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Background: Hepatitis B virus (HBV) is a major global health threat, especially in Sub-Saharan Africa, where Nigeria has a prevalence exceeding 8%. Despite the availability of effective vaccines, inadequate coverage and lack of awareness have resulted in high rates of chronic infections and HBV-attributable liver disease. The study aimed to raise awareness of HBV, enroll participants for HBV screening, determine HBV prevalence across various communities, vaccinate negative cases and link positive cases to care. Methods: A cross-sectional study was conducted in 16 districts of Abuja from April 2022 to March 2023. Participants aged 18 and over were screened for hepatitis B, and those testing negative were offered on-site vaccination. Blood samples were collected and tested using HBV immunochromatographic tests and real-time polymerase chain reaction (RT-PCR) for HBV DNA quantification. Data were collected through interviews and analyzed using R software, with descriptive statistics calculated for continuous and categorical variables. Associations between socio-demographic factors and hepatitis B/vaccine status were assessed using the Chi-square test of independence. Results: Out of 3,245 individuals screened, 141 (4.3%) tested positive for HBV. The highest prevalence was observed in the 20–39 age group (5.9%), with males showing a higher infection rate (5.4%) compared to females (3.7%) [p = 0.02]. The mean age of HBV-positive individuals was significantly lower (30.8 years) than those negative for HBV (36.2 years) [p = < 0.001]. Among 2,506 participants who consented to vaccination, 2,488 received the first dose (99.3%), 1,834 the second dose (73.2%), and 1,100 the third dose (43.9%). Vaccination uptake declined with each subsequent dose, but more older participants completed the third dose. A similar pattern of HBV prevalence was observed across gender and age groups. Conclusion: The study reveals a 4.3% prevalence of hepatitis B, with the highest infection rate among individuals aged 20–39 years, and males showing a higher prevalence than females. Although vaccination uptake was high for the first dose, adherence declined for subsequent doses. These findings highlight the need for targeted public health interventions, particularly among younger adults and males, to improve awareness and vaccination completion. Enhanced community engagement and sustained vaccination efforts are crucial for reducing HBV transmission and achieving better coverage. [ABSTRACT FROM AUTHOR]

Accurate and sensitive near‐infrared (NIR) luminescent lateral flow immunoassay (LFIA) has attracted considerable attention in the field of point‐of‐care testing (POCT). However, the detection accuracy and sensitivity are often compromised by the low fluorescence quantum efficiency (<10%) of the NIR fluorescent probe. Herein, ultrabright NIR AIEgen nanoparticles (PS@AIE830NPs) composed of polystyrene (PS) nanoparticles and NIR aggregation‐induced emission luminogen (AIEgen) with the maximum emission at 830 nm (AIE830) is reported, and its potential to promote an accurate and sensitive detection of complex samples by LFIA is described. The relative quantum yield (QY) of the PS@AIE830NPs was 14.76%, which was superior to that of the polymer embedding method and indocyanine green (ICG)‐based NIR nanoparticles. The PS@AIE830NPs immunolabeled‐LFIA combined with laboratory‐built NIR‐LFIA portable quantitative instruments (detected light range > 800 nm) completely eliminated background interference and allowed highly accurate and sensitive detection without any pre‐treatment steps. The limits of detection (LODs) for aflatoxin B1 (AFB1) in soy sauce, alpha hemolysin (Hla) of Staphylococcus aureus biomarker in joint fluid, and C‐reactive protein (CRP) in human haemolysed samples were 0.01 ng mL−1, 0.02 µg mL−1, and 0.156 mg L−1, respectively, commensurating with those of the corresponding gold standard assays and covering the detection range of interests. It is anticipated that the ultrabright NIR AIEgen nanoparticles will serve as a universally applicable signal probe for NIR‐LFIA diagnostics, promising to expand the range of applications for quantitative detection of complex samples. [ABSTRACT FROM AUTHOR]

ObjectivesTo evaluate the impact of rapid diagnostic testing (RDT) combined with immediate infectious disease (ID) consultation on the treatment of septic patients with positive blood cultures in intensive care units in a setting without 24/7 service.MethodsAdult ICU patients in a tertiary care hospital with positive blood cultures were included from January 2019 to December 2020. The control group underwent routine laboratory testing, and for the intervention group, RDT was applied with immediate ID consultation.ResultsIn 77 out of the 91 patients in the intervention group, the pathogen was identified by RDT. Regarding antimicrobial susceptibility testing (AST), genotypic testing (ePlex®) was successful for Gram-positive cocci, but inadequate for Gram-negative rods. Phenotypic resistance testing with the Accelerate PhenoTest® took too long to be successfully integrated into the intervention. Adaptation of empirical antibiotic therapy was recommended for 72.7% of the patients. Adherence to the ID consultation post-RDT results was high at 82.3%. In the control group, adaptation of the initial antibiotic therapy would have been recommended for 81.8% of patients, if the species identification had been available. Overall adherence to the local antibiotic therapy guideline for sepsis was significantly lower in the control than in the intervention group (27.8% versus 89.3%, p

ABSTRACT Rapid and accurate identification of Staphylococcus aureus (SA) in blood culture specimens is crucial for timely clinical intervention. Traditional Gram staining methods, although widely accessible and cost-effective, exhibit variable sensitivities and specificities in the BACTEC system. We aimed to develop and validate the “STAPH score,” a novel semi-quantitative scoring system that integrates Gram stain morphology and time to positivity to differentiate SA from coagulase-negative staphylococci (CoNS) in blood cultures. We analyzed 148 blood culture specimens from septic patients. Each specimen was assessed independently by two examiners using Gram staining and the STAPH score, which assigns points based on five parameters: cluster size, time to positivity, aerobic enlargement, pint (three-dimensional appearance), and the presence of hemorrhage. Sensitivity and specificity were calculated for various cutoff points. Cohen’s kappa coefficient was used to assess inter-examiner agreement. Of the 148 specimens, 49 (33.1%) were identified as SA and 99 (66.9%) as CoNS. At a STAPH score cutoff of 3 points, the sensitivity was 93.9% (95% confidence interval [CI], 83.1%–98.7%) and specificity was 91.9% (95% CI, 84.7%–96.4%). The kappa coefficient at this cutoff was 0.67 (95% CI, 0.55–0.79). A STAPH score

Abstract Accurate and sensitive near‐infrared (NIR) luminescent lateral flow immunoassay (LFIA) has attracted considerable attention in the field of point‐of‐care testing (POCT). However, the detection accuracy and sensitivity are often compromised by the low fluorescence quantum efficiency ( 800 nm) completely eliminated background interference and allowed highly accurate and sensitive detection without any pre‐treatment steps. The limits of detection (LODs) for aflatoxin B1 (AFB1) in soy sauce, alpha hemolysin (Hla) of Staphylococcus aureus biomarker in joint fluid, and C‐reactive protein (CRP) in human haemolysed samples were 0.01 ng mL−1, 0.02 µg mL−1, and 0.156 mg L−1, respectively, commensurating with those of the corresponding gold standard assays and covering the detection range of interests. It is anticipated that the ultrabright NIR AIEgen nanoparticles will serve as a universally applicable signal probe for NIR‐LFIA diagnostics, promising to expand the range of applications for quantitative detection of complex samples.

Abstract Background Community-acquired pneumonia (CAP) is a significant public health concern and a leading cause of hospitalization and inpatient antimicrobial use in the USA. However, determining the etiologic pathogen is challenging because traditional culture methods are slow and insensitive, leading to prolonged empiric therapy with extended-spectrum antibiotics (ESA) that contributes to increased hospital length of stay, and antimicrobial resistance. Two potential ways to reduce the exposure to ESA are (a) rapid diagnostic assays that can provide accurate results within hours, obviating the need for empiric therapy, and (b) de-escalation following negative bacterial cultures in clinically stable patients. Methods We will conduct a large pragmatic 2 × 2 factorial cluster-randomized controlled trial across 12 hospitals in the Cleveland Clinic Health System that will test these two approaches to reducing the use of ESA in adult patients (age ≥ 18 years) with CAP. We will enroll over 12,000 patients and evaluate the independent and combined effects of routine use of rapid diagnostic testing at admission and pharmacist-led de-escalation after 48 h for clinically stable patients with negative cultures vs usual care. We hypothesize that both approaches will reduce days on ESA. Our primary outcome is the duration of exposure to ESA therapy, a key driver of antimicrobial resistance. Secondary outcomes include detection of respiratory viruses, treatment with anti-viral medications, positive pneumococcal urinary antigen test, de-escalation by 72 h from admission, re-escalation to ESA after de-escalation, total duration of any antibiotic, 14-day in-hospital mortality, intensive care unit transfer after admission, healthcare-associated C. difficile infection, acute kidney injury, total inpatient cost, and hospital length-of-stay. Discussion Our study aims to determine whether identifying an etiological agent early and pharmacist-led de-escalation (calling attention to negative cultures) can safely reduce the use of ESA in patients with CAP. If successful, our findings should lead to better antimicrobial stewardship, as well as improved patient outcomes and reduced healthcare costs. Our findings may also inform clinical guidelines on the optimal management of CAP. Trial registration ClinicalTrials.gov NCT05568654 . Registered on October 4, 2022.

Current methods for the diagnosis of urinary tract infections with antimicrobial susceptibility testing take 2-3 days and require a clinical laboratory. The lack of a rapid, point-of-care antibiotic susceptibility test (AST) has contributed to the misuse of antibiotics when treating urinary tract infections (UTIs) and consequently to the rise of multi-drug-resistant organisms. The current clinical approach has led to reduced treatment options and increased costs of diagnosis and therapy. To address this issue, novel diagnostics are needed for the timely determination of antimicrobial susceptibility. We present a rapid, point-of-care, phenotypic AST device that can report the antibiotic susceptibility/resistance of a uropathogen to a panel of antibiotics in as few as 3 h by utilizing fluorescent-labelling chemistry and a highly sensitive particle-counting instrument. We analysed 744 urine samples from the outpatients and inpatients of two Italian hospitals. The 130 UTI-positive patient urine samples we found were measured using a panel of six common UTI antibiotics plus a growth control. By comparing our results to hospital laboratory urine cultures, we obtained an overall sensitivity = 81%, a specificity = 83%, an SPV (sensitivity predicted value) = 95%, and an RPV (resistance predicted value) = 54%. According to our preliminary data, the sensitivity predicted value for a single antibiotic agent was 95%, thus allowing (in the vast majority of cases) an early (within 3 h) recognition of an effective agent for a single patient.

Background: Community-acquired pneumonia (CAP) is a significant public health concern and a leading cause of hospitalization and inpatient antimicrobial use in the USA. However, determining the etiologic pathogen is challenging because traditional culture methods are slow and insensitive, leading to prolonged empiric therapy with extended-spectrum antibiotics (ESA) that contributes to increased hospital length of stay, and antimicrobial resistance. Two potential ways to reduce the exposure to ESA are (a) rapid diagnostic assays that can provide accurate results within hours, obviating the need for empiric therapy, and (b) de-escalation following negative bacterial cultures in clinically stable patients. Methods: We will conduct a large pragmatic 2 × 2 factorial cluster-randomized controlled trial across 12 hospitals in the Cleveland Clinic Health System that will test these two approaches to reducing the use of ESA in adult patients (age ≥ 18 years) with CAP. We will enroll over 12,000 patients and evaluate the independent and combined effects of routine use of rapid diagnostic testing at admission and pharmacist-led de-escalation after 48 h for clinically stable patients with negative cultures vs usual care. We hypothesize that both approaches will reduce days on ESA. Our primary outcome is the duration of exposure to ESA therapy, a key driver of antimicrobial resistance. Secondary outcomes include detection of respiratory viruses, treatment with anti-viral medications, positive pneumococcal urinary antigen test, de-escalation by 72 h from admission, re-escalation to ESA after de-escalation, total duration of any antibiotic, 14-day in-hospital mortality, intensive care unit transfer after admission, healthcare-associated C. difficile infection, acute kidney injury, total inpatient cost, and hospital length-of-stay. Discussion: Our study aims to determine whether identifying an etiological agent early and pharmacist-led de-escalation (calling attention to negative cultures) can safely reduce the use of ESA in patients with CAP. If successful, our findings should lead to better antimicrobial stewardship, as well as improved patient outcomes and reduced healthcare costs. Our findings may also inform clinical guidelines on the optimal management of CAP. Trial registration: ClinicalTrials.gov NCT05568654. Registered on October 4, 2022. [ABSTRACT FROM AUTHOR]

Abstract Background The entire population of Mozambique is at risk for malaria, which remains one of the leading causes of death. The 2017–2022 National Malaria Strategic Plan focuses on reducing malaria morbidity and mortality in high- and low-transmission areas. This study aimed to estimate the costs and health benefits of six variations of the World Health Organization’s “test-and-treat” strategy among children under five. Methods A decision tree model was developed that estimates the costs and health outcomes for children under five. Data on probabilities, costs, weights for disability-adjusted life years (DALYs), and quality-adjusted life years (QALYs) were based on peer-reviewed, grey literature, and primary data analysis of the 2018 Malaria Indicator Survey. Six scenarios were compared to the status quo and calculated the incremental cost-effectiveness ratio (ICER) in terms of cost per QALY gained, DALY averted, and life saved. Deterministic and probabilistic sensitivity analyses were conducted to understand the effect of parameter uncertainty on the findings. Results In the base case, reaching the target of 100% testing with rapid diagnostic tests (RDTs; Scenario 1) is more cost-effective than improving the testing rate alone by 10% (Scenario 2). Achieving a 100% (Scenario 3) or a 10% increase in treatment rate (Scenario 4) have ICERs that are lower than Scenarios 1 and 2. Both Scenarios 5 and 6, which represent combinations of Scenarios 1–4, have lower ICERs than their constituent strategies on their own, which suggests that improvements in treatment are more cost-effective than improvements in testing alone. These results held when DALYs averted or lives saved were used as health outcomes. Deterministic and probabilistic sensitivity analyses revealed that the cost-effectiveness of Scenarios 1–6 are subject sensitive to parameter uncertainty, though Scenarios 4 and 5 are the optimal choice when DALYs averted or QALYs gained were used as the measure of health outcomes across all cost-effectiveness thresholds. Conclusions Improving testing rates alone among children at risk for malaria has the potential to improve health but may not be the most efficient use of limited resources. Instead, small or large improvements in treatment, whether alone or in conjunction with improvements in testing, are the most cost-effective strategies for children under five in Mozambique.

Background: Sepsis caused by multi-drug-resistant Gram-negative bacilli lead physicians to prescribe broad-spectrum antibiotic therapy, such as carbapenems. Rapid susceptibility testing can help with the rational use of antibiotics. The aim of this study was to measure the clinical impact associated with rapid reporting of Beta-Lacta test (BLT) directly on blood cultures positive with Gram-negative bacilli. Methods: In an observational, multicentric, prospective study, we included patients with sepsis caused by Enterobacterales observed on Gram staining of the positive blood cultures. BLT and antimicrobial susceptibility testing (AST) were performed directly on the blood cultures. Clinical impact was measured on the proportion of patients for whom the probabilistic antibiotic therapy was modified according to BLT, including patients receiving carbapenem. Results: 170 patients were included, of whom 44 (25.9%) were receiving inadequate empirical antibiotic therapy. Among them, 27 (15.9%) benefited from an early modification, according to the BLT results. Among 126 (74.1%) patients receiving appropriate probabilistic antibiotic therapy, we modified the antibiotic therapy for 28 (16.5%) of them, including 4/14 (28.5%) de-escalation from carbapenem to a third-generation cephalosporin. Conclusions: Implementation of BLT performed directly on blood cultures allowed us to rapidly modify the empirical antibiotic therapy for about one-third of patients with sepsis caused by Enterobacterales.

Background: Migrants underuse screening opportunities for HIV, hepatitis B, and hepatitis C despite elevated risk factors for contracting these infections. Language barriers are an often given as reasons for limiting access to services. Translation and communication apps increase communication and overall patient satisfaction in the patient-provider relationship. In the development and adoption of new technology, expectations play an important role. Objective: This study aimed to explore health care professionals' opinions and attitudes regarding their screening practices with migrants and their expectations for a new communication tool that could improve migrants' screening use. Methods: In this qualitative study, a purposive (diverse) sampling method was used to invite doctors and nurses who conduct rapid screening tests with migrants from 4 centers of the French Office of Immigration and Integration in 3 geographic regions of France. Semistructured interviews were conducted to survey their opinions on the rapid testing of migrants, the use of telephone interpreters, the concept of health literacy, and their expectations of a new communication tool that could overcome language barriers and promote rapid screening in the new migrant population. Results: In all, 20 interviews were conducted with 11 doctors and 9 nurses with a median age of 58 (range 25-67) years. Participants favored the integration of an innovative communication tool in the context of rapid screening of migrants. However, there were concerns related to the implementation and added value of the tool while migrants were already reluctant to be screened. Expectations were for a tool that would present information in simplified French or a chosen language but also supports a positive attitude toward screening. Health professionals also expressed the wish that the technology could help with the collection of health data. Conclusions: Feedback from health professionals provides a better understanding of potential formats, characteristics, functions, content, and use of an innovative, digital method to communicate with migrants with limited French proficiency. Findings contribute to the conceptual development of an electronic app and its implementation within the ApiDé study, which aims to validate a digital app to address language barriers to increase the use of screening among migrants with limited French proficiency in France. [ABSTRACT FROM AUTHOR]

Background: The entire population of Mozambique is at risk for malaria, which remains one of the leading causes of death. The 2017–2022 National Malaria Strategic Plan focuses on reducing malaria morbidity and mortality in high- and low-transmission areas. This study aimed to estimate the costs and health benefits of six variations of the World Health Organization's "test-and-treat" strategy among children under five. Methods: A decision tree model was developed that estimates the costs and health outcomes for children under five. Data on probabilities, costs, weights for disability-adjusted life years (DALYs), and quality-adjusted life years (QALYs) were based on peer-reviewed, grey literature, and primary data analysis of the 2018 Malaria Indicator Survey. Six scenarios were compared to the status quo and calculated the incremental cost-effectiveness ratio (ICER) in terms of cost per QALY gained, DALY averted, and life saved. Deterministic and probabilistic sensitivity analyses were conducted to understand the effect of parameter uncertainty on the findings. Results: In the base case, reaching the target of 100% testing with rapid diagnostic tests (RDTs; Scenario 1) is more cost-effective than improving the testing rate alone by 10% (Scenario 2). Achieving a 100% (Scenario 3) or a 10% increase in treatment rate (Scenario 4) have ICERs that are lower than Scenarios 1 and 2. Both Scenarios 5 and 6, which represent combinations of Scenarios 1–4, have lower ICERs than their constituent strategies on their own, which suggests that improvements in treatment are more cost-effective than improvements in testing alone. These results held when DALYs averted or lives saved were used as health outcomes. Deterministic and probabilistic sensitivity analyses revealed that the cost-effectiveness of Scenarios 1–6 are subject sensitive to parameter uncertainty, though Scenarios 4 and 5 are the optimal choice when DALYs averted or QALYs gained were used as the measure of health outcomes across all cost-effectiveness thresholds. Conclusions: Improving testing rates alone among children at risk for malaria has the potential to improve health but may not be the most efficient use of limited resources. Instead, small or large improvements in treatment, whether alone or in conjunction with improvements in testing, are the most cost-effective strategies for children under five in Mozambique. [ABSTRACT FROM AUTHOR]

Background: Sepsis caused by multi-drug-resistant Gram-negative bacilli lead physicians to prescribe broad-spectrum antibiotic therapy, such as carbapenems. Rapid susceptibility testing can help with the rational use of antibiotics. The aim of this study was to measure the clinical impact associated with rapid reporting of Beta-Lacta test (BLT) directly on blood cultures positive with Gram-negative bacilli. Methods: In an observational, multicentric, prospective study, we included patients with sepsis caused by Enterobacterales observed on Gram staining of the positive blood cultures. BLT and antimicrobial susceptibility testing (AST) were performed directly on the blood cultures. Clinical impact was measured on the proportion of patients for whom the probabilistic antibiotic therapy was modified according to BLT, including patients receiving carbapenem. Results: 170 patients were included, of whom 44 (25.9%) were receiving inadequate empirical antibiotic therapy. Among them, 27 (15.9%) benefited from an early modification, according to the BLT results. Among 126 (74.1%) patients receiving appropriate probabilistic antibiotic therapy, we modified the antibiotic therapy for 28 (16.5%) of them, including 4/14 (28.5%) de-escalation from carbapenem to a third-generation cephalosporin. Conclusions: Implementation of BLT performed directly on blood cultures allowed us to rapidly modify the empirical antibiotic therapy for about one-third of patients with sepsis caused by Enterobacterales. [ABSTRACT FROM AUTHOR]

Antigen based rapid diagnostic tests possesses a potential to be utilized along with Gold standard methods to detect Covid-19 infection to cope with the demand of testing. The aim of this study was to determine diagnostic accuracy of electrochemiluminescence based automated antigen detection immunoassay comparing with molecular based test RT-PCR (Covid-19). It was a cross-sectional study conducted in RMI Peshawar, from 1st April 2021 till 30th April 2021. The study comprised 170 individuals who were suspected of having Covid-19. Nasopharyngeal samples taken from suspected individuals were analyzed by RT-PCR and automated antigen test (Elecsys SARS-CoV-2 Antigen) simultaneously. The correlation of SARS-CoV-2 antigen with PCR positive and negative cases was analyzed for specificity, sensitivity respectively. The ECLIA based Elecsys antigen test (Roche) revealed overall sensitivity 72%, specificity 95% and accuracy of 94.9%. Sensitivity of antigen test progressively declined from 94.3% in Ct <25 to 70.8% in Ct 26–29 and then to 47.2% in Ct 30–35. Based on the findings of our study we conclude that automated antigen testing (Elecsys SARS-CoV-2 Antigen) cannot replace molecular based testing like RT PCR. Elecsys SARS-CoV-2 Ag test should be used complementary to RT-PCR in testing algorithms. Frequent testing strategy should be adopted while using automated antigen testing to overcome its limitation in individuals with low viral loads. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance is a growing public health crisis, propelled by inappropriate antibiotic prescription, in particular the over-prescription of antibiotics, prolonged duration of antibiotic therapy and the overuse of broad-spectrum antibiotics. The paediatric population, in particular, those presenting to emergency settings with respiratory symptoms, have been associated with a high rate of antibiotic prescription rates. Further research has now shown that many of these antibiotic prescriptions may have been avoided, with more targeted diagnostic methods to identify underlying aetiologies. The purpose of this systematic review was to assess the impact of rapid diagnostic testing, for paediatric respiratory presentations in the emergency setting, on antibiotic prescription rates. To review the relevant history, a comprehensive search of Medline, EMBASE and Cochrane Database of Systematic Reviews was performed. Eighteen studies were included in the review, and these studies assessed a variety of rapid diagnostic testing tools and outcome measures. Overall, rapid diagnostic testing was found to be an effective method of diagnostic antibiotic stewardship with great promise in improving antibiotic prescribing behaviours. Further studies are required to evaluate the use of rapid diagnostic testing with other methods of antibiotics stewardship, including clinical decisions aids and to increase the specificity of interventions following diagnosis to further reduce rates of antibiotic prescription. [ABSTRACT FROM AUTHOR]

BackgroundResearch studies rely on accurate assessment of entry criteria in order to maintain study integrity and participant safety, however, challenges can exist with HIV studies in international settings.ObjectiveExamine the unexpectedly high proportion of study participants with an undetectable HIV viral load found in Ugandan and Russian research cohorts meeting antiretroviral therapy (ART)-naïve entry criteria.MethodsRussian participants with documented HIV and ART-naïve status were recruited between 2012 and 2015 from clinical and non-clinical sites in St. Petersburg. Participants in Uganda were recruited from Mbarara Regional Referral Hospital from 2011 to 2014 with documented HIV infection via rapid diagnostic testing and recorded ART-naïve in the clinic database. HIV viral load testing of baseline samples was performed; the lower limit of detection was 500 copies/mL in Russia and 40 in Uganda. Due to an unexpectedly high proportion of participants with undetectable viremia, additional tests were performed: enzyme-linked immunosorbent assay HIV testing and testing for ART.ResultsIn Russia, 16% (58/360) had undetectable viremia; 3% (9/360) re-tested HIV-seronegative and 4% (13/360) tested positive for ART. In Uganda 11% (55/482) had undetectable viremia; 5% (26/482) re-tested HIV-seronegative, while

Background Antimicrobial susceptibility testing (AST) is often needed prior to antimicrobial optimization for patients with gram-negative bloodstream infections (GN-BSIs). Rapid AST (rAST) in combination with antimicrobial stewardship (AS) may decrease time to administration of narrower antibiotics. Methods This was a prospective, nonblinded, randomized trial evaluating the impact of a phenotypic rAST method vs conventional AST (cAST) in hospitalized patients with GN-BSI and source control. The primary outcome was time to narrowest effective therapy. Results Two hundred seventy-four patients were randomized and 205 underwent analysis (97 cAST, 108 rAST). Median (interquartile range [IQR]) time to susceptibility results was 23 hours shorter in the rAST group (cAST: 62 [59–67] hours vs rAST: 39 [IQR, 35–46] hours; P  < .001). Median (IQR) time to narrowest effective therapy was similar between groups (cAST: 73 [44–138] hours vs rAST: 64 [42–92] hours; P  = .10). Median (IQR) time to narrowest effective therapy was significantly shorter in a prespecified subgroup of patients not initially on narrowest therapy and during AS working hours (cAST: 93 [56–154] hours vs rAST: 62 [43–164] hours; P  = .004). Significant decreases were observed in median (IQR) time to oral therapy (cAST: 126 [76–209] hours vs rAST: 91 [66–154] hours; P  = .02) and median (IQR) length of hospital stay (cAST: 7 [4–13] days vs rAST: 5 [4–8] days; P  = .04). Conclusions In patients with GN-BSI, rAST did not significantly decrease time to narrowest effective therapy but did decrease time to oral antibiotics and length of hospital stay. Rapid AST using existing microbiology platforms has potential to optimize patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Rapid diagnostic tests (RDTs) for bacteremia allow for early antimicrobial therapy modification based on organism and resistance gene identification. Studies suggest patient outcomes are optimized when infectious disease (ID)-trained antimicrobial stewardship personnel intervene on RDT results. However, data are limited regarding RDT implementation at small community hospitals, which often lack access to on-site ID clinicians. Methods: This study evaluated the impact of RDTs with and without real-time pharmacist intervention (RTPI) at a small community hospital with local pharmacist training and asynchronous support from a remote ID Telehealth pharmacist. Time to targeted therapy (TTT) in patients with bacteremia was compared retrospectively across 3 different time periods: a control without RDT, RDT-only, and RDT with RTPI. Results: Median TTT was significantly faster in both the RDT with RTPI and RDT-only groups compared with the control group (2 vs 25 vs 51 hours respectively; P <.001). TTT was numerically faster for RDT with RTPI compared with RDT-only but did not reach statistical significance (P =.078). Median time to any de-escalation was significantly shorter for RDT with RTPI compared with both RDT-only (14 vs 33 hours; P =.012) and the control group (14 vs 45 hours; P <.001). Median length of stay was also significantly shorter in both RDT groups compared with the control group (4.0 vs 4.1 vs 5.5 hours; P =.013). Conclusion: This study supports RDT use for bacteremia in a small community hospital with ID Telehealth support, suggesting additional benefit with RTPI. [ABSTRACT FROM AUTHOR]

Rapid diagnostic tests (RDTs) facilitate fast and accurate identification of infectious disease microorganisms and are a valuable component of multimodal antimicrobial stewardship (AMS) programs but are currently underutilized in the Asia-Pacific region. An experienced group of infectious diseases clinicians, clinical microbiologists, and a clinical pharmacist used a modified Delphi consensus approach to construct 10 statements, aiming to optimize the utility and applicability of infection-related RDTs for AMS in the Asia-Pacific region. They provide guidance on definition, types, optimal deployment, measuring effectiveness, and overcoming key challenges. The Grading of Recommendations Assessment, Development, and Evaluation system was applied to indicate the strength of the recommendation and the quality of the underlying evidence. Given the diversity of the Asia-Pacific region, the trajectory of RDT development will vary widely; the collection of local data should be prioritized to allow realization and optimization of the full benefits of RDTs in AMS. [ABSTRACT FROM AUTHOR]

Abstract Rapid diagnosis of SARS-CoV-2 during pandemic enables timely treatment and prevention of COVID-19. Evaluating the accuracy and reliability of rapid diagnostic testing kits is crucial for surveillance and diagnosis of SARS-CoV-2 infections in general population, injection drug users, multi-transfused populations, healthcare workers, prisoners, barbers and other high risk populations. The aim of this study was to evaluate performance and effectiveness of nasopharyngeal swab (NSP) and saliva based rapid antigen detection testing kits in comparison with USFDA approved triple target gold standard real-time polymerase chain reaction. A cross-sectional study was conducted on 33,000 COVID-19 suspected patients. From RT-PCR positive patients, nasopharyngeal swab (NSP) and saliva samples were obtained for evaluation of rapid COVID-19 testing kits (RDT). 100/33,000 (0.3%) of specimens were RT-PCR positive for SARS-CoV-2. Among RT-PCR positive, 62% were males, 34% were females, and 4% were children. The NSP-RDT (Lepu Medical China) analysis revealed 53% reactivity among males, 58% reactivity among females, and 25% reactivity among children. However saliva based RDT (Lepu Medical China) analysis showed 21% reactivity among males and 23% among females, and no reactivity in children. False negative results were significantly more pronounced in saliva based RDT as compared to NSP-RDT. The sensitivity of these NSP-RDT and saliva based RDT were 52% and 21% respectively. The RDTs evaluated in this study showed limited sensitivities in comparison to gold standard RT-PCR, indicating that there is a dire need in Pakistan for development of suitable testing to improve accurate COVID-19 diagnosis in line with national demands.

Bloodstream HSV-1 and HSV-2 infections can cause devastating outcomes with high morbidity and mortality, especially in neonates or immunocompromised individuals. Proper patient management for herpes simplex virus (HSV) bloodstream infections is time-sensitive and requires a rapid, accurate, and definitive diagnosis. The absence of the U.S. Food and Drug Administration (FDA)-approved molecular assays for HSV detection in blood, coupled with a lack of consensus on the optimal sample type, underscores the unmet need for improved diagnostics. We prospectively compared the cycle threshold values in paired samples including whole blood (WB), plasma, serum, and peripheral blood mononuclear cells (PBMCs) from patients with bloodstream HSV infections. This analysis employed a modified use of the FDA-cleared Simplexa HSV-1 & 2 Direct assay. The clinical performance in serum was assessed by comparing the results of 247 remnant specimens on this sample-to-answer platform to established laboratory-developed tests in a blinded fashion. Serum samples exhibited significantly lower cycle thresholds than whole blood samples [2.6 cycle threshold (Ct) bias, P < 0.001]. The modified Simplexa assay demonstrated 100% positive percent agreement for the detection of HSV-1 and HSV-2 DNA in serum samples and yielded an overall agreement of 95% (95% CI, 0.92 to 0.97), with a κ statistic of 0.75 (95% CI, 0.62 to 0.86) compared to the composite reference method. Discordance rates were 5.20% for HSV-1 and 0.81% for HSV-2. This investigation demonstrates that serum is an optimal specimen type for HSV detection when compared to several blood compartments. Serum offers a promising sample type for rapid and accurate diagnosis of HSV bloodstream infections using the modified Simplexa assay., Importance: Rapid, accurate, and definitive diagnosis of herpes simplex virus (HSV) infections is crucial in clinical settings for patient management. The absence of FDA-authorized molecular assays for HSV-1/2 detection in blood, coupled with a lack of consensus on the optimal sample type, underscores the need for improved diagnostic methods. Furthermore, rapid diagnosis of HSV bloodstream infections enables timely administration of antiviral treatment, influences patient management decisions for those at high risk, and can contribute to shorter hospital stays, thereby reducing healthcare costs., Competing Interests: The authors declare no conflict of interest.

Objectives Blood culture rapid diagnostic testing (RDT) aids in early organism identification and resistance gene detection. This information allows quicker transition to tailored antimicrobial therapy, improved patient outcomes and prevention of antimicrobial resistance. An antimicrobial treatment algorithm based on RDT results and local antibiograms can serve as a valuable clinical decision-support tool. This study assessed the proportion of appropriate antibiotic therapy recommendations using a novel paediatric RDT-guided treatment algorithm compared with standard care (SC) in paediatric bacteraemia. Methods This was a retrospective, observational study of admitted paediatric patients who received antibiotics for RDT-confirmed bacteraemia. Appropriateness of SC was compared with algorithm-recommended treatment. Antimicrobial appropriateness was defined as in vitro susceptibility to the organism identified through traditional microbiology. Clinical appropriateness took into consideration the ability to tailor therapy within 12 h of RDT results. Appropriateness was evaluated by two blinded, independent reviewers. Key findings Eighty-six blood cultures were included with 15 unique Gram-positive and Gramnegative species or genus identified. Comparative antimicrobial appropriateness of SC and algorithm-recommended treatment was 94.2% (81/86) and 100% (86/86), respectively (P = 0.06). Clinical assessment determined 39.5% (34/86) of SC patients were on appropriate therapy within 12 h of RDT result. Algorithm-recommended therapy was clinically appropriate in 97.7% (84/86) of patients (P < 0.001). There was a median time savings of 42.7 h (IQR 40.6, 49.4) for the patients able to be de-escalated as compared with waiting on final sensitivities. Conclusions Algorithm-guided treatment may allow most patients to be de-escalated to organismtailored therapy earlier in their therapeutic course. [ABSTRACT FROM AUTHOR]

Three rapid diagnostic test panels (Verigene BC-GN, BioFire BCID, and BCID 2 [RUO]) were compared using the Desirability of Outcome Ranking Management of Antimicrobial Therapy (DOOR-MAT) to evaluate potential downstream antimicrobial prescribing decisions resulting from the panels' different organism and resistance detection. BioFire BCID 2 (RUO) had the best mean DOOR-MAT scores. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance is a growing public health crisis, propelled by inappropriate antibiotic prescription, in particular the over-prescription of antibiotics, prolonged duration of antibiotic therapy and the overuse of broad-spectrum antibiotics. The paediatric population, in particular, those presenting to emergency settings with respiratory symptoms, have been associated with a high rate of antibiotic prescription rates. Further research has now shown that many of these antibiotic prescriptions may have been avoided, with more targeted diagnostic methods to identify underlying aetiologies. The purpose of this systematic review was to assess the impact of rapid diagnostic testing, for paediatric respiratory presentations in the emergency setting, on antibiotic prescription rates. To review the relevant history, a comprehensive search of Medline, EMBASE and Cochrane Database of Systematic Reviews was performed. Eighteen studies were included in the review, and these studies assessed a variety of rapid diagnostic testing tools and outcome measures. Overall, rapid diagnostic testing was found to be an effective method of diagnostic antibiotic stewardship with great promise in improving antibiotic prescribing behaviours. Further studies are required to evaluate the use of rapid diagnostic testing with other methods of antibiotics stewardship, including clinical decisions aids and to increase the specificity of interventions following diagnosis to further reduce rates of antibiotic prescription.

Rapid identification of extended-spectrum-b-lactamase (ESBL)-, serine carbapenemase-, and metallo-blactamase (MBL)-producing Enterobacterales directly from positive blood culture (BC) bottles is of paramount importance to early optimize antimicrobial management and infection control measures. In this study, we describe and evaluate an improved variant of direct b-lactam inactivation method, named direct ethylenediaminetetraaceticacid-modified-b-lactam inactivation method (deBLIM). The deBLIM test is designed to detect ESBL or carbapenemase activity and to differentiate serine-carbapenemases from MBLs directly from Enterobacterale-positive BCs. The deBLIM was evaluated on both aerobic and anaerobic BCs spiked with 167 characterized Enterobacterale isolates. The deBLIM showed 100% sensitivity in detecting KPC and OXA-48-like serine carbapenemase, CTX-M, SHV variants, and TEM-10 ESBLs both in aerobic and anaerobic conditions. In contrast, a significant discrepancy between aerobic and anaerobic BCs was observed in detecting MBLs. The sensitivity rate in aerobic BCs was of 100% for all metalloenzyme types, whereas only 56.1% and 80% of VIM and NDM producers were detected in anaerobic bottles, respectively. IMP-producing Escherichia coli NCTC 13476 was also not detected in the anaerobic BC. No false positive result was observed among ESBL producers and broad-spectrum-b-lactamase nonproducers, demonstrating an overall specificity of 100%. The deBLIM could be a cost-effective screening method for the identification of ESBLs, serine carbapenemases, and MBLs directly from Enterobacterale-positive BCs on the same day of bottle positivity detection. Nevertheless, it must be considered its poor performance in detecting MBLs in the anaerobic condition. [ABSTRACT FROM AUTHOR]

Purpose: Gram-negative bacteria (GNB) are a leading cause of bloodstream infections (BSI) and management is complicated by antibiotic resistance. The Accelerate Pheno™ system (ACC) can provide rapid organism identification and antimicrobial susceptibility testing (AST). Methods: A retrospective, pre-intervention/post-intervention study was conducted to compare management of non-critically ill patients with GNB BSI before and after implementation of a bundled initiative. This bundled initiative included dissemination of a clinical decision algorithm, ACC testing on all GNB isolated from blood cultures, real-time communication of results to the Antimicrobial Stewardship Program (ASP), and prospective audit with feedback by the ASP. The pre-intervention period was January 2018 through December 2018, and the post-intervention period was May 2019 through February 2020. Results: Seventy-seven and 129 patients were included in the pre-intervention and post-intervention cohorts, respectively. When compared with the pre-intervention group, the time from Gram stain to AST decreased from 46.1 to 6.9 h (p < 0.001), and the time to definitive therapy (TTDT) improved from 32.6 to 10.5 h (p < 0.001). Implementation led to shorter median total duration of antibiotic therapy (14.2 vs 9.5 days; p < 0.001) and mean hospital length of stay (7.9 vs 5.3 days; p = 0.047) without an increase in 30-day readmissions (22.1% vs 14%; p = 0.13). Conclusion: Implementation of an ASP-bundled approach incorporating the ACC aimed at optimizing antibiotic therapy in the management GNB BSI in non-critically ill patients led to reduced TTDT, shorter duration of antibiotic therapy, and shorter hospital length of stay without adversely affecting readmission rates. [ABSTRACT FROM AUTHOR]

Rapid diagnosis of SARS-CoV-2 during pandemic enables timely treatment and prevention of COVID-19. Evaluating the accuracy and reliability of rapid diagnostic testing kits is crucial for surveillance and diagnosis of SARS-CoV-2 infections in general population, injection drug users, multi-transfused populations, healthcare workers, prisoners, barbers and other high risk populations. The aim of this study was to evaluate performance and effectiveness of nasopharyngeal swab (NSP) and saliva based rapid antigen detection testing kits in comparison with USFDA approved triple target gold standard real-time polymerase chain reaction. A cross-sectional study was conducted on 33,000 COVID-19 suspected patients. From RT-PCR positive patients, nasopharyngeal swab (NSP) and saliva samples were obtained for evaluation of rapid COVID-19 testing kits (RDT). 100/33,000 (0.3%) of specimens were RT-PCR positive for SARS-CoV-2. Among RT-PCR positive, 62% were males, 34% were females, and 4% were children. The NSP-RDT (Lepu Medical China) analysis revealed 53% reactivity among males, 58% reactivity among females, and 25% reactivity among children. However saliva based RDT (Lepu Medical China) analysis showed 21% reactivity among males and 23% among females, and no reactivity in children. False negative results were significantly more pronounced in saliva based RDT as compared to NSP-RDT. The sensitivity of these NSP-RDT and saliva based RDT were 52% and 21% respectively. The RDTs evaluated in this study showed limited sensitivities in comparison to gold standard RT-PCR, indicating that there is a dire need in Pakistan for development of suitable testing to improve accurate COVID-19 diagnosis in line with national demands. [ABSTRACT FROM AUTHOR]

Infected aneurysms caused by Listeria monocytogenes are extremely rare. Therefore, there is no standard procedure for their diagnosis and treatment. A 76-year-old Japanese man with diabetes and hypertension was diagnosed with a left common iliac aneurysm caused by L. monocytogenes, using multidetector computed tomographic angiography and rapid diagnostic testing of the positive blood culture. He was successfully treated with a combination of ampicillin administration, timely surgical debridement, and in-situ Y-graft placement with revascularization and omental implantation. Vancomycin and third-generation cephalosporins, to which L. monocytogenes is resistant, are used as an empirical regimen for infected aneurysms. Therefore, the use of a rapid diagnostic testing is important as it identifies L. monocytogenes within 24 h from obtaining the blood cultures, and guides the administration of the appropriate antibiotics. In-situ Y-graft placement restores nearly normal blood flow, following the confirmation of negative conversion of blood culture in response to the intensive intravenous ampicillin therapy. Appropriate and timely microbiological examinations, in addition to radiographic examinations, can be the key for selecting the optimal therapeutic procedures for each patient and achieving the best possible outcomes.

Background Verigene Blood-Culture Gram-Negative is a rapid diagnostic test (RDT) that detects gram-negatives (GNs) and resistance within hours from gram stain. The majority of the data support the use of RDTs with antimicrobial stewardship (AMS) intervention in gram-positive bloodstream infection (BSI). Less is known about GN BSI. Methods This was a retrospective quasi-experimental (nonrandomized) study of adult patients with RDT-target GN BSI comparing patients pre-RDT/AMS vs post-RDT/pre-AMS vs post-RDT/AMS. Optimal therapy was defined as appropriate coverage with the narrowest spectrum, accounting for source and co-infecting organisms. Time to optimal therapy was analyzed using Kaplan-Meier and multivariable Cox proportional hazards regression. Results Eight-hundred thirty-two patients were included; 237 pre-RDT/AMS vs 308 post-RDT/pre-AMS vs 237 post-RDT/AMS, respectively. The proportion of patients on optimal antibiotic therapy increased with each intervention (66.5% vs 78.9% vs 83.2%; P  < .0001). Time to optimal therapy (interquartile range) decreased with introduction of RDT: 47 (7.9–67.7) hours vs 24.9 (12.4–55.2) hours vs 26.5 (10.3–66.5) hours (P  = .09). Using multivariable modeling, infectious diseases (ID) consult was an effect modifier. Within the ID consult stratum, controlling for source and ICU stay, compared with the pre-RDT/AMS group, both post-RDT/pre-AMS (adjusted hazard ratio [aHR], 1.34; 95% CI, 1.04–1.72) and post-RDT/AMS (aHR, 1.28; 95% CI, 1.01–1.64), improved time to optimal therapy. This effect was not seen in the stratum without ID consult. Conclusions With the introduction of RDT and AMS, both proportion and time to optimal antibiotic therapy improved, especially among those with an existing ID consult. This study highlights the beneficial role of RDTs in GN BSI. [ABSTRACT FROM AUTHOR]

Delayed administration of active anti-infective therapy is associated with increased rates of adverse events, mortality, and costs among sepsis patients. Inherent limitations of conventional culture identification methods and the lengthy turnaround time of antimicrobial susceptibility testing are significant barriers to the timely delivery of life-saving therapy, particularly among antibiotic-resistant infections. Culture-independent diagnostic techniques that detect pathogens and antimicrobial resistance genes within clinical samples present a tremendous benefit to timely diagnosis and management of patients. Improved outcomes for rapid intervention with rapid diagnostics have been documented and include decreased mortality rates, decreased health care delivery costs, and faster delivery of appropriate therapeutics. [ABSTRACT FROM AUTHOR]

A major puzzle in malaria treatment remains the dual problem of underuse and overuse of malaria medications, which deplete scarce public resources used for subsidies and lead to drug resistance. One explanation is that health behaviour, especially in the context of incomplete information, could be driven by beliefs, pivotal to the success of health interventions. The objective of this study is to investigate how population beliefs change in response to an experimental intervention which was shown to improve access to rapid diagnostic testing (RDT) through community health workers (CHWs) and to increase appropriate use of anti-malaria medications. By collecting data on individuals' beliefs on malaria testing and treatment 12 and 18 months after the experimental intervention started, we find that the intervention increases the belief that a negative test result is correct, and the belief that the first-line anti-malaria drugs (artemisinin-based combination therapies or ACTs) are effective. Using mediation analysis, we also explore some possible mechanisms through which the changes happen. We find that the experience and knowledge about RDT and experience with CHWs explain 62.4% of the relationship between the intervention and the belief that a negative test result is correct. Similarly, the targeted use of ACTs and taking the correct dose-in addition to experience with RDT-explain 96.8% of the relationship between the intervention and the belief that the ACT taken is effective. As beliefs are important determinants of economic behaviour and might guide individuals' future decisions, understanding how they change after a health intervention has important implications for long-term changes in population behaviour. [ABSTRACT FROM AUTHOR]

In clinical studies, case definitions are usually designed to optimally match the desired clinical state, because lacking specificity is associated with a risk of bias regarding the study outcome. In preventive medicine, however, high sensitivity is sometimes considered as more critical in order not to overlook infectious individuals, because the latter may be associated with ongoing spread of a transmittable disease. Accordingly, this work was focused on a theoretical model on how the sensitivity of case definitions can be optimized by adding clinical symptoms to diagnostic results for preventive purposes, if the associated reduction in specificity is considered as acceptable. The model was exemplified with an analysis on whether and in how far exposure risk can be reduced by the inclusion of observable symptoms during seroconversion syndrome in case of rapid diagnostic test-based prevention of sexual HIV transmission. The approach provided a high level of safety (negative predictive values close to 1) for the price of a considerably number of false positives (positive predictive values < 0.01 for some subpopulations). When applying such a sensitivity-optimized screening as a “diagnostics as prevention” strategy, the advantages of excellent negative predictive values need to be cautiously balanced against potential undesirable consequences of low positive predictive values.

Current methods for the diagnosis of urinary tract infections with antimicrobial susceptibility testing take 2–3 days and require a clinical laboratory. The lack of a rapid, point-of-care antibiotic susceptibility test (AST) has contributed to the misuse of antibiotics when treating urinary tract infections (UTIs) and consequently to the rise of multi-drug-resistant organisms. The current clinical approach has led to reduced treatment options and increased costs of diagnosis and therapy. To address this issue, novel diagnostics are needed for the timely determination of antimicrobial susceptibility. We present a rapid, point-of-care, phenotypic AST device that can report the antibiotic susceptibility/resistance of a uropathogen to a panel of antibiotics in as few as 3 h by utilizing fluorescent-labelling chemistry and a highly sensitive particle-counting instrument. We analysed 744 urine samples from the outpatients and inpatients of two Italian hospitals. The 130 UTI-positive patient urine samples we found were measured using a panel of six common UTI antibiotics plus a growth control. By comparing our results to hospital laboratory urine cultures, we obtained an overall sensitivity = 81%, a specificity = 83%, an SPV (sensitivity predicted value) = 95%, and an RPV (resistance predicted value) = 54%. According to our preliminary data, the sensitivity predicted value for a single antibiotic agent was 95%, thus allowing (in the vast majority of cases) an early (within 3 h) recognition of an effective agent for a single patient.

Abstract Background Understanding the key characteristics of malaria testing and treatment is essential to the control of a disease that continues to pose a major risk of morbidity and mortality in mainland Tanzania, with evidence of a resurgence of the disease in recent years. The introduction of artemisinin combination therapy (ACT) as the first-line treatment for malaria, alongside policies to promote rational case management following testing, highlights the need for evidence of anti-malarial and testing markets in the country. The results of the most recent mainland Tanzania ACTwatch outlet survey are presented here, including data on the availability, market share and price of anti-malarials and malaria diagnosis in 2016. Methods A nationally-representative malaria outlet survey was conducted between 18th May and 2nd July, 2016. A census of public and private outlets with potential to distribute malaria testing and/or treatment was conducted among a representative sample of administrative units. An audit was completed for all anti-malarials, malaria rapid (RDT) diagnostic tests and microscopy. Results A total of 5867 outlets were included in the nationally representative survey, across both public and private sectors. In the public sector, availability of malaria testing was 92.3% and quality-assured (QA) ACT was 89.1% among all screened outlets. Sulfadoxine–pyrimethamine (SP) was stocked by 51.8% of the public sector and injectable artesunate was found in 71.4% of all screened public health facilities. Among anti-malarial private-sector stockists, availability of testing was 15.7, and 65.1% had QA ACT available. The public sector accounted for 83.4% of the total market share for malaria diagnostics. The private sector accounted for 63.9% of the total anti-malarial market, and anti-malarials were most commonly distributed through accredited drug dispensing outlets (ADDOs) (39.0%), duka la dawa baridi (DLDBs) (13.3%) and pharmacies (6.7%). QA ACT comprised 33.1% of the national market share (12.2% public sector and 20.9% private sector). SP accounted for 53.3% of the total market for anti-malarials across both private and public sectors (31.3 and 22.0% of the total market, respectively). The median price per adult equivalent treatment dose (AETD) of QA ACT in the private sector was $1.40, almost 1.5 times more expensive than the median price per AETD of SP ($1.05). In the private sector, 79.3% of providers perceived ACT to be the most effective treatment for uncomplicated malaria for adults and 88.4% perceived this for children. Conclusions While public sector preparedness for appropriate malaria testing and case management is showing encouraging signs, QA ACT availability and market share in the private sector continues to be sub-optimal for most outlet types. Furthermore, it is concerning that SP continues to predominate in the anti-malarial market. The reasons for this remain unclear, but are likely to be in part related to price, availability and provider knowledge or preferences. Continued efforts to implement government policy around malaria diagnosis and case management should be encouraged.

T2 Magnetic Resonance Candida Panel (T2MR) detects Candida directly in blood. Rapid turnaround time and high negative predictive value make it a useful diagnostic test to support antifungal discontinuation. This retrospective quasi-experiment compared empiric anidulafungin days of therapy (DOTs) in intensive care unit (ICU) patients with suspected candidemia that had negative blood cultures and negative 1,3-β-D-glucan (BDG) versus negative blood cultures and negative T2MR. In 206 ICU patients, median anidulafungin DOTs were 2 (1, 5) compared to 1 (1, 2), respectively (P < 0.001); T2MR was associated with early discontinuation, AdjOR 3.0 95% CI (1.7–5.6), P < 0.001. Proven candidemia after discontinuation of anidulafungin occurred in 3% of BDG and 2% of T2MR patients at a median of 8 and 21 days, respectively. T2MR testing supports safe, early discontinuation of empiric antifungal therapy in ICU patients with suspected candidemia. Prospective studies to better define the role of T2MR in antifungal stewardship are warranted. [ABSTRACT FROM AUTHOR]

Rapid diagnostic tests (RDTs) for bloodstream infections have the potential to reduce time to appropriate antimicrobial therapy and improve patient outcomes. Previously, an in-house, lipid-based, matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) method, Fast Lipid Analysis Technique (FLAT MS), has shown promise as a rapid pathogen identification method. In this study, FLAT MS for direct from blood culture identification was evaluated and compared to FDA-cleared identification methods using the Benefit-risk Evaluation Framework (BED-FRAME) analysis. FLAT MS was evaluated and compared to Bruker Sepsityper and bioMérieux BioFire FilmArray BCID2 using results from a previous study. For this study, 301 positive blood cultures were collected from the University of Maryland Medical Center. The RDTs were compared by their sensitivities, time-to-results, hands-on time, and BED-FRAME analysis. The overall sensitivity of all platforms compared to culture results from monomicrobial-positive blood cultures was 88.3%. However, the three RDTs differed in their accuracy for identifying Gram-positive bacteria, Gram-negative bacteria, and yeast. Time-to-results for FLAT MS, Sepsityper, and BioFire BCID2 were all approximately one hour. Hands-on times for FLAT MS, Sepsityper, and BioFire BCID2 were 10 (±1.3), 40 (±2.8), and 5 (±0.25) minutes, respectively. BED-FRAME demonstrated that each RDT had utility at different pathogen prevalence and relative importance. BED-FRAME is a useful tool that can used to determine which RDT is best for a healthcare center., Competing Interests: The authors declare no conflict of interest.

The increasing availability of rapid diagnostic self-tests (RDSTs) for COVID-19 has played an important and increasing role during the pandemic. However, for many underserved communities, RDSTs potential benefits are offset by problems with usability, accuracy, and equity. Given the increased need for and interest in home testing for acute and chronic diseases, including COVID-19, this piece offers ways that regulatory agencies, federal public health agencies, and test developers should engage with diverse communities to ensure equity throughout test development, implementation, and evaluation. Such engagement will ensure maximum personal and public health benefits for current and future RDSTs under real-world conditions., Competing Interests: No competing financial interests exist., (© Paul K. Drain et al., 2023; Published by Mary Ann Liebert, Inc.)

Background: Migrants are disproportionately affected by HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV). Clinicians, at times, fail to offer rapid diagnostic testing (RDT) for these viruses when a language barrier exists in the patient-clinician relationship, therefore creating missed testing opportunities. Although their effectiveness has been demonstrated elsewhere, conventional, in-person interpreters are costly and underused in practice. Furthermore, clinicians often call upon ad hoc interpreters, which introduces complexities in the clinical relationship. Digital solutions exist to diminish the burden of language barriers; however, the challenges of developing a multilingual and multicultural app have yet to be documented with respect to RDT in the nonfrancophone migrant population in France., Objective: Our goal was to design a multilingual app to overcome language barriers, health literacy barriers, and fears related to being tested to promote RDT of HIV, HBV, and HCV in the nonfrancophone migrant population in France., Methods: A combination of qualitative methods, agile development, and user-centered design was used. We conducted 2 focus groups (FGs) with 12 participants, including physicians, nurses, and social workers conducting RDT, as well as 1 modified Delphi survey with 68 participants including physicians and nurses. FGs explored the content (risk factors and medical history), functions (cultural adaptation and instant translation), and interface ergonomics (graphics and font) needed in the app. The Delphi presented 95 content items that the researchers sought to include in the app., Results: Using FGs to inform the Delphi survey, we scientifically determined the app's content consisting of 95 items using expert consensus, developed a mock-up, and conducted initial user testing. We created an app that contains both migrant and clinician interfaces and includes a sociodemographic, risk assessment, health literacy, and testing barrier questionnaires available in 11 languages. Educational content is related to HIV, HBV, and HCV, along with the ability to understand whether the migrant agrees to be tested., Conclusions: This study allowed us to conceptualize a multilingual app that aims to increase the acceptance of RDT for HIV, HBV, and HCV. The specific features of the Assistant intelligent au dépistage des allophones app were designed to overcome the testing barriers in the nonfrancophone migrant population. The next phase will be an implementation study, as we intend to validate our app., (©Carter Brown, Guillaume Roucoux, Olivia Rousset-Torrente, Saleh Ali, Lisa Yombo-Kokule, John Chaplin, Olivier Chassany, Martin Duracinsky. Originally published in JMIR Formative Research (https://formative.jmir.org), 16.11.2023.)

Based on the unique characteristics of influenza, the concept of “monitoring” influenza vaccine effectiveness (VE) across the seasons using the same observational study design has been developed. In recent years, there has been a growing number of influenza VE reports using the test-negative design, which can minimize both misclassification of diseases and confounding by health care-seeking behavior. Although the test-negative designs offer considerable advantages, there are some concerns that widespread use of the test-negative design without knowledge of the basic principles of epidemiology could produce invalid findings. In this article, we briefly review the basic concepts of the test-negative design with respect to classic study design such as cohort studies or case-control studies. We also mention selection bias, which may be of concern in some countries where rapid diagnostic testing is frequently used in routine clinical practices, as in Japan. [ABSTRACT FROM AUTHOR]

Background: Understanding the key characteristics of malaria testing and treatment is essential to the control of a disease that continues to pose a major risk of morbidity and mortality in mainland Tanzania, with evidence of a resurgence of the disease in recent years. The introduction of artemisinin combination therapy (ACT) as the first-line treatment for malaria, alongside policies to promote rational case management following testing, highlights the need for evidence of anti-malarial and testing markets in the country. The results of the most recent mainland Tanzania ACTwatch outlet survey are presented here, including data on the availability, market share and price of anti-malarials and malaria diagnosis in 2016. Methods: A nationally-representative malaria outlet survey was conducted between 18th May and 2nd July, 2016. A census of public and private outlets with potential to distribute malaria testing and/or treatment was conducted among a representative sample of administrative units. An audit was completed for all anti-malarials, malaria rapid (RDT) diagnostic tests and microscopy. Results: A total of 5867 outlets were included in the nationally representative survey, across both public and private sectors. In the public sector, availability of malaria testing was 92.3% and quality-assured (QA) ACT was 89.1% among all screened outlets. Sulfadoxine–pyrimethamine (SP) was stocked by 51.8% of the public sector and injectable artesunate was found in 71.4% of all screened public health facilities. Among anti-malarial private-sector stockists, availability of testing was 15.7, and 65.1% had QA ACT available. The public sector accounted for 83.4% of the total market share for malaria diagnostics. The private sector accounted for 63.9% of the total anti-malarial market, and anti-malarials were most commonly distributed through accredited drug dispensing outlets (ADDOs) (39.0%), duka la dawa baridi (DLDBs) (13.3%) and pharmacies (6.7%). QA ACT comprised 33.1% of the national market share (12.2% public sector and 20.9% private sector). SP accounted for 53.3% of the total market for anti-malarials across both private and public sectors (31.3 and 22.0% of the total market, respectively). The median price per adult equivalent treatment dose (AETD) of QA ACT in the private sector was $1.40, almost 1.5 times more expensive than the median price per AETD of SP ($1.05). In the private sector, 79.3% of providers perceived ACT to be the most effective treatment for uncomplicated malaria for adults and 88.4% perceived this for children. Conclusions: While public sector preparedness for appropriate malaria testing and case management is showing encouraging signs, QA ACT availability and market share in the private sector continues to be sub-optimal for most outlet types. Furthermore, it is concerning that SP continues to predominate in the anti-malarial market. The reasons for this remain unclear, but are likely to be in part related to price, availability and provider knowledge or preferences. Continued efforts to implement government policy around malaria diagnosis and case management should be encouraged. [ABSTRACT FROM AUTHOR]

Prolonged turnaround time of Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) test results may delay time to notification and treatment of test-positive patients and result in unnecessary antimicrobial use in test-negative patients. This quasi‐experimental study evaluated the impact of NG/CT rapid diagnostic testing (RDT) in an urban emergency department (ED) on treatment appropriateness, time to notification, and cost. Patients tested in December 2013–January 2014 (traditional group, n = 200) were compared with those in December 2014–January 2015 (RDT group, n = 200). There was a significant increase in treatment appropriateness in the RDT group, 72.5% versus 60% ( P = 0.008) and time to results notification was significantly faster (median 17.4 versus 51.5 hours, P = 0.010). Availability of test result prior to discharge was associated with increased treatment appropriateness (odds ratio, 22.65 [95% confidence interval, 2.86–179.68]). The RDT would save approximately $37,000 annually. These results support the use of NG/CT RDT to expand antimicrobial stewardship efforts within the ED. [ABSTRACT FROM AUTHOR]

Introduction: Timely and appropriate therapy is critical in patients with Gram-negative bloodstream infections (GNBSI). Most bacteriology laboratories process blood specimen in the daytime, during laboratory operating hours, and use conventional culture for antimicrobial susceptibility testing (AST). We simulated the potential impact of real-time processing and rapid AST (7 hours) on early adaptation of the antibiotic regimen in intensive care unit (ICU) patients with GNBSI., Methods: All GNBSI episodes occurring in the ICUs of 2 hospitals in Paris were included. Data were collected. For each episode of bacteremia, we simulated the impact of three strategies: (1) Real-time processing coupled with conventional techniques (Gram stain and standard AST); (2) Standard processing coupled with rapid AST; and (3) Real-time processing coupled with rapid AST., Results: We included 109 episodes in 98 patients. Forty-two patients (48%) died during ICU stay. AST results led to a change of the antibiotic regimen in 66 (61%) episodes, mainly de-escalation (54/109, 55%). In standard care, median time from sample collection to definitive AST result was 65.9 hours (±26.7). The three strategies would have reduced time-to-result by 9.2 hours (±7.1), 30.8 hours (±19.7) and 40.0 hours (±20.6) respectively. Compared to standard care, strategies 1, 2 and 3 would have avoided 20, 69 and 90 patient-days of broad-spectrum antibiotics respectively., Conclusion: In addition to real-time processing of blood samples, rapid AST would be the most effective strategy to shorten time-to-result in critical patients with GNBSI., (Copyright © 2023. Published by Elsevier Masson SAS.)

Despite advances in diagnostic technology, significant gaps remain in access to malaria diagnosis. Accurate diagnosis and misdiagnosis leads to unnecessary waste of resources, poor disease management, and contributes to a cycle of poverty in low-resourced communities. Despite much effort and investment, few new technologies have reached the field in the last 30 years aside from lateral flow assays. This suggests that much diagnostic development effort has been misdirected, and/or that there are fundamental blocks to introduction of new technologies. Malaria diagnosis is a difficult market; resources are broadly donor-dependent, health systems in endemic countries are frequently weak, and the epidemiology of malaria and priorities of malaria programmes and donors are evolving. Success in diagnostic development will require a good understanding of programme gaps, and the sustainability of markets to address them. Targeting assay development to such clearly defined market requirements will improve the outcomes of product development funding. Six market segments are identified: (1) case management in low-resourced countries, (2) parasite screening for low density infections in elimination programmes, (3) surveillance for evidence of continued transmission, (4) clinical research and therapeutic efficacy monitoring, (5) cross-checking for microscopy quality control, and (6) returned traveller markets distinguished primarily by resource availability. While each of these markets is potentially compelling from a public health standpoint, size and scale are highly variable and continue to evolve. Consequently, return on investment in research and development may be limited, highlighting the need for potentially significant donor involvement or the introduction of novel business models to overcome prohibitive economics. Given the rather specific applications, a well-defined set of stakeholders will need to be on board for the successful introduction and scaling of any new technology to these markets. [ABSTRACT FROM AUTHOR]