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The study compares an artificial intelligence technology with traditional manual search of literature databases to assess the accuracy and efficiency of retrieving relevant articles for post-market surveillance of in vitro diagnostic and medical devices under the Medical Device Regulation and In Vitro Diagnostic Medical Device Regulation. Over a 3-year period, literature searches and technical assessment searches were performed manually or using the Huma.AI platform to retrieve relevant articles related to the safety and performance of selected in vitro diagnostic and medical devices. The manual search involved refined keyword searches, screening of titles/abstracts / full text, and extraction of relevant information. The Huma.AI search utilized advanced caching techniques and a natural language processing system to identify relevant reports. Searches were conducted on PubMed and PubMed Central. The number of identified relevant reports, precision rates, and time requirements for each approach were analyzed. The Huma.AI system outperformed the manual search in terms of the number of identified relevant articles in almost all cases. The average precision rates per year were significantly higher and more consistent with the Huma.AI search compared with the manual search. The Huma.AI system also took significantly less time to perform the searches and analyze the outputs than the manual search. The study demonstrated that the Huma.AI platform was more effective and efficient in identifying relevant articles compared with the manual approach., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Joanna Reniewicz, Vinay Suryaprakash, Justyna Kowalczyk, Anna Blacha, and Davide Manissero are QIAGEN employees. Greg Kostello, Haiming Tan, Yan Wang, and Patrick Reineke are Huma.AI employees. All the work reported in this manuscript was funded by QIAGEN. No other conflicts of interest to declare., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: The speed at which Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is mutating has made it necessary to frequently assess how these genomic changes impact the performance of diagnostic real-time polymerase chain reaction (RT-PCR) assays. Herein, we describe a generic three-step workflow to assess the effect of genomic mutations on inclusivity and sensitivity of RT-PCR assays., Methods: Sequences collected from the Global Initiative on Sharing All Influenza Data (GISAID) were mapped to a SARS-CoV-2 reference genome to evaluate the position and prevalence of mismatches in the oligonucleotide-binding sites of the QIAstat-Dx, an RT-PCR panel designed to detect SARS-CoV-2. The frequency of mutations and their impact on melting temperature were assessed, and sequences flagged by risk-based criteria were examined in vitro., Results: Out of 8,900,393 SARS-CoV-2 genome sequences analyzed, only 173 (0.0019%) genomes contained potentially critical mutations for the QIAstat-Dx; follow-up in-vitro testing confirmed no impact on the assays' performance., Conclusions: The current study demonstrates that SARS-CoV-2 genetic variants do not affect the performance of the QIAstat-Dx device. It is recommended that manufacturers incorporate this workflow into obligatory post-marketing surveillance activities, as this approach could potentially enhance genetic monitoring of their product., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: All authors were QIAGEN employees at the time of writing this manuscript., (Copyright: © 2024 Kosińska-Selbi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The ability to proactively predict the epidemiological dynamics of infectious diseases such as coronavirus disease 2019 (COVID-19) would facilitate efficient public health responses and may help guide patient management. Viral loads of infected people correlate with infectiousness and, therefore, could be used to predict future case rates., Aim: In this systematic review, we determine whether there is a correlation between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) real-time reverse-transcription polymerase chain reaction (RT-PCR) cycle threshold (Ct) values (a proxy for viral load) and epidemiological trends in patients diagnosed with COVID-19, and whether Ct values are predictive of future cases., Methods: A PubMed search was conducted on August 22 2022, based on a search strategy of studies reporting correlations between SARS-CoV-2 Ct values and epidemiological trends., Results: Data from 16 studies were relevant for inclusion. RT-PCR Ct values were measured from national (n = 3), local (n = 7), single-unit (n = 5), or closed single-unit (n = 1) samples. All studies retrospectively examined the correlation between Ct values and epidemiological trends, and seven evaluated their prediction model prospectively. Five studies used the temporal reproduction number (R t ) as the measure of the population/epidemic growth rate. Eight studies reported a prediction time in the negative cross-correlation between Ct values and new daily cases, with seven reporting a prediction time of ~1-3 weeks, and one reporting 33 days., Conclusion: Ct values are negatively correlated with epidemiological trends and may be useful in predicting subsequent peaks in variant waves of COVID-19 and other circulating pathogens., (© 2023. The Author(s).)

Recent reports from the World Health Organization regarding Influenza A cases of zoonotic origin in humans (H1v and H9N2) and publications describing emergence swine Influenza A cases in humans together with "G4" Eurasian avian-like H1N1 Influenza A virus have drawn global attention to Influenza A pandemic threat. Additionally, the current COVID-19 epidemic has stressed the importance of surveillance and preparedness to prevent potential outbreaks. One feature of the QIAstat-Dx Respiratory SARS-CoV-2 panel is the double target approach for Influenza A detection of seasonal strains affecting humans using a generic Influenza A assay plus the three specific human subtype assays. This work explores the potential use of this double target approach in the QIAstat-Dx Respiratory SARS-Co-V-2 Panel as a tool to detect zoonotic Influenza A strains. A set of recently recorded H9 and H1 spillover strains and the G4 EA Influenza A strains as example of recent zoonotic Flu A strains were subjected to detection prediction with QIAstat-Dx Respiratory SARS-CoV-2 Panel using commercial synthetic dsDNA sequences. In addition, a large set of available commercial human and non-human influenza A strains were also tested using QIAstat-Dx Respiratory SARS-CoV-2 Panel for a better understanding of detection and discrimination of Influenza A strains. Results show that QIAstat-Dx Respiratory SARS-CoV-2 Panel generic Influenza A assay detects all the recently recorded H9, H5 and H1 zoonotic spillover strains and all the G4 EA Influenza A strains. Additionally, these strains yielded negative results for the three-human seasonal IAV (H1, H3 and H1N1 pandemic) assays. Additional non-human strains corroborated those results of Flu A detection with no subtype discrimination, whereas human Influenza strains were positively discriminated. These results indicate that QIAstat-Dx Respiratory SARS-CoV-2 Panel could be a useful tool to diagnose zoonotic Influenza A strains and differentiate them from the seasonal strains commonly affecting humans., (© 2023. The Author(s).)

To estimate the costs and benefits of screening for latent tuberculosis infection (LTBI) in a migrant population in Malaysia. An economic model was developed from a Malaysian healthcare perspective to compare QuantiFERON-TB Gold Plus (QuantiFERON) with the tuberculin skin test (TST). A decision tree was used to capture outcomes relating to LTBI screening followed by a Markov model that simulated the lifetime costs and benefits of the patient cohort. The Markov model did not capture the impact of secondary infections. The model included an R shiny interactive interface to allow adaptation to other scenarios and settings. QuantiFERON is both more effective and less costly than TST (dominant). Compared with QuantiFERON, the lifetime risk of developing active TB increases by approximately 40% for TST due to missed LTBI cases during screening (i.e. a higher number of false negative cases for TST). For a migrant population in Malaysia, QuantiFERON is cost-effective when compared with TST. Further research should consider targeted LTBI screening for migrants in Malaysia based on common risk factors., (© 2023. The Author(s).)

Background: The World Health Organisation (WHO) recommends that testing and treatment for latent tuberculosis infection (LTBI) should be undertaken in high-risk groups using either interferon gamma release assays (IGRAs) or a tuberculin skin test (TST). As IGRAs are more expensive than TST, an assessment of the cost-effectiveness of IGRAs can guide decision makers on the most appropriate choice of test for different high-risk populations. This current review aimed to provide the most up to date evidence on the cost-effectiveness evidence on LTBI testing in high-risk groups-specifically evidence reporting the costs per QALY of different testing strategies., Methods: A comprehensive search of databases including MEDLINE, EMBASE and NHS-EED was undertaken from 2011 up to March 2021. Studies were screened and extracted by two independent reviewers. The study quality was assessed using the Bias in Economic Evaluation Checklist (ECOBIAS). A narrative synthesis of the included studies was undertaken., Results: Thirty-two studies reported in thirty-three documents were included in this review. Quality of included studies was generally high, although there was a weakness across all studies referencing sources correctly and/or justifying choices of parameter values chosen or assumptions where parameter values were not available. Inclusions of IGRAs in testing strategies was consistently found across studies to be cost-effective but this result was sensitive to underlying LTBI prevalence rates., Conclusion: While some concerns remain about uncertainty in parameter values used across included studies, the evidence base since 2010 has grown with modelling approaches addressing the weakness pointed out in previous reviews but still reaching the same conclusion that IGRAs are likely to be cost-effective in high-income countries for high-risk populations. Evidence is also required on the cost-effectiveness of different strategies in low to middle income countries and countries with high TB burden., (© 2022. The Author(s).)

Objectives: Qualitative real-time polymerase chain reaction tests are not designed to provide quantitative or semiquantitative results because cycle threshold (Ct) values are not normalized to standardized controls of known concentration. The aim of this study was to characterize SARS-CoV-2 viral loads based on Ct values, using the QIAstat-Dx® Respiratory SARS-CoV-2 Panel., Methods: Different lineages of SARS-CoV-2 clinical samples and the World Health Organization international standard were used to assess the linearity of the QIAstat-Dx Respiratory SARS-CoV-2 Panel. Limit of detection for the different lineages was characterized., Results: Comparable efficiencies and linearity for all samples resulted in R 2 ≥0.99, covering a dynamic range of 1,000,000-100 copies/mL for the SARS-CoV-2 assay, showing linear correlation between Ct values and viral load down to 300 copies/mL., Conclusion: The SARS-CoV-2 Ct values provided by the QIAstat-Dx® Respiratory SARS-CoV-2 Panel could be used as a surrogate for viral load given the linear correlation between Ct values and viral concentration down to limit of detection. This panel allows to obtain reproducible Ct values for SARS-CoV-2 ribonucleic acid downstream of the sample collection, reducing the sample-to-Ct workflow variability. Ct values can help provide a reliable assessment and comparison of viral loads in patients when tested with the QIAstat-Dx Respiratory SARS-CoV-2 Panel., Competing Interests: Conflict of interest QIAGEN provided support in the form of salaries for all authors (MJF, LP, SJ, RP, CCT, MVV, SNR, GP, DM and JP)., (Copyright © 2022. Published by Elsevier Ltd.)

Introduction: Antimicrobial resistance is an urgent medical challenge. In this two-part study, we investigated the epidemiology and management of carbapenem non-susceptible (Carb-NS) Gram-negative bacteria (GNB) in the UK., Methods: We conducted a retrospective review of data from UK hospitals (ten in part 1, nine in part 2). In part 1, epidemiological data were collected from patients hospitalised between April 2017 and March 2018 with any laboratory detection of Carb-NS GNB, encompassing both colonisation and infection. In part 2, diagnosis and management pathways in a randomly selected population of adults from part 1 with confirmed Carb-NS GNB infection were assessed. Data were obtained from a detailed medical chart review for ≥ 3 months from index (collection date of first positive Carb-NS GNB sample)., Results: Of 42,340 GNB isolates from 36,098 patients colonised/infected with GNB in part 1, 7% were Carb-NS. In 157 patients included in part 2, 234 GNB index samples were collected, of which 197 (82%) were Carb-NS (median number of Carb-NS pathogens per patient, 1; range 1-3). The most frequent Carb-NS isolates were Pseudomonas aeruginosa (36%), Stenotrophomonas maltophilia (29%) and Klebsiella pneumoniae (10%). Median length of hospitalisation was 34 days. Median time from index to appropriate therapy was 3 days, with empirical therapy initiated a median of 1 day before index. Carb-NS infection was believed to contribute to 21 (28%) of 76 deaths during the study., Conclusions: This study highlights the high incidence of Carb-NS GNB colonisation and infection in the UK and the need for improved management of patients with Carb-NS GNB infection., (© 2022. The Author(s).)

Emerging evidence suggests that T-cells play a significant role in COVID-19 immunity both in the context of natural infection and vaccination. Easy to use IGRA assays including QFN SARS are considered attractive alternatives to more "traditional" but laborious methods for detection of SARS-CoV-2-specific T-cell responses. In our Letter we are proposing explanations to an apparently lower than expected T-cell responses (44 % reactive individuals) reported by Krüttgen et al in a small cohort of healthy double vaccinated individuals. These results could have been affected by reporting raw optical density values instead of calculated Interferon-ɣ concentrations which is supported by unexpectedly low mitogen responses in healthy individuals. This study highlights an importance of adhering to good laboratory practice principles as well as overall importance of accurate T-cell immunity assessment using IGRA assays., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Both humoral and cell-mediated responses are associated with immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although our understanding of the potential role of T-cell responses in the context of coronavirus disease 2019 (COVID-19) is rapidly increasing, more information is still needed., Objectives: To provide an overview of the role of T-cell immunity in COVID-19, in the context of natural infection and post-vaccination, and discuss the potential utility of measuring SARS-CoV-2-specific T-cell responses, drawing on experience of the use of interferon-γ release assays (IGRAs) in tuberculosis (TB)., Sources: PubMed articles up to 16 April 2021., Content: T-cell responses can be detected very early in the course of COVID-19, earlier than the detection of antibody responses, and are correlated with COVID-19 outcome. Lower CD4 + and CD8 + T-cell counts are markers of more severe disease, longer duration of viral RNA positivity and increased mortality. In line with natural infection, SARS-CoV-2 vaccination stimulates robust T-cell responses, which probably play an important role in protection; data on long-term T-cell responses are currently limited. The utility of measuring T-cell responses is already well established in both aiding the diagnosis of TB infection using IGRAs, and evaluation of T-cell responses to TB vaccine candidates. A variety of assays have already been developed to measure SARS-CoV-2-specific T-cell responses, including IGRAs, intracellular cytokine staining and activation-induced markers. IGRAs based on SARS-CoV-2 antigens can distinguish between convalescent and uninfected healthy blood donors., Implications: Simple assays for measuring the quantity and function of T-cell responses may have utility in the prognostication of COVID-19, and for monitoring immune responses to SARS-CoV-2 vaccination and population-based immunity to SARS-CoV-2 variants of interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: There is an increasing body of evidence surrounding the importance of a T cell-mediated response to SARS-CoV-2 infection and after COVID-19 vaccination. In this internal feasibility study, we evaluated both the total antibody (IgA, IgM, and IgG) and T cell responses in a cohort of COVID-19 convalescents and vaccinated individuals., Methods: Whole blood specimens were collected weekly from 12 subjects at different time points within/after the COVID-19 mRNA vaccination regimen, and from 4 PCR-confirmed convalescent donors to measure durability of humoral and cell-mediated immune response. T cell and antibody responses were evaluated via the QuantiFERON SARS-CoV-2 research use only (QFN SARS-CoV-2) assay which is an interferon gamma release assay (IGRA) and QIAreach Anti-SARS-CoV-2 total (Anti-CoV-2) test, respectively., Results: In a cohort of recently vaccinated individuals, subjects demonstrated robust total antibody and CD4+/CD8+ T cell response to SARS-CoV-2 mRNA vaccines when followed for 2 months post-2nd dose. In most individuals, T cell response declined between the 1st and 2nd doses suggesting a need for a booster or the completion of the 2-dose vaccine series. In a group of convalescent donors tested with QFN SARS-CoV-2 and Anti-CoV-2 tests, all patients had an antibody and T cell response up to 1 year after natural infection., Conclusion: This small feasibility study demonstrates that the QFN-SARS-CoV-2 test is able to identify CD4+ and CD8+ T cell-mediated responses in SARS-CoV-2-vaccinated subjects and those recovered from COVID-19, alongside a qualitative antibody response detectable via the QIAreach Anti-CoV2 test., (© 2021. The Author(s).)

BACKGROUND: Programmatic management of TB infection is a critical component of the WHO End TB Strategy. Interferon-gamma release assays (IGRAs) overcome some limitations of the tuberculin skin test, but implementation of IGRA testing in low-resource settings is challenging. METHODS: In this feasibility study, we evaluated performance of a novel digital lateral-flow assay, the QIAreach ® QuantiFERON ® TB (QIAreach-QFT) test, against the QuantiFERON ® -TB Gold Plus (QFT-Plus) assay. A population with a mix of risk factors for TB infection (111 donors) were sampled over multiple days. A total of 207 individual blood samples were tested according to the manufacturer´s instructions. RESULTS: The overall percentage agreement was 95.6% (two-sided 95% CI 91.8-98), with a positive percentage agreement (i.e., sensitivity) of 100% (95% CI 94.7-100) and a negative percentage agreement (i.e., specificity) of 95.6% (95% CI 90.6-98.4). All QFT-Plus positive specimens with TB1-Nil and TB2-Nil values less than 1 IU/ml tested positive on QIAreach-QFT. CONCLUSIONS: QIAreach QFT is a deployable, accurate testing solution for decentralised testing. It has the potential to overcome key hurdles for TB infection screening in high-burden settings thus helping to achieve the WHO End TB programme goals.

Objectives: It is unclear whether real-time (rt)-PCR cycle threshold (Ct) values can be utilized to guide clinical and infection-control decisions. This systematic review assesses the association between respiratory pathogen rt-PCR Ct values and clinical presentation or outcomes., Methods: We searched MEDLINE, EMBASE and Cochrane library databases on 14-17 January 2020 for studies reporting the presence or absence of an association between Ct values and clinical presentation or outcomes, excluding animal studies, reviews, meta-analyses, and non-English language studies., Results: Among 33 studies identified (reporting on between 9 and 4918 participants by pathogen), influenza (n = 11 studies; 4918 participants), human rhinovirus (HRV, n = 11; 2012) and respiratory syncytial virus (RSV, n = 8; 3290) were the most-studied pathogens. Low influenza Ct values were associated with mortality in 1/3 studies, with increased disease severity/duration or ICU admission in 3/9, and with increased hospitalization or length of hospital stay (LOS) in 1/6. Low HRV Ct values were associated with increased disease severity/duration or ICU admission in 3/10 studies, and with increased hospitalization or LOS in 1/3. Low RSV Ct values were associated with increased disease severity/duration or ICU admission in 3/6 studies, and with increased hospitalization or LOS in 4/4. Contradictory associations were also identified for other respiratory pathogens., Conclusions: Respiratory infection Ct values may inform clinical and infection-control decisions. However, the study heterogeneity observed in this review highlights the need for standardized workflows to utilize Ct values as a proxy of genomic load and confirm their value for respiratory infection management., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)

Objectives: This systematic review focuses on the use of the in vitro hollow fibre infection model (HFIM) for microbial culture. We summarize the direction of the field to date and propose best-practice principles for reporting of the applications., Methods: Searches in six databases (MEDLINE®, EMBASE®, PubMed®, BIOSIS®, SCOPUS® and Cochrane®) up to January 2020 identified 129 studies meeting our inclusion criteria. Two reviewers independently assessed and extracted data from each publication. The quality of reporting of microbiological and technical parameters was analysed., Results: Forty-seven out of 129 (36.4%) studies did not report the minimum pharmacokinetic parameters required in order to replicate the pharmacokinetic profile of HFIM experiments. Fifty-three out of 129 (41.1%) publications did not report the medium used in the HFIM. The overwhelming majority of publications did not perform any technical repeats [107/129 (82.9%)] or biological repeats [97/129 (75.2%)]., Conclusions: This review demonstrates that most publications provide insufficient data to allow for results to be evaluated, thus impairing the reproducibility of HFIM experiments. Therefore, there is a clear need for the development of laboratory standardization and improved reporting of HFIM experiments., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)

Objective: The aim of this study was to evaluate the QIAstat-Dx® Respiratory SARS-CoV-2 Panel (QIAstat-SARS-CoV-2), which is a closed, fully automated, multiplex polymerase chain reaction (PCR) assay that detects severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and 21 other pathogens that cause respiratory disease., Methods: Nasopharyngeal swabs from patients with or suspected of having coronavirus disease 2019 were collected and tested at Bichat-Claude Bernard Hospital, Paris, France. Using the World Health Organisation-approved real-time-PCR assay developed by the Charité Institute of Virology as the reference, positive percent agreement (PPA) and negative percent agreement (NPA) were calculated., Results: In total, 189 negative and 88 positive samples were analyzed. QIAstat-SARS-CoV-2 had an NPA of 90.48% (95% confidence interval (CI), 85.37%, 94.26%) and a PPA of 94.32% (95% CI, 87.24%, 98.13%). Co-infections were detected by QIAstat-SARS-CoV-2 in 4/277 specimens. The methods exhibited comparable failure rates (23/307 [7.5%] vs. 6/298 [2.0%] for QIAstat-SARS-CoV-2 and reference methods, respectively). The turnaround time was shorter for QIAstat-SARS-CoV-2 compared with the reference method (difference in mean -14:30 h [standard error, 0:03:23; 95% CI, -14:37, -14:24]; P < 0.001)., Conclusions: QIAstat-SARS-CoV-2 shows good agreement with the reference assay, providing faster and accurate results for detecting SARS-CoV-2., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Rapid and widespread increases in carbapenem resistance (CR) necessitate identification of risk factors to guide appropriate interventions., Objectives: We aimed to identify risk factors for CR Gram-negative infection through a systematic literature review., Data Sources: We searched MEDLINE (via OvidSP and PubMed) and Embase (via OvidSP) databases and the Cochrane Central Register of Controlled Trials., Study Eligibility Criteria: Prospective or retrospective cohort and case-control studies reporting quantitative data on risk factors associated with infections due to CR Gram-negative pathogens in hospitalized patients were eligible., Participants: Studies included hospitalized patients with CR infection caused by Gram-negative bacterial pathogens (Enterobacterales and non-fermenters)., Methods: Searches were conducted in January 2018/December 2019 to identify studies published since 2007. Risk factor data were extracted and grouped by factor. The primary metric was proportion of studies reporting a significant association with CR infection for each factor., Results: In total, 92 studies were identified. Risk factors most frequently reported as significantly associated with CR infection (>10 studies) were previous antibiotic use (91.1%; 72/79 studies); previous carbapenem use (82.6%; 57/69); previous colonization (72.7%; 8/11); mechanical ventilation (66.7%; 36/54); previous intensive care unit stay (64.4%; 38/59); dialysis (61.1%; 11/18); catheter (58.0%; 40/69); length of stay in hospital (54.5%; 30/55); comorbidities (52.7%; 39/74); APACHE II (51.7%; 15/29); and intubation (51.4%; 18/35). Risk factors were mostly consistent across different species and sites of infection., Conclusions: Several variables, particularly previous antibiotic use, are strong risk factors for CR infection. Interventions to mitigate against CR infection should target these factors., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Nephrotoxicity and neurotoxicity are commonly associated with polymyxin treatment; however, the emergence of multidrug-resistant Gram-negative bacteria with limited therapeutic options has resulted in increased use of polymyxins., Objectives: To determine the rates of nephrotoxicity and neurotoxicity during polymyxin treatment and whether any factors influence these., Data Sources: Medline, Embase and Cochrane Library databases were searched on 2 January 2020., Study Eligibility Criteria: Studies reporting nephrotoxicity and/or neurotoxicity rates in patients with infections treated with polymyxins were included. Reviews, meta-analyses and reports not in English were excluded., Participants: Patients hospitalized with infections treated with systemic or inhaled polymyxins were included. For comparative analyses, patients treated with non-polymyxin-based regimens were also included., Methods: Meta-analyses were performed using a random-effects model; subgroup meta-analyses were conducted where data permitted using a mixed-effects model., Results: In total, 237 reports of randomized controlled trials, cohort and case-control studies were eligible for inclusion; most were single-arm observational studies. Nephrotoxic events in 35,569 patients receiving polymyxins were analysed. Overall nephrotoxicity rate was 0.282 (95% confidence interval (CI) 0.259-0.307). When excluding studies where >50% of patients received inhaled-only polymyxin treatment or nephrotoxicity assessment was by methods other than internationally recognized criteria (RIFLE, KDIGO or AKIN), the nephrotoxicity rate was 0.391 (95% CI 0.364-0.419). The odds of nephrotoxicity were greater with polymyxin therapies compared to non-polymyxin-based regimens (odds ratio 2.23 (95% CI 1.58-3.15); p < 0.001). Meta-analyses showed a significant effect of polymyxin type, dose, patient age, number of concomitant nephrotoxins and use of diuretics, glycopeptides or vasopressors on the rate of nephrotoxicity. Polymyxin therapies were not associated with a significantly different rate of neurotoxicity than non-polymyxin-based regimens (p 0.051). The overall rate of neurotoxicity during polymyxin therapy was 0.030 (95% CI 0.020-0.043)., Conclusions: Polymyxins are associated with a higher risk of nephrotoxicity than non-polymyxin-based regimens., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic. Disease diagnosis, appropriate clinical management and infection control are all important factors in controlling the spread of SARS-CoV-2. The QIAreach™ Anti-SARS-CoV-2 Total Test (Anti-CoV2) is a rapid, qualitative serological test, using proprietary nanoparticle fluorescence technology to detect total antibody (IgA, IgM, and IgG) against SARS-CoV-2. Here we report the results of the US Food and Drug Administration (FDA) clinical agreement study. Thirty positive plasma or serum samples were taken from consenting individuals with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection ≥14 days from symptom onset. Seventy-five samples from before the believed circulation of SARS-CoV-2 (November 1, 2019) were used to assess specificity. Positive percent agreement (PPA) and negative percent agreement (NPA) were calculated along with the corresponding exact two-sided 95 % confidence intervals (CI) using an FDA Emergency Use Authorized PCR test as the reference method. Anti-CoV2 was shown to have 100 % sensitivity (PPA; 95 % CI 88.4-100 %) and 100 % specificity (NPA; 95 % CI 95.2-100 %). Against 157 pre-pandemic samples, no cross-reactivity was observed with seasonal coronaviruses or other respiratory pathogens tested. Additionally, no interference was observed when samples were spiked with: conjugated bilirubin 0.4 mg/ml; unconjugated bilirubin 0.4 mg/ml; hemoglobin 5 mg/ml; prednisolone 0.12 mg/ml; triglycerides 15 mg/ml. In conclusion, Anti-CoV2 provides accurate qualitative detection of total antibodies against SARS-CoV-2., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

We investigated the impact of appropriate versus inappropriate initial antimicrobial therapy on the clinical outcomes of patients with severe bacterial infections as part of a systematic review and meta-analyses assessing the impact of delay in appropriate antimicrobial therapy. Literature searches of MEDLINE and Embase, conducted on 24 July 2018, identified studies published after 2007 reporting the impact of delay in appropriate antibiotic therapy for hospitalised adult patients with bacterial infections. Results were statistically pooled for outcomes including mortality, hospital length of stay (LOS) and treatment failure. Subgroup analyses were explored by site of infection where data permitted. Inclusion criteria were met by 145 studies, of which 114 reported data on the impact of appropriate versus inappropriate initial therapy. In the pooled analysis, rates of mortality were significantly in favour of appropriate therapy [odds ratio (OR) = 0.44, 95% CI 0.38-0.50]. Across eight studies, LOS was shorter with appropriate therapy compared with inappropriate therapy [mean difference (MD) -2.54 days (95% CI -5.30 to 0.23)], but not significantly so. The incidence of treatment failure was significantly lower in patients who received appropriate therapy compared with patients who received inappropriate therapy (six studies: OR = 0.33, 95% CI 0.16-0.66) as was mean hospital costs (four studies: MD -7.38 thousand US$ or Euros, 95% CI -14.14 to -0.62). Initiation of appropriate versus inappropriate antibiotics can reduce mortality, reduce treatment failure and decrease LOS, highlighting the importance of broad‑spectrum empirical therapy and rapid diagnostics for early identification of the causative pathogen. [Study registration: PROSPERO: CRD42018104669]., (Copyright © 2020. Published by Elsevier Ltd.)

Background: The ability to predict likely prognosis and infectiousness for patients with COVID-19 would aid patient management decisions. Diagnosis is usually via real-time PCR, and it is unclear whether the semi-quantitative capability of this method, determining viral load through cycle threshold (Ct) values, can be leveraged., Objectives: We aim to review available knowledge on correlations between SARS-COV-2 Ct values and patient- or healthcare-related outcomes to determine whether Ct values provide useful clinical information., Sources: A PubMed search was conducted on 1 June 2020 based on a search strategy of (Ct value OR viral load) AND SARS-CoV-2. Data were extracted from studies reporting on the presence or absence of an association between Ct values, or viral loads determined via Ct value, and clinical outcomes., Content: Data from 18 studies were relevant for inclusion. One study reported on the correlation between Ct values and mortality and one study reported on the correlation between Ct values and progression to severe disease; both reported a significant association (p < 0.001 and p = 0.008, respectively). Fourteen studies reported on the correlation between Ct value or viral loads determined via Ct value and disease severity, and an association was observed in eight (57%) studies. Studies reporting on the correlation of viral load with biochemical and haematological markers showed an association with at least one marker, including increased lactate dehydrogenase (n = 4), decreased lymphocytes (n = 3) and increased high-sensitivity troponin I (n = 2). Two studies reporting on the correlation with infectivity showed that lower Ct values were associated with higher viral culture positivity., Implications: Data suggest that lower Ct values may be associated with worse outcomes and that Ct values may be useful in predicting the clinical course and prognosis of patients with COVID-19; however, further studies are warranted to confirm clinical value.

The original article can be found online.

Background: Patients with severe bacterial infections often experience delay in receiving appropriate treatment. Consolidated evidence of the impact of delayed appropriate treatment is needed to guide treatment and improve outcomes., Research Question: What is the impact of delayed appropriate antibacterial therapy on clinical outcomes in patients with severe bacterial infections?, Study Design and Methods: Literature searches of MEDLINE and Embase, conducted on July 24, 2018, identified studies published after 2007 reporting the impact of delayed appropriate therapy on clinical outcomes for hospitalized adult patients with bacterial infections. Where appropriate, results were pooled and analyzed with delayed therapy modeled three ways: delay vs no delay in receiving appropriate therapy; duration of delay; and inappropriate vs appropriate initial therapy. This article reports meta-analyses on the effect of delay and duration of delay., Results: The eligibility criteria were met by 145 studies, of which 37 contributed data to analyses of effect of delay. Mortality was significantly lower in patients receiving appropriate therapy without delay compared with those experiencing delay (OR, 0.57; 95% CI, 0.45-0.72). Mortality was also lower in the no-delay group compared with the delay group in subgroups of studies reporting mortality at 20 to 30 days, during ICU stay, or in patients with bacteremia (OR, 0.57 [95% CI, 0.43-0.76]; OR, 0.47 [95% CI, 0.27-0.80]; and OR, 0.54 [95% CI, 0.40-0.75], respectively). No difference was found in time to appropriate therapy between those who died and those who survived (P = .09), but heterogeneity between studies was high., Interpretation: Avoiding delayed appropriate therapy is essential to reduce mortality in patients with severe bacterial infections., Clinical Trial Registration: PROSPERO; No.: CRD42018104669; URL: www.crd.york.ac.uk/prospero/., (Copyright © 2020. Published by Elsevier Inc.)

Objectives: Many carbapenem-resistant (CR) Gram-negative (GN) pathogens exhibit MDR, meaning few therapeutic options are available for CR-GN infections. Cefiderocol, a siderophore cephalosporin, has demonstrated in vitro efficacy against CR-GN bacteria. In the SIDERO-CR-2014-2016 surveillance study, European clinical isolates comprising carbapenem-non-susceptible (CarbNS) Enterobacterales and MDR non-fermenters were tested against cefiderocol and comparators., Methods: Cefiderocol MICs were determined using iron-depleted CAMHB, and comparators using CAMHB, per recommended CLSI methodology. Carbapenemase gene profiles were determined using PCR., Results: Isolates ( N =  870) from 23 European countries comprised CarbNS Enterobacterales ( n =  457), MDR Pseudomonas aeruginosa ( n =  177) and MDR Acinetobacter baumannii ( n =  236). The most common carbapenemases were KPC (52%), OXA-48-like (19%), VIM (14%) and NDM (8%) in Enterobacterales, VIM (41%) in P. aeruginosa and OXA-23-like (57%) and OXA-24/40-like (37%) in A. baumannii . Most carbapenemase-producing isolates (65%) co-carried ESBLs. Approximately half of P. aeruginosa isolates were negative for carbapenemases, compared with 10% of Enterobacterales and 3% of A. baumannii . A similar proportion of Enterobacterales were susceptible to cefiderocol (81.6%; 79.0% of VIM producers; 51.4% of NDM producers; based on EUCAST breakpoint values) compared with comparator antimicrobial agents, including colistin (76.4%; 93.5% of VIM producers; 78.4% of NDM producers) and ceftazidime/avibactam (76.6%; 1.6% of VIM producers; 2.7% of NDM producers). Of P. aeruginosa isolates, 98.3% were susceptible to cefiderocol (100% of VIM producers), similar to colistin (100%). Against A. baumannii , 94.9% had cefiderocol MIC ≤2 mg/L and 93.6% of isolates were susceptible to colistin., Conclusions: Cefiderocol demonstrated potent activity against CarbNS and MDR GN bacteria, including non-fermenters and a wide variety of MBL- and serine-β-lactamase-producing strains., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)

There is a lack of consensus regarding management of infections with carbapenem- resistant Gram-negative (CR-GN) pathogens. This study comprised a medical chart review to assess patient management in a high CR prevalence setting. Data was collated retrospectively from medical records of patients hospitalized between November 1 st , 2015 and October 31 st , 2016. Of 29 patients, 66% had respiratory tract infections. Median duration of hospitalization was 28 days and ~50% of patients were admitted to the intensive care unit, with 77% remaining for >2 weeks. Median time to obtain respiratory culture results was 5 days. Isolation of patients with diagnosed CR-GN infection took ≥5 days in >50% of patients. A majority (76%) of patients received ≥1 antibiotic before providing a specimen for culture; a total of 17 antibiotic treatments were used. Overall, 72% of patients, and 68% of those with respiratory infections, were discharged alive; 38% were discharged without further antibiotics. The difficulties in achieving effective management in patients with CR-GN infections are largely due to complex co-morbidities, a history of prior antibiotic treatment, and multiple referrals across health care facilities., Competing Interests: Conflict of interest: GG and CV declare no conflict of interest. NP reports grants from Shionogi Ltd, during the conduct of the study. CL, MVO, KT and BC are employees of Shionogi. DM was an employee of Shionogi at the time of the analysis., (©Copyright: the Author(s).)

Objectives: In this study, five SARS-CoV-2 PCR assay panels were evaluated against the accumulated genetic variability of the virus to assess the effect on sensitivity of the individual assays., Design or Methods: As of week 21, 2020, the complete set of available SARS-CoV-2 genomes from GISAID and GenBank databases were used in this study. SARS-CoV-2 primer sequences from publicly available panels (WHO, CDC, NMDC, and HKU) and QIAstat-Dx were included in the alignment, and accumulated genetic variability affecting any oligonucleotide annealing was annotated., Results: A total of 11,627 (34.38%) genomes included single mutations affecting annealing of any PCR assay. Variations in 8,773 (25.94%) genomes were considered as high risk, whereas additional 2,854 (8.43%) genomes presented low frequent single mutations and were predicted to yield no impact on sensitivity. In case of the QIAstat-Dx SARS-CoV-2 Panel, 99.11% of the genomes matched with a 100% coverage all oligonucleotides, and critical variations were tested in vitro corroborating no loss of sensitivity., Conclusions: This analysis stresses the importance of targeting more than one region in the viral genome for SARS-CoV-2 detection to mitigate the risk of loss of sensitivity due to the unknown mutation rate during this SARS-CoV-2 outbreak., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Tuberculosis (TB) is a major cause of childhood morbidity and mortality worldwide. The aim of this review is to describe the management of the child with TB and latent tuberculosis infection (LTBI). To develop this article, a working group reviewed relevant epidemiological and other scientific studies and established practices in conducting LBTI and TB in children. The article describes how to manage the child with LTBI, considering transmission and infectiousness of tuberculosis, contact screening and prioritization of contacts and recommendations on treatment of children with LTBI and how to manage the child with TB considering the susceptibility of children to developing tuberculosis, epidemiology and classification of tuberculosis in children, diagnosis and treatment., (Copyright © 2017 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

Tuberculosis (TB) in migrants represents an important clinical and public health threat, particularly in low TB incidence countries. The current review is aimed to assess issues related to screening and treatment of migrants with latent TB infection or TB disease., (Copyright © 2017 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: This study aims to investigate the effect of country-level school life expectancy on Tuberculosis (TB) incidence to gain further understanding of substantial variation in TB incidence across Europe., Methods: An ecological study examined the prospective association between baseline country-level education in 2000 measured by school life expectancy and TB incidence in 2000-2010 in 40 countries of the WHO European region using quantile regression. Subsequently, to validate the ecological associations between education and TB incidence, an individual-level analysis was performed using case-based data in 29 EU/EEA countries from the European Surveillance System (TESSy) and simulating a theoretical control group., Results: The ecological analysis showed that baseline school life expectancy had a negative prospective association with TB incidence. We observed consistent negative effects of school life expectancy on individuals' TB infections prospectively., Conclusions: These findings suggests that country-level education is an important determinant of individual-level TB infection in the region, and in the absence of a social determinants indicator that is routinely collected for reportable infectious diseases, the adoption of country-level education for reportable infectious diseases would significantly advance the field.

Tuberculosis (TB) control programmes of many low TB incidence countries of the European Union/European Economic Area (EU/EEA) perceive challenges in controlling TB due to high numbers of TB in migrants from high-incidence countries. To assess the extent of TB transmission from the foreign-born to the native-born population, we quantitatively investigated the dynamics of TB transmission between these populations in the EU/EEA, using published molecular epidemiological studies. We searched PubMed and EMBASE databases from 1990 to August 2012. We identified 15 studies performed during 1992-2007 covering 12,366 cases, of which median (range) 49.2% (17.7%-86.4%) were foreign-born. The proportion of clustered isolates ranged between 8.5% and 49.1% of the total number of TB cases genotyped and among these, foreign-born cases were equally or more likely to have unique isolates compared to native-born cases. One third of the clusters were "mixed", i.e. composed of foreign- and native-born cases, involving 0-34.2% of all genotyped cases. Cross-transmission among foreign and native populations was bidirectional, with wide differences across studies. This systematic review provides evidence that TB in a foreign-born population does not have a significant influence on TB in the native population in EU/EEA.

Multidrug-resistant and extensively drug-resistant tuberculosis (TB) are associated with worse treatment outcomes for patients, including higher mortality, than for drug-sensitive tuberculosis. Delamanid (OPC-67683) is a novel anti-TB medication with demonstrated activity against multidrug-resistant disease. Patients who participated in the previously reported randomised, placebo-controlled trial of delamanid and the subsequent open-label extension trial were eligible to participate in a 24-month observational study designed to capture treatment outcomes. Treatment outcomes, as assessed by clinicians and defined by the World Health Organization, were categorised as favourable and unfavourable. Delamanid treatment groups were combined for analysis, based on their duration of treatment. In total, for 421 (87.5%) out of 481 patients from the original randomised controlled trial, consent was granted for follow-up assessments. Favourable outcomes were observed in 143 (74.5%) out of 192 patients who received delamanid for ≥6 months, compared to 126 (55%) out of 229 patients who received delamanid for ≤2 months. Mortality was reduced to 1.0% among those receiving long-term delamanid versus short-term/no delamanid (8.3%; p<0.001). Treatment benefit was also seen among patients with extensively drug-resistant TB. This analysis suggests that treatment with delamanid for 6 months in combination with an optimised background regimen can improve outcomes and reduce mortality among patients with both multidrug-resistant and extensively drug-resistant TB.

Treatment success measured by treatment outcome monitoring (TOM) is a key programmatic output of tuberculosis (TB) control programmes. We performed a systematic literature review on national-level TOM in the 30 European Union (EU)/European Economic Areas (EEA) countries to summarise methods used to collect and report data on TOM. Online reference bibliographic databases PubMed/MEDLINE and EMBASE were searched to identify relevant indexed and non-indexed literature published between January 2000 and August 2010. The search strategy resulted in 615 potentially relevant indexed citations, of which 27 full-text national studies (79 data sets) were included for final analysis. The selected studies were performed in 10 EU/EEA countries and gave a fragmented impression of TOM in the EU/EEA. Publication year, study period, sample size, databases, definitions, variables, patient and outcome categories, and population subgroups varied widely, portraying a very heterogeneous picture. This review confirmed previous reports of considerable heterogeneity in publications of TOM results across EU/EEA countries. PubMed/MEDLINE and EMBASE indexed studies are not a suitable instrument to measure representative TOM results for the 30 EU/EEA countries. Uniform and complete reporting to the centralised European Surveillance System will produce the most timely and reliable results of TB treatment outcomes in the EU/EEA.

The use of fluoroquinolones (FQs) to treat lower respiratory tract infections (LTRI) other than tuberculosis (TB) allows selection of FQ-resistant TB when TB is misdiagnosed. This study maps national guidelines on the use of FQs for LRTI in Europe and determines the risk of FQ-resistant TB upon FQ treatment before TB diagnosis. A questionnaire was developed to map existing national LRTI and community-acquired pneumonia (CAP) guidelines. A systematic review and meta-analysis were performed to determine the risk of FQ-resistant TB if prescribed FQs prior to TB diagnosis. 15 (80%) out of 24 responding European Respiratory Society national delegates reported having national LRTI management guidelines, seven including recommendations on FQ use and one recommending FQs as the first-choice drug. 18 out of 24 countries had national CAP management guidelines, two recommending FQ as the drug of choice. Six studies investigating FQ exposure and the risk of FQ-resistant TB were analysed. TB patients had a three-fold higher risk of having FQ-resistant TB when prescribed FQs before TB diagnosis, compared to non FQ-exposed patients (OR 2.81, 95% CI 1.47-5.39). Although the majority of European countries hold national LRTI/CAP guidelines, our results suggest that a risk of developing FQ resistance exists. Further strengthening of, and adherence to, guidelines is needed to ensure rational use of FQs.

Tuberculosis (TB) is considered to be a disease of poverty, since its incidence is exacerbated by socioeconomic factors, inconsistent or partial treatment practices, and immigration from endemic countries. A prospective country level study, using a comprehensive dataset of TB incidence and prevalence taken from countries within the World Health Organization (WHO) European region, was conducted. We employed quintile regression to investigate the prospective association between baseline (measured in 2000) and a nation's wealth, level of egalitarianism, migration rate, health-related lifestyle and social capital with TB incidence and prevalence over a 10-yr period (2000-2009). We found that ∼50% of TB variation is accounted for by a nation's wealth and level of egalitarianism. We observed a negative prospective association between logged gross domestic product and TB rates, and a positive prospective association between income inequality and TB. National income levels per capita and income inequality are important predictors for TB incidence and prevalence in the WHO European region. They account for 50% of country-level variation, indicating the importance of a combined absolute and relative socioeconomic disadvantage in the development of TB. These findings also provide a tool for forecasting potential fluctuations in the level of TB epidemics in the WHO European region, with respect to socioeconomic changes.

We conducted a systematic review and meta-analysis to assess the evidence for the postulation that inappropriate tuberculosis (TB) regimens are a risk for development of multidrug-resistant (MDR)-TB. MEDLINE, EMBASE and other databases were searched for relevant articles in January 2011. Cohort studies including TB patients who received treatment were selected and data on treatment regimen, drug susceptibility testing results and genotyping results before treatment and at failure or relapse were abstracted from the articles. Four studies were included in the systematic review and two were included in the meta-analysis. In these two studies the risk of developing MDR-TB in patients who failed treatment and used an inappropriate treatment regimen was increased 27-fold (RR 26.7, 95% CI 5.0-141.7) when compared with individuals who received an appropriate treatment regimen. This review provides evidence that supports the general opinion that the development of MDR-TB can be caused by inadequate treatment, given the drug susceptibility pattern of the Mycobacterium tuberculosis bacilli. It should be noted that only two studies provided data for the meta-analysis. The information can be used to advocate for adequate treatment for patients based on drug resistance profiles.

Treating tuberculosis (TB) patients with inappropriate treatment regimens can lead to treatment failure and, thus, patients who have not been cured and/or to the development of (multi)-drug resistance. A systematic review was performed to assess the knowledge of appropriate TB drug regimens among all categories of healthcare workers (HCWs). In January 2011, MEDLINE, EMBASE and other databases were searched for relevant articles. Observational studies published as of the year 2000 that assessed HCW knowledge of TB treatment were selected. A treatment regimen, drug dosage or treatment duration was considered inappropriate if it was not recommended by national guidelines or by the World Health Organization (WHO). Of 1,896 studies, 31 were included from 14 different countries. No study was performed in Europe. In all studies, HCWs with inappropriate knowledge of treatment regimens (8-100%) or treatment duration (5-99%) were observed. The few studies providing detailed data showed that HCWs mainly reported giving treatment regimens with too many drugs and for too long. Knowledge of appropriate doses was also insufficient in most studies. The available studies show that there is a lack of knowledge of national or international TB treatment guidelines and recommendations. Generalisation of the findings to other settings and countries should be done with caution.

A potential threat to the success of new tuberculosis (TB) drugs is the development of resistance. Using drugs in appropriate regimens, such as those recommended in the World Health Organization (WHO) treatment guidelines, prevents the development of resistance. We performed a systematic review to assess the prevalence of inappropriate prescription of TB drugs for the treatment of TB. MEDLINE, EMBASE and other databases were searched for relevant articles in January 2011. Observational studies published from 2000 that included TB patients receiving treatment were selected. A treatment regimen was considered inappropriate if the regimen was not a WHO recommended regimen. 37 studies were included. Inappropriate treatment regimens were prescribed in 67% of studies. The percentage of patients receiving inappropriate regimens varied between 0.4% and 100%. In 19 studies the quality of treatment regimen reporting was low. Despite the fact that assessment of inappropriate treatment was hampered by low quality of reporting, our data indicate a reasonable amount of inappropriate prescription of TB treatment regimens. Thus, there is a risk that new drugs will be used in inappropriate treatment regimens, even with WHO guidelines in place, introducing the risk of resistance development. This article highlights the need to improve implementation of the WHO treatment of TB guidelines.

The European Centre for Disease Prevention and Control (ECDC) and the European Respiratory Society (ERS) jointly developed European Union Standards for Tuberculosis Care (ESTC) aimed at providing European Union (EU)-tailored standards for the diagnosis, treatment and prevention of tuberculosis (TB). The International Standards for TB Care (ISTC) were developed in the global context and are not always adapted to the EU setting and practices. The majority of EU countries have the resources and capacity to implement higher standards to further secure quality TB diagnosis, treatment and prevention. On this basis, the ESTC were developed as standards specifically tailored to the EU setting. A panel of 30 international experts, led by a writing group and the ERS and ECDC, identified and developed the 21 ESTC in the areas of diagnosis, treatment, HIV and comorbid conditions, and public health and prevention. The ISTCs formed the basis for the 21 standards, upon which additional EU adaptations and supplements were developed. These patient-centred standards are targeted to clinicians and public health workers, providing an easy-to-use resource, guiding through all required activities to ensure optimal diagnosis, treatment and prevention of TB. These will support EU health programmes to identify and develop optimal procedures for TB care, control and elimination.

In spite of the growing awareness of emerging drug-resistant Mycobacterium tuberculosis, the extent of inappropriate tuberculosis (TB) case management may be underestimated, even in Europe. We evaluated TB case management in the European Union/European Economic Area countries, with special focus on multidrug-resistant (MDR) and extensively drug-resistant (XDR)-TB, using a purposely developed, standardised survey tool. National reference centres in five countries representing different geographical, socioeconomic and epidemiological patterns of TB in Europe were surveyed. 40 consecutive, original clinical TB case records (30 MDR/XDR-TB cases) were reviewed in each of the five countries. The findings were recorded and, through the survey tool, compared with previously agreed and identified international standards. Deviations from international standards of TB care were observed in the following areas: surveillance (no information available on patient outcomes); infection control (lack of respiratory isolation rooms/procedures and negative-pressure ventilation rooms); clinical management of TB, MDR-TB and HIV co-infection (inadequate bacteriological diagnosis, regimen selection and treatment duration); laboratory support; and diagnostic/treatment algorithms. Gaps between present international standards of care and the management of MDR/XDR-TB patients were identified. Training, increased awareness, promotion of standards and allocation of appropriate resources are necessary to ensure appropriate care and management as well as to prevent further emergence of drug resistance.

Background: Existing international guidelines provide different recommendations for the management of contacts of multidrug-resistant tuberculosis (MDR-TB) patients., Objective: To conduct two systematic reviews with the aim of identifying chemoprophylactic approaches that are effective in contacts of MDR-TB patients to assist in policy making., Design: We systematically searched the Medline, Embase, Central, LILACS, TRIP and BIOSIS Preview databases for studies on the effectiveness of anti-tuberculosis drugs in preventing active TB in persons at risk of developing MDR-TB. This was done as an update of a systematic review from 2006 using the same methodology. In addition, we searched for studies including persons at risk of developing TB after exposure to non-MDR-TB patients who were treated with anti-tuberculosis drugs other than isoniazid or rifampicin., Results: Of 1195 references assessed in the update, one additional study could be included. As the initial review included two studies, the total number of included studies equals three. One study reported no contacts who developed TB, whether or not they received prophylaxis. The other two studies showed non-significant risk differences of 4% (95%CI -3 to 12), and 5% (95%CI -2 to 11), both in favour of chemoprophylaxis. For the additional review, 2480 references were assessed, but none could be included., Conclusion: The attention given to MDR-TB in recent years has not resulted in publications on preventive treatment for contacts of MDR-TB patients. The available evidence is not sufficient to support or reject preventive treatment. Furthermore, the combined available evidence is of very low quality.