1. IDSA guidelines for treatment of UTIs
Harika Yalamanchili
PGY-2

2. IDSA: Infectious Diseases Society of America

3. Definitions
Acute cystitis: infection of the bladder - lower urinary tract
Pyelonephritis: infection of the kidney - the upper urinary tract
Considered uncomplicated in healthy non-pregnant adult women
Complicated UTI
Diabetes
Pregnancy
Symptoms for 7 or more days before seeking care
Hospital acquired infection
Renal failure
Urinary tract obstruction
Presence of an indwelling urethral catheter, stent, nephrostomy tube or urinary diversion
Recent urinary tract instrumentation
Functional or anatomic abnormality of the urinary tract
History of urinary tract infection in childhood
Renal transplantation
Immunosuppression
Uropathogen with broad-spectrum antimicrobial resistance

4. Risk factors for UTIs Recent sexual intercourse Recent spermicide use
History of urinary tract infection
Improper hygiene
Urinary tract structural abnormalities
Immunosuppression
Catheterization

5. Pathogenesis
Begins with colonization of the vaginal introitus by uropathogens from the fecal flora, followed by ascension via the urethra into the bladder
Pyelonephritis develops when pathogens ascend to the kidneys via the ureters

6. Most common uncomplicated UTI uropathogens
Escherichia coli 75-95%
Enterobacteriaceae
Proteus mirabilis
Klebsiella pneumonia
Staphylococcus saprophyticus
Among healthy non-pregnant women, the isolation of organisms such as lactobacilli, enterococci, Group B streptococci, and coagulase-negative staphylococci (other than S. saprophyticus) from voided urine most commonly represents contamination

7. Most common complicated UTI uropathogens
Common pathogens
Pseudomonas
Serratia
Providencia species
Enterococci
Staphylococci
Fungi

8. Diagnosis
Clinical manifestations of cystitis consists of dysuria, frequency, urgency, suprapubic pain, and/or hematuria
Clinical manifestations of pyelonephritis can consist of the above symptoms together with fever, chills, flank pain, CVA tenderness, and nausea/vomiting

9. Diagnosis: Older Populations
For patients >65 years: chronic urinary nocturia, incontinence, and general sense of lack of well-being are common and nonspecific for UTI  should not routinely prompt urine studies
Fever, acute dysuria (<1 week), new or worsening urinary urgency, new incontinence, frequency, gross hematuria, and suprapubic or CVA pain/tenderness are more discriminating symptoms  should prompt urine studies
Cognitively impaired patient who has persistent change in mental status and change in character of the urine that is not responsive to other interventions such as hydration  should prompt urine studies

10. Diagnosis
UA for evaluation of pyuria is the most valuable laboratory diagnostic test for UTI
Pyuria is present in almost all women with acute cystitis or pyelonephritis
Its absence strongly suggests an alternative diagnosis
In young non-pregnant women, the probability of cystitis is >50% with any symptom of UTI and >90% with dysuria and frequency without vaginal discharge or irritation  UA or UC usually adds little and are often not indicated  can empirically treat
Leukocyte esterase: enzyme released by leukocytes  reflects pyuria
Leukocyte esterase may be used to detect >10 leukocytes per high power field
Nitrite: reflects the presence of gram negative bacteria
Convert urinary nitrate to nitrite
Lacks adequate sensitivity for detection of lower colony counts and of other organisms  interpret negative results with caution
False positive nitrite tests can occur with substances that turn the urine red (phenazopyridine or ingestion of beets)

11. Diagnosis: Positive urine culture
In asymptomatic women, standard threshold on a midstream voided urine that is reflective of bladder bacteriuria as opposed to contamination is ≥105 CFU/ml
In symptomatic women with pyuria, lower midstream urine counts (ie, ≥102/mL) have been associated with the presence of bladder bacteriuria
Findings of a colony count <105 but ≥102/mL may still be indicative of a UTI
Lower bacterial counts still representative of infection are also seen in men, patients already on antimicrobials, and with organisms other than E. coli and Proteus species

12. Differential diagnosis
Vaginitis
Urethritis
Structural urethral abnormalities
Painful bladder syndrome
Pelvic inflammatory disease
Nephrolithiasis

13. Uncomplicated UTI Treatment
Nitrofurantoin monohydrate/macrocrystals
100 mg orally BID x 5 days
Should be avoided if there is suspicion for early pyelonephritis
Contraindicated when creatinine clearance is <60 mL/minute.

14. Uncomplicated UTI Treatment
Trimethoprim-sulfamethoxazole
One double strength tablet (160/800 mg) BID x 3 days
Empiric tx should be avoided if the prevalence of resistance is >20% or if TMP-SMX has been taken for cystitis in the preceding 3 months
Alternative: Trimethoprim 100 mg BID x 3 days can be used in place of TMP-SMX and is considered equivalent
Only for specific countries and regions

15. Uncomplicated UTI Treatment
Fosfomycin trometamol
3 grams x 1 dose
Should be avoided if there is suspicion for early pyelonephritis
Becoming more useful due to increased resistance among uropathogens
Clinical outcomes are not yet reported from randomized, controlled studies
Role against MDRO is unknown

16. Uncomplicated UTI Treatment
Pivmecillinam
400 mg BID x 3-7 days
Minimal resistance and ecological adverse effects
An extended gram-negative spectrum penicillin used only for treatment of UTI
Availability limited to some European countries

17. Uncomplicated UTI alternative treatment options
Fluoroquinolones (ofloxacin, ciprofloxacin, and levofloxacin) are highly efficacious in 3 day regimens but have a propensity for collateral damage
Should be reserved for important uses other than acute cystitis
Main concern is the promotion of fluoroquinolone resistance, not only among uropathogens but also other organisms  more serious and difficult to treat infections at other sites, increased rates of MRSA
Beta-Lactam agents
Amoxicillin-clavulanate, cefdinir, cefaclor, and cefpodoxime-proxetil x 3-7 days
Appropriate when other recommended agents cannot be used
Generally have inferior efficacy and more adverse effects
Concern for propagation of ESBL resistance among gram negative bacteria
Amoxicillin or ampicillin should not be used alone for empirical treatment given the relatively poor efficacy and very high prevalence of antimicrobial resistance

18. Treatment Options
Choice should be individualized based on patient circumstances (allergy, tolerability, compliance), local community resistance prevalence, availability, cost
Inability to tolerate po precludes outpatient treatment
If diagnostically uncertain of cystitis versus early pyelonephritis, avoid nitrofurantoin, fosfomycin, and pivmecillinam because they do not achieve adequate renal tissue levels
Use of TMP-SMX in the preceding 3–6 months is an independent risk factor for resistance
Travel outside the US in the preceding 3–6 months is independently associated with resistance
Collateral damage: ecological adverse effects of antimicrobial therapy
Selection of drug-resistant organisms
Colonization or infection with MDR organisms

19. Complicated UTI Treatment
Can tolerate po  oral ciprofloxacin (500 mg BID or 1000 mg extended release daily) or levofloxacin (750 mg daily) x 5-10 days
Moxifloxacin attains lower urinary levels than other fluoroquinolones and is not recommended
Nitrofurantoin, TMP-SMX, fosfomycin and oral beta-lactams are poor choices for empiric oral therapy due to high resistance rates
ESBLs treatment options generally limited to the Carbapenems
Mild cystitis due to ESBL-producing E. coli and low suspicion for pyelonephritis  nitrofurantoin and fosfomycin are reasonable if susceptible
Gram-positive cocci on Gram stain  suggestive of enterococcal UTI Ampicillin (1 g q6h) or Amoxicillin (500 mg po q8h)
May require further imaging
Duration of treatment: 5-10 days

20. Pyelonephritis
In patients suspected of having pyelonephritis, a urine culture and susceptibility test should always be performed

21. Treatment of Outpatient Uncomplicated Pyelonephritis
Oral ciprofloxacin: 500 mg BID x 7 days +/- initial 400-mg dose of IV ciprofloxacin
Alternative: Ciprofloxacin 1000 mg extended release x 7 days or levofloxacin 750 mg x 5 days
Appropriate for patients not requiring hospitalization and prevalence of resistance to fluoroquinolones is not >10%
If >10%, will need to add additional IV dosage
Alternative initial IV therapy: long-acting antimicrobial - 1 g ceftriaxone or a consolidated 24-h dose of an aminoglycoside (One 5-7 mg/kg dose of gentamicin)
Oral TMP-SMX: 160/800 mg (1 DS tablet) BID x 14 days if the uropathogen is known to be susceptible
If susceptibility is not known, an initial IV dose of a long-acting parenteral antimicrobial- 1 g ceftriaxone or a consolidated 24-h dose of an aminoglycoside
Oral Beta-lactam agents are less effective than other available agents and lead to higher relapse rates
If an oral beta-lactam agent is used, an initial IV dose of a long-acting parenteral antimicrobial- 1 g ceftriaxone or a consolidated 24-h dose of an aminoglycoside
Duration: 10–14 days

22. UTIs in Men Much more rare in men than women
Appx 5-8 UTIs per year per 10,000 young to middle-aged men
Traditionally, all UTIs and asymptomatic bacteriuria in men considered complicated
Acute uncomplicated UTIs occur in a small number of men between 15-50
Risk factors: insertive anal intercourse and lack of circumcision
Due to longer urethral length, drier periurethral environment, and antibacterial substances in prostatic fluid
Clinical manifestations: dysuria, frequency, urgency, suprapubic pain, and/or hematuria
Differential:
Dysuria, urinary frequency and urgency, and pyuria can also be seen with acute bacterial prostatitis
May have additional fever, chills, malaise, myalgias, pelvic or perineal pain, or obstructive symptoms such as dribbling and hesitancy (due to acute urinary retention)  DRE  edematous, tender prostate
Underlying chronic prostatitis should be considered in men with cystitis, particularly in those men who have recurrent UTIs
Urethritis
Diagnosis: UA with UC

23. UTIs in Men Treatment options Duration
TMP-SMX one DS tab (160/800 mg) BID
Fluoroquinolones
Ciprofloxacin (500 mg BID or 1000 mg extended release daily) or Levofloxacin ( mg daily)
Nitrofurantoin and beta-lactams should usually not be used in men with cystitis
Do not achieve reliable tissue concentrations
Would be less effective for occult prostatitis
Data for Fosfomycin in men is limited
Duration
Not many studies but traditionally 7-14 days

25. Catheter Associated UTI (CA-UTI)
CA infection: infection occurring in a person whose urinary tract is currently catheterized or has been catheterized within the previous 48 h
CA-UTI: pt with indwelling urethral, indwelling suprapubic, or intermittent catheterization with symptoms or signs compatible with UTI with no other identified source of infection + ≥10^3 CFU/ml of 1 bacterial species in a single catheter urine specimen or in a midstream voided urine specimen from a patient whose urethral, suprapubic, or condom catheter has been removed within the previous 48 h
Unable to be determined if condom catheter used

26. CA-UTI
Signs and symptoms: new onset or worsening of fever, rigors, AMS, malaise, or lethargy with no other identified cause
Flank pain, CVA tenderness, acute hematuria, pelvic discomfort
Removed catheters: dysuria, urgent or frequent urination, or suprapubic pain or tenderness
Spinal cord injury: increased spasticity, autonomic dysreflexia, or sense of unease

27. Catheter Associated Asymptomatic Bacteriuria (CA-ASB)
Patients with indwelling urethral, indwelling suprapubic, or intermittent catheterization with the presence of ≥10^5 CFU/ml of 1 bacterial species in a single catheter urine specimen in a patient without symptoms compatible with UTI
Condom Catheter: Presence of ≥10^5 CFU/ml of 1 bacterial species in a single urine specimen from a freshly applied condom catheter

28. CA-Bacteriuria
CA-bacteriuria is the most frequent health care–associated infection worldwide
Accounts for up to 40% of hospital-acquired infections in US hospitals each year
Incidence of bacteriuria associated with indwelling catheterization is 3-8% per day
Duration of catheterization is the most important risk factor for the development of CA-bacteriuria
Other risk factors:
Not receiving systemic antimicrobial therapy
Female
Positive urethral meatal culture results
Microbial colonization of the drainage bag
Catheter insertion outside the OR
Catheter care violations
Rapidly fatal underlying illness
Older age
Diabetes mellitus
Elevated serum creatinine at the time of catheterization
Approximately 20% of healthcare-associated bacteremias arise from the urinary tract

29. CA Urinalyses Pyuria is not diagnostic of CA-bacteriuria or CA-UTI
Presence, absence, or degree of pyuria should not be used to differentiate CA-ASB from CA-UTI
Pyuria accompanying CA-ASB should not be interpreted as an indication for antimicrobial treatment
Presence or absence of odorous or cloudy urine alone should not be used to differentiate CA-ASB from CA-UTI or as an indication for urine culture or antimicrobial therapy
Screening for and treatment of CA-ASB is not recommended to reduce subsequent CA-bacteriuria or CA-UTI except in specific populations

30. CA-Pathogens E. coli is the most frequent species isolated
Other Enterobacteriaceae: Klebsiella species, Serratia species, Citrobacter species, and Enterobacter species
Pseudomonas aeruginosa
Gram-positive cocci including coag-negative staph and Enterococcus species
Proteus mirabilis
Morganella morganii
Providencia stuartii
Long-term catheterization: usually polymicrobial

31. CA-Treatment Prevention
Education
Very limited use
Condom catheters
Intermittent catheterization
Closed catheter drainage system
Antimicrobial Coated Catheters
UC should be obtained prior to initiating antimicrobial therapy, replace catheter if >2 wks, obtain UC from new catheter or if catheter DCed obtain voided midstream urine specimen
Symptoms appropriate for obtaining a culture and initiating antimicrobial therapy include new CVA tenderness, rigors, or new onset of delirium
Consider treating CA-ASB that persists 48h after short-term indwelling catheter removal in women to reduce the risk of subsequent CA-UTI

32. CA-UTI Treatment Based upon the culture results
In seriously ill patients, empiric antimicrobial choice should be tailored to results of past cultures, use of prior antimicrobial therapy, community prevalence of antimicrobial resistance, and allergies
Urine Gram stain
If nothing available, empiric therapy should provide coverage against gram-negative bacilli
If not seriously ill and do not suspect MDRO, 3rd-gen cephalosporin (Ceftriaxone 1 g IV daily or Cefotaxime 1 g IV q8h) or a fluoroquinolone (Ciprofloxacin at 500 mg PO or 400 mg IV BID or Levofloxacin mg PO or IV daily)
If seriously ill or suspect MDRO, treat with ciprofloxacin, ceftazidime (1 g IV q8) or cefepime (1 g IV q12h)
If suspect ESBL (based on prior cultures), treat with carbapenem
Gram positive cocci on Gram stain  enterococci or staphylococci  empiric IV vancomycin 

33. CA-Treatment
7 days for patients who have prompt resolution of symptoms
10–14 days of treatment for those with a delayed response
5-day regimen of levofloxacin in patients that are not severely ill
3-day antimicrobial regimen may be considered for women >65 yo who develop CA-UTI without upper urinary tract symptoms after an indwelling catheter has been removed
Treatment may need to be extended and a urologic evaluation may need to be performed if the patient does not have a prompt clinical response with defervescence by 72 h

34. Asymptomatic Bacteriuria
Women
Two consecutive voided urine specimens with isolation of the same bacterial strain in quantitative counts ≥10^5 CFU/mL
Men
Single, clean-catch voided urine specimen with 1 bacterial species isolated in a quantitative count ≥10^5 CFU/mL
Catheters (women or men)
A single catheterized urine specimen with 1 bacterial species isolated in a quantitative count ≥10^2 CFU/mL

35. Asymptomatic Bacteriuria Organisms
E. coli is the most common
Characterized by fewer virulence characteristics than are those isolated from women with symptomatic infection
Enterobacteriaceae
Coagulase-negative staphylococci
Enterococcus species
Group B streptococci
Gardnerella vaginalis
Men:
Gram-negative bacilli

36. Asymptomatic Bacteriuria
Screening for or treatment of asymptomatic bacteriuria is not recommended for:
Premenopausal, nonpregnant women
Diabetic women
Older persons living in the community
Elderly, institutionalized subjects
Persons with spinal cord injury
Catheterized patients while the catheter remains in situ

37. Asymptomatic Bacteriuria
Pyuria accompanying asymptomatic bacteriuria is not an indication for antimicrobial treatment
Pregnant women should be screened for bacteriuria by urine culture at least once in early pregnancy, and they should be treated if the results are positive
Asymptomatic bacteriuria in early pregnancy has a fold increased risk of developing pyelonephritis during pregnancy
More likely to experience premature delivery and to have infants of low birth weight
Duration of treatment is 3-7 days
Periodic screening for recurrent bacteriuria should be undertaken following therapy
Screening for and treatment of asymptomatic bacteriuria before TURP is recommended
Antimicrobial therapy should be initiated shortly before the procedure
Antimicrobial therapy should not be continued after the procedure, unless an indwelling catheter remains in place
Screening for and treatment of asymptomatic bacteriuria is recommended before other urologic procedures for which mucosal bleeding is anticipated

38. Resources
Fekete T, Hooton TM. Approach to the adult with asymptomatic bacteriuria. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. (Accessed on December 15, 2014)
Fekete T. Catheter-associated urinary tract infection in adults. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. (Accessed on December 15, 2014)
Gupta K, Hooton TM, Naber KG, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis 2011; 52:e103.
Hooton, TM. Acute complicated cystitis and pyelonephritis. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. (Accessed on December 15, 2014)
Hooton, TM. Acute uncomplicated cystitis, pyelonephritis, and asymptomatic bacteriuria in men. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. (Accessed on December 15, 2014)
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; 50:625.
Hooton TM, Gupta K. Acute uncomplicated cystitis and pyelonephritis in women. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. (Accessed on December 15, 2014)
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; 40:643.

39. Thanks and Gig’em