#231 U Talkin’ UTIs Re: Me?

August 24, 2020 | By Matthew Watto, MD

Don’t Fail While Treating Acute Decompensated Heart Failure

Are U Talkin’ UTIs Re: Me? Infectious Diseases expert, Dr Boghuma Titanji MD, PhD @boghuma (Emory; TED) schools us on the diagnosis and management of urinary tract infections: updated definitions of complicated and uncomplicated UTI, pitfalls of the urinalysis, first line antibiotics, duration of therapy and which agents to use for complicated UTI. This episode is liquid gold!

Listeners can claim Free CE credit through VCU Health at http://curbsiders.vcuhealth.org/ (CME goes live at 0900 ET on the episode’s release date).

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Credits

• Written and Produced by: Matthew Watto MD, FACP 
• Cover Art and Infographic by: Edison Jyang
• Hosts: Matthew Watto MD, FACP; Paul Williams MD, FACP   
• Editor: Molly Heublein MD (written materials); Clair Morgan of nodderly.com
• Guest: Boghuma Kabisen Titanji MD, PhD

Sponsor

The Curbsiders are partnering with VCU Health Continuing Education to offer FREE continuing education credits for physicians and other healthcare professionals. Visit curbsiders.vcuhealth.org and search for this episode to claim credit. See info sheet for further directions. Note: A free VCU Health CloudCME account is required in order to seek credit.

How to Claim VCU CME Credit

Time Stamps

• Sponsor – VCU Health Continuing Education
• 00:30 Intro, disclaimer, guest bio
• 02:50 Guest one-liner, Picks of the Week*: Urban gardening, Behave (book) by Robert Sapolsky
• 08:54 Defining UTI; Framework for UTI
• 16:35 Case 1 – Cath Foley; Acute uncomplicated cystitis; Interpreting the Urinalysis
• 28:00 Women with recurrent UTIs
• 38:55 Case 2 – UTI in a man
• 47:15 Treatment of complicated infections; Duration of therapy
• 52:27 Case 3 – Catheter associated UTI; MRSA UTI
• 61:25 Duration of therapy for bacteremia from UTI
• 64:40 Take home points, plugs and outro
• Sponsor – VCU Health Continuing Education

“Do not repeat someone else’s story. Write your own.” -Dr. Boghuma Titanji

UTI Pearls

1. UTIs are common. Diagnosis is not easy or straightforward. When choosing an antibiotic, avoid collateral damage and keep it brief.
2. First line agents in the US are nitrofurantoin, TMP-SMX or fosfomycin.
3. Infrequent recurrences can be treated with first line agents. Relapses (early return of symptoms) or multiple recurrences warrant a culture to rule out MDRO. 
4. Not all UTIs in men are complicated! First line agents can be used. 
5. For outpatients with complicated UTI, use PO agents that achieve high blood levels (TMP-SMX or Fluoroquinolones) or a single dose IV agent followed by oral therapy. 
6. Seven days treatment is probably sufficient for outpatient men with UTI (Drekonja, JAMA Int Med 2013).
7. It takes 4 hours for Enteric bacteria to convert nitrates in urine to nitrites! Get an early morning sample to avoid false negatives. 
8. Pyuria (+LE or >10 WBC/hpf) is present in almost all patients with UTI (Hooton, UptoDate 2019)
9. Uncomplicated bacteremia (i.e. no sepsis, shock, MDRO, failure to clear cultures or needed I&D) from Enterobacter can safely be treated for 7 days duration (Yahav, Clin Inf Dis 2019).
10. Use oral TMP-SMX or a Fluoroquinolone as step down therapy for patients with bacteremia (expert opinion).

Talkin’ UTIs – Show Notes

Define and Classify UTI

UTI: Significant bacteriuria plus signs and symptoms that localize to the urinary tract.

Bacteriuria – Usually defined as >= 100,000 CFU per mL on culture, but lower CFUs can certainly be significant in a patient with clinical s/s otherwise consistent UTI.

Uncomplicated aka “simple cystitis” – Signs and symptoms that localize to the bladder or lower without systemic or upper tract symptoms (Hooton, UptoDate 2019).

Complicated – Signs and symptoms (s/s) that localize above the bladder and/or systemic symptoms concerning for sepsis (Hooton, UptoDate 2019).

UTIs in women – Simple cystitis is common. See case 1 below.

UTIs in men – Often thought of as complicated because of their infrequency, BUT men can have simple cystitis. See Case 2 below. 

CAUTI – Bacteriuria plus s/s that localize to the urinary tract in a patient with a urinary catheter or recent removal of a urinary catheter. Note: Not all CAUTIs are complicated!

Risk Modifying factors – Dr Titanji notes that patients with uncontrolled diabetes or on immunosuppression are more likely to progress from uncomplicated to complicated UTIs. Therefore, she considers drugs that achieve higher blood and tissue levels outside the bladder. 

Diagnosis of UTI

Color and odor are not reliable s/s for UTI [Cortes-Penfield, Infect Dis Clin North Am 2017]. 

Urinalysis is a good test for ruling out UTI. A positive dipstick for leukocyte esterase (LE) is at least 10 WBCs per HPF, which qualifies as pyuria. The absence of pyuria dramatically lowers the likelihood of UTI [Cortes-Penfield, Infect Dis Clin North Am 2017]. 

Kashlak Pearl: Enteric bacteria (E. coli, Proteus, Klebsiella) convert nitrates to nitrites, but conversion requires 4 hours (Williams, Lancet Inf Dis 2010), thus an early morning sample provides the highest yield. Timing of specimen and hydration status can affect the results.

Case 1 – Young female with uncomplicated UTI. 

Testing is unnecessary in a young woman with classic symptoms (suprapubic pain, dysuria, frequency). Treat with TMP-SMX (3 days therapy if resistance <20%), Nitrofurantoin (for 5 days) or Fosfomycin (single dose, but higher failure rate) or pivmecillinam (not available in US) —IDSA guideline 2010.

What about the patient with recurrent UTIs?

Ask yourself: Is this a recurrence (new infection)? Or a relapse (incomplete/partial treatment)? If symptoms recur very quickly or fail to improve then check a urine culture. If symptoms recur weeks to months later (after complete resolution of symptoms), then treat empirically with first line agents.  For patients with multiple recurrences, Dr Titanji will perform a culture to help guide treatment moving forward —expert opinion.

Kashlak Pearl: Sometimes Dr Titanji will give an antibiotic script to a reliable patient to be used as needed for symptoms —expert opinion. She does not routinely place patients on chronic antibiotic prophylaxis due to risk of selecting resistant organisms.

Methenamine is converted to formaldehyde in the bladder and has some antimicrobial activity. Larger RCTs are needed to confirm efficacy for prevention of UTI (Sihra, Nat Rev Urol 2018), but there is low risk for harm, therefore Dr. Titanji may continue it for patients who report benefit.

D-Mannose is a supplement purported to reduce bacterial adherence to the urinary tract epithelium and therefore prevent infections. There is not clear evidence for benefit or harm (Sihra, Nat Rev Urol 2018), so it’s reasonable to continue it for patients who perceive a benefit.

Case 2 – Urinary tract infection in a man. 

Basic Approach: Is there a structural issue (e.g. BPH, stone disease, stricture, etc.)? Are they sexually active? Dr Titanji performs a urinalysis and urine culture, plus STI testing in at risk men. 

Uncomplicated UTI Treatment: If UTI is uncomplicated (i.e. patient has simple cystitis), then the first line options remain the same for men and women–TMP-SMX, nitrofurantoin or fosfomycin. 

Complicated UTI Treatment: Patients with symptoms of complicated infection require agents that achieve higher levels in the blood (see Antibiotic Pearls below) and upper tract tissues. In stable outpatients with minimal risk for multi-drug resistant organisms (MDRO), a fluoroquinolone can be used or a single dose of IV cephalosporin or ertapenem can be given followed by a course of oral TMP-SMX, amox-clav or cephalosporin for 7-14 days (Hooton, UptoDate 2019). Patients admitted with complicated UTI and lacking MDRO risk factors can receive initial therapy with IV ceftriaxone, pip-tazo or a fluoroquinolone. Sicker patients at risk for MDRO can receive a carbapenem (Hooton, UptoDate 2019). Antibiotic therapy can be narrowed based on culture results. The duration of therapy and when to change from IV to PO antibiotics is based on clinical response to therapy (See pearl below for those with bacteremia).

Dr Titanji referenced this VA Study that found no reduction in early or late recurrence for men with UTI treated for more than 7 days (Drekonja, JAMA Int Med 2013). 

Kashlak Pearl: In patients with complicated UTIs plus bacteremia the switch from IV to PO therapy should be with a highly bioavailable oral option like TMP-SMX or a fluoroquinolone . Dr. Titanji avoids oral beta-lactams in these situations as these have been associated with higher treatment failure rates.

Prostatitis

Prostatitis is common, but it’s usually non-bacterial! Acute bacterial prostatitis (ABP) is rare (Lipsky, Clin Inf Dis 2010)! Dr Titanji points out that patients with ABP often look ill and have fever and/or perineal pain. The prostate is acutely tender on exam and patients may present with acute urinary retention. Duration of therapy for ABP is usually 2-4 weeks depending on the severity (Lipsky, Clin Inf Dis 2010).

Case 3 – Catheter Associated UTI (CAUTI) in a patient with MDRO

In this case we discussed the challenges of CAUTI in patients with paraplegia or quadriplegia. Dr. Titanji points out that these patients may have different s/s depending on the level of their paralysis including vague ones like: increased spasticity, poor appetite, and fatigue. Since these patients are so in tune with their bodies/symptoms she puts more stock in reports of changes in color, odor or other s/s self identified as UTI (expert opinion).

Specimen collection in CAUTI: Ideally a specimen will be collected from a fresh, sterile catheterization. If a catheter cannot be easily replaced (e.g. patient with suprapubic catheter), then take a culture anyway as it will still inform any MDRO present –-expert opinion. Consult your friendly neighborhood ID to help choose antibiotics.

Patients at high risk for multiple drug resistant organisms (MDRO): It is reasonable to start with a big gun, like a carbapenem. Be sure to get urine and blood cultures first. Then, narrow the agent when able (Hooton, UptoDate 2019).

MRSA and UTIs: MRSA UTIs are rare. If present, then assume MRSA bacteremia and seeding from another source (e.g. endocarditis, hardware infection, wound infection, etc) —expert opinion. That said, initial coverage for MRSA in patients with severe sepsis is reasonable especially if you’re unsure of the source —expert opinion.

Gram Negative Bacteremia from UTI – Uncomplicated bacteremia (i.e. no sepsis, shock, MDRO, failure to clear cultures or needed I&D) from Enterobacter can safely be treated for 7 days duration (Yahav, Clin Inf Dis 2019). In patients hospitalized with gram-negative bacteremia achieving clinical stability before day 7, an antibiotic course of 7 days was noninferior to 14 days. There was no increase found in suppurative complications, relapse or all-cause mortality (Yahav, Clin Inf Dis 2019).

Antibiotic Pearls

Drugs for the lower urinary tract (bladder and below): Nitrofurantoin and fosfomycin.

Here is a handy list of antimicrobials that have high oral absorption and thus can achieve high blood levels (source: Paul Sax’s ID Learning Unit blog post). 

• Fluoroquinolones (levofloxacin, ciprofloxacin, moxifloxacin)
• Trimethoprim-sulfamethoxazole (TMP-SMX)
• Metronidazole
• Clindamycin
• Doxycycline
• Rifampin
• Linezolid
• Fluconazole

NOTE: The entire class of beta-lactam and beta-lactam-like antibiotics (penicillins and cephalosporins) are not on this list!

Beta lactams: Not first line for simple cystitis due to collateral damage on the microbiome and possible higher failure rates vs first line agents.

Fluoroquinolones: Resistance is a problem and they are not sufficiently narrow. They also have a Black Box warning for tendinitis and tendon rupture, plus carry additional risk for patients may convulsions, hallucinations, depression, prolonged QTc and Clostridium difficile (Tanne, BMJ 2008). They should not be used for acute cystitis (FDA Press release July 26, 2016).

Links*

1. Behave (book) by Robert Sapolsky
2. Boghuma’s blog theiddoc.net
3. Boghuma’s TED Talk
4. Emory’s ID fellowship program

*The Curbsiders participates in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising commissions by linking to Amazon. Simply put, if you click on our Amazon.com links and buy something we earn a (very) small commission, yet you don’t pay any extra.

Goals

Listeners will appropriately recognize, diagnose and treat the various presentations of urinary tract infection.

Learning objectives

After listening to this episode listeners will…

1. Define UTI and feel confident making the diagnosis of UTI based on lab tests, history and exam findings
2. Differentiate between complicated and uncomplicated UTI
3. Recognize how UTI may presents differently in differ groups (paraplegic, chronic foley catheter, men and women)
4. Choose the appropriate antibiotic and duration with an eye towards antibiotic stewardship
5. Determine an approach to the patient with recurrent UTIs, including who may benefit from long term antibiotic prophylaxis.

Disclosures

Dr Titanji reports no relevant financial disclosures. The Curbsiders report no relevant financial disclosures.

Citation

Titanji BK, Williams PN, Watto MF. “#231 U Talkin’ UTIs Re: Me”. The Curbsiders Internal Medicine Podcast. http://thecurbsiders.com/episode-list Final publishing date August 24, 2020.