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IntroductIon
According to the CDC, UTIs are the most common bacterial infection requiring medical care, resulting in 8.6 million ambulatory care visits in 2007, 23% of which occurred in the ED (CDC 2011). Over 10.8 million patients in the United States visited the ED for the treatment of UTIs between 2006 and 2009 and 1.8 million patients (16.7%) were admit- ted to acute care hospitals (Sammon 2014). The economic burden of using the ED for the treatment of UTIs is estimated at $2 billion annu- ally. In addition, UTIs rank as the No. 1 infection that leads to an anti- biotic prescription after a physician’s visit (Abbo 2014). Catheter-associated UTIs (CA-UTIs) are the most common type of health care–associated infections reported to the National Health- care Safety Network, making up two-thirds of hospital-acquired UTIs (CDC 2017). The symptoms of UTIs are generally mild, and inappro- priate use of antibiotics can lead to antibiotic resistance; therefore, it is important to establish the appropriate criteria for treatment using narrow-spectrum antibiotics for the optimal duration.
Epidemiology Up to 60% of women have at least one symptomatic UTI during their lifetime. Around 10% of women in the United States have one or more episodes of symptomatic UTIs each year. Young, sexu- ally active women 18–24 years of age have the highest incidence of UTIs. About 25% of these women have spontaneous resolution of symptoms, and an equal number become infected (Sobel 2014). The prevalence of UTIs in men is significantly lower than in women, occurring primarily in men with urologic structural abnormalities and in older adult men.
AbbrevIAtIons In thIs chApter ABP Acute bacterial prostatitis ASB Asymptomatic bacteriuria CA-UTI Catheter-associated urinary tract infection CBP Chronic bacterial prostatitis CRE Carbapenem-resistant Enterobacteriaceae ESBL Extended-spectrum β-lactamase IDSA Infectious Diseases Society of America KPC K. pneumoniae carbapenemase MDR Multidrug-resistant NDM New Delhi metallo-β-lactamase SNF Skilled nursing facility
Table of other common abbreviations.
- Analyze patient risk factors and examination data to distinguish different types of UTIs.
- Design an appropriate empiric treatment plan according to the type and severity of UTI for a patient presenting in the inpatient or outpatient setting.
- Justify pharmacotherapy management for special patient populations with asymptomatic bacteriuria.
- Evaluate the role of antimicrobial and non-antimicrobial strategies for the prevention of recurrent UTI.
Reviewed by Vanthida Huang, Pharm.D., FCCP; Wasim S. El Nekidy, Pharm.D., BCPS, BCACP; LaDonna M. Oelschlaeger, Pharm.D., BCPS; Mary L. Foss, Pharm.D., MBA, BCPS; and Gabriella Douglass, Pharm.D., BCACP, AAHIVP, BC-ADM
By Helen S. Lee, Pharm.D., BCPS-AQ ID; and Jennifer Le, Pharm.D., M.A.S.,
FIDSA, FCCP, FCSHP, BCPS-AQ ID
Urinary Tract Infections
LEarnIng ObjEcTIvEs
Pathophysiology Lower UTIs, also known as cystitis, are significantly more prevalent in women than in men. This is primarily because of anatomic differences, including shorter urethral length and moist periurethral environment in women. Urinary tract infections typically start with periurethral contamination by a uropathogen residing in the gut, followed by colonization of the urethra and, finally, migration by the flagella and pili of the pathogen to the bladder or kidney. Bacterial adherence to the uroepithelium is key in the pathogenesis of UTI. Infec- tions occur when bacterial virulence mechanisms overcome efficient host defense mechanisms. Upper UTIs, also known as pyelonephritis, develop when uropathogens ascend to the kidneys by the ureters. Infec- tions can occur when bacteria bind to a urinary catheter, a kidney, or a bladder stone or when they are retained in the uri- nary tract by a physical obstruction. In severe cases of pyelo- nephritis, the affected kidney may be enlarged, with raised
abscesses on the surface (as revealed in imaging studies). Staphylococcus aureus bacteremia or endocarditis can lead to hematogenous seeding of the bacteria to the kidneys, caus- ing suppurative necrosis or abscess formation within the renal parenchyma (Sobel 2014). In contrast, gram-negative bacilli rarely cause kidney infection by the hematogenous route. According to an experimental model of pyelonephritis, the main renal abnormality reported is the inability to maxi- mally concentrate the urine (Sobel 2014). This concentration defect occurs early in the infection and is rapidly reversible with antibiotic therapy. An obstruction can lead to progres- sive destruction of the affected kidney and subsequent renal insufficiency.
Predisposing Factors In the non-pregnant adult woman with a normal urinary tract, bacteriuria infrequently progresses to symptomatic cystitis or pyelonephritis. Common predisposing factors for UTIs are listed in Table 1-1. The urethra is usually colonized with bacte- ria, and sexual intercourse can force bacteria into the female bladder. Furthermore, spermicides increase colonization of the vagina with uropathogens and adherence of Escherichia coli to vaginal epithelial cells. Patients with structural abnormalities develop UTIs largely from obstruction of the urine flow. Urinary stasis increases susceptibility to infection. Men of any age and pregnant women are susceptible to lesions that result in obstruction (Sobel 2014).
Typical causative Organisms and antibiotic resistance Urinary tract infections are primarily caused by gram-negative bacteria, but gram-positive pathogens may also be involved. More than 95% of uncomplicated UTIs are monobacterial. The most common pathogen for uncomplicated UTIs is E. coli (75%–95%), followed by Klebsiella pneumoniae , Staphylococcus saprophyticus , Enterococcus faecalis , group B streptococci, and Proteus mirabilis (Sobel 2014). Distribution of uropatho- gens may differ by type of infection or patient population (Table 1-2). E. coli can cause both uncomplicated and compli- cated UTIs. P. mirabilis , Pseudomonas aeruginosa , and Entero- coccus spp. predominantly cause complicated infections and are more commonly isolated in hospitals and long-term care facilities. Corynebacterium urealyticum is an important noso- comial uropathogen associated with indwelling catheters. S. saprophyticus tends to cause infection in young women who are sexually active, accounting for 5%–15% of acute cystitis in the United States. Coagulase-positive staphylococci can invade the kidney from hematogenous spread, resulting in renal abscesses. Fungi, particularly Candida spp., may cause UTIs in patients with indwelling catheters who are receiving antibiotic therapy. Antibiotic resistance to E. coli has steadily been increasing; thus, incorporating the local antibiotic susceptibility patterns
basELInE KnOwLEdgE sTaTEmEnTs
Readers of this chapter are presumed to be familiar with the following:
- Basic knowledge of UTI pharmacology, including mechanisms of action, adverse effects, and drug interactions Table of common laboratory reference values
addITIOnaL rEadIngs
The following free resources have additional background information on this topic:
- Sobel JD, Kaye D. Urinary tract infections. In: Mandell GL, Bennett JE, eds. Principles and Practice of Infectious Diseases, 8th ed. Philadelphia: Elsevier Saunders, 2014:886-913.
- Infectious Diseases Society of America (IDSA). Guidelines for Acute Uncomplicated Cystitis and Pyelonephritis in Women, 2011.
- IDSA. Guidelines for Catheter-Associated Urinary Tract Infection in Adults, 2010.
- IDSA. Guidelines for Diagnosis and Treatment of Asymptomatic Bacteriuria in Adults, 2005.
- FDA Safety Information and Adverse Event Reporting Program. Fluoroquinolones Antibacterial Drugs: Drug Safety Communication – FDA Advises Restricting Use for Certain Uncomplicated Infections.
- Grabe M, Bartoletti R, Bjerklund Johansen TE, et al, for the European Association of Urology. Guidelines on Urological Infections. 2015.
of E. coli into clinical decision processes is critical to optimal antibiotic selection. According to the Surveillance Network of urine isolates from female outpatients in the United States, E. coli resistance rates to nitrofurantoin, ciprofloxacin, and tri- methoprim/sulfamethoxazole in 2012 were 0.9%, 11.8%, and 22.2%, respectively (Sanchez 2016). Susceptibility rates with cephalosporins and fluoroquinolones among 2013–2014 iso - lates were significantly lower in hospital- than in community- acquired UTIs, and E. coli resistance to ciprofloxacin was 29% in patients 65 and older (Sanchez 2016). The Study for Monitoring Antimicrobial Resistance Trends reported that among 3498 E. coli isolates from hos- pitals in Canada and the United States, extended-spectrum β-lactamase (ESBL) rates increased from 7.8% in 2010 to 18.3% in 2014 (Lob 2016). Of note, percent susceptibilities of E. coli isolates collected in 2014 in the United States to cef- triaxone, cefepime, ciprofloxacin, levofloxacin, piperacillin/ tazobactam, and amikacin were 80.5%, 83.4%, 64,7%, 65.3%, 96.2%, and 99.4%, respectively (Lob 2016). In recent years, worldwide spread of ESBL-producing E. coli such as CTX-M-15 has emerged as a significant cause of community-associated UTIs (Sobel 2014). Highly antibiotic- resistant uropathogens, including AmpC β-lactamase- or carbapenemase-producing Enterobacteriaceae (e.g., New Delhi metallo-β-lactamase [NDM]) and Acinetobacter spp., are increasingly being reported among health care–associated complicated UTIs (Sobel 2014). Carbapenem-resistant Enterobacteriaceae (CRE) is a growing concern worldwide. According to the CDC, an isolate is considered a CRE if it is resistant to imipenem, meropenem, doripenem, or ertapenem by susceptibility testing or if it is identified to have a carbap- enemase by genotype testing (CDC 2015). The CDC is track- ing CRE types such as K. pneumoniae carbapenemase (KPC), NDM, IMP-1, and OXA β-lactamases. Among these, KPC is the most prevalent type in the United States, and NDM is the most antibiotic resistant type, often resistant to new cephalo- sporin/β-lactamase inhibitor combinations (CDC 2017).
GenerAl treAtment
consIderAtIons
The first step in treating UTIs is to classify the type of infec- tion, such as acute uncomplicated cystitis or pyelonephritis, acute complicated cystitis or pyelonephritis, CA-UTI, asymp- tomatic bacteriuria (ASB), or prostatitis (Coyle 2017). The Infectious Diseases Society of America (IDSA) recommends that empiric regimens for uncomplicated UTIs be guided by the local susceptibility, particularly to E. coli. They recom- mend considering trimethoprim/sulfamethoxazole if the local resistance rate is less than 20% and fluoroquinolones if the resistance rate is less than 10% (Gupta 2011). The empiric regimen for complicated UTIs should also be guided by local susceptibility trends of uropathogens, and definitive regi- mens should be tailored according to susceptibility results, when available (Sobel 2014).
Collateral damage should be considered when deciding on treatment for uncomplicated UTIs (Gupta 2011). Collat- eral damage refers to ecological adverse effects, including the selection of drug-resistant organisms from antibiotic use, particularly when broad-spectrum cephalosporins and fluoroquinolones are used to treat UTIs. Broad-spectrum cephalosporins have been associated with subsequent infections caused by vancomycin-resistant enterococci, ESBL-producing K. pneumoniae , β-lactam–resistant A. bau- mannii , and Clostridium difficile infection. Prior use of fluo - roquinolones has been linked to subsequent colonization or infections with methicillin-resistant S. aureus or fluoroquino - lone-resistant P. aeruginosa (Paterson 2004). The preserved in vitro susceptibility of E. coli to nitrofurantoin and fosfo- mycin suggests that they cause limited collateral damage, perhaps because of their minimal effects on bowel flora. Antibiotics with a lower potential for collateral damage are preferred for uncomplicated cystitis because the infection is often self-limiting, even without treatment, and the risk of progression to tissue invasion or sepsis is minimal. In fact, studies have shown that 25%–42% of women with uncompli- cated cystitis achieved clinical cure even though they did not receive antibiotic treatment or received an inactive antibiotic (Hooton 2012).
clinical Presentation Patients with cystitis commonly present with dysuria, hema- turia, frequency, and occasionally suprapubic pain. Pyelone- phritis usually presents with costovertebral angle tenderness, fevers, urgency, dysuria, chills, nausea, and vomiting. Urinary tract infections are classified into complicated or uncompli - cated, depending on the presence or absence of structural abnormality, pregnancy, sex, and renal obstructions. See Table 1-3 for definitions of types of UTIs.
diagnosis A urinalysis is often used to detect UTIs, and a clean-catch dipstick leukocyte esterase test is a rapid screening test for detecting pyuria, with a high sensitivity and specificity for detecting more than 10 WBC/mm 3 in urine (Sobel 2014). Of note, the presence of pyuria is nonspecific and does not always indicate clinical UTI. Furthermore, bacteriuria alone is not a disease and usually does not necessitate treatment. For symptomatic UTIs, most patients have more than 10 leu- kocytes/mm 3 ; however, negative tests for bacteriuria may occur because of low bacterial burden. Organisms like E. coli , Klebsiella spp., Enterobacter spp., Proteus spp., Staphylococ- cus spp., and Pseudomonas spp. reduce nitrate to nitrite in the urine, and the presence of nitrite on a urinalysis is another marker of UTIs. Urine culture is not recommended for managing acute uncomplicated cystitis. However, for acute pyelonephritis and any type of complicated UTIs, a urine culture should be obtained before empiric therapy to optimize the subsequent
definitive antibiotic regimen once the susceptibility results are available. Most symptomatic UTIs have 10 5 CFU/mL or greater, indicating a 95% probability of infection. One study of 226 healthy premenopausal women with acute cysti- tis showed that the detection of 10–10 2 CFU/mL of E. coli in voided clean-catch midstream urine was highly predictive of bladder infection (Hooton 2013). However, detection of Entero- coccus spp. and group B streptococci at any colony count in this population was not predictive of cystitis but suggested urethral contamination (Hooton 2013). Urine in the bladder is normally sterile. In contrast, the ure- thra and periurethral areas are not sterile, and contamination can occur during urine collection. Therefore, proper cleans- ing before urine collection is critical, especially in women, to avoid contamination with bacteria from the urethral areas. Of note, gram-positive organisms and fungi may not reach 10 5 CFU/mL in patients with infection. Specimens with 10 4 CFU/mL or less may contain skin organisms, such as diphth- eroids, Neisseria spp., and staphylococci. Screening for ASB is necessary for select patients (preg- nant women, individuals undergoing invasive genitouri- nary procedures, and renal transplant recipients) (Nicolle 2005). If screening is indicated, urine should be collected by clean-catch midstream, catheterization, or suprapubic aspiration.
goals of Therapy Symptomatic relief is a high priority in patients with UTIs. With appropriate antibiotic therapy, clinical response occurs within 24 hours for cystitis and within 48–72 hours for pyelo- nephritis. Lack of response within 72 hours warrants a further workup with imaging studies. Patients should receive treat- ment with agents that are low in toxicity and that have low potential of changing the normal bowel flora. Resolution of bacteriuria is anticipated to correlate with the susceptibility of the pathogen relative to the antibiotic concentration in the urine, not the serum (Sobel 2014). However, data are currently limited correlating the antibiotic concentration in the urine in anuric or dialysis patients with clinical outcomes, and addi- tional studies in this topic would be useful.
Hydration During UTI management, hydration dilutes the uropatho- gen and removes infected urine by frequent bladder empty- ing (Sobel 2014). However, the bacterial count returns to the prehydration level after hydration is discontinued. Poten- tial problems with forcing fluids include urinary retention in a patient with a partially obstructed bladder and decreased urinary antibiotic concentration. Although hydration removes the infected urine, there is no clear evidence that hydration improves the outcomes of UTI.
Table 1-3. Definition of Types of UTIs
category definition Uncomplicated UTI • Lower urinary symptoms (dysuria, frequency, and urgency) in otherwise healthy non-pregnant women Complicated UTI • Pregnant women, men, obstruction, immunosuppression, renal failure, renal transplantation, urinary retention from neurologic disease, and individuals with risk factors that predispose to persistent or relapsing infection (e.g., calculi, indwelling catheters or other drainage devices)
- Health care associated CA-UTI • Presence of indwelling urinary catheters with signs and symptoms of UTI and no other source of infection
- Presence of ≥ 10^3 CFU/mL in a single catheter urine specimen or in a midstream urine, despite removal of urinary catheter in the previous 48 hr Asymptomatic bacteriuria • Women : Two consecutive voided urine specimens with isolation of the same bacteria at ≥ 10^5 CFU/mL
- Men : A single, clean-catch, voided urine specimen with 1 bacteria isolated 10^5 CFU/mL
- A single catheterized urine specimen with 1 bacteria isolated ≥ 10^2 CFU/mL
CA-UTI = catheter-associated UTI. Information from: 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;5:e103-20; Nicolle LE, Bradley S, Colgan R, et al. Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis 2005;5:643-54; Hooton TM, Bradley SF, Cardenas DD, et al. Diagnosis, prevention, and treatment of catheter-associated urinary tract infection in adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America. Clin Infect Dis 2010;5:625-63.
Table 1-4. Antibiotic Recommendations According to Type of UTIs
antibiotics dose
Therapy duration comments Acute Uncomplicated Cystitis Recommended Agents Nitrofurantoin a^ monohydrate/ macrocrystal
100 mg PO BID 5 days
Trimethoprim/sulfamethoxazole c^ 160/800 mg PO BID 3 days Trimethoprim 100 mg PO BID 3 days Fosfomycin 3 g PO once Once Alternative Agents Amoxicillin/clavulanate 500/125 mg PO q8hr 5–7 days Cefpodoxime proxetil 100 mg PO BID 5–7 days Cefdinir 300 mg PO BID 5–7 days Cephalexin 500 mg PO BID 5–7 days Widely used, but limited data Ciprofloxacinb^ 250 mg PO BID 3 days Levofloxacinb^ 250–500 mg PO daily 3 days Acute Uncomplicated Pyelonephritis Recommended Antibiotics for Outpatient Management Ciprofloxacinb^ 500 mg PO BID 7 days If local FQ resistance is > 10%, give ceftriaxone 1 g IV once or a dose of an aminoglycoside g pending culture results
Ciprofloxacinb^ 1 g ER PO daily 7 days Levofloxacinb^ 750 mg PO daily 5 days Alternatives or Definitive Therapy after susceptibility is confirmed Trimethoprim/sulfamethoxazole c^ 160/800 mg PO BID 14 days Give ceftriaxone 1 g IV once or Cefpodoxime proxetil 200 mg PO BID 10–14 days aminoglycoside^ g^ pending culture results Amoxicillin/clavulanate 500 mg PO TID 10–14 days Inpatient management or in those unable to take oral medications Ciprofloxacin 400 mg IV q12hr 7 days May add aminoglycoside g^ pending culture results. Complete the course with PO Levofloxacin 500 mg IV q24hr 7 days antibiotics after afebrile for 48 hr Ceftriaxone 1 g IV q24hr 14 days Cefepime 1–2 g IV q12hr Piperacillin/tazobactam 3.375 g IV q6hr Acute Complicated Cystitis or CA-UTI without upper tract symptoms Recommended Empiric Therapy Ciprofloxacin 500 mg PO BID 5–7 days
Empiric therapy on the basis of local antibiotic resistance patterns; then streamline on the basis of cultures and treat for 5–7 days
Ciprofloxacin 1 g ER PO daily 5–7 days Levofloxacin 750 mg PO daily 5–7 days Ampicillin/sulbactam 1.5–3 g IV q6hr Ceftriaxone 1 g IV q24hr
antibiotics dose
Therapy duration comments Gentamicin/tobramycin 3–5 mg/kg IV once Pathogen-specific treatment If susceptible, Nitrofurantoin, trimethoprim/sulfamethoxazole, fosfomycin, or PO β-lactams for 7 days ESBL E. coli Nitrofurantoin or fosfomycin
7 days
Acute Complicated Pyelonephritis or Urosepsis or CA-UTI patients who are severely ill Recommended Empiric Therapy for inpatient, not severely ill
See Inpatient Management of Acute Uncomplicated Pyelonephritis
Recommended Empiric Therapy for inpatient, severely ill including urosepsis Ceftriaxone 1 g IV q24hr Add aminoglycoside initially (i.e., gentamicin 5–7 mg/kg once daily). Direct antibiotic therapy according to susceptibility results and treat for total of 14 days
Ceftazidime 1–2 g IV q8hr Cefepime 1 g IV q12hr Piperacillin/tazobactam 3.375–4.5 g IV q6hr Aztreonam 1–2 g IV q8hr Meropenem d^ 1 g IV q8hr Ertapenem d^ 1 g IV q24hr Doripenem d^ 500 mg IV q8hr Antibiotic-resistant (e.g., CRE or Acinetobacter spp.) Colistin Loading dose of CBA (mg) = Css, average target (mg/L) × 2.0 × ideal body weight (kg) up to 300 mg CBA; then maintenance dose according to the look-up table Definitive therapy if susceptible to trimethoprim/sulfamethoxazole 160/800 mg PO BID 14 days Ciprofloxacin 500 mg PO BID 5 days Levofloxacin 750 mg PO daily 5 days CA-UTI (see acute complicated cystitis for stable patients) UTIs and Asymptomatic Bacteriuria in Pregnant Women e Nitrofurantoin monohydrate/ macrocrystals f
100 mg PO BID 5–7 days Except during first trimester or near term
Amoxicillin 500 mg PO TID 3–7 days Amoxicillin/clavulanate 500 mg PO TID 3–7 days Cephalexin 500 mg PO QID 3–7 days Cefpodoxime 100 mg PO BID 3–7 days
Table 1-4. Antibiotic Recommendations According to Type of UTIs ( continued )
Acute Uncomplicated Cystitis Acute uncomplicated cystitis is a mild infection for which 25%–42% of women have early resolution of symptoms, even without active antibiotic treatment (Hooton 2012). Narrow-spectrum oral antibiotics with a low potential for col- lateral damage are preferred. The recommended antibiotics for uncomplicated cystitis are trimethoprim/sulfamethoxaz- ole (if uropathogen resistance is 20% or less), nitrofurantoin monohydrate/macrocrystal, or fosfomycin trometamol. Oral β-lactams, including amoxicillin/clavulanate, cefdinir, cefaclor, and cefpodoxime, are recommended as alternatives (Gupta 2011). Oral β-lactams used for 3–5 days have a clini- cal efficacy of 89% and are less effective than trimethoprim/ sulfamethoxazole or fluoroquinolones (Hooton 2012). Effi - cacy data are limited on narrow-spectrum cephalosporins such as cephalexin, and they are currently not recommended by the IDSA (Hooton 2012). Fluoroquinolones such as ciprofloxacin and levofloxacin have overall high clinical efficacy rates for uncomplicated cystitis. However, because of the concern for increased flu- oroquinolone resistance and serious adverse events, fluoro- quinolones should be reserved as an alternative treatment option when other UTI agents cannot be used (FDA 2016; Gupta 2011).
Therapy duration for most uncomplicated cystitis is short, 3–7 days. Nitrofurantoin is recommended for 5 days, trimethoprim/sulfamethoxazole for 3 days, fluoroquinolones for 3 days, fosfomycin for a single dose, and oral β-lactams for 3–7 days (Gupta 2011).
Acute Uncomplicated Pyelonephritis Most patients with acute uncomplicated pyelonephritis are treated as outpatients with oral antibiotics that achieve high serum and renal tissue concentrations. For clinically stable patients who do not require hospitalization and if local fluo- roquinolone resistance is less than 10%, oral ciprofloxacin for 7 days or levofloxacin for 5 days with or without an initial intra- venous dose of ciprofloxacin or levofloxacin is recommended (Gupta 2011). If the fluoroquinolone resistance rate is 10% or greater, a dose of ceftriaxone 1 g or a consolidated aminogly- coside (e.g., gentamicin 5–7 mg/kg once) is recommended at the initiation of therapy (Gupta 2011). Oral trimethoprim/ sulfamethoxazole is not an optimal agent for empiric ther- apy because of increasing rates of resistance; however, it is highly effective in pyelonephritis and appropriate if the pathogen is susceptible. Compared with trimethoprim/ sulfamethoxazole, oral β-lactams are not as effective because of higher relapse rates. When the susceptibility to
patient care scenario A 54-year-old woman (height 66 inches, weight 71 kg) with well-controlled type 2 diabetes presents to the ED with burning during urination, costovertebral angle ten- derness, chills, and nausea. Your ED attending physician turns to you for a recommendation on empiric antibiotic therapy for the patient’s UTI. Urinalysis was remarkable for WBC greater than 182 per high-power field, nitrite
positive, and large leukocyte esterase. She reports that she has not had UTIs for a few years. Her SCr is 1.1 mg/dL, and she is allergic to trimethoprim/sulfamethoxazole, which causes maculopapular rash. One dose of ondanse- tron 4 mg intravenous push was administered a few min- utes ago. Formulate the initial antibiotic regimen for this patient.
answEr This patient has costovertebral angle tenderness with burning during urination, chills, and nausea, which sug- gest acute pyelonephritis. She does not have urologic structural abnormalities or immunosuppression; thus, her condition is considered uncomplicated. If available, the empiric regimen is determined on the basis of local sus- ceptibility trends. If E. coli resistance to fluoroquinolones is below 10%, ciprofloxacin 400 mg intravenously every 12 hours or levofloxacin 500 mg intravenously every 24 hours can be prescribed empirically until her nausea sub- sides. If E. coli resistance to fluoroquinolones is 10% or greater, a third-generation cephalosporin such as ceftri- axone 1 g intravenously every 24 hours with or without
a consolidated dose of aminoglycoside such as gentami- cin or tobramycin once can be given with the initial regi- men. This patient weighs 71 kg, with ideal body weight of 58.7 kg, and gentamicin 5–7 mg/kg (300–440 mg) intrave- nously once is the suggested dosage. For acute pyelone- phritis, urine culture should be obtained and the antibiotic regimen tailored to susceptibility results. If the culture and susceptibility results confirm the susceptibility to ciprofloxacin or levofloxacin, or trimethoprim/sulfame - thoxazole, this patient can be transitioned to oral cipro- floxacin or levofloxacin to complete the treatment course of 7 days for uncomplicated pyelonephritis.
1. 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;5:e103-20.
- Coyle EA, Prince RA. Urinary tract infections and prostatitis. In: DiPiro JT, Talbert RL, Yee GC, et al, eds. Pharmacotherapy: A Patho-** physiologic Approach, 10th ed. New York: McGraw-Hill, 2017.
trimethoprim/sulfamethoxazole is unknown or when an oral β-lactam is used, an initial parenteral dose of ceftriaxone or consolidated aminoglycoside is recommended (Gupta 2011). Patients with severe symptoms, hemodynamic instability, inability to tolerate oral medications, poor adherence, or any complicating factors (i.e., renal stones) are treated as inpa- tients initially with parenteral antibiotics. Patients hospitalized with pyelonephritis should be treated with an initial parenteral regimen including a fluoroquinolone, an aminoglycoside with or without ampicillin, or an extended-spectrum cephalospo- rin, or penicillin with or without an aminoglycoside (Gupta 2011). The antibiotic selection must be tailored to available susceptibility results. The European Association of Urology suggests initial therapy with an aminoglycoside or carbape- nem if ESBL-producing E. coli rates are high (i.e., greater than 10%), followed by a transition to oral antibiotics if susceptibil- ity results indicate that oral agents are active (Grabe 2015). The recommended therapy for uncomplicated pyelone- phritis is 7 days for fluoroquinolones, 14 days for trimetho- prim/sulfamethoxazole, and 10–14 days for β-lactam agents (Gupta 2011). Persistent high fevers or positive blood cultures (i.e., over the first 3–4 days) suggest the need to investigate for complications, including urinary obstruction and abscess (intrarenal or perinephric). Renal ultrasonography, CT, MRI, and urologic consultation may be useful in this scenario.
ASB and UTIs in Pregnancy Asymptomatic bacteriuria is common during pregnancy, occurring in 2%–10% of pregnant women, and increases the risk of symptomatic UTIs (particularly pyelonephritis) during pregnancy (Nicolle 2005). Pregnant women should be screened for ASB using a urine culture at least once during pregnancy, preferably at 12–16 weeks of gestation (Angelescu 2016). The most common pathogen causing both ASB and symptomatic UTI during pregnancy is E. coli. Cys- titis and ASB during pregnancy are usually treated with oral antibiotics. For pyelonephritis during pregnancy, parenteral antibiotics should be administered for 48 hours before transi- tioning to oral therapy. The safety of antibiotics in pregnancy is of foremost importance when selecting therapy in pregnant women. Tera- togenic concerns with the use of fluoroquinolones, tetracy- clines, and sulfonamides at term significantly limit these antibiotics as treatment options. Trimethoprim/sulfamethox- azole should be avoided during the first trimester of preg- nancy because it can cause folate-sensitive birth defects. Trimethoprim/sulfamethoxazole should also be avoided after 32 weeks of gestation because it can displace bilirubin from albumin and cause kernicterus. β-Lactams, nitrofurantoin, and fosfomycin have been used in pregnant women for ASB and UTIs. All β-lactams (except for ceftriaxone because it may cause kernicterus by bilirubin displacement if administered the day before parturition) and fosfomycin are generally considered safe during pregnancy.
Among the parenteral β-lactams, piperacillin/tazobactam and the carbapenems should be reserved for severe pyelo- nephritis or for patients with an impaired immune system or incomplete urinary drainage. Imipenem/cilastatin has caused adverse fetal effects in animals and should be avoided in pregnant women. Trimester-specific cautions must be considered for nitro - furantoin. Nitrofurantoin can be used during the second tri- mester but should be avoided in the first trimester because of its effects on organogenesis. Nitrofurantoin is contra- indicated near term (i.e., 38–42 weeks) and during labor because of its potential to cause hemolytic anemia in the newborn. For ASB and cystitis, therapy duration is 3–7 days, except for single-dose fosfomycin. Fluoroquinolones should be avoided during pregnancy, according to animal studies, because of their toxic effect on the developing cartilage and high rate of therapeutic abortions in humans (Bar-Oz 2009; Loebstein 1998).
Special Considerations in Lactating Women Urinary tract infections in lactating mothers are treated with antibiotics that are considered safe in lactation. Factors that determine the passage of antibiotics into breast milk are sum- marized in Table 1-5. In general, trimethoprim/sulfamethoxaz- ole, nitrofurantoin, and most β-lactam agents are considered compatible with breastfeeding with minimal risk of toxicity to infants. The American Association of Pediatrics issued a report and concluded that only a few medications (primar- ily radioactive agents and select psychotropic agents) are contraindicated in breastfeeding mothers or are associated with adverse effects in infants (Sachs 2013). Clinicians are referred to LactMed for the most current data on individual antibiotics. Although the potential for direct toxicity associ- ated with antibiotic exposure through breast milk in infants is low, hypersensitivity reactions and changes in bowel flora in infants leading to diarrhea must be monitored while the nurs- ing mother is taking antibiotics.
complicated UTIs Complicated UTIs usually occur in individuals with under- lying conditions that increase the risk of treatment failure. These underlying conditions include poorly controlled diabe- tes, pregnancy, symptoms for 7 or more days before receiv- ing medical care, hospital-acquired UTIs, renal failure, urinary tract obstruction, presence of an indwelling urinary catheter, stent, nephrostomy tube or urinary diversion, functional or anatomic abnormality of the urinary tract, renal transplanta- tion, and immunosuppression. Urinary tract infections in men are uncommon and increase with age. They are often associated with structural or functional abnormality. Therefore, any man presenting with a UTI should be evaluated for structural abnormalities of the urinary tract, with the UTI treated as a complicated UTI until proven otherwise (Sobel 2014).
bloodstream infections who were treated with carbapen- ems (22.1%) compared with those treated with β-lactam/ β-lactamase inhibitors (20.5%) with RR 1.05 (95% CI, 0.83– 1.37). The analysis of seven studies that reported data on definitive therapy indicated similar mortality rates at 15.2% (115 of 767) for carbapenem recipients and 16.2% (32 of 199) for β-lactam/β-lactamase inhibitor recipients (RR 0.62; 95% CI, 0.25–1.52). Therefore, available data do not support rou- tine use of carbapenems as a preferred class for empiric or definite treatment of patients with ESBL Enterobacteriaceae bloodstream infections of urinary source. β-Lactam/β-lact- amase inhibitors are appropriate treatment options. Cefepime is another agent with a potential role as a carbapenem-spar- ing agent for the treatment of ESBL UTIs. In a study of 106 patients with ESBL UTIs, 17 patients received cefepime and 89 patients received a carbapenem without clinical or microbio- logical failures (Kim 2017). Additional studies of cefepime for this indication are needed to better define the role of cefepime. For multidrug-resistant (MDR) organisms, alternatives such as colistin or tigecycline may be necessary (Sobel 2014). Colistin was recently recognized as the preferred polymyxin for the treatment of complicated UTIs because it is renally excreted (Bader 2017; Zavascki 2008). The optimal dosage of colistin is an evolving topic because of considerable interin- dividual variation in plasma concentrations, administration of colistimethate (the prodrug of colistin), and increased risk of nephrotoxicity when the colistin concentration exceeds 2.5 mg/L (Nation 2016). According to recent studies, equa- tions for loading and maintenance doses of colistin aim for an average colistin concentration of 2 mg/L at steady state (Nation 2017). Because of its nephrotoxicity and neuro- toxicity, colistin is reserved primarily for complicated UTIs associated with MDR organisms that are resistant to ami- noglycosides and carbapenems. Tigecycline is often active against ESBL-producing bacteria or Acinetobacter spp. in vitro. However, tigecycline achieves low urinary and serum concentrations because of a large volume of distribution; therefore, tigecycline is not a recommended agent for UTIs, especially those with concurrent bacteremia, unless there are no appropriate alternative agents. For patients with seri- ous penicillin allergy, aztreonam is an appropriate empiric option. The recommended therapy is 10–14 days; however, when complicated by abscesses, longer duration and drain- age should be considered (Grabe 2015; Sobel 2014). Recently, two cephalosporins with β-lactamase inhibitor combinations were approved for the management of com- plicated UTIs: ceftolozane/tazobactam and ceftazidime/ avibactam. Ceftolozane is a new cephalosporin (similar to ceftazidime) with a pyrazole side chain that prevents hydro- lysis by AmpC β-lactamases (van Duin 2016). For the man- agement of complicated UTIs, ceftolozane/tazobactam was compared with levofloxacin in a randomized, double- blind, phase III trial (Wagenlehner 2015). Most patients in
the study had pyelonephritis (656 of 800 patients enrolled), and E. coli was the most commonly isolated uropathogen (629 [78.6%] patients), followed by K. pneumoniae (7.3%) and P. aeruginosa (2.9%). The resistance rate to ceftolozane/tazo- bactam was 2.7% and that to levofloxacin was 26.7% at base- line. Ceftolozane/tazobactam was superior to levofloxacin in microbiologic eradication for the per-protocol groups with Enterobacteriaceae infections (88.9% vs. 78.0%). However, this superiority was not observed when only levofloxacin- susceptible pathogens were analyzed (Wagenlehner 2015). The second combination agent, ceftazidime/avibactam, has avibactam, which is a non–β-lactam β-lactamase inhib- itor. Avibactam prevents the hydrolysis of ceftazidime by diverse types of β-lactamases such as TEM, SHV, CTX-M, AmpC-β-lactamases, and most KPC, but not by the metal- lo-β-lactamases such as NDM (van Duin 2016). In a phase II trial of complicated UTIs, 68 patients received ceftazidime/ avibactam, and 67 patients received imipenem/cilastatin (Vazquez 2012). Sixty-four patients were evaluated, and a favorable clinical response occurred in 24 of 28 (86%) in the ceftazidime/avibactam group and 29 of 36 (81%) in the imi- penem/cilastatin group. E. coli was the most commonly iso- lated uropathogen, occurring at over 92% in both treatment groups. Overall, microbiological responses were similar for the ceftazidime/avibactam group and the imipenem/cilas- tatin group at 70% and 71%, respectively (Vazquez 2012). These two new agents play a potential role in the treatment of complicated UTIs caused by MDR P. aeruginosa or Entero- bacteriaceae spp., particularly CRE strains that are not NDM producers (Alatoom 2017). Of note, until additional data are available, these agents must be used judiciously for serious infections caused by MDR organisms, and their empiric use for infections because of a urinary source in the absence of MDR organisms must be avoided. The optimal treatment of CRE infections originating from urinary source is a complex topic with limited data and het- erogeneity of study designs. Due to wide variations in local rates of CRE infections and prevalence of CRE types, treat- ment strategies differ by region. According to a retrospective cohort study, monotherapy with aminoglycoside was effec- tive for treatment of CRE UTIs (Alexander 2012). In addition, in vitro data suggest synergy with double carbapenem ther- apy, and case series have demonstrated positive outcomes among patients with sepsis or septic shock who received double carbapenem therapy as salvage therapy for compli- cated UTIs (some patients with concurrent bacteremia) (Souli 2017; Oliva 2017; Bulik 2011). However, the published data regarding the role of combination therapy for CRE UTIs are inconclusive. A study from the New York/New Jersey region, the CRE epicenter of the United States of KPC-2 and KPC- types, indicated that the overall 14-day mortality rate of CRE bacteremia is high at 34%, regardless of whether monother- apy or combination therapy was used for definitive therapy
(Satlin 2017). Furthermore, CRE bacteremia of urinary source was an independent factor associated with decreased mor- tality (adjusted OR 0.25; 95% CI, 0.07–0.99; p=0.049). Addi- tional research on treatment options for CRE infections of urinary source is necessary.
Catheter-Associated UTIs Urea-splitting organisms such as Proteus spp., M. morganii , and P. stuartii are often isolated in patients with indwelling uri- nary catheters (Grabe 2015). Urinary catheters may become coated with a biofilm that acts as a reservoir for microorgan- isms and can compromise the action of antibiotics and host defenses. Therefore, urinary catheters should be removed and replaced when CA-UTI is suspected. Catheter-associated UTIs linked to short-term catheterization are usually caused by a single organism, whereas polymicrobial infections are more common with long-term catheterization lasting 30 days or longer (Grabe 2015). Individuals symptomatic with CA-UTI are treated similarly to those with acute complicated cystitis in the absence of upper tract symptoms or complicated pyelonephritis if upper tract symptoms are present (Sobel 2014). A urine culture should be obtained before initiation of antibiotic therapy, if possible, from a newly placed catheter because the bacterial biofilm on the existing catheter can render the culture results less useful (Hooton 2010). In addition, an indwelling catheter that has been in place for 7 days or longer should be removed or replaced before initiating antibiotics (Grabe 2015). The opti- mal treatment duration for CA-UTI has not been well defined. However, the IDSA and the European Association of Urology recommend treating CA-UTI for 7 days in patients who have timely resolution of symptoms and for 10–14 days in those with a delayed clinical response, bacteremia, hypotension, or signs of severe sepsis (Grabe 2015; Hooton 2010). In the absence of symptoms indicative of pyelonephritis, women younger than 65 with CA-UTI may be treated for 3 days after the indwelling catheter is removed (Hooton 2010). Other patients with CA-UTI who are not severely ill may be treated with levofloxacin for 5 days. Asymptomatic candiduria is common among hospital- ized patients with an indwelling urinary catheter. Changing or removing the indwelling catheter clears 20%–40% of asymp- tomatic candiduria (Sobel 2000). Treatment of asymptomatic candiduria with fluconazole effectively eradicates candiduria initially, but 2 weeks after discontinuing therapy, the recur- rence rate was 40% among patients with an indwelling cath- eter (Sobel 2000). Therefore, routine antifungal treatment of asymptomatic candiduria is not recommended, and treatment is reserved primarily for patients undergoing urologic pro- cedures. However, if candiduria persists and a deep-seated infection is suspected, reasons for persistent candiduria should be investigated by performing imaging studies. Flu- conazole is the only azole that achieves high urinary concen- trations. Patients with candiduria with symptoms of Candida
cystitis or pyelonephritis should be treated with fluconazole, except for fluconazole-resistant Candida such as Candida gla- brata and Candida krusei (Fisher 2011). Flucytosine may be used for Candida cystitis caused by fluconazole-resistant Candida strains, but it must be used with caution because of its bone marrow suppression adverse effect and develop- ment of resistance when used alone. Amphotericin B bladder irrigation is going out of favor because of the lack of adequate efficacy data and because its role is limited to patients with C. krusei or fluconazole-resistant C. glabrata cystitis. Urosepsis Most cases of urosepsis are health care associated and occur in patients older than 65 with renal stones who are undergoing lithotripsy. Risk factors associated with urosep- sis are obstruction of the urinary tract because of stones, tumor obstruction, prostate enlargement, urethral stricture, or congenital anomalies (Wagenlehner 2015). According to a prevalence study in health care–associated UTIs, among 1866 patients with a diagnosis of health care–associated UTIs, 70.4% were men, and the mean age was 59.9 years for both men and women (Tandogdu 2016). Urinary tract infec- tions presenting with signs of severe sepsis with hypoten- sion or organ dysfunction must be treated with parenteral broad-spectrum antibiotics initially similar to acute compli- cated pyelonephritis. Definitive therapy should be optimized on the basis of susceptibility results.
Prostatitis The presence of fever with symptoms of cystitis in men may indicate acute bacterial prostatitis (ABP). When symp- toms persist for more than 3 months, chronic bacterial pros- tatitis (CBP) occurs. Most men with CBP have a condition called chronic pelvic pain syndrome. Four main symptoms of CBP and chronic pelvic pain syndrome are urogenital pain, lower urinary tract symptoms including voiding or storage symptoms, psychological issues, and sexual dysfunction (Rees 2015). The most common pathogen for ABP is E. coli , but the spec- trum of pathogens is more variable for CBP, including E. coli , E. faecalis , K. pneumoniae , P. mirabilis , P. aeruginosa , S. aureus , and streptococcal spp. (Grabe 2015). In patients with ABP, a clean-catch midstream urine culture is the most import- ant diagnostic test, together with a physical examination of the abdomen, external genitalia, perineum, and prostate (Nickel 2011). Acute Bacterial Prostatitis Acute bacterial prostatitis requires parenteral therapy initially with bactericidal antibiotics, including broad-spectrum pen- icillin, third-generation cephalosporin, or a fluoroquinolone (Grabe 2015; Nickel 2011). An aminoglycoside can be added to the initial therapy and be continued until the patient becomes afebrile. In less severe cases, an oral fluoroquinolone is prescribed for 10 days (Grabe 2015).
the local context, and feedback on prescribing) were imple- mented in Swedish long-term care facilities to improve anti- microbial use (Pettersson 2011). Although the educational interventions did not affect fluoroquinolone use for the treat - ment of UTIs at the end of the 2-year intervention period, overall antimicrobial use for all infections decreased, and the “wait-and-see” approach (with delay in empiric antibiotics) increased (Pettersson 2011).
recurrent UTIs Recurrent UTI is defined as at least two infections within 6 months, or at least three infections within 1 year. The recur- rence of a UTI may be relapse (i.e., caused by the same uropatho- gen) or reinfection (i.e., caused by different uropathogens). Most recurrences are likely reinfection rather than relapse. The frequency of infections caused by Proteus , Pseudomonas , Klebsiella , Enterobacter spp., antibiotic-resistant E. coli , entero- cocci, and staphylococci increases significantly with recurrent complicated UTIs involving structural abnormalities.
Risk Factors Recurrent UTIs in women are caused by uropathogens that adhere well to the uroepithelial cells. Recurrent UTIs may occur in women of any age, and there may be a genetic pre- disposition because some women are more likely to develop subsequent infections after the first episode of UTI. One study showed that after a first episode of cystitis caused by E. coli in young women, 24% had a second infection within 6 months (Sobel 2014).
Antibiotic Prophylaxis Women with recurrent cystitis can be treated with self-ad- ministration of a short-course therapy (3–5 days) at symp- tom onset. In addition, sexually active women with recurrent UTI can take prophylactic antibiotics (e.g., a single-strength trimethoprim/sulfamethoxazole, nitrofurantoin 50 mg or 100 mg, or a dose of ciprofloxacin 250 mg) at the time of inter- course; they should also avoid the use of a spermicide-con- taining contraceptive. In young women with a history of recurrent UTI, treating ASB with antibiotics was actually associated with an increased risk of recurrence (RR 1.31; 95% CI, 1.21–1.42; p<0.0001). This increased risk occurred even at 12 months after treatment (Cai 2012). Antibiotic prophylaxis should be considered a last resort after behavioral changes (e.g., avoiding spermicide-containing products, early postco- ital voiding, and liberal fluid intake) have proven unsuccess- ful. The potential risks of long-term antibiotic therapy should be discussed with the patient. Long-term antibiotic therapy for 4 weeks may be considered when prevention is clinically warranted and patients with frequent symptomatic relapses desire antibiotic prophylaxis. In acidic urine, methenamine is hydrolyzed to ammo- nia and formaldehyde, which has nonspecific bactericidal activity. Methenamine hippurate 1 g twice daily appears to reduce UTIs in patients without structural abnormalities
(specifically, RR for symptomatic UTI of 0.24; 95% CI, 0.07– 0.89; and bacteriuria of 0.56; 95% CI, 0.37–0.83) (Lee 2012). According to the manufacturer’s package insert, methenam- ine is contraindicated in patients with impaired renal function.
Non-antimicrobial Preventive Strategies Cranberry inhibits one of the adhesins called P-fimbriae and blocks the adherence of bacterial P-fimbriae to uroepithelial cells (Costantini 2017). As a result, cranberry products includ- ing juice, tablets, or capsules may reduce the frequency of recurrent UTIs in women. However, a meta-analysis of 24 studies of 4473 participants showed that cranberry products did not significantly reduce the occurrence of symptomatic UTIs (Jepson 2013). Cranberry capsules are an option in preg- nant women to prevent ASB (Wing 2015). Other adhesin blockers such as d-mannose are used by women to prevent cystitis, but data to support their use are limited. In women with recurrent UTIs, oral administration of D -mannose 2 g or nitrofurantoin 50 mg daily for 6 months, compared with no treatment, significantly decreased the risk of recurrent UTIs. Recurrent UTI rates were 14.6%, 20.4%, and 60.8% for D -mannose, nitrofurantoin, and the no-prophylaxis group, respectively (Kranjcec 2014). In postmenopausal women, replacement with topical estro- gen therapy normalizes the vaginal flora and has been shown to reduce the risk of recurrent UTI. Use of 0.5 mg of estriol vaginal cream at night for 2 weeks followed by twice-weekly administration for 8 months significantly reduced the inci- dence of UTIs compared with placebo (Raz 1993). In addition, estriol use was associated with an increase in vaginal lacto- bacilli from 0% to 60% and a decrease in vaginal colonization with Enterobacteriaceae spp. from 67% to 31% (Raz 1993). Probiotics protect the vagina from bacterial colonization by blocking attachment and producing hydrogen peroxide that is microbicidal to E. coli and other uropathogens. Lac- tobacillus appears to be promising as an antibiotic-sparing agent. In a study of postmenopausal women, a mixture of Lac- tobacillus (including L. rhamnosus GR-1 and L. reuteri RC-14) administered orally twice daily was compared with trimetho- prim/sulfamethoxazole prophylaxis over 1 year (Beerepoot 2012). The mean time to the first UTI was 3 and 6 months for Lactobacillus and trimethoprim/sulfamethoxazole, respec- tively. Resistance to trimethoprim/sulfamethoxazole and amoxicillin increased in women who received trimethoprim/ sulfamethoxazole, but not in those who received Lactobacillus (Beerepoot 2012).
role of AntImIcrobIAl
stewArdshIp proGrAms
Antimicrobial stewardship programs are essential to promote appropriate antibiotic use to optimize therapeutic outcomes and minimize adverse events (including the development of resistance and collateral damage) for UTIs. The diagnosis of UTI is primarily based on clinical presentation rather than
laboratory findings, particularly in the outpatient setting. Selection of empiric antibiotics for UTIs should be based on the severity of the infection and local susceptibility patterns. When antibiotics are indicated, short courses are effective for uncomplicated UTIs, especially cystitis, and in otherwise healthy women. Routine screening and treatment for ASB may lead to unnecessary antibiotic use, unnecessary diagnostic testing, development of antimicrobial resistance, and adverse drug effects_._ Therefore, the decision to screen for bacteriuria in asymptomatic individuals or to initiate antibiotic treatment in the setting of ASB must be weighed carefully to ensure judi- cious use of antibiotics and to prevent the development of antibiotic resistance. Of importance, screening for ASB is not indicated for most patients, including SNF residents and those undergoing non-urologic procedures (Drekonja 2013). In women with uncomplicated UTIs, trying analgesic agents such as ibuprofen for symptomatic relief rather than an immediate antibiotic prescription may be prudent to spare antibiotic use (Gagyor 2012). Of note, in a comparative study with fosfomycin, ibuprofen (400 mg three times daily for 3 days) relieved UTI symptoms in two-thirds of women with uncomplicated UTIs who recovered without any antibiotic use. Therefore, initial symptomatic treatment rather than immediate antibiotic use should be considered in women with uncomplicated UTIs (Gagyor 2012). An antibiotic stewardship program could provide educa- tional programs and cascade the reporting of antibiotic sus- ceptibility results as effective strategies to improve antibiotic prescribing behavior. In a university-based internal medicine clinic, the aggre- gate concordance with antibiotic type, frequency, and dura- tion according to the IDSA guidelines was surprisingly low at 34% (Kim 2015). An antibiotic stewardship program interven- tion that incorporates prospective review and feedback (i.e., for selected cases after positive urine cultures) within health care systems may reduce urine culture ordering and antibi- otic prescribing for catheter-associated ASB (Trautner 2015). In addition, developing and implementing institutional guide- lines to manage catheter-associated ASB may improve appro- priate antibiotic use.
conclusIon
As the most common bacterial infection that requires medical care, UTIs vary greatly by clinical presentation and therapeu- tic management. Urinary tract infections affect a variety of patients with different biological and procedural risk factors (e.g., age, sex, pregnancy, catheters and urologic interven- tions). However, not all bacteriurias require antibiotic therapy, particularly in the presence of ASB. Antibiotic stewardship practices are essential to promote judicious antibiotic use for UTIs. This can significantly reduce antibiotic resistance because UTIs are the most common infections leading to an antibiotic prescription.
references
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practice points In determining appropriate antibiotic regimens for the treatment of UTIs, consider the following:
- Which type of UTI does the patient have?
- What are the local susceptibility rates of^ E. coli^ to trimetho- prim/sulfamethoxazole and the fluoroquinolones?
- What is the most appropriate empiric antibiotic regimen with a low potential for collateral damage for the type of UTI the patient has?
- What is the most appropriate definitive antibiotic regimen with a low potential for collateral damage for the type of UTI the patient has, given the susceptibility results?
- Which antibiotics are safe to use for UTIs during preg- nancy, or which are compatible with breastfeeding?
- What is the recommended therapy duration for the type of UTI the patient has?
- When the patient has UTIs caused by MDR organisms, what are the treatment options?
- What is the role of newer cephalosporin/β-lactamase inhib- itor combinations for the treatment of complicated UTIs?
- Does the patient have any risk factors for recurrence?
- For patients with recurrent UTIs, what are appropriate strategies to prevent future recurrences?
- For patients undergoing urologic procedures, especially renal stone procedures, what is the optimal strategy to minimize the potential for urosepsis postoperatively?
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self-assessment Questions
urinalysis, culture, and susceptibility. Her SCr is 1.1 mg/dL. C.M.’s vital signs are otherwise within normal limits.
- Which one of the following types of UTI does C.M. most likely have? A. Asymptomatic bacteriuria (ASB) B. Uncomplicated cystitis C. Uncomplicated pyelonephritis D. Complicated cystitis
- Which one of the following risk factors most likely contributed to C.M.’s urinary symptoms? A. Age B. Immunosuppressive therapy C. Diabetes D. Hypertension
- Pending results of the urine culture and susceptibility for outpatient management, which one of the following oral therapies is best to recommend as empiric treatment given C.M.’s clinical presentation? A. Cefpodoxime 100 mg twice daily B. Ciprofloxacin 500 mg twice daily C. Fosfomycin 3 g every 2 days D. Trimethoprim/sulfamethoxazole 160 mg/800 mg 1 tablet twice daily
- Two days after her clinic visit, C.M.’s urine culture is positive for greater than 100,000 CFU/mL of vanco- mycin-resistant Enterococcus faecium with the sus- ceptibility results as follows. The laboratory also provided the result of daptomycin ETEST with the MIC of 4 mcg/mL.
100,000 CFU/mL of vancomycin-resistant E. faecium Antibiotic Interpretation Ampicillin Resistant Ciprofloxacin Resistant Levofloxacin Resistant Linezolid Susceptible Nitrofurantoin Susceptible Penicillin Resistant Tetracycline Resistant Tigecycline Susceptible
Which one of the following is best to recommend for C.M.’s UTI? A. Linezolid 400 mg by mouth twice daily for 7 more days B. Fosfomycin 3 g by mouth once
- L.P. is a 21-year-old female college student, otherwise healthy, who presents to the clinic with complaints of burning during urination and frequent urination for 2 days. She denies fevers, chills, or flank pain. L.P. has no known allergies. According to last year’s antibiogram from the student health office, trimethoprim/sulfame- thoxazole resistance to urinary pathogens is estimated to be 24%, and ciprofloxacin resistance is estimated to be 8%. L.P.’s urine dipstick is positive for leukocyte esterase and nitrites. Which one of the following is best to recom- mend for L.P.? A. Amoxicillin/clavulanate 500mg/125mg by mouth twice daily for 5 days B. Levofloxacin 750 mg by mouth once daily for 5 days C. Nitrofurantoin monohydrate macrocrystals 100 mg by mouth twice daily for 5 days D. Trimethoprim/sulfamethoxazole 1 double-strength tablet by mouth twice daily for 3 days
- A 49-year-old woman with uncontrolled diabetes is hos- pitalized with significant flank pain, chills, and a tem- perature of 101.3°F (38.5°C). In her home state, the E. coli resistance rate to ciprofloxacin is 19% and the rate to tri - methoprim/sulfamethoxazole is 30%. She is very uncom- fortable because of flank pain, and her vital signs are blood pressure 140/95 mm Hg, heart rate 85 beats/min- ute, and respiratory rate 23 breaths/minute. Her labora- tory test results are remarkable only for a WBC of 11.3 × 10 3 cells/mm 3. The patient has a history of a maculopap- ular rash associated with penicillin G. She has no history of renal insufficiency. Which one of the following is best to recommend for this patient? A. Ampicillin/clavulanate 3 g intravenously every 6 hours B. Ceftriaxone 1 g intravenously every 24 hours C. Aztreonam 1 g intravenously every 8 hours D. Levofloxacin 750 mg intravenously every 24 hours
Questions 3–6 pertain to the following case.
C.M. is a 36-year-old woman (height 66 inches, weight 57.2 kg) who presents to the transplant nephrology clinic for a sched- uled follow-up appointment. She has a history of hyperten- sion and diabetes, both of which are well controlled. C.M. underwent kidney-pancreas transplantation 6 years ago and currently takes atenolol 50 mg by mouth once daily, tacro- limus 2 mg by mouth twice daily, and prednisone 5 mg by mouth daily. C.M. states that she started to have increased burning during urination yesterday, had to go to the bathroom three times last night, has some hematuria, and is feeling tired this morning. She denies fever, nausea, and vomiting. Clean-catch midstream urine sample has been collected for
