Fungal yield from sterile specimens.

Clinicians may not request fungal culture when it is indicated. For sterile specimens without a specific request for fungal culture, in addition to bacteriology media, we routinely incubated a Sabouraud dextrose agar (SAB) plate for 4 weeks. From 44635 sterile specimens from years 2011 to 2016, 2722 (6.1%) had fungal request. Fungi were identified from 1037 (2.3%) specimens, 292 (0.6%) from specimens with specific fungal request, 574 (1.3%) from bacteriology media, and 171 (0.4%) solely from SAB plate (of 171, 77 were deemed clinically significant and 55 were treated). Relying on request for fungal studies from sterile specimens underdiagnosed fungal infection. Routine fungal culture had a modest incremental yield at a moderately high cost. LAY SUMMARY: Routine fungal culture of sterile specimens had a modest incremental yield to routine bacteriology culture and specific fungal request at a moderately high financial cost.

Quantitative Pneumocystis jirovecii real-time PCR to differentiate disease from colonisation.

We studied a Pneumocystis jirovecii quantitative polymerase chain reaction (qPCR) for distinguishing P. jirovecii disease from colonisation. Eighty-two respiratory samples from 65 patients with qPCR results were analysed against a gold standard clinical diagnosis of Pneumocystis pneumonia. High inter-assay reproducibility using recombinant and clinical material was observed. Contemporaneous samples from the same patient displayed high variability (median difference 2.6 log10 copies/mL, IQR 2.1-3.1 log10 copies/mL). Despite this, area under the receiver operator characteristic curve was 0.8. An optimum cut-off of 2.8 log10 copies/mL (equivalent to CT of 34.0 cycles) had 59% sensitivity and 92% specificity. The median P. jirovecii load was 7.3 log10 copies/mL in HIV patients compared to 2.6 log10 copies/mL in non-HIV patients. Specificity was 100% in non-HIV patients with qPCR of >3.8 log10 copies/mL. qPCR was useful for distinguishing P. jirovecii disease from colonisation. A quantitative standard, standardisation of definitions and methods are required to improve the generalisability of results.

Population Pharmacokinetic Study of Ceftriaxone in Elderly Patients, Using Cystatin C-Based Estimates of Renal Function To Account for Frailty.

Ceftriaxone is widely used for respiratory and urinary infections in elderly and frail patients, but there are few pharmacokinetic studies. A prospective population pharmacokinetic study of ceftriaxone in adults over 65 years old was undertaken. Dried blood spots collected at baseline (predose) and 0.5, 1, 4, 8, and 24 h after administration of 1 g of ceftriaxone were assayed using a validated liquid chromatography-mass spectroscopy analytical method. Frailty was classified using the Edmonton frailty scale and grip strength via a hand dynamometer. Estimates of glomerular filtration rate were determined using creatinine-based and cystatin C-based equations. Of 26 patients recruited, 23 (88%) were vulnerable or very frail. Estimates of drug clearance improved significantly with a cystatin C-based estimate of renal function that accounted for frailty. Simulations indicate that the combined effects of ranges of size and renal function resulted in a 6-fold range in peak ceftriaxone concentrations and 9-fold range in total exposure (area under the concentration-time curve [AUC]). For elderly patients with moderate or severe renal impairment, 48-h dosing results in greater trough concentrations and total exposure than the trough concentrations and total exposure in patients with normal renal function receiving 24-h dosing. Cystatin C-based measures of renal function improved predictions of ceftriaxone clearance in elderly patients.

Contact lens associated keratitis due to Tintelnotia destructans.

We report the first case of Tintelnotia destructans associated keratitis in a contact lens wearer in Australia. Corneal scrape showed fungal elements on direct microscopy leading to a prompt diagnosis of fungal keratitis and early topical and systemic antifungal therapy. The isolate was eventually identified by ITS gene sequencing. This case highlights the importance of accurate identification and antifungal susceptibility testing for the management of fungal keratitis.