aka Microbial Mystery 004
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.
Q1. Would you continue the ceftriaxone or change to another antibiotic? Is this a trick question?
Stop ceftriaxone and change to another antibiotic.
Although the organism is sensitive to ceftriaxone it belongs to the ESCAPPM group of gram-negative bacteria:
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?
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)
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
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.
- 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.