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Hospital-wide outbreak of Burkholderia contaminans caused by prefabricated moist washcloths
Journal of Hospital Infection 77 (2011) 267e270
Available online at www.sciencedirect.com
Journal of Hospital Infection journal homepage: www.elsevierhealth.com/journals/jhin
Hospital-wide outbreak of Burkholderia contaminans caused by prefabricated moist washcloths M. Martin a, *, B. Christiansen b, G. Caspari b, M. Hogardt c, A.J. von Thomsen a, E. Ott d, F. Mattner a a
University of Lübeck, Institute for Medical Microbiology and Hygiene, Lübeck, Germany Universitätsklinikum Schleswig-Holstein, Medizinaluntersuchungsamt and Krankenhaushygiene, Kiel, Germany c Max von Pettenkofer-Institut, Ludwig-Maximillians-Universität München, München, Germany d Medizinische Hochschule Hannover, Institut für Med. Mikrobiologie und Krankenhaushygiene, Arbeitsbereich Krankenhaushygiene, Hannover, Germany b
a r t i c l e i n f o
s u m m a r y
Article history: Received 26 May 2010 Accepted 7 October 2010 Available online 7 January 2011
We experienced a hospital outbreak of Burkholderia contaminans (Burkholderia cepacia Group K) in a German university hospital with two campuses. Cases were defined as the microbiological detection of B. cepacia complex (BCC) in any clinical specimen sent to the laboratory during 30 June to 21 October 2008. Species identification of BCC was performed by recA gene sequencing, followed by pulsed-field gel electrophoresis (PFGE; SpeI digest) for clonal identity. In total, 61 BCC-positive cases were diagnosed at the two campuses. At least nine patients contracted a ventilator-associated pneumonia with BCC. One patient suffered an infection of a pacing wire insertion site and four patients had septicaemia. Sixteen patients died in hospital, none thought to be due to the outbreak strain. BCC was eventually found in packages of moist prefabricated washcloths used for intensive care patients. German healthcare authorities were informed and a Europe-wide alarm (RAPEX) was initiated through the systems to prevent infections in other hospitals. PFGE proved clonal identity between isolates from clinical specimens and washcloths of both campuses. After elimination of the contaminated washcloths no further cases occurred. This example of a relatively newly introduced product raises the question of whether current regulations are adequate to protect consumers. For critically ill patients, care products should be carefully evaluated. In case of infections due to contaminated products, immediate communication to healthcare authorities is required, including RAPEX warning if products are sold across Europe. Ó 2010 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved.
Keywords: Burkholderia contaminans Contaminated washcloths Outbreak Pneumonia RAPEX
Introduction According to the current molecular taxonomy, Burkholderia cepacia complex (BCC) is a group of opportunistic pathogens consisting of 17 different species (10 of them formerly known as genomovars).1,2 A recently described phylotype is Burkholderia contaminans (B. cepacia Group K).3 Organisms within BCC are generally considered to be of low virulence. They are ubiquitously found in the natural environment but also occur as contaminants in man-made products such as pharmaceuticals, cosmetics, * Corresponding author. Current address: University Medical Center Freiburg, Department of Environmental Health Sciences, Division of Infection Control and Hospital Epidemiology, Breisacher Str. 115b, 79106 Freiburg, Germany. Tel.: þ49 761 270 8277; fax: þ49 761 270 8253. E-mail address: [email protected] (M. Martin).
disinfectants and others.4e6 From these potential sources, BCC may colonise and infect susceptible patients in hospital settings. This is well documented in a number of reported outbreaks over recent decades. Affected individuals were not only those with underlying cystic fibrosis but also other immunocompromised patients, or patients with various devices.7,8 Documented sources vary from contaminated medical instruments and disinfectants to alcoholfree mouthwash and body milk.6,9e11 Nevertheless, the detection of BCC in non-cystic fibrosis patients is uncommon and the relevance for these patients is often unclear. Here, we report on an outbreak of B. contaminans which occurred from 30 June to 21 October 2008 in a tertiary care teaching hospital in northern Germany. A descriptive and prospective surveillance was performed to control the outbreak and environmental investigations were carried out to identify the source. To our knowledge this is the first reported outbreak of B. contaminans with
0195-6701/$ e see front matter Ó 2010 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jhin.2010.10.004
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M. Martin et al. / Journal of Hospital Infection 77 (2011) 267e270
the source being a relatively new care product for intensive care patients. Methods Hospital setting The tertiary care university hospital in the North of Germany consists of two campuses. Both of these hospitals (A and B) have about 1200 beds and five and six intensive care units (ICUs), respectively. At both campuses all ICUs are situated in different buildings. Each hospital has its own infection control team (ICT) communicating on a regular basis with each other. Case definition and identification of cases Case patients were defined as patients from whom BCC had been identified in any clinical specimen sent to the microbiological laboratory between 1 January and 31 October 2008. Patient charts were reviewed using a standardised data collection form. Infections were defined according to Centers for Disease Control and Prevention criteria (available online). Retrospective database analyses back to 1 January 2008 were conducted to identify all cases at both sites. Microbiological methods Clinical specimens were cultured according to appropriate methods for the different materials sent to the laboratory. Preliminary phenotypic identification of BCC was performed according to standard microbiological characteristics (Columbia blood agar, McConkey agar, oxidase reaction for suspected colonies) and by using the VitekÒ II system (bioMérieux, Marcy l’Etoile, France). Definite species identification was performed by rec-A gene sequencing using primers BCR1 and BCR2.12 To investigate clonal identity, BCC isolates were typed by pulsed-field gel electrophoresis (PFGE, SpeI digest). The discriminatory power of PFGE was tested with 20 epidemiologically unrelated strains (data not shown) and macrorestriction profiles were visually compared and interpreted according to the criteria of Tenover et al.13 Environmental samples such as mineral water, non-alcoholic mouthwashes, contact cultures of patients’ environments, prefabricated washcloths and others were investigated for BCC. Liquids were analysed by filtration through a 0.45 mm cellulose membrane filter and cultivation on Columbia blood agar at 37 C for 48 h. Suspected colonies were phenotypically identified by Vitek II system. Quantification of bacterial load of different lots of washcloths was performed as follows: one single washcloth was transferred into 100 mL sterile saline for 30 min at room temperature. Then 100 mL were plated on TSA agar and incubated at 37 C for 48 h. If this culture was negative, the remaining liquid (stored at 8 C) was filtered through a 0.45 mm cellulose membrane filter and cultured on Columbia blood agar at 37 C for 48 h. The number of colonies was counted thereafter. The identity of suspect colonies was confirmed using Vitek II system. Results Timescale of the outbreak in hospital B At the start of September 2008, the ICT of hospital B was aware of three patients positive for BCC in respiratory secretions in ICU B1. The ICT discussed this finding with the healthcare staff at this ICU. The recommendation not to use mineral water for mouth hygiene was renewed and the awareness of other possible external sources
for these bacteria was discussed. A few days later, three additional patients were diagnosed with BCC, two again in ICU B1, one in another (ICU B2). This made the initial suspicion that the strains were introduced from an external source more likely, and prospective active surveillance as well as environmental investigations were started. During this time, two additional BCC-positive patients in a third ICU (ICU B3) were identified. At the beginning of October, another five patients had been diagnosed with BCC obtained from respiratory secretions. On 2 October 2008, prefabricated moist washcloths were suspected as the source of the outbreak by the ICT of hospital A, and hospital B was informed. In all ICUs the stock was cleared and written information was given to all wards by the ICT. The last patient with BCC was identified in hospital B on 12 October 2008. In hospital A the last patient suspected to be involved in this outbreak was identified on 21 October 2008. Retrospective database analysis at both hospitals showed the first patients who fitted the case definition at the end of June 2008 in hospital A, and mid-August in hospital B, respectively. A total of 61 patients were finally found to be BCC positive as detected from microbiological cultures. Outcome hospital A and B None of the patients had medical conditions usually associated with BCC infection such as cystic fibrosis. Strains were first detected in respiratory specimens in 42 patients, in wound swabs in seven (two tracheostomy swab), in central vein catheters in four, in vaginal swabs in two and in one patient each from blood culture, pleural fluid, catheter specimen of urine, pacer electrode, and two other specimens. Two patients had secondary positive blood cultures. Eight patients suffered from BCC-induced pneumonia in hospital B, and at least one in hospital A. The antibiotic treatment usually included ciprofloxacin or cotrimoxazole. In hospital A, four patients had septicaemia. Sixteen patients died in hospital (three in hospital B, 13 in hospital A). All patients died as a result of their underlying disease process. Epidemiological data of hospitalised patients Demographic characteristics and diagnoses of case patients in hospitals A and B are shown in Table I. All patients in hospital B had an ICU stay prior to the first detection of BCC (median duration of ICU stay: 14 days; range: 6e16 days). In hospital A all patients but one had an ICU stay (median duration of ICU stay: 13 days; range: 0e44 days). Environmental results in hospital B Since BCC was initially detected in respiratory specimens of patients, we focused our initial environmental investigation on medical equipment and products used for ventilator care and mouth hygiene. Forty-three bottles of still mineral water of different lots were analysed for BCC. All bottles were negative but positive for Pseudomonas spp. and Acinetobacter spp. Four different types of alcohol-free mouthwash (25 bottles) did not show any bacterial growth. Samples from direct patient environment (contact cultures) from two different ICUs did not show growth of BCC. In response to the suspicions raised by the ICT at hospital A that prefabricated moist washcloths could be the possible source, we collected 12 packages of six different lots of these washcloths at different ICUs. Ten of the 12 initially analysed packages showed bacterial growth (one Stenotrophomonas maltophilia, all others BCC). Some packages were already unsealed, hence a secondary contamination could not be excluded. We subsequently analysed seven sealed packages and found three of five different batches
M. Martin et al. / Journal of Hospital Infection 77 (2011) 267e270 Table I Demographics and clinical characteristics of patients with B. contaminans-positive cultures Variables
Hospital A
No. of patients 42 Male 31 Female 11 Age (years) Mean 63.0 Range 22e87 Hospital admission diagnosis Cardiovascular e Gastrointestinal e Trauma e Infection e Other e Duration of ICU stay prior to first diagnosis (days) Median 13 Range 0e44 Specimen of first detection Respiratory secretion 25 Wound swab 6 Blood 1 Other 10 Infection Pneumonia 1 Wound infection 2 Bloodstream infection 4 2 Othera Colonisation 33 Death 13 Related to infection 0
Hospital B 19 13 6 63.9 46e82 9 6 3 1 0 14 6e66 17 1 0 1 8 1 0 0 10 3 0
e, no data available. a Other infections were a urinary tract infection and a dermatological infection.
positive for BCC. The quantitative analysis of the bacterial concentrations of sealed packages showed contamination ranging from 4 cfu to 5.6 107 cfu per washcloth. Microbiological findings For 37 isolates of BCC from the different sources (26 patients from both hospitals and 11 washcloth isolates from both laboratories) PFGE analysis revealed three closely related strains indistinguishable from one or other of these three outbreak strains. The rec-A gene sequencing of three isolates, one patient and two washcloth isolates from the different laboratories, identified the BCC subtype B. contaminans for all three isolates. Termination of the outbreak In discussion with leading nursing staff and clinic management it was decided to eliminate the prefabricated washcloths, which had been introduced in 2007. Healthcare authorities were informed so as to reduce the risk for other possible users of these washcloths. As it became obvious that this cosmetic product was also distributed to other European countries, authorities initiated a Europeanwide alert report via the RAPEX system (available online). This is a rapid alert system for dangerous consumer products and cosmetics, with the exception of foods, medical devices and pharmaceuticals. Since then, no replacement prefabricated washing system has been introduced throughout our hospital and the use of soap and water has been recommended. Discussion Bacteria belonging to B. cepacia complex are rarely detected as pathogens of nosocomial infections.14 The detection of BCC from clinical samples suggests an environmental source. However, the timely recognition of this outbreak was hampered by the fact that
269
the first cases did not occur in clusters but as single cases in different ICUs or after transfer from ICU to general wards. In June the first cases occurred in non-cystic fibrosis patients but the outbreak investigation only started in September 2008 at hospital A and B, when a cluster in an ICU was obvious. This partly explains the duration of the outbreak (about five months) and the number of patients involved. Identified sources for reported BCC outbreaks include therapeutic water, indigo-carmine dye to tint tube feedings, albuterol therapy, chlorhexidine, moisterising body milk and alcohol-free mouthwash.6,10,11,15e19 To our knowledge we report here the first BCC outbreak associated with prefabricated moist washcloths, a relatively new product for patient care. Prefabricated washcloths were introduced into the patient care market about 10 years ago. They are available as cosmetic as well as medical products. Most of these washing systems are not only for washing the patient but also contain moisturising products, so they are two-in-one products. They are sold as body washing systems for immobile patients and patients with special needs, such as ICU patients, to make daily body care easier and faster. One package of such a body washing system for daily body care contains up to eight moist washcloths and should be used for one patient at one time. As we collected the washing systems at different ICUs for laboratory tests we found that the systems were used differently. Some nurses did not use them at all, some used them just for cleaning of the perineal region and others used the washing system for everyday body care. This variable qualitative and quantitative use may be an explanation for the different numbers of affected patients on the two sites as well as the variable number in the single ICUs in this outbreak. Furthermore, leaving unused prefabricated moist washcloths in the unsealed package for further utilisation made another reservoir for various secondary pathogens and a possible source of infection for patients obvious. The washing system used here was declared as a cosmetic product. Quality controls are regulated by the European Council directive 76/768/EEC (available online), the German provisions, consumer products and feeding products law (LFGB) (available online), the cosmetic good manufacturer practice (GMP) and the Leitfaden des Industrieverbands Körperpflege- und Waschmittel e. V. (IKW) zum mikrobiologischen Qualitätsmanagement.20,21 These regulations specify the microbiological quality of cosmetic products as follows: cfu for 1 g of product 5 103 and absence of the pathogens Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans, Escherichia coli in 0.1 g of the product. These limiting values and the analytical methods are close to those given in the European Pharmacopoeia (Ph. Eur.) for topical non-sterile products. In contrast to the Ph. Eur. these standards do not state anything about the frequency of testing. Our quantitative analysis of the washcloths showed bacterial growth of more than the given limit of 5 103 cfu per 1 g and the presence of Gram-negative non-fermenting rods in three out of the five tested lots. BCC are non-fermenting, as Gram-negative bacilli such as P. aeruginosa and are recognised contaminants of industrial products.22 Medical and cosmetic products such as the one causing this outbreak do not have to be sterile if they are solely for topical use. Medical products require higher standards of control, regulated by the European Council directive 93/42/EEC (available online). From our experience that single batches can be highly contaminated, we recommend the use of routine microbiological testing of care products (per batch) for ICU patients. This product testing can be performed according to the standards of cosmetic products or the Ph. Eur. as the analytical methods, limits of cfu per gram and required absence of the above mentioned organisms are similar. In our opinion the manufacturer of care products should be asked to document these microbiological tests especially if the products are
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made for the care of vulnerable patients. If the products are declared as medical devices the hospital may request the manufacturer to provide a statement of infection risk of his product based on the European Council directive for medical devices (93/42/EEC). After eliminating the washcloths from the daily care of our patients, our major concern was to inform other possible users.23 We immediately passed on information to the authorities. The authorities confirmed the distribution of the washing systems to other European countries and an alert report was given through the well-established RAPEX system (available online) for consumer products. Unfortunately we have no knowledge of the experience of other users, nor whether they observed an outbreak of BCC during the same period. It therefore cannot be ascertained if the alert report actually prevented harm to other patients. In conclusion, we describe a large outbreak of B. contaminans involving 61 patients, some with severe infections. Eliminating the detected source e an intrinsically highly contaminated body care product e terminated the outbreak. Contaminated body care products are a potential source of infections for critically ill patients. Such products should only be used in ICU settings once the infection risks have been assessed. Early detection of uncommon pathogens in patients, even if they are of low virulence, and informing healthcare authorities can prevent further patients from harmful infections.
Acknowledgements We express our gratitude to Mrs F. Behrmann, Mr B. Grabowski and Mrs R. Simon for their assistance in resolving this outbreak and Mrs B. Pape for her technical assistance. Conflict of interest statement None declared. Funding sources None.
References 1. Vanlaere E, Baldwin A, Gevers D, et al. Taxon K, a complex within the Burkholderia cepacia complex, comprises at least two novel species, Burkholderia contaminans sp. nov. and Burkholderia lata sp. nov. Int J Syst Evol Microbiol 2009;59:102e111. 2. Vanlaere E, Lipuma JJ, Baldwin A, et al. Burkholderia latens sp. nov., Burkholderia diffusa sp. nov., Burkholderia arboris sp. nov., Burkholderia seminalis sp. nov. and Burkholderia metallica sp. nov., novel species within the Burkholderia cepacia complex. Int J Syst Evol Microbiol 2008;58:1580e1590.
3. Mahenthiralingam E, Baldwin A, Dowson CG. Burkholderia cepacia complex bacteria: opportunistic pathogens with important natural biology. J Appl Microbiol 2008;104:1539e1551. 4. Oie S, Kamiya A. Microbial contamination of antiseptics and disinfectants. Am J Infect Control 1996;24:389e395. 5. Oie S, Kamiya A. Bacterial contamination of commercially available ethacridine lactate (acrinol) products. J Hosp Infect 1996;34:51e58. 6. Alvarez-Lerma F, Maull E, Terradas R, 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. 7. Abe K, D’Angelo MT, Sunenshine R, et al. Outbreak of Burkholderia cepacia bloodstream infection at an outpatient hematology and oncology practice. Infect Control Hosp Epidemiol 2007;28:1311e1313. 8. Bureau-Chalot F, Piednoir E, Pierrat C, Santerne B, Bajolet O. [Nosocomial Burkholderia cepacia outbreak in an intensive pediatric care unit.]. Arch Pediatr 2003;10:882e886. 9. Rutala WA, Weber DJ, Thomann CA, John JF, Saviteer SM, Sarubbi FA. An outbreak of Pseudomonas cepacia bacteremia associated with a contaminated intra-aortic balloon pump. J Thorac Cardiovasc Surg 1988;96:157e161. 10. Heo ST, Kim SJ, Jeong YG, Bae IG, Jin JS, Lee JC. Hospital outbreak of Burkholderia stabilis bacteraemia related to contaminated chlorhexidine in haematological malignancy patients with indwelling catheters. J Hosp Infect 2008;70:241e245. 11. Kutty PK, Moody B, Gullion JS, et al. Multistate outbreak of Burkholderia cenocepacia colonization and infection associated with the use of intrinsically contaminated alcohol-free mouthwash. Chest 2007;132:1825e1831. 12. Mahenthiralingam E, Bischof J, Byrne SK, et al. DNA-Based diagnostic approaches for identification of Burkholderia cepacia complex, Burkholderia vietnamiensis, Burkholderia multivorans, Burkholderia stabilis, and Burkholderia cepacia genomovars I and III. J Clin Microbiol 2000;38:3165e3173. 13. Tenover FC, Arbeit RD, Goering RV, et al. Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterial strain typing. J Clin Microbiol 1995;33:2233e2239. 14. Kohlenberg A, Schwab F, Geffers C, Behnke M, Ruden H, Gastmeier P. Timetrends for Gram-negative and multidrug-resistant Gram-positive bacteria associated with nosocomial infections in German intensive care units between 2000 and 2005. Clin Microbiol Infect 2008;14:93e96. 15. 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;29:364e366. 16. Gravel D, Sample ML, Ramotar K, Toye B, Oxley C, Garber G. Outbreak of Burkholderia cepacia in the adult intensive care unit traced to contaminated indigo-carmine dye. Infect Control Hosp Epidemiol 2002;23:103e106. 17. Hamill RJ, Houston ED, Georghiou PR, et al. An outbreak of Burkholderia (formerly Pseudomonas) cepacia respiratory tract colonization and infection associated with nebulized albuterol therapy. Ann Intern Med 1995;122: 762e766. 18. Kaitwatcharachai C, Silpapojakul K, Jitsurong S, Kalnauwakul S. An outbreak of Burkholderia cepacia bacteremia in hemodialysis patients: an epidemiologic and molecular study. Am J Kidney Dis 2000;36:199e204. 19. Matrician L, Ange G, Burns S, et al. Outbreak of nosocomial Burkholderia cepacia infection and colonization associated with intrinsically contaminated mouthwash. Infect Control Hosp Epidemiol 2000;21:739e741. 20. Cosmetics e Good Manufacturing Practices (GMP). Guidelines on good manufacturing practices (ISO 22716:2007); German version EN ISO 22716:2007; 2007. 21. Leitfaden für Mikrobiologisches Qualitätsmanagement kosmetischer Mittel. ln: Industrieverband Körperpflege und Waschmittel e. V.; 1998. 22. Mahenthiralingam E, Baldwin A, Drevinek P, et al. Multilocus sequence typing breathes life into a microbial metagenome. PLoS One 2006;1:e17. 23. Vonberg RP, Gastmeier P. Hospital-acquired infections related to contaminated substances. J Hosp Infect 2007;65:15e23.
Available online at www.sciencedirect.com
Journal of Hospital Infection journal homepage: www.elsevierhealth.com/journals/jhin
Hospital-wide outbreak of Burkholderia contaminans caused by prefabricated moist washcloths M. Martin a, *, B. Christiansen b, G. Caspari b, M. Hogardt c, A.J. von Thomsen a, E. Ott d, F. Mattner a a
University of Lübeck, Institute for Medical Microbiology and Hygiene, Lübeck, Germany Universitätsklinikum Schleswig-Holstein, Medizinaluntersuchungsamt and Krankenhaushygiene, Kiel, Germany c Max von Pettenkofer-Institut, Ludwig-Maximillians-Universität München, München, Germany d Medizinische Hochschule Hannover, Institut für Med. Mikrobiologie und Krankenhaushygiene, Arbeitsbereich Krankenhaushygiene, Hannover, Germany b
a r t i c l e i n f o
s u m m a r y
Article history: Received 26 May 2010 Accepted 7 October 2010 Available online 7 January 2011
We experienced a hospital outbreak of Burkholderia contaminans (Burkholderia cepacia Group K) in a German university hospital with two campuses. Cases were defined as the microbiological detection of B. cepacia complex (BCC) in any clinical specimen sent to the laboratory during 30 June to 21 October 2008. Species identification of BCC was performed by recA gene sequencing, followed by pulsed-field gel electrophoresis (PFGE; SpeI digest) for clonal identity. In total, 61 BCC-positive cases were diagnosed at the two campuses. At least nine patients contracted a ventilator-associated pneumonia with BCC. One patient suffered an infection of a pacing wire insertion site and four patients had septicaemia. Sixteen patients died in hospital, none thought to be due to the outbreak strain. BCC was eventually found in packages of moist prefabricated washcloths used for intensive care patients. German healthcare authorities were informed and a Europe-wide alarm (RAPEX) was initiated through the systems to prevent infections in other hospitals. PFGE proved clonal identity between isolates from clinical specimens and washcloths of both campuses. After elimination of the contaminated washcloths no further cases occurred. This example of a relatively newly introduced product raises the question of whether current regulations are adequate to protect consumers. For critically ill patients, care products should be carefully evaluated. In case of infections due to contaminated products, immediate communication to healthcare authorities is required, including RAPEX warning if products are sold across Europe. Ó 2010 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved.
Keywords: Burkholderia contaminans Contaminated washcloths Outbreak Pneumonia RAPEX
Introduction According to the current molecular taxonomy, Burkholderia cepacia complex (BCC) is a group of opportunistic pathogens consisting of 17 different species (10 of them formerly known as genomovars).1,2 A recently described phylotype is Burkholderia contaminans (B. cepacia Group K).3 Organisms within BCC are generally considered to be of low virulence. They are ubiquitously found in the natural environment but also occur as contaminants in man-made products such as pharmaceuticals, cosmetics, * Corresponding author. Current address: University Medical Center Freiburg, Department of Environmental Health Sciences, Division of Infection Control and Hospital Epidemiology, Breisacher Str. 115b, 79106 Freiburg, Germany. Tel.: þ49 761 270 8277; fax: þ49 761 270 8253. E-mail address: [email protected] (M. Martin).
disinfectants and others.4e6 From these potential sources, BCC may colonise and infect susceptible patients in hospital settings. This is well documented in a number of reported outbreaks over recent decades. Affected individuals were not only those with underlying cystic fibrosis but also other immunocompromised patients, or patients with various devices.7,8 Documented sources vary from contaminated medical instruments and disinfectants to alcoholfree mouthwash and body milk.6,9e11 Nevertheless, the detection of BCC in non-cystic fibrosis patients is uncommon and the relevance for these patients is often unclear. Here, we report on an outbreak of B. contaminans which occurred from 30 June to 21 October 2008 in a tertiary care teaching hospital in northern Germany. A descriptive and prospective surveillance was performed to control the outbreak and environmental investigations were carried out to identify the source. To our knowledge this is the first reported outbreak of B. contaminans with
0195-6701/$ e see front matter Ó 2010 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jhin.2010.10.004
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M. Martin et al. / Journal of Hospital Infection 77 (2011) 267e270
the source being a relatively new care product for intensive care patients. Methods Hospital setting The tertiary care university hospital in the North of Germany consists of two campuses. Both of these hospitals (A and B) have about 1200 beds and five and six intensive care units (ICUs), respectively. At both campuses all ICUs are situated in different buildings. Each hospital has its own infection control team (ICT) communicating on a regular basis with each other. Case definition and identification of cases Case patients were defined as patients from whom BCC had been identified in any clinical specimen sent to the microbiological laboratory between 1 January and 31 October 2008. Patient charts were reviewed using a standardised data collection form. Infections were defined according to Centers for Disease Control and Prevention criteria (available online). Retrospective database analyses back to 1 January 2008 were conducted to identify all cases at both sites. Microbiological methods Clinical specimens were cultured according to appropriate methods for the different materials sent to the laboratory. Preliminary phenotypic identification of BCC was performed according to standard microbiological characteristics (Columbia blood agar, McConkey agar, oxidase reaction for suspected colonies) and by using the VitekÒ II system (bioMérieux, Marcy l’Etoile, France). Definite species identification was performed by rec-A gene sequencing using primers BCR1 and BCR2.12 To investigate clonal identity, BCC isolates were typed by pulsed-field gel electrophoresis (PFGE, SpeI digest). The discriminatory power of PFGE was tested with 20 epidemiologically unrelated strains (data not shown) and macrorestriction profiles were visually compared and interpreted according to the criteria of Tenover et al.13 Environmental samples such as mineral water, non-alcoholic mouthwashes, contact cultures of patients’ environments, prefabricated washcloths and others were investigated for BCC. Liquids were analysed by filtration through a 0.45 mm cellulose membrane filter and cultivation on Columbia blood agar at 37 C for 48 h. Suspected colonies were phenotypically identified by Vitek II system. Quantification of bacterial load of different lots of washcloths was performed as follows: one single washcloth was transferred into 100 mL sterile saline for 30 min at room temperature. Then 100 mL were plated on TSA agar and incubated at 37 C for 48 h. If this culture was negative, the remaining liquid (stored at 8 C) was filtered through a 0.45 mm cellulose membrane filter and cultured on Columbia blood agar at 37 C for 48 h. The number of colonies was counted thereafter. The identity of suspect colonies was confirmed using Vitek II system. Results Timescale of the outbreak in hospital B At the start of September 2008, the ICT of hospital B was aware of three patients positive for BCC in respiratory secretions in ICU B1. The ICT discussed this finding with the healthcare staff at this ICU. The recommendation not to use mineral water for mouth hygiene was renewed and the awareness of other possible external sources
for these bacteria was discussed. A few days later, three additional patients were diagnosed with BCC, two again in ICU B1, one in another (ICU B2). This made the initial suspicion that the strains were introduced from an external source more likely, and prospective active surveillance as well as environmental investigations were started. During this time, two additional BCC-positive patients in a third ICU (ICU B3) were identified. At the beginning of October, another five patients had been diagnosed with BCC obtained from respiratory secretions. On 2 October 2008, prefabricated moist washcloths were suspected as the source of the outbreak by the ICT of hospital A, and hospital B was informed. In all ICUs the stock was cleared and written information was given to all wards by the ICT. The last patient with BCC was identified in hospital B on 12 October 2008. In hospital A the last patient suspected to be involved in this outbreak was identified on 21 October 2008. Retrospective database analysis at both hospitals showed the first patients who fitted the case definition at the end of June 2008 in hospital A, and mid-August in hospital B, respectively. A total of 61 patients were finally found to be BCC positive as detected from microbiological cultures. Outcome hospital A and B None of the patients had medical conditions usually associated with BCC infection such as cystic fibrosis. Strains were first detected in respiratory specimens in 42 patients, in wound swabs in seven (two tracheostomy swab), in central vein catheters in four, in vaginal swabs in two and in one patient each from blood culture, pleural fluid, catheter specimen of urine, pacer electrode, and two other specimens. Two patients had secondary positive blood cultures. Eight patients suffered from BCC-induced pneumonia in hospital B, and at least one in hospital A. The antibiotic treatment usually included ciprofloxacin or cotrimoxazole. In hospital A, four patients had septicaemia. Sixteen patients died in hospital (three in hospital B, 13 in hospital A). All patients died as a result of their underlying disease process. Epidemiological data of hospitalised patients Demographic characteristics and diagnoses of case patients in hospitals A and B are shown in Table I. All patients in hospital B had an ICU stay prior to the first detection of BCC (median duration of ICU stay: 14 days; range: 6e16 days). In hospital A all patients but one had an ICU stay (median duration of ICU stay: 13 days; range: 0e44 days). Environmental results in hospital B Since BCC was initially detected in respiratory specimens of patients, we focused our initial environmental investigation on medical equipment and products used for ventilator care and mouth hygiene. Forty-three bottles of still mineral water of different lots were analysed for BCC. All bottles were negative but positive for Pseudomonas spp. and Acinetobacter spp. Four different types of alcohol-free mouthwash (25 bottles) did not show any bacterial growth. Samples from direct patient environment (contact cultures) from two different ICUs did not show growth of BCC. In response to the suspicions raised by the ICT at hospital A that prefabricated moist washcloths could be the possible source, we collected 12 packages of six different lots of these washcloths at different ICUs. Ten of the 12 initially analysed packages showed bacterial growth (one Stenotrophomonas maltophilia, all others BCC). Some packages were already unsealed, hence a secondary contamination could not be excluded. We subsequently analysed seven sealed packages and found three of five different batches
M. Martin et al. / Journal of Hospital Infection 77 (2011) 267e270 Table I Demographics and clinical characteristics of patients with B. contaminans-positive cultures Variables
Hospital A
No. of patients 42 Male 31 Female 11 Age (years) Mean 63.0 Range 22e87 Hospital admission diagnosis Cardiovascular e Gastrointestinal e Trauma e Infection e Other e Duration of ICU stay prior to first diagnosis (days) Median 13 Range 0e44 Specimen of first detection Respiratory secretion 25 Wound swab 6 Blood 1 Other 10 Infection Pneumonia 1 Wound infection 2 Bloodstream infection 4 2 Othera Colonisation 33 Death 13 Related to infection 0
Hospital B 19 13 6 63.9 46e82 9 6 3 1 0 14 6e66 17 1 0 1 8 1 0 0 10 3 0
e, no data available. a Other infections were a urinary tract infection and a dermatological infection.
positive for BCC. The quantitative analysis of the bacterial concentrations of sealed packages showed contamination ranging from 4 cfu to 5.6 107 cfu per washcloth. Microbiological findings For 37 isolates of BCC from the different sources (26 patients from both hospitals and 11 washcloth isolates from both laboratories) PFGE analysis revealed three closely related strains indistinguishable from one or other of these three outbreak strains. The rec-A gene sequencing of three isolates, one patient and two washcloth isolates from the different laboratories, identified the BCC subtype B. contaminans for all three isolates. Termination of the outbreak In discussion with leading nursing staff and clinic management it was decided to eliminate the prefabricated washcloths, which had been introduced in 2007. Healthcare authorities were informed so as to reduce the risk for other possible users of these washcloths. As it became obvious that this cosmetic product was also distributed to other European countries, authorities initiated a Europeanwide alert report via the RAPEX system (available online). This is a rapid alert system for dangerous consumer products and cosmetics, with the exception of foods, medical devices and pharmaceuticals. Since then, no replacement prefabricated washing system has been introduced throughout our hospital and the use of soap and water has been recommended. Discussion Bacteria belonging to B. cepacia complex are rarely detected as pathogens of nosocomial infections.14 The detection of BCC from clinical samples suggests an environmental source. However, the timely recognition of this outbreak was hampered by the fact that
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the first cases did not occur in clusters but as single cases in different ICUs or after transfer from ICU to general wards. In June the first cases occurred in non-cystic fibrosis patients but the outbreak investigation only started in September 2008 at hospital A and B, when a cluster in an ICU was obvious. This partly explains the duration of the outbreak (about five months) and the number of patients involved. Identified sources for reported BCC outbreaks include therapeutic water, indigo-carmine dye to tint tube feedings, albuterol therapy, chlorhexidine, moisterising body milk and alcohol-free mouthwash.6,10,11,15e19 To our knowledge we report here the first BCC outbreak associated with prefabricated moist washcloths, a relatively new product for patient care. Prefabricated washcloths were introduced into the patient care market about 10 years ago. They are available as cosmetic as well as medical products. Most of these washing systems are not only for washing the patient but also contain moisturising products, so they are two-in-one products. They are sold as body washing systems for immobile patients and patients with special needs, such as ICU patients, to make daily body care easier and faster. One package of such a body washing system for daily body care contains up to eight moist washcloths and should be used for one patient at one time. As we collected the washing systems at different ICUs for laboratory tests we found that the systems were used differently. Some nurses did not use them at all, some used them just for cleaning of the perineal region and others used the washing system for everyday body care. This variable qualitative and quantitative use may be an explanation for the different numbers of affected patients on the two sites as well as the variable number in the single ICUs in this outbreak. Furthermore, leaving unused prefabricated moist washcloths in the unsealed package for further utilisation made another reservoir for various secondary pathogens and a possible source of infection for patients obvious. The washing system used here was declared as a cosmetic product. Quality controls are regulated by the European Council directive 76/768/EEC (available online), the German provisions, consumer products and feeding products law (LFGB) (available online), the cosmetic good manufacturer practice (GMP) and the Leitfaden des Industrieverbands Körperpflege- und Waschmittel e. V. (IKW) zum mikrobiologischen Qualitätsmanagement.20,21 These regulations specify the microbiological quality of cosmetic products as follows: cfu for 1 g of product 5 103 and absence of the pathogens Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans, Escherichia coli in 0.1 g of the product. These limiting values and the analytical methods are close to those given in the European Pharmacopoeia (Ph. Eur.) for topical non-sterile products. In contrast to the Ph. Eur. these standards do not state anything about the frequency of testing. Our quantitative analysis of the washcloths showed bacterial growth of more than the given limit of 5 103 cfu per 1 g and the presence of Gram-negative non-fermenting rods in three out of the five tested lots. BCC are non-fermenting, as Gram-negative bacilli such as P. aeruginosa and are recognised contaminants of industrial products.22 Medical and cosmetic products such as the one causing this outbreak do not have to be sterile if they are solely for topical use. Medical products require higher standards of control, regulated by the European Council directive 93/42/EEC (available online). From our experience that single batches can be highly contaminated, we recommend the use of routine microbiological testing of care products (per batch) for ICU patients. This product testing can be performed according to the standards of cosmetic products or the Ph. Eur. as the analytical methods, limits of cfu per gram and required absence of the above mentioned organisms are similar. In our opinion the manufacturer of care products should be asked to document these microbiological tests especially if the products are
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made for the care of vulnerable patients. If the products are declared as medical devices the hospital may request the manufacturer to provide a statement of infection risk of his product based on the European Council directive for medical devices (93/42/EEC). After eliminating the washcloths from the daily care of our patients, our major concern was to inform other possible users.23 We immediately passed on information to the authorities. The authorities confirmed the distribution of the washing systems to other European countries and an alert report was given through the well-established RAPEX system (available online) for consumer products. Unfortunately we have no knowledge of the experience of other users, nor whether they observed an outbreak of BCC during the same period. It therefore cannot be ascertained if the alert report actually prevented harm to other patients. In conclusion, we describe a large outbreak of B. contaminans involving 61 patients, some with severe infections. Eliminating the detected source e an intrinsically highly contaminated body care product e terminated the outbreak. Contaminated body care products are a potential source of infections for critically ill patients. Such products should only be used in ICU settings once the infection risks have been assessed. Early detection of uncommon pathogens in patients, even if they are of low virulence, and informing healthcare authorities can prevent further patients from harmful infections.
Acknowledgements We express our gratitude to Mrs F. Behrmann, Mr B. Grabowski and Mrs R. Simon for their assistance in resolving this outbreak and Mrs B. Pape for her technical assistance. Conflict of interest statement None declared. Funding sources None.
References 1. Vanlaere E, Baldwin A, Gevers D, et al. Taxon K, a complex within the Burkholderia cepacia complex, comprises at least two novel species, Burkholderia contaminans sp. nov. and Burkholderia lata sp. nov. Int J Syst Evol Microbiol 2009;59:102e111. 2. Vanlaere E, Lipuma JJ, Baldwin A, et al. Burkholderia latens sp. nov., Burkholderia diffusa sp. nov., Burkholderia arboris sp. nov., Burkholderia seminalis sp. nov. and Burkholderia metallica sp. nov., novel species within the Burkholderia cepacia complex. Int J Syst Evol Microbiol 2008;58:1580e1590.
3. Mahenthiralingam E, Baldwin A, Dowson CG. Burkholderia cepacia complex bacteria: opportunistic pathogens with important natural biology. J Appl Microbiol 2008;104:1539e1551. 4. Oie S, Kamiya A. Microbial contamination of antiseptics and disinfectants. Am J Infect Control 1996;24:389e395. 5. Oie S, Kamiya A. Bacterial contamination of commercially available ethacridine lactate (acrinol) products. J Hosp Infect 1996;34:51e58. 6. Alvarez-Lerma F, Maull E, Terradas R, 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. 7. Abe K, D’Angelo MT, Sunenshine R, et al. Outbreak of Burkholderia cepacia bloodstream infection at an outpatient hematology and oncology practice. Infect Control Hosp Epidemiol 2007;28:1311e1313. 8. Bureau-Chalot F, Piednoir E, Pierrat C, Santerne B, Bajolet O. [Nosocomial Burkholderia cepacia outbreak in an intensive pediatric care unit.]. Arch Pediatr 2003;10:882e886. 9. Rutala WA, Weber DJ, Thomann CA, John JF, Saviteer SM, Sarubbi FA. An outbreak of Pseudomonas cepacia bacteremia associated with a contaminated intra-aortic balloon pump. J Thorac Cardiovasc Surg 1988;96:157e161. 10. Heo ST, Kim SJ, Jeong YG, Bae IG, Jin JS, Lee JC. Hospital outbreak of Burkholderia stabilis bacteraemia related to contaminated chlorhexidine in haematological malignancy patients with indwelling catheters. J Hosp Infect 2008;70:241e245. 11. Kutty PK, Moody B, Gullion JS, et al. Multistate outbreak of Burkholderia cenocepacia colonization and infection associated with the use of intrinsically contaminated alcohol-free mouthwash. Chest 2007;132:1825e1831. 12. Mahenthiralingam E, Bischof J, Byrne SK, et al. DNA-Based diagnostic approaches for identification of Burkholderia cepacia complex, Burkholderia vietnamiensis, Burkholderia multivorans, Burkholderia stabilis, and Burkholderia cepacia genomovars I and III. J Clin Microbiol 2000;38:3165e3173. 13. Tenover FC, Arbeit RD, Goering RV, et al. Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterial strain typing. J Clin Microbiol 1995;33:2233e2239. 14. Kohlenberg A, Schwab F, Geffers C, Behnke M, Ruden H, Gastmeier P. Timetrends for Gram-negative and multidrug-resistant Gram-positive bacteria associated with nosocomial infections in German intensive care units between 2000 and 2005. Clin Microbiol Infect 2008;14:93e96. 15. 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;29:364e366. 16. Gravel D, Sample ML, Ramotar K, Toye B, Oxley C, Garber G. Outbreak of Burkholderia cepacia in the adult intensive care unit traced to contaminated indigo-carmine dye. Infect Control Hosp Epidemiol 2002;23:103e106. 17. Hamill RJ, Houston ED, Georghiou PR, et al. An outbreak of Burkholderia (formerly Pseudomonas) cepacia respiratory tract colonization and infection associated with nebulized albuterol therapy. Ann Intern Med 1995;122: 762e766. 18. Kaitwatcharachai C, Silpapojakul K, Jitsurong S, Kalnauwakul S. An outbreak of Burkholderia cepacia bacteremia in hemodialysis patients: an epidemiologic and molecular study. Am J Kidney Dis 2000;36:199e204. 19. Matrician L, Ange G, Burns S, et al. Outbreak of nosocomial Burkholderia cepacia infection and colonization associated with intrinsically contaminated mouthwash. Infect Control Hosp Epidemiol 2000;21:739e741. 20. Cosmetics e Good Manufacturing Practices (GMP). Guidelines on good manufacturing practices (ISO 22716:2007); German version EN ISO 22716:2007; 2007. 21. Leitfaden für Mikrobiologisches Qualitätsmanagement kosmetischer Mittel. ln: Industrieverband Körperpflege und Waschmittel e. V.; 1998. 22. Mahenthiralingam E, Baldwin A, Drevinek P, et al. Multilocus sequence typing breathes life into a microbial metagenome. PLoS One 2006;1:e17. 23. Vonberg RP, Gastmeier P. Hospital-acquired infections related to contaminated substances. J Hosp Infect 2007;65:15e23.