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UTI Uncomplicated: Acute Simple Cystitis (FL INITIAL Autonomous Practice - Differential Diagnosis)

2 Contact Hours

Only FL APRNs will receive credit for this course.

This course is only applicable for Florida nurse practitioners who need to meet the autonomous practice initial licensure requirement.

This peer reviewed course is applicable for the following professions:

Advanced Registered Nurse Practitioner (ARNP)

This course will be updated or discontinued on or before Saturday, March 25, 2023

Urinary tract infections (UTIs) include cystitis (infection of the bladder/lower urinary tract) and pyelonephritis (infection of the kidney/upper urinary tract). This topic discusses the approach to women and men with typical symptoms of acute simple cystitis when there is no concern that the infection has extended beyond the bladder. When there is concern that the infection has possibly extended beyond the bladder this is considered to be a complicated UTI. This approach to categorizing UTI differs from other conventions.

After completing this course, the participant will be able to meet the following objectives:

Discriminate between acute uncomplicated UTI and complicated UTI.
Relate the epidemiology and risk factors for acute simple cystitis for both sexes.
Describe the pathogenesis of UTIs.
State the microbial spectrum associated with UTIs.
Relate the microbial resistance trends associated with various antimicrobial agents.
Compare and contrast the difficulties in diagnosing acute simple cystitis for either sex.
Describe the diagnostic approach to diagnosing acute simple cystitis in terms of health history, physical examination and laboratory/diagnostic tests for both men and women.
State the data the clinician ascertains which leads to the diagnosis of acute simple cystitis in both men and women.
Compare and contrast the signs and symptoms of acute simple cystitis and other relevant differential diagnoses.
Review the therapeutic agents used to treat acute simple cystitis.
Describe the management of the patient with acute simple cystitis in terms of antimicrobial agents, i.e., name, dosage, route of administration and length of administration.
Describe the follow-up for patients with acute simple cystitis.

CEUFast Inc. did not endorse any product, or receive any commercial support or sponsorship for this course. The Planning Committee and Authors do not have any conflict of interest.

Last Updated: 3/9/2021

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Author: Pamela Downey (MSN, ARNP)

Introduction

Urinary tract infections (UTIs) include cystitis (infection of the bladder/lower urinary tract) and pyelonephritis (infection of the kidney/upper urinary tract). The pathogenesis of UTI begins with colonization of the vaginal introitus or urethral meatus by uropathogens from the fecal flora, followed by ascension via the urethra into the bladder. Pyelonephritis develops when pathogens ascend to the kidneys via the ureters. Pyelonephritis can also be caused by seeding of the kidneys from bacteremia. It is possible that some cases of pyelonephritis are associated with seeding of the kidneys from bacteria in the lymphatics.

This topic will review the approach to women and men with typical symptoms of cystitis when there is no concern that the infection has extended beyond the bladder. This is called acute simple cystitis. When there is concern that the infection has possibly extended beyond the bladder (e.g., when there is flank pain or other features suggestive of pyelonephritis, pelvic or perineal pain (in men), fever, and/or other signs of systemic illness, including sepsis) this is considered to be a complicated UTI. This approach to categorizing UTI differs from other conventions.

Terminology

Acute simple cystitis refers to an acute UTI that is presumed to be confined to the bladder. Such infections lack signs or symptoms that suggest an infection extending beyond the bladder or systemic infection.

If any of the following signs or symptoms are present in the setting of pyuria and bacteriuria, this patient is considered to have acute complicated UTI and should be managed differently.

Fever (>99.9°F/37.7°C) – This temperature threshold is not well defined and should be individualized, considering baseline temperature, other potential contributors to an elevated temperature, and the risk of poor outcomes should empiric antimicrobial therapy be inappropriate.
Other signs or symptoms of systemic illness (including chills or rigors, significant fatigue or malaise beyond baseline).
Flank pain
Costovertebral angle tenderness
Pelvic or perineal pain in men

By this definition, pyelonephritis is a complicated UTI, regardless of patient characteristics.

Patients with underlying urologic abnormalities (such as nephrolithiasis, strictures, stents, or urinary diversions), immunocompromising conditions (such as neutropenia or advanced HIV infection), or poorly controlled diabetes mellitus are not necessarily considered to have a complicated UTI if they have no concerning symptoms for the upper tract or systemic infection. These patients can be considered to be at higher risk for more serious infection and have not traditionally been included in studies evaluating the antibiotic regimens typically used for acute simple cystitis. Such patients should be followed more closely and/or have a low threshold to manage them as complicated UTI (e.g., if they have subtle signs or symptoms that could be suggestive of more extensive infection). Many patients with significant urologic abnormalities come to clinical attention for UTI because of signs or symptoms consistent with complicated UTI as defined here (rather than features of simple cystitis alone).

Certain populations, such as pregnant women and renal transplant recipients, have unique management considerations and thus are not included in the above categorization.

Epidemiology

Acute simple cystitis among women is extremely common.^1,2Anatomically speaking, the shorter distance from the anus to the urethra likely explains why women are at higher risk for UTIs than men.

Among otherwise healthy women, risk factors for acute simple cystitis include¹^,3,4:

Sexual Activity
- Recent sexual intercourse
- Sexually active women tend to have more UTIs than do women who are not sexually active.
- Having a new sexual partner
History of UTI(s)
Certain types of birth control
- Use of spermicide-coated condoms, diaphragms, and spermicides
Female anatomy
- A woman has a shorter urethra than a man does, which shortens the distance that bacteria must travel to reach the bladder.
Menopause
- After menopause, a decline in circulating estrogen causes changes in the urinary tract that increases the risk of infection.

Acute simple cystitis occurs in a very small proportion of men between 15 and 50 years of age. The incidence is approximately five to eight UTIs per year per 10,000 young to middle-aged men.^5,6Symptomatic UTI is much less common in men than in women due to longer urethral length, drier periurethral environment resulting in less frequent colonization around the urethra, and antibacterial substances in prostatic fluid.

Among otherwise healthy men, risk factors associated with acute simple cystitis include⁷:

Insertive anal intercourse
Lack of circumcision

Other comorbidities which increase the risk factors for UTIs include:

Urinary tract abnormalities
- Babies born with urinary tract abnormalities that do not allow urine to leave the body normally or cause urine to back up in the urethra have an increased risk of UTIs.
Blockages in the urinary tract such as kidney stones or an enlarged prostate which can trap urine in the bladder.
A suppressed immune system such as diabetes mellitus, HIV/AIDS, etc.
Catheter use including people who are hospitalized, people with neurological problems that make it difficult to control their ability to urinate and people who are paralyzed.
A recent urinary procedure, i.e., urinary surgery or an examination of a person’s urinary tract that involves medical instruments.

Thus, culture and susceptibility testing are essential for the management of patients who have such risk factors. Even in the absence of specific risk factors, resistance in E. coli can be a major issue.

Pathogenesis of UTIs

Pathogenesis of Urinary Tract Infection

Microbiology

Microbial Spectrum

UTIs are caused by both Gram-negative and Gram-positive bacteria, as well as, by certain fungi. Uropathogens include1,^8-10:

Uropathogenic Escherichia coli (UPEC) (75% incidence)
Klebsiella pneumoniae (6% incidence)
Staphylococcus saprophyticus (6% incidence)
Enterococcus faecalis (5% incidence)
Group B Streptococcus (GBS) (3% incidence)
Proteus mirabilis (2% incidence)
Pseudomonas aeruginosa (1% incidence)
Staphylococcus aureus (1% incidence)
Candida spp. (1% incidence)

Among otherwise healthy nonpregnant women, the isolation of organisms such as lactobacilli, enterococci, Group B streptococci, and coagulase-negative staphylococci other than S. saprophyticus from voided midstream urine most commonly represents contamination of the urine specimen.^11,12Nevertheless, it may be appropriate to consider these organisms the likely causative agent in symptomatic women when found in voided midstream urine at high counts and with pure growth (i.e., without growth of other bacteria). That such organisms are rarely the cause of acute simple cystitis in such women is supported by a study of 202 premenopausal, nonpregnant women with acute simple cystitis who collected a midstream, clean-catch urine, and subsequently underwent urethral catheterization to collect a bladder urine specimen.¹³ There was high concordance between growth on voided and catheterized specimens for E. coli , K. pneumoniae, and S. saprophyticus. In contrast, enterococci and Group B streptococci were isolated from 20 and 25 voided specimens, respectively, but only from two corresponding catheterized specimens each. In the majority of specimens with these organisms, growth was <104 CFU/mL, and E. coli was also isolated.

Resistance Trends

Expected susceptibility patterns of E. coli should inform the empiric antimicrobial selection for acute simple cystitis. Increasing rates of resistance have been reported globally.

Risk factors for multi-resistant gram-negative UTIs include: (Table 1)

Table 1: Risk Factors for Multi-Resistance Gram-Negative UTIs
Suspect Multidrug-resistant Gram-negative UTI in Patients with a History of the following in the past 3 Months
A multidrug-resistant gram-negative urinary isolate
Inpatient stay at a health care facility (e.g., hospital, nursing home, long-term acute care facility)
Use of a fluoroquinolone, TMP-SMX, or a broad-spectrum beta-lactam (e.g., third or later generation cephalosporin)*
Travel to parts of the world with high rates of multidrug-resistant organisms¶
Multidrug resistance refers to nonsusceptibility to at least one agent in three or more antibiotic classes. This includes isolates that produce an extended-spectrum beta-lactamase (ESBL). * This includes a single antibiotic dose given for prophylaxis prior to prostate procedures. ¶ The prevalence of multidrug resistance is not well documented in all parts of the world. Some countries where the prevalence is particularly high include India, Israel, Spain, and Mexico.

Ongoing monitoring of local prevalence of resistance is necessary for optimization of empiric therapy.

The in vitro susceptibility of E. coli varies considerably by geographic region. In four large studies, overall resistance rates were higher in medical centers in the United States than in Canada, and higher in Portugal and Spain than in other European countries.^14-17 In general, resistance rates >20% were reported in all regions for ampicillin and in many regions for trimethoprim (with or without sulfamethoxazole).

Nitrofurantoin and Fosfomycin have demonstrated good in vitro activity in all countries investigated¹⁴^-17 and are thus appropriate first-line agents for acute simple cystitis when there are no clear risk factors for resistance.¹⁸

Resistance rates for first and second generation oral cephalosporins and amoxicillin-clavulanic acid are regionally variable but generally <10%.

Fluoroquinolone resistance rates have been <10% in most parts of North America and Europe, but there has been a clear trend of increasing resistance over time.^14-20

In a study of E. coli urinary isolates from outpatients in the United States, resistance rates to ciprofloxacin increased from 3 to 17% between 2000 and 2010.¹⁹ In a population-based study of over 5000 E. coli urinary isolates collected in Minnesota between 2005 and 2009, the incidence of urinary isolates resistant to fluoroquinolones and/or TMP-SMX increased among older adult patients and those with community-associated isolates, but not among health care-associated cases.²⁰ One caveat in interpreting these data is that passive laboratory-based surveillance methods tend to overestimate true resistance rates since they are skewed by urine cultures obtained from patients who may have failed initial therapy or who have specific risk factors for resistance, such as recent travel or antimicrobial use.^21-23

TMP-SMX is the agent for which there are the most data to guide clinical use:

Identified risk factors for resistance in women with acute simple cystitis include²⁴^-27:
- Use of TMP-SMX in the preceding three to six months
- Travel, particularly international travel

For other antimicrobial agents, there are insufficient data to determine the resistance levels at which the likelihood of failure outweighs the potential benefits. The decision depends on individual practitioner discretion. In addition, it is important for clinicians to understand that local resistance rates reported in hospital antibiograms are often skewed by cultures of samples obtained from hospitalized patients or those with complicated infection and may not accurately predict susceptibilities in women with acute simple community-acquired cystitis, in whom resistance rates tend to be lower.^28,29

Nevertheless, resistant infections are increasing in number, including those caused by extended-spectrum beta-lactamase (ESBL)-producing strains. An increase in ESBL-producing isolates has been described among patients with acute simple cystitis worldwide.^30-32 In particular, a specific strain of E. coli, sequence type 131 (ST131), has emerged globally as a major cause of fluoroquinolone-resistant and ESBL-producing E. coli UTIs.³³

Prologue

Symptoms of cystitis can occasionally be subtle and more difficult to ascertain in older women. Older women can have a number of nonspecific urinary symptoms (such as chronic dysuria or urinary incontinence) that mimic symptoms of cystitis, even when there is no evidence of UTI.

A systematic review of studies evaluating the diagnosis of UTI among community-dwelling adults older than 65 years suggested that symptoms such as chronic urinary nocturia, incontinence, and general sense of lack of well-being were common and nonspecific for UTI.³⁴ In contrast, acute dysuria (less than one week duration), new or worsening urinary urgency, new incontinence, frequency, gross hematuria, and suprapubic pain or tenderness were more discriminating symptoms. Fever was also a discriminating feature, although patients with cystitis symptoms and fever are considered to have a complicated UTI.

Similarly, among debilitated patients, many generalized signs or symptoms, such as falls, change in functional status, and change in mental status, are frequently attributed to UTI, but growing evidence indicates that these are not reliable predictors of bacteriuria or cystitis.

In one cohort study of nursing home residents, among clinical features that prompted evaluation for UTI (including change in gait or falls, change in functional status, fever or chills), only acute dysuria, change in the character of urine (gross hematuria, change in color or odor), and change in mental status were associated with the presence of both pyuria and bacteriuria.³⁵

Other studies that controlled for comorbidities have found no association between bacteriuria in nursing home patients and nonspecific mental status changes (such as increased restlessness, confusion, or aggression).³⁶ Among those with bacteriuria, there also appears to be no association between these nonspecific mental status changes and urinary markers of inflammation (i.e., interleukin-6).³⁷

Furthermore, treatment of bacteriuria in patients with acute delirium or nonspecific symptoms is not associated with improvement in mental or functional status (but is associated with Clostridium difficile).^38,39

Although cloudy or smelly urine may be associated with bacteriuria (as demonstrated in nursing home residents³⁸, there is no evidence of benefit to treating patients with only these complaints as having a UTI prior to the onset of usual cystitis symptoms. Color and odor of urine are influenced by ingestion of certain foods, dehydration, and other noninfectious factors. Thus, increased fluid intake and careful observation are reasonable initial approaches to patients who complain of changes in odor or color of urine.

Fever, chills, rigors, and other signs of systemic illness are not compatible with a diagnosis of acute simple cystitis and raise the possibility of pyelonephritis or other complication of UTI.

Diagnostic Approach

Clinical Suspicion and Evaluation

Health History

Acute simple cystitis should be suspected in patients who have acute symptoms of dysuria, urinary frequency or urinary urgency, and/or suprapubic pain, and additionally, for men, flank, pelvic, or perineal pain. The presence/absence of vaginal symptoms (e.g., vaginal pruritus or discharge) is important to obtain. The probability of cystitis is greater than 50% in women with any of these symptoms and greater than 90% in women who have dysuria and frequency without vaginal discharge or irritation. Hematuria is also often observed.⁴⁰
Fever, chills, rigors, and other signs of systemic illness are not compatible with a diagnosis of acute simple cystitis and raise the possibility of pyelonephritis, prostatitis (in men), or other complications of UTI.

Physical Examination

Physical examination is often not necessary for the diagnosis, but if performed, should include:

Assessment for fever
Costovertebral angle tenderness
Abdominal tenderness
Suprapubic tenderness

A pelvic examination is indicated if symptoms or signs suggesting vaginitis or urethritis are present.

Among sexually active young women, a pelvic examination should be performed, particularly if symptoms are not convincing for a UTI, to evaluate for cervical motion or uterine tenderness, which would be suggestive of pelvic inflammatory disease.

A digital rectal examination should be performed on men who present with symptoms of pelvic or perineal pain to evaluate for a tender or edematous prostate that would suggest acute prostatitis.

Prostatitis should be considered in men presenting with cystitis symptoms that are recurrent or are accompanied by pelvic or perineal pain or fever.

If fever (>99.9°F/37.7°C), other signs or symptoms of systemic illness (including chills, rigors, or marked fatigue or malaise beyond baseline), flank pain, or costovertebral angle tenderness are present, these signs and symptoms are not compatible with a diagnosis of acute simple cystitis and raise the possibility of pyelonephritis, prostatitis, or other complications of a UTI. These patients should be evaluated and managed as potentially having a complicated UTI.

Laboratory/Diagnostic Tests

Urinalysis (either by microscopy or by dipstick) for evaluation of pyuria

Pyuria is present in almost all men and women with acute simple cystitis, but its absence strongly suggests an alternative diagnosis.^41,42
Urinalysis is not indicated in women with typical symptoms of acute simple cystitis (in whom the diagnosis can reliably be made on symptoms alone), but it can be helpful in cases in which the clinical presentation is atypical.
For most women with suspected acute simple cystitis, particularly those with classic symptoms, no additional testing is warranted to make the diagnosis.
However, in women who have clinical features that are suggestive, but not clearly diagnostic of cystitis (such as atypical urinary symptoms), urinalysis is a useful diagnostic tool, as the absence of pyuria on urinalysis suggests a diagnosis other than cystitis.
Apart from the classic features listed above, features that should prompt urine testing include:
New or worsening urinary urgency
New incontinence
Gross hematuria
Chronic urinary nocturia, chronic incontinence, general malaise, and cloudy or malodorous urine are nonspecific findings that should not routinely prompt urine testing to evaluate for cystitis.
Urine testing is not routinely done in elderly or debilitated patients with nonspecific changes in mental or functional status in the absence of focal urinary tract symptoms, and instead hydrate, carefully observe, and assess other potential contributing factors.⁴³ If fever is also present, evaluation for infection, including complicated UTI, is warranted.

Urine dipsticks are commercially available strips that detect the presence of leukocyte esterase (an enzyme released by leukocytes, reflecting pyuria) and nitrite (reflecting the presence of Enterobacteriaceae, which convert urinary nitrate to nitrite).

The dipstick test is most accurate for predicting UTI when positive for either leukocyte esterase or nitrite, with a sensitivity of 75% and a specificity of 82%.⁴⁰ However, results of the dipstick test provide little useful information when the clinical history is strongly suggestive of UTI, since even negative results for both tests do not reliably rule out infection in such cases.

Urine culture with susceptibility data

A urine culture should be performed in all patients with symptoms suggestive of cystitis.
Urine culture and susceptibility testing should be performed on patients with risk factors for more serious infection, such as those with underlying urologic abnormalities, immunocompromising conditions, and poorly controlled diabetes, regardless of other risk factors for resistance.
Urine culture and susceptibility testing are generally unnecessary in women with acute simple cystitis but should be performed in patients who are at risk for infection with a resistant organism.

Midstream urine culture is recommended to confirm the diagnosis of UTI in men, using colony count criteria of ≥103 colony-forming units/mL of a predominant species.44 In women in whom coliform bacteria (e.g., Escherichia coli) are isolated, lower colony counts are likely to represent infecting organisms.13,45 It is unknown if the same is true for men.

The most accurate method for assessing pyuria is to examine an unspun, voided midstream urine specimen with a hemocytometer. An abnormal result is ≥10 leukocytes/microL.42 White blood cell casts in the urine are diagnostic of upper tract infection, which would indicate a complicated UTI.

Urine Gram stain may be helpful in guiding the choice of empiric therapy pending culture results.
Pregnancy testing is appropriate in women of childbearing potential when the possibility of pregnancy cannot be reasonably excluded by history alone.
Blood testing is not warranted.

Determining the Microbial Etiology

The causative organisms and their antimicrobial susceptibility profiles are frequently predictable in women with acute simple cystitis. As a result, routine cultures for such infections are often not necessary for management decisions. However, given the increasing prevalence of antimicrobial resistance among uropathogens, obtaining a urine culture prior to initiation of therapy is warranted in patients who have risk factors for antimicrobial resistance, as well as, in patients at risk for more serious infection (e.g., those with underlying urologic abnormalities, immunocompromising conditions, and poorly controlled diabetes mellitus).

If voided urine cultures are sent to the laboratory, the clinician should ask the laboratory to quantify E. coli, if it grows, to at least 103 colony-forming units/mL to improve sensitivity. Moreover, E. coli should not necessarily be considered a contaminant if it grows in mixed flora since almost any growth of E. coli in voided urine in a symptomatic patient reflects bladder growth.¹³ The growth of organisms generally thought to be contaminants (such as lactobacilli, enterococci, Group B streptococci, and non-saprophyticus coagulase-negative staphylococci) may be considered causative when found in voided midstream urine at high counts and with pure growth.

Diagnosis

The clinical diagnosis of cystitis is made in a patient who has classic signs and symptoms (i.e., dysuria, urinary frequency, urgency, and/or suprapubic pain). For patients who have atypical urinary symptoms, the diagnosis is supported by the presence of pyuria (on microscopy or dipstick), and bacteriuria (on urinalysis and/or urine culture).

The clinical diagnosis of acute simple cystitis excludes fever (>99.9°F/37.7°C), other signs or symptoms of systemic illness (including chills, rigors, or marked fatigue or malaise beyond baseline), flank pain, costovertebral angle tenderness, pelvic or perineal pain, or other features suggestive of pyelonephritis or prostatitis. The presence of any of these features suggests pyelonephritis or extension of the infection beyond the bladder, and the patient is considered to have an acute complicated UTI. Any of these above features may also suggest an alternative diagnosis, potentially acute bacterial prostatitis in men.

Bacteriuria with or without pyuria in the absence of any symptom that could be attributable to a UTI is called asymptomatic bacteriuria and generally does not warrant treatment in nonpregnant patients who are not undergoing urologic procedures.

There is a lower threshold to consider patients with risk factors for more serious infection as having acute complicated UTI, for example, if they have subtle signs or symptoms of possible upper tract or systemic infection. Such risk factors include:

Urologic abnormalities (e.g., nephrolithiasis, strictures, stents, or urinary diversions)
Immunocompromising conditions (e.g., neutropenia or advanced HIV infection)
Poorly controlled diabetes mellitus

Differential Diagnosis

Both infectious and noninfectious processes can cause symptoms of dysuria, frequency, urgency, suprapubic pain, and/or hematuria.¹²

Acute Bacterial Prostatitis

Dysuria, urinary frequency and urgency, and pyuria can also be seen with acute bacterial prostatitis.
The presence of fever, chills, malaise, myalgias, pelvic or perineal pain, or obstructive symptoms such as dribbling and hesitancy (due to acute urinary retention) in a man with symptoms of cystitis suggests acute bacterial prostatitis.
Pain radiating to the tip of the penis has also been described in patients with acute prostatitis, but the sensitivity and specificity of this symptom have not been validated. Any of these signs and symptoms should prompt performance of a gentle digital rectal examination, and the finding of an edematous and tender prostate helps to confirm this alternate diagnosis.

Chronic Bacterial Prostatitis

Underlying chronic prostatitis should be considered in men with cystitis, particularly in those men who have recurrent UTIs caused by the same strain of bacteria.

Urethritis

Should be considered in sexually active men and women with dysuria, particularly those with pyuria on urinalysis but no bacteriuria. Causes of urethritis include:
- Candida species
- Chlamydia
- Gonorrhea
- Herpes simplex virus
- Noninfectious irritants, such as a contraceptive gel
- Trichomoniasis
Physical examination for penile ulcerations and urethral discharge should be performed.
Laboratory tests for men should include:
- Evaluation of a urethral swab specimen Gram stain
- Diagnostic tests for Neisseria gonorrhoeae and Chlamydia trachomatis
- A urethral Gram stain demonstrating leukocytes and predominant gram-negative rods suggests E. coli urethritis, which may precede or accompany urinary tract infection.46

Vaginitis

In women with dysuria, the presence of vaginal discharge or odor, pruritus, dyspareunia, and absence of urinary frequency or urgency should prompt consideration of vaginitis. Causes of vaginitis include:

Yeast infection
Trichomoniasis
Bacterial vaginosis

Painful Bladder Syndrome

This is a diagnosis of exclusion in women who have ongoing discomfort related to the bladder with symptoms of dysuria, frequency, and/or urgency but no evidence of infection or other identifiable cause.

Pelvic Inflammatory Disease (PID)

Lower abdominal or pelvic pain and fever are the most common clinical findings in patients with PID, although dysuria may also be present.
The findings of mucopurulent endocervical discharge or cervical motion tenderness on pelvic examination are strongly suggestive of PID.

Review of Therapeutic Agents Used to Treat Acute Simple Cystiti

β-lactam Antibiotics Mechanism of Action: β-lactam antibiotics (beta-lactam antibiotics) are a class of broad-spectrum antibiotics, consisting of all antibiotic agents that contain a beta-lactam ring in their molecular structures. Most β-lactam antibiotics work by inhibiting cell wall biosynthesis in the bacterial organism and are the most widely used group of antibiotics. Bacteria often develop resistance to β-lactam antibiotics by synthesizing a β-lactamase, an enzyme that attacks the β-lactam ring. To overcome this resistance, β-lactam antibiotics are often given with β-lactamase inhibitors such as clavulanic acid.
Cephalosporins	Cefadroxil Cefdinir Cefodoxime
Penicillin	Ampicillin
Beta-lactamase inhibitor combination	Amoxicillin-clavulanate
Fluoroquinolone Antibiotics Mechanism of Action: Fluoroquinolones, which contain a fluorine atom in their chemical structure, are effective against both Gram-negative and Gram-positive bacteria.
Fluoroquinolone Antibiotics	Ciprofloxacin Levofloxacin Norfloxacin Ofloxacin
Co-trimoxazole Antibiotic Mechanism of Action: Trimethoprim and sulfamethoxazole have a greater effect when given together than when given separately, because they inhibit successive steps in the folate synthesis pathway. They are given in a one-to-five ratio in their tablet formulations so that when they enter the body their concentration in the blood and tissues is roughly one-to-twenty — the exact ratio required for a peak synergistic effect between the two.
Co-trimoxazole Antibiotic	Trimethoprim/ Sulfamethoxazole (TMP-SMX)
Fosfomycin Mechanism of Action: Fosfomycin is a novel class of antibacterial with a chemical structure unrelated to other known antibiotics. It is a bactericidal drug that disrupts cell wall synthesis by inhibiting phosphoenolpyruvate synthetase and thus interferes with the production of peptidoglycan.
Nitrofurantoin monohydrate macrocrystals Mechanism of Action: Nitrofurantoin is bactericidal The mechanism of action is unique and complex. The drug works by damaging bacterial DNA, since its reduced form is highly reactive. This is made possible by the rapid reduction of nitrofurantoin inside the bacterial cell by flavoproteins (nitrofuran reductase) to multiple reactive intermediates that attack ribosomal proteins, DNA, pyruvate metabolism and other macromolecules within the cell.

Management

Antimicrobial Selection*

*All antimicrobial agent dosages presuppose normal renal function.

Men

Although cystitis in men is generally classified in the literature as a complicated UTI, it is reasonable to consider a healthy man without a neurogenic bladder who has mild to moderate dysuria, urinary frequency and/or urgency, with no symptoms or signs of infection outside the bladder, as having simple cystitis. For empiric antimicrobial treatment of such men, one of the first-line regimens recommended for women is advocated:

Nitrofurantoin monohydrate/macrocrystals
- 100 mg orally twice daily
Trimethoprim-sulfamethoxazole (TMP-SMX)
- One double-strength tablet [160 mg TMP/800 mg SMX] orally twice daily
Fosfomycin
- 3 grams of powder mixed in water as a single dose

The choice among them should be individualized based on patient circumstances (allergy, tolerability, and expected adherence), local community resistance prevalence, availability, and cost. If the patient has taken one of the agents in the preceding three months, a different one should be selected (see Table 1 above). Based on data on UTI in women, empiric TMP-SMX should be avoided if the regional prevalence of resistance is known to exceed 20%.^47,48Nitrofurantoin or Fosfomycin are particularly useful if multidrug resistance is documented or suspected. Beta-lactams can be used cautiously if other options are not appropriate because of allergy/intolerance or concerns about resistance.

Nitrofurantoin, Fosfomycin, and beta-lactams do not achieve reliable tissue concentrations in the prostate and may not adequately treat subclinical prostatitis. Consequently, for men who have more severe cystitis symptoms or concern about early involvement of the prostate, a fluoroquinolone for empiric therapy is advocated since they achieve more reliable tissue concentrations.^5,7

Ciprofloxacin 500 mg orally twice daily or 1000 mg extended release once daily OR
Levofloxacin 750 mg orally once daily

Because of concerns about the adverse effects of fluoroquinolones, they should only be used if there is concern about subclinical prostatitis or more severe illness.⁴⁹ If a fluoroquinolone is used, patients should be advised about the uncommon but potentially serious musculoskeletal and neurologic adverse effects.

Once susceptibility testing results are available, subsequent therapy should be tailored as appropriate.

Duration of Therapy in Men

There are no studies that have evaluated the optimal duration of antimicrobial therapy in men with cystitis.

Fluoroquinolones can be given a course as short as five days
- In a trial of patients with complicated cystitis or pyelonephritis, five days of levofloxacin was equivalent to 10 days of ciprofloxacin.⁵⁰
Other agents can be given for seven days
Fosfomycin is given as a single dose, but there is no experience with the use of this regimen in men with simple cystitis.

In men with simple cystitis who have no signs or symptoms suggestive of pyelonephritis or prostatitis (e.g., fever, flank pain, pelvic pain, prostatic tenderness on digital rectal exam if this part of the examination is performed), a seven-day or shorter course of an antimicrobial to which the infecting strain is susceptible is likely to be sufficient.

Women

The selection of an antimicrobial regimen for acute simple cystitis where the acute UTI is presumed to be confined to the bladder and there are no signs or symptoms that suggest an upper tract or systemic infection depends on the risk of infection with a multidrug-resistant (MDR) gram-negative organism (see Table 1 above).

Low Risk for Resistance

For patients who do not have risk factors for an MDR gram-negative infection one of the preferred first-line antimicrobial regimens should be chosen for empiric therapy of acute simple cystitis¹⁸:

First-line Antimicrobial Options

The preferred agents for empiric therapy of acute simple cystitis should strike a favorable balance between efficacy and adverse effects (including the risk of selecting for resistant organisms).18 If the patient has taken one of the agents in the preceding three months, a different one should be selected. The preferred agents are:

Nitrofurantoin monohydrate/macrocrystals
- Dosed at 100 mg orally twice daily for five days.
- Randomized trials suggest a 79 to 92% clinical cure rate with a five- to seven-day regimen, with minimal resistance promotion.51-53 Higher rates of failure occurred with shorter courses.54 It has minimal propensity to select for resistant organisms.
- Nitrofurantoin should be avoided if there is suspicion for early pyelonephritis or if the creatinine clearance is <30 mL/minute.
- Observational studies have suggested that the agent is effective and safe with mild renal impairment, even in older women.55-58
Trimethoprim-sulfamethoxazole (TMP-SMX) or Trimethoprim
- Dosed as one double-strength tablet (160/800 mg) orally twice daily for three days.
- Randomized trials suggest a 79 to 100% clinical cure rate with a three- to seven-day regimen.51,59-61
- Empiric TMP-SMX should be avoided if the regional prevalence of resistance is known to exceed 20%.47,48
- In some regions, trimethoprim (100 mg twice daily for three days) is used in place of TMP-SMX and is considered equivalent.62
Fosfomycin
- Dosed as 3 grams of powder mixed in water as a single oral dose.
- One randomized trial reported an early clinical cure rate of 91% and a bacterial cure rate similar to nitrofurantoin63, and a meta-analysis demonstrated no difference in cure rates between Fosfomycin and other agents, including fluoroquinolones, TMP-SMX and nitrofurantoin.64
- However, in a subsequent open-label trial, a single dose of Fosfomycin resulted in lower clinical (58 versus 70%) and microbiologic (63 versus 74%) success rates at 28 days compared with nitrofurantoin given three times daily for five days.65 Lower than expected clinical success rates in both groups may be a result of the definition used in this study (complete resolution of UTI signs and symptoms rather than improvement of signs and symptoms, as used in other trials). It is not clear whether the open-label trial design influenced the findings.66
- One benefit of Fosfomycin is that it appears to have minimal propensity to select for resistant organisms, although susceptibility testing for Fosfomycin is not routinely available in most clinical laboratories.
- Fosfomycin should be avoided if there is suspicion for early pyelonephritis.

None of the first-line antimicrobial agents clearly outweighs the others in terms of the efficacy/adverse effects balance, with the exception that resistance is more likely with TMP-SMX and possibly Fosfomycin is somewhat less effective. The optimal antimicrobial in one region may be different from that in another depending on resistance prevalence. Thus, the choice among them should be individualized based on patient circumstances (allergy, tolerability, and expected adherence), local community resistance prevalence, availability, cost, and patient and provider threshold for failure. If the patient has taken one of the agents in the preceding three months, a different one should be selected.
If all these are appropriate options based on patient circumstances and prior urinary isolates, nitrofurantoin or TMP-SMX rather than Fosfomycin is preferred. Fosfomycin retains activity against many MDR isolates, but overuse may result in increasing rates of resistance. Fosfomycin is reserved for suspected MDR infections when there are no other oral options.

These antimicrobial options and suggested treatment durations for acute simple cystitis are the same for any adult woman with acute simple cystitis, regardless of age. A systematic review of studies evaluating treatment of cystitis in community-dwelling adults ≥65 years of age concluded that the optimal regimens are the same as those recommended for younger adults and that shorter antimicrobial courses (three to six days) resulted in similar outcomes as longer ones (7 to 14 days).⁶⁷ However, since these studies excluded women with urinary tract abnormalities, immunocompromising conditions, or poorly controlled diabetes mellitus, it is reasonable to use a longer duration of therapy (e.g., 7 days) in women with such comorbidities.

If there is diagnostic uncertainty regarding cystitis versus early pyelonephritis, the patient is treated as having an acute complicated UTI (which includes pyelonephritis). In particular, the use of nitrofurantoin and Fosfomycin should be avoided in such cases because they do not achieve adequate renal tissue levels.¹⁸

Alternative Antimicrobial Options

If any factors (such as allergies or intolerances or a history of a urinary isolate resistant to these agents within the prior three months or concern for resistance) preclude the use of the above first-line antimicrobials, oral beta-lactams are acceptable options⁶¹^,68,69:

Amoxicillin-clavulanate
- 500 mg orally twice daily for five to seven days
Cefpodoxime
- 100 mg orally twice daily for five to seven days
Cefdinir
- 300 mg orally twice daily for five to seven days
Cefadroxil
- 500 mg orally twice daily for five to seven days
Ampicillin or Amoxicillin should not be used for empiric treatment given the high prevalence of resistance to these agents.^14-17,62

In general, beta-lactams are second-line agents because they are less effective and have more potential adverse effects than other UTI antimicrobials.^62,69,70

If beta-lactams cannot be used (e.g., because of severe allergy) reasonable alternative fluoroquinolone agents include:

Ciprofloxacin
- 250 mg orally twice daily for three days or 500 mg extended release orally daily for three days
Levofloxacin
- 250 mg orally daily for three days
Other less commonly used fluoroquinolones that are effective include:
- Ofloxacin
- Norfloxacin

Multiple randomized trials have demonstrated that fluoroquinolones are very effective for treatment of acute cystitis and that fluoroquinolones are more effective than beta-lactams.^{60,68,69,71-77} However, increasing rates of resistance mitigate the utility of the fluoroquinolone class. Furthermore, because of concerns about the adverse effects of fluoroquinolones, the risk-benefit balance for acute cystitis favors the use of fluoroquinolones only if other agents (including beta-lactams) cannot be used. When possible, fluoroquinolones should be reserved for more serious infections than acute simple cystitis.^49,78 If a fluoroquinolone is used, patients should be advised about the uncommon but potentially serious musculoskeletal and neurologic adverse effects.

If a patient has reasons not to use any of the first-line agents, beta-lactams, or fluoroquinolones, urine culture and susceptibility testing should be obtained, and an antimicrobial is selected based on those results. For acute simple cystitis, studies among women without comorbidities have suggested that deferring antimicrobial therapy until these results are available is a safe strategy.⁷⁹

Analgesics can be used for symptomatic therapy in the interim for women with mild to moderate symptoms. Symptoms of acute simple cystitis should respond to antimicrobial therapy within 48 hours. In fact, dysuria is usually diminished within a few hours after the start of antimicrobial therapy.⁸⁰ In the interim, for some patients with severe dysuria, a urinary analgesic such as over-the-counter oral phenazopyridine three times daily as needed may be useful to relieve discomfort. A two-day course is usually sufficient to allow time for symptomatic response to antimicrobial therapy and minimized inflammation. Phenazopyridine should not be used chronically since it may mask symptoms requiring clinical evaluation.

If there are concerns about deferring antimicrobials (e.g., because of significant bladder symptoms), it is reasonable to treat empirically with an agent (e.g., first-line option, beta-lactam, or fluoroquinolone) that was initially avoided because of concerns for possible resistance while awaiting culture results. If susceptibility results allow, any of these options can be used for directed therapy of acute simple cystitis, with the preferences and duration of treatment noted above. Alternately, if there are concerns about potential treatment failure with oral agents in patients with risk factors for more serious infection (e.g., an underlying urologic condition or immunocompromising condition), the patient can be treated with an initial intravenous agent.

First-line Antimicrobial Options

The preferred agents for empiric therapy of acute simple cystitis should strike a favorable balance between efficacy and adverse effects (including the risk of selecting for resistant organisms).¹⁸ If the patient has taken one of the agents in the preceding three months, a different one should be selected. The preferred agents are:

High Risk for Resistance

For patients who have risk factors for an MDR gram-negative infection, urine culture and susceptibility testing should be obtained first. For empiric treatment, unless the patient has a history of an isolate with documented resistance to these agents in the last three months, oral options

Nitrofurantoin monohydrate/macrocrystals
- 100 mg orally twice daily for five days
Fosfomycin
- 3 grams of powder mixed in water as a single dose

If all these are appropriate options based on patient circumstances (allergies, intolerances, and drug interactions) and prior urinary isolates, nitrofurantoin is advocated. The use of Fosfomycin is reserved for documented MDR gram-negative infections when there are no other oral options. In the United States, resistance to all oral options is still uncommon among outpatients with E. coli cystitis.

Studies have suggested that nitrofurantoin and Fosfomycin still retain clinical activity against some MDR organisms, including ESBL-producing isolates.^32,70,81,82 As an example, in a case-control study including 113 patients with ESBL-producing E. coli UTIs, no resistance to Fosfomycin was detected and clinical cure rates were high (93%).⁷⁰

If none of these agents can be used because of resistance or other concerns, antimicrobial therapy is deferred until a regimen can be selected based on results of culture and susceptibility testing. For acute simple cystitis, studies among women without comorbidities have suggested that deferring antimicrobial therapy until these results are available is a safe strategy.⁷⁹ Analgesics can be used for symptomatic therapy in the interim for women with mild to moderate symptoms.

If there are concerns about deferring antimicrobials (e.g., because of significant bladder symptoms), it is reasonable to treat empirically with an agent (e.g., first-line option, beta-lactam, or fluoroquinolone) that was initially avoided because of concerns for possible resistance while awaiting culture results. If susceptibility results allow, any of these options can be used for directed therapy of acute simple cystitis, with the preferences and duration of treatment discussed above. Alternately, if there are concerns about potential treatment failure with oral agents in patients with risk factors for more serious infection (e.g., an underlying urologic condition or immunocompromising condition), the patient can be treated with an initial intravenous agent.

Antimicrobial Sparing Strategies

Given that acute simple cystitis is associated with increasing antimicrobial resistance and has a low risk of progression to invasive disease in patients without risk factors for serious infection, antimicrobial sparing management strategies for some women with simple cystitis are of increasing interest (e.g., anti-inflammatory drugs or delayed treatment), but warrant further study before they can be routinely employed.^79,83,84

In one trial of 241 women with acute simple cystitis without risk factors for complications, those randomly assigned to treatment with ibuprofen (400 mg three times daily for three days) had a higher mean symptom burden compared with those who received Fosfomycin as a single 3 g dose.⁸⁴ Fewer women in the ibuprofen group received any antimicrobials compared with the Fosfomycin group (35 versus 100%), but they were more likely to require additional therapy with antimicrobials in follow-up and had a higher rate of serious adverse events, including five cases of pyelonephritis (2%) compared with one case (0.4%) in the Fosfomycin group. Similar findings were observed in a trial comparing diclofenac with norfloxacin.⁸⁵Thus, pending additional data, anti-inflammatory agents alone cannot be recommended as an initial approach to management of symptomatic acute simple cystitis.

Patients with Urologic Abnormalities

In many cases, patients with underlying functional or anatomic urinary tract abnormalities (such as an indwelling catheter, urethral stent, neurogenic bladder, nephrolithiasis) have systemic symptoms (such as fever or autonomic dysreflexia) in the setting of UTI and are thus managed as having a complicated UTI.

For those who appear to have only acute simple cystitis without upper tract or systemic symptoms, it is reasonable to cautiously treat them as outlined previously. However, because these patients were not included in efficacy studies of the regimens used for simple cystitis, they should be monitored closely for treatment failure (e.g., persistent symptoms after initiation of empiric therapy) and follow initial urine cultures to ensure that the empirically chosen regimen was appropriate. Furthermore, since the antimicrobial durations listed above have not been well studied in patients with urologic dysfunction, a longer duration of therapy (e.g., one to two weeks, depending on the agent chosen) is reasonable. It is also reasonable to have a lower threshold to treat such patients as having a complicated UTI (e.g., for more subtle symptoms of pyelonephritis or systemic infection).

In addition, other treatment measures in addition to antimicrobial therapy may be warranted. These include more frequent intermittent catheterization, changing out an indwelling catheter prior to obtaining a urine culture (particularly if it has been in place for longer than one or two weeks), or urologic/urogynecologic consultation.

Follow-up

Follow-up urine cultures are not needed in patients with acute simple cystitis whose symptoms resolve on antimicrobials.

Patients who have persistent symptoms after 48 to 72 hours of empiric antimicrobial therapy or have recurrent symptoms within a few weeks of treatment should have an additional evaluation for other potential conditions that may be causing those symptoms and for factors that might be compromising clinical response. This includes urine culture and empiric treatment with another antimicrobial agent. Subsequent treatment should be tailored to the susceptibility profile of the causative organism isolated. If symptoms persist in the setting of appropriate antimicrobial therapy, urologic assessment and radiographic imaging (generally with computed tomography) may be appropriate to evaluate for anatomic abnormalities that would interfere with the response to antimicrobial treatment.

Dedicated urologic evaluation is probably not necessary in young healthy men with no obvious complicating factors who have a single episode of simple cystitis that responds promptly to antimicrobial treatment.^86,87 Men with recurrent cystitis should be evaluated for predisposing features or causative factors (such as prostatic hypertrophy or other urinary tract obstruction). In particular, recurrent infection with the same strain of bacteria should prompt evaluation for chronic prostatitis.

Summary And Recommendations

The term acute simple cystitis refers to an acute infection that is confined to the bladder in a nonpregnant individual. Such infections lack features that suggest infection extends beyond the bladder, such as fever (>99.9°F/37.7°C), other signs or symptoms of systemic illness (including chills, rigors, and marked fatigue or malaise beyond baseline), flank pain, pelvic or perineal pain (men) and costovertebral angle tenderness. This definition is distinct from traditional categorizations of UTI and is more focused on the clinical presentation and severity of illness.

Acute simple cystitis occurs in a small number of men between 15 and 50 years of age. Symptomatic UTI is much less common in men than in women. This is due to longer urethral length, drier periurethral environment (with less frequent colonization around the urethra), and antibacterial substances in prostatic fluid.

Escherichia coli is the most frequent microbial cause of cystitis, with occasional infections caused by other species of Enterobacteriaceae, such as Klebsiella pneumoniae and Proteus mirabilis, and other bacteria, such as Staphylococcus saprophyticus. The microbial spectrum of cystitis in patients with recent antimicrobial or other health care exposures may be broader and also include other gram-negative bacilli (e.g., Pseudomonas), enterococci, and staphylococci. Increasing rates of resistance in uropathogens have been reported globally. Risk factors for UTI with resistant organisms include recent antimicrobial use, health care exposures, and travel to parts of the world where multidrug-resistant (MDR) organisms are prevalent.

The classic clinical manifestations of cystitis consist of dysuria, urinary frequency, urinary urgency, and suprapubic pain. Symptoms of cystitis can be difficult to assess in older or debilitated women, who can have a number of nonspecific urinary symptoms (such as chronic dysuria or urinary incontinence) that could mimic symptoms of cystitis. Laboratory diagnostic tools for cystitis consist of urinalysis (either by microscopy or by dipstick) and urine culture with susceptibility data. A urine culture should be performed in all men with symptoms suggestive of cystitis.

For women with classic symptoms of cystitis, no additional testing is warranted to make the diagnosis. For women who have atypical urinary symptoms, the diagnosis is supported by the presence of pyuria and bacteriuria on urinalysis and/or culture. Chronic nocturia, chronic incontinence, general malaise, and cloudy or malodorous urine are nonspecific findings that should not routinely prompt urine testing to evaluate for cystitis.

The diagnosis of acute simple cystitis can be made in a man who presents with typical urinary symptoms, pyuria, and bacteriuria on urine culture in the absence of fever or other systemic symptoms, pelvic or perineal pain, costovertebral angle tenderness, and other features suggestive of pyelonephritis or acute prostatitis.

Men with recurrent cystitis should undergo evaluation for prostatitis. Urologic evaluation is probably not necessary in healthy young men with no obvious complicating factors who have a single episode of cystitis that responds promptly to antimicrobial treatment.

Fever, chills, or malaise suggest a complicated UTI (including pyelonephritis) or bacterial prostatitis. In particular, pelvic or perineal pain, pain radiating to the tip of the penis, or obstructive symptoms such as dribbling and hesitancy (due to acute urinary retention) in a man with symptoms of cystitis suggest bacterial prostatitis. Chronic prostatitis should be considered in all men with cystitis, particularly in those men who have recurrent infections. Urethritis must be considered in sexually active men, and diagnostic tests for Neisseria gonorrhoeae and Chlamydia trachomatis are warranted.

For empiric antimicrobial therapy of men with acute simple cystitis, nitrofurantoin monohydrate/macrocrystals, TMP-SMX, or Fosfomycin are suggested. Beta-lactams are an alternative. However, if there are severe cystitis symptoms or concern about early involvement of the prostate, a fluoroquinolone is preferred. Once susceptibility testing results are available, subsequent therapy should be tailored as appropriate. The duration depends on the agent used (fluoroquinolones are given for five days, Fosfomycin is given as a single dose, and other agents are given for seven days).

The selection of an antimicrobial regimen for acute simple cystitis depends on the likelihood of infection with an MDR gram-negative isolate. Prior to initiation of therapy, urine culture and susceptibility testing are warranted for patients who have risk factors for antimicrobial resistance or for more serious infection (e.g., those with underlying urologic abnormalities, immunocompromising conditions, and poorly controlled diabetes mellitus).

For patients who do not have risk factors for an MDR gram-negative infection, the first-line antimicrobial agents include nitrofurantoin monohydrate/macrocrystals(100 mg twice daily for five days), TMP-SMX (one double strength tablet [160/800 mg] twice daily for three days), Fosfomycin (3 grams of powder mixed in water as a single dose). If all these are appropriate options based on patient circumstances, local resistance rates, and prior urinary isolates, nitrofurantoin or TMP-SMX rather than Fosfomycin is suggested.
Oral beta-lactams are appropriate alternative options for those who cannot use any of the first-line antimicrobials. If beta-lactams cannot be used, a fluoroquinolone is reasonable, but these should be reserved for more serious infections than acute simple cystitis, if possible, because of concerns of adverse effects.
For patients who have risk factors for an MDR gram-negative infection, oral options include nitrofurantoin (100 mg orally twice daily for five days), Fosfomycin (3 grams of powder mixed in water as a single dose) unless the patient has a history of an isolate with documented resistance to these agents in the past three months. If all these are appropriate options based on patient circumstances, local resistance rates, and prior urinary isolates, nitrofurantoin is suggested. Culture and susceptibility results should be used to guide directed therapy.
If none of these options are appropriate because of resistance or other concerns, antimicrobial therapy should be deferred until a regimen can be selected based on results of culture and susceptibility testing. For acute simple cystitis, studies among women without comorbidities have suggested that deferring antimicrobial therapy until these results are available is a safe strategy. However, if there is concern about deferring antimicrobial therapy (e.g., because of bothersome symptoms or risk factors for more serious infection), options include using one of the oral regimens for simple cystitis that was not chosen because of the possibility of resistance or using an initial dose of a parenteral agent, as used in acute complicated UTI.
Patients who have acute simple cystitis in the setting of underlying functional or anatomic urinary tract abnormalities (such as an indwelling catheter, urethral stent, neurogenic bladder, history of nephrolithiasis) may warrant more frequent catheterization, changing out an indwelling catheter, or urologic/urogynecologic consultation. Additionally, a longer duration of antimicrobial therapy is appropriate since shorter durations have not been well studied in such patients.
Patients who have persistent symptoms after 48 to 72 hours of empiric antimicrobial therapy or have recurrent symptoms within a few weeks of treatment should have urine submitted for culture and susceptibility testing. If symptoms persist in the setting of appropriate antimicrobial therapy, radiographic imaging to evaluate for anatomic abnormalities is appropriate.

Case Study

Scenario/Situation/Patient Description

Ms. Vinge is a 63-year-old, retired, caucasian female who reports acute onset of urinary frequency and urgency with gross hematuria beginning 0830 this morning. She denies fever, chills, rigors, flank pain, costovertebral angle tenderness. She denies vaginal discharge or itching and reports no sexual activity in the past 10 years. LMP 1999. No travel outside of the country since 2009.

PMH: Osteoporosis-diagnosed 2005
C-section Dec. 1989
T& A 1955

NKDA

Current medications:

Ibandronate sodium 150 mg once a month
Tylenol 500 mg prn
Motrin 200 mg prn

Physical examination:

Afebrile.
Neuro: Alert, oriented, cooperative, follows all commands appropriately. PERRLA.
HEENT: WNL
Lungs: CTA. No rales, rhonchi or wheezes.
Cardiac: HR 70 regular, regularity. No murmurs nor rubs. BP 130-140/70-84.
Abdominal: Abdomen soft, non-tender with bowel sound in all quadrants. No costovertebral angle tenderness or suprapubic tenderness.
GU: Urine cloudy with gross hematuria.
PVS: No edema.

Interventions/Strategies

Midstream urine culture collected and sent to lab.

Discussion of Outcomes

Results of urine culture showed Escherichia coli > 103 colony-forming units/mL

Strengths and Weaknesses

Patient is considered to be low risk for antimicrobial resistance.
TMP-SMX 160/800 mg orally ordered twice daily X 3 days.

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References

Foxman B. Urinary tract infection syndromes: occurrence, recurrence, bacteriology, risk factors, and disease burden. Infect Dis Clin North Am 2014; 28:1-13..
Schappert SM, Rechtsteiner EA. Ambulatory medical care utilization estimates for 2007. Vital Health Stat 13 2011; :1.
Hooton TM, Scholes D, Hughes JP, et al. A prospective study of risk factors for symptomatic urinary tract infection in young women. N Engl J Med 1996; 335:468.
Scholes D, Hooton TM, Roberts PL, et al. Risk factors associated with acute pyelonephritis in healthy women. Ann Intern Med 2005; 142:20.
Krieger JN, Ross SO, Simonsen JM. Urinary tract infections in healthy university men. J Urol 1993; 149:1046.
Vorland LH, Carlson K, Aalen O. An epidemiological survey of urinary tract infections among outpatients in Northern Norway. Scand J Infect Dis 1985; 17:277.
Hooton TM, Stamm WE. Diagnosis and treatment of uncomplicated urinary tract infection. Infect Dis Clin North Am 1997; 11:551.
Nielubowicz GR, Mobley HL. Host–pathogen interactions in urinary tract infection. Nature Rev Urol. 2010;7:430–441.
Kline KA, Schwartz DJ, Lewis WG, Hultgren SJ, Lewis AL. Immune activation and suppression by group B Streptococcus in a murine model of urinary tract infection. Infect Immun. 2011;79:3588–3595.
Ronald A. The etiology of urinary tract infection: traditional and emerging pathogens. Am J Med. 2002;113 (Suppl 1A):14S–19S.
Hooton TM. Clinical practice. Uncomplicated urinary tract infection. N Engl J Med 2012; 366:1028.
Gupta K, Trautner B. In the clinic. Urinary tract infection. Ann Intern Med 2012; 156:ITC3.
Hooton TM, Roberts PL, Cox ME, Stapleton AE. Voided midstream urine culture and acute cystitis in premenopausal women. N Engl J Med 2013; 369:1883.
Kahlmeter G. Prevalence and antimicrobial susceptibility of pathogens in uncomplicated cystitis in Europe. The ECO.SENS study. Int J Antimicrob Agents 2003; 22 Suppl 2:49.
Kahlmeter G, ECO.SENS. An international survey of the antimicrobial susceptibility of pathogens from uncomplicated urinary tract infections: the ECO.SENS Project. J Antimicrob Chemother 2003; 51:69.
Naber KG, Schito G, Botto H, et al. Surveillance study in Europe and Brazil on clinical aspects and Antimicrobial Resistance Epidemiology in Females with Cystitis (ARESC): implications for empiric therapy. Eur Urol 2008; 54:1164.
Zhanel GG, Hisanaga TL, Laing NM, et al. Antibiotic resistance in Escherichia coli outpatient urinary isolates: final results from the North American Urinary Tract Infection Collaborative Alliance (NAUTICA). Int J Antimicrob Agents 2006; 27:468.
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 Microbiology and Infectious Diseases. Clin Infect Dis 2011; 52:e103.
Sanchez GV, Master RN, Karlowsky JA, Bordon JM. In vitro antimicrobial resistance of urinary Escherichia coli isolates among U.S. outpatients from 2000 to 2010. Antimicrob Agents Chemother 2012; 56:2181.
Swami SK, Liesinger JT, Shah N, et al. Incidence of antibiotic-resistant Escherichia coli bacteriuria according to age and location of onset: a population-based study from Olmsted County, Minnesota. Mayo Clin Proc 2012; 87:753.
Gupta K, Hooton TM, Miller L, Uncomplicated UTI IDSA Guideline Committee. Managing uncomplicated urinary tract infection--making sense out of resistance data. Clin Infect Dis 2011; 53:1041.
Richards DA, Toop LJ, Chambers ST, et al. Antibiotic resistance in uncomplicated urinary tract infection: problems with interpreting cumulative resistance rates from local community laboratories. N Z Med J 2002; 115:12.
Ti TY, Kumarasinghe G, Taylor MB, et al. What is true community-acquired urinary tract infection? Comparison of pathogens identified in urine from routine outpatient specimens and from community clinics in a prospective study. Eur J Clin Microbiol Infect Dis 2003; 22:242.
Brown PD, Freeman A, Foxman B. Prevalence and predictors of trimethoprim-sulfamethoxazole resistance among uropathogenic Escherichia coli isolates in Michigan. Clin Infect Dis 2002; 34:1061.
Metlay JP, Strom BL, Asch DA. Prior antimicrobial drug exposure: a risk factor for trimethoprim-sulfamethoxazole-resistant urinary tract infections. J Antimicrob Chemother 2003; 51:963.
Colgan R, Johnson JR, Kuskowski M, Gupta K. Risk factors for trimethoprim-sulfamethoxazole resistance in patients with acute uncomplicated cystitis. Antimicrob Agents Chemother 2008; 52:846.
Olson RP, Harrell LJ, Kaye KS. Antibiotic resistance in urinary isolates of Escherichia coli from college women with urinary tract infections. Antimicrob Agents Chemother 2009; 53:1285.
Miller LG, Tang AW. Treatment of uncomplicated urinary tract infections in an era of increasing antimicrobial resistance. Mayo Clin Proc 2004; 79:1048.
Talan DA, Krishnadasan A, Abrahamian FM, et al. Prevalence and risk factor analysis of trimethoprim-sulfamethoxazole- and fluoroquinolone-resistant Escherichia coli infection among emergency department patients with pyelonephritis. Clin Infect Dis 2008; 47:1150.
Paterson DL. "Collateral damage" from cephalosporin or quinolone antibiotic therapy. Clin Infect Dis 2004; 38 Suppl 4:S341.
Schito GC, Naber KG, Botto H, et al. The ARESC study: an international survey on the antimicrobial resistance of pathogens involved in uncomplicated urinary tract infections. Int J Antimicrob Agents 2009; 34:407.
Ho PL, Yip KS, Chow KH, et al. Antimicrobial resistance among uropathogens that cause acute uncomplicated cystitis in women in Hong Kong: a prospective multicenter study in 2006 to 2008. Diagn Microbiol Infect Dis 2010; 66:87.
Lautenbach E. Editorial commentary: flying under the radar: the stealth pandemic of Escherichia coli sequence type 131. Clin Infect Dis 2013; 57:1266.
Mody L, Juthani-Mehta M. Urinary tract infections in older women: a clinical review. JAMA 2014; 311:844.
Juthani-Mehta M, Quagliarello V, Perrelli E, et al. Clinical features to identify urinary tract infection in nursing home residents: a cohort study. J Am Geriatr Soc 2009; 57:963.
Sundvall PD, Ulleryd P, Gunnarsson RK. Urine culture doubtful in determining etiology of diffuse symptoms among elderly individuals: a cross-sectional study of 32 nursing homes. BMC Fam Pract 2011; 12:36.
Sundvall PD, Elm M, Ulleryd P, et al. Interleukin-6 concentrations in the urine and dipstick analyses were related to bacteriuria but not symptoms in the elderly: a cross sectional study of 421 nursing home residents. BMC Geriatr 2014; 14:88.
Dasgupta M, Brymer C, Elsayed S. Treatment of asymptomatic UTI in older delirious medical in-patients: A prospective cohort study. Arch Gerontol Geriatr 2017; 72:127.
Potts L, Cross S, MacLennan WJ, Watt B. A double-blind comparative study of norfloxacin versus placebo in hospitalised elderly patients with asymptomatic bacteriuria. Arch Gerontol Geriatr 1996; 23:153.
Bent S, Nallamothu BK, Simel DL, et al. Does this woman have an acute uncomplicated urinary tract infection? JAMA 2002; 287:2701.
Stamm WE. Measurement of pyuria and its relation to bacteriuria. Am J Med 1983; 75:53.
Wilson ML, Gaido L. Laboratory diagnosis of urinary tract infections in adult patients. Clin Infect Dis 2004; 38:1150.
Nace DA, Drinka PJ, Crnich CJ. Clinical uncertainties in the approach to long term care residents with possible urinary tract infection. J Am Med Dir Assoc 2014; 15:133.
Lipsky BA, Ireton RC, Fihn SD, et al. Diagnosis of bacteriuria in men: specimen collection and culture interpretation. J Infect Dis 1987; 155:847.
Stamm WE, Counts GW, Running KR, et al. Diagnosis of coliform infection in acutely dysuric women. N Engl J Med 1982; 307:463.
Barnes RC, Daifuku R, Roddy RE, Stamm WE. Urinary-tract infection in sexually active homosexual men. Lancet 1986; 1:171.
Gupta K. Emerging antibiotic resistance in urinary tract pathogens. Infect Dis Clin North Am 2003; 17:243.
Raz R, Chazan B, Kennes Y, et al. Empiric use of trimethoprim-sulfamethoxazole (TMP-SMX) in the treatment of women with uncomplicated urinary tract infections, in a geographical area with a high prevalence of TMP-SMX-resistant uropathogens. Clin Infect Dis 2002; 34:1165.
FDA Drug Safety Communication: FDA advises restricting fluoroquinolone antibiotic use for certain uncomplicated infections; warns about disabling side effects that can occur together. http://www.fda.gov/Drugs/DrugSafety/ucm500143.htm (Accessed on May 26, 2016
Peterson J, Kaul S, Khashab M, et al. A double-blind, randomized comparison of levofloxacin 750 mg once-daily for five days with ciprofloxacin 400/500 mg twice-daily for 10 days for the treatment of complicated urinary tract infections and acute pyelonephritis. Urology 2008; 71:17.
Gupta K, Hooton TM, Roberts PL, Stamm WE. Short-course nitrofurantoin for the treatment of acute uncomplicated cystitis in women. Arch Intern Med 2007; 167:2207.
McKinnell JA, Stollenwerk NS, Jung CW, Miller LG. Nitrofurantoin compares favorably to recommended agents as empirical treatment of uncomplicated urinary tract infections in a decision and cost analysis. Mayo Clin Proc 2011; 86:480.
Huttner A, Verhaegh EM, Harbarth S, et al. Nitrofurantoin revisited: a systematic review and meta-analysis of controlled trials. J Antimicrob Chemother 2015; 70:2456.
Hooton TM, Winter C, Tiu F, Stamm WE. Randomized comparative trial and cost analysis of 3-day antimicrobial regimens for treatment of acute cystitis in women. JAMA 1995; 273:41.
Singh N, Gandhi S, McArthur E, et al. Kidney function and the use of nitrofurantoin to treat urinary tract infections in older women. CMAJ 2015; 187:648.
Oplinger M, Andrews CO. Nitrofurantoin contraindication in patients with a creatinine clearance below 60 mL/min: looking for the evidence. Ann Pharmacother 2013; 47:106.
By the American Geriatrics Society 2015 Beers Criteria Update Expert Panel. American Geriatrics Society 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc 2015; 63:2227.
Santos JM, Batech M, Pelter MA, Deamer RL. Evaluation of the Risk of Nitrofurantoin Lung Injury and Its Efficacy in Diminished Kidney Function in Older Adults in a Large Integrated Healthcare System: A Matched Cohort Study. J Am Geriatr Soc 2016; 64:798.
Arredondo-García JL, Figueroa-Damián R, Rosas A, et al. Comparison of short-term treatment regimen of ciprofloxacin versus long-term treatment regimens of trimethoprim/sulfamethoxazole or norfloxacin for uncomplicated lower urinary tract infections: a randomized, multicentre, open-label, prospective study. J Antimicrob Chemother 2004; 54:840.
Iravani A, Klimberg I, Briefer C, et al. A trial comparing low-dose, short-course ciprofloxacin and standard 7 day therapy with co-trimoxazole or nitrofurantoin in the treatment of uncomplicated urinary tract infection. J Antimicrob Chemother 1999; 43 Suppl A:67.
Kavatha D, Giamarellou H, Alexiou Z, et al. Cefpodoxime-proxetil versus trimethoprim-sulfamethoxazole for short-term therapy of uncomplicated acute cystitis in women. Antimicrob Agents Chemother 2003; 47:897.
Warren JW, Abrutyn E, Hebel JR, et al. Guidelines for antimicrobial treatment of uncomplicated acute bacterial cystitis and acute pyelonephritis in women. Infectious Diseases Society of America (IDSA). Clin Infect Dis 1999; 29:745.
Stein GE. Comparison of single-dose fosfomycin and a 7-day course of nitrofurantoin in female patients with uncomplicated urinary tract infection. Clin Ther 1999; 21:1864.

Falagas ME, Vouloumanou EK, Togias AG, et al. Fosfomycin versus other antibiotics for the treatment of cystitis: a meta-analysis of randomized controlled trials. J Antimicrob Chemother 2010; 65:1862.
Huttner A, Kowalczyk A, Turjeman A, et al. Effect of 5-day nitrofurantoin vs single-dose fosfomycin on clinical resolution of uncomplicated lower urinary tract infection in women: A randomized clinical trial. JAMA 2018; doi:10.1001/jama.2018.3627.
Datta R, Juthani-Mehta M. Nitrofurantoin vs Fosfomycin: Rendering a Verdict in a Trial of Acute Uncomplicated Cystitis. JAMA 2018; 319:1771.
Lutters M, Vogt-Ferrier NB. Antibiotic duration for treating uncomplicated, symptomatic lower urinary tract infections in elderly women. Cochrane Database Syst Rev 2008; :CD001535.
Auquer F, Cordón F, Gorina E, et al. Single-dose ciprofloxacin versus 3 days of norfloxacin in uncomplicated urinary tract infections in women. Clin Microbiol Infect 2002; 8:50.
Hooton TM, Scholes D, Gupta K, et al. Amoxicillin-clavulanate vs ciprofloxacin for the treatment of uncomplicated cystitis in women: a randomized trial. JAMA 2005; 293:949.
Rodríguez-Baño J, Alcalá JC, Cisneros JM, et al. Community infections caused by extended-spectrum beta-lactamase-producing Escherichia coli. Arch Intern Med 2008; 168:1897.
Nicolle LE, Madsen KS, Debeeck GO, et al. Three days of pivmecillinam or norfloxacin for treatment of acute uncomplicated urinary infection in women. Scand J Infect Dis 2002; 34:487.
Henry D, Ellison W, Sullivan J, et al. Treatment of community-acquired acute uncomplicated urinary tract infection with sparfloxacin versus ofloxacin. The Sparfloxacin Multi Center UUTI Study Group. Antimicrob Agents Chemother 1998; 42:2262.
Richard GA, Mathew CP, Kirstein JM, et al. Single-dose fluoroquinolone therapy of acute uncomplicated urinary tract infection in women: results from a randomized, double-blind, multicenter trial comparing single-dose to 3-day fluoroquinolone regimens. Urology 2002; 59:334.
Fourcroy JL, Berner B, Chiang YK, et al. Efficacy and safety of a novel once-daily extended-release ciprofloxacin tablet formulation for treatment of uncomplicated urinary tract infection in women. Antimicrob Agents Chemother 2005; 49:4137.
Henry DC Jr, Bettis RB, Riffer E, et al. Comparison of once-daily extended-release ciprofloxacin and conventional twice-daily ciprofloxacin for the treatment of uncomplicated urinary tract infection in women. Clin Ther 2002; 24:2088.
Vogel T, Verreault R, Gourdeau M, et al. Optimal duration of antibiotic therapy for uncomplicated urinary tract infection in older women: a double-blind randomized controlled trial. CMAJ 2004; 170:469.
Zalmanovici Trestioreanu A, Green H, Paul M, et al. Antimicrobial agents for treating uncomplicated urinary tract infection in women. Cochrane Database Syst Rev 2010; :CD007182.
Hooton TM, Besser R, Foxman B, et al. Acute uncomplicated cystitis in an era of increasing antibiotic resistance: a proposed approach to empirical therapy. Clin Infect Dis 2004; 39:75.
Little P, Moore MV, Turner S, et al. Effectiveness of five different approaches in management of urinary tract infection: randomised controlled trial. BMJ 2010; 340:c199.
Klimberg I, Shockey G, Ellison H, et al. Time to symptom relief for uncomplicated urinary tract infection treated with extended-release ciprofloxacin: a prospective, open-label, uncontrolled primary care study. Curr Med Res Opin 2005; 21:1241.
Qiao LD, Chen S, Yang Y, et al. Characteristics of urinary tract infection pathogens and their in vitro susceptibility to antimicrobial agents in China: data from a multicenter study. BMJ Open 2013; 3:e004152.
Jansåker F, Frimodt-Møller N, Sjögren I, Dahl Knudsen J. Clinical and bacteriological effects of pivmecillinam for ESBL-producing Escherichia coli or Klebsiella pneumoniae in urinary tract infections. J Antimicrob Chemother 2014; 69:769.
Bleidorn J, Gágyor I, Kochen MM, et al. Symptomatic treatment (ibuprofen) or antibiotics (ciprofloxacin) for uncomplicated urinary tract infection?--results of a randomized controlled pilot trial. BMC Med 2010; 8:30.
Gágyor I, Bleidorn J, Kochen MM, et al. Ibuprofen versus fosfomycin for uncomplicated urinary tract infection in women: randomised controlled trial. BMJ 2015; 351:h6544.
Kronenberg A, Bütikofer L, Odutayo A, et al. Symptomatic treatment of uncomplicated lower urinary tract infections in the ambulatory setting: randomised, double blind trial. BMJ 2017; 359:j4784.
Lipsky BA. Urinary tract infections in men. Epidemiology, pathophysiology, diagnosis, and treatment. Ann Intern Med 1989; 110:138.
Abarbanel J, Engelstein D, Lask D, Livne PM. Urinary tract infection in men younger than 45 years of age: is there a need for urologic investigation? Urology 2003; 62:27.

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UTI Uncomplicated: Acute Simple Cystitis (FL INITIAL Autonomous Practice - Differential Diagnosis)

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