Alcaligenes xylosoxidans Bloodstream Infections in Outpatient Oncology Office: Discussion

Discussion

This large outbreak (N = 12) of A. xylosoxidans bloodstream infections was caused by 1 strain, which was also isolated from CVC biofilm. Symptoms of bloodstream infection probably occurred when flushes detached bacteria from the CVC biofilm. The prospective study found that 3 (10%) of 29 patients had A. xylosoxidans–positive blood cultures. Our case–control and prospective studies support the association of A. xylosoxidans bloodstream infection and CVCs, and our molecular biologic studies confirm A. xylosoxidans biofilm of the same outbreak strain on a CVC. A. xylosoxidans outbreaks reported to date have been associated with healthcare and contamination of hospital products,^{[1,2,5,12-14]} but none occurred in an outpatient setting.

The cause of this outbreak most likely was the use of contaminated multidose vials of heparin or saline flushes, leading to the formation of an A. xylosoxidans biofilm on CVCs. Case-patient 1 had been hospitalized from late October through early November at Hospital A. During November 13–19, 2001, this case-patient had had blood collected and her CVC line flushed numerous times at Office B; on November 19, culture result indicated A. xylosoxidans infection, which was successfully treated. We observed multiple breaches in infection control at Office B: use of unlabeled, prefilled syringes, poor hand hygiene, and lack of glove use. The CVC of case-patient 1 may have been flushed by using the same syringe and needle inserted into multidose vials, causing contamination of the vials. Another possible route of contamination is through artificial fingernails. A cluster of Serratia marcescens and A. xylosoxidans bacteremia cases linked to multidose heparin vials contaminated by a nurse with artificial fingernails has been reported;^[22] however, the artificial fingernails from the nurse at Office B were unavailable for testing. We suspect that multidose vials were contaminated with A. xylosoxidans and subsequently used on other patients from November 12 through December 18, 2001, when all case-patients had overlapping visits at Office B and received CVC flushes. A culture from an open, supposedly sterile saline bottle grew B. circulans, which suggests possible breaches in infection control. Multidose heparin and saline vials have been reported as the cause of outbreaks of hepatitis C,^[23,24] S. marcescens,^[25] and Pseudomonas aeruginosa^[26] infections.

Although the heparin and the saline vials could have been contaminated from case-patient 1 in November, casepatients who subsequently received flushes from these vials may not have become immediately ill with symptoms of bloodstream infection. A. xylosoxidans biofilm could have developed on their CVCs and intermittently caused clinical illness when the CVCs were manipulated; i.e., flushing dislodged the biofilm and caused symptomatic bacteremia. Although indwelling catheters are frequently colonized with biofilm shortly after insertion,^[27] colonization does not necessarily lead to infection; bloodstream infection symptoms from an organism in contaminated intravenous solutions have been delayed for as long as 421 days after exposure.^[28] The finding of an asymptomatic patient with a CVC with A. xylosoxidans biofilm supports this. A number of variables may be associated with detachment of microbial cells from a biofilm,^[29] resulting in erosion or sloughing. Flushing, which could mechanically shear the biofilm, could result in detachment of cells or aggregates that could in turn colonize the bloodstream and cause signs and symptoms of bacteremia. This phenomenon has been recently reported.^[28]

The case-patients in this outbreak had their CVCs removed and were treated with antimicrobial agents. The presence of A. xylosoxidans biofilm and the mechanism of bloodstream infection after disruption by catheter flushing suggests that eradication of infection would require catheter removal, as reported by others.^[4,9] Previously, recurrent A. xylosoxidans bacteremia has been reported in those patients whose indwelling catheters were not removed.^[11] Formation of A. xylosoxidans biofilm provides an explanation for the organism most commonly causing bacteremia in patients with CVCs.^[7,10]

The California Code of Regulations, Title 17, Section 2500,^[30] requires all healthcare professionals to immediately report outbreaks of any cause; however, this outbreak was not recognized early on. The initial cluster of patients at Office B had symptoms and positive blood cultures growing this uncommon organism for 6 weeks before the cases were reported to the Los Angeles County Department of Public Health. Because outpatient settings may lack surveillance systems, outbreaks may not be recognized immediately, thus potentially exposing more patients. In addition, some of the symptoms of bloodstream infection were initially attributed to side effects of chemotherapy. Because 10% of patients in our prospective cohort study had blood cultures positive for A. xylosoxidans, further studies are needed to determine whether active surveillance for patients with CVCs would help recognize infections.

Because we noted not only infection control breaches but also that unlicensed office personnel were manipulating the CVCs, line flushes, infusions, and blood collection through CVCs, we reported the situation to the California Medical Board and the California Department of Health Services. Although no California state regulations for infection control in outpatient physician's offices exist, the California Department of Health Services and Los Angeles County Department of Public Health recommended that the oncology office improve infection control standards; handling, storage, exposure, and access to pharmaceuticals; and improve medical record documentation. New infection control policies were established, and the office subsequently hired new, properly licensed registered nurses and nurse practitioners to handle insertion of intravenous catheters and administration of intravenous medications and chemotherapy. After proper education of the oncology office staff and removal of multidose vials of heparin and saline, no more A. xylosoxidans bloodstream infections were reported from Office B.

Our investigation has limitations. We did not culture A. xylosoxidans from the multidose vials. The original vials, used when the outbreak began, had already been discarded and were not available for testing by the time we were notified in January 2002. Our investigation was also limited by the absence of medical records indicating when nursing staff accessed the CVCs. Although the contamination of multidose vials remains suggestive, we suspect that they were the most likely source. The outbreak ended after discontinuing their use and enacting improved infection control practices. The organism could have been introduced into multidose vials by a needle or syringe used on an infected patient or by the artificial fingernails of the nurse, through gaps in infection control.

For patients who received infusion therapy at home, receipt of therapy in an outpatient clinic or physician's office was an independent risk factor for bloodstream infection.^[31] Therefore, clinicians need to be vigilant because minor breaches in infection control can lead to large outbreaks with uncommon human pathogens, especially in patients with CVCs. Clinicians also need to ensure that appropriate infection control practices are adhered to consistently, especially in outpatient care settings, where oversight of infection control procedures may be absent. Unlike standards that exist for nursing homes or hospitals, no written standards regarding infection control in outpatient settings exist from the California Department of Health Services or the California Medical Board. However, routine monitoring and adherence to infection control could prevent outbreaks. Clinicians providing care in outpatient settings should review appropriate infection control standards and consider establishing written policies to ensure that standards are met. As healthcare delivery continues to move toward outpatient care,^[32] the lack of formal infection control procedures and accountability in the outpatient office setting can lead to large disease outbreaks;^[33,34] the need for oversight in this setting should be considered.

Our investigation helps characterize the mechanisms of A. xylosoxidans bloodstream infection in immunocompromised patients with CVCs. It provides a better understanding of how biofilm formation in a CVC can result in a clinical infectious disease process with this uncommon organism. Substantial illness and death can occur in outpatient settings that lack formal oversight. This outbreak highlights an unaddressed infection control problem in the outpatient setting for regulating agencies to further review.