Reduction of Contamination with Antibiotics on Surfaces and in Environmental Air in Three European Hospitals Following Implementation of a Closed-System Drug Transfer Device.

PURPOSE: Occupational exposure of nurses to antibiotics may result in adverse health effects such as hypersensitivity, allergic reactions, resistance, and anaphylactic shock. The purpose of this study was to measure surface and air contamination with antibiotics in three hospitals during the preparation of the drugs using conventional techniques or using the Tevadaptor® closed-system drug transfer device (CSTD). METHODS: Surface contamination was measured by taking wipe samples. Stationary air samples were collected in preparation areas and personal air samples were collected in the working environment of the nurses. Contamination was reassessed after several weeks following implementation of the CSTD. Surface contamination was compared before and after CSTD introduction. Vancomycin, meronem, augmentin, ceftriaxone, cefotaxime, piperacillin, and benzylpenicillin were monitored. Wipe and air samples were analyzed using liquid chromatographytandem mass spectrometry (LC-MS/MS). RESULTS: Using conventional preparation techniques, widespread contamination with antibiotics up to 767 ng cm-2 was detected. After implementation of the CSTD, contamination levels significantly decreased for the most frequently prepared antibiotics in the three hospitals.Using the conventional preparation technique, three antibiotics were detected in environmental air of seven nurses in two hospitals (0.01-5 µg m-3), and one antibiotic was found in environmental air above a preparation surface (0.02 µg m-3). After implementation of the CSTD, the same antibiotic was detected in environmental air above the same preparation surface (1.39 µg m-3) but no antibiotics were detected in environmental air of the nurses in the three hospitals. CONCLUSIONS: Using the conventional preparation techniques, surfaces and air were widely contaminated with antibiotics whereas the use of the CSTD significantly reduced contamination. Systematic use of a CSTD significantly reduces exposure to hazardous antibiotics and consequently reduces potential adverse health effects for healthcare providers.

Environmental contamination, product contamination and workers exposure using a robotic system for antineoplastic drug preparation.

Environmental contamination, product contamination and technicians exposure were measured following preparation of iv bags with cyclophosphamide using the robotic system CytoCare. Wipe samples were taken inside CytoCare, in the clean room environment, from vials, and prepared iv bags including ports and analysed for contamination with cyclophosphamide. Contamination with cyclophosphamide was also measured in environmental air and on the technicians hands and gloves used for handling the drugs. Exposure of the technicians to cyclophosphamide was measured by analysis of cyclophosphamide in urine. Contamination with cyclophosphamide was mainly observed inside CytoCare, before preparation, after preparation and after daily routine cleaning. Contamination outside CytoCare was incidentally found. All vials with reconstituted cyclophosphamide entering CytoCare were contaminated on the outside but vials with powdered cyclophosphamide were not contaminated on the outside. Contaminated bags entering CytoCare were also contaminated after preparation but non-contaminated bags were not contaminated after preparation. Cyclophosphamide was detected on the ports of all prepared bags. Almost all outer pairs of gloves used for preparation and daily routine cleaning were contaminated with cyclophosphamide. Cyclophosphamide was not found on the inner pairs of gloves and on the hands of the technicians. Cyclophosphamide was not detected in the stationary and personal air samples and in the urine samples of the technicians. CytoCare enables the preparation of cyclophosphamide with low levels of environmental contamination and product contamination and no measurable exposure of the technicians.

Hazardous drug residue on exterior vial surfaces: evaluation of a commercial manufacturing process.

PURPOSE: Hazardous drug residue on the exterior surface of drug vials poses a potential risk for exposure of health care workers involved in handling these products. The purpose of this article is to heighten the awareness of this serious issue and to evaluate a commercial manufacturing process for removing and containing hazardous drug (HD) residue on exterior vial surfaces. Additionally, findings from this study are interpreted, incorporated into the current body of evidence, and discussed by experts in this field. METHODS: This study includes separate evaluations for the presence or absence of surface drug contamination on the vials of 3 HD products: 5-fluorouracil, cisplatin, and methotrexate. The drug products were packaged in vials using a patented prewashing/decontamination method, application of a polyvinylchloride (PVC) base, and use of clear glass vials. An additional step of encasing the vial in a shrink-wrapped sheath was used for 5-fluorouracil and cisplatin. RESULTS: Of all 5-fluorouracil (110 vials), methotrexate (60 vials), and cisplatin (60 vials) tested, only 2 had detectable amounts of surface residue. One 5-fluorouracil vial was found to have approximately 4 mg of 5-fluorouracil on the surface of the vial. The second contaminated vial was cisplatin, which was discovered to have 131 ng of platinum, equal to 200 ng of cisplatin or 0.2 µL of cisplatin solution, on the vial sheath. CONCLUSION: Using validated extraction and analytic methods, all but 2 of the 230 tested vials were found to be free of surface drug contamination. Pharmacy leaders need to take an active role in promoting the need for clean HD vials. Manufacturers should be required to provide their clients with data derived from externally validated analytic studies, reporting the level of HD contamination on the exterior of their vial products.

Use of a closed system drug-transfer device eliminates surface contamination with antineoplastic agents.

PURPOSE: To evaluate the effectiveness of a closed system drug-transfer device, EquaShield®, at reducing surface contamination with antineoplastic agents throughout an ambulatory cancer chemotherapy infusion center. METHODS: Surfaces throughout the cancer center were sampled three times. The first samples were obtained in June 2010 without prior cleaning to measure baseline levels of contamination of the current technique (Chemo Dispensing Pin, B. Braun Medical Inc.). The second samples were obtained in August 2010 after the implementation of the closed system drug-transfer device and cleaning to evaluate if the contamination was removed. The third samples were obtained in August 2011. Wipe samples were taken from five positions in the pharmacy and from five positions in the infusion suite. Wipe samples were also collected from two positions in office areas. Samples were analyzed for cyclophosphamide and 5-fluorouracil. RESULTS: The results from the first two sets of samples showed contamination with cyclophosphamide on about half of the positions at all locations during both collection periods. However, levels of contamination were very low and mostly just above the detection limit of the analytical method. The highest level of contamination was found on the door and handle in the pharmacy. Contamination with 5-fluorouracil was only observed on the dispensing counter in the pharmacy during the second collection period. The results from the third and final collection period showed no contamination with cyclophosphamide or 5-fluorouracil in the pharmacy, the infusion suite or in offices of the cancer center. CONCLUSION: Implementation of the closed system drug-transfer device for preparing and administering chemotherapy eliminated surface contamination with cytotoxic agents at the ambulatory cancer chemotherapy infusion center.

Exposure of family members to antineoplastic drugs via excreta of treated cancer patients.

PURPOSES: (a) To measure the urinary excretion of antineoplastic drugs of three patients during 48 h after the administration of cyclophosphamide (two patients) and 5-fluorouracil (one patient). (b) To evaluate environmental contamination with antineoplastic drugs via excreta of patients in the home setting. (c) To evaluate exposure of family members to antineoplastic drugs by measuring the drugs in their urine during the 48 h after completion of the chemotherapy by the patients. METHODS: Two patients were administered cyclophosphamide by i.v. bolus injection. One patient was administered 5-fluorouracil by i.v. bolus injection and thereafter immediately administered the same drug by continuous infusion for 46 h. Urine samples from the patients administered cyclophosphamide and their family members, and wipe samples from their home environment, were analysed for the unchanged form of cyclophosphamide. For 5-fluorouracil, the urine samples from the patient and the family member were analysed for the 5-fluorouracil metabolite α-fluoro-ß-alanine. Wipe samples were analysed for 5-fluorouracil. Drugs were detected and quantified with gas chromatography in tandem with mass spectroscopy-mass spectroscopy or by high-performance liquid chromatography with ultraviolet-light detection. RESULTS: A total of 35 and 16 urine samples were collected from the three patients and their family members, respectively. The drugs were detected in all samples. Cyclophosphamide was detected at levels of 0.03-7.34 ng/cm(2) in 8 of the 12 wipe samples obtained from the homes of the patients administered cyclophosphamide. For the patient administered 5-fluorouracil, drug levels in his home environment were below the limit of detection. CONCLUSION: We demonstrated contamination of the home setting and exposure of family members to cyclophosphamide via the excreta of outpatient receiving chemotherapy. Exposure of the family member of the patient administered 5-fluorouracil was also demonstrated. These findings indicate the importance of strict precautions by the members of treated cancer patients as well as healthcare workers, to reduce the risk of exposure to antineoplastic drugs.

Reduction in Surface Contamination With Cyclophosphamide in 30 US Hospital Pharmacies Following Implementation of a Closed-System Drug Transfer Device.

PURPOSE: In a follow-up to a previous study, surface contamination with the antineoplastic drug cyclophosphamide was compared in 30 US hospital pharmacies from 2004 to 2010 following preparation with standard drug preparation techniques or the PhaSeal closed system drug transfer device (CSTD). METHODS: Wipe samples were taken from biological safety cabinet (BSC) surfaces, BSC airfoils (the front leading edge of the BSC), floors in front of BSCs, and countertops in the pharmacy, and they were analyzed for contamination with cyclophosphamide. Contamination was reassessed after a minimum of 6 months following the implementation of the CSTD. Surface contamination (ng/cm(2)) was compared between the 2 techniques and between the previous and current test periods and evaluated with the Kruskal-Wallis test. RESULTS: With the use of CSTD compared to the standard preparation techniques, a significant reduction in levels of contamination with cyclophosphamide was observed (P < .0001). Median values for surface contamination with cyclophosphamide were reduced by 86% compared to 95% in the previous study. CONCLUSIONS: The CSTD significantly reduced, but did not totally eliminate, surface contamination with cyclophosphamide. In addition to other protective measures, increased usage of CSTDs should be employed to help protect health care workers from exposure to hazardous drugs.

Reduction in surface contamination with antineoplastic drugs in 22 hospital pharmacies in the US following implementation of a closed-system drug transfer device.

PURPOSE: Surface contamination with the antineoplastic drugs cyclophosphamide, ifosfamide, and 5-fluorouracil was compared in 22 US hospital pharmacies following preparation with standard drug preparation techniques or the PhaSeal® closed-system drug transfer device (CSTD). METHODS: Wipe samples were taken from biological safety cabinet (BSC) surfaces, BSC airfoils, floors in front of BSCs, and counters and analyzed for contamination with cyclophosphamide, ifosfamide, and 5-fluorouracil. Contamination was reassessed several months after the implementation of the CSTD. Surface contamination (ng/cm(2)) was compared between the two techniques and evaluated with the Signed Rank Test. RESULTS: Using the CSTD compared to the standard preparation techniques, a significant reduction in levels of contamination was observed for all drugs (cyclophosphamide: p < 0.0001; ifosfamide: p < 0.001; 5-fluorouracil: p < 0.01). Median values for surface contamination with cyclophosphamide, ifosfamide, and 5-fluorouracil were reduced by 95%, 90%, and 65%, respectively. CONCLUSIONS: Use of the CSTD significantly reduces surface contamination when preparing cyclophosphamide, ifosfamide, and 5-fluorouracil as compared to standard drug preparation techniques.

Surface contamination of chemotherapy drug vials and evaluation of new vial-cleaning techniques: results of three studies.

PURPOSE: The results of three studies that describe the external contamination of chemotherapy drug vials are presented. New techniques for the improved decontamination of vials containing cisplatin are also described. SUMMARY: Study 1 evaluated the external contamination of drug vials with cyclophosphamide and ifosfamide in a pharmacy setting. Widespread contamination of the outside of drug vials was found with each drug. Study 2 evaluated the surface contamination of drug vials with cyclophosphamide and fluorouracil in three pharmacies. Sporadic contamination with fluorouracil was detected, while cyclophosphamide was found on most vials. In study 3, investigators compared the decontamination abilities of a standard decontamination procedure at the manufacturer level with an improved decontamination procedure and the use of sleeves to further decrease contamination. Though the methods of each study reported herein differed, the outcomes were similar. All chemotherapy drug vials studied demonstrated levels of contamination with the drug well above the limit of detection. Improved decontamination procedures, combined with the use of protective sleeves, reduced the level of platinum contamination by 90%, suggesting that standard decontamination procedures should be reconsidered. CONCLUSION: The results of these studies are consistent with several others that have reported contamination of the outside surface of drug vials for a number of chemotherapy drugs. Contamination can be reduced by using decontamination equipment and protective sleeves during the manufacturing process.