What are disadvantages of ampicillin and chloramphenicol in the treatment of Haemophilus influenzae type b (Hib) meningitis?

Updated: Jul 09, 2018
  • Author: Prateek Lohia, MD, MHA; Chief Editor: Niranjan N Singh, MBBS, MD, DM, FAHS, FAANEM  more...
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Answer

Previously, ampicillin and chloramphenicol were recommended for the treatment of Hib meningitis. However, resistance to both these antibiotics has emerged. Specifically, strains of Hib produce beta-lactamase and others are resistant through reduced affinity for penicillin-binding proteins. Hib resistance to ampicillin may be found in beta-lactamase negative strains that have shown increasing prevalence in the past few years in Japan and elsewhere.

Alarmingly, some of these strains are also demonstrating resistance to cefotaxime and ceftriaxone. In situations where such beta-lactamase negative/ceftriaxone-resistant Hib strains are encountered, high-dose ceftriaxone (150 mg/kg/d) may be the treatment of choice. [22]

Resistance to chloramphenicol is mediated through bacterial elaboration of chloramphenicol acetyltransferase, which is found in more than half of all Hib isolates from children in some countries.

The emergence of resistant strains of Hib has been especially troublesome in developing nations, where the availability and cost of newer antibiotics may prevent patients infected with these strains from being effectively treated. Between 1994 and 2002, a Kenyan hospital noted that resistance susceptibilities to various antibiotics for H influenzae isolates were amoxicillin (66%), chloramphenicol (66%), and TMP-sulfa (38%). Most of this resistance was found in the Hib strains. [23]

In addition to the growing problem of resistance, chloramphenicol has other disadvantages. Toxic effects (eg, bone marrow suppression, diminished myocardial contractility) render it less desirable for use in children. Myocardial toxicity is more likely to arise in individuals in shock, which may be the case in fulminant Hib sepsis/meningitis.

Serum chloramphenicol levels must be monitored because of the considerable individual variation in pharmacokinetics. In addition, chloramphenicol has several interactions with drugs that are commonly used in the setting of meningitis. Coadministration with phenytoin may increase chloramphenicol concentration, and chloramphenicol may affect serum levels of phenytoin. Coadministration with phenobarbital may decrease chloramphenicol concentration.

These kinds of interactions do not arise with third-generation cephalosporins, whose pharmacokinetic reliability eliminates the necessity for monitoring of antimicrobial levels.


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