Elizabethkingia meningoseptica, formerly known as Chryseobacterium meningosepticum, is a non-motile, non-fastidious, catalase and oxidase-positive, aerobic, glucose-non-fermentative, Gram-negative bacillus that was first defined by Elizabeth O. King in 1959 [1]. The Elizabethkingia genus has been noted due to the genetic makeup that facilitates a large degree of genetic variability and subsequent antimicrobial resistance. This, combined with lack of literature reports on the wide distribution in nature and of adequate treatment regimens have led to high mortality rates in hospital-settings, particularly in intensive care units (ICUs), since 2004 [2].

E. meningoseptica is isolated most frequently from soil, saltwater, and freshwater and from dry and moist clinical environmental and equipment surfaces, intravenous lipid solutions, and municipal water supplies, including those adequately chlorinated [3]. Although nearly ubiquitous in nature, it is an uncommon human pathogen. E. meningoseptica predominately causes outbreaks of meningitis in immunocompromised patients, particularly in premature newborns and infants in neonatal ICUs of developing countries [4]. The bacterium is a rare cause of nosocomial pneumonia, endocarditis, and meningitis in immunocompromised adults. More recently, in the past few years, it has been found to cause soft tissue infection and sepsis in immunocompetent adults [5].

In a study from Wisconsin, 48 cases of Elizabethkingia infection were reported during an outbreak, which resulted in 17 deaths in a 5-month period beginning in November 2015 [6]. Another case series showed that the yearly incidence of E. meningoseptica bacteremia increased substantially from 2002 to 2006 (from 6.8–13.1 to 26.6–39.9 per 100,000 admissions; P = 0.006) [7].

Moreover, Elizabethkingia, similar to its genetic relative Chryseobacterium species, is inherently extensively drug resistant. It is resistant to a broad spectrum of antibiotic classes, including macrolides, tetracyclines, linezolid, polymyxin group, chloramphenicol, aminoglycosides, and beta-lactam drugs [8]. Vancomycin, rifampicin, new fluoroquinolones, piperacillin-tazobactam, and minocycline are the current preferred empirical choices for treating E. meningoseptica infections.

E. meningoseptica is an important emerging opportunistic bacterium that primarily occurs in nosocomial settings. It is unclear which treatment regimen is most effective and what factors are associated with adverse outcomes. The aim of this study is to describe the clinical features and outcomes of E. meningoseptica infections in a tertiary care center in Karachi, Pakistan.

The study received an exemption from ethical approval from the Aga Khan University Ethics Review Committee (ERC #2019-1786-4439) and requirement of informed consent was waived due to retrospective nature of study. Data was anonymized and no personal identifiers were collected.

This was an observational study of patients admitted between January 2013 and December 2018, with E. meningoseptica infections. All patients were confirmed to have a positive clinical culture specimen for E. meningoseptica along with signs and symptoms consistent with infection. All patients presumed to be colonized but not infected were excluded. Data were collected on a structured proforma from the Hospital Information Management Systems. Identification and susceptibility of E. meningoseptica isolated from cultures were performed by automated systems in accordance with Clinical Laboratory Standards Institute recommendations. Identification of E. meningoseptica was determined by a Vitek 2 system (bioMerieux, Marcy-l’Étoile, France).

Sixteen patients with E. meningoseptica infections were identified between 2013 and 2018, 13 of whom required hospital admission, constituting an infection rate of 2.9 per 100,000 admissions. The median age was 29 years for six males and seven females, with ages ranging from 3 days to 83 years. The most common comorbid conditions were diabetes (5/13) and hypertension (5/13). The average Charlson’s comorbidity index was 3.3. Three patients had underlying malignancy, and five patients had a history of repeated hospitalization. Eleven patients were admitted to the ICU. Eight of 13 patients had bacteremia with E. meningosepticum, and the most common source of bacteremia was central line-associated bloodstream infection in six patients. Among other sites of infection, one had urinary tract infection, two had meningitis, two had pneumonia, and one had infective endocarditis. Nine patients had mono-microbial growth, whereas four had polymicrobial growth in culture. Of 13 patients, eight required a Foley catheter and nine required a central venous catheter, endotracheal intubation, and mechanical ventilation. The clinical characteristics of all 13 patients are summarized in Table 1. E. meningosepticum was sensitive to quinolones in five of 13 isolates. Two of the E. meningosepticum isolates were multi- drug resistant with sensitivity only to minocycline, which was the drug used for definitive treatment. The susceptibility pattern of all isolates is summarized in Figure 1. Five of 13 patients were treated with a quinolone, four with cotrimoxazole, and four with minocycline. However, culture appropriate antibiotics were not initiated in two patients. The most common co-infection was with multi-drug resistant Acinetobacter (n = 2) or Pseudomonas aeruginosa (n = 2). Five of 13 patients died, two cases were referred for palliative care in view of advanced underlying malignancy, and the median length of hospital stay was 13 days. All five patients who died had a history of repeat hospitalization and significant comorbidities. All five of these patients were mechanically ventilated and underwent invasive catheterization. E. meningoseptica was isolated from the blood of three patients and from tracheal aspirate in one patient who had undergone esophagectomy, thoracotomy, and tracheostomy. Death could be attributed to E. meningoseptica infection in two of five patients. One patient had repeated isolation of the organism from blood cultures due to infective endocarditis, and the other had nosocomial pneumonia after prolonged hospitalization.

Our study identified and analyzed Elizabeth meningoseptica infections in patients with underlying comorbidities, particularly in patients that required frequent hospitalizations. While many isolated case reports and series have been reported [11- 16], only a few [17] have included more than four Elizabethkingia cases (Table 2). There are no reports on Elizabethkingia cases from Pakistan. Our study identified 16 patients in the last six years with Elizabethkingia meningosepticum infections. Unlike other case series with predominantly neonatal cases [17], our patients had a median age of 29 years. Similar to other case reports, the infections were urinary tract infection and meningitis [11,16]. The outcomes have been variable, with significant mortality among neonates [17]. However, patients with isolates susceptible to quinolones and treated with Ciprofloxacin had better survival outcomes [14]. This result is similar to patients that of who were treated with a quinolone in our study.

E. meningosepticum is resistant to most commonly used antimicrobials; therefore, options for treatment are limited. Most studies have established that clinical isolates are resistant to aminoglycosides and beta lactams, with notable exception of piperacillin-tazobactam, and show sensitivities to fluroquinolones and tetracyclines [15]. These patterns were consistent with the results of this study.

This study is a single-center case series with several inherent limitations such as the small sample size and unavailability of molecular testing and minimum inhibitory concentration data on all isolates. However, this study is the largest to date and the first from Pakistan, to report clinical features and treatment outcomes of E. meningoseptica infections. Moreover, it offers insight into the sensitivity pattern of this organism in our region. E. meningosepticum is an emerging nosocomial pathogen that causes mortality in patients requiring intensive care.