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SAEM Clinical Images Series: The Color Purple

purple urine

A 64-year-old female with a history of quadriplegia and bladder rupture secondary to a motor vehicle accident two years ago, complicated by chronic indwelling suprapubic foley, presents from her skilled nursing facility with fever, oliguria, tachycardia, low blood pressure, and a change in the color of her urine.

Vitals: T 100.4°F; HR 126; BP 105/74; RR 24

General: Pleasant but mildly confused morbidly obese female smelling strongly of urine

Genitourinary: Poorly maintained indwelling suprapubic catheter with purulence noted around the ostomy and purple urine in her foley tubing and bag

Urinalysis (UA): 168 WBC, >182 RBC, Large leukocyte esterase, Positive nitrite

This is a case of Purple Urine Bag syndrome (PUBS), an uncommon subset of CAUTI that generally occurs in female patients with constipation and an indwelling foley. Although not fully understood, it is thought that the long stool transit time of constipation allows GI flora to break tryptophan down into indoles which travel to the liver via the portal system where they become indoxyl sulfate, which is excreted into the urine. Bacterial enzymes there catalyze this to indoxyl which oxidizes in alkaline urine to both indigo (blue) and indirubin (red), the combination of which, plus interaction with the plastic catheter tubing, causes the vivid purple discoloration. Risk factors include women, chronically catheterized, elderly, recurrent UTI, institutionalization, and chronic constipation.

Causative organisms are primarily gram-negative and include Proteus mirabilis, Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa, Morganella morganii, and Enterococcus species.

Take-Home Points

  • PUBS is a rare subset of CAUTI primarily caused by gram-negative bacteria.
  • It is predominantly found in women, chronically catheterized, institutionalized, and constipated patients.
  • Treatment is appropriate antibiotics and improved foley hygiene, foley exchange as well as improved bowel regimen to increase stool transit time.

  • Meekins Pauline, Ramsay Amy, Ramsay Michael. Purple Urine Bag Syndrome. West J Emerg Med. 2012 Dec;13(6):499-500. 2. Scleszka Laura, Swan Tricia. October 9, 2020. Can Urine Color Guide Management? [online] EMRA. Available at: https://www.emra.org/emresident/article/purple-urine-bag-syndrome/ [Accessed 19 Dec. 2022]

Copyright

Images and cases from the Society of Academic Emergency Medicine (SAEM) Clinical Images Exhibit at the 2021 SAEM Annual Meeting | Copyrighted by SAEM 2021 – all rights reserved. View other cases from this Clinical Image Series on ALiEM.

By |2023-08-14T09:14:36-07:00Aug 14, 2023|Infectious Disease, SAEM Clinical Images|
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ALiEM AIR Series | Infectious Disease 2023 Module

ALiEMU AIR Series infectious disease 2023

Welcome to the AIR Infectious Disease Module! After carefully reviewing all relevant posts in the past 12 months from the top 50 sites of the Digital Impact Factor [1], the ALiEM AIR Team is proud to present the highest quality online content related to related to infectious diseases in the Emergency Department. 6 blog posts met our standard of online excellence and were approved for residency training by the AIR Series Board. More specifically, we identified 1 AIR and 5 Honorable Mentions. We recommend programs give 3 hours of III credit for this module.

AIR Stamp of Approval and Honorable Mentions

In an effort to truly emphasize the highest quality posts, we have 2 subsets of recommended resources. The AIR stamp of approval is awarded only to posts scoring above a strict scoring cut-off of ≥30 points (out of 35 total), based on our scoring instrument. The other subset is for “Honorable Mention” posts. These posts have been flagged by and agreed upon by AIR Board members as worthwhile, accurate, unbiased, and appropriately referenced despite an average score.

Take the AIR Infectious Disease Module at ALiEMU

Interested in taking the AIR quiz for fun or asynchronous (Individualized Interactive Instruction) credit? Please go to the above link. You will need to create a free, 1-time login account.

Highlighted Quality Posts: Infectious Disease

SiteArticleAuthorDateLabel
SGEMLumbar punctures in febrile infants with positive urinalysis – it’s just overkillDennis Ren, MDDecember 31, 2022AIR
EMDocsBacterial MeningitisMounir Contreras Cejin, MD January 28, 2023HM
ALiEMThe Febrile InfantCorey Ziemba, MD, Justin Hacnik, MD and J.D. Cambron, DOMarch 29, 2023HM
EMCritApproach to CNS infectionJosh Farkas, MDAugust 15, 2022HM
Core EMUpdates in STI CareDaniel Imas, MDMarch 17, 2022HM
REBEL EMShort course antibiotics for Peds CAPMarco Propersi, DODec 5, 2022HM

(AIR = Approved Instructional Resource; HM = Honorable Mention)

 

If you have any questions or comments on the AIR series, or this AIR module, please contact us!

Thank you to the Society of Academic Emergency Medicine (SAEM) and the Council of EM Residency Directors (CORD) for jointly sponsoring the AIR Series! We are thrilled to partner with both on shaping the future of medical education.

 

Reference

  1. Lin M, Phipps M, Chan TM, et al. Digital Impact Factor: A Quality Index for Educational Blogs and Podcasts in Emergency Medicine and Critical Care. Ann Emerg Med. 2023;82(1):55-65. doi:10.1016/j.annemergmed.2023.02.011, PMID 36967275
By |2023-07-21T14:46:01-07:00Jul 20, 2023|ALiEMU, Approved Instructional Resources (AIR series), Expert Peer Reviewed (Clinical), Infectious Disease|
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The Febrile Infant: Incorporating the 2021 American Academy of Pediatrics guidelines

Can you trust a febrile infant?

“No” has been, and continues to be, the resounding answer over the last 40 years as researchers and clinicians work to determine the optimal evaluation and management of the well-appearing young febrile infant [1].

The goal remains to identify infants with bacterial infections in this at-risk cohort of patients while also considering the balance of cost-effectiveness on a population scale and the potential for iatrogenic harm with evaluation such as unnecessary lumbar punctures, unnecessary antibiotics, and unnecessary hospitalization. Fortunately, bacteremia and bacterial meningitis in this age group are uncommon [2]. Unfortunately, delayed or missed diagnosis can be devastating [1-3].

In the most recent 2021 Clinical Practice Guideline, the American Academy of Pediatrics (AAP) aims to provide guidance with 3 separate age-based algorithms for the evaluation and management of the well-appearing febrile infant [4]. These guidelines were made possible by the recent PECARN, Step by Step, and other studies and the invaluable information they have provided [5-7].

Who’s included?

  • Well-appearing febrile infants
    • The AAP acknowledges that clinician experience is likely the best determinate of what is “well-appearing”, further admitting that there is no measure or definition of either “experience” or “well-appearing”
  •  Febrile
    • Rectal temperatures of  38.0C or 100.4F at home in the past 24 hours or determined in a clinical setting
    • Subjective fevers at home are excluded
  •  Gestation
    • Between 37-42 weeks
    • Premature infants excluded
  • Age
    • Days 8 to 60 and have been discharged home following birth

Who is not included?

  • Preterm or infants with congenital/chromosomal abnormalities
  • Infants with focal bacterial infections
  • Cellulitis, omphalitis, septic arthritis, osteomyelitis
  •  Bronchiolitis
    • With or without a positive RSV test
  •  Immunocompromised
    • Either suspected or known deficiency
  • Immunizations in the previous 48 hours

It should also be noted that the AAP has named the following as high-risk inflammatory markers that will be referenced in the soon-to-be-discussed guidelines [4,5].

  • Temperature >101.3F (38.5C)
  • C-reactive protein (CRP) > 20 mg/L
  • Procalcitonin >0.5 ng/mL
  • Absolute neutrophil count (ANC) >4000 mm3  (or 5200 mm3 if your facility does not have procalcitonin available)

The Groups

While the AAP makes the distinction of an age 0-7 days group from the age 8-21 days, they provide no specific recommendations about emergency department (ED) management in the youngest group [4]. Despite this, these infant groups are likely best evaluated and managed similarly in the ED:

  • Urinalysis (UA) +/- urine culture if indicated by UA
  • Blood culture
  • Lumbar puncture (LP)
    • Cell count, Gram stain, glucose, protein, bacterial culture, and enterovirus PCR (if available)
  • Admission

Inflammatory markers are not required to determine ED management in this age group but may guide inpatient clinicians.

Treatment

  • Ampicillin IV or IM
  • Ceftazidime IV or IM or gentamicin IV or IM

The addition of acyclovir to IV antibiotics depends on the following risk factors which increase the likelihood of HSV:

  • Maternal genital HSV lesions or fever 48 hours before or after delivery
  • Infants with vesicles, seizures, hypothermia, mucous membrane ulcers
  • CSF pleocytosis with a negative Gram stain result
  • Leukopenia, thrombocytopenia, or elevated AST/ALT levels

Although many febrile infants in this group will still require a full evaluation for sepsis, there are some new alternatives in patients meeting certain criteria. At the minimum, all 22-28 day old infants will need:

  • UA +/- culture
  • Blood culture
  • Inflammatory markers (ANC, CRP, procalcitonin)

Further management of a well-appearing infant in this group can be based on the following pathways:

    1. If UA positive with negative inflammatory markers
      • LP may be performed but is not required
      • IV antibiotics and admission are required regardless
    2. If UA negative with negative inflammatory markers, then there are 2 options
      • Perform LP
        • If LP negative, then the patient can be given a dose of parenteral antibiotics and discharged home with close follow-up in 24 hours.
        • If LP is traumatic or pleocytosis is present, administer antibiotics and admit.
      • Defer LP
        • Antibiotics may be administered, but the patient should be admitted.
    3. If UA negative and ANY positive inflammatory marker (procalcitonin > 0.5 mg/mL, CRP >20 mg/L, ANC >4000, or temperature >101.3F), LP is required
      1. If LP positive
        • Admit with IV antibiotics
      2. If LP negative
        • Admit +/- antibiotics, OR
        • Discharge home after one dose of parenteral antibiotic with 24-hour follow-up

Treatment

  • Same antibiotic options as the day 0-21 infants

The nuances of this group’s decision tree revolve around the inflammatory markers.

Each infant in this group should have the following completed:

  • Urinalysis
  • Blood Cultures
  • Inflammatory markers (CRP, ANC, and procalcitonin)

If everything is negative (UA & inflammatory markers):

  • Infants may be discharged home without antibiotics and with close follow-up within 36 hours.

If inflammatory markers are negative:

  • Infants with a positive urinalysis and negative inflammatory markers may be treated with oral antibiotics.
    • They may be either admitted to the hospital for observation or discharged with 24-hour follow-up.
    • No LP needed.

If inflammatory markers are positive:

  • A LP may be performed if the clinician feels it necessary but is not required.
    • If performed and CSF is negative the infant may be discharged with close follow-up.
    • Given high risk of bacteremia with elevated inflammatory markers in this age group, a dose of parenteral antibiotics prior to discharge is appropriate.
  • If LP deferred:
    • Administer parenteral antibiotics, and likely admit to hospital.
    • The caveat to this is if they have viral testing completed that is positive and are well appearing.
      • Example: A 48-day-old infant presents with a fever of 100.6F, CRP of 22 mg/L, and otherwise normal procalcitonin, ANC, and UA. The mother reports that an older brother has had a runny nose. Viral PCR testing is positive for rhinovirus. Seeing as the UA is negative, the infant appears well with a positive viral test, they may go home with shared decision-making and close outpatient follow-up, despite a positive inflammatory marker (CRP 22 mg/L) [3].

Treatment

Urinary Tract Infection:

  • Ceftriaxone (IV/IM) or cephalexin/cefixime as oral options.

Concern for Bacteremia/Meningitis:

  • Ceftriaxone + vancomycin
  • May add acyclovir for the above-mentioned antiviral treatment indications.

What should be done if the viral panel is positive?

  • Children 29 days or older with fever from a documented viral source can be managed according to their clinical presentation and can go outside the algorithm.
  • This requires a documented positive viral swab and not just a presentation consistent with a viral syndrome.
  • UTI is common in this age group, and a UA should be obtained [8].

Conclusion

Over the course of nearly the last half century there has been a lack of clear evidence-based guidelines in evaluating the young febrile infant [1]. Although serious bacterial infections in these young, febrile infants are uncommon, studies show that in the first month of life, bacteremia can be present in nearly 3% of febrile infants, with bacterial meningitis occurring in about 1% [2]. The absence of consensus regarding management has led to significant costs due to hospitalizations and their associated iatrogenic complications [9]. In the movement to create new recommendations, shifting epidemiology pushed changes in previous guidelines with a new focus on the use of the now widely available inflammatory markers [10].  With the advent of multiple large-scale studies and the recent improvements in lab testing, the newly updated AAP guidelines provide recommendations on how to manage this challenging population [4-7].

Take Home Points

  • These management strategies can only be used in WELL-APPEARING infants – if they’re ill-appearing, do a complete workup.
  • Evaluation of febrile infants 0-21 days remains the same – do everything (blood culture, UA +/- culture, LP with CSF studies), give antibiotics, and admit.
  • For those infants 22-28 days, get the UA, blood culture, and inflammatory markers to guide management.
    • Not all febrile infants in the 22-28 day subset need an LP, though it should still be obtained in certain clinical circumstances, and discussed between  provider and parents in other situations
  • In infants ≤28 days, a complete workup is still needed even if a viral source is present.
  • Febrile infants 29-60 days old may be sent home after a negative workup with close follow-up.

References:

    1. Roberts KB. Young, febrile infants: a 30-year odyssey ends where it started. JAMA. 2004 Mar 10;291(10):1261-2. PMID: 15010450.
    2. Biondi EA, Lee B, Ralston SL, et al. Prevalence of Bacteremia and Bacterial Meningitis in Febrile Neonates and Infants in the Second Month of Life: A Systematic Review and Meta-analysis.JAMA Network Open. 2019 Mar; 2(3). PMID: 30901044.
    3. Baker MD, Avner JR, Bell LM. Failure of infant observation scales in detecting serious illness in febrile, 4- to 8-week old infants. Pediatrics. 1990;85(6):1040–1043. PMID: 2339027
    4. Pantell RH, Roberts KB, Adams WG, et al. Clinical Practice Guideline: Evaluation and Management of Well Appearing Febrile Infants 8 to 60 Days Old. Pediatrics. 2021;148(2):e2021052228. PMID: 34281996
    5. Kuppermann N, Dayan PS, Levine DA, et al. A Clinical Prediction Rule to Identify Febrile Infants 60 Days and Younger at Low Risk for Serious Bacterial Infections. JAMA Pediatr. 2019;173(4):342-351. PMID: 30776077
    6. Gomez B, Mintegi S, Bressan S, et al. Validation of the “Step-by-Step” approach in the management of young febrile infants. The Journal of Pediatrics. 2016 Aug; 138(2):e20154381. PMID: 27382134
    7. Nguyen THP, Young BR, Poggel LE, et al. Roseville Protocol for the Management of Febrile Infants 7-60 Days. Hosp Pediatr. 2020 Dec 17:hpeds.2020-0187. PMID: 33334815
    8. Shaikh N, Morone NE, Bost JE, Farrell MH. Prevalence of urinary tract infection in childhood: a meta-analysis. Pediatr Infect Dis J. 2008;27(4):302-308. PMID: 18316994
    9. Coyle C, Brock G, Wallihan R, Leonard JC. Cost Analysis of Emergency Department Criteria for Evaluation of Febrile Infants Ages 29 to 90 Days. J Pediatr. 2021 Apr;231:94-101.e2. doi: 10.1016/j.jpeds.2020.10.033. Epub 2020 Oct 31. PMID:33130155.

    Milcent K, Faesch S, Gras-Le Guen C, et al. Use of Procalcitonin Assays to Predict Serious Bacterial Infection in Young Febrile Infants [published correction appears in JAMA Pediatr. 2016 Jun 1;170(6):624].JAMA Pediatr. 2016;170(1):62-69. doi:10.1001/jamapediatrics.2015.3210 PMID: 26595253

By |2023-04-09T20:40:05-07:00Mar 29, 2023|Expert Peer Reviewed (Clinical), Infectious Disease, Pediatrics, PEM Pearls|
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SAEM Clinical Images Series: A Rare Cause of Post-traumatic Neck Pain

neck pain

A 15-year-old male presents to the pediatric Emergency Department (ED) for evaluation of neck pain for three weeks. The patient is vague as to the development of his symptoms, but his mother reveals patient was assaulted by peers three weeks ago and has had progressively worsening neck pain and stiffness. The patient states symptoms have gotten to the point where he is unable to turn his head but denies fevers, chills, nausea, vomiting, focal weakness, or sensory changes.

Vitals: Temp: 99.4°F; HR 80; RR 18; SpO2 98% on room air

Constitutional: No distress, sitting rigidly in bed.

Neck: Cervical midline tenderness noted with rigid neck and severe tenderness with manipulation, no swelling, erythema, or masses noted.

HEENT: No pharyngeal injection, no visible masses in the oropharynx, no trismus.

CV: Regular rate and rhythm, no murmurs, rubs, or gallops. Good peripheral perfusion.

Abdomen: Soft, non-distended and non-tender.

Neuro: 5/5 motor function to the bilateral upper and lower extremities, normal sensory examination, cranial nerves intact. Negative Kernig’s sign.

White blood cell (WBC) count: 9.5

Platelets: 639

Glucose: 105

CRP: 128

ESR: 100

CSF: Color- Clear; Nucleated Cells- 1; Protein- 25; Glucose- 6

This patient was found to have septic arthritis of the atlantooccipital (AO) joint, noted on the CT shown above, with joint space narrowing and erosion (red arrow) of the right AO joint with associated soft tissue swelling and effusion. Seen on the MRI is further confirmation of the findings suggested on CT of septic arthritis, with additional noting of attenuation of the prevertebral space of C2/C3 suggestive of phlegmon, bilateral AO joint arthritis, and involvement of the atlantoaxial joint, all of which can be seen on the above sagittal cut of the MRI, with the most notable being the pre-vertebral phlegmon (red arrow).

Septic arthritis of the facet joints is a rarity, particularly in pediatrics and in the cervical spine; case reports largely describe a lumbar location in elderly adults with predisposing comorbidities (intravenous drug use, diabetes, immunosuppression) for spontaneous infection. There are no published case reports of traumatic, pediatric AO joint septic arthritis. This patient developed septic arthritis following trauma. As with peripheral septic arthritis, the most common cause is hematogenous spread, and even non-penetrating trauma can predispose a joint to infection as likely occurred in this case. Septic arthritis of the facet joints presents similarly to spondylodiscitis, generally with fever, neck or back pain, and elevated inflammatory markers such as CRP/ESR. If left untreated, it can be a dangerous and refractory cause of sepsis that leads to deadly complications such as concomitant epidural access formation. Oftentimes patients are initially misdiagnosed and re-present multiple times as the preferred image modality for diagnosis is MRI which is not always readily available or ordered. In general, treatment generally includes weeks-long courses of intravenous (IV) antibiotics, though this patient was discharged on oral antibiotics after significant symptomatic improvement on IV therapy after four days.

Take-Home Points

  • Septic arthritis of the cervical facet joints, namely the AO joint, is a rare cause of neck pain in patients with fever and elevated inflammatory markers, and can present after trauma. Generally, it is hematogenously spread and associated with comorbidities such as diabetes, intravenous drug use, and immunosuppression, it should be considered in patients with refractory symptoms or in which there is strong suspicion as it can have dangerous complications.
  • The preferred imaging modality for diagnosis is MRI, though CT can be useful in making the diagnosis radiographically. Treatment generally consists of weeks of IV antibiotics.

  • Sethi S, Vithayathil MK. Cervical facet joint septic arthritis: a real pain in the neck. BMJ Case Rep. 2017 Aug 3;2017:bcr2016218510. doi: 10.1136/bcr-2016-218510. PMID: 28775081; PMCID: PMC5612571.
  • Narváez J, Nolla JM, Narváez JA, Martinez-Carnicero L, De Lama E, Gómez-Vaquero C, Murillo O, Valverde J, Ariza J. Spontaneous pyogenic facet joint infection. Semin Arthritis Rheum. 2006 Apr;35(5):272-83. doi: 10.1016/j.semarthrit.2005.09.003. PMID: 16616150.

Copyright

Images and cases from the Society of Academic Emergency Medicine (SAEM) Clinical Images Exhibit at the 2021 SAEM Annual Meeting | Copyrighted by SAEM 2021 – all rights reserved. View other cases from this Clinical Image Series on ALiEM.

By |2023-02-25T21:14:43-08:00Feb 27, 2023|Infectious Disease, Pediatrics, SAEM Clinical Images, Trauma|
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SAEM Clinical Images Series: A Rash You Don’t Want to Miss

rash

A 54-year-old female with a past medical history of diabetes presented to the Emergency Department (ED) for evaluation of unresponsiveness. The patient was found unresponsive by her spouse, who notes she had missed several doses of insulin over the past few days. EMS notes the glucometer read ‘HIGH’ on fingerstick. The patient remains unresponsive on presentation and is unable to contribute further history.

Vital Signs: BP 148/105; HR 120; RR 24; Pulse Oximetry 98% on room air; Temperature 97.7°F

Constitutional: Patient is morbidly obese, unresponsive, and toxic-appearing.

Cardiovascular: Regular rhythm with tachycardia. No murmur.

Pulmonary: Pulmonary effort is normal. Lungs clear to auscultation bilaterally.

Abdomen: Abdomen is soft and non-distended. Unable to assess for tenderness given unresponsiveness.

Skin: Cool, pale, mottled. Large gangrenous, draining, foul-smelling wound on proximal left thigh. There is necrotic, malodorous, black skin noted over the left lower abdomen and left upper thigh.

Neurological: Unresponsive. GCS 3.

White blood cell (WBC) count: 20.5

Comprehensive metabolic panel (CMP): K 5.8; Cr 2.06; BUN 86; Glucose >600

Venous blood gas (VBG): pH<7; lactate 3.4; bicarbonate 7

These photographs show advanced Fournier’s Gangrene, a form of necrotizing fasciitis located in the genitals, perineum, or perianal region. Rapid involvement of our surgical colleagues is crucial, as these patients will not recover without the debridement of affected tissues. Aggressive fluid resuscitation and broad-spectrum antibiotics can be initiated after a surgical consult is made.

This patient presented with impressive visual evidence of advanced disease including severe ecchymosis, but our clinical suspicion must be high as Fournier’s is rapidly progressing and carries a high mortality rate (may be upwards of 30%). Earlier symptoms are genital or perineal pain which may be associated with itching, lethargy, or fever. The biggest exam finding to keep in mind is ‘pain out of proportion to the exam’ as up to 40% of these patients may present without localized symptoms. Advanced disease, as seen in this patient, can present with crepitus and severe ecchymosis of tissue involved. This patient was also found to be in DKA, as evidenced by her laboratory findings. This case should serve as a reminder that it is vital to perform a proper skin examination in patients presenting with hyperglycemia. Ultimately in this case, the patient was intubated for airway protection and started on vasopressors for cardiovascular support in the setting of septic shock. She went into VTach arrest and was successfully defibrillated before further decompensating and becoming asystolic.

Take-Home Points

  • The first task after suspected diagnosis of Fournier’s Gangrene is a page to your surgery service for evaluation and emergent debridement in the OR (depending on your institution this may be general surgery, urology, or both). After your patient is on the path to definitive management, you can begin aggressive fluid administration and broad-spectrum antibiotics (gram-positive, gram-negative, and anaerobic coverage needed).
  • Fournier’s Gangrene is a clinical diagnosis. Imaging may assist in atypical or borderline cases, but should never result in delay of surgical evaluation and treatment. Crepitus and ecchymotic tissue are very late findings; have high clinical suspicion inpatients with signs of swelling, erythema, and pain.

  • Shyam DC, Rapsang AG. Fournier’s gangrene. Surgeon. 2013 Aug;11(4):222-32. doi: 10.1016/j.surge.2013.02.001. Epub 2013 Apr 8. PMID: 23578806.
  • Ustin JS, Malangoni MA. Necrotizing soft-tissue infections. Crit Care Med. 2011 Sep;39(9):2156-62. doi: 10.1097/CCM.0b013e31821cb246. Erratum in: Crit Care Med. 2011 Nov;39(11):2592. Dosage error in article text. PMID: 21532474.
  • Harbrecht BG, Nash NA. Necrotizing Soft Tissue Infections: A Review. Surg Infect (Larchmt). 2016 Oct;17(5):503-9. doi: 10.1089/sur.2016.049. Epub 2016 Aug 2. PMID: 27483003.
  • Singh A, Ahmed K, Aydin A, Khan MS, Dasgupta P. Fournier’s gangrene. A clinical review. Arch Ital Urol Androl. 2016 Oct 5;88(3):157-164. doi: 10.4081/aiua.2016.3.157. PMID: 27711086.
  • Sarani B, Strong M, Pascual J, Schwab CW. Necrotizing fasciitis: current concepts and review of the literature. J Am Coll Surg. 2009 Feb;208(2):279-88. doi: 10.1016/j.jamcollsurg.2008.10.032. Epub 2008 Dec 12. PMID: 19228540.
  • Tintinalli JE, Ma O, Yealy DM, Meckler GD, Stapczynski J, Cline DM, Thomas SH. eds. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 9e. McGraw Hill; 2020. p.592- 593.

Copyright

Images and cases from the Society of Academic Emergency Medicine (SAEM) Clinical Images Exhibit at the 2021 SAEM Annual Meeting | Copyrighted by SAEM 2021 – all rights reserved. View other cases from this Clinical Image Series on ALiEM.

By |2022-11-06T10:25:45-08:00Nov 28, 2022|Dermatology, Infectious Disease, SAEM Clinical Images|
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SAEM Clinical Image Series: Eye Pain

necrotizing

A 59-year-old gentleman experiencing homelessness with a history of hepatocellular carcinoma, hepatitis C, alcohol use disorder, and tobacco dependence presented to the emergency department (ED) with severe, worsening right eye pain, blurry vision, swelling, redness, and purulent discharge after scraping his upper face on concrete during a mechanical fall two weeks prior. Of note, his partner presented to the ED at the same time with a necrotic infection of the breast as well as multiple skin lesions reportedly due to insect bites.

Vitals: T 102.4°F; HR 108; BP 121/94

Head: Lice nits visible in his hair

Eye: Unable to open right eye without assistance; eyelids crusted and necrotic with underlying orbicularis oculi muscle visible; EOM full but painful in all fields of gaze; visual acuity 20/60 in each eye; pupils 2 mm, equal and minimally reactive.

White blood cell (WBC) count: 27,600/μl

Comprehensive metabolic panel (CMP): Na 121; K 2.8; Cl 83; AST 113; ALT 45

Wound culture: Positive for MRSA, Streptococcus pyogenes, Enterobacter cloacae, and Staphyloccocus epidermis

This patient’s presentation is consistent with periorbital necrotizing fasciitis complicated by severe sepsis.

This patient had type 1 necrotizing fasciitis given the polymicrobial source of infection with both aerobic and anaerobic organisms growing from his wound culture. Type 2 necrotizing fasciitis is attributable to streptococcal and/or staphylococcal infection alone. Group A strep is the most common organism responsible for necrotizing fasciitis, found in about 50% of cases.

Independent risk factors for necrotizing fasciitis include advanced age, diabetes mellitus, heart disease, liver cirrhosis, alcohol use disorder, and trauma. Furthermore, persons who experience homelessness are at risk of skin lesions due to insect bites, burns, and physical trauma which predispose them to secondary bacterial infections because of inadequate hygiene resources.

A systematic review of periorbital necrotizing fasciitis showed that 35% of cases were triggered by trauma, while 14% were caused by other infections such as acute dacryocystitis, sinus infections, and infections of the parotid glands.  Thus, it is likely that the patient’s contact with his partner who had a necrotic soft tissue infection secondary to insect bites, as well as his recent trauma to the eye, predisposed his development of this condition.

Initiation of broad-spectrum intravenous (IV) antibiotics with vancomycin, piperacillin/tazobactam, and clindamycin, as well as IV fluids.

In this case, the patient received the above antibiotics, underwent operative debridement, frequent wound care including dilute hypochlorous acid, local vancomycin administered via intra-orbital catheter, as well as lid reconstruction with glabellar flap. He was ultimately discharged on a two-week course of oral moxifloxacin and linezolid, healing well at his one-month follow-up appointment.

 

Take-Home Points

  • Skin problems are a common reason that persons experiencing homelessness seek medical care, given their risk factors for both primary insults and subsequent superinfection.
  • Common sources of infection for periorbital necrotizing fasciitis include trauma, surgery, and other infections of the upper face.
  • The standard of care for periorbital necrotizing fasciitis consists of IV and local antibiotics, and operative debridement.

  • Amrith S, Hosdurga Pai V, Ling WW. Periorbital necrotizing fasciitis — a review. Acta Ophthalmol. 2013 Nov;91(7):596-603. doi: 10.1111/j.1755-3768.2012.02420.x. Epub 2012 Apr 20. PMID: 22520175.

Copyright

Images and cases from the Society of Academic Emergency Medicine (SAEM) Clinical Images Exhibit at the 2021 SAEM Annual Meeting | Copyrighted by SAEM 2021 – all rights reserved. View other cases from this Clinical Image Series on ALiEM.

 

By |2022-01-19T13:59:38-08:00Jan 31, 2022|Dermatology, Infectious Disease, Ophthalmology, SAEM Clinical Images|
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Oral Antivirals for Treatment of Mild-Moderate COVID-19 Infection

Background

Two new oral agents were given Emergency Use Authorization to be used in patients with mild-moderate COVID-19 at high risk of progression to severe infection, molnupiravir and nirmatrelvir/ritonavir (Paxlovid) [1,2]. Prior to this authorization, most evidence-based COVID therapies were parenteral and required significant healthcare resources to coordinate and administer.

Comparison

Nirmatrelvir/ritonavir [3]Molnupiravir [4]
Mechanism

Protease inhibitor leadings to interruption of viral replication

Ritonavir has no role in treating COVID-19, it is only included to boost levels of nirmatrelvir via CYP3A4 inhibition

Increased frequency of RNA mutations and impaired replication [5]
Efficacy vs Placebo (Hospitalization or Death)0.8% vs 6.3% (CI -7.21 to -4.03)6.8% vs 9.7% (CI -5.9 to -0.1)
Drug InteractionsCYP3A4 inducers, inhibitors, and substrates

May decrease efficacy of hormonal contraceptives, non-hormonal contraceptives should be considered

Contraindicated medications include: amiodarone, carbamazepine, clozapine, colchicine, dihydroergotamine, dronedarone, flecainide, lovastatin, ranolazine, sildenafil, simvastatin

Many other important interactions exist so care should be taken to assess all medication interactions

N/A
Cost*Patient: $0

US government: $530 [6]

Patient: $0

US Government: $700 [7]

Dose300 mg/100 mg BID for 5 days

Must be started within 5 days of symptom onset

800 mg BID for 5 days

Must be started within 5 days of symptom onset

NotesApproved for patients ≥ 12 years old AND ≥ 40 kg

Not approved for inpatient initiation

If patient is hospitalized, continuation is up to the discretion of the provider

Not used as pre-/post-exposure prophylaxis

Approved for patients ≥ 18 years

Not approved for inpatient initiation

If patient is hospitalized, continuation is up to the discretion of the provider

Not used as pre-/post-exposure prophylaxis

Renal/Hepatic Dose AdjustmentseGFR  ≥30 to <60 mL/min: 150 mg/100 mg BID

eGFR <30 mL/min: Not recommended

Child-Pugh class C: Not recommended

None

*Note: The US federal government has purchased 10 million doses of nirmatrelvir/ritonavir and 3 million doses of molnupiravir [8,9]. These supplies will be allocated to states and territories as needed and will be available to patients at no charge. 

Evidence:

Nirmatrelvir/ritonavir (Paxlovid)

Paxlovid was evaluated in the EPIC-HR trial, which is not fully published at this time [3]. This was a phase 2/3, double-blinded, randomized placebo controlled trial including nonhospitalized, unvaccinated patients adults with mild-moderate COVID-19 within 5 days of symptom onset with at least 1 risk factor† for development of severe illness from COVID-19. Exclusion criteria included patients with a history of COVID-19 infection or COVID vaccination. Patients were given Paxlovid 300 mg/100 mg or placebo BID for 5 days. The primary outcome was hospitalization or death at day 28. The modified intention-to-treat1 (mITT1) group excluded patients who did not receive nor were expected to receive COVID-19 mAb treatment. In the mITT1 group, the primary outcome occurred in 0.8% of patients receiving Paxlovid vs 6.3% of patients in the placebo group (8/1039 vs 66/1046, CI -7.21 to -4.03).

These results appear quite robust with a fragility index of 37. Additionally, in patients with detectable COVID antibodies there was less of an impact of the study medication. However, these patients still appeared to have some benefit (0.2% vs 1.5%, CI -2.45 to -0.23) which suggests that vaccinated patients may still benefit from Paxlovid.

†Risk factors for progression to severe disease: BMI >25, chronic lung disease, asthma, chronic kidney disease, current smoker, immunosuppressive disease or immunosuppressive treatment, cardiovascular disease, hypertension, sickle cell disease, neurodevelopmental disorders, active cancer, medically-related technological dependence, or age >60 years

Molnupiravir 

Molnupiravir was evaluated in the MOVe-OUT trial [10]. This was a phase 3, double-blinded, randomized, placebo controlled trial including nonhospitalized, unvaccinated adults with mild-moderate COVID-19 within 5 days of symptom onset with at least 1 risk factor‡ for development of severe illness from COVID-19. Exclusion criteria included anticipated hospitalization within 48 hours, eGFR <30 or dialysis dependent, pregnancy, and COVID vaccination. Patients were able to receive steroids but not monoclonal antibodies (mAbs) nor remdesivir. Patients were given molnupiravir 800 mg or placebo BID for 5 days. The primary outcome was hospitalization or death at 29 days. In the mITT population, the primary outcome occurred in 6.8% of patients in the study group vs 9.7% in the placebo group (48/709 vs 68/699, CI -5.9 to -0.1). Death occurred in 1 patient on molnupiravir and in 9 patients on placebo (0.1% vs 1.3%, RRR 89%, CI 14 to 99).

Despite the above results, this may not be the positive trial it initially appears. First of all, for the primary outcome, the fragility index is 0, meaning that if 1 more patient in the study group experienced the primary outcome then it would have changed the statistical significance. Additionally, when the mITT analysis was adjusted for sex, the absolute risk reduction remained 2.8% but the confidence interval was not significant (-5.7 to 0.1). Lastly, in the subgroup analysis, there was no benefit in patients that had positive COVID antibody tests and there was a slight preference towards placebo over molnupiravir (3.7% vs 1.4%, ARR 2.3, CI -1.7 to 7.1). This suggests that vaccinated patients may not benefit from this therapy as much (or at all) as compared to unvaccinated patients.

‡Risk factors for progression to severe disease: age >60 years, active cancer, chronic kidney disease, COPD, BMI ≥30, heart failure, coronary artery disease, cardiomyopathy, or diabetes mellitus

Note: Both the EPIC-HR and MOVe-OUT studies were funded by their respective pharmaceutical company.

Bottom Line:

  • Nirmatrelvir/ritonavir (Paxlovid) and molnupiravir are approved under FDA EUAs for patients with mild-moderate COVID infection at high risk of severe disease within 5 days of symptom onset
  • Both medications appear to reduce death or hospitalization within a month, with most benefit likely to be experienced by unvaccinated patients
  • Nirmatrelvir/ritonavir (Paxlovid) appears to be more effective but also has many more drug interactions and contraindications

Want to learn more about EM Pharmacology?

Read other articles in the EM Pharm Pearls Series and find previous pearls on the PharmERToxguy site.

References:

  1. O’Shaughenessy J. Food and Drug Administration. Molnupiravir Emergency Use Authorization 108. December 23, 2021. https://www.fda.gov/media/155053/download
  2. O’Shaughenessy J. Food and Drug Administration. Nirmatrelvir/ritonavir Emergency Use Authorization 105. December 22, 2021. https://www.fda.gov/media/155049/download
  3. Nirmatrelvir/ritonavir. Package insert. Pfizer, Inc. 2021. https://www.fda.gov/media/155050/download
  4. Molnupiravir. Package insert. Merck Sharp & Dohme Corp. 2021. https://www.merck.com/eua/molnupiravir-hcp-fact-sheet.pdf
  5. Kabinger F, Stiller C, Schmitzová J, et al. Mechanism of molnupiravir-induced SARS-CoV-2 mutagenesis. Nat Struct Mol Biol. 2021;28(9):740-746. doi: 10.1038/s41594-021-00651-0. PMID: 34381216.
  6. Mishra M. U.S. to buy 10 mln courses of Pfizer’s COVID-19 pill for $5.3 bln. Reuters. Accessed January 12, 2022. https://www.reuters.com/business/healthcare-pharmaceuticals/us-govt-buy-10-mln-courses-pfizers-covid-19-pill-529-bln-2021-11-18/
  7. Willyard C. How antiviral pill molnupiravir shot ahead in the COVID drug hunt. Nature. Published online October 8, 2021. doi: 10.1038/d41586-021-02783-1. PMID: 34625735.
  8. Paxlovid (nirmatrelvir/PF-07321332 and ritonavir). U.S. Department of Health & Human Services: Office of the Assistant Secretary of Preparedness and Response. Updated: January 12, 2022. Accessed January 12, 2022. https://www.phe.gov/emergency/events/COVID19/investigation-MCM/Paxlovid/Pages/default.aspx
  9. Molnupiravir (MK-4482). U.S. Department of Health & Human Services: Office of the Assistant Secretary of Preparedness and Response. Updated: January 12, 2022. Accessed January 12, 2022. https://www.phe.gov/emergency/events/COVID19/investigation-MCM/molnupiravir/Pages/default.aspx
  10. Jayk Bernal A, Gomes da Silva MM, Musungaie DB, et al. Molnupiravir for oral treatment of covid-19 in nonhospitalized patients. N Engl J Med. Published online December 16, 2021. doi: 10.1056/NEJMoa2116044. PMID: 34914868.
By |2022-01-15T19:00:38-08:00Jan 15, 2022|EM Pharmacy Pearls, Infectious Disease, Tox & Medications|
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