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. No Patient or Public Contribution. RELEVANCE TO CLINICAL PRACTICE: Measures to increase attitudes towards infection prevention and control, antibiotic stewardship and multidrug resistance is recommended. Measures should be taken to overcome organisational challenges. A clarification of the nurses' role in antibiotic stewardship is needed.

A man in his fifties with dry cough and pleural effusion. / En mann i 50-årene med tørrhoste og pleuravæske.

BACKGROUND: Pulmonary tuberculosis is a major public health issue worldwide and is frequently overlooked, particularly in our part of the world. More caution with regard to symptoms could facilitate faster diagnosis, better treatment, and decreased morbidity and mortality. CASE PRESENTATION: We describe the disease course in a middle-aged man presenting with non-productive cough, right-sided pleural effusion and fatigue. Approximately 3 months passed before he was diagnosed with pulmonary tuberculosis and pleuritis. Because of his mild symptoms and non-specific radiographic findings, he was initially treated with antibiotics covering typical and atypical pneumonia, resulting in some improvement which led to a delay in diagnosis. Thoracic CT examination eventually revealed right upper lobe cavitation, increasing right-sided pleural effusion, right-sided mediastinal and hilar lymphadenopathy, and thickened right-sided pleura and pericardium. Induced sputum samples confirmed growth of M. tuberculosis, the mycobacterium tuberculosis complex was confirmed with PCR analysis, and direct microscopy showed acid-fast bacilli. The patient was successfully treated with standard tuberculostatic drugs: rifampin, isoniazid, pyrazinamide and ethambutol. INTERPRETATION: Tuberculosis is frequently overlooked, both in hospitals and in primary care. Symptoms may be mild or non-characteristic in the early stage, and a simple chest x-ray is unsuitable to exclude the diagnosis.

A man in his eighties with gait problems and elevated CRP. / En mann i 80-årene med gangvansker og høy CRP-verdi.

BACKGROUND: Rapid detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in hospitals is essential for early isolation and treatment. However, false positive test results can have adverse consequences for patient safety. CASE PRESENTATION: A man in his eighties was admitted to hospital with fatigue and new-onset gait and balance difficulties, without fever or symptoms of focal infection, but with elevated C-reactive protein. On admission, he tested positive on screening for SARS-CoV-2 using a fully automated rapid reverse transcription polymerase chain reaction (RT-PCR) test. He was placed together with two patients with confirmed COVID-19 infection in cohort isolation. Due to very low exposure risk and nonspecific symptoms, the primary and multiple subsequent test swabs were analysed using RT-PCR analyses guided by laboratory personnel, and all gave negative results. The patient had several risk factors for developing severe COVID-19 illness, but fortunately he remained COVID-19 negative on repeated tests. INTERPRETATION: The case presentation highlights the danger of false-positive SARS-CoV-2 test results, and the importance of interpreting a diagnostic test in the context of pretest probability and test accuracy. It also underlines the risk of using cohort isolation instead of individual isolation.

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.

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 <1.00, 1.00 to <4.00 and >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.

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.

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.

Twenty years of endophthalmitis: Incidence, aetiology and clinical outcome.

PURPOSE: To review the incidence, aetiology and outcomes of endophthalmitis during a 20-year period in a Norwegian university hospital. METHODS: Single-centre retrospective review. Medical records of all patients admitted to Stavanger University Hospital with suspected endophthalmitis between January 1999 and December 2018 were reviewed. RESULTS: We identified 84 eyes of 81 patients. Postoperative endophthalmitis (PE) was seen in 64 eyes (76%), endogenous endophthalmitis in thirteen eyes (15%), trauma in four eyes (5%) and three eyes (4%) had keratitis-associated endophthalmitis. Administration of intravitreal injections (IVI) was the most common cause (30%), followed by cataract surgery (CS) (21%). Of 40238 IVI, 23 PE cases were identified (incidence, 0.057%; 95% confidence interval [CI] 0.036-0.086%). Of 39697 CS, 12 PE cases were identified (incidence, 0.030%; 95%CI 0.016-0.053%). After introduction of intracameral cefuroxime PE incidence after CS decreased from 0.10% in 1999-2003 to 0.015% in 2004-2018 (p = 0.003). Eighty-four per cent of organisms were Gram-positive. Coagulase-negative staphylococci accounted for 54% of culture-proven cases, and 89% of post-IVI culture-proven cases. Thirty eyes (36%) either regained their previous vision or lost ≤1 Early Treatment Diabetic Retinopathy Study line. One third of endophthalmitis cases had a favourable visual outcome of logMAR 0.2 or better. CONCLUSION: PE after IVI occurred in 1 in 1750 procedures, and was the most common cause of PE. The incidence of PE after CS has decreased >sixfold since 2003, to 1 in 6700 surgeries. A high proportion of low-virulence bacterial species may have contributed to the favourable visual outcome.

Determination of the susceptibility of Mycobacterium tuberculosis to pyrazinamide in liquid and solid media assessed by a colorimetric nitrate reductase assay.

OBJECTIVES: The aim of this study was to develop and evaluate two colorimetric nitrate reductase-based antibiotic susceptibility (CONRAS) tests, the CONRAS-liquid test and the CONRAS-LJ test, to enable susceptibility testing of Mycobacterium tuberculosis to pyrazinamide. To enhance the growth of M. tuberculosis in 7H9 broth with acid pH (6.0), the effect of three potential growth-promoting substances (reconstitution fluid, fastidious organism supplement and epidermal growth factor) was evaluated. METHODS: Seventy-five M. tuberculosis strains were tested for susceptibility to pyrazinamide in the CONRAS-liquid test performed in Middlebrook 7H9 broth, and 77 M. tuberculosis strains were tested for susceptibility to pyrazinamide in the CONRAS-LJ test performed on Löwenstein-Jensen medium. The BACTEC 460TB system, sequencing of the pncA gene and Wayne's assay were used as reference tests. Growth of 10 M. tuberculosis strains in conventional 7H9 broth and in acid 7H9 broth with and without growth-promoting substances added was evaluated by the nitrate reductase assay. RESULTS: By using the BACTEC 460TB system as the reference test, the sensitivity and specificity of the CONRAS-liquid test (100 mg/L pyrazinamide) tested on 75 M. tuberculosis strains were 87.5% and 83.7%, respectively. The corresponding sensitivity and specificity of the CONRAS-LJ test (1200 mg/L pyrazinamide) tested on 77 M. tuberculosis strains were 100% and 84.1%, respectively. The mean turn around time of the CONRAS-liquid test was significantly shorter than that of the CONRAS-LJ test (mean, 9.4 and 14.5 days, respectively; P < 0.001). In addition, no effect of growth-promoting substances on the growth of M. tuberculosis in a broth with acid pH was seen. CONCLUSIONS: The CONRAS tests were rapid, cheap and easy to perform and interpret. Both tests should be evaluated on extended strain batteries in multicentre studies before they can be considered for use in susceptibility testing of M. tuberculosis to pyrazinamide in resource-limited settings.

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.

Isoniazid and rifampicin resistance-associated mutations in Mycobacterium tuberculosis isolates from Yangon, Myanmar: implications for rapid molecular testing.

OBJECTIVES: To evaluate the frequency and nature of mutations in genes associated with resistance to rifampicin and isoniazid in Mycobacterium tuberculosis isolates collected from Yangon, Myanmar. METHODS: Ninety-six isoniazid-resistant M. tuberculosis isolates, including 29 multidrug-resistant isolates, were analysed for mutations in the rpoB, katG, inhA, oxyR and ahpC genes. RESULTS: Mutations in the rpoB gene were detected in 25 (86.2%) of the 29 rifampicin-resistant isolates. Of the 96 isoniazid-resistant isolates, 61 (63.5%) had mutations in codon 315 of the catalase-peroxidase-encoding gene (katG). Mutations in codon 315 were observed at a higher frequency in the multidrug-resistant isolates than in the isoniazid-resistant isolates (86.2% versus 53.7%, respectively, P = 0.003). Mutations in the oxyR-ahpC promoter region and in the inhA gene were observed in 14.6% and 2.1% of the isolates, respectively. Genotyping performed on the 96 M. tuberculosis isolates revealed a total of 94 different genotyping patterns. A distinct genotypic pattern was found in 92 isolates, whereas 4 isolates belonged to two clusters with identical genotypes, suggesting that the majority of the isolates were not from an outbreak of a single drug-resistant clone. CONCLUSIONS: This study provides the first molecular characterization of isoniazid- and rifampicin-resistant M. tuberculosis isolates from Myanmar and gives information on the molecular basis for rifampicin and isoniazid drug resistance in M. tuberculosis. The study generates useful information for the development of potential rapid molecular drug susceptibility tests.

Use of microbiology tests in the era of increasing AMR rates- a multicentre hospital cohort study.

Background: Effective use of microbiology test results may positively influence patient outcomes and limit the use of broad-spectrum antibiotics. However, studies indicate that their potential is not fully utilized. We investigated microbiology test ordering practices and the use of test results for antibiotic decision-making in hospitals. Methods: A multicentre cohort study was conducted during five months in 2014 in Medical departments across three hospitals in Western Norway. Patients treated with antibiotics for sepsis, urinary tract infections, skin and soft tissue infections, lower respiratory tract infections or acute exacerbations of chronic obstructive pulmonary disease were included in the analysis. Primary outcome measures were degree of microbiology test ordering, compliance with microbiology testing recommendations in the national antibiotic guideline and proportion of microbiology test results used to inform antibiotic treatment. Data was obtained from electronic- and paper medical records and charts and laboratory information systems. Results: Of the 1731 patient admissions during the study period, mean compliance with microbiology testing recommendations in the antibiotic guideline was 89%, ranging from 81% in patients with acute exacerbations of chronic obstructive pulmonary disease to 95% in patients with sepsis. Substantial additional testing was performed beyond the recommendations with 298/606 (49%) of patients with lower respiratory tract infections having urine cultures and 42/194 (22%) of patients with urinary tract infections having respiratory tests. Microbiology test results from one of the hospitals showed that 18% (120/672) of patient admissions had applicable test results, but only half of them were used for therapy guidance, i.e. in total, 9% (63/672) of patient admissions had test results informing prescription of antibiotic therapy. Conclusions: This study showed that despite a large number of microbiology test orders, only a limited number of tests informed antibiotic treatment. To ensure that microbiology tests are used optimally, there is a need to review the utility of existing microbiology tests, test ordering practices and use of test results through a more targeted and overarching approach.

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.

Circulating antibodies to lipoarabinomannan in relation to sputum microscopy, clinical features and urinary anti-lipoarabinomannan detection in pulmonary tuberculosis.

An enzyme-linked immunosorbent assay (ELISA)-based investigation of anti-lipoarabinomannan (LAM) antibody levels in the sera of patients with acid-fast bacilli (AFB)-positive pulmonary tuberculosis (PTB), AFB-negative PTB and non-TB respiratory tract symptoms was conducted. The anti-LAM results were further evaluated using urine LAM detection and a clinical diagnostic score (DS) system as references. Using sputum AFB as a reference, positive anti-LAM was found in 66.9% of 139 AFB-positive PTB, 34.4% of 61 AFB-negative PTB and 23.5% of 800 non-TB patients and in 8% of 50 healthy individuals. The positive and negative predictive values were 48.7% and 87.4%, respectively. Using the DS as a reference, the sensitivity and specificity were 50.5% and 78.3%, respectively, whereas 45.8% of urine LAM positives and 77.9% of urine LAM negatives were correctly identified by the anti-LAM ELISA. In TB endemic areas a negative anti-LAM could be of practical value, particularly when other indicators of PTB are negative. Using any of these methods as a reference, a positive anti-LAM would mislead in about one-quarter of cases. Had all the 3 methods been combined and at least 2 positive tests sufficed, 90.6% of AFB-positive PTB, 52.5% of AFB-negative PTB and 94.9% of non-TB patients would have been correctly diagnosed. Apart from the possible impact of HIV, the low accuracy of the current assay could be due to intravascular formation of LAM-anti-LAM complexes, latent TB or environmental mycobacterial infections.