Information for Physicians

Disinfection and sterilization are the most effective measures to prevent health care-associated infections (HAI). Evidence-based recommendations which are strongly supported by well-designed experimental, clinical or epidemiological studies are categorized as Category IA in the CDC system. The use of sterile critical medical and surgical devices and instruments that enter normally sterile tissue or the vascular system is categorized as IA. A sterile item must be free from all living microorganisms. In practice this state is achieved if the probability of a living microorganism being present on an item is equal to or less than 1:1,000,000 (sterility assurance level, SAL). Safety standards such as the SAL can be met using the probability function of microbial inactivation of the sterilization process. However the verification of the benefit of sterile products which correspond to the quality level of SAL is beyond the statistical limits which are approximately accessible in epidemiological or clinical studies (see CDC, 2008: “SAL was strictly arbitrary and not associated with any adverse outcomes (e.g., patient infections)”). High standards such as the SAL are applied in health care systems where maximum of health protection should be guaranteed. Further examples of strict standards are laid down in the EU-drinking water regulation (COUNCIL DIRECTIVE 98/83/EC of 3 November 1998). It states the limit for pesticides, (e.g. insecticides or herbicides) despite their toxicological profile, at 0.1 µg per L, it corresponds to a pesticide-free water quality. The advantages of values such as the SAL or the drinking water limits of pesticides lie in the fact that prevention is guaranteed as far as possible and not restricted by statistical limits which are given in experimental or clinical studies.
 

When airborne microbes can penetrate the barrier of medical packaging, the minimum infective dose of the heterogeneous microbiological species is the one key factor for possible consequences, because a rather small number of entering microbes can be expected. The minimum infective dose is dependent on the susceptibility of the host (e.g. age, health status) the virulence of the pathogen and the route of exposure. It can range from one to millions of microorganisms. For example, the lowest infective dose of M. tuberculosis may be less than 10 bacilli (ID50 <10). Because the most typical airborne microorganisms such as fungi or aerobic bacilli, e.g., Bacillus subtilis, are organisms of low virulence, further specific circumstances must be present to increase the risk of serious health care-associated infections.
 

Gunaratne et al. (2006) associate the recontamination of 43 of 679 disposable plastic syringes with Aspergillus fumigatus with sub-optimal storage conditions during the 6 months after the tsunami in Sri Lanka. They concluded that the use of the syringes with these storage conditions was one of the most likely causes for Aspergillus fumigatus meningitis in 5 women. The infections followed spinal anaesthesia for caesarean section in two hospitals. Patients with intramuscular and intravenous injections didn’t show any Aspergillus infection. The specific type of administration and entry into an area of low immunological resistance was an additional condition for the observed infections.     
 

It must also be kept in mind that a single airborne microbial cell can be the starting point for an outbreak of hospital acquired infections if they are enabled to multiply and if the contaminated stock solution is used for a batch of hundreds or thousands single doses. Outbreaks of this type are frequently traced back to microbes which are not commonly known for patient to patient transmissions in hospitals.
 

Kainer et al. (2012) described a fungal (Exserohilum rostratum) meningitis outbreak in a clinic (clinic A) where vials of contaminated methylprednisolone were administered that were prepared by a single compounding pharmacy. Mostly epidural injections were applied, 58 of 656 patients who were treated with methylprednisolone developed infections. A significant increase of the infection rate was found for patients who received older vials (vial age >50 days) compared with those who were treated with more recent vials. This indicates that fungal growth was present in the vials during the storage at room temperature and that high microbial doses caused the infections.
 

A HAI outbreak or a single HAI followed by transmission of pathogens through sterilized products when it was compromised by a small hole in the packaging or by ingress of microbes through the porous packaging material can not be traced back easily to this recontamination because other routes of transmission have to be considered and can not be ruled out as causative factors. The attainment of the product’s sterility at the SAL of 1:1,000,000 at the point of use must be verified by suitable methods such as the consideration of the filtration efficiency and the estimation of recontamination by airborne microbes during storage and transport (see also: Dunkelberg H. Maintenance of Sterility: Base of Aseptic Procedures. Dtsch Arztebl Int 2016;113:737).

References
Gunaratne PS, Wijeyaratne CN, Chandrasiri P, et al. An outbreak of Aspergillus meningitis following spinal anaesthesia for caesarean section in Sri Lanka: a post-tsunami effect? Ceylon Med. J.2006;51:137-142
Kainer MA, Reagan DR, Nguyen DB, et al. Fungal infections associated with contaminated methylprednisolone in Tennessee. N Engl J Med 2012;367:2194-203