Oral versus intravenous antibiotic treatment of moderate-to-severe community-acquired pneumonia: a propensity score matched study.

Community-acquired Pneumonia (CAP) guidelines generally recommend to admit patients with moderate-to-severe CAP and start treatment with intravenous antibiotics. This study aims to explore the clinical outcomes of oral antibiotics in patients with moderate-to-severe CAP. We performed a nested cohort study of an observational study including all adult patients presenting to the emergency department of the Haga Teaching Hospital, the Netherlands, between April 2019 and May 2020, who had a blood culture drawn. We conducted propensity score matching with logistic and linear regression analysis to compare patients with moderate-to-severe CAP (Pneumonia Severity Index class III-V) treated with oral antibiotics to patients treated with intravenous antibiotics. Outcomes were 30-day mortality, intensive care unit admission, readmission, length of stay (LOS) and length of antibiotic treatment. Of the original 314 patients, 71 orally treated patients were matched with 102 intravenously treated patients. The mean age was 73 years and 58% were male. We found no significant differences in outcomes between the oral and intravenous group, except for an increased LOS of + 2.6 days (95% confidence interval 1.2-4.0, p value < 0.001) in those treated intravenously. We conclude that oral antibiotics might be a safe and effective treatment for moderate-to-severe CAP for selected patients based on the clinical judgement of the attending physician.

A reference standard for urinary tract infection research: a multidisciplinary Delphi consensus study.

The absence of a consensus-based reference standard for urinary tract infection (UTI) research adversely affects the internal and external validity of diagnostic and therapeutic studies. This omission hinders the accumulation of evidence for a disease that imposes a substantial burden on patients and society, particularly in an era of increasing antimicrobial resistance. We did a three-round Delphi study involving an international, multidisciplinary panel of UTI experts (n=46) and achieved a high degree of consensus (94%) on the final reference standard. New-onset dysuria, urinary frequency, and urinary urgency were considered major symptoms, and non-specific symptoms in older patients were not deemed indicative of UTI. The reference standard distinguishes between UTI with and without systemic involvement, abandoning the term complicated UTI. Moreover, different levels of pyuria were incorporated in the reference standard, encouraging quantification of pyuria in studies done in all health-care settings. The traditional bacteriuria threshold (105 colony-forming units per mL) was lowered to 104 colony-forming units per mL. This new reference standard can be used for UTI research across many patient populations and has the potential to increase homogeneity between studies.

Virological failure after switch to long-acting cabotegravir and rilpivirine injectable therapy: an in-depth analysis.

BACKGROUND: Long-acting (LA) injectable therapy with cabotegravir (CAB) and rilpivirine (RPV) is currently used as maintenance treatment for HIV-1, and has a low risk for virological failure (VF). Although the risk is low, the circumstances and impact of VF in the real-world setting merits further evaluation. METHODS: We performed an in-depth clinical, virological and pharmacokinetic analysis on the reasons behind, and the impact of VF during LA CAB/RPV therapy in five cases from the Netherlands. Genotypic resistance testing was performed after the occurrence of VF and drug plasma (trough) concentrations were measured after VF was established and on any other samples to assess on-treatment drug levels. CAB and RPV drug levels that were below the first quartile of the population cut-off (

Diagnostic accuracy of urine biomarkers for urinary tract infection in older women: a case-control study.

OBJECTIVES: Urinary tract infection (UTI) is common among older women. However, diagnosis is challenging because of frequent chronic lower urinary tract symptoms, cognitive impairment, and a high prevalence of asymptomatic bacteriuria (ASB). Current urine diagnostics lack specificity, leading to unnecessary treatment and antimicrobial resistance. This study aimed to evaluate the diagnostic accuracy of 12 urine biomarkers for diagnosing UTI in older women. METHODS: In this case-control study, cases were women ≥65 years with ≥2 new-onset lower urinary tract symptoms, pyuria, and one uropathogen ≥104 CFU/mL. Controls were asymptomatic and classified as ASB (one uropathogen ≥105 CFU/mL), negative culture, or mixed flora. Urine biomarker concentrations were measured through liquid chromatography-mass spectrometry and ELISA. Diagnostic accuracy parameters of individual biomarkers and a biomarker model were derived from receiver operating characteristic curves. RESULTS: We included 162 community-dwelling and institutionalized older women. Five urine inflammatory biomarkers demonstrated high discriminative ability (area under the curve ≥0.80): interleukin 6, azurocidin, neutrophil gelatinase-associated lipocalin, tissue inhibitor of metalloproteinases 2, and C-X-C motif chemokine 9. Azurocidin exhibited the highest diagnostic accuracy (sensitivity 86% [95% CI 75%-93%] and specificity 89% [95% CI 82%-94%] at 16.7 ng/mmol creatinine). A combined biomarker and pyuria model showed improved diagnostic accuracy in patients with UTI and ASB, compared with pyuria alone. DISCUSSION: We identified several urine biomarkers that accurately differentiated older women with UTI from asymptomatic women, including ASB. These findings represent a potential advancement towards improved diagnostics for UTI in older women and warrant validation in a diverse population.

Rapid Response to Remdesivir in Hospitalised COVID-19 Patients: A Propensity Score Weighted Multicentre Cohort Study.

INTRODUCTION: Remdesivir is a registered treatment for hospitalised patients with COVID-19 that has moderate clinical effectiveness. Anecdotally, some patients' respiratory insufficiency seemed to recover particularly rapidly after initiation of remdesivir. In this study, we investigated if this rapid improvement was caused by remdesivir, and which patient characteristics might predict a rapid clinical improvement in response to remdesivir. METHODS: This was a multicentre observational cohort study of hospitalised patients with COVID-19 who required supplemental oxygen and were treated with dexamethasone. Rapid clinical improvement in response to treatment was defined by a reduction of at least 1 L of supplemental oxygen per minute or discharge from the hospital within 72 h after admission. Inverse probability of treatment-weighted logistic regression modelling was used to assess the association between remdesivir and rapid clinical improvement. Secondary endpoints included in-hospital mortality, ICU admission rate and hospitalisation duration. RESULTS: Of 871 patients included, 445 were treated with remdesivir. There was no influence of remdesivir on the occurrence of rapid clinical improvement (62% vs 61% OR 1.05, 95% CI 0.79-1.40; p = 0.76). The in-hospital mortality was lower (14.7% vs 19.8% OR 0.70, 95% CI 0.48-1.02; p = 0.06) for the remdesivir-treated patients. Rapid clinical improvement occurred more often in patients with low C-reactive protein (≤ 75 mg/L) and short duration of symptoms prior to hospitalisation (< 7 days) (OR 2.84, 95% CI 1.07-7.56). CONCLUSION: Remdesivir generally does not increase the incidence of rapid clinical improvement in hospitalised patients with COVID-19, but it might have an effect in patients with short duration of symptoms and limited signs of systemic inflammation.

Evaluation of an integrated care pathway for out-of-hospital treatment of older adults with an acute moderate-to-severe lower respiratory tract infection or pneumonia: protocol of a mixed methods study.

INTRODUCTION: Older adults with an acute moderate-to-severe lower respiratory tract infection (LRTI) or pneumonia are generally treated in hospitals causing risk of iatrogenic harm such as functional decline and delirium. These hospitalisations are often a consequence of poor collaboration between regional care partners, the lack of (acute) diagnostic and treatment possibilities in primary care, and the presence of financial barriers. We will evaluate the implementation of an integrated regional care pathway ('The Hague RTI Care Bridge') developed with the aim to treat and coordinate care for these patients outside the hospital. METHODS AND ANALYSIS: This is a prospective mixed methods study. Participants will be older adults (age≥65 years) with an acute moderate-to-severe LRTI or pneumonia treated outside the hospital (care pathway group) versus those treated in the hospital (control group). In addition, patients, their informal caregivers and treating physicians will be asked about their experiences with the care pathway. The primary outcome of this study will be the feasibility of the care pathway, which is defined as the percentage of patients treated outside the hospital, according to the care pathway, whom fully complete their treatment without the need for hospitalisation within 30 days of follow-up. Secondary outcomes include the safety of the care pathway (30-day mortality and occurrence of complications (readmissions, delirium, falls) within 30 days); the satisfaction, usability and acceptance of the care pathway; the total number of days of bedridden status or hospitalisation; sleep quantity and quality; functional outcomes and quality of life. ETHICS AND DISSEMINATION: The Medical Research Ethics Committee Leiden The Hague Delft (reference number N22.078) has confirmed that the Medical Research Involving Human Subjects Act does not apply to this study. The results will be published in international peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN68786381.

Definitions of Urinary Tract Infection in Current Research: A Systematic Review.

Defining urinary tract infection (UTI) is complex, as numerous clinical and diagnostic parameters are involved. In this systematic review, we aimed to gain insight into how UTI is defined across current studies. We included 47 studies, published between January 2019 and May 2022, investigating therapeutic or prophylactic interventions in adult patients with UTI. Signs and symptoms, pyuria, and a positive urine culture were required in 85%, 28%, and 55% of study definitions, respectively. Five studies (11%) required all 3 categories for the diagnosis of UTI. Thresholds for significant bacteriuria varied from 103 to 105 colony-forming units/mL. None of the 12 studies including acute cystitis and 2 of 12 (17%) defining acute pyelonephritis used identical definitions. Complicated UTI was defined by both host factors and systemic involvement in 9 of 14 (64%) studies. In conclusion, UTI definitions are heterogeneous across recent studies, highlighting the need for a consensus-based, research reference standard for UTI.

Using Design Thinking for Co-Creating an Integrated Care Pathway Including Hospital at Home for Older Adults with an Acute Moderate-Severe Respiratory Infection in the Netherlands.

Introduction: Acute respiratory infections are common in frail, community-dwelling older people and are accompanied by considerable diagnostic and prognostic uncertainties. Inadequately coordinated care is associated with unnecessary hospital referral and admission with potential iatrogenic harm. Therefore, we aimed to co-create a regional integrated care pathway (ICP), including a hospital at home journey. Developing the ICP: Tasked with using design thinking methodology, stakeholders from regional healthcare facilities, together with patient representatives, were assigned to different focus groups based on their expertise. The focus of each session was to co-create ideal patient journeys suitable for embedding in the ICP. Results: Based on these sessions, a regional cross-domain ICP was developed that comprises three patient journeys. The first journey included a hospital at home track, the second a tailored visit, with priority assessment, to regional emergency departments, and the third concerned referral to readily available nursing home 'recovery-beds' under the supervision of an elderly care medicine specialist. Conclusion: Using design thinking and involving end-users during the whole process, we created an ICP for community-dwelling frail older people with moderate-severe acute respiratory infections. This resulted in three realistic patient journeys, including a hospital at home track, which will be implemented and evaluated in the near future.

Outcomes of community-acquired pneumonia using the Pneumonia Severity Index versus the CURB-65 in routine practice of emergency departments.

Background: The Pneumonia Severity Index (PSI) and the CURB-65 score assess disease severity in patients with community-acquired pneumonia (CAP). We compared the clinical performance of both prognostic scores according to clinical outcomes and admission rates. Methods: A nationwide retrospective cohort study was conducted using claims data from adult CAP patients presenting to the emergency department (ED) in 2018 and 2019. Dutch hospitals were divided into three categories: "CURB-65 hospitals" (n=25), "PSI hospitals" (n=19) and hospitals using both ("no-consensus hospitals", n=15). Main outcomes were hospital admission rates, intensive care unit admissions, length of hospital stay, delayed admissions, readmissions and all-cause 30-day mortality. Multilevel logistic and Poisson regression analysis were used to adjust for potential confounders. Findings: Of 50 984 included CAP patients, 21 157 were treated in CURB-65 hospitals, 17 279 in PSI hospitals and 12 548 in no-consensus hospitals. The 30-day mortality was significantly lower in CURB-65 hospitals versus PSI hospitals (8.6% and 9.7%, adjusted odds ratio (aOR) 0.89, 95% CI: 0.83-0.96, p=0.003). Other clinical outcomes were similar between CURB-65 hospitals and PSI hospitals. No-consensus hospitals had higher admission rates compared to the CURB-65 and PSI hospitals combined (78.4% and 81.5%, aOR 0.78, 95% CI: 0.62-0.99). Interpretation: In this study, using the CURB-65 in CAP patients at the ED is associated with similar and possibly even better clinical outcomes compared to using the PSI. After confirmation in prospective studies, the CURB-65 may be recommended over the use of the PSI since it is associated with lower 30-day mortality and is more user-friendly.

Drug-drug interaction: decreased posaconazole trough concentrations during concomitant flucloxacillin treatment.

BACKGROUND AND OBJECTIVES: Posaconazole is used as prophylaxis of invasive fungal disease in immune-compromised haematological patients with prolonged neutropenia after intensive chemotherapy. During routine therapeutic drug monitoring of posaconazole, we repeatedly observed low posaconazole serum concentrations in patients that were concomitantly treated with flucloxacillin. A possible interaction between flucloxacillin and posaconazole was explored in this case series. PATIENTS AND METHODS: Posaconazole trough serum concentrations during and before/after flucloxacillin treatment were collected from 10 patients. RESULTS: With a median concentration of 0.5 mg/L (IQR 0.3-0.6), the posaconazole trough serum concentration decreased by 47% during flucloxacillin treatment compared with the concentration before/after flucloxacillin treatment (0.9 mg/L, IQR 0.6-1.3). As a result, the posaconazole target trough concentration of ≥0.7 mg/L was only achieved in five out of nine patients during flucloxacillin treatment. CONCLUSIONS: Careful monitoring of posaconazole serum trough concentrations is recommended when concomitant use of flucloxacillin cannot be avoided.

Intravesical aminoglycoside instillations as prophylaxis for recurrent urinary tract infection: patient satisfaction, long-term safety and efficacy.

Background: Recurrent urinary tract infections (UTIs) are common, especially in women. When oral antimicrobial prophylaxis is ineffective or not possible due to allergies or antimicrobial resistance, intravesical aminoglycoside instillations (IAIs) are a non-systemic alternative. Objectives: To assess treatment satisfaction, long-term safety and efficacy of IAIs for recurrent UTI. Methods: We conducted a cohort study using data collected between January 2013 and June 2022 at the Leiden University Medical Center. Adult patients with recurrent UTI who received prophylactic IAI were eligible for inclusion. Treatment satisfaction was assessed through a survey. Data on serum aminoglycoside concentrations, cystoscopy results and number of recurrences were obtained through chart review. Number of recurrences and UTI characteristics were compared between patients on and off IAI using Poisson and logistic mixed effects models. Results: Forty-four patients were included (median follow-up time 976 days) and 323 UTIs occurred during follow-up. Overall treatment satisfaction was high (median 79.2/100). All but one patient had undetectable serum aminoglycoside levels and no malignancies were found on follow-up cystoscopy. IAI increased the time to first recurrence (102 days versus 36 days, P = 0.02), reduced the number of recurrences (rate ratio 0.75, 95% CI 0.56-0.99, P = 0.04) and the necessity for systemic antibiotics (OR 0.33, 95% CI 0.13-0.86, P = 0.02). Conclusions: In patients with recurrent UTI, IAI was associated with high treatment satisfaction, and was found to be a safe and effective alternative to oral antimicrobial prophylaxis.

Bacillus Calmette-Guérin vaccine for prevention of COVID-19 and other respiratory tract infections in older adults with comorbidities: a randomized controlled trial.

OBJECTIVES: To test whether Bacillus Calmette-Guérin (BCG) vaccination would reduce the incidence of COVID-19 and other respiratory tract infections (RTIs) in older adults with one or more comorbidities. METHODS: Community-dwelling adults aged 60 years or older with one or more underlying comorbidities and no contraindications to BCG vaccination were randomized 1:1 to BCG or placebo vaccination and followed for 6 months. The primary endpoint was a self-reported, test-confirmed COVID-19 incidence. Secondary endpoints included COVID-19 hospital admissions and clinically relevant RTIs (i.e. RTIs including but not limited to COVID-19 requiring medical intervention). COVID-19 and clinically relevant RTI episodes were adjudicated. Incidences were compared using Fine-Gray regression, accounting for competing events. RESULTS: A total of 6112 participants with a median age of 69 years (interquartile range, 65-74) and median of 2 (interquartile range, 1-3) comorbidities were randomized to BCG (n = 3058) or placebo (n = 3054) vaccination. COVID-19 infections were reported by 129 BCG recipients compared to 115 placebo recipients [hazard ratio (HR), 1.12; 95% CI, 0.87-1.44]. COVID-19-related hospitalization occurred in 18 BCG and 21 placebo recipients (HR, 0.86; 95% CI, 0.46-1.61). During the study period, 13 BCG recipients died compared with 18 placebo recipients (HR, 0.71; 95% CI, 0.35-1.43), of which 11 deaths (35%) were COVID-19-related: six in the placebo group and five in the BCG group. Clinically relevant RTI was reported by 66 BCG and 72 placebo recipients (HR, 0.92; 95% CI, 0.66-1.28). DISCUSSION: BCG vaccination does not protect older adults with comorbidities against COVID-19, COVID-19 hospitalization, or clinically relevant RTIs.

Current Pyuria Cutoffs Promote Inappropriate Urinary Tract Infection Diagnosis in Older Women.

BACKGROUND: Pre-existing lower urinary tract symptoms (LUTS), cognitive impairment, and the high prevalence of asymptomatic bacteriuria (ASB) complicate the diagnosis of urinary tract infection (UTI) in older women. The presence of pyuria remains the cornerstone of UTI diagnosis. However, >90% of ASB patients have pyuria, prompting unnecessary treatment. We quantified pyuria by automated microscopy and flowcytometry to determine the diagnostic accuracy for UTI and to derive pyuria thresholds for UTI in older women. METHODS: Women ≥65 years with ≥2 new-onset LUTS and 1 uropathogen ≥104 colony-forming units (CFU)/mL were included in the UTI group. Controls were asymptomatic and classified as ASB (1 uropathogen ≥105 CFU/mL), negative culture, or mixed flora. Patients with an indwelling catheter or antimicrobial pretreatment were excluded. Leukocyte medians were compared and sensitivity-specificity pairs were derived from a receiver operating characteristic curve. RESULTS: We included 164 participants. UTI patients had higher median urinary leukocytes compared with control patients (microscopy: 900 vs 26 leukocytes/µL; flowcytometry: 1575 vs 23 leukocytes/µL; P < .001). Area under the curve was 0.93 for both methods. At a cutoff of 264 leukocytes/µL, sensitivity and specificity of microscopy were 88% (positive and negative likelihood ratio: 7.2 and 0.1, respectively). The commonly used cutoff of 10 leukocytes/µL had a poor specificity (36%) and a sensitivity of 100%. CONCLUSIONS: The degree of pyuria can help to distinguish UTI in older women from ASB and asymptomatic controls with pyuria. Current pyuria cutoffs are too low and promote inappropriate UTI diagnosis in older women. Clinical Trials Registration. International Clinical Trials Registry Platform: NL9477 (https://trialsearch.who.int/Trial2.aspx?TrialID=NL9477).

Development and validation of an early warning model for hospitalized COVID-19 patients: a multi-center retrospective cohort study.

BACKGROUND: Timely identification of deteriorating COVID-19 patients is needed to guide changes in clinical management and admission to intensive care units (ICUs). There is significant concern that widely used Early warning scores (EWSs) underestimate illness severity in COVID-19 patients and therefore, we developed an early warning model specifically for COVID-19 patients. METHODS: We retrospectively collected electronic medical record data to extract predictors and used these to fit a random forest model. To simulate the situation in which the model would have been developed after the first and implemented during the second COVID-19 'wave' in the Netherlands, we performed a temporal validation by splitting all included patients into groups admitted before and after August 1, 2020. Furthermore, we propose a method for dynamic model updating to retain model performance over time. We evaluated model discrimination and calibration, performed a decision curve analysis, and quantified the importance of predictors using SHapley Additive exPlanations values. RESULTS: We included 3514 COVID-19 patient admissions from six Dutch hospitals between February 2020 and May 2021, and included a total of 18 predictors for model fitting. The model showed a higher discriminative performance in terms of partial area under the receiver operating characteristic curve (0.82 [0.80-0.84]) compared to the National early warning score (0.72 [0.69-0.74]) and the Modified early warning score (0.67 [0.65-0.69]), a greater net benefit over a range of clinically relevant model thresholds, and relatively good calibration (intercept = 0.03 [- 0.09 to 0.14], slope = 0.79 [0.73-0.86]). CONCLUSIONS: This study shows the potential benefit of moving from early warning models for the general inpatient population to models for specific patient groups. Further (independent) validation of the model is needed.

Analysis of Variation Between Diagnosis at Admission vs Discharge and Clinical Outcomes Among Adults With Possible Bacteremia.

Importance: Misdiagnosis of infection is among the most commonly made diagnostic errors and is associated with increased morbidity and mortality. Little is known about how often misdiagnosed site of infection occurs and its association with clinical outcomes. Objectives: To evaluate the discrepancy between admission and discharge site of infection diagnoses among patients with suspected bacteremia, to explore factors associated with discrepant diagnoses, and to evaluate the association with clinical outcomes. Design, Setting, and Participants: This cohort study used electronic records of 1477 adult patients who were admitted to the hospital for suspected bacteremia from April 1, 2019, to May 31, 2020, and who had blood cultures taken at the emergency department at Haga Teaching Hospital, The Hague, the Netherlands. Suspected infection sites were classified into 8 categories at admission and discharge. Misdiagnosed site was defined as a discrepancy between the suspected site of infection at admission and at discharge. Main Outcomes and Measures: Clinical outcomes were 30-day mortality, intensive care unit admission, length of hospital stay, and antibiotic use, analyzed with logistic and linear regression. Risk factors for misdiagnosed site were determined using regression analysis. Results: A total of 1477 patients (820 [55.5%] male; median [IQR] age, 68 [56-78] years) were analyzed. The rate of misdiagnosed site of infection was 11.6% (171 of 1477); 3.1% of all patients (46 of 1477) ultimately had no infection. No association was found between misdiagnosis and 30-day mortality (adjusted odds ratio [aOR], 0.8; 95% CI, 0.3-1.9; P = .60), intensive care unit admission (aOR, 1.3; 95% CI, 0.6-3.0; P = .54), and hospital length of stay (adjusted increase of stay, 15.5%; 95% CI, -3.1% to 37.7%; P = .11). Misdiagnosed site was associated with receiving broad-spectrum antibiotics (aOR, 4.0; 95% CI, 1.8-8.8; P < .001). Older age, dementia, a positive urine sediment test result without urinary symptoms, and suspicion of an intravascular, central nervous system, or bone and joint infection were risk factors for misdiagnosed site of infection. Conclusions and Relevance: In this cohort study, misdiagnosed site of infection occurred in 1 of 9 patients and was not associated with worse short-term clinical outcomes. Clinicians should be aware of risk factors associated with misdiagnosed site of infection and potential inappropriate antibiotic use.

Is shorter always better? The pros and cons of treating Gram-negative bloodstream infections with 7 days of antibiotics.

Accumulating evidence from randomized controlled trials (RCTs) supports 7 days treatment for uncomplicated Gram-negative bacteraemia. However, some patient populations were not well represented in these RCTs, including critically ill patients, immunocompromised patients and those with MDR bacteria. In this debate document, we discuss the pros and cons for treating patients with Gram-negative bacteraemia with a 7 day antibiotic course. We surmise that the patients who were not well represented in the RCTs are probably those who have most to lose from the drawbacks of prolonged antibiotic courses, including adverse events, superinfections and resistance development. Treatment durations among these patients can be managed individually, with C-reactive protein or procalcitonin guidance or by clinical measures, and with care to discontinue antibiotics as soon as the patient recovers clinically from the infection.

Bacillus Calmette-Guérin vaccine to reduce healthcare worker absenteeism in COVID-19 pandemic, a randomized controlled trial.

OBJECTIVES: The COVID-19 pandemic increases healthcare worker (HCW) absenteeism. The bacillus Calmette-Guérin (BCG) vaccine may provide non-specific protection against respiratory infections through enhancement of trained immunity. We investigated the impact of BCG vaccination on HCW absenteeism during the COVID-19 pandemic. METHODS: HCWs exposed to COVID-19 patients in nine Dutch hospitals were randomized to BCG vaccine or placebo in a 1:1 ratio, and followed for one year using a mobile phone application. The primary endpoint was the self-reported number of days of unplanned absenteeism for any reason. Secondary endpoints included documented COVID-19, acute respiratory symptoms or fever. This was an investigator-funded study, registered at ClinicalTrials.gov (NCT03987919). RESULTS: In March/April 2020, 1511 HCWs were enrolled. The median duration of follow-up was 357 person-days (interquartile range [IQR], 351 to 361). Unplanned absenteeism for any reason was observed in 2.8% of planned working days in the BCG group and 2.7% in the placebo group (adjusted relative risk 0.94; 95% credible interval, 0.78-1.15). Cumulative incidences of documented COVID-19 were 14.2% in the BCG and 15.2% in the placebo group (adjusted hazard ratio (aHR) 0.94; 95% confidence interval (CI), 0.72-1.24). First episodes of self-reported acute respiratory symptoms or fever occurred in 490 (66.2%) and 443 (60.2%) participants, respectively (aHR: 1.13; 95% CI, 0.99-1.28). Thirty-one serious adverse events were reported (13 after BCG, 18 after placebo), none considered related to study medication. CONCLUSIONS: During the COVID-19 pandemic, BCG-vaccination of HCW exposed to COVID-19 patients did not reduce unplanned absenteeism nor documented COVID-19.

Hypokalaemia in patients treated with intravenous flucloxacillin: Incidence and risk factors.

INTRODUCTION: Hypokalaemia is a potentially life-threatening adverse event of flucloxacillin with unknown incidence. The risk of flucloxacillin-induced hypokalaemia has recently been suggested to be increased among females compared to males. The aim of this study is to describe the incidence and to determine the influence of sex and other risk factors on flucloxacillin-induced hypokalaemia. METHODS: A retrospective single-centre cohort study was performed. Patients treated with intravenous flucloxacillin for >24 hours between January 2017 and October 2020, a baseline potassium level of ≥3.5 mmol/L and potassium measurement during treatment were included. The primary endpoint was incidence of hypokalaemia defined as the percentage of patients with a potassium measurement <3.5 mmol/L during flucloxacillin treatment. Logistic regression modelling was used to establish risk factors for hypokalaemia. RESULTS: A total of 835 patients were included, 58.2% male and median age 71.0 years (interquartile range 61.0-81.0). The incidence of hypokalaemia was 23.7% (28.4% in females vs 20.4% in males). A dose-dependent relation between sex and the incidence of hypokalaemia was found. The risk of hypokalaemia was 4.41 (95% confidence interval 1.47-13.24) times higher in females compared to males when receiving a flucloxacillin dose of >8 g/24 h. No sex differences were found for lower daily doses. Other risk factors for hypokalaemia were older age, concomitant antibiotic use, lower bodyweight, lower baseline plasma potassium concentration and longer treatment duration. CONCLUSION: Hypokalaemia is a frequent complication in patients treated with intravenous flucloxacillin. Females receiving >8 g intravenous flucloxacillin per day are more prone to develop hypokalaemia compared to males.