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Background. Bronchoalveolar lavage (BAL) is currently not recommended in noncritically ill patients for the diagnosis of SARS-CoV-2 infection. Indeed, the diagnosis is based on the RT-PCR test on a nasopharyngeal swab (NPS) and abnormal findings on the chest CT scan. However, the sensitivity of the NPS and the specificity of the chest CT scan are low. Results of BAL in case of negative NPS testing are underreported, especially in the subgroup of immunocompromised patients. Objectives. The added value of BAL in the management of unstable, but noncritically ill patients, suspected of having SARS-CoV-2 infection despite one previous negative NPS and the side effects of the procedure for the patients and the health-care providers, were assessed during the epidemic peak of the COVID-19 outbreak in Belgium. Methods. This multicentric study included all consecutive noncritically ill patients hospitalized with a clinical and radiological suspicion of SARS-CoV-2 infection but with a negative NPS. BAL was performed according to a predefined decisional algorithm based on their state of immunocompetence, the chest CT scan features, and their respiratory status. Results. Among the 55 patients included in the study, 14 patients were diagnosed with a SARS-CoV-2 infection. Interestingly, there was a relationship between the cycle threshold of the RT-PCR and the interval of time between the symptom onset and the BAL procedure (Pearso n ' s correlation coefficient = 0.8 , p = 0.0004). Therapeutic management was changed in 33 patients because another infectious agent was identified in 23 patients or because an alternative diagnosis was made in 10 patients. In immunocompromised patients, the impact of BAL was even more marked (change in therapy for 13/17 patients). No significant adverse event was noted for patients or health-care staff. All health-care workers remained negative for SARS-CoV-2 NPS and serology at the end of the study. Conclusions. In this real-life study, BAL can be performed safely in selected noncritically ill patients suspected of SARS-CoV-2 infection, providing significant clinical benefits that outweigh the risks. [ABSTRACT FROM AUTHOR]

Background: Therapeutic drug monitoring of tacrolimus is a major support to patient management and could help improve the outcome of lung transplant recipients, by minimizing the risk of rejections and infections. However, despite the wide use of tacrolimus as part of maintenance immunosuppressive regimens after lung transplantation, little is known about its pharmacokinetics in this population. Better knowledge of the pharmacokinetics of tacrolimus in lung transplant recipients, and the development of tools dedicated to its therapeutic drug monitoring, could thus help improve their outcome., Objectives: The aims of this study were (i) to characterize the population pharmacokinetics of tacrolimus in lung transplant recipients, including the influence of biological and pharmacogenetic covariates; and (ii) to develop a Bayesian estimator of the tacrolimus area under the blood concentration-time curve from time zero to 12 hours (AUC(12)) for its therapeutic drug monitoring in lung transplant recipients., Methods: A population pharmacokinetic model was developed by nonlinear mixed-effects modelling using NONMEM® version VI, from 182 tacrolimus full concentration-time profiles collected in 78 lung transplant recipients within the first year post-transplantation. Patient genotypes for the cytochrome P450 3A5 (CYP3A5) A6986G single nucleotide polymorphism (SNP) were characterized by TaqMan allelic discrimination. Patients were divided into an index dataset (n = 125 profiles) and a validation dataset (n = 57 profiles). A Bayesian estimator was derived from the final model using the index dataset, in order to determine the tacrolimus AUC(12) on the basis of a limited number of samples. The predictive performance of the Bayesian estimator was evaluated in the validation dataset by comparing the estimated AUC(12) with the trapezoidal AUC(12)., Results: Tacrolimus pharmacokinetics were described using a two-compartment model with Erlang absorption and first-order elimination. The model included cystic fibrosis (CF) and CYP3A5 polymorphism as covariates. The relative bioavailability in patients with CF was approximately 60% of the relative bioavailability observed in patients without CF, and the transfer rate constant between the transit compartments was 2-fold smaller in patients with CF than in those without CF (3.32 vs 7.06 h-1). The apparent clearance was 40% faster in CYP3A5 expressers than in non-expressers (24.5 vs 17.5 L/h). Good predictive performance was obtained with the Bayesian estimator developed using the final model and concentrations measured at 40 minutes and at 2 and 4 hours post-dose, as shown by the mean bias (1.1%, 95% CI -1.4, 3.7) and imprecision (9.8%) between the estimated and the trapezoidal AUC(12). The bias was >20% in 1.8% of patients., Conclusion: Population pharmacokinetic analysis showed that lung transplant patients with CF displayed lower bioavailability and a smaller transfer rate constant between transit compartments than those without CF, while the apparent clearance was faster in CYP3A5 expressers than in non-expressers. The Bayesian estimator developed in this study provides an accurate prediction of tacrolimus exposure in lung transplant patients, with and without CF, throughout the first year post-transplantation. This tool may allow routine tacrolimus dose individualization and may be used to conduct clinical trials on therapeutic drug monitoring of tacrolimus after lung transplantation.

In 1999, all clinical Staphylococcus aureus isolates from patients admitted to a Belgian University hospital were tested for decreased vancomycin susceptibility. Three vancomycin-intermediate Staphylococcus aureus (VISA) and four hetero-VISA strains were detected among 2145 isolates tested. They emerged from strains that belonged to locally endemic methicillin-resistant S. aureus (MRSA) genotypes in three patients who had received repeated courses of vancomycin therapy. A cystic fibrosis patient with MRSA/VISA-associated broncho-pulmonary exacerbation was successfully treated by continuous vancomycin infusion plus fusidic acid followed by oral minocycline-fusidic acid. Two other patients had VISA recovered from specimens of undetermined clinical significance. Emergence of VISA variants of endemic MRSA strains in Belgium warrants active microbiological surveillance and careful monitoring of vancomycin therapy. Therapy with high-dose vancomycin administered by continuous infusion in combination with other antimicrobials may be a therapeutic option worth investigating for VISA infection.