Background

Elizabethkingia is a bacterial genus that is commonly detected in the environment (particularly soil and water) but that rarely causes human infection.^{[1, 2]} However, following an increased incidence of Elizabethkingia infections among patients in intensive care units since 2004, Elizabethkingia has been identified as an emerging pathogen in hospital settings.^[2]

Elizabethkingia infections are associated with a high mortality rate because of the lack of effective therapeutic regimens, antibiotic resistance, and virulence.^{[2, 3, 2]} However, Elizabethkingia rarely causes disease in otherwise healthy individuals.^[4]

In the United States, approximately 5-10 cases of Elizabethkingia infection are reported in each state annually, in addition to occasional small localized outbreaks, typically in healthcare settings.^[1]

According to the Wisconsin Department of Health Services, Elizabethkingia infections typically result in fever, shortness of breath, chills, or cellulitis, and the infection is confirmed with laboratory testing.^[5] Elizabethkingia infections have also been known to cause neonatal meningitis and, among immunocompromised persons, meningitis, bloodstream infections, and respiratory infections.^[1]

Elizabethkingia was first discovered in 1959 by Elizabeth O. King.^[6]King was an American bacteriologist who was working on an unclassified bacteria associated with meningitis in infants. In 2005, the genus was renamed Elizabethkingia.^[7]It consists of yellow pigment–producing, nonmotile, catalase-positive, oxidase-positive, non–glucose-fermenting, gram-negative bacilli. They grow poorly on MacConkey agar and are considered glucose oxidizers.

The genus Elizabethkingia has four species—Elizabethkingia anophelis, Elizabethkingia meningoseptica, Elizabethkingia endophytica, and Elizabethkingia miricola.

Elizabethkingia anophelis

E anophelis, a gram-negative bacteria, has been isolated from Anopheles mosquitoes and has been known to cause respiratory tract illness in humans.^[8]The role of mosquitoes in the transmission of E anophelis is unclear.^[6]

2015-2016 Elizabethkingia outbreak in Wisconsin, Michigan, and Illinois

E anophelis is associated with an ongoing outbreak in Wisconsin, Michigan, and Illinois. The current Elizabethkingia outbreak was first recognized in November 2015.^[4]The cases in these states represent the first reported US outbreak of E anophelis and the largest known outbreak of Elizabethkingia on record. As of June 16, 2016, 63 cases have been confirmed as part of the outbreak, resulting in 20 deaths.^{[4, 5]}

Six potential cases of Elizabethkingia infection were reported in Wisconsin between December 29, 2015, and January 4, 2016, prompting the state to establish statewide surveillance. On January 20, 2016, the Centers for Disease Control and Prevention (CDC) issued a nationwide call for cases, asking states to watch for cases similar to the ones reported in Wisconsin and to submit isolates for testing by the CDC. Following this call for nationwide vigilance, an isolate sent from Michigan was found to match the bacteria involved in the Wisconsin outbreak. An isolate sent from Illinois was also found to be a match.^[1]

This outbreak has primarily involved older adults (>65 years) and other patients with serious underlying health conditions. The infection typically presents as septicemia and can be fatal if treatment with appropriate antibiotics is delayed. The mortality rate of the current outbreak is approximately 30%, although it is unclear whether Elizabethkingia infection or an underlying cause (or both) has been the cause of death in these cases.^[1]

Clinicians should consider Elizabethkingia as a possible etiology among patients with underlying health issues and bloodstream infections of unknown etiology.^[4]

To date, most cases have been bloodstream infections, but Elizabethkingia has been isolated from other sites (respiratory tract, joints) in some patients.

Following the recognition of this outbreak, the CDC has asked that states send isolates of all species of Elizabethkingia for further testing to confirm whether the isolate is from the main outbreak cluster or an unrelated case. The recent call for case-finding has shown that some cases of Elizabethkingia infection may be unrecognized.^[4]

As of June 16, 2016, the Wisconsin Department of Health Services and the CDC, through a comprehensive ongoing investigation, has concluded the following^[5]:

Product and environmental samples from facilities that have treated patients with E anophelis infections have tested negative for E anophelis, and no evidence suggests that Elizabethkingia has been spread by a single healthcare facility.
Patients who have been treated in the same units where E anophelis infection has been discovered have tested negative for Elizabethkingia based on nose and throat swabs, indicating no person-to-person spread.

Elizabethkingia meningoseptica

E meningoseptica (formerly called Flavobacterium meningosepticum and, from 1994-2005, Chryseobacterium meningosepticum), is an environmental pathogen that is associated with opportunistic infection in humans. It has been associated with neonatal meningitis outbreaks in the setting of prematurity, particularly in underdeveloped countries.

In 2014, Teo et al reported that some infections that had been attributed to E meningoseptica in the past were in fact caused by E anophelis, based on whole-genome sequencing.^[9]

During a 22-month outbreak of E meningoseptica infection involving 30 patients in a London, UK, critical care unit, matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) was used to help identify the pathogen, which had been previously undiagnosed.^[10]

Pathophysiology

The role of mosquitoes in the transmission of E anophelis is unclear.^[6]

Epidemiology

Elizabethkingia outbreak in Wisconsin, Michigan, and Illinois (2015-2016)

E anophelis is associated with an ongoing outbreak in Wisconsin, Michigan, and Illinois, first recognized in November 2015.^[4]The cases in these states represent the first reported outbreak of E anophelis in the United States and the largest known outbreak of Elizabethkingia on record. As of June 16, 2016, 63 cases have been confirmed as part of the outbreak, resulting in 20 deaths.^{[4, 5]}

Prognosis

The mortality rate associated with the current multistate Elizabethkingia outbreak is approximately 30%, although it is unclear whether Elizabethkingia infection or an underlying cause has been the cause of death in these cases.^[1]

Factors associated with a poor outcome among patients with E meningoseptica infection include hypoalbuminemia, increased pulse rate at infection onset, and presence of central venous line.^[11]

Clinical Presentation

Centers for Disease Control and Prevention. Elizabethkingia. Centers for Disease Control and Prevention. Available at http://www.cdc.gov/elizabethkingia/about/index.html. April 12, 2016; Accessed: April 14, 2016.
Lin JN, Lai CH, Yang CH, Huang YH. Elizabethkingia Infections in Humans: From Genomics to Clinics. Microorganisms. 2019 Aug 28. 7 (9):[QxMD MEDLINE Link].
Teo J, Tan SY, Liu Y, Tay M, Ding Y, Li Y, et al. Comparative genomic analysis of malaria mosquito vector-associated novel pathogen Elizabethkingia anophelis. Genome Biol Evol. 2014 May 6. 6 (5):1158-65. [QxMD MEDLINE Link].
McQuiston J. Deadly Midwest Outbreak of Elizabethkingia. Medscape News and Perspective. Available at http://www.medscape.com/viewarticle/861096. April 1, 2016; Accessed: April 14, 2016.
Wisconsin Department of Health Services. Elizabethkingia. Wisconsin Department of Health Services. Available at https://www.dhs.wisconsin.gov/disease/elizabethkingia.htm. April 13, 2016; Accessed: April 14, 2016.
Kim KK, Kim MK, Lim JH, Park HY, Lee ST. Transfer of Chryseobacterium meningosepticum and Chryseobacterium miricola to Elizabethkingia gen. nov. as Elizabethkingia meningoseptica comb. nov. and Elizabethkingia miricola comb. nov. Int J Syst Evol Microbiol. 2005 May. 55 (Pt 3):1287-93. [QxMD MEDLINE Link].
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Kämpfer P, Matthews H, Glaeser SP, Martin K, Lodders N, Faye I. Elizabethkingia anophelis sp. nov., isolated from the midgut of the mosquito Anopheles gambiae. Int J Syst Evol Microbiol. 2011 Nov. 61 (Pt 11):2670-5. [QxMD MEDLINE Link].
Teo J, Tan SY, Liu Y, Tay M, Ding Y, Li Y, et al. Comparative genomic analysis of malaria mosquito vector-associated novel pathogen Elizabethkingia anophelis. Genome Biol Evol. 2014 May 6. 6 (5):1158-65. [QxMD MEDLINE Link].
Moore LS, Owens DS, Jepson A, Turton JF, Ashworth S, Donaldson H, et al. Waterborne Elizabethkingia meningoseptica in Adult Critical Care. Emerg Infect Dis. 2016 Jan. 22 (1):9-17. [QxMD MEDLINE Link].
Hung PP, Lin YH, Lin CF, Liu MF, Shi ZY. Chryseobacterium meningosepticum infection: antibiotic susceptibility and risk factors for mortality. J Microbiol Immunol Infect. 2008 Apr. 41 (2):137-44. [QxMD MEDLINE Link].
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Hsu MS, Liao CH, Huang YT, Liu CY, Yang CJ, Kao KL, et al. Clinical features, antimicrobial susceptibilities, and outcomes of Elizabethkingia meningoseptica (Chryseobacterium meningosepticum) bacteremia at a medical center in Taiwan, 1999-2006. Eur J Clin Microbiol Infect Dis. 2011 Oct. 30 (10):1271-8. [QxMD MEDLINE Link].
Issack MI, Neetoo Y. An outbreak of Elizabethkingia meningoseptica neonatal meningitis in Mauritius. J Infect Dev Ctries. 2011 Dec 13. 5 (12):834-9. [QxMD MEDLINE Link].
Tak V, Mathur P, Varghese P, Misra MC. Elizabethkingia meningoseptica: an emerging pathogen causing meningitis in a hospitalized adult trauma patient. Indian J Med Microbiol. 2013 Jul-Sep. 31 (3):293-5. [QxMD MEDLINE Link].
Han MS, Kim H, Lee Y, Kim M, Ku NS, Choi JY, et al. Relative Prevalence and Antimicrobial Susceptibility of Clinical Isolates of Elizabethkingia Species Based on 16S rRNA Gene Sequencing. J Clin Microbiol. 2017 Jan. 55 (1):274-280. [QxMD MEDLINE Link].