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UTI's

TESTING FOR UTI
​New techniques for testing for UTI include ATP bioluminescence. Growing bacteria produce ATP, and a panel of antibodies against 13 uropathogens gives identification results in 20min for 10x3 CFU/ml. (10)

UTI w/ CKD
​Bactrim and nitrofurantoin give insufficient urine concentrations if CrCl<50ml/min; however, ciprofloxacin does give above the MIC for urinary pathogens.  Levofloxacin can give sufficient levels if CrCl<50ml/min, but both moxifloxacin or gemifloxacin do not. (1,2)  Cefazolin and ceftriaxone achieve very high urine concentration and subtherepaeutic concentrations with renal insufficiency is unlikely. Urethritis/cystitis with chronic renal insufficiency can be treated with selected fluoroquinolones (ciprofloxacin, levofloxacin) and trimethoprim alone.(1) 

Urine concentrations of sulfamethoxazole falls to subtherapeutic concentrations in patients with creatinine clearances <50 ml/min (30). but urine trimethoprim remains high even with marked renal insufficiency (8). The authors of one paper suggest to prescribe trimethoprim alone, in reduced dosage, for the treatment of uncomplicated cystitis in patients with a low creatinine clearance. (1) 

For pyelonephritis, as cipro does not cover enterococcus, this species can be treated with ampicillin, piperacillin-tazobactam, ticarcillin-clavulanate and vanco if penicillin allergy and daptomycin does get good urine concentration as well. Ertapenem is another option but does not have good coverage  of P. aeruginosa or Enterococcus species.  (3)  Pyelonephritis in patients with GFR between 10- to 50-ml/min should get reduction of dosage to avoid high serum concentrations with Ciprofloxacin or levofloxacin are suggested as first choices for empiric therapy. (1)

Here is a good table breaking down the antibiotics excretion compared to peak serum levels of common antibiotics. The MIC for 90% of the bacteria that commonly cause UTI is usually <16 μg/ml.  (1)

CYSTITIS
Cipro better than augmentin in women shown in RCT in 2005​. (7)  Imipenem and ertapenem are approved for the treatment of UTI, however not meropenem. (1) One RCT found drinking 1.5L more than normal intake had lower rate of UTI with  1.7 (95% CI, 1.5-1.8) UTI's per 12mo in the water group compared with 3.2 (95% CI, 3.0-3.4) in the control group. (9)

PCKD
Published reports indicate trimethoprim-sulfamethoxazole, ciprofloxacin, and chloramphenicol can reach therapeutic concentrations be in the cyst fluid of PCKD patients (5,6). However, penicillins, cephalosporins, and aminoglycosides do not reach sufficient cyst concentrations (4).

CONFUSION AS A SYMPTOM
A systematic review found poor evidence quality with differing opinions from different authors. (11) 

  1. Gilbert, David N. "Urinary tract infections in patients with chronic renal insufficiency." Clinical Journal of the American Society of Nephrology 1.2 (2006): 327-331.​
  2. Gasser TC, Ebert SC, Graversen PH, Madsen PO: Ciprofloxacin pharmacokinetics in patients with normal and impaired renal function. Antimicrob Agents Chemother 31:709–712, 1987.​
  3. Wexler HM: In vitro activity of ertapenem: Review of recent studies. J Antimicrob Chemother 53[Suppl 2]: 11–21, 2004
  4. Muther, Richard S., and William M. Bennett. "Concentration of antibiotics in simple renal cysts." The Journal of urology 124.5 (1980): 596.
  5. Elzinga LW, Golper TA, Rashad AL, Carr ME, Bennett WM: Trimethoprim-sulfamethoxazole in cyst fluid from autosomal dominant polycystic kidneys. Kidney Int32: 884–888, 1987
  6. Elzinga LW, Golper TA, Rashad AL, Carr ME, Bennett WM: Ciprofloxacin activity in cyst fluid from polycystic kidneys. Antimicrob Agents Chemother 32: 844–847, 1988
  7. Hooton TM, Scholes D, Gupta K, Stapleton AE, Roberts PL, Stamm WE: Amoxicillin-clavulanate vs ciprofloxacin for the treatment of uncomplicated cystitis in women: A randomized trial. JAMA 293: 949–955, 2005
  8. Craig WA, Kunin CM: Trimethoprim-sulfamethoxazole: Pharmacodynamic effects of urinary pH and impaired renal clearance. Ann Intern Med 78: 491–497, 1973
  9. Hooton, Thomas M., et al. "Effect of increased daily water intake in premenopausal women with recurrent urinary tract infections: a randomized clinical trial." JAMA internal medicine(2018).
  10. Dong, T., & Zhao, X. (2015). Rapid Identification and Susceptibility Testing of Uropathogenic Microbes via Immunosorbent ATP-Bioluminescence Assay on a Microfluidic Simulator for Antibiotic Therapy. Analytical Chemistry, 87(4), 2410–2418.
  11. Mayne, Sean, et al. "The scientific evidence for a potential link between confusion and urinary tract infection in the elderly is still confusing-a systematic literature review." BMC geriatrics 19.1 (2019): 32.
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