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Outbreaks of healthcare-associated fungal infections have repeatedly been described over recent years, often caused by new or uncommon species. Candida auris, a recently described multidrug-resistant yeast species, is certainly the most worrisome species having caused several severe healthcare outbreaks of invasive infections, on four continents. Also, large nosocomial outbreaks due to uncommon fungal species such as Exserohilum rostratum and Sarocladium kiliense, were both linked to contamination of medical products, however the source of another outbreak, caused by Saprochaete clavata, remains unresolved. Furthermore, these outbreaks identified new populations under threat in addition to those commonly at risk for invasive fungal infections, such as immunosuppressed and intensive care unit patients. All of these outbreaks have highlighted the usefulness of a high level of awareness, rapid diagnostic methods, and new molecular typing tools such as Whole Genome Sequencing (WGS), prompt investigation and aggressive interventions, including notification of public health agencies. This review summarizes the epidemiological and clinical data of the majority of healthcare-associated outbreaks reported over the last 6 years caused by uncommon or new fungal pathogens, as well as the contribution of WGS as support to investigate the source of infection and the most frequent control measures used. Keywords: Healthcare-associated fungal outbreak, Candida auris, Exserohilum rostratum, Sarocladium kiliense, Saprochaete clavata, Prevention, Whole genome sequencing Background fungal species and other less immunocompromised popula- Until the last decades, only a small number of fungal patho- tions remained a rare phenomenon. gens such as Aspergillus, Candida, Pneumocystis jirovecii, Nevertheless, several recent reports have highlighted and Mucorales have been involved in healthcare-associated the emergence of new healthcare-associated outbreak fungal outbreaks [1–3]. Furthermore, these outbreaks were phenomena due to fungal species previously unknown limited to well-defined at-risk populations. Indeed, neutro- or uncommon in clinical practice. Interestingly, these penic patients, including patients treated for acute leukemia, fungal outbreaks affected both weak patients and healthy severely ill patients during their stay in intensive care unit individuals. (ICU), and neonates hospitalized in neonatal ICU, were the Thus, a new species of Candida, Candida auris,has main populations that suffered from these severe infections been recently identified and is now considered a notorious . The occurrence of sporadic episodes related to other healthcare-associated yeast causing invasive infections with high treatment rate failures . Diversely, during the * Correspondence: email@example.com; firstname.lastname@example.org past 6 years, rarely isolated fungi have been involved in Département de microbiologie clinique, unité de contrôle et de prévention healthcare-associated outbreaks; among these, Exserohilum du risque infectieux, Hôpital Avicenne, Groupe Hospitalier rostratum and Sarocladium kiliense were related to Paris-Seine-Saint-Denis, Assistance Publique - Hôpitaux de Paris (APHP), Bobigny, France contamination of medical products and represented a high IAME, UMR 1137, Université Paris 13, Sorbonne Paris Cité, Paris, France public health threat. Also, others healthcare-associated Full list of author information is available at the end of the article © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Bougnoux et al. Antimicrobial Resistance and Infection Control (2018) 7:45 Page 2 of 9 outbreaks due to uncommon fungal species, such as auris seems to have a high propensity for patient-to- Saprochaete clavata, are still unresolved as no source of patient transmission in healthcare settings, possibly contamination has yet been documented. related to environmental contamination, or transient Increased vigilance and usage of advanced technologies person or device colonization . are needed to rapidly identify the likely sources of these The serious threat posed by C. auris prompted the US infections in order to efficiently guide epidemiological Center for Disease prevention and Control (CDC) to investigations and initiate appropriate control measures. issue an alert in June 2016 addressed to healthcare Since many publications have so far been interested in facilities on notifying cases of C. auris to local or public classical fungal infections, we aim to decipher the most health authorities . Public Health England also notable healthcare-associated outbreaks caused in the published guidelines for actively identifying and reporting last 6 years by uncommon or new fungal pathogens C. auris to prevent its nosocomial transmission and (summarized in Table 1). In order to highlight the most the European CDC (ECDC)  issued a health alert for recent insights related to these outbreaks, we focused on strict vigilance of C. auris cases. (i) the epidemiological, clinical, and microbiological data, C. auris was first described in 2009 from a patient’s (ii) the contribution of the WGS typing method for ear swab in Japan . The first three cases of nosocomial outbreak investigation, and (iii) the recommendations to bloodstream infections related to C. auris were described manage cases and control transmission of these uncommon in South Korea in 2011 . These three cases highlighted fungi in healthcare facilities. the feature of persistent candidemia despite fluconazole and amphotericin B therapy. Thereafter, in a short span of Main text 6 years, cases of C. auris fungaemia and deep-seated Epidemiology and clinical presentation of recently infections have been reported from hospitals across four reported healthcare-associated fungal outbreaks due to continents . C. auris is probably underdiagnosed as this New or uncommon fungal species yeast is often phenotypically misidentified as Candida Candida auris haemulonii, Candida famata,or Candida sake by Over the past 6 years, Candida auris, a multidrug- commercial biochemical identification systems [12, 13]. resistant (MDR) Candida species, has emerged on four C. auris causes infections in patients, ranging from continents as a yeast associated with hospital outbreaks neonates to elderly, with well-recognized risk factors for with high rates of clinical treatment failure. C. auris invasive candidiasis. Indeed, among the 41 C. auris deep causes invasive infections in severely compromised infections observed during 2012–2015; 73%, occurred in patients, is mostly resistant to fluconazole and exhibits patients having a central venous catheter (CVC), 61% variable susceptibility to other azoles, amphotericin B, with a urinary catheter, 51% had undergone recent and echinocandins. Unlike other Candida species, C. surgery, and 41% had diabetes mellitus . Moreover, Table 1 Healthcare-associated outbreaks due to four new or uncommon fungal pathogens Species Year Country N° of cases Infection sites At risk Source Main preventive References population measures Candida auris Since 2011 Four > 500 IFI and Risk of invasive Human and Improve hand [3–14, 36–50] continents colonization candidiasis environmental hygiene surfaces Contact isolation Improve environmental desinfection Saprochaete clavata Sept 2011- France 30 Blood and Hematological Unknown Define and [15–17] (formerly Geotrichum Oct 2012 Italy 3 colonization malignancies Unknown identify at risk clavatum) Oct-Dec 2014 Spleen, liver, Hematological population lung malignancies Search for a common source Sarocladium kiliense June 2013- Chile 67 Blood Chemotherapy Antinausea Recall of all [21–23] (formerly Acremonium Jan 2014 (8 hospitals 16 Blood Chemotherapy ondansetron ondansetron kiliense) Nov 2013 in Santiago) 3 Blood Stem cell (company A) lots of the March- Colombia transplantation Ondansetron company A May 2011 Greece (company A) CVC Exserohilum rostratum Sept 2012- USA 751 Paraspinal/ Epidural/ MPA Recall of the 3 [24–28, 33–35] Oct 2013 (20 states) spinalMeninges paraspinal (compounded contaminated lots Peripheral joint injection of MPA drug) CVC Central venous catheter, MPA Methylprednisolone acetate Bougnoux et al. Antimicrobial Resistance and Infection Control (2018) 7:45 Page 3 of 9 approximately 41% of patients were prescribed antifungal of patients had gut colonization. Moreover, diarrhea therapy when C. auris was isolated . The median time previous to or associated with fungemia was reported from admission to infection was 19 days (range 9–36), for 61.5% of cases, suggesting the role of a subsequent and 61% of patients had a bloodstream infection. The gut translocation in the occurrence of these bloodstream overall crude in-hospital mortality rate of C. auris infections. The case fatality rate at day 60 was 80%, with candidemia ranges from 30 to 60% . death occurring at a median of 7 days following Between April 2015 and July 2016, the first European diagnosis . nosocomial outbreak, was described in a London cardio- Phylogenetic analysis of the French outbreak identified thoracic center , where 50 C. auris cases (average a single clone (clone A) which accounted for 16 of the age 53 years, range 19–78) were reported. Among them, 18 outbreak cases and that was distinct from sporadic 44% (22/50) developed possible or proven infection with isolates . This finding provides additional, although a 18% (9/50) candidemia rate, also some cases occurred not definite evidence, for a common source of contam- despite treatment with echinocandins. ination in this health care facility outbreak. However, Moreover, the ECDC reported an outbreak of 33 C. epidemiological and microbiological investigations did auris bloodstream infections that occurred in 2016 in not lead to a documented source of infection. the surgical ICU of a hospital in Spain. One case of C. Since the 2012 French outbreak, the epidemic clone A auris isolated from a blood culture was also reported in of S. clavata has been identified several times in France November 2015 by the German national reference in small clustered or sporadic cases . In Italy, three center for invasive fungal infections. Finally, one case of cases of G. clavatum bloodstream infections were invasive candidiasis, due to an isolate of C. auris, was also reported in one hematological ward in 2016 . All reported in Norway, but the infection was probably patients received cytarabine and developed G. clavatum acquired abroad as the patient concerned was transferred infection within 3 weeks from therapy initiation. In all from a hospital outside of the European Union . cases, visceral localizations (spleen, liver, and lung) were A large majority of C. auris isolates are fluconazole documented by a total body computed tomography scan. resistant (93%), and amphotericin B and echinocandin A prolonged antifungal therapy with high doses of resistance rates are approximately 30–40% and 5–10%, liposomal amphotericin-B was necessary to obtain fever respectively. Almost half of isolates are MDR (resistant resolution; one patient did however die. to two or more antifungal classes), and a small percentage S. clavata, previously reported as G. clavatum, had are pandrug resistant . Therefore, C. auris infections rarely been isolated from human samples before this pose a serious challenge regarding identification and outbreak [21, 22]. Its ecology, reservoir, and importance therapy, especially in developing countries where modern in agriculture and food are unknown . This species identification facilities (molecular identification and MALDI- is closely related to the known human pathogen Magnu- TOF mass-spectrometry) and access to antifungals other siomyces capitatus (previously known as Geotrichum than fluconazole are limited. capitatum) and these two species are often misidentified. Both are resistant to echinocandins, which are recom- Saprochaete clavata mended in hematology wards in case of candidemia or Several cases of rapidly fatal infections due to the fungus febrile neutropenia of unknown origin. Sporadic cases Saprochaete clavata, formerly Geotrichum clavatum, and outbreaks of fungemia due to M. capitatus have were reported in France within a short period of time in been reported in patients with acute hematological three health care facilities, suggesting a common source malignancies, and these outbreaks have sometimes been of contamination . Thus, between September 2011 related to contaminated dairy products . In the and October 2012, a nationwide alert collected 30 cases French S. clavata outbreak, results of local investigations of invasive infections in 14 centers, including an out- of fungal contamination of food, blood products, break of 18 cases over 8 weeks in 10 health care facilities medical devices, and environmental samples were all located in 10 different French regions. The French alert negative . was internationally relayed by the ECDC and CDC but no other country was concerned . Sarocladium kiliense Half of the 30 cases reported in the French outbreak An outbreak of Sarocladium kiliense, formerly Acremo- were male patients with a median age of 63 years. Most nium kiliense, bloodstream infections occurred from of the patients (70%) were hospitalized for acute myeloid June 2013 to January 2014 and included a cluster of leukemia, were exposed to cytarabine (80%), and all cases at eight hospitals in Santiago, Chile . All 67 cases received blood products. S. clavata was recovered patients infected with S. kiliense were under chemotherapy from blood in 87% cases (26/30), from bronchoalveolar and received the same antinausea medication (ondanse- fluid or tracheal aspirates in 40% cases (12/30), and 60% tron), produced by the same pharmaceutical company in Bougnoux et al. Antimicrobial Resistance and Infection Control (2018) 7:45 Page 4 of 9 Colombia. Two out of three lots of unopened ondanse- epidemic in the United States, a public health threat of tron, tested by the Chilean Ministry of Health, yielded historically unprecedented magnitude. vials contaminated with S. kiliense, forcing a recall of all Indeed, subsequent investigations revealed a multistate ondansetron in Chile made by the Colombian manufac-  outbreak of fungal infections, primarily Exserohilum turer. Subsequently, Colombian officials discovered 16 rostratum, caused by epidural, paraspinal, and peripheral other infected patients who received ondansetron also joint injections of fungus-contaminated lots of methyl- from the same Colombian pharmaceutical company. prednisolone acetate (MPA) produced by a single com- Culturing and conventional DNA sequence identification pounding pharmacy [27, 28]. More than 13,000 people methods confirmed that ondansetron was contaminated were exposed to three lots of contaminated MPA and in with S. kiliense . October 2013, 751 had developed fungal infections S. kiliense has been implicated previously in healthcare- following their MPA injections and resulting in 64 related infections, but the lack of available typing methods deaths. Specimens from patients were tested for the has precluded the ability to substantiate sources. The use presence of fungi, and laboratory evidence confirmed of WGS-based typing to investigate fungal outbreaks has the presence of E. rostratum in 153 case patients (20%). become integral to epidemiologic investigations. The The fungal infection cases presented a broad spectrum WGS-based typing analysis demonstrated that the patient of clinical disease, reflecting the differences in pathogen- isolates from Chile and Colombia were nearly genetically esis, exposure route, and host risk factors . A total of indistinguishable from those recovered from the 233 patients only had meningitis, 325 only had unopened medication vials, indicating the likely presence paraspinal/spinal infection, 33 only had peripheral joint of a single-source infection . infection, 151 had meningitis and paraspinal/spinal In 2013 Ioakimidou et al. reported an unusual cluster infection, two had paraspinal/spinal infection and of possible catheter-related bloodstream infections due peripheral joint infection, and seven had a stroke . to S. kiliense (A. kiliense) in patients who underwent The overall attack rate was 5.5 cases per 100 exposed hematopoietic stem cell transplantation . Three persons . Case patients had received a median of one febrile transplanted patients repeatedly yielded the injection (range, 1–6) of implicated MPA lots, with a fungus from blood cultures taken through a CVC during median age of 64 years (range, 15–97 years), and median a short period of 1.5 months (March to May 2011) in a incubation period of 48 days (range, 0–249 days) from Hematology Department in Thessaloniki, Greece. The the last injection to diagnosis . identification of S. kiliense was confirmed by sequencing Cohort analysis of patients who had been given the internal transcribed spacer (ITS) region of three epidural or paraspinal glucocorticoid injections in isolates (one from each patient). In accordance with Tennessee showed that the infection risk was higher antifungal susceptibility testing, the patients received among patients exposed to: one specific lot among the voriconazole in addition to CVC removal. The outcome three contaminated lots, older vials, higher doses, was favorable for all the patients. multiple procedures, and in patients in whom a transla- S. kiliense, a hyaline mold formerly known as Acremo- minar approach to epidural glucocorticoid injection was nium kiliense, is a ubiquitous soil saprophyte commonly used . Tests carried out at CDC and Food and Drug found in the environment and occasionally infecting Administration laboratories on the preservative-free humans. Its pathogenicity in immunocompetent patients MPA vials confirmed the presence of E. rostratum in is low and usually is related to inoculation of the fungus unopened vials from two of the three recalled lots. These via a penetrating injury that often leads to a granuloma laboratory results strengthen the link between the formation. A. kiliense has been described as a cause of preservative-free MPA vials and the outbreak resulting mycetoma, keratitis, endophthalmitis, endocarditis, con- from a series of sterility assurance failures . tinuous ambulatory peritoneal dialysis-associated peri- The major cause of this outbreak was E. rostratum,a tonitis, and catheter-related fungaemia . However, dematiaceous (black) mold found in soil and plants the presence of underlying immunological disorders can debris worldwide, however it is more common in predispose to the development of a usually fatal systemic tropical and subtropical areas . This black mold infection such as peritonitis . usually infects plants and rarely causes disease in humans. Of the approximately 30 cases of Exserohilum Exserohilum rostratum infections reported in the literature before this outbreak, In September 2012, the CDC was notified of several the most common presentations were skin, corneal, and cases of meningitis in Tennessee, including one patient sinus infections . Because Exserohilum rarely causes with culture-confirmed Aspergillus fumigatus meningitis human infections, relatively little is known about its 46 days after an epidural steroid injection. This patient physiopathology and management, particularly in the was the index case of the largest fungal infection case of central nervous system (CNS) infections. How Bougnoux et al. Antimicrobial Resistance and Infection Control (2018) 7:45 Page 5 of 9 the pathogen entered the CNS, in this outbreak, is The largest fungal outbreak of healthcare-associated unclear. It may be rarely by direct inoculation of the infections investigated using WGS typing was caused by contaminated material into the subarachnoid space by the black soil mold E. rostratum, responsible for a inadvertent puncture of the dura during the glucocorticoid number of cases of meningitis in the USA. Owing to injection, or more likely, by direct contiguous spread from epidemiological investigations, the use of MPA injections the site of injection. contaminated with E. rostratum was quickly demon- strated to be responsible for the outbreak [37, 38]. Dif- ferent lots of MPA from a single compounding Whole-genome sequence typing: A New molecular tool pharmacy were positive with E. rostratum. However, it for uncommon fungal outbreak investigations was not possible to demonstrate the genetic relationship Whole-genome sequence (WGS) typing is a new between the fungal isolates due to the lack of relevant molecular approach that enables genotyping of any typing methods for that given species. WGS typing was microorganism without genetic insights or prior know- eventually used to analyse and compare the genomes of ledge of the natural population diversity in that species. both the clinical isolates and those from MPA vials Thus, it can be used when no other conventional originating from different lots . It initially demonstrated method is available for molecular genotyping. Indeed, that the isolates were highly clonal, strongly suggesting a when an outbreak is caused by an uncommon fungal single common source. Secondly, it demonstrated that clin- species there is usually little epidemiological information ical isolates could not be distinguished from those from the available regarding dissemination, genetic diversity, and/ MPA vials, confirming that MPA was the source of infec- or population structure for the species; standard tion. Interestingly, WGS analysis also showed that these E. methods for molecular genotyping are often not suitable rostratum isolates were haploid and nearly identical, only and lack comprehensive resolution. For these unusual differing by less than 2 SNPs between any pair of isolates. fungal pathogens, WGS typing can be highly valuable for In contrast, hundreds of thousands of SNPs differentiated allowing first molecular comparisons of strains . the isolates responsible for the outbreak and unrelated WGS typing is based on the analysis of whole single- control isolates. These huge differences between unrelated nucleotide polymorphisms (SNPs) within each genome, and related genome strains unearths interesting questions which allows investigating genome-wide variation be- and may indeed suggest that the unrelated control strains tween isolates. The relationships between the isolates belonged to different cryptic species. Nonetheless, this can then be inferred from the number of SNPs differing studyhighlighted thepower of theWGS typing to provide between them. SNP distances determine genetic related- accurate information about the relatedness of the isolates of ness. Another advantage of WGS typing is that it rare species, here E. rostratum, when no genetic informa- permits the production of “de novo assembly” for these tion was available. unusual pathogens lacking published reference genomes. The same approach was then used to investigate the Whole-genome sequencing is also useful for getting healthcare-associated outbreak of S. kiliense bloodstream information characterized important traits, such as the infections associated with the administration of contami- level of ploidy, the size of assembled genome, etc. nated antinausea medication among oncology patients in WGS typing has a high discriminatory power to relate Colombia and Chile . Once again, WGS typing strains. However, its current limitation is that it must be confirmed a common source of infections in the two performed in a laboratory in which the different steps of countries related to the contaminated medication. the process are well established, including sequence Indeed, genomes of isolates from infected patients of the acquisition and bioinformatics for handling and analysing two countries and from the different lots of contami- the data . Considerable challenges remain due to the nated medication were nearly indistinguishable from one lack of common standards, particularly for investigating another. No more than 5 SNPs were detected between fungal genomes because they are much larger than those any pair of isolates; for reference the genome size of S. of bacteria and viruses and have a variable level of ploidy. kiliense is approximately 36 MB. Recent years have been rich in large fungal outbreaks In France, S. clavata, another previously unrecognized caused by very unusual fungal species (Table 1). These fungal pathogen, was implicated for different clusters of outbreaks, due to either yeasts or mold, have signaled infections in leukemic patients . The use of WGS typing the beginning of a new era of fungal outbreak investiga- identified a single clone for most cases. However, it was not tion based on the comparison of the whole genomes of possible to connect it to a common source of infection. outbreak strains by using WGS. WGS typing permits An interesting secondary outcome of these three studies investigation into several fungal outbreaks due to was that a large panel of assembled genomes from the uncommon fungal species allowing researchers to three species was produced for the first time. Some of decipher epidemiological clues [34–36]. them were from related strains, including genomes from Bougnoux et al. Antimicrobial Resistance and Infection Control (2018) 7:45 Page 6 of 9 the outbreak strains, while others were from unrelated general infection prevention measures but also the control strains, from the same or different countries. importance of warning alert systems. Indeed, the specifi- These genome sequences served as the basis for city of these outbreaks emphasizes the value of monitoring constructing databases to study genetic variations in these systems. Concerning C. auris, the risk of misidentification unusual species, which had never been done before. Thus, was high and it has been suggested that C. auris should be in addition to their power for genotyping, WGS data suspected in several situations, such as: a) when identifica- generated during outbreak investigations can also to be tion cannot be obtained using traditional biochemical used to better understand the biology, the virulence, and mycological methods, and b) when resistance to more even possible therapeutic targets in these species. than one antifungal drug is detected for an isolate with an Recently, the nearly simultaneous global emergence of ambiguous identification . Furthermore, concerning a novel species of Candida, C. auris, capable of causing the other described species such as S. clavata, E. rostra- hospital-acquired multidrug-resistant infections, has tum,and S. kiliense, the published studies highlighted sev- likely represented one of the more complex challenges eral points as the common source of contamination (E. in terms of epidemiological investigation. In 2009, when rostratum and S. kiliense) and the specific populations at C. auris was first isolated from the external ear canal in risk. It seems fundamental to introduce warning alert a Japanese hospital patient, no information about this systems that could help practitioners and health authorities species or its putative reservoir was available. Since the to react quickly to prepare in the event of an outbreak. publication of the first C. auris genome sequence in These warning alerts could be implemented in specific 2015 , a large number of C. auris strains have been populations e.g., immunosuppressed patients. sequenced for investigating different outbreaks. Their Given the risk of nosocomial transmission of C. auris, analysis suggests that the pandemic is due to recent and it is necessary to promptly implement infection control independent emergences of different clonal populations measures to limit its spread. Similar to other Candida of C. auris, rather than to the worldwide spread of a species, colonized and infected C. auris patients share dominant clone. Indeed, phylogenetic analysis of the the same risk factors, including diabetes mellitus, whole genome SNPs from strains isolated from three abdominal surgery, broad-spectrum antibiotics, and continents showed that there is a strong phylogeo- presence of CVCs . Healthcare acquired infections graphic structure, with the strains grouping into unique typically occur several weeks (10–50 days) into a clades by geographic regions . The strains from the patient’s hospital stay . same geographic region, such as South Asia, South Hand transmission and persistent contamination of America, or South Africa, were highly clonal and environmental surfaces within healthcare facilities have belonged to a specific clade, with very few SNPs differ- been associated with outbreaks; thus, CDC recommen- ences (16-70 SNPs). In contrast, tens of thousands of dations are based on standard and contact precautions SNPs differentiated strains from different continents. . As for other Candida species, transmission could In addition, recent investigations showed that in a occur through healthcare workers (HCW) hands; given country, strains isolated from patients hospitalized however unlike others HCW seem not to be colonized in different hospitals or towns can be virtually identical long term. Indeed, as suggested by two different studies, (only a few SNP differences) allowing precise tracking of carriage seems to be rare. The most recent study  clonal spreading in the different clusters. Finally, a highlighted that during an outbreak only four among recent study showed almost identical (less than 5 SNP 145 HCW were hand carriers. However systematic sam- differences) C. auris isolates from the surface environ- pling of the hands, nose, axilla, groin, and throat of 258 ment of one hospitalized patient and his own isolates, HCW conducted as part of the UK investigation identi- which further suggested that the spread within health fied only a single HCW with a positive nares swab, who care settings was possible . Overall, WGS exclusively later tested negative from the same site, suggesting tran- provided unambiguous data on the genome sequences sient carriage . and on the number of SNPs differentiating isolates. All hospitalized patients with C. auris infection or Those can easily be shared between laboratories but also colonization should be housed in single rooms with centralized for a global investigation of the pandemic environmental precautions. During outbreak investigations, . As mentioned above for other uncommon species, Cauris has been isolated from medical equipment likely these data have also been used to further study genetics originating from patient’sskinshedding. Explaining of the biology and the virulence of C. auris . why considerable attention has focused on the efficacy of disinfectants used for skin decolonization and environmen- From infection control point of view tal decontamination. The various fungal outbreaks described within the last Indeed, several authors suggested that contaminated sur- 6 years have highlighted not only the importance of faces in healthcare facilities may be an important source of Bougnoux et al. Antimicrobial Resistance and Infection Control (2018) 7:45 Page 7 of 9 Table 2 Interventions needed in case of Candida auris outbreak Interventions proposed Usefulness 1-Notify public health agency Undoubted 2-Place patient (colonized or infected) in a single room Undoubted 3-Institute Contact Precautions for colonized or infected patients Undoubted 4-Screen all contact patients (defined as roommates) once a week and before leaving the medical ward Uncertainty how best to monitor 5-Reinforce environmental cleaning 3× day with 1000 ppm chlorine based, vaporized H2O2 Undoubted 6-Reduce duration of invasive procedures in colonized patients Undoubted 7-Skin decolonization (colonized patients) with 10% w/w iodinated povidone No clear data acquisition [48–50]. Experimentally, C. auris and other disinfectants had a relatively poor activity against all Candida species persisted for 7 days or up to 4 weeks on Candida species . moist and dry surfaces, respectively . Moreover, C. Limiting the spread of C. auris needs rapid multifa- auris exhibited a greater propensity to survive on surfaces ceted interventions (Table 2) including contact isola- than C. albicans, but not C. parapsilosis or C. glabrata. In tion, enhancing environmental disinfection, screening comparison to common bacterial pathogens, Candida spe- contact populations, and skin decolonization for colonized cies were recovered with similar frequencies from dry sur- patients. However, there is uncertainty as to how best moni- faces and were recovered significantly more often from tor prolonged colonization (https://www.cdc.gov/fungal/dis- moist areas such as sinks. Moreover, C. auris has the cap- eases/candidiasis/c-auris-infection-control.html). There are acity to form antifungal resistant biofilms sensitive to the no clear data on the efficacy of decolonization measures for disinfectant chlorhexidine in vitro . Correspondingly, patients colonized with C. auris, although chlorhexidine has during an outbreak in London, Schelenz et al. imple- been tested for that purpose during outbreaks [15, 49]. mented extreme environmental decontamination measures for cleaning and disinfection of the patient rooms and Conclusions equipment using 1000 ppm chlorine-based products three Currently, invasive fungal infections have undoubtedly times a day. On discharge or transfer of a C. auris positive been identified as having a major negative impact on hu- patient, the room was subjected to terminal cleaning with man health. Indeed, they are a real threat during the 10,000 ppm chlorine-based detergent and all cleaned hospital course of the weakest. Data from epidemio- equipment was left in the room to be disinfected with logical studies has allowed better identification of hydrogen peroxide vapour. patients at risk and major prevention measures have The CDC recommends thorough daily and terminal been evaluated to decrease the global burden of fungal disinfection of room surfaces and shared medical infections. However, when a new situation occurs, such equipment in rooms of patients with C. auris infec- as a healthcare outbreak due to a fungal species, it is dif- tion (https://www.cdc.gov/fungal/diseases/candidiasis/ ficult to evaluate which are the most appropriate control c-auris-infection-control.html). Although many disin- measures to implement rapidly, in part, because health- fectants are registered as disinfectants against Can- care fungal outbreaks are rare phenomena. Nevertheless, dida species by the Environmental Protection Agency, during recent years we have suffered from four large it is recommended that a disinfectant effective against healthcare fungal outbreaks due to uncommon and new Clostridium difficile spores should be used, such as species of fungi, which have been responsible for chlorine-based products. hundreds of infection cases. The analysis of these rare Several recent studies evaluated the efficacy in vitro of epidemic phenomena is a unique opportunity to learn disinfectants used for skin decolonization and environ- how to rapidly identify the first cases, to implement mental decontamination during hospital outbreaks [53– adequate control measures even when published data 55]. All showed differences between products; activity are lacking, and to reinforce the awareness of the public also varied with different formulations. Indeed, chlor- health community with regards to this new fungal risk. hexidine gluconate, iodinated povidone, chlorine and H O vapour demonstrated effective killing activity 2 2 Abbreviations against C. auris when used in clinical practice. However, CDC: Center for disease prevention and control; CVC: Central venous among disinfectants utilised for skin decolonization, catheter; ECDC: European center for disease prevention and control; HCW: Healthcare workers; ICU: Intensive care unit; MALDI-TOF: Matrix-assisted chlorhexidine was much less inhibitory at 3 min contact laser desorption ionization-time of flight; MDR: Multidrug-resistant; time compared to iodinate povidone used at 10% . MPA: Methylprednisolone acetate; WGS: Whole-genome sequencing; Similarly, the widely used quaternary ammonium WGST: Whole-genome sequence-based typing Bougnoux et al. Antimicrobial Resistance and Infection Control (2018) 7:45 Page 8 of 9 Acknowledgements 9. European Center for Disease Control and Prevention. http://ecdc.europa.eu/ Not applicable. en/publications/Publications/Candida-in-healthcare-settings_19-Dec-2016. pdf. Accessed 20 Dec 2016. 10. Satoh K, Makimura K, Hasumi Y, Nishiyama Y, Uchida K, Yamaguchi H. Funding Candida auris sp. nov., a novel ascomycetous yeast isolated from the Not applicable. external ear canal of an inpatient in a Japanese hospital. Microbiol Immunol. 2009;53(1):41–4. Availability of data and materials 11. Lee WG, Shin JH, Uh Y, Kang MG, Kim SH, Park KH, Jang HC. First three Not applicable. reported cases of nosocomial fungemia caused by Candida auris. J Clin Microbiol. 2011;49(9):3139–42. Authors’ contributions 12. Chowdhary A, Voss A, Meis JF. Multidrug-resistant Candida auris:'new kid on MEB, SB and JRZ analysed and interpreted the litterature regarding the the block' in hospital-associated infections? J Hosp Infect. 2016;94(3):209–12. healthcare associated fungal outbreaks due to new and uncommon species. 13. Kathuria S, Singh PK, Sharma C, Prakash A, Masih A, Kumar A, Meis JF, MEB, SB and JRZ were equal contributor in writing the manuscript. All Chowdhary A. Multidrug-resistant Candida auris misidentified as Candida authors read and approved the final manuscript. haemulonii: characterization by matrix-assisted laser desorption ionization- time of flight mass spectrometry and DNA sequencing and its antifungal Ethics approval and consent to participate susceptibility profile variability by Vitek 2, CLSI broth microdilution, and Not applicable. Etest method. J Clin Microbiol. 2015;53(6):1823–30. 14. Lockhart SR, Etienne KA, Vallabhaneni S, Farooqi J, Chowdhary A, Govender NP, Colombo AL, Calvo B, Cuomo CA, Desjardins CA, Berkow EL, Castanheira Consent for publication M, Magobo RE, Jabeen K, Asghar RJ, Meis JF, Jackson B, Chiller T, Litvintseva Not applicable. AP. 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Vallabhaneni S, Kallen A, Tsay S, Chow N, Welsh R, Kerins J, Kemble SK, Pacilli Submit your next manuscript to BioMed Central M, Black SR, Landon E, Ridgway J, Palmore TN, Zelzany A, Adams EH, Quinn M, Chaturvedi S, Greenko J, Fernandez R, Southwick K, Furuya EY, Calfee DP, and we will help you at every step: Hamula C, Patel G, Barrett P, MSD LP, Berkow EL, Moulton-Meissner H, Noble- • We accept pre-submission inquiries Wang J, Fagan RP, Jackson BR, Lockhart SR, Litvintseva AP, Chiller TM. Investigation of the first seven reported cases of Candida auris, a globally � Our selector tool helps you to ﬁnd the most relevant journal emerging invasive, multidrug-resistant fungus - United States, may 2013- � We provide round the clock customer support august 2016. MMWR Morb Mortal Wkly Rep. 2016;65(44):1234–7. � Convenient online submission 42. Lesho EP, Bronstein MZ, McGann P, Stam J, Kwak Y, Maybank R, McNamara J, Callahan M, Campbell J, Hinkle MK, Walsh EE. Importation, mitigation, and � Thorough peer review genomic epidemiology of Candida auris at a large teaching hospital. Infect � Inclusion in PubMed and all major indexing services Control Hosp Epidemiol. 2018;39(1):53–7. � Maximum visibility for your research 43. Sharma C, Kumar N, Pandey R, Meis JF, Chowdhary A. Whole genome sequencing of emerging multidrug resistant Candida auris isolates in India Submit your manuscript at demonstrates low genetic variation. New Microbes New Infect. 2016;13:77–82. www.biomedcentral.com/submit
Antimicrobial Resistance and Infection Control – Springer Journals
Published: Mar 27, 2018
Keywords: Healthcare-associated fungal outbreak; Candida auris; Exserohilum rostratum; Sarocladium kiliense; Saprochaete clavata; Prevention; Whole genome sequencing
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