CONTENTS
- Rapid Reference 🚀
- Diagnosis
- Imaging
- Management
- Podcast
- Questions & discussion
- Pitfalls
- PDF of this chapter (or create customized PDF)
rapid reference
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.
diagnosis
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.
imaging
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.
resuscitation
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.
decompression
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.
antibiotics: general principles
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.
preferred antibiotics for uroseptic shock
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.
antibiotic selection based on gram stain
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.
antibiotics for uroseptic shock in the ICU: common errors
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.
podcast
Follow us on iTunes
The Podcast Episode
Want to Download the Episode?
Right Click Here and Choose Save-As
questions & discussion
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).
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)
References
- 10923955 Holloway J, Joshi N, O'Bryan T. Positive urine nitrite test: an accurate predictor of absence of pure enterococcal bacteriuria. South Med J. 2000 Jul;93(7):681-2 [PubMed]
- 16723596 Gavin PJ, Suseno MT, Thomson RB Jr, Gaydos JM, Pierson CL, Halstead DC, Aslanzadeh J, Brecher S, Rotstein C, Brossette SE, Peterson LR. Clinical correlation of the CLSI susceptibility breakpoint for piperacillin- tazobactam against extended-spectrum-beta-lactamase-producing Escherichia coli and Klebsiella species. Antimicrob Agents Chemother. 2006 Jun;50(6):2244-7. doi: 10.1128/AAC.00381-05 [PubMed]
- 17599303 Czaja CA, Scholes D, Hooton TM, Stamm WE. Population-based epidemiologic analysis of acute pyelonephritis. Clin Infect Dis. 2007 Aug 1;45(3):273-80. doi: 10.1086/519268 [PubMed]
- 20300389 Kalra OP, Raizada A. Approach to a patient with urosepsis. J Glob Infect Dis. 2009 Jan;1(1):57-63. doi: 10.4103/0974-777X.52984 [PubMed]
- 21140281 Lee SJ, Lee DS, Choe HS, Shim BS, Kim CS, Kim ME, Cho YH. Antimicrobial resistance in community-acquired urinary tract infections: results from the Korean Antimicrobial Resistance Monitoring System. J Infect Chemother. 2011 Jun;17(3):440-6. doi: 10.1007/s10156-010-0178-x [PubMed]
- 22057699. Perez F, Bonomo RA. Can we really use ß-lactam/ß-lactam inhibitor combinations for the treatment of infections caused by extended-spectrum ß-lactamase-producing bacteria? Clin Infect Dis. 2012 Jan 15;54(2):175-7. doi: 10.1093/cid/cir793. [PubMed]
- 22057701 Rodríguez-Baño J, Navarro MD, Retamar P, Picón E, Pascual Á; Extended-Spectrum Beta-Lactamases–Red Española de Investigación en Patología Infecciosa/Grupo de Estudio de Infección Hospitalaria Group. β-Lactam/β-lactam inhibitor combinations for the treatment of bacteremia due to extended-spectrum β-lactamase-producing Escherichia coli: a post hoc analysis of prospective cohorts. Clin Infect Dis. 2012 Jan 15;54(2):167-74. doi: 10.1093/cid/cir790 [PubMed]
- 22915465 Vardakas KZ, Tansarli GS, Rafailidis PI, Falagas ME. Carbapenems versus alternative antibiotics for the treatment of bacteraemia due to Enterobacteriaceae producing extended-spectrum β-lactamases: a systematic review and meta-analysis. J Antimicrob Chemother. 2012 Dec;67(12):2793-803. doi: 10.1093/jac/dks301 [PubMed]
- 24928854 Park SH, Choi SM, Chang YK, Lee DG, Cho SY, Lee HJ, Choi JH, Yoo JH. The efficacy of non-carbapenem antibiotics for the treatment of community-onset acute pyelonephritis due to extended-spectrum β-lactamase-producing Escherichia coli. J Antimicrob Chemother. 2014 Oct;69(10):2848-56. doi: 10.1093/jac/dku215. [PubMed]
- 25808934 Ledochowski S, Abraham PS, Jacob X, Dumitrescu O, Lina G, Lepape A, Piriou V, Wallet F, Friggeri A. Relevance of blood cultures in acute pyelonephritis in a single-center retrospective study. Intern Emerg Med. 2015 Aug;10(5):607-12. doi: 10.1007/s11739-015-1223-7 [PubMed]
- 26542304. Harris PN, Wei JY, Shen AW, Abdile AA, Paynter S, Huxley RR, Pandeya N, Doi Y, Huh K, O'Neal CS, Talbot TR, Paterson DL. Carbapenems versus alternative antibiotics for the treatment of bloodstream infections caused by Enterobacter, Citrobacter or Serratia species: a systematic review with meta-analysis. J Antimicrob Chemother. 2016 Feb;71(2):296-306. doi: 10.1093/jac/dkv346. [PubMed]
- 26905806. Reyner K, Heffner AC, Karvetski CH. Urinary obstruction is an important complicating factor in patients with septic shock due to urinary infection. Am J Emerg Med. 2016 Apr;34(4):694-6. doi: 10.1016/j.ajem.2015.12.068. [PubMed]
- 27016557 Wenzler E, Danziger LH. Urinary Tract Infections: Resistance Is Futile. Antimicrob Agents Chemother. 2016 Mar 25;60(4):2596-7. doi: 10.1128/AAC.00006-16. [PubMed]
- 27712137 Bader MS, Loeb M, Brooks AA. An update on the management of urinary tract infections in the era of antimicrobial resistance. Postgrad Med. 2017 Mar;129(2):242-258. doi: 10.1080/00325481.2017.1246055 [PubMed]
- 28034519 Moy S, Sharma R. Treatment Outcomes in Infections Caused by “SPICE” (Serratia, Pseudomonas, Indole-positive Proteus, Citrobacter, and Enterobacter) Organisms: Carbapenem versus Noncarbapenem Regimens. Clin Ther. 2017 Jan;39(1):170-176. doi: 10.1016/j.clinthera.2016.11.025 [PubMed]
- 28320724 Cheng L, Nelson BC, Mehta M, Seval N, Park S, Giddins MJ, Shi Q, Whittier S, Gomez-Simmonds A, Uhlemann AC. Piperacillin-Tazobactam versus Other Antibacterial Agents for Treatment of Bloodstream Infections Due to AmpC β-Lactamase-Producing Enterobacteriaceae. Antimicrob Agents Chemother. 2017 May 24;61(6):e00276-17. doi: 10.1128/AAC.00276-17 [PubMed]
- 29135902 Chaudhari PP, Monuteaux MC, Bachur RG. Should the Absence of Urinary Nitrite Influence Empiric Antibiotics for Urinary Tract Infection in Young Children? Pediatr Emerg Care. 2020 Oct;36(10):481-485. doi: 10.1097/PEC.0000000000001344 [PubMed]
- 30125680 McKamey L, Venugopalan V, Cherabuddi K, Borgert S, Voils S, Shah K, Klinker KP. Assessing antimicrobial stewardship initiatives: Clinical evaluation of cefepime or piperacillin/tazobactam in patients with bloodstream infections secondary to AmpC-producing organisms. Int J Antimicrob Agents. 2018 Nov;52(5):719-723. doi: 10.1016/j.ijantimicag.2018.08.007 [PubMed]
- 31563203 Dubbs SB, Sommerkamp SK. Evaluation and Management of Urinary Tract Infection in the Emergency Department. Emerg Med Clin North Am. 2019 Nov;37(4):707-723. doi: 10.1016/j.emc.2019.07.007 [PubMed]
- 31608743 Bader MS, Loeb M, Leto D, Brooks AA. Treatment of urinary tract infections in the era of antimicrobial resistance and new antimicrobial agents. Postgrad Med. 2020 Apr;132(3):234-250. doi: 10.1080/00325481.2019.1680052 [PubMed]
- 33774453 Lei B, Harfouch N, Scheiner J, Demissie S, Hayim M. Can obstructive urolithiasis be safely excluded on contrast CT? A retrospective analysis of contrast-enhanced and noncontrast CT. Am J Emerg Med. 2021 Mar 22;47:70-73. doi: 10.1016/j.ajem.2021.03.059 [PubMed]