UroPharma produced #intravesical drug-delivery technology to bring, under licence, better cystitis (lower #UTI) treatments.
For decades, historical presumptions have led healthcare into #AMR “quicksand” through flawed cystitis treatments.
The presumption: #Antibiotic treatment to kill #cystitis uropathogens “outside the system” equates with systemic tissue #infection #treatments. That is completely wrong. We should have known that straight away.
#Pharmacokinetic analyses end after renal filtration, ignoring #intravesical factors but antibiotics don’t confront cystitis bacteria until entering bladder urine. The pathogens are extra-systemic! Intravesical factors complexify the treatments immensely.
Here’s how: #Urinary antibiotic inflow is diluted commensurate with antecedent intravesical urine volume, the norm being ~200-300ml, but the range is wider, increasing tail-end dilution at the upper end. Therefore, achieving renal filtrate’s antibiotic concentration (present in renal calyces) in the bladder could take many hours offering bacteria time for biofilm development and, thus, protected time for mutation to AMR, which, in turn, protects them from the rising antibiotic concentration.
Antibiotic entry into bladder urine is rate limited by renal filtration (averaging ~1ml/minute), so intravesical therapeutic build-up is slow, leaving bacteria in a subtherapeutic pool for many bacterial generations.
Antibiotic MIC, established for systemic treatments at narrow-ranging plasma pH, may vary wildly from MIC at widely variant urinary pH, undermining efficacy.
Every cystitis-treating clinician, microbiologist, #drugsafety regulator, AMR czar can analyse this themselves by tracking the molecules in their mind, but the analysis is now published: https://www.mdpi.com/2079-6382/13/4/328
AMR following cystitis treatments continue relentlessly, despite best #antibioticstewardship. The time has come to blame the flawed, complicated #oral/systemic treatment approach, not careful prescribers. Furthermore, we must abide by #betterdrugtreatment principles, including #directtargeting, which trumps pharmacokinetic complexity and idiosyncrasies (a tenet taught to every pharmacology student) and consider the entire drug journey.