Photodynamic antimicrobial chemotherapy coupled with the use of the photosensitizers methylene blue and temoporfin as a potential novel treatment for Staphylococcus aureus in burn infections

Photodynamic antimicrobial chemotherapy (PACT) is a novel alternative antimicrobial therapy that elicits a broad mechanism of action and therefore has a low probability of generating resistance. Such properties make PACT ideally suited for utilization in localized applications such as burn wounds. The aim of this study was to determine the antimicrobial activity of MB and temoporfin against both a S. aureus isolate and a P. aeruginosa isolate in light (640 nm) and dark conditions at a range of time points (0–20 min). A Staphylococcus aureus isolate and a Pseudomonas aeruginosa isolate were treated in vitro with methylene blue (MB) and temoporfin under different conditions following exposure to light at 640 nm and in no-light (dark) conditions. Bacterial cell viability [colony-forming units (c.f.u.) ml−1] was then calculated. Against P. aeruginosa , when MB was used as the photosensitizer, no phototoxic effect was observed in either light or dark conditions. After treatment with temoporfin, a reduction of less than one log (7.00×107 c.f.u. ml−1) was observed in the light after 20 min of exposure. However, temoporfin completely eradicated S. aureus in both light and dark conditions after 1 min (where a seven log reduction in c.f.u. ml−1 was observed). Methylene blue resulted in a loss of S. aureus viability, with a two log reduction in bacterial viability (c.f.u. ml−1) reported in both light and dark conditions after 20 min exposure time. Temoporfin demonstrated greater antimicrobial efficacy than MB against both the S. aureus and P. aeruginosa isolates tested. At 12.5 µM temoporfin resulted in complete eradication of S. aureus . In light of this study, further research into the validity of PACT, coupled with the photosensitizers (such as temoporfin), should be conducted in order to potentially develop alternative antimicrobial treatment regimes for burn wounds.</jats:p

The prescribable drugs with efficacy in experimental epilepsies (PDE3) database for drug repurposing research in epilepsy

Objective Current antiepileptic drugs (AEDs) have several shortcomings. For example, they fail to control seizures in 30% of patients. Hence, there is a need to identify new AEDs. Drug repurposing is the discovery of new indications for approved drugs. This drug “recycling” offers the potential of significant savings in the time and cost of drug development. Many drugs licensed for other indications exhibit antiepileptic efficacy in animal models. Our aim was to create a database of “prescribable” drugs, approved for other conditions, with published evidence of efficacy in animal models of epilepsy, and to collate data that would assist in choosing the most promising candidates for drug repurposing. Methods The database was created by the following: (1) computational literature‐mining using novel software that identifies Medline abstracts containing the name of a prescribable drug, a rodent model of epilepsy, and a phrase indicating seizure reduction; then (2) crowdsourced manual curation of the identified abstracts. Results The final database includes 173 drugs and 500 abstracts. It is made freely available at www.liverpool.ac.uk/D3RE/PDE3. The database is reliable: 94% of the included drugs have corroborative evidence of efficacy in animal models (for example, evidence from multiple independent studies). The database includes many drugs that are appealing candidates for repurposing, as they are widely accepted by prescribers and patients—the database includes half of the 20 most commonly prescribed drugs in England—and they target many proteins involved in epilepsy but not targeted by current AEDs. It is important to note that the drugs are of potential relevance to human epilepsy—the database is highly enriched with drugs that target proteins of known causal human epilepsy genes (Fisher's exact test P‐value < 3 × 10−5). We present data to help prioritize the most promising candidates for repurposing from the database. Significance The PDE3 database is an important new resource for drug repurposing research in epilepsy