416 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS INTRODUCTION Almost everything that we know about the ill effects on patients of receiving pharmaceutical preparations that are contaminated with micro- organisms has been learned from hospital practice, and without doubt it is in hospitals that most of the trouble is seen. This is not surprising, because patients often come to hospital with pre-exisfing diseases that make them particularly susceptible to infection, and in hospital many of them are necessarily subjected to procedures--diagnostic, surgical and pharma- cological-that further increase this susceptibility and some of these procedures expose the patient to specific hazards from contaminated preparations. The chance that such a complication would be recognized and attributed to the contaminated product is greater in hospital than outside but even in hospitals an isolated infection from a medicament is relatively difficult to detect, and the fact that a number of patients in the same hospital often have received the same preparation greatly increases the chance of recognizing ill effects due to it. Therefore, although there is little information about illness attributable to contaminated medicines in general practice, we should be wrong to assume that it does not occur. Even less is known about the significance for the user of microbially contaminated cosmetic preparations. Cosmetics are applied mainly to the normal skin of healthy persons, and there is little reason to believe that the common microbial contaminants would cause disease in these circum- stances. If used by members of the general community who have a pre- existing skin disease, the ill effects if any would be very difficult to attribute to the preparation. Certain cosmetic preparations--notably hand creams and lotions--find their way into hospitals, and their microbial state then becomes a matter for serious concern. CO•qSEQUENCaS OF ^DMINISTm•NO CO•qT^MIN^TED MEDIC^MENTS BY V^RIOUS ROUTES Whether infection occurs, and the form it takes, depends very much on the route of administration, the dose of organisms, and the class of person to whom the contaminated preparation is administered. Injection Organisms may be implanted directly into the tissue by injection. Unless there is pre-existing disease of the heart valves, or a foreign body in the circulatory system, the intravenous injection of small numbers of most organisms is without ill effect. Serious consequences therefore mainly

MICRO-ORGANISMS IN PHARMACEUTICAL AND COSMETIC PREPARATIONS 417 follow I he intravenous injection of fluids in which organisms have multiplied before injection and the organisms are nearly always Gram-negative bacilli, including members of the pseudomonas, ldebsiella, enterobacter and serratia groups. The same serious clinical consequences--bacteraemic shock and generalized septic infection--occur in all classes of patient and with most of the Gram-negative bacilli, but Flavobacterium meningosepticum, which causes severe and usually fatal infection in newborn infants when applied to the body surface, causes only a short episode of fever when given intravenously to adults in enormous doses (1). The resistance of the meninges to small numbers of organisms is believed to be significantly lower than that of the bloodstream, but in practice meningitis following the intraspinal injection of contaminated fluids--now fortunately uncommon--is usually also attributable to Gram- negative bacteria that can multiply in the fluids. On the other hand, sepsis following subcutaneous or intramuscular injection may be due to a much wider variety of organisms, including Staphylococcus aureus, haemolytic streptococci and the clostridia. With the possible exception of the haemolytic streptococci, the minimum infective dose of these organisms on injection into absolutely healthy tissues is generally high, but if the contaminated medicament has a necrotic or vaso- constrictive action only a minute dose of organisms is necessary for infection. Infections following subcutaneous or intramuscular injection are nowadays rarely caused by organisms present in the preparation, and more often by contamination with organisms from the injector or the skin of the patient. Solutions that contain Gram-negative bacteria in large numbers usually cause only local inflammation on subcutaneous injection unless the recipient has a greatly lowered general resistance to infection. Implantation into wounds and normally sterile areas o.f the body surface Again, most of the infections attributable to medicaments are due to Gram-negative bacilli. Infection of wounds and secondary infection of pre-existing skin lesions with organisms present in creams and lotions have been described by Noble and Savin (2), and by Bassett, Stokes and Thomas (3), but it was sometimes difficult to assess the ill effect on the patients. Contaminated fluids used for irrigation of the bladder have caused out- breaks of urinary-tract infection (4, 5). Respiratory infection with Gram- negative bacteria more often results from the contamination of apparatus than of medicaments, but Mertz, Scharer and McClement (6) described an