Antibacterial Agents

PENICILLINS, CEPHALOSPORINS, AND IMIPENEM

Historically, radiculitis, paraplegia, hemiplegia, and convulsions occurred after penicillin was administered into the CSF, but because this route of administration has been abandoned, such reactions are exceedingly rare. The neurotoxic clinical manifestations of penicillins, cephalosporins, and imipenem include myoclonus, seizures, confusion, hallucinations, encephalopathy, nystagmus, and agitation. Imipenem, cefazolin, and benzyl penicillin are the most epileptogenic. '31' These drugs antagonize the inhibitory neurotransmitter GABA. Risk factors for neurotoxicity are high-dose intravenous use (e.g., greater than 30 to 40 million units of benzyl penicillin per day), decreased renal function, abnormal blood-brain barrier, cardiopulmonary bypass, age more than 50 years, pre-existing disease of the CNS, concurrent use of drugs that may lower the seizure threshold (such as theophylline or ciprofloxacin), and concomitant use of nephrotoxic drugs. Blockade of a system for transporting the beta lactams out of the CSF in diseases causing meningeal inflammation adds to the risk of increased meningeal antibiotic penetration during inflammation.

Penicillin gluteal injection may cause sudden and irreversible paraplegia. The actual incidence of such a complication is not known, but there have been eight cases reported in the literature. The proposed mechanism is accidental injection intra-arterially, causing distal spasm and the upstream ascent of penicillin with ensuing embolic or spastic occlusion, or both, of the anterior spinal artery. Treatment of this complication is unsatisfactory, but it can be prevented by giving injections in the lateral thighy

Penicillins and cephalosporins have also been reported to cause recurrent aseptic meningitis. y Ampicillin has been reported to aggravate weakness in myasthenia gravis. Intrathecal beta lactams have the potential to cause adhesive arachnoiditis. '31]

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