Diagnosis and Management of Urinary Tract Infections: A Disease Stratification M
Diagnosis and Management of Urinary Tract Infections: A Disease Stratification Model
Part II: Targeted Management and Syndrome Specific Antibiotic Therapy
Author: Scott A. Gallagher, MD, Staff Physician, Department of Emergency Medicine, Aspen Valley Hospital, Aspen, CO.
Peer Reviewer: Robin R. Hemphill, MD, Assistant Program Director, Emergency Medicine Residency, San Antonio Uniformed Services Health Educator Consortium, Fort Sam Houston, TX; Assistant Professor, Department of Emergency Medicine, Vanderbilt University, Nashville, TN.
Urinary tract infection: common, easy-to-diagnose, and routine, yet difficult to manage in an outcome-effective manner. In fact, few infectious conditions present a greater challenge for cost-effective antibiotic use. Accordingly, optimizing management of patients with urinary tract infection (UTI) requires stratifying individuals according to severity of disease, location of the infection, and accounting for other, underlying host risk factors.
There are many ways to clinically stratify patients with UTI and none is perfect. Frequently, patients are classified into such categories as uncomplicated UTI (cystitis), uncomplicated acute pyelonephritis, complicated pyelonephritis, and complicated UTI. There is some overlap in these presentations, and the need for hospitalization vs. outpatient therapy will vary according to the severity of the illness and preferred route for antibiotic administration.
Fortunately, in the case of uncomplicated UTI, cure rates are still adequate with three-day courses of attractively priced medications such as trimethoprim-sulfamethoxazole. Treatment failures, however, are seen in a significant percentage of these patients, who will then require intensification of coverage with a fluoroquinolone, such as ciprofloxacin, which remains the gold standard for UTIs, in general. However, newer fluoroquinolones, such as levofloxacin and trovafloxacin, also are available, although physicians should note differing indications for complicated vs. uncomplicated UTI in this drug class. Patients with systemic signs and symptoms will require IV therapy, usually with a quinolone or cephalosporin.
In the concluding part of this two-part series, Scott A. Gallagher, MD, focuses on various UTI syndromes and identifies treatment options according to severity, sex of the patient, pregnancy, and other factors. Detailed treatment tables are provided.
—The Editor
Clinical Syndromes
Asymptomatic Bacteriuria in Women. The overall prevalence of ABU in women of childbearing age is 4-7% but rarely is of clinical importance. The prevalence of bacteriuria does not differ from that of age-matched, sexually active, nonpregnant women; however, the risk of progression to pyelonephritis in pregnant women is greatly increased from 1.4% to 28.0%. Prevalence is doubled in women with lower socioeconomic class, sickle cell hemoglobinopathies (including sickle cell trait), diabetes mellitus, and those with anatomic abnormalities of the urinary tract. All pregnant women should be screened for bacteriuria in the first trimester, preferably around 16 weeks, and treatment should be started promptly if identified. Urine culture remains the standard for screening for bacteriuria. Early identification and irradication are essential because of the risks associated with pyelonephritis, including low birth weight, prematurity, anemia, gestational hypertension, preeclampsia, amnionitis, septic shock, ARDS, and death.1-3
Children. Infants and children with ABU represent a low-risk group unlike those with symptomatic bacteriuria who often develop high-grade reflux, recurrences, pyelonephritis, and renal scarring. Untreated ABU in infants and young girls carries a small risk of pyelonephritis but most have a tendency to spontaneously become abacteriuric, particularly after achieving normal voiding habits. The risk of developing acute pyelonephritis in girls with untreated ABU is associated with a change in bacterial strain, often as a result of antibiotic treatment. Low-virulence strains lacking the ability to adhere and cause symptoms associated with ABU may be commensal with the host and even protect against infection by more virulent strains. Treatment is associated with a high recurrence rate—generally by new strains that carry the risk of being more virulent. While there is controversy, ABU in children should generally be left untreated as long as a child’s voiding habits and urinary tract are otherwise normal. Some have even questioned the need for treatment in the presence of renal scarring, as ABU caused by bacteria with low virulence seem to protect against infection with virulent strains. Children with voiding disorders, including infrequent voiding, should be referred for consideration of combined treatment of the voiding disorder and bacteriuria, possibly followed by long-term antibiotic prophylaxis. It is important to differentiate ABU from infection in children with neurogenic disorders, such as spina bifida, who are managed with clean intermittent catheterization (CIC) and may present with fever and coincidental but unrelated bacteriuria. Fever in these patients is not necessarily a consequence of bacteriuria, and alternative sources of infection should be explored. In these situations, DMSA scans may be helpful in differentiating children with pyelonephritis from children with fever and coincidental bacteriuria.4-6
Elderly. In older adults, routine screening and treatment for ABU appears to be unwarranted. A relationship between ABU and mortality in older adults has been proposed and disputed. While antibiotic therapy does reduce the occurrence of positive follow-up cultures in older ambulatory women, no clinical advantage of treatment has been demonstrated.7 Similarly, in catheterized patients, antibiotics have no effect on the incidence of febrile episodes and are associated with a marked increase in antibiotic-resistant organisms.8 Antibiotics may be warranted, however, under certain conditions in catheterized patients: isolation of bacterial strains known to cause a high incidence of bacteremia, such as Serratia marcescens; patients at high risk for serious complications, such as renal transplant or granulocytopenic patients; and patients undergoing surgery, particularly those involving the genitourinary tract or prostheses. The question of whether postcatheterization ABU should be treated is unresolved. Most women younger than 65 years resolve their bacteriuria spontaneously within 14 days, compared with only 4% of older women. At this time, the natural history of antibiotic therapy for post-catheterization bacteriuria is unclear.9
Cystitis
Women. In young, sexually active, nonpregnant woman who have not been recently treated with antimicrobials, an uncomplicated UTI is likely allowing for an abbreviated workup for probable cystitis. It is important to attempt to differentiate cystitis from vaginitis and urethritis. The usual organisms causing acute cystitis come from a remarkably narrow spectrum of etiologic agents with highly predictable antibiotic susceptibility profiles: Escherichia coli in 80%, Staphylococcus saprophyticus in 5-15%, and occasionally Klebsiella species, Proteus mirablis, or other microorganisms.10 In patients with typical symptoms, short-course antibiotic therapy is given empirically for presumed cystitis. Although localization studies indicate that as many as 30% of patients who present clinically with a cystitis-like syndrome may have subclinical upper urinary tract involvement, none of the currently available localization tests are feasible or accurate for use in practice.11 Generally, no follow-up testing is done unless the symptoms persist or recur, which should prompt performance of urinalysis and urine culture.12
Pregnancy. In pregnancy, the frequency of acute bacterial cystitis is 0.3-1.3%.13 The clinical presentation of cystitis in pregnancy may go unrecognized if the symptoms of urinary frequency, urgency, nocturia, and suprapubic discomfort are attributed to the pregnancy alone. All of these complaints are commonly reported by pregnant women without urinary tract infections. Dysuria is the most specific complaint suggestive of cystitis in pregnancy and warrants evaluation. It is important to consider pyelonephritis when dysuria is present because 40% of pregnant women with pyelonephritis also may only have symptoms of lower tract involvement. The diagnosis is made on the basis of a combination of the presence of typical cystitis symptoms, the absence of upper urinary tract symptomatology, and positive laboratory findings (urinalysis and urine culture). The organisms involved are the same as in asymptomatic bacteriuria.1,2
Children. Acute cystitis in children is not associated with renal scarring and rarely causes any long-term morbidity. Irritative lower tract symptoms such as urgency, frequency, enuresis, and dysuria may be seen in the absence of bacterial cystitis. These symptoms also occur in the setting of vulvitis, urethritis, and dysfunctional voiding, such as is seen with the urgency-frequency syndrome. This self-limiting condition is manifest by frequency and urgency during the day, without nocturia or enuresis. Fever is not frequent, although it may be present in infants.4
Men. Acute uncomplicated UTI in men less than 50 years old is very uncommon and often associated with behavioral risk factors such as lack of circumcision, having female partners colonized with E. coli, or engaging in anal intercourse. The same uropathogenic strains of E. coli that cause pyelonephritis in young women can also cause uncomplicated UTI in young men, usually cystitis. Clinically, these infections often present as cystitis, but in some patients they mimic urethritis, causing urethral discharge and urethral leukocytosis.12
Pyelonephritis
Women. The clinical spectrum of acute pyelonephritis in young women ranges from gram-negative septicemia to a cystitis-like illness with mild flank pain.14 The diagnosis of acute pyelonephritis requires a clinical presentation of fever, chills, and flank pain that is accompanied by positive urinalysis (bacteriuria and pyuria) and urine culture. In general, the term should not be used if flank pain is absent, unless there are underlying conditions that may preclude the presence of flank pain. Similarly, in women without objective evidence of fever, one should be alert for alternative diagnoses, including cholecystitis, pelvic inflammatory disease, and diverticulitis.15
Pregnancy. In pregnant women, pyelonephritis is more common during the second half of pregnancy, presumably because of the increase in ureteral obstruction and stasis of urine as pregnancy progresses. It is usually unilateral and predominantly right-sided as a result of uterine dextrorotation. Hospitalization is generally recommended for these patients because of the risk of serious complications to the mother and fetus, however, outpatient therapy may be appropriate for select patients at less than 24-weeks gestation.16 Complications include pulmonary injury with respiratory insufficiency and adult respiratory distress syndrome (ARDS), hemolysis and significant anemia with risk for hemodynamic instability, transient renal dysfunction, perinephric cellulitis or abscess, septic shock syndrome, and preterm labor and delivery. Additionally, many of these women are unable to tolerate oral medications because of nausea and vomiting. The differential diagnosis of pyelonephritis during pregnancy primarily includes appendicitis (because the appendix is more superior during pregnancy), chorioamnionitis (because it is one of the most common obstetric infections), pneumonia, nephrolithiasis, and renal abscess.
Routine laboratory evaluation at the time of admission includes a complete blood count, serum electrolytes, creatinine, and a urine culture. Blood cultures do not need to be universally obtained in pregnant women with pyelonephritis. Although approximately 15% of pregnant patients with pyelonephritis have bacteremia, most do not become seriously ill, blood cultures do not influence empiric therapy, results tend to parallel those of the urine cultures, and rare discrepant results do not alter the clinical management. Blood cultures should be reserved for women who appear septic, have medical complications, or are not responding to conventional antibiotic therapy. A shielded chest x-ray and arterial blood gas should be obtained in patients with signs of respiratory compromise, such as tachypnea or dyspnea. Fetal exposure to radiation is minimal with a shielded chest x-ray and no adverse sequelae have been associated with this study. The patient is kept intravenously hydrated with either normal saline or Ringer’s solution to ensure urine output of at least 30-50 mL per hour. A Foley catheter is unnecessary for measuring urine output and may, in fact, be a source of infection. Bladder catheterization should be reserved for those who are seriously ill. If preterm labor is already present or develops during hospitalization, transfer to a hospital with a level III nursery may be indicated in case delivery ensues.1,2,13
Children. Pyelonephritis represents the most severe type of UTI in children, and is associated with obstructive uropathy or vesicoureteral reflux in approximately 50% of patients. There is potential for significant morbidity and irreversible renal damage. While older children typically present with fever and flank pain or tenderness, infants and young children may present only with nonspecific symptoms, such as irritability, poor feeding, failure to gain weight, vomiting, and diarrhea. Fever may be absent in neonates, but is usually present in most infants and children. Localization studies, such as DMSA renal scans, suggest that laboratory and clinical findings have high false-negative rates, making accurate diagnosis of pyelonephritis difficult, particularly in younger children.4 For these reasons, diagnosis and treatment are often delayed, increasing the risk of renal sequelae, such as renal scarring.
Recurrent Infection
Females. The vast majority of recurrent UTIs in women are the result of reinfection. The initial infecting strain may persist in the fecal reservoir after elimination from the urinary tract and may subsequently recolonize the introitus and bladder, resulting in recurrent UTI. Reinfection is common among women, even in those without evidence of genitourinary tract abnormalities, which occur in approximately 30-50% within one year after initial infection. Recurrence is approximately 20-30 times more likely with acute cystitis than pyelonephritis.17 Occasionally, recurrences are caused by a persistent focus of infection. Causes of bacterial persistence in women include noncompliance, inadequate antibiotic coverage, acquired or pre-existing bacterial resistance, infected renal calculi, infected paraurethral glands, papillary necrosis (analgesic abuse), and genitourinary tract abnormalities such as ureteral duplication, urothelial polyp, atrophic kidney, urethral diverticula, ureteral stump, urachal cyst, enterovesical or vesicovaginal fistula, and medullary sponge kidney.18
Children. Recurrent infection is common in children, occurring in 18% of male and 26% of female infants, and 32% of boys and 40% of girls in potty-training and school age groups. Recurrent UTI in children is usually caused by reinfection, and only rarely as the result of a persistent infected focus. Identification is important because of the need for imaging (if not performed following the first UTI) and management of vesicoureteral reflux or voiding dysfunction. Suspicion of a persistent focus in a child who is not improving is an indication for imaging studies to evaluate the possibility of genitourinary tract abnormality or perinephric or renal abscess. Rarely, a CT may be indicated to evaluate for segmental involvement in pyelonephritis (lobar nephronia). Recurrences more than one year after the initial infection are rare in infants and uncommon in older children, with most occurring within the first year.19
Treatment
Asymptomatic Bacteriuria. With the exception of pregnancy and surgery, treatment of ABU is generally not indicated. In pregnancy, a mother’s chance of developing pyelonephritis is reduced 80% if she receives antibiotic therapy.13 There is controversy over the optimal duration of antibiotic therapy, however, a three- to seven-day course is generally recommended with either a penicillin or cephalosporin because of their proven efficacy and safety during gestation. Sulfonamides and nitrofurantoin may also be used, with the awareness that sulfonamides given near term could result in fetal hyperbilirubinemia and that nitrofurantoin can cause hemolysis in the setting of G6PD deficiency. Repeat cultures should be obtained within seven days of treatment to confirm eradication of bacteriuria, and the patient should be monitored with follow-up urine cultures monthly until delivery. Persistent infection following the first course of treatment may be treated with a second course of antibiotics according to the antibiotic sensitivities of the organism. Subsequent treatment failure should prompt urologic evaluation to rule out the presence of a structural abnormality, and consideration should be given to suppressive antibiotic therapy, either daily or postcoital, until delivery.1
Cystitis. For acutely symptomatic young women with cystitis, the preferred treatment is a three-day course with trimethoprim-sulfamethoxazole (TMP-SMX) or fluoroquinolone. (See Table 1.) TMP-SMX should be considered the first-line agent in women who can tolerate this agent and in areas in which resistance is infrequent because the quinolones, while effective, are considerably more expensive and there is concern about promoting bacterial resistance. Quinolones may be considered first-line in patients with allergies to other drugs or in areas where trimethoprim resistance is high (> 10%). Single-dose therapy has lost favor because of fewer cures and increased recurrence rates, while the seven-day course has greater potential for side effects, is more expensive, and has not been shown to improve the therapeutic effect. Some sources would suggest that patients with UTI symptoms for greater than five days, the elderly, diabetics, immunocompromised patients, males, those with flank pain but no fever, those with fever but no other constitutional findings, etc., require longer than three days of therapy.3,14,20 For patients with severe dysuria, 1-2 days of analgesics, such as phenazopyridine 200 mg TID, may be helpful.12
| Table 1. Available Treatment Regimens for Urinary Tract Infections1-4,13,17,29 | ||||
| Condition | Medication | Dose and Duration | Route | Notes |
| Acute Uncomplicated UTI | Adult females: | 1-day course | ||
| Fosfomycin | 3.0 g | po x 1 | a, b | |
| 3-day course | ||||
| Trimethoprim-Sulfamethoxazole
Trimethoprim Norfloxacin Ciprofloxacin Ofloxacin Lomefloxacin Trovafloxacin Levofloxacin Enoxacin |
160/180 mg
100 mg 400 mg 250 mg 200 mg 400 mg 100 mg 250 mg 200 mg |
po q12
po q12 po q12 po q12 po q12 po q24 po q24 po q24 po q12 |
||
| Diabetes, Recurrence, older than 65 yrs. | ||||
| Men: | 7-day course | c | ||
| Trimethoprim-Sulfamethoxazole
Trimethoprim Norfloxacin Ciprofloxacin Ofloxacin Lomefloxacin Enoxacin Trovafloxacin Levofloxacin |
160/180 mg
100 mg 400 mg 250 mg 400 mg 400 mg 400 mg 200 mg 250 mg |
po q12
po q12 po q12 po q12 po q12 po q24 po q12 po q24 po q24 |
||
| Pregnancy: | 7-day course | d | ||
| Amoxicillin
Ampicillin Nitrofurantoin Cefpodoxime Cephalexin Cefadroxil Trimethoprim-Sulfamethoxazole |
250 mg
250 mg 100 mg 100 mg 500 mg 500 mg 160/180 mg |
po q8
po q8 po q6 po q12 po q6 po q12 po q12 |
e
f |
|
| Pediatrics: | 3 to 10-day course | g | ||
| Trimethoprim-Sulfamethoxazole
Nitrofurantoin
|
8-10 mg/kg/d TMP
40 mg/kg/d SMX 5-7 mg/kg/d 8-10 mg/kg/d 25-100 mg/kg/d |
po divided q12 po divided q6 po divided q12 po divided q6 |
e
|
|
| Condition | Medication | Dose and Duration | Route | Notes |
| Acute Uncomplicated pyelonephritis | Adult females, outpatient: | 10 to 14-day course | h | |
| Trimethoprim-Sulfamethoxazole
Norfloxacin Ciprofloxacin Ofloxacin Lomefloxacin Enoxacin Levofloxacin |
160/180 mg
400 mg 500 mg 200-300 mg 400 mg 400 mg 250 mg |
po q12
po q12 po q12 po q12 po q24 po q12 po q24 |
||
| Adult females, hospitalized: | 14-day course; IV UNTIL AFEBRILE, THEN PO | i | ||
| Trimethoprim-Sulfamethoxazole
Ceftriaxone Ciprofloxacin Ofloxacin Gentamicin (± Ampicillin) |
160/800 mg
1-2 g 200-400 mg 200-400 mg 1 mg/kg (1 g) |
IV q12
IV q24 IV q12 IV q12 IV q8 (q6) |
||
| Pregnancy: | 14-day course; IV UNTIL AFEBRILE, THEN PO | |||
| Ceftriaxone
Gentamicin (± Ampicillin) Aztreonam Cefazolin Cefoxitin Cefotetan Trimethoprim-Sulfamethoxazole |
1-2 g
1 mg/kg (1 g) 1 g 1-2 g 1-2 g 1-2 g 160/800 mg |
IV q24
IV q8 (q6) IV q8-12 IV q8 IV q6 IV q12 IV q12 |
j f |
|
| Pediatrics: | 14-day course | h,i,k | ||
| Gentamicin
+ Ampicillin Cefotaxime Ceftriaxone |
5-7 mg/kg/d
100-200 mg/kg/d 80-100 mg/kg/d 50-100 mg/kg/d |
IV divided q8
IV divided q6 IV divided q6-8 IV divided q12-24 |
||
| Condition | Medication | Dose and Duration | Route | Notes |
| Complicated urinary tract infection | Adult, outpatient: | 10 to 14-day course | l | |
| Norfloxacin
Ciprofloxacin Ofloxacin Lomefloxacin Enoxacin Trimethoprim-Sulfamethoxazole Levofloxacin |
400 mg
500 mg 200-300 mg 400 mg 400 mg 160/180 mg 250 mg |
po q12
po q12 po q12 po q24 po q12 po q12 po q24 |
||
| Adult, hospitalized: | 14 to 21-day course | m | ||
| Gentamicin (+ Ampicillin)
Ciprofloxacin Ofloxacin Ceftriaxone Aztreonam Ticarcillin-Clavulanate Imipenem-Cilastatin |
1 mg/kg (1 g)
200-400 mg 200-400 mg 1-2 g 1 g 3.2 g 250-500 mg |
IV q8 (q6)
IV q12 IV q12 IV q24 IV q8-12 IV q8 IV q6-8 |
||
| ____________________________________________________________________________________________________
Notes a) Fosmomycin less effective vs. E. coli than TMP/SMX or FQ. b) Consider short course of analgesics for dysuria such as Phenazopyridine 200 mg tid for 1-2 days. c) UTI in men is rare, recommend empiric therapy as in women. Use minimum of seven-day course in cystitis, 10-14 days in pyelonephritis. Avoid Nitrofurantoin since ineffective in occult prostatitis. d) Other contraindicated medications in pregnancy include the following: Tetracycline (teeth malformation), Erythromycin (maternal cholestatic jaundice), Chloramphenicol (toxic gray syndrome), Fluoroquinolones (defective cartilage formation). e) Hemolytic anemia risk in patients with G6PD deficiency. f) Not approved in pregnancy although widely used. Sulfa medications associated with hyperbilirubinemia near term. Trimethoprim is a potential teratogen in 1st trimester. g) Optimal duration of treatment of uncomplicated lower UTI in children controversial, data to support oral therapy ranging from three to 10 days h) In select patients, may consider parenterally administered ceftriaxone to initiate outpatient therapy. i) Consider switching to oral medication when patient afebrile 24-48 hours. j) Potential ototoxicity and nephrotoxicity. Alter dose in women with transient renal dysfunction. k) Inpatient vs. outpatient therapy is controversial. Consider outpatient therapy for nontoxic children and infants older than 3 months in select patients. Also controversial is combined vs. monotherapy. l ) Infections that occur in patient with structurally or functionally abnormal urinary tract, or caused by resistant organisms. m) Consider Ampicillin plus Gentamicin, or Imipenem plus Cilastatin as initial empiric therapy for seriously ill, hospitalized patients to cover against Pseudomona aeruginosa and enterococci. May require prolonged therapy. Modify therapy once antibiotic susceptibilities available. ____________________________________________________________________________________________________ |
||||
For the symptomatic catheterized patient who develops lower abdominal pain without fever or other evidence of systemic infection, an oral antibiotic alone may be sufficient. Catheterized patients with fever or signs of bacteremia, however, should be treated with appropriate systemic antibiotics based on urine gram stain after obtaining cultures of urine and blood. Treatment for 7-10 days is usually sufficient, and patients can often be switched to an oral quinolone or TMP/SMX in few days as symptoms resolve. Removal or replacement of the urethral catheter is reasonable during antibiotic therapy because of the likelihood of bacteria sequestered in a biofilm on the catheter surface. Prior to instituting therapy, sources of infection outside of the urinary tract and catheter obstruction should be ruled out.21
Treatment regimens in pregnancy are generally longer, from 7-10 days, using the same antimicrobial agents as used to treat ABU. Several antibiotics are contraindicated in pregnancy including fluoroquinolones, tetracyclines, and chloramphenicol. Trimethoprim is a potential teratogen, and sulfa drugs compete with bilirubin for albumin-binding sites, and are, thus, relatively contraindicated in the first and third trimesters, respectively. Fluoroquinolones are associated with cartilage deterioration in young animals and should not be used in pregnancy. Tetracyclines may cause congenital malformations and staining of decidual teeth. Chloramphenicol is associated with the risk of aplastic anemia and grey syndrome in the fetus with cardiovascular collapse.1
In children, agents that have been used successfully include sulfonamides, TMP-SMX, nitrofurantoin, trimethoprim, and oral cephalosporins. Ampicillin- and amoxicillin-resistant organisms are common. This drawback has been diminished by the combination of clavulanic acid with amoxicillin. However, this antibiotic is associated with a higher incidence of side effects, is expensive, and is no more effective than the usual drugs. The optimal duration of treatment of acute uncomplicated lower UTIs in children is controversial. As compared to other regimens, three-day therapy has significantly lower recurrence rates than single-dose therapy and cure rates equivalent to conventional 7-10 day therapy, with the advantages of decreased costs, improved compliance, decreased side effects, and decreased effect on the fecal flora.22,23
Pyelonephritis. Patients with suspected acute pyelonephritis require a greater degree of assurance of immediate therapeutic success than with cystitis. This is particularly important in children and pregnant patients because the prevention of serious morbidity may be influenced by the rapidity of effective therapy.24 The optimal duration of treatment for women with acute uncomplicated pyelonephritis is less clearly defined than for acute uncomplicated cystitis. Generally, a 10-14 day course of a quinolone is recommended, although there are no published studies to suggest a course of less than 14-days is effective. Patients must be stratified into those who can be managed as outpatients with oral antibiotic therapy, and those who are ill enough to warrant inpatient, parenteral antibiotic therapy.
Patients with severe pain, nausea, vomiting, dehydration, inability to take oral fluids or medications, or concerns about compliance or complicating factors should be admitted for parenteral antibiotics. When the patient has been afebrile for 24-48 hours, the antibiotic can be changed to oral form to complete 14 days of therapy. Fluoroquinolones are reasonable empiric therapy for mild to moderate illness because the spectrum of activity is broad and high renal parenchymal levels are achieved following oral administration. TMP-SMX is a reasonable alternative if the prevalence of resistance is low or susceptibility is known. If the two-week regimen fails, a longer course of 4-6 weeks should be considered because renal parenchymal disease is more difficult to eradicate than bladder mucosal infections.
Infections with Enterococcus and Pseudomonas are difficult to treat and may need longer therapy. Inpatient therapy, with intravenous antibiotics (ampicillin and gentamicin, TMP-SMX, ceftriaxone, or fluoroquinolone) initially may be required if the patient’s clinical condition suggests a toxic picture or inability to tolerate oral antibiotics. If fever has not resolved by 72 hours, radiologic imaging studies such as ultrasonography or intravenous pyelography should be done to rule out obstruction. Ultrasonography or computed tomography scan, to evaluate for renal abscess or mass, should be considered early in the hospital course if urosepsis does not resolve quickly. The urine culture should be repeated 1-2 weeks after completing therapy to document clearing of the infection. If the culture remains positive, a deep tissue infection is likely, and a four- to six-week course of antibiotics is recommended. For recurrences, a six- to 12-month regimen of prophylaxis may be required.
In pregnant patients, empiric intravenous antibiotic therapy is begun based on common pathogens. Numerous successful regimens have been employed, including ampicillin in conjunction with gentamicin, cephalosporins (ceftriaxone, cefazolin, cefoxitin, cefotetan), and extended-spectrum cephalosporins (mezlocillin, piperacillin). Most pregnant patients with pyelonephritis will become afebrile within 48 hours of the commencement of antibiotic administration. If a patient has not clinically improved after 48-72 hours of therapy, further investigation is necessary to determine the cause. Antibiotic therapy is discontinued when the patient has remained afebrile for at least 24 hours. Follow-up should include frequent urine cultures and consideration of suppressive therapy with 100 mg nitrofurantoin at bedtime until delivery.
In children with pyelonephritis, most would concur with a 10- to 14-day course of antibiotic therapy. There is considerable controversy, however, over the need for hospitalization and treatment with parenteral antibiotics vs. outpatient therapy with oral drugs. Nontoxic children more than 3 months of age can generally be treated as outpatients as long as compliance is not an issue. It is reasonable to initiate therapy with 1-2 days of a long-acting, third-generation cephalosporin, such as ceftriaxone, administered intramuscularly, followed by 10-14 days of oral antibiotics and, according to some, prophylaxis until uroradiographic evaluation. This approach virtually ensures compliance and adequate antimicrobial coverage until the urine culture and sensitivity results are known. Toxic children and infants less than 3 months of age with suspected pyelonephritis should be considered candidates for immediate hospitalization and parenteral therapy, such as an aminoglycoside and ampicillin. Alternatively, one of the newer third-generation cephalosporins may be used, but these are more expensive and do not provide comprehensive coverage of gram-positive organisms, including Enterococcus. Parenteral antibiotic therapy should be continued for 7-14 days in neonates, although oral outpatient therapy to complete a full 10- to 14-day course can be substituted in patients more than 2 months of age when afebrile for 24-48 hours.
Recurrent UTI. In women with cystitis whose symptoms do not resolve by the end of treatment or recur within two weeks, a urine culture should be obtained for antimicrobial testing. One should assume that the organism is not susceptible to the original regimen and retreat with a seven-day regimen using another agent. Symptoms of cystitis that recur after two weeks should be treated as a sporadic infection. Pyelonephritis symptoms that recur within two weeks should also be have a urine culture and treatment for 14-days with an antimicrobial different to the original agent. Renal ultrasound or CT should be considered to evaluate for genitourinary tract abnormalities, complications of pyelonephritis, or evidence of renal or perirenal abscesses. A true relapse, confirmed by repeat culture of the same organism, warrants longer-course therapy (2-6 weeks) based on susceptibility testing.
Children with recurrent UTIs should be given antibiotic prophylaxis with TMP-SMX, trimethoprim or nitrofurantoin for 4-6 months until voiding habits are improved or vesicoureteral reflux resolves with or without surgery. This approach is extremely effective in avoiding breakthrough infection while attempting to attain diurnal and subsequently nocturnal continence.19
Prevention
Females. Unfortunately, in young sexually active women there are few acceptable ways of preventing UTIs. Certainly, contraceptive methods other than a diaphragm and spermicide should be tried. The guilt and fear of sexually associated UTIs, though not sexually transmitted, have the potential to interfere with a couple’s sexual fulfillment. Among women with frequent infections, three main management strategies may be considered: continuous antimicrobial prophylaxis, postcoital prophylaxis, and patient-administered self-treatment. While regular or intermittent antimicrobial prophylaxis will prevent most recurrences, concern about the emergence of resistance limits the usefulness of this approach. Post-coital micturation and the ingestion of cranberry or blueberry juices are unproven methods of prevention in younger women.25 In postmenopausal women, local estrogen replacement with topical vaginal cream can prevent infection in those who remain sexually active and who also have frequent episodes of acute cystitis. No studies have addressed the relation of coitus and UTI in postmenopausal women or in women who have undergone hysterectomy.26 Daily ingestion of 300 mL of cranberry juice can reduce the incidence of bacteriuria and pyuria in elderly women, although this approach has not been studied in younger women.27,28
Catheterized Patients. In catheterized patients, bacteriuria cannot be postponed indefinitely, however, two hygienic principles may help: keep the catheter system closed and remove the catheter as soon as possible. Urine specimens should be obtained by needle aspiration from ports in the distal catheter to keep the urine "closed" to the contaminated environment. Because of the 3-10% incidence per day of bacteriuria, attention should be directed as removing the catheter as soon as possible. Antibacterial bladder irrigation and silver-coated catheters have not been conclusively shown to lower the incidence of catheter-associated bacteriuria. Systemic antibiotics postpone the onset of bacteriuria for several days, but are associated with the emergence of resistant bacteria. In general, unless the patient is at high risk for the complications of catheter-associated bacteriuria (i.e., renal transplant and granulocytopenic patients), antibiotic prophylaxis for short-term catheterization is not warranted.
Children. Normalizing the activity of both the bowel and bladder is the best defense against recurrent infection in children. A careful history may give important clues in regard to correctable voiding and bowel dysfunction. Some children require only a time-voiding schedule to which they void every 2-3 hours, whereas others, in addition, need to have the bladder instability treated with anticholinergic medications.19 In male infants, circumcision may help to prevent UTI by removal of the mucosal surface necessary for bacterial adherence.
Summary
Urinary tract infections encompass a broad range of clinical scenarios, involving both sexes and all ages. The majority of UTIs encountered in the ED occur in otherwise healthy, young women who present with symptoms of acute, uncomplicated bacterial cystitis or pyelonephritis. These patients are at low risk for occult genitourinary tract abnormalities and respond predictably to empiric antibiotic therapy initiated by the ED physician. A distinction, however, must be made between complicated and uncomplicated UTIs because of implications regarding the potential for morbidity, as well as the type and extent of treatment and evaluation required. (See Table 2.)
| Table 2. Recommended Antibiotics for UTI | |
| Uncomplicated UTI-Cystitis | |
| Trimethoprim/Sulfamethoxazole | 160/180 mg po bid x 3 days |
| Ciprofloxacin | 250 mg po bid x 3 days |
| Trovafloxacin | 100 mg po qd x 3 days |
| Levofloxacin | 250 mg po qd x 3 days |
| Acute Uncomplicated Pyelonephritis—Outpatient | |
| Ciprofloxacin | 500 mg po bid x 10-14 days |
| Acute Uncomplicated Pyelonephritis—Inpatient | |
| Ciprofloxacin | 200-400 mg IV q12 |
| Ceftriaxone | 1-2 g IV q24 |
| Complicated UTI—Hospitalized | |
| Ciprofloxacin ± Aminoglycoside OR Aztreonam | 200-400 mg IV q12 |
| _________________________________________________________________ | |
Complicated UTIs may occur in men, children, pregnant women, elderly or immunocompromised patients, and those with neurologic disorders. Infection in these settings ranges from mild cystitis to life-threatening urosepsis, and may be more difficult to treat because of associated structural or functional genitourinary tract abnormalities, resistant organisms, or inadequate host defenses. During pregnancy, both the mother and fetus may suffer serious complications, including ARDS, anemia, renal dysfunction, septic shock syndrome, preterm labor, and delivery as a result of pyelonephritis. Emphasis must be placed on prompt, appropriate therapy and referral in the setting of UTI and bacteriuria in pregnancy.
The old and very young present diagnostic dilemmas as they often do not present with the classic signs and symptoms of UTI, but are at risk of serious sequelae including urosepsis and permanent renal impairment. Infection in children and males must not go unrecognized because of the risk of occult genitourinary tract abnormalities with development of subsequent renal scarring and vesicoureteral reflux. The elderly may also have complicating factors, such as chronic indwelling catheters or significant comorbid illness. Similarly, patients who have diabetes, HIV, granulocytopenia, or are undergoing renal transplantation surgery have increased risk of developing severe infection and are treated according to more conservative algorithms. Special consideration must be given to this group of patients who require prompt, appropriate therapy and evaluation to avoid prolonged infection or serious sequelae in the setting of UTI.
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