Thirty to fifty percent of hospitalize patients receive intravenous therapy which requires the preparation and handling of the medicine before administration to the patient.1 Parenteral medications are usually given out in single- and multiple-dose vials (SDVs and MDVs). A SDV is a vial of liquid medication intended for parenteral administration (injection or infusion) that is meant for use in a single patient for a single case/procedure/injection.2 A MDV is a vial of liquid medication intended for parenteral administration (injection or infusion) that contains more than one dose of medication. MDVs should be dedicated to a single patient whenever possible.3

The revised version of United States Pharmacopeia (USP) Chapter 797 is a comprehensive document that describes standards and procedures to minimize the risk of contamination of compounded parenteral products. The chapter includes evidence-based instructions for pharmacy design, washing, garbing, cleaning, quality assurance, and personnel training and evaluation designed to improve compounding practices in all pharmacies that compound parenteral products.4 However, sterile compounding procedures vary widely across the countries. In our country the majority of the reconstitution of injectable drugs is carried out right before the administration to the patient by the nursing staff. Prevalence of bacterial contamination of SDVs which were used more than once has been reported 5.6% in one of Iranian hospitals.5 Fungal contamination of SDVs and microbial contamination of vials containing preservative were not examined in this report. The information regarding extrinsic microbial contamination of injectable drugs and potentially serious adverse events is slight in our country and still no measure has been taken to improve standards for intravenous therapy. We designed this study to understand the prevalence of contaminations of intravenous medications in our hospital and to design future intervention which could be made by infection control staff to prevent the contaminations of the injectable drugs.

A total of 205 vials (165 SDVs and 40 MDVs) were tested from 18 wards and units, with 29 medication types. Table 1 shows sampled medications from different wards/units. All vials were being used within their expiration period, and no vial had expired. No statistical difference was observed between contamination rate and the number of days that the vials were opened. A total of 115 (56.10%) vials were kept at room temperature, the rest at 4°C.

Bacterial contamination was identified in 11 of 205 (5.36%) of vials. Contamination rate for SDVs and MDVs were 4.85% and 7.50% respectively. There was no significant difference in the frequency of contamination of different type of vials. Contaminations were found in three internal wards, emergency ward, Intensive Care Unit (ICU), transplant unit, and interventional bronchoscopy unit. The highest contamination rate was 14.28% (2/14) for vials used for interventional bronchoscopy unit and the lowest was 4.54% (1/22) for vials used for one of the internal wards which named as internal ward 3.

The most frequent contaminated solution was insulin NPH 100U/mL. No mixed contamination was detected in any of vials. Gram-positive and gram-negative bacteria were involved in 9 (81.82%) and 1 (9.09%) of contaminations, respectively. Fungal contamination was detected in one sample (9.09%). Therefore, gram-positive bacteria were more significantly involved (p<0.05) in vial contaminations. Most commonly identified microorganisms were part of the normal commensally flora with the highest frequency for Staphylococcus epidermidis (4/11 or 36.36%). Table 2 shows the distribution of contaminated vials in different wards/units of the hospital along with the contaminating microorganism and the characteristics of the vials.

Six (54.54%) of contaminated vials were not marked with patient's name, which indicated that they were probably used for more than one patient.

Our data show a contamination rate of 5.36% with bacteria and fungi, in the content of the SDVs and MDVs used in different wards/units of a pulmonary teaching hospital in Iran. In principle, preparation, storage and transportation of Compounded Sterile Preparations (CSPs) require aseptic conditions and trained personnel. USP Chapter 797 is a comprehensive document that describes standards and procedures to minimize the risk contamination of CSPs.6 But standards for CSPs in developing countries may be limited by lack of resources (trained personnel and facilities). Non-standard preparation and handling of vials (which are assumed to be sterile) result in contamination rates, ranging from 0% to 27%.7

SDVs are preservative free vials which are intended to be used only once. Puncturing SDVs multiple times and pooling preservative free solutions may cause the potential contamination risk, possibly leading to severe infections in patients.8,9 In the current study 165 of 205 vials (80.49%) were SDVs that were used as multiple-dose vials. This finding is more than reported percentage of 50% in the literature.10,11

On the other hand MDVs contain antibacterial preservatives and may be used more than once when preparation and storage is according to the manufacturer's recommendations. (e.g., insulin, some heparin, lignocaine and octeotride products).8 If MDVs must be used for more than one patient, they should not be kept or accessed in the immediate patient treatment area. This is to prevent inadvertent contamination of the vial through direct or indirect contact with potentially contaminated surfaces or equipment that could then lead to infections in next patients. If a MDVs enters the immediate patient treatment area, it should be dedicated to that patient only and discarded after use.3

It must be noticed that a preservative does not prevent non-bacterial and non-fungal contaminations (e.g., viral, protozoa, and prion pathogens) and does not prevent growth of microorganisms in low temperature.7 MDVs remain prone to bacterial contamination and the use of them has been reported to be a potential source of infections in different studies.12–17 Our study also shows that microorganisms can survive in the presence of a preservative as 3 of the contaminated vials were insulin. The sterility of multidose insulin vials was determined up to 50 days by Rathod et al. They showed bacterial contaminations in 8 of 69 insulin vials and concluded that antibacterial preservatives were more effective at room temperature than at refrigerator temperature.18 Other study by Jackson et al. verified that prefilled insulin syringes remained sterile for up to one month after preparation when they were prepared using good aseptic technique and stored in the patient's refrigerator.19

The sterility of a CSP is directly related to employment of the best practice and quality standards. Safe preparation and handling of CPSs within a properly operating unidirectional airflow in an ISO class 5 clean room in accordance with USP chapter 797 requirements is the best way to avoid bacterial or fungal contamination.20,21 The standardization then the centralization of the preparations and reconstitution of CPSs by infection prevention and control experts makes it possible to reduce contamination risk related to injectable drugs.22 Although the requirements of USP chapter 797 may appear complicated, expensive, and even unattainable in developing countries, the first step to establish quality standards could be made through training of health care workers according to recommendations from CDC and WHO.23,24 The most applied recommendations include dating MDVs after opening and discarding them on the manufacture's dates, discarding SDVs after opening, and emphasizing the need for proper aseptic technique. Simple aseptic techniques that could be implemented in each hospital setting may be summarizes as: performing hand hygiene before preparing medications for administration; using gloves, face mask, and avoidance of talking during an injection;25 wiping the outsides of vials with 70% isopropyl alcohol swabs before opening and aspirating the contents of vials using a 5p.m. filter straw26; and considering practical guidelines for lipid based emulsions that supports bacterial growth such as propofol.27 Moreover reconstitution of high risk level intravenous treatments by a centralized hospital pharmacy service under sterile conditions is the next measure to reduce both infection risk and cost due to discarding expensive vials.

In conclusion infection preventionists in developing countries should improve sterile compounding of injectable products in a hospital. Although implementation of the guidelines from professional pharmacy organizations, such as the American Society of Health-System Pharmacists (ASHP) and the National Association of Boards of Pharmacy (NABP) guarantees patient safety, understanding the problems and limitations in a hospital is essential to develop a regional standard procedure.

There is no conflict of interest that should be disclosed by the authors.