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Cottrell, K.

Publications and source records attributed to Cottrell, K..

2 recordsLinked to original sources

The upper respiratory tract microbiome of Australian Aboriginal and Torres Strait Islander children in ear and nose health and disease.

ObjectiveTo examine the nasal microbiota in relation to otitis status and nose health in Indigenous Australian children. MethodsChildren aged 2-7 years were recruited from two northern Australian (Queensland) communities. Clinical histories were obtained through parent interview and review of the medical record. Nasal cavity swabs were obtained, and the childs ears, nose and throat were examined. DNA was extracted and analysed by 16S rRNA amplicon next generation sequencing of the V3/V4 region in combination with previously generated culture data. Results103 children were recruited (mean 4.7 years), 17 (16.8%) were healthy, i.e. normal examination and no history of otitis media (OM). Nasal microbiota differed significantly in relation to otitis status and nose health. Children with historical OM had higher relative abundance of Moraxella compared to healthy children, despite both having healthy ears at the time of swabbing. Children with healthy noses had higher relative abundance of S. aureus compared to those with rhinorrhoea. Dolosigranulum was correlated to Corynebacterium in healthy children. Haemophilus and Streptococcus correlated across phenotypes. Ornithobacterium was absent/low relative abundance in healthy children and clustered around otopathogens. It correlated with Helcococcus and Dichelobacter. ConclusionsDolosigranulum and Corynebacterium form a synergism that promotes URT/ear health in Indigenous Australian children. Ornithobacterium likely represents Candidatus Ornithobacterium hominis and in this population is correlated with a novel bacterium which appears to be related to poor upper respiratory tract/ear health. ImportanceRecurring and chronic infections of the ear (otitis media) are disproportionately prevalent in disadvantaged communities across the globe, and in particular, within Indigenous communities. Despite numerous intervention strategies, otitis media persists as a major health issue and is the leading cause of preventable hearing loss. In disadvantaged communities, this hearing loss is associated with negative educational and social development outcomes, and consequently, poorer employment prospects and increased contact with the justice system in adulthood. Thus, a better understanding of the microbial ecology is needed in order to identify new targets to treat, as well as prevent the infections. This study used a powerful combination of 16S rRNA sequencing and extended culturomics to show that Dolosigranulum pigrum, a bacterium previously identified as a candidate protective species, may require co-colonisation with Corynebacterium pseudodiptheriticum in order to prevent otitis media. Additionally, emerging and potentially novel pathogens and bacteria were identified.

microbiology↗

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↗