Escaping bugs

aka Microbial Mystery 005

A 13 year-old female presented to the emergency department looking unwell and septic. She was started on ceftriaxone IV. A diagnosis of pyelonephritis was subsequently made, with no evidence of obstruction on ultrasound.

You are notified by the microbiology lab that her urine culture results are consistent with a urinary tract infection, with a pure culture of Enterobacter cloacae that is sensitive to ceftriaxone.


Questions

Q1. Would you continue the ceftriaxone or change to another antibiotic? Is this a trick question?

Answer and interpretation

Stop ceftriaxone and change to another antibiotic.

and

No.


Q2. Why?

Answer and interpretation

Although the organism is sensitive to ceftriaxone it belongs to the ESCAPPM group of gram-negative bacteria:

  • Enterobacter
  • Serratia
  • Citrobacter
  • Acinetobacter or Aeromonas (depending on which reference you use!)
  • Proteus
  • Providentia
  • Morganella

These bacteria like to throw a sucker punch by being sensitive to ceftriaxone on the initial culture and sensitivity report (they are all Enterobacteriaceae except Acinetobacter).  They all share a chromosomally-encoded cephalosporinase (a type of beta-lactamase) that is inducible. Thus they tend to develop cephalosporin resistance during treatment.

The cephalosporinase enzyme is not inhibited by beta-lactamase inhibitors like clavulinic acid.

Finally, for the uber-technical, the enzyme is an AmpC β-lactamase (Ambler molecular class C, Bush-Jacoby-Medeiros functional group 1). Other species may have similar resistance genes derived from this enzyme but carried on plasmids (e.g. E. coli and Klebsiella spp.).


Q3. What are the appropriate initial antibiotics for severe pyelonephritis?

Answer and interpretation

In Australia the suggested initial antibiotic choice is:

gentamicin 4 to 6 mg/kg (child <10 years: 7.5 mg/kg; ≥10 years: 6 mg/kg) IV, daily (adjust dose for renal function)

and

amoxicillin 2g (child: 50 mg/kg up to 2 g) IV, 6-hourly

In the event of penicillin allergy, gentamicin alone is generally sufficient. In patients for whom gentamicin is inappropriate, third generation cephalosporins are the second-line empiric treatment:

ceftriaxone 1 g (child: 25 mg/kg up to 1 g) IV, daily

or

cefotaxime 1 g (child: 25 mg/kg up to 1 g) IV, q8h

but this does not provide adequate treatment for Enterococcus infections.

Antibiotics should continue for 10-14 days and be guided by culture and sensitivities (but remember the ESCAPPM caveat!). A follow up urine culture following the completion of treatment should be performed.


References
  • Antibiotic Therapeutic Guidelines (2010) [website]
  • Mandell GL, Bennet JE, Dolan R. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, 7th ed (2009), Churcill Livingstone. [mdconsult.com]
  • Venkatesh B, et al. Data Interpretation in Critical Care Medicine (2003), Butterworth Heinemann.

Microbial Mystery LITFL FB 700 2

CLINICAL CASES

Microbial Mystery

Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also the Innovation Lead for the Australian Centre for Health Innovation at Alfred Health and Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of two amazing children.

On Twitter, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

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