|Year : 2015 | Volume
| Issue : 1 | Page : 117-119
Outbreak of Burkholderia cepacia complex bacteremia in a chemotherapy day care unit due to intrinsic contamination of an antiemetic drug
T Singhal, S Shah, R Naik
Department of Infection Control, Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute, Mumbai, Maharashtra, India
|Date of Submission||19-Dec-2013|
|Date of Acceptance||29-Apr-2014|
|Date of Web Publication||5-Jan-2015|
Department of Infection Control, Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute, Mumbai, Maharashtra
Source of Support: None, Conflict of Interest: None
Background: In the end of 2009, a large number of patients with cancer undergoing chemotherapy at the day care unit of a private hospital in Mumbai, India developed Burkholderia cepacia complex (BCC) blood stream infection (BSI). Objective: The objectives were to identify the source of the outbreak and terminate the outbreak as rapidly as possible. Materials and Methods: All infection control protocols and processes were reviewed. Intensive training was started for all nursing staff involved in patient care. Cultures were sent from the environment (surfaces, water, air), intravenous fluids, disinfectants and antiseptics and opened/unopened medication. Results: A total of 13 patients with cancer with tunneled catheters were affected with BCC BSI. The isolates were of similar antimicrobial sensitivity. No significant breach of infection control protocols could be identified. Cultures from the prepared intravenous medication bags grew BCC. Subsequently, culture from unused vials of the antiemetic granisetron grew BCC, whereas those from the unopened IV fluid bag and chemotherapy medication were negative. On review, it was discovered that the outbreak started when a new brand of granisetron was introduced. The result was communicated to the manufacturer and the brand was withdrawn. There were no further cases. Conclusions: This outbreak was thus linked to intrinsic contamination of medication vials. We acknowledge a delay in identifying the source as we were concentrating more on human errors in medication preparation and less on intrinsic contamination. We recommend that in an event of an outbreak, unopened vials be cultured at the outset.
Keywords: Burkholderia, bacteremia, contamination, drug, nosocomial
|How to cite this article:|
Singhal T, Shah S, Naik R. Outbreak of Burkholderia cepacia complex bacteremia in a chemotherapy day care unit due to intrinsic contamination of an antiemetic drug. Indian J Med Microbiol 2015;33:117-9
|How to cite this URL:|
Singhal T, Shah S, Naik R. Outbreak of Burkholderia cepacia complex bacteremia in a chemotherapy day care unit due to intrinsic contamination of an antiemetic drug. Indian J Med Microbiol [serial online] 2015 [cited 2018 Apr 20];33:117-9. Available from: http://www.ijmm.org/text.asp?2015/33/1/117/148405
| ~ Introduction|| |
Burkholderia cepacia is an aerobic gram negative bacillus found in various aquatic environments. It is classified as 10 serovars, collectively termed as the Burkholderia cepacia complex (BCC).  It is an organism of low virulence which causes respiratory disease in patients with cystic fibrosis and various nosocomial infections (NI). NI caused by BCC include blood stream infections (BSI), pneumonias, surgical wound infections and genitourinary tract infections. Outbreaks of NI due to BCC have been commonly reported in literature and generally linked to contamination of various fluids used in hospitals. 
In the end of 2009, several patients with cancer with implanted central venous catheters undergoing chemotherapy in a day care unit of a large tertiary care private health care institution in Mumbai, India developed BCC bacteremia. This was the first outbreak of NI in a hospital that was commissioned a few months back. This outbreak was causing significant morbidity in those affected and tremendous anxiety among the hospital medical oncology team. A systematic investigation was launched to identify the source of the outbreak.
| ~ Materials and Methods|| |
The setting is a large 700-bedded multispecialty private health care institution in the metropolitan city of Mumbai, India that was commissioned in January 2009. The infection control protocols have been drafted based on Centers for Disease Control (CDC) and World Health Organization (WHO) guidelines, implemented since hospital commissioning and regularly audited. Outbreak investigations were initiated following recovery of Burkholderia cepacia from peripheral and central blood cultures in patients undergoing cancer chemotherapy who presented with fever to the outpatient department.
The process of medication preparation was reviewed. The medication was prepared by mixing the chemotherapy drug and the antiemetic granisetron in the intravenous bag in the laminar flow. Granisetron was given prophylactically in all patients since the chemotherapy medication was highly emetogenic. As a first step, compliance to all infection control protocols was assessed, corrected if so required and made more stringent. Hand hygiene was reinforced, medication preparation and administration was regulated, use of only collapsible/closed intravenous fluid bags initiated. The process of insertion of ports was reviewed. Microbiologic cultures were taken from environmental surfaces, water, air, laminar air flow, hands of the health care staff/surgeons and skin cleaning antiseptics. The entire day care unit was fogged and disinfected. A literature search was conducted and possible sources of infection were identified. Prepared chemotherapy medication, opened and unopened intravenous fluid bags were cultured. Finally, cultures from all unopened chemotherapy medication and antiemetic vials were also sent.
| ~ Results|| |
A total of 13 patients (12 females, one male) had BCC bacteremia during the outbreak that lasted 2 months. The study population included 10 women with breast cancer and 3 others with haematologic malignancy (acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML) and Burkitt's lymphoma one each). The mean period between catheter insertion and development of bacteremia was 65 days (range 2-144 days). All the Burkholderia isolates had identical susceptibility and were sensitive to all commonly used antibiotics such as beta lactams, quinolones, beta lactam beta lactamase inhibitor combinations and carbapenems.
All patients were initiated on appropriate antimicrobial therapy. All survived that episode of bacteremia but 11 required removal of the implanted catheter for clinical resolution. The mean period between culture positivity and removal of catheter was 12 days (range 4-21 days). The tips of all the implanted catheters grew Burkholderia cepacia with antimicrobial sensitivity identical to that isolated from the blood.
Cultures from air, water, laminar flow, disinfectants including 2% alcoholic chlorhexidine, 10% aqueous povidone iodine and 70% ethanol were negative. Cultures from the environmental surfaces grew bacillus species. The prepared chemotherapy medication grew Burkholderia cepacia. Cultures of the unopened constituents of prepared chemotherapy medication i.e., intravenous fluid bags, chemotherapy medication were sterile but granisetron vials grew Burkholderia cepacia. Cultures of the unopened granisetron vials (same batch) were repeatedly positive. The antibiotic susceptibility of the Burkholderia isolates were identical to each other and to those isolated from patients. This indicates that this point source outbreak was due to intrinsic contamination of the antiemetic drug granisetron. The results were communicated to the manufacturer, the brand was withdrawn. There were no further cases.
| ~ Discussion|| |
This outbreak of BCC bacteremia was thus conclusively linked to intrinsic contamination of anti emetic drug granisetron. This probably happened during the process of manufacturing. This outbreak caused significant morbidity and increase in treatment costs in cancer patients and considerable anxiety among the treating oncologists in a newly commissioned hospital. There was a delay in determining the source since intrinsic contamination of the unopened vials was not suspected. When the prepared chemotherapy medication bags were culture positive, human error and breach of infection control practices was suspected and there was delay in culturing unopened vials.
Previous BCC bacteremia's have been linked to extrinsic contamination of antiseptics including alcohol/chlorhexidine, multi-dose vials of ringer lactate used as water for injection, and mannitol. ,, Intrinsic contamination of medication causing BCC bacteremias similar to the ones seen in this study has also been reported. These include contamination of ultrasound gel, albuterol solution for nebulisation, water for injection, moisturising body milk and intravenous bromopride. ,,,,
We acknowledge nonavailability of pulse field gel electrophoresis (PFGE) or multilocus sequence typing (MLST) as a limitation in proving clonal relatedness of all isolates. However, identical susceptibility patterns, identification of a single common source and cessation of the outbreak after withdrawing the incriminated medication are reasonable indirect evidence of a common source outbreak. We recommend that all medication vials opened and unopened should be cultured at the outset in the event of a BCC outbreak to detect intrinsic contamination early.
| ~ References|| |
Gautam V, Singhal L, Ray P. Burkholderia cepacia complex: Beyond pseudomonas and acinetobacter. Indian J Med Microbiol 2011;29:4-12.
Vonberg RP, Gastmeier P. Hospital-acquired infections related to contaminated substances. J Hosp Infect 2007;65:15-23.
Lee S, Han SW, Kim G, Song do Y, Lee JC, Kwon KT. An outbreak of Burkholderia cenocepacia associated with contaminated chlorhexidine solutions prepared in the hospital. Am J Infect Control 2013;41:e93-6.
De Smet B, Veng C, Kruy L, Kham C, van Griensven J, Peeters C, et al
. Outbreak of Burkholderia cepacia bloodstream infections traced to the use of Ringer lactate solution as multiple-dose vial for catheter flushing, Phnom Penh, Cambodia. Clin Microbiol Infect 2013;19:832-7.
Souza Dias MB, Cavassin LG, Stempliuk V, Xavier LS, Lobo RD, Sampaio JL, et al
. Multi-institutional outbreak of Burkholderia cepacia complex associated with contaminated mannitol solution prepared in compounding pharmacy. Am J Infect Control 2013;41:1038-42.
Hutchinson J, Runge W, Mulvey M, Norris G, Yetman M, Valkova N, et al
. Burkholderia cepacia infections associated with intrinsically contaminated ultrasound gel: The role of microbial degradation of parabens. Infect Control Hosp Epidemiol 2004;25:291-6.
Martins IS, Pellegrino FL, Freitas AD, Santos Mda S, Ferraiuoli GI, Vasques MR, et al
. Case-crossover study of Burkholderia cepacia complex bloodstream infection associated with contaminated intravenous bromopride. Infect Control Hosp Epidemiol 2010;31:516-21.
Douce RW, Zurita J, Sanchez O, Cardenas Aldaz P. Investigation of an outbreak of central venous catheter-associated bloodstream infection due to contaminated water. Infect Control Hosp Epidemiol 2008;29:364-6.
Alvarez-Lerma F, Maull E, Terradas R, Segura C, Planells I, Coll P, et al
. Moisturizing body milk as a reservoir of Burkholderia cepacia: Outbreak of nosocomial infection in a multidisciplinary intensive care unit. Crit Care 2008;12:R10.
Ghazal SS, Al-Mudaimeegh K, Al Fakihi EM, Asery AT. Outbreak of Burkholderia cepacia bacteremia in immunocompetent children caused by contaminated nebulized sulbutamol in Saudi Arabia. Am J Infect Control 2006;34:394-8.