Objectives MSSA bloodstream infections (BSIs) are associated with considerable mortality. Data regarding therapeutic drug monitoring (TDM) and pharmacological target attainment of the β-lactam flucloxacillin are scarce. Patients and methods We determined the achievement of pharmacokinetic/pharmacodynamic targets and its association with clinical outcome and potential toxicity in a prospective cohort of 50 patients with MSSA-BSI. Strain-specific MICs and unbound plasma flucloxacillin concentrations (at five different timepoints) were determined by broth microdilution and HPLC–MS, respectively. Results In our study population, 48% were critically ill and the 30 day mortality rate was 16%. The median flucloxacillin MIC was 0.125 mg/L. The median unbound trough concentration was 1.7 (IQR 0.4–9.3), 1.9 (IQR 0.4–6.2) and 1.0 (IQR 0.6–3.4) mg/L on study day 1, 3 and 7, respectively. Optimal (100% fT>MIC) and maximum (100% fT>4×MIC) target attainment was achieved in 45 (90%) and 34 (68%) patients, respectively, throughout the study period. Conversely, when using the EUCAST epidemiological cut-off value instead of strain-specific MICs, target attainment was achieved in only 13 (26%) patients. The mean unbound flucloxacillin trough concentration per patient was associated with neurotoxicity (OR 1.12 per 1 mg/L increase, P = 0.02) and significantly higher in deceased patients (median 14.8 versus 1.7 mg/L, P = 0.01). Conclusions Flucloxacillin pharmacological target attainment in MSSA-BSI patients is frequently achieved when unbound flucloxacillin concentrations and strain-specific MICs are considered. However, currently recommended dosing regimens may expose patients to excessive flucloxacillin concentrations, potentially resulting in drug-related organ damage.

SUMMARY Nasal glial heterotopia (NGH) is a rare congenital, non-neoplastic displacement of cerebral tissue in extracranial sites. Together with a case report of NGH, we present the first systematic review of all published cases in order to summarise the relevant clinical findings and appropriate therapy, making the available evidence accessible to decision makers. A total of 72 original publications including 152 NGH cases were identified. The male:female ratio was 3:2. Most patients were children under 18 years (130 patients) and only 8% of cases were diagnosed in adults. The main clinical presentation forms were asymptomatic masses around the nasal root as well as nasal congestion. Magnetic resonance imaging was performed in 39% of patients, computed tomography in 22% of patients and a combination of both in 20% of patients. A diagnostic biopsy was performed in only 7 patients. All patients underwent surgical treatment and recurrence was reported in 14 patients within the first year of follow-up. In conclusion, NGH should be considered as a differential diagnosis of nasal masses in children. MRI is mandatory in order to exclude a connection to the central nervous system. Complete resection is curative treatment.

Recently, a third of middle ear effusions have been shown to harbor fungal DNA by polymerase chain reaction (PCR). This suggests that fungi, in addition to being an important sinus pathogen, may also play an important role in acute and serous otitis media. Bipolaris is an important sinus pathogen whose role in infections of the ear is unknown. In this study, we assessed if Bipolaris DNA was present in 19 middle ear effusions that were PCR positive for the presence of fungi. Primer pair specific for Bipolaris spicifera was tested against DNA from various bacterial and fungal species to demonstrate its specificity and was subsequently used on DNA isolated from effusions to determine if Bipolaris-specific DNA was present. None of the nineteen specimens tested positive for Bipolaris by PCR or standard culture technique. This suggests that while fungi may play an important role in otitis media, this study does not support a role for Bipolaris as a middle ear pathogen and may reflect regional differences in its prevalence.