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:
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.
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.
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.
Acute simple cystitis among women is extremely common.1,2 Anatomically 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:
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.5,6 Symptomatic 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:
Other comorbidities which increase the risk factors for UTIs include:
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.
UTIs are caused by both Gram-negative and Gram-positive bacteria, as well as, by certain fungi. Uropathogens include1,8-10:
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.11,12 Nevertheless, 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.
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)
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).
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:
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
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.
Physical examination is often not necessary for the diagnosis, but if performed, should include:
A pelvic examination is indicated if symptoms or signs suggesting vaginitis or urethritis are present.
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.
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.
Urinalysis (either by microscopy or by dipstick) for evaluation of pyuria
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).
Urine culture with susceptibility data
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.
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.
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.
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:
Both infectious and noninfectious processes can cause symptoms of dysuria, frequency, urgency, suprapubic pain, and/or hematuria.12
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:
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.
Beta-lactamase inhibitor combination
Mechanism of Action: Fluoroquinolones, which contain a fluorine atom in their chemical structure, are effective against both Gram-negative and Gram-positive bacteria.
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.
Trimethoprim/ Sulfamethoxazole (TMP-SMX)
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.
*All antimicrobial agent dosages presuppose normal renal function.
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:
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%.47,48 Nitrofurantoin 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
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.
There are no studies that have evaluated the optimal duration of antimicrobial therapy in men with 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.
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).
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:
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:
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:
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.
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:
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
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.
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.85 Thus, pending additional data, anti-inflammatory agents alone cannot be recommended as an initial approach to management of symptomatic acute simple cystitis.
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 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.
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).
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
Midstream urine culture collected and sent to lab.
Results of urine culture showed Escherichia coli > 103 colony-forming units/mL
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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