Recurrent urinary tract infections (UTIs) are defined as two episodes of acute bacterial cystitis, along with associated symptoms within the last six months or three episodes within the last one year. Recurrent UTIs are more common in the female population.
Several conditions may predispose to an increased risk of UTIs in both men and women.
Immunodeficiency typically does not lead to isolated recurrent UTIs.
Approximately one in three women suffers an uncomplicated urinary tract infection (UTI) before the age of 24. The lifetime prevalence of at least one symptomatic UTI in women has been estimated to be over 50%, with about 26% of women demonstrating a recurrence during six months of follow-up after treatment of initial UTI. In a study in the primary care setting, 53% of women aged more than 55 years, and 36% of younger women reported a recurrence within 1 year.
Acute simple cystitis presents with symptoms of urinary frequency or urgency, dysuria, and suprapubic pain. The probability of cystitis is greater than 90 percent in women with dysuria and frequency without vaginal discharge or irritation. The presence of fever, chills, rigors, marked fatigue, or malaise suggests that the infection has extended beyond the bladder and is now regarded as acute complicated cystitis. Clinical features of pyelonephritis include fever, chills, flank pain, costovertebral angle tenderness, nausea, and vomiting. Symptoms of cystitis are often but not universally present in patients with pyelonephritis. In a study in 113 women, it was found that the presence of hematuria and urgency as symptoms of initial urinary infection were the strongest predictors of a second infection. Elderly or debilitated patients can present with more generalized symptoms of infection (like fever and chills) without clear localization to the urinary tract.
In women who have very rapid recurrences of cystitis after treatment, clinical clues should be sought to attempt to classify the recurrent infection as reinfection (i.e., new infection after the previous one was completely eradicated) or relapse (i.e., re-emergence of the previous infection, which was incompletely eradicated). A recurrence is termed as reinfection if the interval between two episodes is greater than 2 weeks, or if a different strain of uropathogen is documented or if a sterile culture (with patient off antibiotics) was documented in between two episodes of UTI. If the interval between the two episodes is less than two weeks, it is defined as relapse. Relapsing infection often requires additional evaluation with urological imaging.
In the case of women with a history of recurrent UTI who present with typical symptoms, no further urine evaluation is necessary, and the diagnosis of recurrent cystitis can be made clinically. If symptoms are non-specific or chronic, further urine testing during a symptomatic episode should be done to rule out acute cystitis. Urine culture should only be performed in the setting of a severe infection or high risk of antibiotic resistance (multidrug-resistant isolate; recent inpatient admission; recent antibiotic use; a history of travel to India, Israel, Spain, or Mexico).
Urological imaging is advised for only a select group of women. Indications for urological imaging include relapsing infection, persistent hematuria after treatment; a history of the passage of stones; or repeated isolation of Proteus from the urine, which is often associated with renal stones. Preferred modalities of imaging include CT scan and renal ultrasound.
A variety of sampling methods have been described to establish the diagnosis of UTI in the pediatric population, however, obtaining the urine sample utilizing suprapubic aspiration or catheterization, might result in lower contamination, and more reliable results. Moreover, if the urine sample has been collected through a plastic bag, several more steps should be undertaken to rule out the possibility of UTI, including dipstick evaluation, and microscopic analysis. Presence of leukocyte esterase and nitrite, and possibility of pyuria and bacteriuria, both should be excluded in order to rule out the impression of UTI. Utilizing a clean voided midstream urine sample for the diagnosis is limited to toilet-trained children.
Applying cystoscopy solely for the diagnosis of UTI is rarely indicated as it might induce the process of ascending lower urinary tract infection; however, it might be used in a few circumstances, including post-operative exclusion and management of possible ureteral injuries. Furthermore, the optimal recommended type of fluid used during cystoscopy has been investigated. For instance, in the study conducted by Lauren N. Siff et al. during 8 months in the urogynecology departments of the joined clinics within e Cleveland health system, the authors explored the significantly higher rate of UTI in those patients who have undergone cystoscopy with 10% dextrose water in comparison with normal saline. All cystoscopies were planned to exclude intraoperative ureteral injuries during complicated urogynecology procedures.
Acute uncomplicated UTI is mostly managed in the outpatient setting. In fact, women with typical symptoms of acute cystitis can be prescribed antibiotic therapy over the telephone. The decision for hospitalization should be taken on a case-by-case basis. Most patients with persistent fever, pain, inability to take oral medication, or poor medication adherence should be managed inpatient.
The management of recurrent cystitis is otherwise similar to that of isolated cystitis. Urine culture should be obtained prior to initiating therapy in some clinical scenarios:
The first line options for empiric antibiotic therapy are:
If the above options cannot be used, oral beta-lactams are the next best choice. Amoxicillin-clavulanate 500 mg twice daily, cefdinir (300 mg twice daily), cefadroxil (500 mg twice daily), and cefpodoxime (100 mg twice daily), each given for five to seven days. Ampicillin or amoxicillin should be avoided due to high rates of resistance. If the beta-lactams cannot be used, fluoroquinolones such as levofloxacin (250 mg daily) and ciprofloxacin (250 mg twice daily), for three days, are good alternatives. Fluoroquinolones are contraindicated in pregnancy.
For inpatient management of patients with risk factors for multi-drug resistant (MDR) pathogen infection, carbapenems (imipenem 500 mg intravenously (IV) six-hourly, or meropenem 1 gram IV eight-hourly, or doripenem 500 mg eight hourly) are used. If no risk factors for MDR are present, ceftriaxone (1 gram IV daily) or piperacillin-tazobactam (3.375 grams IV six hourly) can be used. Fluoroquinolones (ciprofloxacin or levofloxacin), both oral and parenteral, are also good alternatives. For critically ill patients, carbapenems (as above) along with vancomycin are typically used.
Symptoms should respond to antibiotic therapy within 48 hours of initiation of therapy. If no improvement is noticed within 48 hours of initiation of therapy, repeat urine culture should be obtained along with urologic imaging to rule out complications such as renal abscess or pyelonephritis.
Clinicians should not perform a post-treatment test of cure urinalysis or urine culture in asymptomatic patients. Repeat urine cultures should be obtained to guide further management when UTI symptoms persist following antimicrobial therapy.
Most recurrent UTIs have no long term sequelae and recover fully. The mortality associated with acute uncomplicated cystitis in women is negligible. However, in terms of morbidity, each episode of UTI results in a loss of 1.2 days of attendance at class/work. Younger patients without preexisting comorbidities have the best prognosis. Some factors that are associated with a worse prognosis may include older age, recent urinary instrumentation, recent hospitalization or antibiotic therapy, preexisting diabetes mellitus, sickle cell anemia, or chronic renal disease. UTIs occurring in the setting of certain anatomical abnormalities such as renal calculi, obstruction, hydronephrosis, colovesical fistula, or bladder exstrophy also have a worse prognosis.
Risk factors for complications include urinary tract obstruction, recent instrumentation, and elderly or patients with diabetes mellitus (particularly for emphysematous pyelonephritis and papillary necrosis). Acute pyelonephritis can also be complicated by the infection progressing to a renal abscess, perinephric abscess, papillary necrosis, or emphysematous pyelonephritis. This may present as the failure of symptoms to improve even after 48 hours of appropriate antibiotic therapy and requires further evaluation with urological imaging. Patients with complicated UTI can present directly with bacteremia, sepsis, multiple organ system failure, or acute renal failure.
Several preventive measures can be taken to reduce further recurrences of UTI. Patients should be advised to increase fluid intake to at least 2 liters per day. In a study on 140 women, increased intake of water resulted in decreased incidence of cystitis episodes by 1.5 (95% CI 1.2-1.8) (mean 1.7 versus 3.2 episodes). Topical vaginal estrogen (vaginal ring/insert/cream) is recommended in postmenopausal women with vulvovaginal atrophy (genitourinary syndrome of menopause) to reduce the risk of future UTIs, provided there are no contraindications to estrogen therapy. Other behavioral modifications include wiping from front to back and early postcoital voiding. There is no conclusive evidence on the role of cranberry juice in the reduction of episodes of recurrent UTI.
Antibiotic prophylaxis should only be offered after other preventive modalities and only in women with a confirmed diagnosis of recurrent cystitis. In some situations, the toxicities and adverse effects of using antibiotic prophylaxis may outweigh the risk of recurrent UTI as cystitis rarely results in a poor outcome. The adverse effects may include direct drug toxicity, development of resistance, alteration of the microbiome, and/or Clostridioides difficile infection. In women with cystitis episodes, which are temporally associated with sexual activity, postcoital antibiotics may be advised to reduce the risk of adverse effects without compromising the efficacy of the drug. In other cases, continuous prophylaxis may be used. The drugs used in continuous, as well as postcoital prophylaxis, are largely similar. The need for antibiotic prophylaxis should be reevaluated after six months.
Recurrent UTIs often have a typical presentation of dysuria, urinary frequency or urgency, and suprapubic pain with/without fever, chills, flank pain, costovertebral angle tenderness, and nausea/vomiting. The diagnosis is often not in question. But, according to literature, there exists a gap in the perception of the symptom severity between the physician and the patient, which may be attributed to misinformation, misconceptions, or miscommunication.
The primary care physician is often the point of first medical contact in the care of a patient with UTI. A proper history and physical exam should be conducted in a patient with recurrent UTIs. In several situations, it may be imperative to involve the nephrologist, as deemed necessary according to the severity, or the persistent nature of the disease. In cases of suspected urinary tract obstruction, the radiologist has an important role in helping to determine the cause using the necessary imaging. The nurses are also vital members of the interprofessional group as they will monitor the patient's vital signs and assist with the education of the patient and family. The pharmacist should ensure that the right antibiotics are chosen on a case to case basis. The clinical presentation may be more complicated in a pregnant woman as the widespread inflammation may present as abdominal pain and may be falsely interpreted to be of obstetrical etiology. In such cases, the first point of contact may be an obstetrician. A unique aspect of the management of recurrent UTIs is the self-diagnosis and self-treatment of UTI by the patient. This can be done if the patient is motivated, has a good relationship with the physician, and has clearly documented recurrent UTIs. It has been demonstrated to have similar efficacy as conventional therapy. [Level 1 evidence]
The American Urological Association guidelines® are evidence-based guidelines for recurrent UTI that are reviewed by an interprofessional expert committee. The current guidelines, published in 2019, have been developed after an exhaustive review of current medical literature from peer-reviewed journals.
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