Biology subjects

Norton, R.

Publications and source records attributed to Norton, R..

3 recordsLinked to original sources

bioRxiv2020

Burkholderia pseudomallei clinical isolates are highly susceptible in vitro to cefiderocol, a novel siderophore cephalosporin

Cefiderocol is a novel cephalosporin designed to treat multidrug resistant Gram-negative infections. By forming a chelated complex with ferric iron, cefiderocol is transported into the periplasmic space via bacterial iron transport systems and primarily binds to penicillin-binding protein 3 (PBP3) to inhibit peptidoglycan synthesis. This mode of action results in cefiderocol having greater in vitro activity against many Gram-negative bacilli than currently used carbapenems, {beta}-lactam/{beta}-lactamase inhibitor combinations, and cephalosporins. Thus, we investigated the in vitro activity of cefiderocol (S-649266) against a total of 271 clinical isolates of Burkholderia pseudomallei from Australia. The collection was comprised of primary isolates (92.3%) and subsequent isolates (7.7%). Minimum inhibitory concentrations (MIC) of cefiderocol ranged from [≤]0.03 to 32 mg/L, where the MIC90 was 1 mg/L and 16 mg/L for primary and subsequent isolates, respectively. Based upon non-species specific (Gram-negative bacilli) clinical breakpoints for cefiderocol (MIC [≤] 4 mg/L), twelve isolates (4.4%) would be classified as non-susceptible. Further testing for co-resistance to meropenem, ceftazidime, trimethoprim-sulfamethoxazole, amoxicillin-clavulanate and doxycycline was performed on a subset of isolates with elevated cefiderocol MICs ([≥]2 mg/L, 4.8%) and 84.6% of these isolates exhibited resistance to at least one of these antimicrobials. Cefiderocol was found to be highly active in vitro against B. pseudomallei primary clinical isolates. This novel compound shows great potential for the treatment of melioidosis in endemic countries and should be explored further.

microbiology↗

bioRxiv2019

Prospective evaluation of beta-lactamase detection in penicillin susceptible Staphylococcus aureus by interpretation of the penicillin disc edge

Penicillin susceptible Staphylococcus aureus (PSSA) may occasionally be encountered as a cause of complicated S. aureus infection, such as endocarditis or bloodstream infections. Clinicians may choose to treat these patients with penicillin over a semi-synthetic penicillin derivative, such as flucloxacillin or oxacillin, due to a favourable Pk/Pd profile. In this study, we prospectively evaluated the penicillin disc (1-IU) method for detection of blaZ, with interpretation of the penicillin edge according to EUCAST recommendations. 472 PSSA isolates were collected between September 2014 to December 2015 from three clinical microbiology laboratories in Queensland, Australia. Initial antimicrobial susceptibility testing was performed by the Vitek 2 system. Real-time PCR for blaZ was performed following phenotypic testing with the 1-IU penicillin disc and the PCR used as the gold standard for detection of penicillinase. The prevalence of blaZ amongst the isolates was 7%. The sensitivity, specificity, positive predictive value and negative predictive value of the penicillin disc method was 97%, 95%, 61% and 100% when compared to blaZ PCR. In summary, the penicillin disc zone size and edge interpretation is a reliable method for detection of blaZ in S. aureus isolates that otherwise test susceptible to penicillin by Vitek 2 AST.

microbiology↗

bioRxiv2018

Using Network Analysis to Localize the Epileptogenic Zone from Invasive EEG Recordings in Intractable Focal Epilepsy

Treatment of medically intractable focal epilepsy (MIFE) by surgical resection of the epileptogenic zone (EZ) is often effective provided the EZ can be reliably identified. Even with the use of invasive recordings, the clinical differentiation between the EZ and normal brain areas can be quite challenging, mainly in patients without MRI detectable lesions. Consequently, despite relatively large brain regions being removed, surgical success rates barely reach 60-65%. Such variable and unfavorable outcomes associated with high morbidity rates are often caused by imprecise and/or inaccurate EZ localization. We developed a localization algorithm that uses network-based data analytics to process invasive EEG recordings. This network algorithm analyzes the centrality signatures of every contact electrode within the recording network and characterizes contacts into susceptible EZ based on the centrality trends over time. The algorithm was tested in a retrospective study that included 42 patients from four epilepsy centers. Our algorithm had higher agreement with EZ regions identified by clinicians for patients with successful surgical outcomes and less agreement for patients with failed outcomes. These findings suggest that network analytics and a network systems perspective of epilepsy may be useful in assisting clinicians in more accurately localizing the EZ.\n\nAUTHOR SUMMARYEpilepsy is a disease that results in abnormal firing patterns in parts of the brain that comprise the epileptogenic network, known as the epileptogenic zone (EZ). Current methods to localize the EZ for surgical treatment often requires observations of hundreds of thousands of EEG data points measured from many electrodes implanted in a patients brain. In this paper, we used network science to show that EZ regions may exhibit specific network signatures before, during and after seizure events. Our algorithm computes the likelihood of each electrode being in the EZ and tends to agree more with clinicians during successful resections and less during failed surgeries. These results suggest that a networked analysis approach to EZ localization may be valuable in a clinical setting.

neuroscience↗