Xpert MTB/RIF ultra for rapid diagnosis of extrapulmonary tuberculosis in a high‑income low‑tuberculosis prevalence setting

The diagnosis of extrapulmonary tuberculosis (EPTB) is often challenging due to paucibacillary nature of the disease. Xpert MTB/RIF Ultra (Ultra) has been developed to improve detection of Mycobacterium tuberculosis complex (MTC) in paucibacillary specimens. The objective of the study was to assess the performance of Ultra for the diagnosis of EPTB in a high-income low TB prevalence country. Extrapulmonary samples received for TB diagnostics at two hospitals in Norway between January 2015 and January 2016 were prospectively and consecutively included. Defrosted samples were subjected to Ultra. Culture and routine PCR tests were used as reference standard. A total of 82 samples, 10 culture and/or routine PCR positive (confirmed TB) samples and 72 culture and routine PCR negative samples were included in analysis. The overall sensitivity and specificity of Ultra were 90% (9/10, 95% CI 56–100) and 99% (71/72, 95% CI 93–100), respectively. Ultra was positive in 6/7 smear negative confirmed TB samples. To conclude, Ultra showed a high sensitivity and specificity in extrapulmonary specimens and may contribute to a rapid diagnosis of EPTB in a low TB prevalence setting.publishedVersio

Risk assessment and antibody responses to SARS-CoV-2 in healthcare workers

Background: Preventing infection in healthcare workers (HCWs) is crucial for protecting healthcare systems during the COVID-19 pandemic. Here, we investigated the seroepidemiology of SARS-CoV-2 in HCWs in Norway with low-transmission settings. Methods: From March 2020, we recruited HCWs at four medical centres. We determined infection by SARS-CoV-2 RT-PCR and serological testing and evaluated the association between infection and exposure variables, comparing our findings with global data in a meta-analysis. Anti-spike IgG antibodies were measured after infection and/or vaccination in a longitudinal cohort until June 2021. Results: We identified a prevalence of 10.5% (95% confidence interval, CI: 8.8–12.3) in 2020 and an incidence rate of 15.0 cases per 100 person-years (95% CI: 12.5–17.8) among 1,214 HCWs with 848 person-years of follow-up time. Following infection, HCWs (n = 63) mounted durable anti-spike IgG antibodies with a half-life of 4.3 months since their seropositivity. HCWs infected with SARS-CoV-2 in 2020 (n = 46) had higher anti-spike IgG titres than naive HCWs (n = 186) throughout the 5 months after vaccination with BNT162b2 and/or ChAdOx1-S COVID-19 vaccines in 2021. In a meta-analysis including 20 studies, the odds ratio (OR) for SARS-CoV-2 seropositivity was significantly higher with household contact (OR 12.6; 95% CI: 4.5–35.1) and occupational exposure (OR 2.2; 95% CI: 1.4–3.2). Conclusion: We found high and modest risks of SARS-CoV-2 infection with household and occupational exposure, respectively, in HCWs, suggesting the need to strengthen infection prevention strategies within households and medical centres. Infection generated long-lasting antibodies in most HCWs; therefore, we support delaying COVID-19 vaccination in primed HCWs, prioritising the non-infected high-risk HCWs amid vaccine shortage.publishedVersio

The Performances of Three Commercially Available Assays for the Detection of SARS‐CoV‐2 Antibodies at Different Time Points Following SARS‐CoV‐2 Infection

The aim of this study was to evaluate the performances of three commercially available antibody assays for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies at different time points following SARS-CoV-2 infection. Sera from 536 cases, including 207 SARS-CoV-2 PCR positive, were tested for SARS-CoV-2 antibodies with the Wantai receptor binding domain (RBD) total antibody assay, Liaison S1/S2 IgG assay and Alinity i nucleocapsid IgG assay and compared to a two-step reference ELISA (SARS-CoV-2 RBD IgG and SARS-CoV-2 spike IgG). Diagnostic sensitivity, specificity, predictive values and Cohen’s kappa were calculated for the commercial assays. The assay’s sensitivities varied greatly, from 68.7% to 95.3%, but the specificities remained high (96.9%–99.1%). The three tests showed good performances in sera sampled 31 to 60 days after PCR positivity compared to the reference ELISA. The total antibody test performed better than the IgG tests the first 30 days and the nucleocapsid IgG test showed reduced sensitivity two months or more after PCR positivity. Hence, the test performances at different time points should be taken into consideration in clinical practice and epidemiological studies. Spike or RBD IgG tests are preferable in sera sampled more than two months following SARS-CoV-2 infection.publishedVersio

Attitudes and self-efficacy towards infection prevention and control and antibiotic stewardship among nurses : a mixed-methods study

Aims: To gain a comprehensive understanding of nurses' infection control practices, antibiotics stewardship attitudes and self-efficacy when caring for patients with multidrug-resistant bacterial infections in a hospital setting. Background: Multidrug-resistant bacteria cause a substantial health burden by complicating infections and prolonging hospital stays. Attitudes and self-efficacy can inform professional behaviour. Nurses' attitudes and self-efficacy concerning multidrug-resistant bacteria, infection prevention and control and antibiotic stewardship are vital in keeping patients safe. Design: A descriptive and convergent mixed-methods design involving quantitative and qualitative approaches was used. Methods: Two hundred and seventeen nurses working in clinical practice at seven different hospital wards (i.e., general medicine, surgical, haematological and oncology) at a Norwegian university hospital were invited to participate. Data were collected in February and March 2020 via two questionnaires: the Multidrug-Resistant Bacteria Attitude Questionnaire and the General Perceived Self-Efficacy Scale (n = 131) and four focus group interviews (n = 22). The data were analysed using descriptive statistics and systematic text condensation. Results: Most nurses showed moderate knowledge, adequate behavioural intentions towards infection prevention and antibiotic stewardship, and high self-efficacy. However, they reported negative emotions towards their knowledge level and negative emotions towards nursing care. The nurses appeared uncertain about their professional influence and role in antibiotic stewardship practices. Organisational and relational challenges and ambivalent perceptions of nurses' role were potential explanations. Conclusion: Nurses report moderate attitudes and high self-efficacy when caring for patients with multidrug-resistant bacterial infections. This study suggests that nurses experience organisational and relational factors in their work environment that challenge their attitudes towards infection prevention and control and antibiotic stewardship practices. Measures that strengthen their knowledge and emotional response underpin correct infection prevention and control behaviour. A role clarification is needed for antibiotic stewardship.publishedVersio

Xpert MTB/RIF ultra for rapid diagnosis of extrapulmonary tuberculosis in a high‑income low‑tuberculosis prevalence setting

The diagnosis of extrapulmonary tuberculosis (EPTB) is often challenging due to paucibacillary nature of the disease. Xpert MTB/RIF Ultra (Ultra) has been developed to improve detection of Mycobacterium tuberculosis complex (MTC) in paucibacillary specimens. The objective of the study was to assess the performance of Ultra for the diagnosis of EPTB in a high-income low TB prevalence country. Extrapulmonary samples received for TB diagnostics at two hospitals in Norway between January 2015 and January 2016 were prospectively and consecutively included. Defrosted samples were subjected to Ultra. Culture and routine PCR tests were used as reference standard. A total of 82 samples, 10 culture and/or routine PCR positive (confirmed TB) samples and 72 culture and routine PCR negative samples were included in analysis. The overall sensitivity and specificity of Ultra were 90% (9/10, 95% CI 56–100) and 99% (71/72, 95% CI 93–100), respectively. Ultra was positive in 6/7 smear negative confirmed TB samples. To conclude, Ultra showed a high sensitivity and specificity in extrapulmonary specimens and may contribute to a rapid diagnosis of EPTB in a low TB prevalence setting

Microbial risk factors for treatment failure of pivmecillinam in community‐acquired urinary tract infections caused by ESBL‐producing Escherichia coli

The aim of this study was to identify microbial risk factors for treatment failure of pivmecillinam in community‐acquired urinary tract infections (ca‐UTIs) caused by ESBL‐producing Escherichia coli. Eighty‐nine ESBL‐producing E. coli isolated from women suffering from ca‐UTIs were included. The susceptibilities to mecillinam were determined using MIC gradient strip. Whole genome sequencing was performed on a MiSeq platform, and genome assembly was performed using SPAdes v3.11.0. Neither mecillinam MICs nor ESBL genotypes were associated with treatment outcome of patients treated with pivmecillinam. Specific STs, however, showed significant differences in treatment outcome. Patients infected with ST131 were more likely to experience treatment failure compared to patients infected with non‐ST131 (p 0.02) when adjusted for pivmecillinam dose, mecillinam MIC and severity of infection. Patients infected with ST69 were more often successfully treated compared to patients infected with non‐ST69 (p 0.04). Patients infected with blaCTX‐M‐15 ST131 strains were more likely to experience treatment failure than those infected with non‐blaCTX‐M‐15 ST131 strains (p 0.02). The results suggest that specific STs are associated with the clinical efficacy of pivmecillinam. Further studies with a larger number of strains, including a larger number of mecillinam resistant strains, are needed to confirm these results

Microbial risk factors for treatment failure of pivmecillinam in community‐acquired urinary tract infections caused by ESBL‐producing Escherichia coli

The aim of this study was to identify microbial risk factors for treatment failure of pivmecillinam in community‐acquired urinary tract infections (ca‐UTIs) caused by ESBL‐producing Escherichia coli. Eighty‐nine ESBL‐producing E. coli isolated from women suffering from ca‐UTIs were included. The susceptibilities to mecillinam were determined using MIC gradient strip. Whole genome sequencing was performed on a MiSeq platform, and genome assembly was performed using SPAdes v3.11.0. Neither mecillinam MICs nor ESBL genotypes were associated with treatment outcome of patients treated with pivmecillinam. Specific STs, however, showed significant differences in treatment outcome. Patients infected with ST131 were more likely to experience treatment failure compared to patients infected with non‐ST131 (p 0.02) when adjusted for pivmecillinam dose, mecillinam MIC and severity of infection. Patients infected with ST69 were more often successfully treated compared to patients infected with non‐ST69 (p 0.04). Patients infected with blaCTX‐M‐15 ST131 strains were more likely to experience treatment failure than those infected with non‐blaCTX‐M‐15 ST131 strains (p 0.02). The results suggest that specific STs are associated with the clinical efficacy of pivmecillinam. Further studies with a larger number of strains, including a larger number of mecillinam resistant strains, are needed to confirm these results

Diagnosis of extrapulmonary tuberculosis using the MPT64 antigen detection test in a high-income low tuberculosis prevalence setting

Background Extrapulmonary tuberculosis (EPTB) poses diagnostic challenges due to the paucibacillary nature of the disease. The immunochemistry-based MPT64 antigen detection test (MPT64 test) has shown promising results for diagnosing EPTB in previous studies performed in low-resource settings, with higher sensitivity than microscopy and culture. The aim of this study was to investigate the performance of the MPT64 test in a routine clinical setting in a high-income low TB prevalence country. Methods Extrapulmonary samples sent for TB diagnostics to microbiology and pathology laboratories at three regional tertiary care hospitals in Norway in a one-year period were included and subjected to the MPT64 test in parallel to the routine TB diagnostic tests. Results Samples from 288 patients were included and categorised as confirmed TB cases (n = 26), clinically diagnosed TB cases (n = 5), non-TB cases (n = 243) and uncategorised (n = 14), using a composite reference standard (CRS). In formalin-fixed biopsies, the sensitivity (95% CI) of the MPT64 test, microscopy, PCR-based tests pooled, and culture was 37% (16–62), 20% (4–48), 37% (16–62) and 50% (23–77), respectively, against the CRS. The MPT64 test showed a good positive predictive value (88%) and an excellent specificity (99, 95% CI 92–100) in formalin-fixed biopsies. In fine-needle aspirates, pus and fluid samples, the test performance was lower. Conclusions The MPT64 test was implementable in pathology laboratories as part of routine diagnostics, and although the sensitivity of the MPT64 test was not better than culture in this setting, the test supplements other rapid diagnostic methods, including microscopy and PCR-based tests, and can contribute to strengthen the diagnosis of EPTB in formalin-fixed biopsies in the absence of culture confirmation

Pyrazinamide Resistance among South African Multidrug-Resistant Mycobacterium tuberculosis Isolates▿

Pyrazinamide is important in tuberculosis treatment, as it is bactericidal to semidormant mycobacteria not killed by other antituberculosis drugs. Pyrazinamide is also one of the cornerstone drugs retained in the treatment of multidrug-resistant tuberculosis (MDR-TB). However, due to technical difficulties, routine drug susceptibility testing of Mycobacterium tuberculosis for pyrazinamide is, in many laboratories, not performed. The objective of our study was to generate information on pyrazinamide susceptibility among South African MDR and susceptible M. tuberculosis isolates from pulmonary tuberculosis patients. Seventy-one MDR and 59 fully susceptible M. tuberculosis isolates collected during the national surveillance study (2001 to 2002, by the Medical Research Council, South Africa) were examined for pyrazinamide susceptibility by the radiometric Bactec 460 TB system, pyrazinamidase activity (by Wayne's assay), and sequencing of the pncA gene. The frequency of pyrazinamide resistance (by the Bactec system) among the MDR M. tuberculosis isolates was 37 of 71 (52.1%) and 6 of 59 (10.2%) among fully sensitive isolates. A total of 25 unique mutations in the pncA gene were detected. The majority of these were point mutations that resulted in amino acid substitutions. Twenty-eight isolates had identical mutations in the pncA gene, but could be differentiated from each other by a combination of the spoligotype patterns and 12 mycobacterial interspersed repetitive-unit loci. A high proportion of South African MDR M. tuberculosis isolates were resistant to pyrazinamide, suggesting an evaluation of its role in patients treated previously for tuberculosis as well as its role in the treatment of MDR-TB

Stratification by interferon-γ release assay level predicts risk of incident TB

Introduction Targeted testing and treatment of latent TB infection (LTBI) are priorities on the global health agenda, but LTBI management remains challenging. We aimed to evaluate the prognostic value of the QuantiFERON TB-Gold (QFT) test for incident TB, focusing on the interferon (IFN)-γ level, when applied in routine practice in a low TB incidence setting. Methods In this large population-based prospective cohort, we linked QFT results in Norway (1 January 2009–30 June 2014) with national registry data (Norwegian Surveillance System for Infectious Diseases, Norwegian Prescription Database, Norwegian Patient Registry and Statistics Norway) to assess the prognostic value of QFT for incident TB. Participants were followed until 30 June 2016. We used restricted cubic splines to model non-linear relationships between IFN-γ levels and TB, and applied these findings to a competing risk model. Results The prospective analyses included 50 389 QFT results from 44 875 individuals, of whom 257 developed TB. Overall, 22% (n=9878) of QFT results were positive. TB risk increased with the IFN-γ level until a plateau level, above which further increase was not associated with additional prognostic information. The HRs for TB were 8.8 (95% CI 4.7 to 16.5), 19.2 (95% CI 11.6 to 31.6) and 31.3 (95% CI 19.8 to 49.5) times higher with IFN-γ levels of 0.35 to 4.00 IU/mL, respectively, compared with negative tests (<0.35 IU/mL). Conclusions Consistently, QFT demonstrates increased risk of incident TB with rising IFN-γ concentrations, indicating that IFN-γ levels may be used to guide targeted treatment of LTBI