randomised controlled trial was conducted in 18 neonatal intensive care units in England. PARTICIPANTS: Participants were babies who required a peripherally inserted central venous catheter (of 1 French gauge in size). INTERVENTIONS: The interventions were an antimicrobial-impregnated peripherally inserted central venous catheter (coated with rifampicin-miconazole) or a standard peripherally inserted central venous catheter, allocated randomly (1 : 1) using web randomisation. MAIN OUTCOME MEASURE: Study 1 - time to first bloodstream infection, sampled between 24 hours after randomisation and 48 hours after peripherally inserted central venous catheter removal. Study 2 - cost-effectiveness of the antimicrobial-impregnated peripherally inserted central venous catheter compared with the standard peripherally inserted central venous catheters. Study 3 - risk-adjusted bloodstream rates in the trial compared with those in neonatal units in England. For study 3, the data used were as follows: (1) case report forms and linked death registrations; (2) case report forms and linked death registrations linked to administrative health records with 6-month follow-up; and (3) neonatal health records linked to infection surveillance data. RESULTS: Study 1, clinical effectiveness - 861 babies were randomised (antimicrobial-impregnated peripherally inserted central venous catheter, n = 430; standard peripherally inserted central venous catheter, n = 431). Bloodstream infections occurred in 46 babies (10.7%) randomised to antimicrobial-impregnated peripherally inserted central venous catheters and in 44 (10.2%) babies randomised to standard peripherally inserted central venous catheters. No difference in time to bloodstream infection was detected (hazard ratio 1.11, 95% confidence interval 0.73 to 1.67; p = 0.63). Secondary outcomes of rifampicin resistance in positive blood/cerebrospinal fluid cultures, mortality, clinical outcomes at neonatal unit discharge and time to peripherally inserted central venous catheter removal were similar in both groups. Rifampicin resistance in positive peripherally inserted central venous catheter tip cultures was higher in the antimicrobial-impregnated peripherally inserted central venous catheter group (relative risk 3.51, 95% confidence interval 1.16 to 10.57; p = 0.02) than in the standard peripherally inserted central venous catheter group. Adverse events were similar in both groups. Study 2, economic evaluation - the mean cost of babies' hospital care was £83,473. Antimicrobial-impregnated peripherally inserted central venous catheters were not cost-effective. Given the increased price, compared with standard peripherally inserted central venous catheters, the minimum reduction in risk of bloodstream infection for antimicrobial-impregnated peripherally inserted central venous catheters to be cost-effective was 3% and 15% for babies born at 23-27 and 28-32 weeks' gestation, respectively. Study 3, generalisability analysis - risk-adjusted bloodstream infection rates per 1000 peripherally inserted central venous catheter days were similar among babies in the trial and in all neonatal units. Of all bloodstream infections in babies receiving intensive or high-dependency care in neonatal units, 46% occurred during peripherally inserted central venous catheter days. LIMITATIONS: The trial was open label as antimicrobial-impregnated and standard peripherally inserted central venous catheters are different colours. There was insufficient power to determine differences in rifampicin resistance. CONCLUSIONS: No evidence of benefit or harm was found of peripherally inserted central venous catheters impregnated with rifampicin-miconazole during neonatal care. Interventions with small effects on bloodstream infections could be cost-effective over a child's life course. Findings were generalisable to neonatal units in England. Future research should focus on other types of antimicrobial impregnation of peripherally inserted central venous catheters and alternative approaches for preventing bloodstream infections in neonatal care. TRIAL REGISTRATION: Current Controlled Trials ISRCTN81931394. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 57. See the NIHR Journals Library website for further project information.

Babies who are born too early or who are very sick require intensive care after birth and during early life. Most will have a long, narrow, plastic tube, called a catheter, inserted into a vein. The catheter is used to give babies fluids containing medicines and nutrition to keep them well and help them grow. The catheter can remain in place for several days or weeks. But the presence of plastic tubing in the vein increases the risk of infection. This study aimed to find out whether or not catheters coated with antimicrobial medicines, called rifampicin and miconazole, could reduce the risk of infection. These medicines act by stopping germs from growing on the catheter, but do not harm the baby or interfere with other treatments. A randomised controlled trial was carried out in 18 neonatal units in England. Whenever a baby needed a catheter, their parents were asked for consent to participate in the trial. The baby was then randomised, similar to tossing a coin, to receive either the antimicrobial catheter or a standard one. A total of 861 babies participated. We followed up all babies in the same way until after the catheter was removed to compare how often babies in each group had an infection. It was found that antimicrobial catheters were no better or worse at preventing infection than standard catheters. Antimicrobial catheters cost more and we found no evidence of benefit; these results suggest that their use in neonatal intensive care is not justified. It was calculated that further research on ways to reduce infection may be good value for money, depending on the costs of this research. The babies who took part in this study were typical of babies in England receiving catheters, meaning that the results can be applied across the NHS. Future research should focus on catheters that contain other types of antimicrobials and alternative ways of preventing infection.

The impact of antimicrobial stewardship programme on regulating the policy adherence and antimicrobial usage in selected intensive care units in a tertiary care center - A prospective interventional study.

Purpose: Antimicrobial resistance (AMR) presents a significant threat to human health. The root cause for this global problem is irrational antimicrobial usage. Antimicrobial stewardship (AMS) emphasises on the appropriate use of antibiotics and ensures strict implementation of antimicrobial policy guidelines. This study was conducted to evaluate the impact of auditing of AMS programme on regulating the antimicrobial policy adherence and antimicrobial usage in hospital intensive care units. Materials and Methods: This was a prospective interventional study. It consisted of pre-implementation and implementation phases 6 months each. Two hundred and eighty patients were enrolled. Details of antibiotic consumption, surgical prophylaxis, culture/sensitivity patterns, de-escalation rates, etc., were collected in both phases. The implementation phase, in addition, included stewardship audit rounds. Results: In pre-implementation phase and implementation phases: policy adherence rates were 23.7% and 41.8%, respectively, de-escalation rates were 22.73% and 43.48%, respectively. Cultures were sent before the initiation of antimicrobials in 36.73% cases during the pre-implementation phase, which improved to 60.41% during the implementation phase. Defined daily dose (DDD) for the antibiotics was 98.66 DDD 100BD during the pre-implementation phase, which reduced to 91.62 DDD 100BD in the implementation phase. Total days of therapy (DOT) in the pre-implementation phase were 561 DOT1000BD, which reduced to 463 DOT1000BD during the implementation phase. Conclusions: Implementation of continuous monitoring of the AMS programme, therefore, has a definite role in reducing the antimicrobial consumption and improving the compliance to the policy guidelines. A more robust study for a prolonged period is, however, necessary to have a better analysis of the outcome.

[Buyers' club†: an alternative for access to treatment†?] / Buyers' club†: une alternative pour l'accès au traitement†?

Rapid medication management for patients infected with HIV, HCV or HBV is key in optimizing a more favourable clinical response, in terms of morbidity, mortality, quality-of-life and reduced risk of transmission. If a drug is expensive, access to treatment for an uninsured patient with limited resources can be a hurdle that leads to forgoing healthcare for economic reasons. The buyers' club's objective is to provide logistics and/or financial assistance to a patient aiming to import qualitative generics for his personal use at an affordable price oversea. The drug is purchased on the internet.

La prise en charge médicamenteuse rapide pour les patients infectés par le VIH, le VHC ou le VHB est un élément clé pour obtenir une réponse clinique favorable en termes de morbidité, mortalité, et qualité de vie, et elle permet de diminuer les risques de transmission. Lorsqu'un médicament est cher, l'accès aux traitements pour un·e patient·e sans assurance avec des ressources limitées est une barrière qui peut conduire à renoncer aux soins pour des raisons économiques. Un buyers' club est une structure dont l'objectif est d'apporter une aide logistique et/ou financière à un·e patient·e qui souhaite importer à titre personnel un médicament de qualité et efficace à des conditions économiquement plus favorables. L'achat du médicament se fait par internet.

Purchase and use of antimicrobials in the hospital sector of Vietnam, a lower middle-income country with an emerging pharmaceuticals market.

INTRODUCTION: Antimicrobial use is associated with emergence of antimicrobial resistance. We report hospital antimicrobial procurement, as a surrogate for consumption in humans, expenditure and prices in public hospitals in Vietnam, a lower middle-income country with a high burden of drug resistant infections. METHOD: Data on antimicrobial procurement were obtained from tender-winning bids from provincial health authorities and public hospitals with detailed bids representing 28.7% (1.68 / 5.85 billion US $) of total hospital medication spend in Vietnam. Antimicrobials were classified using the Anatomical Therapeutic Chemical (ATC) Index and the 2019 WHO Access, Watch, Reserve (AWaRe) groups. Volume was measured in number of Defined Daily Doses (DDD). Antimicrobial prices were presented per DDD. RESULTS: Expenditure on systemic antibacterials and antifungals accounted for 28.6% (US $482.6 million/US $1.68 billion) of the total drug bids. 83% of antibacterials (572,698,014 DDDs) by volume (accounting for 45.5% of the antibacterials spend) were domestically supplied. Overall, the most procured antibacterials by DDD were second generation cephalosporins, combinations of penicillins and beta-lactamase inhibitors, and penicillins with extended spectrum. For parenteral antibacterials this was third generation cephalosporins. The average price for antibacterials was US $15.6, US $0.86, US $0.4 and US $11.7 per DDD for Reserve, Watch, Access and non-recommended/unclassified group antibacterials, respectively. CONCLUSIONS: Antimicrobials accounted for a substantial proportion of the funds spent for medication in public hospitals in Vietnam. The pattern of antibacterial consumption was similar to other countries. The high prices of Reserve group and non-recommended/unclassified antibacterials suggests a need for a combination of national pricing and antimicrobial stewardship policies to ensure appropriate accessibility.

Overview: The Ongoing Threat of Antimicrobial Resistance.

The effectiveness of antibiotics continues to erode because of the relentless spread of antimicrobial resistance (AMR). Public and private foundations, professional organizations, and international health agencies recognize the threat posed by AMR and have issued calls for action. One of the main drivers of AMR is overprescription of antibiotics, both in human and in veterinary medicine. The One Health concept is a response from a broad group of stakeholders to counter the global health threat posed by AMR. In this article, we discuss current trends in AMR and suggest strategies to mitigate its ongoing dissemination.

Drug utilization, rationality, and cost analysis of antimicrobial medicines in a tertiary care teaching hospital of Northern India: A prospective, observational study.

BACKGROUND: The burden of bacterial infections is huge and grossly under-represented in the current health-care system. Inappropriate use of antimicrobial medicines (AMMs) poses a potential hazard to patients by causing antibiotic resistance. This study was conducted to assess the: (i) AMM consumption and use patterns in patients attending the outpatients and inpatients of Medicine and Surgery departments of the hospital. (ii) Appropriateness of the AMM in the treatment prescribed, and (iii) cost incurred on their use in admitted patients. MATERIALS AND METHODS: An observational, prospective study was conducted among inpatients and outpatients of the Medicine and Surgery departments of a tertiary care hospital of northern India. Analysis of 2128 prescriptions and 200 inpatient records was performed using a predesigned format. The use of AMMs was reviewed using anatomical therapeutic chemical classification and defined daily doses (DDDs). To evaluate the expenditure incurred on AMMs, ABC analysis was performed. RESULTS: AMMs were prescribed to 37.9% outpatients and 73% of admitted patients. The percentage encounters with AMMs was 40.6% (medicine) and 25.6% (surgery) outpatients. The total DDDs/100 patient days of AMMs in medicine and surgery were 3369 and 2247. Bacteriological evidence of infection and AMM sensitivity was present in only 8.5% of cases. Over 90% of AMMs were prescribed from the hospital essential medicines list. Most of the AMMs were administered parenterally (64.9%). Multiple AMMs were prescribed more to inpatients (84.2% vs. 4.2% outpatients). Overall, expenditure on AMM was 33% of the total cost of treatment on medicine. ABC analysis showed that 74% of the expenditure was due to newer, expensive AMM, which constituted only 9% of the AMM used. The AMM therapy was found to be appropriate in 88% of cases as per Kunin's criteria for rationality. CONCLUSION: AMMs are being commonly prescribed without confirmation of AMM sensitivity in the hospital. A large proportion of expenditure is being incurred on expensive AMM used in a few number of patients. There is a need for developing a policy for rational use of AMM in the health facility.

Eight years of sales surveillance of antimicrobials for veterinary use in Germany-What are the perceptions?

A surveillance system for sales volumes of antimicrobial agents for veterinary use was established in Germany in 2011. Since then, pharmaceutical companies and wholesalers have been legally obliged to report annual volumes of veterinary antimicrobial products sold to veterinary practices or clinics located in Germany. The evaluation of sales volumes for eight consecutive years resulted in a considerable total decrease by 58% from 1706 tons to 722 tons. During the investigation period, two legally binding measures to control the risk of antimicrobial resistance resulting from the veterinary use of antimicrobials were introduced, a) the German treatment frequencies benchmarking in 2014 and b) the obligation to conduct susceptibility testing for the use of cephalosporins of the 3rd and 4th generation and of fluoroquinolones in 2018. Both had a marked impact on sales volumes. Nonetheless, the category of Critically Important Antimicrobials as defined by the World Health Organization kept accounting for the highest share on sales volumes in Germany in 2018 with 403 tons, despite an overall reduction by 53%. Sales surveillance is considered essential for data retrieval on a global scale and inter-country comparison. However, the usability of a surveillance system based on sales data for risk management of antimicrobial resistance has limitations. The German system does not include off-label use of antimicrobial products authorized for human medicine and does not allow for identification of areas of high risk according to animal species, farm and production types and indications for treatment. For further reduction and enhanced promotion of a prudent use of antimicrobials, targeted measures would be required that could only be deducted from use data collected at farm or veterinary practice level. A surveillance system based on use data is currently lacking in Germany but will be established according to Regulation (EU) 2019/6 on veterinary medicinal products.

Health gains and financial risk protection afforded by public financing of selected malaria interventions in Ethiopia: an extended cost-effectiveness analysis.

BACKGROUND: Malaria is a public health burden and a major cause for morbidity and mortality in Ethiopia. Malaria also places a substantial financial burden on families and Ethiopia's national economy. Economic evaluations, with evidence on equity and financial risk protection (FRP), are therefore essential to support decision-making for policymakers to identify best buys amongst possible malaria interventions. The aim of this study is to estimate the expected health and FRP benefits of universal public financing of key malaria interventions in Ethiopia. METHODS: Using extended cost-effectiveness analysis (ECEA), the potential health and FRP benefits were estimated, and their distributions across socio-economic groups, of publicly financing a 10% coverage increase in artemisinin-based combination therapy (ACT), long-lasting insecticide-treated bed nets (LLIN), indoor residual spraying (IRS), and malaria vaccine (hypothetical). RESULTS: ACT, LLIN, IRS, and vaccine would avert 358, 188, 107 and 38 deaths, respectively, each year at a net government cost of $5.7, 16.5, 32.6, and 5.1 million, respectively. The annual cost of implementing IRS would be two times higher than that of the LLIN interventions, and would be the main driver of the total costs. The averted deaths would be mainly concentrated in the poorest two income quintiles. The four interventions would eliminate about $4,627,800 of private health expenditures, and the poorest income quintiles would see the greatest FRP benefits. ACT and LLINs would have the largest impact on malaria-related deaths averted and FRP benefits. CONCLUSIONS: ACT, LLIN, IRS, and vaccine interventions would bring large health and financial benefits to the poorest households in Ethiopia.

A survey of retail prices of antimicrobial products used in small-scale chicken farms in the Mekong Delta of Vietnam.

BACKGROUND: In the Mekong Delta region of Vietnam, high quantities of products containing antimicrobial are used as prophylactic and curative treatments in small-scale chicken flocks. A large number of these contain antimicrobial active ingredients (AAIs) considered of 'critical importance' for human medicine according to the World Health Organization (WHO). However, little is known about the retail prices of these products and variables associated with the expense on antimicrobials at farm level. Therefore, the aims of the study were: (1) to investigate the retail price of antimicrobials with regards to WHO importance criteria; and (2) to quantify the antimicrobial expense incurred in raising chicken flocks. We investigated 102 randomly-selected small-scale farms raising meat chickens (100-2000 per flock cycle) in two districts in Dong Thap (Mekong Delta) over 203 flock production cycles raised in these farms. Farmers were asked to record the retail prices and amounts of antimicrobial used. RESULTS: A total of 214 different antimicrobial-containing products were identified. These contained 37 different AAIs belonging to 13 classes. Over half (60.3%) products contained 1 highest priority, critically important AAI, and 38.8% 1 high priority, critically important AAI. The average (farm-adjusted) retail price of a daily dose administered to a 1 kg bird across products was 0.40 cents of 1 US$ (₵) (SE ± 0.05). The most expensive products were those that included at least one high priority, critically important AAI, as well as those purchased in one of the two study districts. Farmers spent on average of ₵3.91 (SE ± 0.01) on antimicrobials per bird over the production cycle. The expense on antimicrobials in weeks with disease and low mortality was greater than on weeks with disease and high mortality, suggesting that antimicrobial use had a beneficial impact on disease outcomes (χ2 = 3.8; p = 0.052). Farmers generally used more expensive antimicrobials on older flocks. CONCLUSIONS AND RECOMMENDATION: The retail prices of antimicrobial products used in chicken production in Mekong Delta small-scale chicken farms are very low, and not related to their relevance for human medicine. Farmers, however, demonstrated a degree of sensitivity to prices of antimicrobial products. Therefore, revising pricing policies of antimicrobial products remains a potential option to curb the use of antimicrobials of critical importance in animal production.

Clinical indications treated with unregistered antimicrobials: regulatory challenges of antimicrobial resistance and access to effective treatment for patients.

Objective Increasing antimicrobial resistance and a concurrent paucity of new antimicrobials marketed increases the risk that patients will develop infections resistant to currently available drugs. This study aimed to determine the range of clinical indications for which unregistered antimicrobials are prescribed at two tertiary hospitals in South Australia to identify any trends over a 2-year period. The effects of recent regulatory changes to the Special Access Scheme (SAS) were assessed. Methods Data were extracted from application forms submitted to the Therapeutic Goods Administration to access unregistered antimicrobials via the SAS pathway at two Australian tertiary hospitals for the period July 2015-June 2017. Average weighted antimicrobial prices were retrieved from the hospital iPharmacy (DXC Technology, Macquarie Park, NSW, Australia) dispensing system. To estimate the effect of a new access pathway (Category C), the SAS classification for each application was retrospectively assessed over time with each regulatory change. Results Between July 2015 and June 2017, 477 SAS applications for 29 different antimicrobials were submitted for 353 patients at the two hospitals. The most common indications were tuberculosis (43.6%) and refractory Helicobacter pylori (10%). Regulatory changes reduced the proportion of applications requiring preapproval for access. Conclusions Although the introduction of a new pathway has decreased the administrative burden when accessing unregistered antimicrobials, this study highlights the range of clinical conditions for which there are no registered drugs available in Australia. What is known about the topic? With increasing antimicrobial resistance and a paucity of novel antimicrobials entering the market, access to older, previously less-used antimicrobials is increasingly important in clinical practice. Accessing unregistered antimicrobials is common practice in Australian hospitals, but the range of clinical indications for which they are used is unclear. What does this paper add? Increasing antimicrobial resistance and a concurrent paucity of new antimicrobials being marketed globally is increasing the risk that patients may develop infections that cannot be treated with registered products. This study describes the range of clinical conditions for which registered antimicrobials are not available or appropriate, illustrating the challenges associated with sustainable access to effective treatments. What are the implications for practitioners? Access to effective antimicrobials in a timely manner is essential for optimal patient outcomes. Reliance on unregistered products is associated with increased risks regarding timely access to safe, quality-assured, effective medicines.

Impact of infection control measures on the related costs and the amount of broad-spectrum antimicrobial agents used in a hospital: A time-series analysis.

Health care-associated infections (HAIs) worsen patient prognoses and increase medical costs. Antimicrobial stewardship (AMS), which involves appropriate use of antimicrobial agents and antiseptics, may be beneficial for addressing the issue of HAIs. In hospitals, an infection control team (ICT) plays an important role on the appropriate use of antimicrobial agents and antiseptics based on AMS. We aimed to conduct a time-series analysis of the efficacies of infection control measures in terms of related costs, amount of broad-spectrum antimicrobial agents used (carbapenems and quinolones), and methicillin-resistant Staphylococcus aureus (MRSA) detection rates. This retrospective cross-sectional study included in-hospital patients treated at a single institute between January 2012 and December 2015. The intervention start point (initiation of infection control measures) was January 2014. All survey items were subjected to segmented regression analysis using an autoregressive integrated moving average (ARIMA) model. Differences between pre-intervention and postintervention levels and their trends were assessed, using a statistical significance cutoff of P < .05. The infection control costs demonstrated a significantly increasing trend, despite significant decreases in the amount of carbapenems used. Accordingly, the implementation of infection control measures was associated with increased costs, whereas carbapenem use decreased immediately after intervention. Postintervention levels, trends of quinolone use, or MRSA detection rates did not reveal significant changes. Although implementation of infection control measures induced gradual increases in related costs, these measures led to immediate reductions in carbapenem use. Our study findings will support the establishment of more effective and economical infection control measures.

Economic and Behavioral Influencers of Vaccination and Antimicrobial Use.

Despite vast improvements in global vaccination coverage during the last decade, there is a growing trend in vaccine hesitancy and/or refusal globally. This has implications for the acceptance and coverage of a potential vaccine against COVID-19. In the United States, the number of children exempt from vaccination for "philosophical belief-based" non-medical reasons increased in 12 of the 18 states that allowed this policy from 2009 to 2017 (1). Meanwhile, the overuse and misuse of antibiotics, especially in young children, have led to increasing rates of drug resistance that threaten our ability to treat infectious diseases. Vaccine hesitancy and antibiotic overuse exist side-by-side in the same population of young children, and it is unclear why one modality (antibiotics) is universally seen as safe and effective, while the other (vaccines) is seen as potentially hazardous by some. In this review, we consider the drivers shaping the use of vaccines and antibiotics in the context of three factors: individual incentives, risk perceptions, and social norms and group dynamics. We illustrate how these factors contribute to the societal and individual costs of vaccine underuse and antimicrobial overuse. Ultimately, we seek to understand these factors that are at the nexus of infectious disease epidemiology and social science to inform policy-making.