JSTOR

Methods

We conducted a case‐control study to assess possible risk factors for infection with B. cepacia. Case patients had been treated at the clinic between June 1 and December 31, 2004, and had had at least 1 blood culture positive for B. cepacia. Case finding was performed through surveillance blood cultures. Control patients were randomly chosen by selecting every fiftieth name from the clinic appointment book for the period between June 1 and December 31, 2004. Data on case and control patients were abstracted from clinic medical records. SAS, version 8 (SAS Institute) was used to perform univariate analysis and to calculate exact odds ratios (ORs) and 95% confidence intervals (CIs). P values less than .05 were considered statistically significant.

Infection control procedures were reviewed, including medication preparation and administration, cleaning, and disinfection. We cultured samples of unopened medications and samples from environmental surfaces in the clinic. A total of 50 environmental samples were obtained for testing. The isolates available from case patients' blood cultures and indwelling intravenous catheter cultures were sent to the Division of Healthcare Quality Promotion for confirmation of identity. The identity of the isolates was confirmed and compared using pulsed‐field gel electrophoresis (PFGE) following digestion with the restriction enzyme SpeI.⁴

Results

A total of 10 case patients were identified; 8 were identified on the basis of clinical cultures of symptomatic patients, and 2 were identified on the basis of surveillance blood cultures. All case patients had implanted subcutaneous port catheters; 9 were receiving chemotherapy when the B. cepacia was recovered, and 1 had completed treatment and was receiving periodic catheter flushes. All 10 case patients had been hospitalized, and 2 case patients had neutropenia (defined as an absolute neutrophil count of less than 500 cells/mm³) at hospital admission.

Surveillance blood cultures revealed 39 potentially exposed patients with indwelling intravenous catheters who were treated at the clinic during the exposure period. Of these 39 patients, 10 (25.6%) had blood cultures positive for B. cepacia, 19 (48.7%) had blood cultures negative for B. cepacia, 5 (12.8%) had had indwelling catheters removed prior to blood testing, and 5 (12.8%) had no blood return from their catheters. In our case‐control study, none of the control subjects with an indwelling intravenous catheter had a blood culture positive for B. cepacia.

We analyzed the risk of B. cepacia infection by age, sex, type of venous access, disease type, receipt of intravenous chemotherapy, receipt of antimicrobial therapy at time of culture, and clinic visits (Table 1). Patients who had indwelling intravenous catheters, who were currently receiving chemotherapy, and who had 7 or more clinic visits during the study period were more likely to become a case patient, compared with patients who had other types of venous access, who were receiving other types of therapy (eg, transfusions or post‐chemotherapy medication), and who had fewer than 7 clinic visits during the study period. We also assessed the number of clinic visits by 2‐week intervals and found that patients treated during the 6‐week period between July 12 and August 20, 2004, were most likely to become case patients (Table 1). All 10 case patients were treated at least once during 3 weeks of this 6‐week period.

Table 1.  Case‐Control Study of Risk Factors for Burkholderia cepacia Bloodstream Infection Among Outpatients at a Hematology and Oncology Clinic in Georgia, 2004‐05

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For the 11 medications administered to patients from multidose bottles, we found that exposure to dexamethasone, doxorubicin, heparin, saline, and ondansetron were more common among case patients than control patients (Table 2). For the 12 medications administered from single‐dose bottles, only exposure to cyclophosphamide was more common among case patients, compared with control patients. Patients who received cyclophosphamide also received 1 or more medications from a multidose bottle during the same visit.

Table 2.  Medications Used Among Case and Control Patients During the Period 1 June–31 December, 2004, That Were Significantly Associated With Burkholderia cepacia Infection

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We identified potential opportunities for contamination of intravenous medications. Multidose bottles of saline, ondansetron, and dexamethasone were accessed using a single needle and syringe, to combine the medications. During the preparation of chemotherapy medications, the same needle was also used to withdraw multiple types of chemotherapy agents to inject into different bags of fluid. Minor breaches in aseptic technique during medication preparation and administration were also noted.

B. cepacia was not recovered from environmental samples obtained in the clinic. A total of 4 isolates were available for molecular typing, and they had indistinguishable PFGE patterns; the isolates were identified as B. cepacia, genomovar I. An isolate from a patient who was not treated at the clinic but was admitted to the local hospital with B. anthina (genomovar VIII) infection showed a distinctly different PFGE pattern than isolates recovered from case patients.

Discussion

We investigated 10 cases in which B. cepacia was recovered from the blood of outpatients treated at a hematology and oncology clinic and found that case patients were more likely than control patients to have been exposed to various medications from multidose bottles. A review of medication preparation technique revealed opportunities for contamination and cross‐contamination of these medications.

Breaches in aseptic technique during medication preparation could have led to contamination of 1 or more of the multidose medications. A common needle and syringe were used to access multiple multidose vials. Contamination of any one of these would have led to widespread contamination. Because these medications were not used up simultaneously, new vials of medication could have easily become contaminated and thus prolonged the existence of the pathogen in the medication for weeks. Our finding that receipt of several medications obtained from multidose bottles were risk factors for infection supports this hypothesis.

The ability of B. cepacia to colonize indwelling intravenous catheters and propagate there likely contributed to this outbreak.^5,6 The presence of organic material on indwelling catheters, especially those that have been implanted for long periods of time, creates a favorable environment for bacterial colonization and the establishment of a microbial biofilm.⁷ This risk is clearly enhanced if these catheters are exposed to contaminated medications. The establishment of a microbial biofilm would also explain why some of the case patients in this outbreak were detected many months after the identified high‐risk exposure period.

Our findings also demonstrate one of the major challenges of investigating outbreaks of catheter‐related infections. The potential for catheters to become colonized and for infections to occur long after exposures should prompt clinicians to carefully evaluate the need for implanted catheters once treatment has concluded. The presence of a nonfunctioning catheter would clearly represent a potential risk with no apparent benefit.

There were several limitations to this analysis. It is not possible to know whether the cases that were identified later represented exposures to a common source of contamination or a reintroduction of the organism into the clinic. Our ability to detect a possible environmental source was hampered by the fact that sampling occurred 6 months after diagnosis of the first case patient. Finally, our ORs were most likely affected by confounding as a result of variables such as access type, type of disease, current receipt of chemotherapy, and number of clinic visits, because the type of access is often determined by the type of chemotherapy and the type of disease, which in turn can influence the number of clinic visits.

Our investigation, like others,^8,9 may support recommendations that single‐dose bottles of medication be used when possible, especially when the medication is used for patients with indwelling intravenous catheters. When medications from multidose bottles must be used, aseptic technique must be carefully followed to avoid contamination. Needles and syringes should not be reused to access multiple multidose vials. Our investigation also highlights the importance of critically evaluating the need to keep an implanted catheter in place once treatment is complete.