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Antimicrobial Resistance in the bladder.

From our CMO Professor Scott Glickman


Colleagues:


In medical and surgical services spanning primary through intensive care, we are dogged by UTI with their acute and long-term complications: treatment failures, recurrences, urosepsis, antimicrobial resistance (AMR) and high costs. Despite continuous improvements in antibiotic stewardship, these problems show little sign of abating.


Something else must be involved.


Antibiotic overuse and misuse shouldn’t be blamed exclusively to the extent of ignoring other fundamentals of pharmacology and microbiology. I suggest that even with microbial sensitivity-based treatment, oral antibiotics are so inefficiently delivered into the bladder that even with the most robust drug stewardship, they risk all the problems noted, with which we now contend routinely.


Consider these fundamentals:

Plasma antibiotic concentration augmented by some renal secretion and water reabsorption, dripped into the bladder through ureters, sometimes dilutes into high-volume antibiotic-naive urine pools. In such circumstances, bacteria sensing the threat have opportunity to mutate, phenotypically express latent AMR genes or leave the compartment before having to confront a bactericidal concentration.

If bacteria adapt or leave before the therapeutic level is reached, subsequent bactericidal concentration in-situ might only kill laggers or wash over biofilms at that point.

Oral antibiotics absorbed, intrusively course through the system, then leave it to arrive at the intravesical battleground, offering no therapeutic value before reaching it.


Antibiotic drip-feed into the bladder cavity is taken for granted as sound in cystitis treatments. However, gradual concentration build-up is not how antimicrobials are seen to be used in nature. Drug drip-feed into the intravesical space, suitable for waste disposal seems inefficient for reliable antimicrobial action in the bladder. It seems to offer the pharmacological equivalent, in some cases, of “closing the stable door after the horses have bolted." Of course, successful treatments abound but so do failures, recurrences and AMR, which threaten patients and society more widely.


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