I'm pleased to present this paper we published with CMI recently on the potential use of flomoxef to treat infections caused by OXA-48 producing Enterobacterales. https://t.co/pSCBtvSy7U

It’s lucky we have a famously competent state, a well-funded health service, & courts with plenty of time on their hands, or I’d be worrying that this is a terrible decision

@APTlivuni @VineetD1509 Also worth highlighting that a lot of the pre-clinical and PK work for this drug was done in the University of Liverpool. @shampadaspkpd @NikkiFarringto1 @NIHRCRF_Lpool 11/11

The article is open-access, so please read if you are interested in more detail. With thanks to my co-authors @APTlivuni and @VineetD1509 10/n

The main benefit of this drug is that it is effective against ESBL-producers but spares use of carbapenems, and therefore reduces carbapenem selection pressure for carbapenem-resistance. 9/n

The EMA and MHRA also approved a licence for use in HAP/VAP, on the basis of the pulmonary PK study and previously demonstrated efficacy of cefepime monotherapy for the treatment of HAP, and bacteraemias assoicated with cUTI or HAP/VAP 8/n

As a result of these trials, the combination has been approved in the USA, EU and UK for the treatment of complicated UTIs (with some minor differences in approval between jurisdictions) earlier this year. 7/n

Another important trial linked below, done in Liverpool, is a pulmonary PK trial for the combination demonstrating appropriate pulmonary distribution of the combination for the treatment of HAP. 6/n https://t.co/lI6xSdnhBm

The main trial for cefepime/enmetazobactam is linked below. In short, it showed superiority to piperacillin-tazobactam for the treatment of complicated UTIs on a number of measures, including efficacy against ESBL-producers. 5/n https://t.co/iqNM0FExPc

(Tazobactam does inhibit ESBLs in vitro, but clinical evidence such as the MERINO trial shows it does not do so in the clinical setting) 4/n

Enmetazobactam is a modification of tazobactam to beta-lactamase inhibitory activity against ESBL. The combination with cefepime, therefore, is an BL/BLI combination that is efficacious against ESBL- and AmpC-producing Enterobacterales 3/n

As people will know, cefepime is a broad-spectrum cephalosporin with Gram-positive and -negative (including anti-pseudomonal) activity and is stable to degradation by AmpC. However, it remains susceptible to degradation by ESBLs. 2/n

Pleased to shared our publication of this open-access review of cefepime/enmetazobactam, a novel beta-lactam/beta-lactamase inhibitor combination approved earlier this year . 1/n https://t.co/3c00xguXXu

A seven-day course of antibiotics for hospitalized patients with bloodstream infections is just as effective as a 14-day course, according to new findings presented at #IDWeek2024. Learn more:

Very few people realise that the vast majority of hospice and palliative care is provided by charity - not by the NHS. I think this is a national scandal. Please RT if you do too 🙏

Not for the first time, all Nobel Prizes in scientific disciplines this year have been awarded to men

Thank you to all the co-authors for their hard work with this. @VineetD1509 @Sara_E_Boyd @AleGerada @gardp_amr @APTlivuni

Flomoxef is being tested in a neonatal sepsis trial in LMIC settings, predominantly because it is effective against ESBL producers. However, it will be interesting if any data comes from this showing clinical efficacy against incidental OXA-48 producers. https://t.co/Ax9pwiSQE6

Given the paucity of alternate β-lactam agent active against OXA-48, and the high cost of those that do, an off-patent agent with activity against OXA-48 like flomoxef may be useful in LMIC settings where these agents are unavailable or unaffordable.

However, as you can see, cefoxitin sensitive isolates - all producing OXA-48) - universally had a low flomoxef MIC. The upshot is that flomoxef may be suitable for use treating infections by OXA-48 producers.

Of the 246 isolates we eventually determined an MIC for, these are the flomoxef (and meropenem) MIC results. Cefoxitin resistance is a marker of AmpC production, so cefoxitin resistant strains should be resistant to flomoxef, given it is degraded by AmpC.