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Volume 150, No. 2324

Published June 1, 2020

Review article: Biomedical intelligence

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    Aurélien Emmanuel Martinez, Claude Scheidegger, Veronika Bättig, Stefan Erb (Author)

    Oral antibiotic therapy in people who inject drugs (PWID) with bacteraemia

    Bacterial infections are a major cause of morbidity and mortality in people who inject drugs (PWID). Patients with bacteraemia have a particularly high risk of complications and are usually treated with intravenous antibiotics. Intravenous treatment is challenging in certain PWID because of difficult venous access and a high rate of catheter-associated complications. Therefore, oral treatment alternatives must be considered.

    This review discusses the potential options for oral antimicrobial treatment of gram-positive and gram-negative bacteraemia in PWID and the evidence for them.

    Data on oral antibiotic treatment of bacteraemia in PWID is scarce. Whenever possible, a course of intravenous antibiotic treatment should precede the switch to an oral regimen. For Staphylococcus aureus bacteraemia, there is growing evidence that initial intravenous antibiotics can be switched to oral treatment (e.g., a fluoroquinolone and rifampin or linezolid) when the patient is clinically stable and source control has been achieved. However, regimen selection remains challenging due to pharmacokinetic/pharmacodynamic issues, potential toxicity and drug-drug interactions of oral antibiotics. For some streptococcal bacteraemia, oral amoxicillin is probably a reasonable option. The best existing evidence for oral antibiotic treatment is for gram-negative bacteraemia, which, if susceptible, can be treated successfully with oral fluoroquinolones. Oral antibiotic options for fluoroquinolone-resistant gram-negative bacteraemia are very limited, although in selected patients oral trimethoprim-sulfamethoxazole can be considered.

    In conclusion, treatment of bacteraemia in PWID remains very complex, and an interdisciplinary approach is essential in order to select the best therapy for this vulnerable group of patients.

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    Patrick Roth, Andreas F. Hottinger, Thomas Hundsberger, Heinz Läubli, Philippe Schucht, Michael Reinert, Christoph Mamot, Ulrich Roelcke, Gianfranco Pesce, Silvia Hofer, Michael Weller (Author)

    A contemporary perspective on the diagnosis and treatment of diffuse gliomas in adults

    Gliomas are intrinsic brain tumours, which are classified by the World Health Organization (WHO) into different grades of malignancy, with glioblastoma being the most frequent and most malignant subtype (WHO grade IV). Mutations in the isocitrate dehydrogenase (IDH) 1 or 2 genes are frequent in lower (WHO II/III) grade tumours but typically absent in classical glioblastoma. IDH mutations are associated with a better prognosis compared with IDH wild-type tumours of the same WHO grade. Following detection of a tumour mass by imaging, maximum safe surgery as feasible is commonly performed to reduce mass effect and to obtain tissue allowing histopathological diagnosis and molecular assessment. Radiotherapy has been the mainstay in the treatment of diffuse gliomas for several decades. It provides improved local control, but is not curative. Furthermore, several randomised trials have shown that the addition of alkylating chemotherapy, either temozolomide or nitrosourea-based regimens, to radiotherapy results in prolonged survival. Tumour-treating fields (TTFields) have emerged as an additional treatment option in combination with maintenance temozolomide treatment for patients with newly diagnosed glioblastoma. Treatment at recurrence is less standardised and depends on the patient’s performance status, symptom burden and prior treatments. Bevacizumab prolongs progression-free survival in newly diagnosed and recurrent glioblastoma, but does not impact overall survival. However, in Switzerland and some other countries, it is still considered a valuable treatment option to reduce clinical symptom burden. Given the generally poor outcome for these patients, various novel treatment approaches are currently being explored within clinical trials including immunotherapeutic strategies such as immune checkpoint inhibition and the brain-penetrant proteasome inhibitor marizomib.

Original article

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    Myriam Boukamel, Yves Fougère, Mario Gehri, Joan Carles Suris, Isabelle Rochat, Damien Miletto, Spyridoula Kyrilli, Athina Fouriki, Pierre Alex Crisinel (Author)

    Prevalence of tuberculosis in migrant children in Switzerland and relevance of current screening guidelines

    AIMS

    Since 2016, Swiss guidelines recommend screening of all migrant children <5 years of age for tuberculosis (TB) and to screen older children only if they have risk factors for tuberculosis. Our goals were to describe the epidemiology of latent tuberculosis in migrant children at the Lausanne University Hospital, to identify determinants of latent tuberculosis and tuberculosis disease, and to evaluate the risk of a false-positive tuberculin skin test when using a positivity limit of 5 mm.

    METHODS

    Newly arrived migrant children 0–18 years of age were prospectively enrolled from 31 August 2015 to 31 August 2017. Every migrant child was assessed for the risk of tuberculosis exposure and tuberculosis disease and was administered a tuberculin skin test. A tuberculosis-spot test was performed in children ≥5 years of age when the tuberculin skin test was positive. Children with clinical and/or radiological signs of tuberculosis disease were further investigated. Children ≥5 years of age with a positive tuberculosis-spot test and children <5 years of age with a positive tuberculin skin test, without clinico-radiological signs of tuberculosis disease received a diagnosis of latent tuberculosis. A false-positive tuberculin skin test result was diagnosed in children ≥5 years of age when the tuberculosis-spot test was negative. Potential determinants of tuberculosis (latent tuberculosis and tuberculosis disease) and of false-positive tuberculin skin tests were identified. Student’s t-test or the Kruskal-Wallis test were used for continuous variables and the chi-square test or Fisher’s exact test for categorical variables. All variables with a p-value <0.05 were included in a multivariate logistic regression model.

    RESULTS

    Two hundred and fifty-three patients were eligible for the study. The median age of the patients was 8.1 years (interquartile range [IQR] 4.5–12.8) and 104 (41%) were female. Twenty-four percent of the patients (62/253) came from a country with a moderate–high incidence of tuberculosis disease (≥80 cases per 100,000 individuals). Twenty-eight patients (11%) had positive tuberculin skin tests, and tuberculosis was confirmed in 17 (6.7%) of these patients (16 with latent tuberculosis and 1 with tuberculosis disease). On multivariate analysis, moderate–high incidence of tuberculosis disease in the country of origin (adjusted odds ratio [aOR] 18.8, 95% confidence interval [CI] 5.1–68.6; p <0.001), older age (aOR 1.1, 95% CI 1.0–1.3; p = 0.025), and contact with a tuberculosis disease patient (aOR 8, 95% CI 1.8–36.2; p = 0.007) were associated with a diagnosis of tuberculosis. Among the 23 children over 5 years of age who had a positive tuberculin skin test with measurement available, a measure between 5–9 mm was more frequent in case of a false-positive tuberculin skin test (5/9, 56% vs 0/14, 0%, p = 0.002). BCG vaccination was the only predictor of a false-positive tuberculin skin test (p = 0.03).

    CONCLUSION

    Screening migrant children ≥5 years of age for tuberculosis could confer a public health benefit even in the absence of other risk factors. The limit of tuberculin skin test positivity could be raised from ≥5 mm to ≥10 mm to decrease the rate of false-positive results. A national assessment of migrant children between the ages of 5 and 15 should be carried out to confirm our findings.

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    Brigitta Zumbrunn, Odile Stalder, Andreas Limacher, Peter E. Ballmer, Stefano Bassetti, Edouard Battegay, Jürg Hans Beer, Michael Brändle, Daniel Genné, Daniel Hayoz, Christoph Henzen, Lars Christian Huber, Pierre-Auguste Petignat, Jean-Luc Reny, Peter Vollenweider, Drahomir Aujesky (Author)

    The well-being of Swiss general internal medicine residents

    BACKGROUND

    Physician well-being has an impact on productivity and quality of care. Residency training is a particularly stressful period.

    OBJECTIVE

    To assess the well-being of general internal medicine (GIM) residents and its association with personal and work-related factors.

    METHODS

    We conducted an anonymous electronic survey among GIM residents from 13 Swiss teaching hospitals. We explored the association between a reduced well-being (≥5 points based on the Physician Well-Being Index [PWBI]) and personal and work-related factors using multivariable mixed-effects logistic regression.

    RESULTS

    The response rate was 54% (472/880). Overall, 19% of residents had a reduced well-being, 60% felt burned out (emotional exhaustion), 47% were worried that their work was hardening them emotionally (depersonalisation), and 21% had career choice regret. Age (odds ratio [OR] 1.19, 95% confidence interval [CI] 1.05–1.34), working hours per week (OR 1.04 per hour, 95% CI 1.01–1.07) and <2.5 rewarding work hours per day (OR 3.73, 95% CI 2.01–6.92) were associated with reduced well-being. Administrative workload and satisfaction with the electronic medical record were not. We found significant correlations between PWBI score and job satisfaction (rs = -0.54, p<0.001), medical errors (rs = 0.18, p<0.001), suicidal ideation (rs = 0.12, p = 0.009) and the intention to leave clinical practice (rs = 0.38, p <0.001)

    CONCLUSIONS

    Approximately 20% of Swiss GIM residents appear to have a reduced well-being and many show signs of distress or have career choice regret. Having few hours of rewarding work and a high number of working hours were the most important modifiable predictors of reduced well-being. Healthcare organisations have an ethical responsibility to implement interventions to improve physician well-being.