MICRO-ORGANISMS IN PHARMACEUTICAL AND COSMETIC PREPARATIONS 419 Bacteria present in liquid soaps and hand creams used by members of the hospital staff may be a serious source of danger to patients. In an epidemic of septicaemia due to Klebsiella in patients with intravenous catheters (20), the causative strain was found in the communal hand cream used by the staff. Ingestion Salmonellae are the only intestinal pathogens known to have been acquired by the ingestion of oral medicaments, and gastro-enteritis has followed the administration of thyroid tablets (10) and of capsules of carmine (21, 22). In the latter case, the infecting dose appears to have been about 30 000 salmonellae, but the infection rate was not recorded. Sal- monella (including typhoid) and dysentery infection may be conveyed from one patient to another in barium enema fluids by reflux of faecal matter into the reservoir (23). Recent evidence suggests that the presence in liquid medicines for oral use of other Gram-negative bacilli such as Ps. aeruginosa may also be undesirable, even though they do not cause intestinal disease. Septic infections with Ps. aeruginosa in general hospital wards are usually sporadic, and many of them appear to be auto-infections with bacteria from the patient's own bowel (24, 25). Hospital patients have much higher carrier- rates of this organism than do healthy persons outside hospital, and acquire many new strains during their stay in hospital (25). In studies of the faecal acquisition of Ps. aeruginosa at St Bartholomew's Hospital, London (26), strains appeared seldom to be acquired by 'contact' from other patients or from environmental sources in the ward. On a number of occasions they could be traced to the food, but on one occasion they were found in a medicament for oral use, peppermint water. Four patients were known to have received this, and one became colonized the medicine contained at most 14x 10 a organisms ml -•. This might not have been considered of importance had the Public Health Laboratory Service Working Party not also found Ps. aeruginosa in 15 of 33 samples of peppermint water from a number of different hospitals, and in a number of other aqueous mixtures (27). Buck and Cooke (28) found that the ingestion of at least 106 Ps. aeru- ginosa is necessary for intestinal colonization of normal persons, and that colonization is transient unless an antibiotic is given at the same time see also (29).

420 JOURNAL OF TIlE SOCIETY OF COSMETIC CHEMISTS POTENTIALLY PATHOGENIC BACTERIA FOUND IN PHARMACEUTICAL PRODUCTS Organisms that contaminate medicaments and cause disease to patients are nearly all Gram-negative bacilli. One of them, Salmonella, is an 'absolute' pathogen, which causes clinical infection in healthy persons when given by a natural route. It causes a diarrhoeal disease, but outbreaks attributed to pharmaceutical products have been relatively infrequent. The main source of salmonellae is infected vertebrate animals, and it is therefore not surprising that medicaments of animal origin, such as thyroid extract, should occasionally be contaminated with them. The reason why carmine should contain salmonellae is less clear, particularly since the same serotype (Salm. cubana) was isolated from cochineal insects from both Peru and the Canary Islands, and from dye manufactured in several countries (21, 22). The evidence that arthropods have an independent role in the epidemiology of salmonella infection has been summarized by -Wilson and Miles (30). Salmonellae have also been isolated repeatedly from natural products of wholly vegetable origin, presumably as a result of contamination from an animal source, and outbreaks of infection in hospital patients have followed the feeding of dietary supplements of brewer's yeast and cotton-seed protein (31, 32). It is clear, therefore, that salmonellae might be introduced into medicines in any organic natural product. The rest of the organisms found in medicines that cause disease are 'conditional pathogens', that is to say, they are harmless to completely healthy adults unless injected into the tissues or into normally sterile areas of the body such as the bladder, but may cause serious disease in the very young and in persons who are susceptible because of pre-existing disease. But only some of the conditionally pathogenic Gram-negative bacteria are found frequently as contaminants in pharmaceutical products. These are mainly 'free-living' types that do not form part of the normal body flora (Fig. 1). Enterobacteria that are found in the normal bowel, such as Escherichia coli, Proteus spp., and possibly some of the klebsiellas, may cause disease but have a limited ability to survive and multiply outside the body. They are seldom found in medicines. Other enterobacteria, notably members of the enterobacter and serratia groups, and some of the klebsiellas, are almost entirely free-living, are less often found in the normal body flora, and appear as contaminants in a wide range of fluids in hospital.