In January 2022, an interesting study was published that discussed the importance of a subtle yet management-altering urinalysis finding in women with a simple urinary tract infection. What is this finding and how does it affect management of UTIs in women?
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A 48-year-old woman presents with a complaint of dysuria, frequent urination, urgency, and foul-smelling urine for the last 3 days.
She denies fever, chills, flank pain, or gross hematuria.
She has had a hysterectomy for dysplasia, and has no other medical history.
Her clean catch urine shows:
Microscopy shows many bacteria, <5 squamous epithelial cells/high- power field (HPF); > 2 RBC/HPF RBCs; > 10 WBC/HPF WBC, urobilinogen 1.5 mg/dL, no budding yeast.
Question:
Positive urobilinogen is predictive of microbial resistance to ciprofloxacin.
The combination of high specific gravity and an elevated urobilinogen is predictive of microbial resistance to trimethoprim-sulfamethoxazole.
Protein spilling in combination with an elevated urobilinogen is predictive of microbial resistance to trimethoprim-sulfamethoxazole.
Alkaline pH is predictive of microbial resistance to nitrofurantoin.
Discuss a simple clue that predicts nitrofurantoin treatment failure in otherwise healthy women with a simple UTI.
A recently published study found that in women with a simple UTI, an alkaline urinary pH >8 predicts a high rate of microbial resistance to nitrofurantoin. The study found that cefazolin, ciprofloxacin, and TMP/SMX retained effectiveness and were much more effective than nitrofurantoin at higher urine pH levels.
Given the unavoidable delay in culture and antimicrobial sensitivity data, emergency physicians typically initiate empiric antibiotics to treat simple UTIs. The Infectious Diseases Society of America (IDSA) and the Society of Academic Emergency Medicine (SAAEM) recommend nitrofurantoin or trimethoprim-sulfamethoxazole (TMP/SMX) as equal first-line antibiotic options in this scenario. Other recommended, equivalent first line antibiotics are fosfomycin or pivmecillinam (UpToDate) or cefazolin, or ciprofloxacin (Sheele).
The study by Sheele reconfirmed that the most commonly cultured bacteria in simple UTI were Escherichia species at 52.3% (n = 7035); Enterococcus species, 7.1% (n = 965); and Proteeae group, 6.7% (n = 906). The proteeae group produces urease, which renders the urine increasingly alkaline as the infection progresses.
The authors found a strong correlation between a urine pH > 8 and microbial resistance to nitrofurantoin. More specifically, at urine pH 5-7,the majority (80%) of urine samples were sensitive to nitrofurantoin, whereas only 66% were sensitive to nitrofurantoin at a urine pH 8-9 and only 55% at a urine pH 9.
They concluded that physicians should consider an antibiotic other than nitrofurantoin (they suggested TMP/SMX , cefazolin, ciprofloxacin) when empirically treating patients with a UTI who have an alkaline urine with a pH ≥ 8.
Neither specific gravity nor protein spilling or urobilinogen levels are associated with any particular antibiotic resistance in women with a simple (or complicated) UTI.
Urobilinogen is a colorless pigment produced from the breakdown of bilirubin by gut bacteria. The majority of this compound is excreted in feces, and a small amount is reabsorbed and excreted in the urine. When bilirubin production increases because of red blood cell destruction (hemolysis) or liver disease, urobilinogen levels rise in the urine. On the other hand, when insufficient bilirubin reaches the gut due to decreased bile flow, urobilinogen production is reduced, resulting in extremely low or absent urinary urobilinogen levels. For these reasons, a urobilinogen test is used with other tests to help detect liver, gallbladder, or red blood cell problems.
J.M. Sheele et al. Alkaline Urine In The Emergency Department Predicts Nitrofurantoin Resistance, Journal of Emergency Medicine, 2021.10.022.
Hooton TM, et al. Acute simple cystitis in women. UpToDate. (Updated Feb 2022) (Accessed March 15, 2022)
Gupta K, Hooton TM, Naber KG, et al. International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis and Pyelonephritis in Women: A 2010 update by the Infectious Diseases Society of America and the European Society for Micro- biology and Infectious Diseases. Clin Infect Dis 2011;52:e103–20.
Liu H, Zhu J, Hu Q, Rao X. Morganella morganii, a non-negligent opportunistic pathogen. Int J Infect Dis 2016;50:10–17.
Bush LM, Vazquez-Pertejo MT. Proteeae infections. Accessed March 15, 2022.
Roxe DM. Urinalysis. In: Walker HK, Hall WD, Hurst JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths; 1990. Chapter 191.
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