Elizabethkingia Infections 

Updated: Feb 03, 2017
Author: Meenal Malviya, MBBS, MD; Chief Editor: Michael Stuart Bronze, MD 

Overview

Background

Elizabethkingia is a bacterial genus that is commonly detected in the environment (particularly soil and water) but that rarely causes human infection.[1] 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.

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

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.[4]  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.[5] King was an American bacteriologist who was working on an unclassified bacteria associated with meningitis in infants. In 2005, the genus was renamed Elizabethkingia.[6] 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.[7] The role of mosquitoes in the transmission of E anophelis is unclear.[5]

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.[3] 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, 3]

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.[3]

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.[3]

As of June 16, 2016, the Wisconsin Department of Health Services and the CDC, through a comprehensive ongoing investigation, has concluded the following:[4]

  • 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.[8]

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.[9]

Pathophysiology

The role of mosquitoes in the transmission of E anophelis is unclear.[5]

Epidemiology

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]

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.[3] 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, 3]  

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.[10]

 

Presentation

History

Elizabethkingia are opportunistic pathogens that typically cause illness among immunocompromised patients and patients with underlying medical conditions.

According to the Wisconsin Department of Health Services, Elizabethkingia infections typically result in fever, shortness of breath, chills, or cellulitis.[4] Elizabethkingia infections have also been known to cause neonatal meningitis, and, among immunocompromised persons, meningitis, bloodstream infections, and respiratory infections.[1]

Most patients identified during the current multistate outbreak have been older (>65 years), and all have had at least one serious underlying illness.[1]

Patients with multiple comorbid conditions (especially cancer, diabetes mellitus, chronic kidney disease or end-stage renal disease being treated with dialysis, alcoholism, alcoholic cirrhosis, immunocompromising conditions, immunosuppressive treatment) should prompt a high index of suspicion for Elizabethkingia infections.

 

DDx

Diagnostic Considerations

E meningoseptica may show colistin-resistant and vancomycin-sensitive growth, which is paradoxic for a gram-negative bacterium. It resembles Burkholderia cepacia, which is also a nonfermenter and does not grow well on MacConkey agar. These two can be differentiated using the indole test or the Pyr test, both of which should be clearly negative for B cepacia and positive for E meningoseptica.

Automated bacterial identification system results should be observed with caution, especially when a patient with gram-negative bacteremia does not improve with broad-spectrum antibiotic therapy, because several bacteria, including Aeromonas salmonicida[6] and Sphingobacterium species, may be confused with this bacterium, especially the atypical ones. However, unlike many other Aeromonas species such as Aeromonas hydrophilia and Aeromonas punctata, A salmonicida is indole-negative, which can help in distinguishing it in doubtful cases.[11, 12]

 

Workup

Approach Considerations

Elizabethkingia infections are diagnosed based on culture from sterile sites, usually blood.[3]

Bacterial detection software in some clinical laboratories may misidentify Elizabethkingia as other bacteria. When such cases result in identification of F meningosepticum or C meningosepticum, the CDC has advised that these results be reported to the state health department for consultation and that the infection be treated presumptively as infection with E anophelis.[3]

State clinical microbiology laboratories can characterize the isolates using pulsed-field gel electrophoresis, a method that can correctly identify the Elizabethkingia genus. Isolates sent to the CDC's Special Bacteriology Reference Laboratory are confirmed as the species E anophelis based on the pathogen's protein profile, acquired using the mass spectrometry method MALDI-ToF and optical mapping of the bacterial genome.[3]

 

Treatment

Approach Considerations

Elizabethkingia is typically resistant to antibiotics used to treat gram-negative infections, including extended-spectrum beta-lactams, aminoglycosides, tetracycline, and chloramphenicol. Vancomycin has been used to treat nonneonatal Elizabethkingia meningitis in the past, but it has a high minimum inhibitory concentration (MIC). Alternatives include ciprofloxacin, minocycline, trimethoprim-sulfamethoxazole, rifampin, and novobiocin.[13]

Treatment of the 2015-2016 ElizabethkingiaOutbreak in Wisconsin, Michigan, and Illinois

Elizabethkingia infections involved in the current multistate outbreak typically manifest as septicemia and can be fatal if treatment with appropriate antibiotic therapy is delayed. Patients with underlying health issues and bloodstream infections of unknown etiology should prompt consideration of Elizabethkingia as a possible cause.

These Elizabethkingia infections have been found to be susceptible to several antibiotics, including fluoroquinolones, minocycline, rifampin, and trimethoprim/sulfamethoxazole. If possible, combination treatment is recommended over monotherapy. For best results, treatment should be selected based on antimicrobial susceptibility testing on a case-by-case basis.[3]

Bacterial detection software in some clinical laboratories may misidentify Elizabethkingia as other bacteria. When such cases result in identification of F meningosepticum or C meningosepticum, the CDC has advised that these results be reported to the state health department for consultation and that the infection be treated presumptively as infection with E anophelis.[3]

Prevention

Infection-control measures in healthcare settings

In the context of the current Elizabethkingia outbreak, the Wisconsin Department of Health Services (DHS) Division of Public Health (DPH) recommends contact precautions in addition to standard precautions during the management of patients with Elizabethkingia infections. The DPH recommends contact precautions for the duration of admission in acute-care facilities. Receiving facilities should be made aware of the patient’s infection status upon transfer.

 

Medication

Medication Summary

Vancomycin has been used to treat nonneonatal Elizabethkingia meningitis in the past, but it has a high minimum inhibitory concentration (MIC). Vancomycin has been used in combination with other agents, including rifampin; however, its usefulness has been questioned.[14]

Elizabethkingia shows some susceptibility to fluoroquinolones, whereas its susceptibility to doxycycline and trimethoprim varies. This often leads to an inappropriate choice of antibiotics for initial empirical therapy and results in treatment failures. It is resistant to multiple antibiotics, especially beta-lactams, as it produces two beta-lactamases, extended-spectrum beta-lactamase and a carbapenem-hydrolyzing metallo beta-lactamase, conferring resistance to many extended-spectrum beta-lactam antibiotics, aztreonam, and carbapenems. However, various studies have found E meningoseptica to be sensitive to piperacillin and piperacillin/tazobactam.[15, 16, 17] Antimicrobial resistance may vary depending on the species and region and time of bacterial isolation.

The 2015/2016 Elizabethkingia infections in Wisconsin, Michigan, and Illinois were found to be susceptible to several antibiotics, including fluoroquinolones, minocycline, rifampin, and trimethoprim/sulfamethoxazole. If possible, combination treatment is recommended over monotherapy.

An extensive 2017 survey by Han et al, from Seoul, Republic of Korea, studied 86 isolates of Elizabethkingia species, of which 17 were E meningoseptica, 18 were E miricola, and 51 were E anophelis. Over 90% of E meningoseptica and E anophelis isolates were susceptible to piperacillin-tazobactam and rifampin. In contrast, all E miricola isolates were susceptible to fluoroquinolones except ciprofloxacin.[18]

This helps to summarize the potential empiric choices for each of the species described above.

Antibiotics

Class Summary

Antibiotics should be selected based on antimicrobial susceptibility testing on a case-by-case basis.[3] Combination antibiotic treatment is encouraged.

Levofloxacin (Levaquin)

Fluoroquinolone antibiotic that is the l-stereoisomer of ofloxacin. Inhibits DNA gyrase activity, which in turn promotes breakage of DNA strands.

Ciprofloxacin (Cipro, Cipro XR, ProQuin XR)

Fluoroquinolone antibiotic. It inhibits DNA gyrase in susceptible organisms, and therefore promotes breakage of double-stranded DNA.

Minocycline (Minocin)

Tetracycline antibiotic. It inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria.

Rifampin (Rifadin)

Inhibits DNA-dependent RNA polymerase by binding to beta subunit, which in turn blocks RNA transcription; potent enzyme inducer.

Trimethoprim/sulfamethoxazole (Bactrim, Cotrim)

Blocks 2 consecutive steps in the biosynthesis of nucleic acids and proteins essential to many bacteria. Trimethoprim inhibits dihydrofolate reductase, thereby blocking production of tetrahydrofolic acid from dihydrofolic acid. Sulfamethoxazole inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid.