Contamination of non-sterile pharmaceuticals in hospitals

and community environments

Pharmaceutical Microbiology 2, Lecture 2

Dr. Mohammad Abu Sini

Al-Zaytoonah University of Jordan
mohammad.abusini@zuj.edu.jo

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 The significance of microbial contamination

• Outbreaks of medicament- related infections had been reported since the early part of
the 20th century, but it was only in the 1960s and 1970s that the significance of this
contamination to the patient was more fully understood.

• Even disinfectants, antiseptics and other products are known to be at risk, especially
products with more nutritious components such as carbohydrates, amino acids,
vitamins and enough water.

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 Hazard to health
• The majority of infections caused by medications are probably not recognized or reported.

• Once the doctors recognize an infection caused by contaminated medicament, there is a

moral obligation to withdraw the offending product, with subsequent retrospective
investigations of the incident.

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 Source and control of contamination
• In manufactures: Quality must be built of the product at all stages of the process and not
assessed at the end of manufacture:

1. Raw materials like water and those of animal origin must be of a high microbiological
standard.

2. All processing equipments should be cleaned after use to prevent cross-contamination.

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 Source and control of contamination
3. Manufacture should take place in suitable premises, supplied with filtered air (the
environmental requirements vary according to the type of product being made.)

4. Staff should have good health and have knowledge of the importance of personal and
production hygiene.

5. Suitable packaging of the end product to protect it from contamination during its shelf-life.

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 Hospital manufacture….Water
• Water for pharmaceutical manufacture requires some further treatment, usually by
distillation, reverse osmosis or deionization, or a combination of these depending on
the intended use of water.

• Water should be stored at temperature in excess of 80°C and circulated in the

distribution system at a flow rate of 1 – 2 m / sec to prevent the build-up of bacterial
biofilms in the piping.

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 Hospital manufacture….Environment
• Free living opportunist pathogens, such as Ps. aeruginosa can be found in all wet sites,
such as drains, sinks and taps.

• Cleaning equipment, such as mops, buckets, cloths etc. may be responsible for
distributing these organisms around the pharmacy. If stored wet, they provide a
convenient niche for microbial growth resulting in heavy contamination.

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 Hospital manufacture….Environment

• Good manufacturing practices (GMP) require, for example:

1. Installing heating traps in sink U-bends

2. Proper maintenance and storage of equipment, including cleaning equipment.

3. Cleaning of production units by contractors based on pharmaceutical specifications.

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 Hospital manufacture….Packaging
• Storage and organizers such as cardboard and card liners are unsuitable for packaging
pharmaceuticals, as they are heavily contaminated with bacterial or fungal spores. These
have now been replaced by non-biodegradable plastic materials.

• Reusable containers must be thoroughly washed and dried, and never refilled directly.

• Repackaging of products purchased in bulk into smaller containers will increase handling,
hence increases the risk of contamination twice as often as those in the original pack.

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 In Use.. Human sources
• All multi-dose products are subject to contamination from a number of source uses, no
matter whether products are used in hospital or in the community.

• During normal usage, the patient may contaminate his / her medicine with his / her own
microbial flora.

• Topical products are more at risk since the product will probably be applied by hand thus
introducing contaminants from the resident skin flora.

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 In Use.. Human sources
• Zinc-based products used in the treatment and prevention of bed-sores in long-
stay and geriatric patients may become contaminated during use .

• Nursing staff should wash their hands between attendings to patients to prevent
the transfer of contaminants to medicaments during administration.

• It is important to raise the level of awareness on cross-contamination among staff

and the general public through widespread publicity and the provision of easily
accessible hand disinfection stations on the wards.
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 In Use ….. Environmental sources
• Few airborne contaminants may settle in products left open to the atmosphere. Some
airborne contaminants will die during storage with the rest probably remain at a static level
of about 100 – 1000 colony forming units (CFU) per gram or per millilitre.

• Water-borne contaminants may be accidentally introduced into hospital products by wet

hands and the level of contamination may exceed one million CFU/ gm or/ ml.

• The problem is compounded by stocks kept in multi-dose pots for use by several patients
in the same ward over an extended period of time.
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 In Use …. Equipment sources
• Patients and nursing staff may use applicators (pads, sponges, brushes, spatulas) during
medication administration, particularly for topical products.

• Disposable applicators or swabs could always be used.

• Complex equipment used in the course of patient treatment such as humidifiers, incubators,
ventilators, resuscitators should be decontaminated with chemical disinfectants.

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 The extent of microbial contamination
A. Contamination in manufacture:
• A wide range of products was found to be contaminated with Staphylococcus albus,
Bacillus subtilis, yeasts and molds, in addition E.coli was found in a variety of tablets.

• The famous Swedish outbreak: many patients were infected with Salmonella caused by
contaminated thyroid tablets. Other patients had severe eye infections following the use
of hydrocortisone eye ointment contaminated with Ps. Aeruginosa.

• In the UK, removal of Crown immunity from the NHS in 1991 meant that manufacturing
operations in hospitals were then subject to the full licensing provisions of the Medicines
Act 1968, and to comply fully with the EC Guide to GMP.

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 The extent of microbial contamination
B. Contamination in use:

• In hospitals, higher rates of contamination are seen in products after opening and use.

• Medicines in hospitals are more likely to be contaminated than those in the general
community.

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Factors determining the outcome of a medicament-
borne infection
• A patient ’s response to the microbial challenge of a contaminated medicine may be
diverse and unpredictable, perhaps with serious consequences. Clinical reactions may
range from:
1. Inconvenient local infections of wounds or broken skin caused from contact with a
contaminated cream….

2. To gastrointestinal infections from the ingestion of contaminated oral products….

3. Even to serious widespread infections such as bacteremia or septicemia, leading

sometimes to death.

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 Type and degree of microbial contamination

• Microorganisms that contaminate medicines and cause disease in patients may be

classified as true pathogens or opportunistic pathogens.

• Pathogenic bacteria like Clostridium tetani and Salmonella spp. rarely occur in products,
but when present it will cause serious problems.

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Type and degree of microbial contamination

• Wound infections from using contaminated dusting powders have been reported including
several cases of neonatal death from talcum powder containing Cl. tetani.

• Opportunistic pathogens such as Ps. aeruginosa, Klebsiella, Serratia ..etc. survive in a wide
range of pharmaceutical products and may present in high numbers (106 to 107 CFU/gm or/ml)
with no sign of visible contamination.

• Compromised hospital patients, i.e. elderly, burned, traumatized or immunosuppressed

patients, are considered to be particularly at risk from infection with opportunistic pathogens.

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 The route of administration
• Contaminated products injected directly into the bloodstream or instilled into the eyes
cause the most serious problems.

• Injectable and ophthalmic solutions are simple solutions to be contaminated with

gram negative opportunist pathogens, where their numbers might exceed 106 CFU.

• Intrathecal and epidural injections are frequently given through a bacterial filter.

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 Resistance of the patient
• Hospital patients are more exposed and susceptible than those treated in general community.

• Neonates, the elderly, diabetics and patients traumatized by surgery or accident may have
impaired defense mechanisms.

• All medicines given to people with leukemia and those treated with immunosuppressive
agents should be sterile.

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