Factors Determining the outcome of a Medicament-Borne Infection

FACTORS  DETERMINING  THE  OUTCOME  OF A  MEDICAMENT-BORNE  INFECTION

Although impossible to quantify, the use of contaminated medicines has undoubtedly contributed to the spread of cross-infection in hospitals; undeniably, such nosocomial (hospital-acquired) infections have also extended the length of stay in hospital with concomitant costs. A patient’s response to the microbial challenge of a contaminated medicine may be diverse and unpredictable, perhaps with serious consequences. Clinical reactions may not be evident in one patient, yet in another may be indisputable, illustrating one problem in the recognition of medicament-borne infections. Clinical reactions may range from inconvenient local infections of wounds or broken skin, caused possibly from contact with a contaminated cream, to gastrointestinal infections from the ingestion of contaminated oral products, to serious widespread infections such as a bacteraemia or septicaemia, possibly resulting in death, as caused by the administration of contaminated infusion fluids. Undoubtedly, the most serious outbreaks of infection have been seen in the past where contaminated products have been injected directly into the bloodstream of patients whose immunity is already compromised by their underlying disease or therapy.

The outcome of any episode is determined by a combination of several factors, among which the type and degree of microbial contamination, the route of administration and the patient’s resistance are of particular importance.

A) Type And Degree Of Microbial Contamination

Microorganisms that contaminate medicines and cause disease in patients may be classified as true pathogens or opportunist pathogens. Pathogenic organisms like Clostridium tetani and Salmonella spp. rarely occur in products, but when present cause serious problems. Wound infections and several cases of neonatal death have resulted from use of talcum powder containing Cl. tetani. Outbreaks of salmonellosis have followed the inadvertent ingestion of contaminated thyroid and pancreatic powders. On the other hand, opportunist pathogens like Ps. aeruginosa, Klebsiella, Serratia and other free-living organisms are more frequently isolated from medicinal products and, as their name suggests, may be pathogenic if given the opportunity. The main concern with these organisms is that their simple nutritional requirements enable them to survive in a wide range of pharmaceuticals, and thus they tend to be present in high numbers, perhaps in excess of 10⁶–10⁷ CFU/g or CFU/ml. The product itself, however, may show no visible sign of contamination. Opportunist pathogens can survive in disinfectants and antiseptic solutions that are normally used in the control of hospital cross-infection, but which, when contaminated, may even perpetuate the spread of infection. Compromised hospital patients, i.e. elderly, burned, traumatized or immunosuppressed patients, are considered to be particularly at risk from infection with these organisms, whereas healthy patients in the general community have given little cause for concern.

The critical dose of microorganisms that will initiate an infection is largely unknown and varies not only between species but also within a species. Animal and human volunteer studies have indicated that the infecting dose may be reduced significantly in the presence of trauma or foreign bodies or if accompanied by a drug having a local vasoconstrictive action.

B)                       Route Of Administration

As stated previously, contaminated products injected directly into the bloodstream or instilled into the eye cause the most serious problems. Intrathecal and epidural injections are potentially hazardous procedures. In practice, epidural injections are frequently given through a bacterial filter. Injectable and ophthalmic solutions are often simple solutions and provide Gram-negative opportunist pathogens with sufficient nutrients to multiply during storage; if contaminated, a bioburden of 10⁶ CFU as well as the production of endotoxins should be expected. TPN fluids, formulated for individual patients’ nutritional requirements, can also provide more than adequate nutritional support for invading contaminants. Ps. aeruginosa, the notorious contaminant of eye drops, has caused serious ophthalmic infections, including the loss of sight in some cases. The problem is compounded when the eye is damaged through the improper use of contact lenses or scratched by fingernails or cosmetic applicators.

The fate of contaminants ingested orally in medicines may be determined by several factors, as is seen with contaminated food. The acidity of the stomach may provide a successful barrier, depending on whether the medicine is taken on an empty or full stomach and also on the gastric emptying time. Contaminants in topical products may cause little harm when deposited on intact skin. Not only does the skin itself provide an excellent mechanical barrier, but few contaminants normally survive in competition with its resident microbial flora. Skin damaged during surgery or trauma or in patients with burns or pressure sores may, however, be rapidly colonized and subsequently infected by opportunist pathogens. Patients treated with topical steroids are also prone to local infections, particularly if contaminated steroid drugs are inadvertently used.

C)                        Resistance Of The Patient

A patient’s resistance is crucial in determining the outcome of a medicament-borne infection. Hospital patients are more exposed and susceptible to infection than those treated in the general community. Neonates, elderly people, diabetics and patients traumatized by surgery or accident may have impaired defence mechanisms. People suffering from leukaemia and those treated with immunosuppressants are most vulnerable to infection; there is an undeniable case for providing all medicines in a sterile form for these patients.