Pharmaceutical Importance of the Major Categories of Microorganisms

PHARMACEUTICAL IMPORTANCE OF THE MAJOR CATEGORIES OF MICROORGANISMS

Table 2.4 indicates the ways in which the different types of microorganism are considered relevant in pharmacy. The importance of viruses derives exclusively from their pathogenic potential, and because of their lack of intrinsic metabolism they are not susceptible to antibiotics. Partly for these reasons, viral infections are among the most dangerous and difficult to cure, and of all the categories of microorganism, only viruses appear in (the most serious) Hazard Category 4 as classified by the Advisory Committee on Dangerous Pathogens. Because they are not free living, viruses are incapable of growing on manufactured medicines or raw materials, so they do not cause product spoilage, and they have no synthetic capabilities that can be exploited in medicines manufacture. Viruses are relatively easy to destroy by heat, radiation or toxic chemicals, so they do not represent a problem from this perspective. In this, they contrast with prions; although some authorities would question the categorization of these infectious agents as microorganisms, they are included here because of their undoubted ability to cause, as yet incurable, fatal disease, and their extreme resistance to lethal agents. Pharmacists and healthcare personnel in general should be aware of the ability of prions to easily withstand sterilizing conditions that would be satisfactory for the destruction of all other categories of infectious agent.

There are examples of bacteria that are important in each of the different ways indicated by the column headings of Table 2.4. Many of the medically and pharmaceutically important bacteria are pathogens, and some of these pathogens are of longstanding notoriety as a result of their ability to resist the activity of antibiotics and biocides (disinfectants, antiseptics and preservatives). In addition to these long-established resistant organisms, other bacteria have given more recent cause for concern including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VSE) and multiply resistant Mycobacterium tuberculosis. While penicillin and cephalosporin antibiotics are produced by fungal species, the majority of the other categories of clinically important antibiotics are produced by species of bacteria, notably streptomycetes. In addition, a variety of bacteria are exploited commercially in the manufacture of other medicines including steroids, enzymes and carbohydrates. The ability of bacteria to grow on diverse substrates ensures that their potential as agents of spoilage in manufactured medicines and raw materials is well recognized, and the ability of many species to survive drying means that they survive well in dust and so become important as contaminants of manufactured medicines. The ability to survive not only in dry conditions but in other adverse environments (heat, radiation, toxic chemicals) is well exemplified by bacterial spores, and their pre-eminence at or near the top of the ‘league table’ of resistance to lethal agents has resulted in spores acting as the indicator organisms that have to be eliminated in most sterilization processes .

Like bacteria, fungi are able to form spores that survive drying, so they too arise commonly as contaminants of manufactured medicines. However, the degree of resistance presented by the spores is usually less than that exhibited by bacteria, and fungi do not represent a sterilization problem. Fungi do not generally create a significant infection hazard either; relatively few fungal species are considered major pathogens for animals that possess a fully functional immune system. There are, however, several fungi which, while representing little threat to immuno-competent individuals, are nevertheless capable of initiating an infection in persons with impaired immune function; the term ‘opportunist pathogens’ is used to describe microorganisms (of all types) possessing this characteristic. In this context it is worth noting that the immune-comopromised represent an increasingly large group of patients, and this is not just because of HIV/AIDS. Several other conditions or drug treatments impair immune function, e.g. congenital immunodeficiency, cancer (particularly leukaemia), radiotherapy and chemotherapy, the use of systemic corticosteroids and immunosuppressive drugs (often following tissue or organ transplants), severe burns and malnutrition.

Protozoa are of significance largely owing to the pathogenic potential of a few species. Because protozoa do not possess cell walls they do not survive drying well (unless in the form of cysts), so they are not a problem in the manufacturing environment—and even the encysted forms do not display resistance to sterilizing processes to match that of bacterial spores. It should be noted that protozoal infections are not currently a major problem to human health in temperate climates, although they are more troublesome in veterinary medicine and in the tropics. There are concerns that the geographical ranges of protozoal infections such as malaria may extend substantially if current fears about global warming translate into reality.