Antifungals in UTI

I am currently working on a proposal to switch our main formulary echinocandin to Micafungin for cost & simplicity purposes (no loading dose as compared to caspo), working on an “approved indications” for both meds. I’m under the impression that neither option is recommended for treatment of UTI, but I have never actually substantiated this. Let’s see what we can find.

Candida Urinary Tract Infections - Treatment
Clinical Infectious Diseases, 2011

• most lab reports of candiduria represent colonization or procurement contamination (often these are good ASP opportunities as they are treated for no reason)
• fluconazole is preferred as a candida treatment in urine as it concentrates well (as unchanged drug; highly water soluble; 10-fold times the plasma level!), possibly even as compared to other azoles
  • itra/vori/posa have terrible urine concentration
  • article lists flucytosine PO as a valid alternative despite high side effects (concentrates well in urine), but does not appear to be available in Canada
  • amphoB concentrates well, can also do bladder irrigation
• search for predisposing factors when you find candiduria, because you can find things like DM, GU structural abnormalities, deminished renal function… that you wouldn’t have otherwise found!
• watch out with asymptomatic candiduria in hospitalized patients, in case they are at risk of it going systemic. Change the catheter!
• glabrata and krusei are more likely to be fluc resistant
• AmphoB candida resistance is rare, esp in albicans
  • pilot studies show potential for single 1mg/kg dose that will lead to urine concentrations > MIC for days to months post dose!
  • lipid amphoB are less nephrotoxic but concentrate worse in urine. potential for tx failure
  • high relapse after bladder irrigation method, generally don’t use it
• the drugs that concentrate poorly in urine may do better for pyelo due to increased renal concentrations, but fluc is still preferred
• use at least 400mg of fluc regardless of renal failure. hmm.
• so, turns out this article actually doesn’t mention the echinocandins beyond the fact that their role is unclear due to their poor urine contentrations. Oh well, I learned a lot anyway. Will be a good reference to come back to for details on specific GU infections (I didn’t go into the prostatitis section, for example)

Treatment of candiduria with micafungin: A case series
Canadian Journal of Infectious Diseases and Medical Microbiology, 2007

• glabrata UTI increasing in frequency, can be seen in patients who’ve received fluconazole
• 3 cases of successful UTI tx (fluc resistant albicans, glabrata, glabrata again)
• echinocandins are less active against parapsilosis ?

A case of Candida glabrata severe urinary sepsis successfully treated with micafungin
Medical Mycology Case Reports, 2014

• Pt with fluc-resistant glabrata in patient also with advanced renal failure
• 20% chance of glabrata (50-70% chance of albicans)
• Micafungin clearance is not affected by renal dysfunction, so it is safe to use in renal failure (especially compared to fluc, amphoB, etc!)
• all echinocandins have poor glomerular filtration and tubular secretion = poor urine concentration (think I’ve figured that out by now)
  • therefore, use has historically been avoided in UTI
• still probably has excellent tissue penetration - including kidneys
• treated patient with 200 mg daily of micafungin, double the usual dose. Trying to achieve higher renal concentration. No adverse effects were seen
  • this dose is formally indicated for invasive candidiasis not responding to standard dosing
  • pt also had hypoalbuminemia; would have had more free serum micafungin, possibly contributing to the treatment success

The 2016 IDSA guidelines for Candiduria do not recommend echinocandins, amphoB is preferred (non-liposomal, 1-7 days!). They may work if upper infection is suspected, but are still last-line. There are mentions of case reports of treatment failures for glabrata UTI.

My take-away: we should be preferentially using amphoB (non-liposomal) for symptomatic candiduria when fluconazole is not a valid option for whatever reason. Will definitely not be putting UTI on the recommended indications list for caspo/mica.

Linking those amphoB dosing studies here for future reference (not super relevant for this research)

Fisher JF, Hicks BC, DiPiro JT, Venable J, Fincher R-M . Efficacy of a single intravenous dose of amphotericin B in urinary infections caused by Candida. J Infect Dis 1987;156:685-7.
Fisher JF, Woeltje K, Espinel-Ingroff A, Stanfield J, DiPiro JT . Efficacy of a single intravenous dose of amphotericin B for Candida urinary tract infections: further favorable experience. Clin Microbiol Infect 2003;9:1024-7.