Enumerating the economic cost of antimicrobial resistance per antibiotic consumed to inform the evaluation of interventions affecting their use

Background Antimicrobial resistance (AMR) poses a colossal threat to global health and incurs high economic costs to society. Economic evaluations of antimicrobials and interventions such as diagnostics and vaccines that affect their consumption rarely include the costs of AMR, resulting in sub-optimal policy recommendations. We estimate the economic cost of AMR per antibiotic consumed, stratified by drug class and national income level. Methods The model is comprised of three components: correlation coefficients between human antibiotic consumption and subsequent resistance; the economic costs of AMR for five key pathogens; and consumption data for antibiotic classes driving resistance in these organisms. These were used to calculate the economic cost of AMR per antibiotic consumed for different drug classes, using data from Thailand and the United States (US) to represent low/middle and high-income countries. Results The correlation coefficients between consumption of antibiotics that drive resistance in S. aureus, E. coli, K. pneumoniae, A. baumanii, and P. aeruginosa and resistance rates were 0.37, 0.27, 0.35, 0.45, and 0.52, respectively. The total economic cost of AMR due to resistance in these five pathogens was $0.5 billion and$2.9 billion in Thailand and the US, respectively. The cost of AMR associated with the consumption of one standard unit (SU) of antibiotics ranged from $0.1 for macrolides to$0.7 for quinolones, cephalosporins and broad-spectrum penicillins in the Thai context. In the US context, the cost of AMR per SU of antibiotic consumed ranged from $0.1 for carbapenems to$0.6 for quinolones, cephalosporins and broad spectrum penicillins. Conclusion The economic costs of AMR per antibiotic consumed were considerable, often exceeding their purchase cost. Differences between Thailand and the US were apparent, corresponding with variation in the overall burden of AMR and relative prevalence of different pathogens. Notwithstanding their limitations, use of these estimates in economic evaluations can make better-informed policy recommendations regarding interventions that affect antimicrobial consumption and those aimed specifically at reducing the burden of AMR

Real-Time EEG Signal Classification for Monitoring and Predicting the Transition Between Different Anaesthetic States.

Quantitative identification of the transitions between anaesthetic states is very essential for optimizing patient safety and quality care during surgery but poses a very challenging task. The state-of-the-art monitors are still not capable of providing their manifest variables, so the practitioners must diagnose them based on their own experience. The present paper proposes a novel real-time method to identify these transitions. Firstly, the Hurst method is used to pre-process the de-noised electro-encephalograph (EEG) signals. The maximum of Hurst's ranges is then accepted as the EEG real-time response, which induces a new real-time feature under moving average framework. Its maximum power spectral density is found to be very differentiated into the distinct transitions of anaesthetic states and thus can be used as the quantitative index for their identification

Community-level consumption of antibiotics according to the AWaRe (Access, Watch, Reserve) classification in rural Vietnam

Objectives To review community-level consumption of antibiotics in rural Vietnam, according to the WHO Access, Watch, Reserve (AWaRe) classification of 2019, and identify factors associated with the choice of these antibiotics. Methods In this cross-sectional study, data on antibiotic purchases were collected through a customer exit survey of 20 community antibiotic suppliers in Ba Vi District, Hanoi, between September 2017 and July 2018. Antibiotic consumption was estimated through the number of antibiotic encounters, the number of DDDs supplied and the number of treatment days (DOTs) with antibiotics, and analysed according to the AWaRe classification. The factors associated with watch-group antibiotic supply were identified through multivariable logistic regression analysis. Results In total, there were 1342 antibiotic encounters, with access-group antibiotics supplied in 792 encounters (59.0%), watch-group antibiotics supplied in 527 encounters (39.3%) and not-recommended antibiotics supplied in 23 encounters (1.7%). No reserve-group antibiotics were supplied. In children, the consumption of watch-group antibiotics dominated in all three measures (54.8% of encounters, 53.0% of DOTs and 53.6% of DDDs). Factors associated with a higher likelihood of watch-group antibiotic supply were: private pharmacy (OR, 4.23; 95% CI, 2.8–6.38; P < 0.001), non-prescription antibiotic sale (OR, 2.62; 95% CI, 1.78–3.87; P < 0.001) and children (OR, 2.56; 95% CI, 1.84–3.55; P < 0.001). Conclusions High consumption of watch-group antibiotics was observed, especially for use in children. The frequent supply of watch-group antibiotics at private pharmacies reconfirms the need for implementing pharmacy-targeted interventions in Vietnam

C-reactive protein point of care testing in the management of acute respiratory infections in the Vietnamese primary healthcare setting - a cost benefit analysis

Aim We assess the cost-benefit implications of C-reactive protein (CRP) testing in reducing antibiotic prescription for acute respiratory infection in Viet Nam by comparing the incremental costs of CRP testing with the economic costs of antimicrobial resistance averted due to lower antibiotic prescribing. Findings Patients in the CRP group and the controls incurred similar costs in managing their illness, excluding the costs of the quantitative CRP tests, provided free of charge in the trial context. Assuming a unit cost of $1 per test, the incremental cost of CRP testing was$0.93 per patient. Based on a previous modelling analysis, the 20 percentage point reduction in prescribing observed in the trial implies a societal benefit of $0.82 per patient. With the low levels of adherence to the test results observed in the trial, CRP testing would not be cost-beneficial. The sensitivity analyses showed, however, that with higher adherence to test results their use would be cost-beneficial.</p

Improving antibiotic prescribing for community-acquired pneumonia in a provincial hospital in Northern Vietnam

Objectives To test the effectiveness of a quality improvement programme to promote adherence to national quality standards (QS) for patients hospitalized with community-acquired pneumonia (CAP), exploring the factors that hindered improvements in clinical practice. Methods An improvement bundle aligned to the QS was deployed using plan-do-study-act methodology in a 600 bed hospital in northern Vietnam from July 2018 to April 2019. Proposed care improvements included CURB65 score guided hospitalization, timely diagnosis and inpatient antibiotic treatment review to limit the spectrum and duration of IV antibiotic use. Interviews with medical staff were conducted to better understand the barriers for QS implementation. Results The study found that improvements were made in CURB65 score documentation and radiology results available within 4 h (P < 0.05). There were no significant changes in the other elements of the QS studied. We documented institutional barriers relating to the health reimbursement mechanism and staff cultural barriers relating to acceptance and belief as significant impediments to implementation of the standards. Conclusions Interventions led to some process changes, but these were not utilized by clinicians to improve patient management. Institutional and behavioural barriers documented may inhibit wider national uptake of the QS. National system changes with longer term support and investment to address local behavioural barriers are likely to be crucial for future improvements in the management of CAP, and potentially other hospitalized conditions, in Vietnam

Point-of-care C-reactive protein testing to reduce inappropriate use of antibiotics for non-severe acute respiratory infections in Vietnamese primary health care: a randomised controlled trial

Background Inappropriate antibiotic use for acute respiratory tract infections is common in primary health care, but distinguishing serious from self-limiting infections is difficult, particularly in low-resource settings. We assessed whether C-reactive protein point-of-care testing can safely reduce antibiotic use in patients with non-severe acute respiratory tract infections in Vietnam. Method We did a multicentre open-label randomised controlled trial in ten primary health-care centres in northern Vietnam. Patients aged 1–65 years with at least one focal and one systemic symptom of acute respiratory tract infection were assigned 1:1 to receive either C-reactive protein point-of-care testing or routine care, following which antibiotic prescribing decisions were made. Patients with severe acute respiratory tract infection were excluded. Enrolled patients were reassessed on day 3, 4, or 5, and on day 14 a structured telephone interview was done blind to the intervention. Randomised assignments were concealed from prescribers and patients but not masked as the test result was used to assist treatment decisions. The primary outcome was antibiotic use within 14 days of follow-up. All analyses were prespecified in the protocol and the statistical analysis plan. All analyses were done on the intention-to-treat population and the analysis of the primary endpoint was repeated in the per-protocol population. This trial is registered under number NCT01918579. Findings Between March 17, 2014, and July 3, 2015, 2037 patients (1028 children and 1009 adults) were enrolled and randomised. One adult patient withdrew immediately after randomisation. 1017 patients were assigned to receive C-reactive protein point-of-care testing, and 1019 patients were assigned to receive routine care. 115 patients in the C-reactive protein point-of-care group and 72 patients in the routine care group were excluded in the intention-to-treat analysis due to missing primary endpoint. The number of patients who used antibiotics within 14 days was 581 (64%) of 902 patients in the C-reactive protein group versus 738 (78%) of 947 patients in the control group (odds ratio [OR] 0·49, 95% CI 0·40–0·61; p Interpretation C-reactive protein point-of-care testing reduced antibiotic use for non-severe acute respiratory tract infection without compromising patients' recovery in primary health care in Vietnam. Health-care providers might have become familiar with the clinical picture of low C-reactive protein, leading to reduction in antibiotic prescribing in both groups, but this would have led to a reduction in observed effect, rather than overestimation. Qualitative analysis is needed to address differences in context in order to implement this strategy to improve rational antibiotic use for patients with acute respiratory infection in low-income and middle-income countries.</p

Xpert MTB/RIF Ultra versus Xpert MTB/RIF for the diagnosis of tuberculous meningitis: a prospective, randomised, diagnostic accuracy study

Background: Xpert MTB/RIF Ultra (Xpert Ultra) might have higher sensitivity than its predecessor, Xpert MTB/RIF (Xpert), but its role in tuberculous meningitis diagnosis is uncertain. We aimed to compare Xpert Ultra with Xpert for the diagnosis of tuberculous meningitis in HIV-uninfected and HIV-infected adults. Methods: In this prospective, randomised, diagnostic accuracy study, adults (≥16 years) with suspected tuberculous meningitis from a single centre in Vietnam were randomly assigned to cerebrospinal fluid testing by either Xpert Ultra or Xpert at baseline and, if treated for tuberculous meningitis, after 3–4 weeks of treatment. Test performance (sensitivity, specificity, and positive and negative predictive values) was calculated for Xpert Ultra and Xpert and compared against clinical and mycobacterial culture reference standards. Analyses were done for all patients and by HIV status. Findings: Between Oct 16, 2017, and Feb 10, 2019, 205 patients were randomly assigned to Xpert Ultra (n=103) or Xpert (n=102). The sensitivities of Xpert Ultra and Xpert for tuberculous meningitis diagnosis against a reference standard of definite, probable, and possible tuberculous meningitis were 47·2% (95% CI 34·4–60·3; 25 of 53 patients) for Xpert Ultra and 39·6% (27·6–53·1; 21 of 53) for Xpert (p=0·56); specificities were 100·0% (95% CI 92·0–100·0; 44 of 44) and 100·0% (92·6–100·0; 48 of 48), respectively. In HIV-negative patients, the sensitivity of Xpert Ultra was 38·9% (24·8–55·1; 14 of 36) versus 22·9% (12·1–39·0; eight of 35) by Xpert (p=0·23). In HIV co-infected patients, the sensitivities were 64·3% (38·8–83·7; nine of 14) for Xpert Ultra and 76·9% (49·7–91·8; ten of 13) for Xpert (p=0·77). Negative predictive values were 61·1% (49·6–71·5) for Xpert Ultra and 60·0% (49·0–70·0) for Xpert. Against a reference standard of mycobacterial culture, sensitivities were 90·9% (72·2–97·5; 20 of 22 patients) for Xpert Ultra and 81·8% (61·5–92·7; 18 of 22) for Xpert (p=0·66); specificities were 93·9% (85·4–97·6; 62 of 66) and 96·9% (89·5–91·2; 63 of 65), respectively. Six (22%) of 27 patients had a positive test by Xpert Ultra after 4 weeks of treatment versus two (9%) of 22 patients by Xpert. Interpretation: Xpert Ultra was not statistically superior to Xpert for the diagnosis of tuberculous meningitis in HIV-uninfected and HIV-infected adults. A negative Xpert Ultra or Xpert test does not rule out tuberculous meningitis. New diagnostic strategies are urgently required