CONTENTS

• Rapid Reference 🚀
• Diagnosis
• Imaging
• Management
  • Resuscitation
  • Decompression & source control
  • Antibiotics
    • General principles
    • Preferred antibiotics
    • If gram stain is known
    • Common antibiotic errors
• Podcast
• Questions & discussion
• Pitfalls

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rapid reference

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diagnostic tests

• Urinalysis & urine culture.
• Blood culture x2.
• Procalcitonin.
• Imaging, either:
  • CT scan (especially if >35 YO).
  • Renal ultrasonography (especially if <35 YO and immediately available).
  • 🔑 If obstruction, consult urology STAT for decompression.

resuscitation (more)

• Judicious fluid resuscitation (typically ~1-2 liters).
• Early vasopressor support (e.g., peripheral norepinephrine).
• Stress dose steroid: consider for patients on vasopressors (50 mg hydrocortisone IV q6hr).

antibiotics (more)

• Piperacillin-tazobactam is usually preferred.
• Meropenem may be used if concern about ESBL organisms.

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diagnosis

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what is urosepsis?

• Cystitis (bladder infection) by itself rarely causes sepsis.
• Urosepsis nearly always results from infection that ascends to the kidneys (pyelonephritis), often spilling into the bloodstream causing bacteremia.

urinalysis

• Urinalysis is sensitive:
  • Urosepsis is nearly always accompanied by pyuria (>10 WBC per high power field).
  • Absence of pyuria largely excludes urosepsis (unless the patient is neutropenic or an obstruction is present).
• Urinalysis is nonspecific:
  • Abnormal urinalysis is common among healthy elderly patients due to colonization with bacteria (asymptomatic bacteriuria).

diagnosis requires additional supporting evidence

• Diagnosing urosepsis requires additional clinical information beyond an abnormal urinalysis.   For example:
  • (a)  Clinical history suggestive of urosepsis (e.g., urgency, frequency, dysuria, suprapubic or flank pain, hematuria).
  • (b)  Imaging evidence (e.g., CT scan reveals pyelonephritis).
  • (c)  Abnormal urinalysis with diligent exclusion of all other common sources of infection (e.g., normal CXR, unremarkable CT of the abdomen/pelvis, and no other localizing signs/symptoms).

blood cultures

• When possible, blood cultures should be obtained prior to antibiotics.
• The utility of blood cultures has been questioned, as they will generally match the urine culture results.(25808934)  However, this line of argumentation is flawed.  Blood cultures will be most useful in patients who initially appear to have urosepsis, but later are diagnosed with something else (e.g., endocarditis or ascending cholangitis).  Unfortunately, studies usually exclude such patients due to retrospective inclusion of only patients with a final diagnosis of pyelonephritis.

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imaging

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reasons to obtain imaging 

• (#1) Detection of complications, for example:
  • 10% of patients have urinary obstruction, which requires immediate drainage to achieve source control.(26905806)  Obstruction causes pressure and bacteria to back up into the glomeruli, leaking into systemic circulation and exacerbating sepsis.  If obstruction is detected, urology should be consulted immediately for stent placement (or, if that isn't an option, percutaneous nephrostomy drainage by interventional radiology).
  • Perinephric or prostate abscess (which may require surgical or percutaneous drainage).
  • Emphysematous pyelonephritis or, less commonly, emphysematous cystitis (which may require surgical resection).
• (#2) Detection of an alternative diagnosis:
  • Elderly patients often have positive urinalysis due to asymptomatic bacteriuria, so this can be a red herring.  Therefore, a positive urinalysis plus abdominal pain does not necessarily diagnose urosepsis.  The patient might have another cause of abdominal sepsis (e.g., cholecystitis or diverticulitis) plus asymptomatic bacteriuria.

imaging in older urosepsis patients

• CT scan is optimal.  This provides immediate and definitive imaging, which will help motivate and guide intervention (most urologists won't come into the hospital at 2 AM for a positive ultrasound).
• If the only concern is nephrolithiasis, a noncontrast (“stone protocol”) CT scan is adequate.  However, if there is a possibility of other abdominopelvic pathology, then a contrast CT scan may be more appropriate.  The addition of contrast does not reduce the accuracy for diagnosis of nephrolithiasis, but it may help detect other pathology.(33774453)

imaging in younger urosepsis patients

• Younger patients are at higher risk from harm due to radiation.  They are also less likely to have an unusual presentation or anatomic complication.
• Bedside ultrasonography to exclude hydronephrosis may be adequate in these patients.   This isn't quite as easy as it looks.  If images are suboptimal or interpretation is unclear, there should be a low threshold to obtain a formal study or second opinion from a more experienced clinician.

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resuscitation

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This is similar to resuscitation of other septic patients.  The only difference here is that patients with urosepsis may tend to recover a bit faster than those with other sources of sepsis.  Therefore, patients who are requiring only low-dose vasopressors don't necessarily need a central line.

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decompression

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Foley catheter placement

• A foley catheter should generally be placed for measurement of urine output (as an indicator of adequate systemic perfusion).
• In some cases (e.g., urosepsis due to prostatic hypertrophy), the foley itself may also help by decompressing the infection.

source control in cases with obstruction (typically an obstructing stone)

• Source control requires relief of the obstruction.  Decompression may be done by urology (e.g., stent placement) or interventional radiology (percutaneous nephrostomy tube placement).  Urologic stent placement is generally preferable, as this allows only a single procedure to be performed.
• Sometimes decompression releases bacteria into the blood, causing patients to deteriorate.  Thus, patients should  ideally receive antibiotics and hemodynamic stabilization immediately – before intervention.

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antibiotics: general principles

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Urosepsis is somewhat unique among infections because a causative organism is nearly always cultured.  This allows for de-escalation of antibiotics within 2-3 days of admission.  Initial therapy should be sufficiently broad to cover any likely pathogen.

what are we targeting?  

• The vast majority of urosepsis is due to gram-negative rods (mostly E. coli).(17599303)
• Occasionally the culprit is a gram-positive (mostly enterococci, but occasionally Staph. saprophyticus).
• Pseudomonas is possible, albeit unlikely.  Some other series have reported rates of pseudomonas between 2-5%.(20300389, 21140281, 27712137)

urine gram stain

• Some hospitals are able to perform STAT gram stains on urine, which can be extremely helpful.
  • Gram-positive detected:  May tailor therapy to focus on enterococcus and Group B streptococci.
  • Gram-negative detected:  Focus on gram-negative coverage.
• The regimens below are designed in the absence of a urine gram stain (realistically, gram stain usually isn't immediately available).

urine nitrites

• Nitrites are generated by gram-negative enteric pathogens, but not gram-positives.(29135902, 10923955)
  • In urinary tract infection with gram-positives or Pseudomonas, nitrites are detected only rarely (~5% of cases).(31563203)
  • In urinary tract infection with gram-negatives, nitrites are commonly detected (~40% of cases).
• Therefore:
  • Positive nitrites has a likelihood ratio for gram-negative infection of ~8.
  • Negative nitrites has a likelihood ratio for gram-negative infection of ~0.6 (this provides little useful information).
• Given that the prevalence of gram-negative infection is ~95% to begin with, a positive urinary nitrite result results in post-test probability of gram-negative infection >99%.  This might be useful in determining the necessity of covering for gram-positive pathogens, if a urinary gram stain isn't available.

favorable pharmacology

• Several factors are working in our favor here:
  • In the absence of obstruction, the flow of urine tends to clear bacteria from the kidneys and bladder.
  • If an antibiotic excreted by the kidney is used, it will be concentrated in the urine leading to very high drug levels.  This can allow for clinical cure, even if the organism is “resistant” at drug concentrations which are achieved in the blood (although this shouldn't be relied upon in septic patients who may have bacteremia).(27016557)
• These factors shouldn't lead us to be sloppy in antibiotic selection.  However, at the same time, not every drug-resistant organism must be treated with meropenem (more on this below).(24928854)

lack of consensus!

• Above are treatment recommendations from common sources.  These recommendations vary widely.  Some of this variability may reflect irregularities in the definition of “complicated” versus “uncomplicated” pyelonephritis.
• Below is one attempt at antibiotic selection, based on available evidence (as cited).  Please be aware that this doesn't represent a universal consensus.  Furthermore, this won't necessarily apply perfectly to every geographic locale, depending on your antibiogram.

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preferred antibiotics for uroseptic shock

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Community-acquired uroseptic shock can generally be treated using a single antibiotic.  Below are preferred options.

🥇 generally preferred option:  piperacillin-tazobactam 

• Strengths:
  • Excellent gram-negative coverage, including pseudomonas.
  • Coverage of community-acquired gram-positives (e.g., enterococcus faecalis and Staph saprophyticus).
  • Adequate coverage for AmpC enterobacteriaceae (piperacillin-tazobactam not be ideal for them, but emerging evidence suggests that it is adequate).(28034519, 26542304, 28320724, 30125680)
  • Low rate of causing C. difficile, when compared to other broad-spectrum antibiotics.
• Weaknesses:
  • The main limitation of piperacillin-tazobactam is that it's not optimal for extended-spectrum beta-lactamase (ESBL) gram-negatives.  Some reports indicate that ESBL are being seen increasingly in the community, particularly in certain geographic locales.  Fortunately, piperacillin-tazobactam may often be adequate for ESBL species, especially urinary tract infection with ESBL E. Coli.(22057701, 22057699, 16723596, 22915465)  
  • Piperacillin is generally safe in patients with a history of penicillin allergy, but in some cases this may remain a concern. (discussed further here)

🥈 runner-up:  meropenem

• Strengths:
  • Excellent gram-negative coverage, including pseudomonas.
  • Coverage of community-acquired gram-positives (e.g., enterococcus faecalis and Staph saprophyticus).
  • Excellent coverage for AmpC enterobacteriaceae as well as ESBL gram-negatives.  This can make meropenem a good choice for nosocomial urosepsis, or in contexts with high rates of ESBL species.
  • Allergy to meropenem is largely nonexistent, so meropenem can be confidently used in patients with a history of numerous antibiotic allergies (including anaphylaxis to penicillins or cephalosporins).
• Weaknesses:
  • For most patients from the community, meropenem is unnecessarily broad.  So infectious disease colleagues may laugh at you.  Try to de-escalate before anyone notices (as soon as culture results return, which generally happens pretty rapidly with urosepsis).

🥉 a solid option:  cefepime

• Strengths:
  • Excellent gram-negative coverage, including pseudomonas and AmpC enterobacteriaceae.
• Weaknesses
  • Will miss ESBL species entirely (worse coverage of these when compared to either piperacillin-tazobactam or meropenem).
  • Misses all enterococci species.
  • May cause delirium.

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antibiotic selection based on gram stain

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gram negative rod

• This is usually the case.
• Antibiotic selection is generally the same as described in the above section (e.g. piperacillin-tazobactam, meropenem, or cefepime).

gram positive cocci

• The primary concern here would generally be enterococci.
• If the patient is already on an antibiotic covering community acquired enterococci (e.g., piperacillin-tazobactam or meropenem) and the patient is improving, then nothing more needs to be done.
• If the patient is on an antibiotic which doesn't cover enterococci (e.g., ceftriaxone or cefepime), then this should be switched to a different antibiotic.  Daptomycin or linezolid might be reasonable options here, given their broad-spectrum coverage of enterococci (including vancomycin-resistant enterococci).  A single dose of daptomycin provides coverage for 24-48 hours, which could be sufficient to provide coverage until speciation results are available.

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antibiotics for uroseptic shock in the ICU: common errors

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common error #1:  using a fluoroquinolone 

• Fluoroquinolones are poor drugs for use in critically ill patients for several reasons, as explored here.
• Over-use of fluoroquinolones in the community has led to increasing antibiotic resistance (e.g. ciprofloxacin resistance among E. coli is reaching 15%).
• Fluoroquinolones simply are no longer adequate coverage for urosepsis.

common error #2:  using ceftriaxone

• Ceftriaxone is generally fine for urosepsis admitted to the ward.  And it will generally get the job done OK in the ICU as well.  However, it's not an ideal medication for the sickest uroseptic shock patients for the following reasons:
• 1) Main problem:  AmpC inducible beta-lactamase
  • Many species of gram-negative organisms have inducible beta-lactamases (AmpC-type).  These bacteria may appear to be sensitive to an antibiotic en vitro, but in vivo the bacteria will up-regulate its beta-lactamases and become resistant.  The main offenders here highlighted in pink above.
  • Based on the antibiogram, it may appear that ceftriaxone or ceftazidime has very good gram-negative coverage.  However, accounting for the many species which may have AmpC beta-lactamases, this coverage actually isn't terrific.
• 2) Enterococcus:  Commonly used cephalosporins don't cover enterococcus (the only cephalosporin with enterococcal activity is ceftaroline).
• 3) Pseudomonas:  Pseudomonas isn't a major uropathogen, so this may not be a huge problem.  
• 4)  Lower urinary drug levels.(31608743)  Ceftriaxone is cleared by the liver and kidneys, so its urinary penetration may be less impressive than antibiotics which are solely cleared by the kidneys (e.g., most other beta-lactam antibiotics).

common error #3:  over-use of vancomycin

• Methicillin-resistant staph aureus (MRSA) is an extremely uncommon cause of community-acquired urosepsis.  For example, the table shown above reported staph aureus in 0.25% of cases admitted from the community.(17599303)  The vast majority of these cases are presumably methicillin-sensitive staph aureus, leaving the incidence of methicillin-resistant staph aureus well below 0.25%.
  • Incidentally, if staph aureus is detected in the urine this should trigger suspicion of some other infectious process (e.g. endocarditis with hematogenous seeding of the kidneys).
• If a resistant gram-positive pathogen is involved in urosepsis, the most likely culprit is vancomycin-resistant enterococci (VRE).  Vancomycin won't help with this.  So if you want to use an agent that covers resistant gram-positives, the most logical choices are either linezolid or daptomycin (drugs that will cover both MRSA and VRE).  None of these agents are really needed for community-acquired urosepsis, but at least linezolid or daptomycin would make more sense than vancomycin.

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podcast

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questions & discussion

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To keep this page small and fast, questions & discussion about this post can be found on another page here.

• Incorrectly assuming a patient with abnormal urinalysis has urosepsis, causing you to miss an alternative source of infection.
• Failure to obtain adequate imaging, thereby ignoring a urinary obstruction that requires emergent drainage.
• Treatment with a fluoroquinolone, ceftriaxone, ceftazidime, or vancomycin (explanation that these are suboptimal choices above).

Guide to emoji hyperlinks 

•  = Link to online calculator.
•  = Link to Medscape monograph about a drug.
•  = Link to IBCC section about a drug.
•  = Link to IBCC section covering that topic.
•  = Link to FOAMed site with related information.
•  = Link to supplemental media.

Going further

• Urosepsis (Chris Nickson, LITFL)
• Interpretation of bedside urinalysis (Mike Cadogan, LITFL)
• UTI: More than you ever wanted to know (Justin Morgenstern, first 10 in EM)
• Urinalysis pitfalls (Brit Long & Alex Koyfman, EP Monthly)
• UTI myths & misconceptions (Anton Helman, EMCases)