Combining branched copolymers with additives generates stable thermoresponsive emulsions with in situ gelation upon exposure to body temperature.

Branched copolymer surfactants (BCS) containing thermoresponsive polymer components, hydrophilic components, and hydrophobic termini allow the formation of emulsions which switch from liquid at room temperature to a gel state upon heating. These materials have great potential as in situ gel-forming dosage forms for administration to external and internal body sites, where the emulsion system also allows effective solubilisation of a range of drugs with different chemistries. These systems have been reported previously, however there are many challenges to translation into pharmaceutical excipients. To transition towards this application, this manuscript describes the evaluation of a range of pharmaceutically-relevant oils in the BCS system as well as evaluation of surfactants and polymeric/oligomeric additives to enhance stability. Key endpoints for this study are macroscopic stability of the emulsions and rheological response to temperature. The effect of an optimal additive (methylcellulose) on the nanoscale processes occurring in the BCS-stabilised emulsions is probed by small-angle neutron scattering (SANS) to better comprehend the system. Overall, the study reports an optimal BCS/methylcellulose system exhibiting sol-gel transition at a physiologically-relevant temperature without macroscopic evidence of instability as an in situ gelling dosage form.

Antibiotic resistance in patients with chronic ear discharge awaiting surgery in Nepal.

SETTING: Biratnagar Eye Hospital, Biratnagar, Nepal, which offers ear surgery for chronic suppurative otitis media (CSOM). OBJECTIVE: In patients with CSOM awaiting surgery, to determine the 1) sociodemographic characteristics 2) bacterial isolates and their antibiotic resistance patterns and 3) characteristics of those refused surgery, including antibiotic resistance. DESIGN: A cohort study using hospital data, January 2018-January 2020. RESULTS: Of 117 patients with CSOM and awaiting surgery, 64% were in the 18-35 years age group, and 79% were cross-border from India. Of 118 bacterial isolates, 80% had Pseudomonas aeruginosa and 16% had Staphylococcus aureus. All isolates showed multidrug resistance to nine of the 12 antibiotics tested. The lowest antibiotic resistance in P. aeruginosa was for vancomycin (29%) and moxifloxacin (36%), and for S. aureus, this was vancomycin (9%) and amikacin (17%). Fourteen (12%) patients underwent surgery: myringoplasty (n = 7, 50%), cortical mastoidectomy with tympanostomy (n = 4, 29%) and modified radical mastoidectomy (n = 3, 21%). Those infected with P. aeruginosa and with resistance to over six antibiotics were significantly more likely to be refused for surgery. CONCLUSION: Patients awaiting ear surgery were predominantly infected with multidrug-resistant P. aeruginosa and were consequently refused surgery. This study can help inform efforts for improving surgical uptake and introducing cross-border antimicrobial resistance surveillance.

LIEU: Hôpital ophtalmologique de Biratnagar, Népal, qui propose des interventions chirurgicales de l'oreille aux patients atteints d'otite moyenne chronique suppurée (CSOM). OBJECTIF: Déterminer 1) les caractéristiques sociodémographiques, 2) les isolats bactériens et leurs profils de résistance aux antibiotiques et 3) les caractéristiques des patients se voyant refuser la chirurgie (dont résistance aux antibiotiques) chez les patients atteints de CSOM en attente de chirurgie. MÉTHODE: Étude de cohorte réalisée à l'aide de données hospitalières, janvier 2018-janvier 2020. RÉSULTATS: Sur les 117 patients atteints de CSOM en attente de chirurgie, 64% appartenaient à la tranche d'âge des 18­35 ans et 79% étaient des patients transfrontaliers en provenance d'Inde. Sur 118 isolats bactériens, 80% étaient des isolats de Pseudomonas aeruginosa et 16% de Staphylococcus aureus. Tous les isolats ont montré une résistance à neuf des 12 antibiotiques testés. Les plus faibles résistances chez P. aeruginosa étaient celles à la vancomycine (29%) et à la moxifloxacine (36%). Pour S. aureus, il s'agissait de celles à la vancomycine (9%) et à l'amikacine (17%). Quatorze (12%) patients ont subi une intervention chirurgicale : myringoplastie (n = 7, 50%), mastoïdectomie corticale avec tympanotomie (n = 4, 29%) et mastoïdectomie radicale modifiée (n = 3, 21%). Les patients infectés par P. aeruginosa avec une résistance à plus de six antibiotiques étaient significativement plus susceptibles de se voir refuser la chirurgie. CONCLUSION: Les patients en attente de chirurgie de l'oreille étaient principalement infectés par un isolat multirésistant de P. aeruginosa, et se sont donc vu refuser la chirurgie. Cette étude peut permettre d'orienter les efforts visant à améliorer le taux de chirurgies réalisées et à mettre en place une surveillance transfrontalière des résistances antimicrobiennes.

Matrix-assisted laser desorption ionization time-of-flight mass spectrometry for the rapid identification of yeasts causing bloodstream infections.

Few studies have systematically standardised and evaluated matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) for identification of yeasts from bloodstream infections. This is rapidly becoming pertinent for early identification of yeasts and appropriate antifungal therapy. We used 354 yeast strains identified by polymerase chain reaction (PCR) sequencing for standardisation and 367 blind clinical strains for validation of our MALDI-TOF MS protocols. We also evaluated different sample preparation methods and found the on-plate formic acid extraction method as most cost- and time-efficient. The MALDI-TOF assay correctly identified 98.9% of PCR-sequenced yeasts. Novel main spectrum projections (MSP) were developed for Candida auris, C. viswanathii and Kodamaea ohmeri, which were missing from the Bruker MALDI-TOF MS database. Spectral cut-offs computed by receiver operating characteristics (ROC) analysis showed 99.4% to 100% accuracy at a log score of ≥ 1.70 for C. tropicalis, C. parapsilosis, C. pelliculosa, C. orthopsilosis, C. albicans, C. rugosa, C. guilliermondii, C. lipolytica, C. metapsilosis, C. nivariensis. The differences in the species-specific scores of our standardisation and blind validation strains were not statistically significant, implying the optimal performance of our test protocol. The MSPs of the three new species also were validated. We conclude that MALDI-TOF MS is a rapid, accurate and reliable tool for identification of bloodstream yeasts. With proper standardisation, validation and regular database expansion, its efficiency can be further enhanced.