CONTENTS

• Rapid Reference 🚀
• Diagnosis
  • Urinalysis
• Imaging
• Management:
  • Resuscitation
  • Decompression & source control
  • Antibiotics
    • General principles
    • Preferred antibiotics for initial broad-spectrum coverage
    • If gram stain is known
• 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.

foley catheter

• If the bladder is distended, attempt placement of a foley catheter.
• If the patient has a chronic foley catheter:
  • Remove it and place a fresh catheter.
  • Obtain urinalysis & culture via the fresh catheter.

sepsis resuscitation 📖

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

antibiotics 📖

• Piperacillin-tazobactam 💉 is often preferred.

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urosepsis diagnosis

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what is urosepsis?

• Cystitis (bladder infection) by itself rarely causes sepsis.
  • Finding inflammation and bacteria in the bladder doesn't necessarily indicate urosepsis.
• Urosepsis nearly always results from infection that ascends to the kidneys (pyelonephritis), often spilling into the bloodstream causing bacteremia.

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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urinalysis

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overall performance of 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).

urine nitrites

• Nitrites are generated by gram-negative enteric pathogens (Enterobacteriaceae), 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-negative Enterobacteriaceae, 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.

pH

• pH >8 may suggest urease-producing organisms (e.g., Proteus or Providencia spp.).(Vincent 2023)

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).

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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).
  • Note that Staphylococcus aureus is almost never a pathogen for community-acquired urosepsis.  Therefore, these patients do not need MRSA coverage.
• Pseudomonas is possible, albeit unlikely. Some other series have reported rates of pseudomonas between 2-5%.(20300389, 21140281, 27712137)

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.  However, 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. (However, as always, antibiotic selection may also depend on prior culture results, drug allergies, and local antibiograms.)

🏆 piperacillin-tazobactam: generally preferred option

• Strengths:
  • Excellent gram-negative coverage, including pseudomonas.
  • Coverage of community-acquired gram-positives (e.g., enterococcus faecalis and Staph saprophyticus).
  • Lower 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)

🏆 meropenem: for sickest patients with risk factors for ESBL species

• 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.
• Weaknesses:
  • For most patients from the community, meropenem is unnecessarily broad.

cefepime: solid choice

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

🤷‍♂️ ceftriaxone: not ideal for sickest patients

• Ceftriaxone is fine for patients admitted to the ward. And ceftriaxone will generally get the job done OK in the ICU as well. However, it's not an ideal medication for the sickest septic shock patients for the following reasons:
  • No enterococcal coverage.
  • No pseudomonal coverage.
  • No ESBL or AmpC-inducible beta-lactamase coverage.
  • Broad utilization of ceftriaxone has started to reduce the sensitivity of E. coli to ceftriaxone in some areas.
  • Uniquely low urinary levels.(31608743) Ceftriaxone is largely cleared by the liver, so its urinary penetration is less impressive than antibiotics which are solely cleared by the kidneys.  In contrast, most other beta-lactam antibiotics are cleared by the kidneys, so they achieve extremely high urinary drug levels.  

rarely utilized: aminoglycosides

• Aminoglycoside (+/- ampicillin) may be utilized in unusual situations (e.g., multiple drug allergies).  However, this strategy requires meticulous dosing and is limited by nephrotoxicity.

👎 do not use: fluoroquinolone

• Discussed further here: 📖

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antibiotic selection based on gram stain

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gram negative rod

• Most patients will be found to have a gram-negative rod.  This doesn't require switching antibiotics:  antibiotics listed in the section above will be fine (e.g. piperacillin-tazobactam, meropenem, or cefepime).
• If the patient is known to have a gram negative rod prior to starting antibiotics (e.g., based on a STAT urinary gram stain), aztreonam 💉 would be a reasonable consideration since this focuses purely on gram-negatives.

gram positive cocci

• The primary concern here would generally be enterococci, or less often staphylococcus saprophyticus.  For community-acquired urosepsis Enterococcus faecalis is more common, but patients with antibiotic/healthcare exposure could harbor Enterococcus faecium (with increased rates of vancomycin-resistant enterococci).
• If the patient is already on an antibiotic covering community-acquired enterococci (e.g., piperacillin-tazobactam) and the patient is improving, then nothing else usually needs to be done.  Follow the patient clinically and wait for organism identification and sensitivities.
• If the patient isn't on enterococcal coverage  (e.g., ceftriaxone/cefepime) or the patient is deteriorating, then antibiotics should be transitioned towards better gram-positive coverage:
  • Vancomycin 💉 is a reasonable choice for patients at low risk of VRE (vancomycin-resistant enterococci).
  • For patients with risk factors for VRE, linezolid 💉 or daptomycin 💉 are reasonable choices. A single dose of daptomycin provides coverage for 24 hours (GFR >30) or 48 hours (GFR <30), which is often enough time to provide coverage until speciation results are available.
• 🔑 Follow up on the culture and speciation closely.  Most patients will have Enterococcus faecalis, in which case antibiotics can usually be narrowed to ampicillin 💉.

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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.

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