Systemic antibiotic prophylaxis is part of the regimen for selective decontamination of the digestive tract (SDD) used for infection prevention in intensive care. It is given to prevent infections by potentially pathogenic microorganisms which are present in the oropharynx or gastrointestinal tract upon admission to the intensive care unit, i.e. primary endogenous infections. The topical non-absorbable antibiotics are given to prevent secondary endogenous infections. Exogenous infections are prevented by the conventional hygienic measures. An antibiotic used for systemic prophylaxis should have a spectrum covering both community-acquired microorganisms (e.g. pneumococci) and hospital-acquired potentially pathogenic microorganisms, without affecting the indigenous flora. Furthermore, the penetration in bronchial secretions should be adequate and the incidence of side effects should be low. Cefotaxime being one of the few antibiotics which meet all these criteria has therefore been used in most SDD trials. The duration of systemic prophylaxis has been determined empirically and can generally be confined to the first four days. Emergence of resistance against cefotaxime is rare due to the combination with topical nonabsorbable antibiotics.