50 Years of UTIs and Treatments -- Has Much Changed?

Abstract and Introduction

Abstract

Urinary tract infections (UTIs) have burdened mankind long before a causative agent was even found, dating all the way back to ancient Egypt. Up until the past 80 years, there was no extremely effective treatment of UTI. However, that all changed with the emergence of antibiotics. Once nitrofurantoin was introduced and its efficacy was noted for UTI, it became and remained the drug of choice for first-line therapy. Antimicrobial stewardship is one significant change in the last 50 years that has limited the use of antibiotics to "only when necessary" and with the right medication to prevent development of resistance. The diagnosis of UTI has improved; more tests (e.g., urinalysis, urine cultures) have been developed than just the color/cloudiness test. The treatment of complicated and recurrent UTI has also made considerable progress in the last 50 years, along with principles of prevention.

Introduction

A urinary tract infection (UTI) is an infection of the lower and/or upper genitourinary tact. A UTI is diagnosed based on the presence of a pathogen in the urinary tract and with an associated group of symptoms. Dysuria is the key symptom of bacterial cystitis. Frequency, urgency, hematuria, and supra pubic pain are variably present and can be associated with other diagnoses (Brubaker, Carberry, Nardos, Carter-Brooks, & Lowder, 2018). UTIs are further categorized as uncomplicated, complicated, recurrent, and catheter-associated (see Table 1) (Bartoletti, Cai, Wagenlehmer, Naber, & Johansen, 2016).

UTIs have been a burden for mankind long before bacteria were recognized as the causative agent. One of the oldest written medical records, dating back to ancient Egypt, was the Ebers papyrus, which contained treatment for urine retention and excessive urination (Nickel, 2005). Throughout history, there are detailed descriptions and classifications of urinary symptoms that document treatments that range from conservative (herbs, bed rest) to invasive procedures, including surgery for stones, abscesses, and retention (Nickel, 2005).

A UTI is one of the most common infectious diseases, especially in women. It is estimated that UTIs affect greater than 30% of the population worldwide (Bartoletti et al., 2016). In the United States, there are more than 8 million ambulatory visits annually for UTI; 21% are emergency room visits, and 84% of those are women (Brubaker et al., 2018).

The majority of community-acquired UTIs are caused by the organism Escherichia coli (E. coli). Other organisms include Klebsiella pneuemoniae, Proteus mirabili, and E. faecalis.

Table 1. Classification of Urinary Tract Infection (UTI)
Classification of UTI	Description
Uncomplicated	Acute, sporadic, or recurrent lower (uncomplicated cystitis), and/or upper (uncomplicated pyelonephritis) UTI; limited to non-pregnant women with no known relevant anatomical and functional abnormalities within the urinary tract or co-morbidities.
Complicated	All UTIs not defined as uncomplicated (i.e., all men, pregnant women, patients with relevant anatomical or functional abnormalities of the urinary tract, indwelling urinary catheters, renal diseases, and/or with other concomitant immunocompromising diseases).
Recurrent	Recurrences of uncomplicated and/or complicated UTI, with two cultures proven UTI in the last 6 months at least 2 weeks apart or with a different pathogen.
Relapse	UTI with the same pathogen within 2 weeks of completing appropriate antibiotic therapy.
Catheter-associated	Catheter-associated urinary tract infection (CAUTI) refers to a UTI occurring in a person whose urinary tract is currently catheterized or has had a catheter in place within the past 48 hours.

Table 2. Components of Microbial Stewardship When Prescribing Antibiotics
1. Consider the precise indication for antibiotic treatment. 2. Choose the appropriate compound. 3. Use the appropriate dosage. 4. Consider the appropriate route of administration. 5. Consider administration timing and treatment length. 6. Consider symptoms related to the presence of microorganisms. 7. Consider antibiotic resistance rates in the area and for the patient. 8. Consider previous recent treatments. 9. Antibiotic treatments should be based on detailed knowledge of pharmacological behavior of the chosen antibiotic compound, characteristics of the pathogen being treated, and interactions between the two.

Table 3. Treatment and Screening for Asymptomatic Bacteriuria (ASB)
Individuals Who Should Not Be Screened or Treated for ASB	Individuals Who Should Be Screened and Treated for ASB
Healthy non pregnant women Older functionally impaired community dwelling or long-term care facilities Diabetic patients Renal transplant patients greater than 1 month Patients with spinal cord injury Patients with indwelling catheter or ISC Known neurogenic bladder	Pregnant women Renal transplant patients less than 1 month Patients undergoing endourological procedures Patients undergoing implantation of urologic devices

Source: Nicolle et al., 2019.

Table 4. Suggested Antibiotic Prophylaxis
Daily	Postcoital (within 2 hours of coitus)
Trimethoprim/sulfamethoxazole (TMP/SMX) (40 mg/200 mg daily or three times per week)	TMP/SMX (40 mg/200 mg to 80 mg/400 mg)
Trimethoprim (100 mg daily)
Cephalexin (125 mg to 250 mg daily)	Cephalexin (250 mg)
Cefaclor (250 mg daily)	Nitrofurantoin (50 mg to 100 mg daily)
Nitrofurantoin (50 mg to 100 mg daily)	Norfloxacin (200 mg)
Norfloxacin (200 mg daily)
Fosfomycin (3 g every 10 days)