- Email: [email protected]
Outbreak of Burkholderia cepacia bacteraemia in a tertiary care centre due to contaminated ultrasound probe gel
Accepted Manuscript Outbreak of Burkholderia cepacia bacteraemia in a tertiary care centre due to contaminated ultrasound probe gel Rehab Abdelfattah, Suliman Aljumaah, Ahmed Alqahtani, Sahar Althawadi, Irene Barron, Saleh Almofada PII:
S0195-6701(17)30516-9
DOI:
10.1016/j.jhin.2017.09.010
Reference:
YJHIN 5224
To appear in:
Journal of Hospital Infection
Received Date: 20 July 2017 Accepted Date: 12 September 2017
Please cite this article as: Abdelfattah R, Aljumaah S, Alqahtani A, Althawadi S, Barron I, Almofada S, Outbreak of Burkholderia cepacia bacteraemia in a tertiary care centre due to contaminated ultrasound probe gel, Journal of Hospital Infection (2017), doi: 10.1016/j.jhin.2017.09.010. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Outbreak of Burkholderia cepacia bacteraemia in a tertiary care centre due to contaminated ultrasound probe gel
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Authors; 1- Rehab Abdelfattah; King Faisal Specialist Hospital and Research Center.
Address correspondence to Rehab Abdelfattah, MD MPH- King Faisal Specialist Hospital
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& Research Center, P.O.Box 3354, Riyadh 11211, MBC-89, Saudi Arabia. Email: [email protected].
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2- Suliman Aljumaah; King Faisal Specialist Hospital and Research Center 3- Ahmed Alqahtani; King Faisal Specialist Hospital and Research Center 4- Sahar Althawadi; King Faisal Specialist Hospital and Research Center
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5- Irene Barron; King Faisal Specialist Hospital and Research Center
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6- Saleh Almofada; King Faisal Specialist Hospital and Research Center
All authors have read and approved the submission of the manuscript to JHI. Total word count= 2800
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ABSTRACT Background. Burkholderia cepacia is a significant opportunistic organism in hospitalized and
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immunocompromised patients, particularly in cystic fibrosis [1] Aims. We describe the epidemiological investigation of an outbreak of B. cepacia bacteraemia Methods. The study examined 14 patients during their admission to three ICUs (Intensive Care
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Units) in a tertiary care hospital between January–June 2016. The outbreak involved 9 (57%)
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female and 6 (43%) male patients. All patients were adults of ages ranging from 19–85 years with a median age of 52 years. Patients’ medical charts, laboratory cultures, exposures, and central line insertion procedures were reviewed.
Findings. B. cepacia was isolated from the blood cultures of 14 patients resulting from
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contamination of the gel applied to the ultrasound probe used to guide the insertion of a central venous catheter. Molecular pathogen typing using pulsed field gel electrophoresis showed 95% similarity between the B. cepacia isolates from the blood of these patients and
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those isolated from the ultrasound gel.
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Conclusions. Ongoing surveillance and prompt investigation of unusual disease outbreaks are vital for identifying sources of contamination of B. cepacia and protecting at-risk patients. Sound epidemiological methods are very important for identifying the source of any hospital infection outbreak. KEYWORDS
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Burkholderia Cepacia, Bacteremia, Outbreak investigations, Intensive care units, Ultrasound
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probe cover, Opportunistic infections.
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INTRODUCTION Burkholderia cepacia is an aerobic gram-negative bacterium that can survive in soil and wet
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environments for a long periods of time.[1-4] B. cepacia is more commonly a colonizer rather than an infecting organism.[1, 2] It is intrinsically resistant to aminoglycosides and first- and second-generation Cephalosporins [5]. B. cepacia pseudo-bacteraemia has been described in
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many studies, but true bacteraemia is rare.[2]
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B. cepacia poses few medical risks to healthy individuals.[2] However, it is a known to cause hospital-acquired infections, especially in immunocompromised patients and patients with chronic lung diseases, such as cystic fibrosis.[1-4] Outbreaks of B. cepacia bacteraemia are often associated with contaminated intravenous (IV) medications, medical devices, or skin
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disinfectants.[1-4] Transmission of B. cepacia by person-to-person contact, contact with
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5]
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contaminated surfaces, or exposure to B. cepacia in the environment has also been reported.[2,
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METHODS Ethical approval for this study was granted from the local institutional review boards on 5
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March 2017. The tertiary care facility where the B. cepacia outbreak occurred is a large and advanced referral hospital in Riyadh, Saudi Arabia, that includes over 1500 hospital beds. It has a total of nine intensive care units (ICUs). The B. cepacia bacteraemia outbreak was reported in
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three of these ICUs: ICU-A, ICU-B, and ICU-C. The outbreak occurred between January 8, 2016 and June 15, 2016 (Figure 1). In January of 2016, the Department of Infection Control and
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Hospital Epidemiology noticed a cluster of three cases of bacteraemia caused by an unusual organism: B. cepacia. A case definition was developed as clinical laboratory identified blood isolates of B. cepacia in inpatient and outpatient units and in all age groups (adult and children). A retrospective review of medical records and laboratory culture results from 2014–2015
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revealed no previous cases of B. cepacia bacteraemia in these ICUs.
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The first three cases of B. cepacia bacteraemia occurred in January of 2016. The cluster involved three patients admitted to the ICU between January 4–11, 2016. The first patient was
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a 62-year-old male admitted with anasarca following a kidney transplant. He had one positive blood culture for B. cepacia 4 days following admission, which was treated with Trimethoprim Sulfamethoxazole and Meropenem. The second patient was a 42-year-old female admitted with a metastatic neuro-endocrine tumor who had four positive blood cultures for B. cepacia. The first one was reported 8 days after admission. The third patient was a 36-year-old female admitted with End-Stage Renal Disease (ESRD) and multiple pathological bone fractures. She
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had one positive blood culture for B. cepacia 7 days after admission. All patients were treated successfully with Meropenem. Table 1 summarizes the patients’ demography, date clinical
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history and outcomes.
We conducted environmental and epidemiological investigations after the first few cases.
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However, no significant epidemiological associations or positive environmental cultures were reported. Active surveillance for similar cases was ongoing using the stated case definition. No
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cases were reported during February 2016.
In March, a 47-year-old female patient was admitted to ICU-B with Acute Respiratory Distress
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Syndrome (ARDS). The patient had one positive blood culture for B. cepacia. However, the second culture was negative, and no treatment for B. cepacia was given. An additional 19-yearold male patient admitted to the same ICU (ICU-B) had B. cepacia isolated from the catheter tip,
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but blood cultures were only positive for multidrug resistant (MDR) Pseudomonas aeruginosa. In April, five new cases were reported, suggesting the existence of a common source of
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contamination. Two patients had sustained a road traffic accident (RTA) and were referred from a peripheral hospital for surgical reconstruction procedures. Both patients had one positive blood culture for B. cepacia on the same day of admission. These blood cultures were collected immediately after central line insertion. The blood samples collected from the central line of these two patients were positive for B. cepacia, while blood cultures from peripheral lines were negative. One patient was treated with Meropenem and the second patient received TMP/SMX
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(Trimethoprim- Sulfamethoxazole). Over the following 3 weeks, B. cepacia was isolated from the blood of three more patients. Two patients had been admitted with severe sepsis and
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Multi-Organ Failure (MOF), and the third patient had been diagnosed with hemorrhagic encephalopathy, Hospital Associated Pneumonia (HAP), and a Clostridium difficile infection. Two patients died of septic shock. More cases occurred during May and June. The clinical
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details are outlined in Table 1.
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All B. cepacia isolates were tested for antibiotic susceptibility by utilizing the VITEK 2 system (bioMérieux) according to the manufacturer’s instructions. The following antibiotics were tested: ceftazidime, meropenem, levofloxacin, trimethoprim-sulfamethoxazole (TMP-SMX), minocycline, and ticarcillin-clavulanic acid. All 14 blood isolates displayed identical susceptibility
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profiles, with a high susceptibility to TMP-SMX, ceftazidime, and meropenem.
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To identify the source of the B. cepacia infections, various consumables used by all 14 patients were investigated including central lines (CL), injection fluid/medications, central line insertion
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techniques, products, and surfaces. A total of 97 environmental samples were collected in early May 2016. Environmental samples from the three ICUs involved in the B. cepacia outbreak included CL insertion kits, CVC insertion trolleys, sterile saline used for flushing the lines after insertion, Chloraprep (other than what is included in the CVC kit), and syringes.
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Molecular typing of pathogens by pulsed field gel electrophoresis (PFGE) was performed on the B. cepacia isolates. Briefly this involved taking single colonies of the isolate and inoculating a 3
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mL trypticase soy broth with overnight incubation at 37°C in a shaker incubator. Cells were harvested by centrifugation at 1900 g for 10 min. Bacterial pellets were suspended in SE buffer (75 mM NaCl, pH 8.0; 25 mM EDTA, pH 8.0), and the final cell density was adjusted to 1.40 at a
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wavelength of 610 nm. Plugs were prepared by mixing 500 μl aliquots of cell suspensions and 500 μl of 1.6% low melting point (LMP) agarose. This agar-cell suspension mixture was
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immediately distributed into the wells of the plug molds and they were allowed to solidify at 4°C for 30 min. The plugs were transferred into tubes containing 1 ml of lysis buffer (50 mM Tris HCl, pH 8.0; 50 mM EDTA, pH 8.0; 1% sarcosine; 1 mg/ml proteinase K) and incubated overnight in a water bath at 55°C. Plugs were washed with 5 ml of sterile purified water at room
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temperature for 5 min, followed by four washes (30 min each) with 5 ml TE buffer (10 mM Tris– HCl, pH 8.0; 1 mM EDTA, pH 8.0) at room temperature. A plug slice 3×5 mm wide was put into a 1.5 ml microcentrifuge tube containing 200 μl of 1X restriction buffer and 50 U of SpeI. The
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mixture was incubated overnight at 37°C. Plug slices were inserted wells of 1% agarose gel, which were overlaid with 1% LMP agarose dissolved in 0.5X TBE. After solidification, the gel was
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run with a CHEF-Mapper apparatus in 3 L of 0.5X TBE buffer at an initial switch time of 2.2 s, a final switch time of 54.2 s, a running time of 22 h, a gradient of 6 V/cm, an angle of 120°, and a temperature of 14°C. The gel was stained for 30 min in 300 ml of sterile distilled water containing 1 μg/ml ethidium bromide. The gel was then de-stained by washing with 2 L of distilled water for 30 minutes. Gel images were digitized using a UV gel image acquisition camera (Gel Doc XR). Comparisons were performed using Bio-Numeric version 7.5 software.
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DNA fragments on each gel were normalized using a Lambda molecular weight standard to allow comparisons between gels. Cluster analysis was performed using the Dice coefficient. A
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2.0% band tolerance and an optimization of 4.0% were selected to compare the DNA profiles.
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[6]
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RESULTS We gathered information regarding all IV fluids and medications administered before or on the
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same collection day of the positive blood cultures. No multi-use vials or medication were used in the three ICUs during the outbreak. We conducted a case-control study among all 14 patients and 32 matching controls who were admitted to the same ICUs during the same timeframe
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during the outbreak. The three most frequently utilized IV fluids and medications were fentanyl, heparin, and magnesium sulphate. This analysis showed that there was no single IV
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fluid or medication utilized in the bacteraemia cases and not in the controls. Thus, we excluded IV fluids and medications as a potential source of the outbreak.
To exclude B. cepacia respiratory colonization, all 14 medical charts were reviewed and all of
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them had BAL (Broncho-alveolar lavage)/ respiratory cultures done as part of the case management. However, all these cultures were negative for B. cepacia, which suggested that a
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respiratory source or colonization were unlikely. Because of the concomitant B. cepacia outbreaks reported by the United States Center for Disease Control (US-CDC) in five different
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states linked to contaminated oral liquid docusate, all 14 medical charts were reviewed for the use of oral liquid Docusate before a positive blood culture for B. cepacia was confirmed. Results showed that of the 14 patients, only one patient (who had B. cepacia isolated from the central catheter tip) was given the medication. Therefore, docusate as a source of the outbreak was also excluded.
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Epidemiological investigations and line-listing of all patients elucidated that 11/14 patients (79%) had a positive blood culture for B. cepacia, which was collected directly from the CL
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immediately after insertion. All 14 patients had a bedside CL inserted at ICU-A, ICU-B, or ICU-C and all were admitted to different rooms in those units. ICU-A, ICU-B, and ICU-C all had the same medical and nursing management team. The CL type that was inserted in all 14 patients
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was a triple-lumen CVC, so randomly collected kits for all different CL types available in the hospital, were collected and cultured under standard aseptic techniques. Each kit had eight
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different parts. Therefore, eight samples were collected from each CVC kit including a line flush, catheter tip, three pieces of lumen, syringe flush, dilator flush and tip, Lidocaine, Chloraprep, and the transducer. All cultures from the CL kits were negative for B. cepacia.
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By reviewing the steps of CVC insertion, it was noted that all patients underwent an ultrasoundguided CVC insertion, and that was the only common factor among all 14 cases. Subsequent investigations focused on the probability that the common source of contamination might be
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linked to the ultrasound use during the CVC insertion. Cultures were collected from ultrasound
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machines from the three ICUs, as well as from ultrasound probe cover kits available in these three units.
The ultrasound probe cover kit contained various components, including the probe cover telescope folded within the kit, an ultrasound gel sachet, and two rubber bands. Each component was tested, and B. cepacia was cultured from the ultrasound gel sachet. Samples
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from unopened stocks of the same product with different lot numbers were obtained from ICU-
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B and cultured. These ultrasound gel samples were also positive for B. cepacia.
Investigations revealed that the contaminated product was available only in the three ICUs involved in the outbreak (ICU-A, ICU-B, and ICU-C), and these ICUs directly purchased the
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product from the vendor. Other units, such as the Department of Emergency Medicine,
Operative Rooms, and Cardiac and Pediatric ICUs, used an ultrasound probe cover kit from a
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different manufacturer that was distributed from the hospital medical stores. As a precautionary step, this product was also tested, and the samples were negative for B. cepacia. Molecular typing of pathogens by pulsed field gel electrophoresis (PFGE) confirmed the similarity between the B. cepacia isolates from the blood of the 14 patients and the organism
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isolated from the ultrasound gel (Figure 2).
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Findings were immediately reported to the manufacturer, local vendor, local authorities, and our sister hospital in Jeddah. No cases of B. cepacia were reported in Jeddah Hospital, most
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likely because this product was used for non-invasive procedures. Corrective action was undertaken by hospital-wide withdrawal of the contaminated product. Since then, no additional cases have been reported.
DISCUSSION
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The outbreak investigation demonstrated that ultrasound gel was the source of this B. cepacia outbreak as evidenced by culturing the same strain from patients and the contaminated gel.
of the contaminated gel resulted in termination of the outbreak.
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Extensive investigations did not reveal any other linked products or processes and replacement
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Previous studies have linked B. cepacia outbreaks to different contaminated products, such as multi-use vials of ringer lactate [4], albuterol solution for nebulization,[7-9] chlorohexidine,[10,
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11] fentanyl,[12] mannitol solution,[13] heparin injection,[14] moisturizing body milk,[15] reverse osmosis dialysis water,[16] other IV medications and solutions, various medical devices, and skin disinfectants. A previous study linked an outbreak of B. cepacia complex recovered from sputum of 18 patients to extrinsic contamination of multi-dose albuterol used for
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nebulization treatment in these patients. [17] In 2007, a study linked intrinsically contaminated alcohol-free mouthwash to a multi-state outbreak of B. cepacia. [18] A recent study in 2015 reported that a total of 13 cancer patients with tunneled catheters were affected by a B.
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cepacia blood stream infection. The outbreak was linked to intrinsic contamination of anti-
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emetic medication vials. [19] In August 2016, the US-CDC confirmed 60 cases of infections caused by B. cepacia complex in eight states and continued to urge clinicians to report any infections caused by B. cepacia in non-cystic fibrosis patients. This outbreak was linked to the contaminated oral liquid, docusate. [20] This outbreak investigation linked B. cepacia bacteraemia to contaminated ultrasound gel, which was included in the ultrasound probe cover kit. Molecular typing of pathogens by PFGE
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confirmed the similarity between B. cepacia isolated from the blood of the 14 patients involved in the outbreak and the organism isolated from ultrasound gel sachets. The intrinsic
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contamination is most likely to have occurred during the manufacturing process.
Products that are supposed to be sterile can become contaminated during the manufacturing
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process, leading to infections. Invasive procedures put patients at higher risk for infection, particularly immunocompromised ICU patients. The case control study excluded IV fluids and
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medications as a point source for the outbreak. Central line insertion procedure review was important to recognize possible sources of contamination. Live and continuous communication of the outbreak and the investigation progress with the stakeholders was vital. Collaboration between different departments, as well as the local authorities, worked well towards
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terminating the outbreak by withdrawal of the contaminated product.
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This outbreak report highlights the potential role of B. cepacia in causing outbreaks particularly in intensive care units. Prompt and in-depth investigations of B. cepacia bacteraemia clusters
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are vital for identifying sources of contamination.
Acknowledgment;
No financial support was provided relevant to this article.
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All authors report no conflict of interest relevant to this article. All authors submitted the ICMJE
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form for disclosure of potential conflicts of interest.
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References
6. 7.
8.
9.
10.
11.
12.
13.
14.
15.
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SC
5.
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4.
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3.
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2.
Antony B, Cherian EV, Boloor R, Shenoy KV. A sporadic outbreak of Burkholderia cepacia complex bacteraemia in pediatric intensive care unit of a tertiary care hospital in coastal Karnataka, South India. Indian J Pathol Microbiol, 2016. 59(2): p. 197-9. Doit C, Loukil C, Simon A-M, Ferroni A, Fontan J-E, Bonacorsi S, et al. Outbreak of Burkholderia cepacia bacteraemia in a pediatric hospital due to contamination of lipid emulsion stoppers. J Clin Microbiol, 2004. 42(5): p. 2227-30. Wiener-Well Y, Segonds C, Mazuz B, Kopuit P, Assous MV. Successful outbreak investigation of Burkholderia cepacia complex bacteremia in intensive care patients. Am J Infect Control, 2014. 42(5): p. 580-1. 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(9): p. 832-7. Pegues DA. Burkholderia cepacia complex. Infectious Disease and Antimicrobial Agents. 2017; Available from: http://www.antimicrobe.org/b19.asp. Gautom RK. Rapid pulsed-field gel electrophoresis protocol for typing of Escherichia coli O157:H7 and other Gram-negative organisms in 1 day. J Clin Microbiol, 1997. 35(11): p. 2977-80. Hamill RJ, Houston ED, Georghiou PR, Wright CE, Koza MA, Cadle RM, et al. An outbreak of Burkholderia (formerly Pseudomonas) cepacia respiratory tract colonization and infection associated with nebulized albuterol therapy. Ann Intern Med, 1995. 122(10): p. 762-6. 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(6): p. 394-8. Memish ZA, Stephens G, Balkhy HH, Cunningham G, Francis C, Poff G, et al. Outbreak of Burkholderia cepacia bacteremia in immunocompetent children caused by contaminated nebulized sulbutamol in Saudi Arabia. Am J Infect Control, 2009. 37(5): p. 431-2. Ko S, An HS, Bang JH, Park SW. An outbreak of Burkholderia cepacia complex pseudobacteremia associated with intrinsically contaminated commercial 0.5% chlorhexidine solution. Am J Infect Control, 2015. 43(3): p. 266-8. Tandel K, Bhatt P, Sen S, Gupta RM, Hazra N, Praharaj AK, et al. Burkholderia cepacia pseudobacteremia traced to contaminated antiseptic used for skin antisepsis prior to blood collection. Reviews in Medical Microbiology, 2016. 27(4): p. 136-140. Moehring RW, Lewis SS, Isaacs PJ, Schell WA, Thomann WR, Althaus MM,et al. Outbreak of bacteraemia due to Burkholderia contaminans linked to intravenous fentanyl from an institutional compounding pharmacy. Jama Internal Medicine, 2014. 174(4): p. 606-612. Souza Dias MB, Cavassin LG, Stempliuk V, Xavier LS, Lobo RD, Sampaio JL, et al.Multiinstitutional outbreak of Burkholderia cepacia complex associated with contaminated mannitol solution prepared in compounding pharmacy. American Journal of Infection Control, 2013. 41(11): p. 1038-1042. van Laer F, Raes D, Vandamme P, Lammens C, Sion JP, Vrints C, et al. An outbreak of Burkholderia cepacia with septicemia on a cardiology ward. Infection Control and Hospital Epidemiology, 1998. 19(2): p. 112-113. 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. Critical Care, 2008. 12(1).
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1.
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RI PT
SC
20.
M AN U
19.
TE D
18.
EP
17.
Yan H, Shi L, Alam MJ, Li L, Yang L, Yamasaki S. Usefulness of Sau-PCR for molecular epidemiology of nosocomial outbreaks due to Burkholderia cepacia which occurred in a local hospital in Guangzhou, China. Microbiology and Immunology, 2008. 52(5): p. 283-286. Estivariz CF, Bhatti LI, Pati R, Jensen B, Arduino MJ, Jernigan D, et al. An outbreak of Burkholderia cepacia associated with contamination of albuterol and nasal spray. Chest, 2006. 130(5): p. 1346-53. Kutty PK, Moody B, Gullion JS, Zervos M, Ajluni M, Washburn R, et al. Multistate outbreak of Burkholderia cenocepacia colonization and infection associated with the use of intrinsically contaminated alcohol-free mouthwash. Chest, 2007. 132(6): p. 1825-1831. Singhal T, Shah S, Naik R. Outbreak of Burkholderia cepacia complex bacteraemia in a chemotherapy day care unit due to intrinsic contamination of an antiemetic drug. Indian Journal of Medical Microbiology, 2015. 33(1): p. 117-119. Herrera G, Hernández C, Ayala MS, Flórez C, Teherán AA, Ramírez JD. Evaluation of a Multilocus Sequence Typing (MLST) scheme for Leishmania (Viannia) braziliensis and Leishmania (Viannia) panamensis in Colombia. Parasit Vectors, 2017. 10(1): p. 236.
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16.
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Table 1. Demography and clinical features of patients who developed Burkholderia cepacia
bacteraemia
Male
1/4/2016
42
Female
1/10/2016
1/18/2016
36
Female
1/11/2016
1/17/2016
47
Female
3/20/2016
3/20/2016
19
Male
2/18/2016
27
Male
4/3/2016
3/21/2016 ((from catheter tip) 4/4/2016
60
Female
3/21/2016
4/10/2016
46
Male
4/15/2016
4/16/2016
82
Female
4/25/2016
4/25/2016
62
Female
4/18/2016
4/27/2016
77
Male
5/9/2016
5/13/2016
85
Male
5/27/2016
5/27/2016
Clinical diagnosis Anasarca, HAP
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Treatment received
TMP-SMX+ Meropenem Multiple Neuro- Meropenem endocrine tumor, for pancreatectom y ESRD, multiple Meropenem pathological bone fracture ARDS, No Atypical/Fungal treatment pneumonia given Post BMT, No GVHD, sepsis treatment caused by XDR- given PA RTA, fracture Meropenem femur and intraabdominal HMG SLE flare up, Meropenem sever sepsis with MOF Post poly TMP-SMX trauma, HAP Acute Meropenem Hemorrhagic + stroke, HAP, C Tiecoplanin Diff Intractable TMP-SMX sepsis with MOF Septic shock Ceftazidime due to aspiration pneumonia Acute kidney Ceftazidime injury, intestinal
Patient outcome; survived Yes
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62
Date of positive culture 1/8/2016
Yes
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Date of admission
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Gender
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Age
Yes
Yes
No
Yes
No
Yes Yes
No
Yes
No
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Female
6/4/2016
6/4/2016
35
Female
5/27/2016
6/8/2016
Infected abdominal wall hematomapost C Section
No treatment given Meropenem
No
Yes
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66
obstruction and sepsis Sever sepsis with MOF
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HAP: Hospital acquired pneumonia, TMP-SMX: Trimethoprim-Sulfamethoxazole, ESRD: End stage renal disease, ARDS: Acute respiratory distress syndrome, MOF: Multi organ failure, BMT: Bone marrow transplant, GVHD: Graft versus host disease, XDR-PA: Extreme drug resistant pseudomonas aeruginosa, RTA: Road traffic accident, HMG: Hemorrhage, SLE: System lupus erythematosus, C Diff: Clostridium difficile, C Section: Cesarean section.
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Outbreak of Burkholderia cepacia bacteremia in tertiary care center; figure # 1
Time line of Burkholderia Cepacia outbreak 16
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14
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12 10 8 6
0
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2
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4
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Epidemic curve showing cumulative number of patient with Burkholderia Cepacia bacteremia before and after withdrawal of the contaminated product. The date of complete withdrawal of the contaminated ultra sound gel was 15th Jun, 2016. Active surveillance continued 6 months after that and no positive cases were detected.
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Figure 2. Dendrogram based on the molecular types (PFGE results) of the B. cepacia isolates: Samples # 5, 11, 15, and 16 are isolates recovered from the ultrasound gel and the rest are clinical isolates from patients. See Supplementary table 1 for further information on isolates.
S0195-6701(17)30516-9
DOI:
10.1016/j.jhin.2017.09.010
Reference:
YJHIN 5224
To appear in:
Journal of Hospital Infection
Received Date: 20 July 2017 Accepted Date: 12 September 2017
Please cite this article as: Abdelfattah R, Aljumaah S, Alqahtani A, Althawadi S, Barron I, Almofada S, Outbreak of Burkholderia cepacia bacteraemia in a tertiary care centre due to contaminated ultrasound probe gel, Journal of Hospital Infection (2017), doi: 10.1016/j.jhin.2017.09.010. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Outbreak of Burkholderia cepacia bacteraemia in a tertiary care centre due to contaminated ultrasound probe gel
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Authors; 1- Rehab Abdelfattah; King Faisal Specialist Hospital and Research Center.
Address correspondence to Rehab Abdelfattah, MD MPH- King Faisal Specialist Hospital
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& Research Center, P.O.Box 3354, Riyadh 11211, MBC-89, Saudi Arabia. Email: [email protected].
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2- Suliman Aljumaah; King Faisal Specialist Hospital and Research Center 3- Ahmed Alqahtani; King Faisal Specialist Hospital and Research Center 4- Sahar Althawadi; King Faisal Specialist Hospital and Research Center
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5- Irene Barron; King Faisal Specialist Hospital and Research Center
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6- Saleh Almofada; King Faisal Specialist Hospital and Research Center
All authors have read and approved the submission of the manuscript to JHI. Total word count= 2800
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ABSTRACT Background. Burkholderia cepacia is a significant opportunistic organism in hospitalized and
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immunocompromised patients, particularly in cystic fibrosis [1] Aims. We describe the epidemiological investigation of an outbreak of B. cepacia bacteraemia Methods. The study examined 14 patients during their admission to three ICUs (Intensive Care
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Units) in a tertiary care hospital between January–June 2016. The outbreak involved 9 (57%)
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female and 6 (43%) male patients. All patients were adults of ages ranging from 19–85 years with a median age of 52 years. Patients’ medical charts, laboratory cultures, exposures, and central line insertion procedures were reviewed.
Findings. B. cepacia was isolated from the blood cultures of 14 patients resulting from
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contamination of the gel applied to the ultrasound probe used to guide the insertion of a central venous catheter. Molecular pathogen typing using pulsed field gel electrophoresis showed 95% similarity between the B. cepacia isolates from the blood of these patients and
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those isolated from the ultrasound gel.
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Conclusions. Ongoing surveillance and prompt investigation of unusual disease outbreaks are vital for identifying sources of contamination of B. cepacia and protecting at-risk patients. Sound epidemiological methods are very important for identifying the source of any hospital infection outbreak. KEYWORDS
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Burkholderia Cepacia, Bacteremia, Outbreak investigations, Intensive care units, Ultrasound
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probe cover, Opportunistic infections.
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INTRODUCTION Burkholderia cepacia is an aerobic gram-negative bacterium that can survive in soil and wet
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environments for a long periods of time.[1-4] B. cepacia is more commonly a colonizer rather than an infecting organism.[1, 2] It is intrinsically resistant to aminoglycosides and first- and second-generation Cephalosporins [5]. B. cepacia pseudo-bacteraemia has been described in
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many studies, but true bacteraemia is rare.[2]
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B. cepacia poses few medical risks to healthy individuals.[2] However, it is a known to cause hospital-acquired infections, especially in immunocompromised patients and patients with chronic lung diseases, such as cystic fibrosis.[1-4] Outbreaks of B. cepacia bacteraemia are often associated with contaminated intravenous (IV) medications, medical devices, or skin
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disinfectants.[1-4] Transmission of B. cepacia by person-to-person contact, contact with
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5]
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contaminated surfaces, or exposure to B. cepacia in the environment has also been reported.[2,
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METHODS Ethical approval for this study was granted from the local institutional review boards on 5
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March 2017. The tertiary care facility where the B. cepacia outbreak occurred is a large and advanced referral hospital in Riyadh, Saudi Arabia, that includes over 1500 hospital beds. It has a total of nine intensive care units (ICUs). The B. cepacia bacteraemia outbreak was reported in
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three of these ICUs: ICU-A, ICU-B, and ICU-C. The outbreak occurred between January 8, 2016 and June 15, 2016 (Figure 1). In January of 2016, the Department of Infection Control and
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Hospital Epidemiology noticed a cluster of three cases of bacteraemia caused by an unusual organism: B. cepacia. A case definition was developed as clinical laboratory identified blood isolates of B. cepacia in inpatient and outpatient units and in all age groups (adult and children). A retrospective review of medical records and laboratory culture results from 2014–2015
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revealed no previous cases of B. cepacia bacteraemia in these ICUs.
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The first three cases of B. cepacia bacteraemia occurred in January of 2016. The cluster involved three patients admitted to the ICU between January 4–11, 2016. The first patient was
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a 62-year-old male admitted with anasarca following a kidney transplant. He had one positive blood culture for B. cepacia 4 days following admission, which was treated with Trimethoprim Sulfamethoxazole and Meropenem. The second patient was a 42-year-old female admitted with a metastatic neuro-endocrine tumor who had four positive blood cultures for B. cepacia. The first one was reported 8 days after admission. The third patient was a 36-year-old female admitted with End-Stage Renal Disease (ESRD) and multiple pathological bone fractures. She
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had one positive blood culture for B. cepacia 7 days after admission. All patients were treated successfully with Meropenem. Table 1 summarizes the patients’ demography, date clinical
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history and outcomes.
We conducted environmental and epidemiological investigations after the first few cases.
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However, no significant epidemiological associations or positive environmental cultures were reported. Active surveillance for similar cases was ongoing using the stated case definition. No
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cases were reported during February 2016.
In March, a 47-year-old female patient was admitted to ICU-B with Acute Respiratory Distress
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Syndrome (ARDS). The patient had one positive blood culture for B. cepacia. However, the second culture was negative, and no treatment for B. cepacia was given. An additional 19-yearold male patient admitted to the same ICU (ICU-B) had B. cepacia isolated from the catheter tip,
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but blood cultures were only positive for multidrug resistant (MDR) Pseudomonas aeruginosa. In April, five new cases were reported, suggesting the existence of a common source of
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contamination. Two patients had sustained a road traffic accident (RTA) and were referred from a peripheral hospital for surgical reconstruction procedures. Both patients had one positive blood culture for B. cepacia on the same day of admission. These blood cultures were collected immediately after central line insertion. The blood samples collected from the central line of these two patients were positive for B. cepacia, while blood cultures from peripheral lines were negative. One patient was treated with Meropenem and the second patient received TMP/SMX
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(Trimethoprim- Sulfamethoxazole). Over the following 3 weeks, B. cepacia was isolated from the blood of three more patients. Two patients had been admitted with severe sepsis and
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Multi-Organ Failure (MOF), and the third patient had been diagnosed with hemorrhagic encephalopathy, Hospital Associated Pneumonia (HAP), and a Clostridium difficile infection. Two patients died of septic shock. More cases occurred during May and June. The clinical
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details are outlined in Table 1.
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All B. cepacia isolates were tested for antibiotic susceptibility by utilizing the VITEK 2 system (bioMérieux) according to the manufacturer’s instructions. The following antibiotics were tested: ceftazidime, meropenem, levofloxacin, trimethoprim-sulfamethoxazole (TMP-SMX), minocycline, and ticarcillin-clavulanic acid. All 14 blood isolates displayed identical susceptibility
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profiles, with a high susceptibility to TMP-SMX, ceftazidime, and meropenem.
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To identify the source of the B. cepacia infections, various consumables used by all 14 patients were investigated including central lines (CL), injection fluid/medications, central line insertion
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techniques, products, and surfaces. A total of 97 environmental samples were collected in early May 2016. Environmental samples from the three ICUs involved in the B. cepacia outbreak included CL insertion kits, CVC insertion trolleys, sterile saline used for flushing the lines after insertion, Chloraprep (other than what is included in the CVC kit), and syringes.
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Molecular typing of pathogens by pulsed field gel electrophoresis (PFGE) was performed on the B. cepacia isolates. Briefly this involved taking single colonies of the isolate and inoculating a 3
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mL trypticase soy broth with overnight incubation at 37°C in a shaker incubator. Cells were harvested by centrifugation at 1900 g for 10 min. Bacterial pellets were suspended in SE buffer (75 mM NaCl, pH 8.0; 25 mM EDTA, pH 8.0), and the final cell density was adjusted to 1.40 at a
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wavelength of 610 nm. Plugs were prepared by mixing 500 μl aliquots of cell suspensions and 500 μl of 1.6% low melting point (LMP) agarose. This agar-cell suspension mixture was
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immediately distributed into the wells of the plug molds and they were allowed to solidify at 4°C for 30 min. The plugs were transferred into tubes containing 1 ml of lysis buffer (50 mM Tris HCl, pH 8.0; 50 mM EDTA, pH 8.0; 1% sarcosine; 1 mg/ml proteinase K) and incubated overnight in a water bath at 55°C. Plugs were washed with 5 ml of sterile purified water at room
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temperature for 5 min, followed by four washes (30 min each) with 5 ml TE buffer (10 mM Tris– HCl, pH 8.0; 1 mM EDTA, pH 8.0) at room temperature. A plug slice 3×5 mm wide was put into a 1.5 ml microcentrifuge tube containing 200 μl of 1X restriction buffer and 50 U of SpeI. The
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mixture was incubated overnight at 37°C. Plug slices were inserted wells of 1% agarose gel, which were overlaid with 1% LMP agarose dissolved in 0.5X TBE. After solidification, the gel was
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run with a CHEF-Mapper apparatus in 3 L of 0.5X TBE buffer at an initial switch time of 2.2 s, a final switch time of 54.2 s, a running time of 22 h, a gradient of 6 V/cm, an angle of 120°, and a temperature of 14°C. The gel was stained for 30 min in 300 ml of sterile distilled water containing 1 μg/ml ethidium bromide. The gel was then de-stained by washing with 2 L of distilled water for 30 minutes. Gel images were digitized using a UV gel image acquisition camera (Gel Doc XR). Comparisons were performed using Bio-Numeric version 7.5 software.
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DNA fragments on each gel were normalized using a Lambda molecular weight standard to allow comparisons between gels. Cluster analysis was performed using the Dice coefficient. A
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2.0% band tolerance and an optimization of 4.0% were selected to compare the DNA profiles.
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[6]
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RESULTS We gathered information regarding all IV fluids and medications administered before or on the
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same collection day of the positive blood cultures. No multi-use vials or medication were used in the three ICUs during the outbreak. We conducted a case-control study among all 14 patients and 32 matching controls who were admitted to the same ICUs during the same timeframe
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during the outbreak. The three most frequently utilized IV fluids and medications were fentanyl, heparin, and magnesium sulphate. This analysis showed that there was no single IV
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fluid or medication utilized in the bacteraemia cases and not in the controls. Thus, we excluded IV fluids and medications as a potential source of the outbreak.
To exclude B. cepacia respiratory colonization, all 14 medical charts were reviewed and all of
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them had BAL (Broncho-alveolar lavage)/ respiratory cultures done as part of the case management. However, all these cultures were negative for B. cepacia, which suggested that a
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respiratory source or colonization were unlikely. Because of the concomitant B. cepacia outbreaks reported by the United States Center for Disease Control (US-CDC) in five different
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states linked to contaminated oral liquid docusate, all 14 medical charts were reviewed for the use of oral liquid Docusate before a positive blood culture for B. cepacia was confirmed. Results showed that of the 14 patients, only one patient (who had B. cepacia isolated from the central catheter tip) was given the medication. Therefore, docusate as a source of the outbreak was also excluded.
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Epidemiological investigations and line-listing of all patients elucidated that 11/14 patients (79%) had a positive blood culture for B. cepacia, which was collected directly from the CL
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immediately after insertion. All 14 patients had a bedside CL inserted at ICU-A, ICU-B, or ICU-C and all were admitted to different rooms in those units. ICU-A, ICU-B, and ICU-C all had the same medical and nursing management team. The CL type that was inserted in all 14 patients
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was a triple-lumen CVC, so randomly collected kits for all different CL types available in the hospital, were collected and cultured under standard aseptic techniques. Each kit had eight
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different parts. Therefore, eight samples were collected from each CVC kit including a line flush, catheter tip, three pieces of lumen, syringe flush, dilator flush and tip, Lidocaine, Chloraprep, and the transducer. All cultures from the CL kits were negative for B. cepacia.
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By reviewing the steps of CVC insertion, it was noted that all patients underwent an ultrasoundguided CVC insertion, and that was the only common factor among all 14 cases. Subsequent investigations focused on the probability that the common source of contamination might be
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linked to the ultrasound use during the CVC insertion. Cultures were collected from ultrasound
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machines from the three ICUs, as well as from ultrasound probe cover kits available in these three units.
The ultrasound probe cover kit contained various components, including the probe cover telescope folded within the kit, an ultrasound gel sachet, and two rubber bands. Each component was tested, and B. cepacia was cultured from the ultrasound gel sachet. Samples
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from unopened stocks of the same product with different lot numbers were obtained from ICU-
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B and cultured. These ultrasound gel samples were also positive for B. cepacia.
Investigations revealed that the contaminated product was available only in the three ICUs involved in the outbreak (ICU-A, ICU-B, and ICU-C), and these ICUs directly purchased the
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product from the vendor. Other units, such as the Department of Emergency Medicine,
Operative Rooms, and Cardiac and Pediatric ICUs, used an ultrasound probe cover kit from a
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different manufacturer that was distributed from the hospital medical stores. As a precautionary step, this product was also tested, and the samples were negative for B. cepacia. Molecular typing of pathogens by pulsed field gel electrophoresis (PFGE) confirmed the similarity between the B. cepacia isolates from the blood of the 14 patients and the organism
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isolated from the ultrasound gel (Figure 2).
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Findings were immediately reported to the manufacturer, local vendor, local authorities, and our sister hospital in Jeddah. No cases of B. cepacia were reported in Jeddah Hospital, most
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likely because this product was used for non-invasive procedures. Corrective action was undertaken by hospital-wide withdrawal of the contaminated product. Since then, no additional cases have been reported.
DISCUSSION
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The outbreak investigation demonstrated that ultrasound gel was the source of this B. cepacia outbreak as evidenced by culturing the same strain from patients and the contaminated gel.
of the contaminated gel resulted in termination of the outbreak.
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Extensive investigations did not reveal any other linked products or processes and replacement
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Previous studies have linked B. cepacia outbreaks to different contaminated products, such as multi-use vials of ringer lactate [4], albuterol solution for nebulization,[7-9] chlorohexidine,[10,
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11] fentanyl,[12] mannitol solution,[13] heparin injection,[14] moisturizing body milk,[15] reverse osmosis dialysis water,[16] other IV medications and solutions, various medical devices, and skin disinfectants. A previous study linked an outbreak of B. cepacia complex recovered from sputum of 18 patients to extrinsic contamination of multi-dose albuterol used for
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nebulization treatment in these patients. [17] In 2007, a study linked intrinsically contaminated alcohol-free mouthwash to a multi-state outbreak of B. cepacia. [18] A recent study in 2015 reported that a total of 13 cancer patients with tunneled catheters were affected by a B.
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cepacia blood stream infection. The outbreak was linked to intrinsic contamination of anti-
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emetic medication vials. [19] In August 2016, the US-CDC confirmed 60 cases of infections caused by B. cepacia complex in eight states and continued to urge clinicians to report any infections caused by B. cepacia in non-cystic fibrosis patients. This outbreak was linked to the contaminated oral liquid, docusate. [20] This outbreak investigation linked B. cepacia bacteraemia to contaminated ultrasound gel, which was included in the ultrasound probe cover kit. Molecular typing of pathogens by PFGE
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confirmed the similarity between B. cepacia isolated from the blood of the 14 patients involved in the outbreak and the organism isolated from ultrasound gel sachets. The intrinsic
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contamination is most likely to have occurred during the manufacturing process.
Products that are supposed to be sterile can become contaminated during the manufacturing
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process, leading to infections. Invasive procedures put patients at higher risk for infection, particularly immunocompromised ICU patients. The case control study excluded IV fluids and
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medications as a point source for the outbreak. Central line insertion procedure review was important to recognize possible sources of contamination. Live and continuous communication of the outbreak and the investigation progress with the stakeholders was vital. Collaboration between different departments, as well as the local authorities, worked well towards
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terminating the outbreak by withdrawal of the contaminated product.
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This outbreak report highlights the potential role of B. cepacia in causing outbreaks particularly in intensive care units. Prompt and in-depth investigations of B. cepacia bacteraemia clusters
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are vital for identifying sources of contamination.
Acknowledgment;
No financial support was provided relevant to this article.
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All authors report no conflict of interest relevant to this article. All authors submitted the ICMJE
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form for disclosure of potential conflicts of interest.
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References
6. 7.
8.
9.
10.
11.
12.
13.
14.
15.
RI PT
SC
5.
M AN U
4.
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3.
EP
2.
Antony B, Cherian EV, Boloor R, Shenoy KV. A sporadic outbreak of Burkholderia cepacia complex bacteraemia in pediatric intensive care unit of a tertiary care hospital in coastal Karnataka, South India. Indian J Pathol Microbiol, 2016. 59(2): p. 197-9. Doit C, Loukil C, Simon A-M, Ferroni A, Fontan J-E, Bonacorsi S, et al. Outbreak of Burkholderia cepacia bacteraemia in a pediatric hospital due to contamination of lipid emulsion stoppers. J Clin Microbiol, 2004. 42(5): p. 2227-30. Wiener-Well Y, Segonds C, Mazuz B, Kopuit P, Assous MV. Successful outbreak investigation of Burkholderia cepacia complex bacteremia in intensive care patients. Am J Infect Control, 2014. 42(5): p. 580-1. 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(9): p. 832-7. Pegues DA. Burkholderia cepacia complex. Infectious Disease and Antimicrobial Agents. 2017; Available from: http://www.antimicrobe.org/b19.asp. Gautom RK. Rapid pulsed-field gel electrophoresis protocol for typing of Escherichia coli O157:H7 and other Gram-negative organisms in 1 day. J Clin Microbiol, 1997. 35(11): p. 2977-80. Hamill RJ, Houston ED, Georghiou PR, Wright CE, Koza MA, Cadle RM, et al. An outbreak of Burkholderia (formerly Pseudomonas) cepacia respiratory tract colonization and infection associated with nebulized albuterol therapy. Ann Intern Med, 1995. 122(10): p. 762-6. 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(6): p. 394-8. Memish ZA, Stephens G, Balkhy HH, Cunningham G, Francis C, Poff G, et al. Outbreak of Burkholderia cepacia bacteremia in immunocompetent children caused by contaminated nebulized sulbutamol in Saudi Arabia. Am J Infect Control, 2009. 37(5): p. 431-2. Ko S, An HS, Bang JH, Park SW. An outbreak of Burkholderia cepacia complex pseudobacteremia associated with intrinsically contaminated commercial 0.5% chlorhexidine solution. Am J Infect Control, 2015. 43(3): p. 266-8. Tandel K, Bhatt P, Sen S, Gupta RM, Hazra N, Praharaj AK, et al. Burkholderia cepacia pseudobacteremia traced to contaminated antiseptic used for skin antisepsis prior to blood collection. Reviews in Medical Microbiology, 2016. 27(4): p. 136-140. Moehring RW, Lewis SS, Isaacs PJ, Schell WA, Thomann WR, Althaus MM,et al. Outbreak of bacteraemia due to Burkholderia contaminans linked to intravenous fentanyl from an institutional compounding pharmacy. Jama Internal Medicine, 2014. 174(4): p. 606-612. Souza Dias MB, Cavassin LG, Stempliuk V, Xavier LS, Lobo RD, Sampaio JL, et al.Multiinstitutional outbreak of Burkholderia cepacia complex associated with contaminated mannitol solution prepared in compounding pharmacy. American Journal of Infection Control, 2013. 41(11): p. 1038-1042. van Laer F, Raes D, Vandamme P, Lammens C, Sion JP, Vrints C, et al. An outbreak of Burkholderia cepacia with septicemia on a cardiology ward. Infection Control and Hospital Epidemiology, 1998. 19(2): p. 112-113. 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. Critical Care, 2008. 12(1).
AC C
1.
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RI PT
SC
20.
M AN U
19.
TE D
18.
EP
17.
Yan H, Shi L, Alam MJ, Li L, Yang L, Yamasaki S. Usefulness of Sau-PCR for molecular epidemiology of nosocomial outbreaks due to Burkholderia cepacia which occurred in a local hospital in Guangzhou, China. Microbiology and Immunology, 2008. 52(5): p. 283-286. Estivariz CF, Bhatti LI, Pati R, Jensen B, Arduino MJ, Jernigan D, et al. An outbreak of Burkholderia cepacia associated with contamination of albuterol and nasal spray. Chest, 2006. 130(5): p. 1346-53. Kutty PK, Moody B, Gullion JS, Zervos M, Ajluni M, Washburn R, et al. Multistate outbreak of Burkholderia cenocepacia colonization and infection associated with the use of intrinsically contaminated alcohol-free mouthwash. Chest, 2007. 132(6): p. 1825-1831. Singhal T, Shah S, Naik R. Outbreak of Burkholderia cepacia complex bacteraemia in a chemotherapy day care unit due to intrinsic contamination of an antiemetic drug. Indian Journal of Medical Microbiology, 2015. 33(1): p. 117-119. Herrera G, Hernández C, Ayala MS, Flórez C, Teherán AA, Ramírez JD. Evaluation of a Multilocus Sequence Typing (MLST) scheme for Leishmania (Viannia) braziliensis and Leishmania (Viannia) panamensis in Colombia. Parasit Vectors, 2017. 10(1): p. 236.
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Table 1. Demography and clinical features of patients who developed Burkholderia cepacia
bacteraemia
Male
1/4/2016
42
Female
1/10/2016
1/18/2016
36
Female
1/11/2016
1/17/2016
47
Female
3/20/2016
3/20/2016
19
Male
2/18/2016
27
Male
4/3/2016
3/21/2016 ((from catheter tip) 4/4/2016
60
Female
3/21/2016
4/10/2016
46
Male
4/15/2016
4/16/2016
82
Female
4/25/2016
4/25/2016
62
Female
4/18/2016
4/27/2016
77
Male
5/9/2016
5/13/2016
85
Male
5/27/2016
5/27/2016
Clinical diagnosis Anasarca, HAP
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Treatment received
TMP-SMX+ Meropenem Multiple Neuro- Meropenem endocrine tumor, for pancreatectom y ESRD, multiple Meropenem pathological bone fracture ARDS, No Atypical/Fungal treatment pneumonia given Post BMT, No GVHD, sepsis treatment caused by XDR- given PA RTA, fracture Meropenem femur and intraabdominal HMG SLE flare up, Meropenem sever sepsis with MOF Post poly TMP-SMX trauma, HAP Acute Meropenem Hemorrhagic + stroke, HAP, C Tiecoplanin Diff Intractable TMP-SMX sepsis with MOF Septic shock Ceftazidime due to aspiration pneumonia Acute kidney Ceftazidime injury, intestinal
Patient outcome; survived Yes
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62
Date of positive culture 1/8/2016
Yes
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Date of admission
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Gender
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Age
Yes
Yes
No
Yes
No
Yes Yes
No
Yes
No
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Female
6/4/2016
6/4/2016
35
Female
5/27/2016
6/8/2016
Infected abdominal wall hematomapost C Section
No treatment given Meropenem
No
Yes
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obstruction and sepsis Sever sepsis with MOF
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HAP: Hospital acquired pneumonia, TMP-SMX: Trimethoprim-Sulfamethoxazole, ESRD: End stage renal disease, ARDS: Acute respiratory distress syndrome, MOF: Multi organ failure, BMT: Bone marrow transplant, GVHD: Graft versus host disease, XDR-PA: Extreme drug resistant pseudomonas aeruginosa, RTA: Road traffic accident, HMG: Hemorrhage, SLE: System lupus erythematosus, C Diff: Clostridium difficile, C Section: Cesarean section.
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Outbreak of Burkholderia cepacia bacteremia in tertiary care center; figure # 1
Time line of Burkholderia Cepacia outbreak 16
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14
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12 10 8 6
0
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2
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4
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Epidemic curve showing cumulative number of patient with Burkholderia Cepacia bacteremia before and after withdrawal of the contaminated product. The date of complete withdrawal of the contaminated ultra sound gel was 15th Jun, 2016. Active surveillance continued 6 months after that and no positive cases were detected.
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Figure 2. Dendrogram based on the molecular types (PFGE results) of the B. cepacia isolates: Samples # 5, 11, 15, and 16 are isolates recovered from the ultrasound gel and the rest are clinical isolates from patients. See Supplementary table 1 for further information on isolates.