February 21, 2015

Clinical Vignette 22

A middle-aged woman with newly diagnosed autoimmune hepatitis on high-dose prednisolone (50 mg daily) presented acutely with 3 days of fever with headache, followed by an acute change in mental state a day before hospitalisation. Clinically, she was slightly drowsy (GCS = 12) and disoriented, with neck stiffness and photophobia. The urgent non-contrast CT head was normal, and her white blood cell count (WBC) was elevated at 21,000/ml of blood (mostly neutrophils). She was prescribed intravenous vancomycin, ceftriaxone, ampicillin and acyclovir, and lumbar puncture was performed 3 hours after arrival at the hospital (we don’t have the efficiency of many developed countries in this respect, where lumbar punctures are often performed down at the emergency department!). This showed cerebral spinal fluid (CSF) pleocytosis with 880 WBC/ml of CSF – mostly lymphocytes.

The next day, the Microbiology Laboratory reported the growth of a Gram-positive rod from the anaerobic blood culture bottle.

Question 1: What is the likely cause of her infection?

Question 2: What antimicrobial agents would you recommend for the treatment of the infection?

[Updated 28th February 2015]

In this context, given the immunosuppression, clinical presentation of meningo-encephalitis, and the presence of Gram-positive rods from the anaerobic bottle, the patient very likely (and actually did) have Listeria monocytogenes bacteraemia with meningo-encephalitis.

During my training, the recommended treatment for this condition was a combination of high-dose ampicillin with gentamicin. Indeed, certain respectable guidebooks, such as the John Hopkins Antibiotics Guide, still recommends combination therapy. However, recent modest-sized  case series from Spain – one published in the Journal of Antimicrobial Chemotherapy in 2009, and a second in BMC Infectious Diseases in 2011, both suggest that the addition of gentamicin was at best associated with no difference in outcomes and at worst with increased mortality. This seems to be in line with many recent works on the efficacy of combination antibiotic therapy in various other severe bacterial infections.

Personally, I would no longer advocate the addition of gentamicin to ampicillin for the treatment of this condition, particularly in adults.

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Clinical vignette, Infectious diseases, Public Health


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