Background Chloroquine, a quinolone antimalarial drug, is known to potentially inhibit pH-dependent viral replication of the SARS-CoV-2 infection. Therefore, chloroquine is considered as a treatment option for coronavirus disease 2019 (COVID-19). Chloroquine is known for prolonging the QT interval, but limited data are available on the extent of this QT-prolonging effect. Objective To assess the QTc-prolonging potential of chloroquine in COVID-19 patients and to evaluate whether this prolongation increases with the cumulative dose of chloroquine and is associated with the peak plasma concentration of chloroquine. Furthermore, the number of patients who prematurely discontinued treatment or had an adjustment in dose due to QTc-interval prolongation was established. Methods A retrospective, observational study was performed in patients aged over 18 years, hospitalised for a suspected or proven infection with COVID-19, and therefore treated with chloroquine, with a baseline electrocardiogram (ECG) performed prior to the start of treatment and at least one ECG after starting the treatment. Results In total, 397 patients were included. The mean increase in QTc interval throughout the treat

BackgroundVancomycin is effective against gram-positive bacteria and the first-line antibiotic for treatment of proven coagulase-negative staphylococcal infections. The aim of this study is bipartite: first, to assess the percentage of therapeutic initial trough serum concentrations and second, to evaluate the adequacy of the therapeutic range in interrelationship with the observed MIC-values in neonates.MethodsIn this study, preterm and term neonates admitted at a tertiary NICU in the Netherlands from January 2009 to December 2012 and treated with vancomycin for a proven gram-positive infection were included. Trough serum concentrations were measured prior to administration of the 5th dose. Trough concentrations in the range of 10 to 15 mg/L were considered therapeutic. Staphylococcal species minimal inhibitory concentrations (MIC’s) were determined using the E-test method. Species identification was performed by matrix-assisted laser desorption/ionisation mass spectrometry.ResultsOf the 112 neonates, 53 neonates (47%) had sub-therapeutic initial trough serum concentrations of vancomycin, whereas 22% had supra-therapeutic initial trough serum concentrations. In all patients doses were adjusted on basis of the initial trough concentration. In 40% (23/57) of the neonates the second trough concentration remained sub-therapeutic. MIC’s were determined for 30 coagulase-negative Staphylococcus isolates obtained from 19 patients. Only 4 out of 19 subjects had a trough concentration greater than tenfold the MIC.ConclusionsForty-seven percent of the neonates had sub-therapeutic initial trough serum concentrations of vancomycin. The MIC-data indicate that the percentages of underdosed patients may be greater. It may be advisable to increase the lower limit of the therapeutic range for European neonates.

Vancomycin trough serum concentrations were below therapeutic range (8-15 mg/L) in 58% of 124 pediatric oncology patients receiving 60 mg/kg/d divided qid. Patients <6 and between 6 and 12 years had significantly lower trough concentrations than patients >12 years. A vancomycin dosage of 60 mg/kg/d is inadequate for pediatric oncology patients >12 years.

Amikacin is an aminoglycoside antibiotic that is frequently used for the treatment of neonatal late‐onset sepsis, for which therapeutic drug monitoring (TDM) is advised. In order to decrease the TDM associated burden of plasma sampling, a noninvasive TDM method using saliva samples was investigated.MethodsThis was a prospective single‐centre, observational feasibility study with 23 premature and term neonates from whom up to 8 saliva samples were collected, together with residual plasma from clinical routine. Amikacin concentrations in saliva and plasma were quantified with liquid chromatography–tandem mass spectrometry. A population pharmacokinetic analysis was performed to develop an integrated pharmacokinetic model of amikacin in plasma and saliva and for the identification of covariates. TDM performance of different sampling regimens was evaluated using Monte Carlo simulations in a fictional cohort of representative neonates (n = 10 000).ResultsAmikacin could be detected in saliva and a saliva compartment was appended to a 2‐compartment plasma model. First‐order absorption (k13) of the saliva compartment was 0.0345 h−1 with an interindividual variability of 45.3%. The rate of first‐order elimination (k30) was 0.176 h−1. Postmenstrual age had a significant negative covariate effect on k13, with an exponent of −4.3. Target attainment increased from 77.6 to 79.2% and from 79.9 to 83.2% using 1–to 5 saliva samples or 1–5 plasma samples, respectively.ConclusionTDM of amikacin using saliva samples results in target attainment comparable to plasma samples and may be beneficial for (premature) neonates with late‐onset sepsis.