MICRO-ORGANISMS IN PHARMACEUTICAL AND COSMETIC PREPARATIONS 423 The flee-living Gram-negative organisms are so metabolically diverse that it may be only a matter of time before one will appear that is able to multiply in the chosen bacteriostat. CONTAMINATED MEDICAMENTS THAT ARE OF CLINICAL SIGNIFICANCE Solutions for injection Multiple-dose containers are now seldom used in Great Britain, and serious trouble from the injection of fluids in single-dose containers is fortunately rare. It would be wrong to assume, however, that it never occurs, or that when it does it is easily detected. Between October 1970 and March 1971, there were some 350 cases of bacteraemia in hospitals in the United States, caused by two different 'free-living' enterobacteria but all associated with the intravenous injection of fluids from a single commercial source (44, 45). The organisms had multiplied on the outer surface of the synthetic cap liner, and were introduced into the body of the fluid only by manipulation of the cap. The association of these cases with the contamin- ated product appears not to have been recognized for some months, and in a number of hospitals was established only by retrospective investigation. A much smaller outbreak due to intravenously administered glucose saline occured in Britain in 1966, but no account of it has been published. In this case also, bottles of fluid were contaminated with several different enterobacterial strains, but the organisms were in the fluid itself, and in numbers insufficient to cause turbidity. Liquid medicines and topical applications This subject is discussed in detail by Hooper (27). A general improve- ment in the bacterial quality of liquid medicines is a desirable objective, and would remove one--though probably not the most important--of the sources from which hospital patients become colonized with Ps. aeruginosa. If Hooper's conclusions are correct, and the main source of contamina- tion is the pharmacy water and the aqueous stock solutions, this should be relatively easy to achieve. It would have the additional advantage of removing a potential source of cross-contamination of other fluids, notably disinfectants and lotions, made up in the pharmacy.

424 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS Skin-care preparations These substances fall into an important 'grey area' between the pharma- ceutical and cosmetic fields, and have hitherto been somewhat neglected. The two main areas of danger are the fluids and creams applied to the hands of staff during and after washing, and those used for the skin care of newborn infants. Hand creams from non-pharmaceutical sources may be used in hospitals. In the U.S.A., frequent and heavy contamination was found in previously unopened containers of four of 26 brands sampled (46). Ayliffe, Barrowcliff and Lowbury (47) found that 22 of 67 communal jars of hand cream in use in British hospital wards were contaminated, seven with Ps. aeruginosa and six with Klebsiella. Many of the fluids and creams used on the skin in hospitals contain antibacterial substances, such as hexachlorophane and chloroxylenols, which have poor activity against Gram-negative bacilli, with which they often become contaminated either in bulk or during use in the wards (47-49). Disinfectants A revolution in the handling of disinfectants has taken place in recent years, and it is now common practice for them to be issued at use dilution from the pharmacy. Several instances of the mass contamination of hospital supplies of disinfectants with Gram-negative rods have been recorded (3, 42, 50). For a summary of outbreaks of sepsis spread by disinfectant solutions see Bassett (51). CONCLUSION The most urgent clinical problems arising from the contamination of pharmaceutical products, and of cosmetic products used in the medical field, are caused by the multiplication of 'free-living' types of Gram- negative bacteria. That this happens so often is attributable to failure to recognize the ability of the organisms to multiply in fluids apparently devoid of nutrient, and the remarkable ability of some of them to resist the activity of commonly used bacteriostatic and disinfectant substances. Some of this contamination may occur in the pharmacy, and un- doubtedly much more is added in the course of re-use of preparations in the