Chryseobacterium indologenes: an emerging infection in the USA

Abstract

Nursing home-associated infections and antibiotic resistant pathogens constitute common and serious problems in the geriatric population. Chryseobacterium indologenes, a non-motile Gram-negative rod, though widely distributed in nature, is an uncommon human pathogen. Typically thought of as an organism of low virulence, it may cause serious infections, particularly among the immunocompromised. The majority of reported cases are nosocomial, often associated with immunosuppression or indwelling catheters. It has been reported as the causative agent in bacteraemia, peritonitis, pneumonia, empyema, pyelonephritis, cystitis, meningitis and central venous catheter-associated infections. We report a rare case of C. indologenes infection affecting a nursing home resident in the USA and we provide a review of similar cases. This report emphasises the importance of individualised treatment and promotes awareness about this organism as one of several emerging pathogens in immunocompromised adults and in the frail elderly who are often nursing home residents, in the Western Hemisphere.

Background

The elderly, including frail nursing home residents, adults with advanced or chronic illnesses regardless of age, immunocompromised patients whether due to systemic illness or medications and patients with indwelling devices or tubes, are especially prone to acquiring healthcare-associated infections. The emergence of new infections and antibiotic-resistant organisms increases this vulnerability even more. Chryseobacterium indologenes appears to be one of the new human pathogens all the more fearsome because of its exceptional antibiotic resistance.¹

C. indologenes belongs to the Chryseobacterium genus, previously known as Flavobacterium. The genus is composed of six species where Chryseobacterium meningosepticum, in current taxonomy named Elizabethkingia meningosepticum, is reported as the most pathogenic, while C. indologenes was reported to have low virulence.² C. indologenes is a yellow-pigmented, non-motile, oxidase positive, glucose non-fermentative, Gram-negative rod-shaped bacterium widely distributed in nature. Other clinically significant Gram-negative rod-shaped microorganisms commonly associated with urinary tract infections or sepsis are shown in the flow-diagram (figure 1).

Figure 1.

Aerobic Gram-negative rods associated with urinary tract infection.

Until 1996, C. indologenes had been only rarely implicated in bacteraemia in humans. Since then, the numbers of reported cases of C. indologenes infections are steadily increasing. The majority of reported infections have been from Taiwan³ and only about 10% have been outside of Asia. A few reports have come from Australia, India, Europe and the USA^{4 5} (table 1). There are many reported cases of C. indologenes in paediatric populations,^{8 11} as well as in immunocompromised, hospitalised patients^12–14 with severe illness and or with indwelling devices.^7–9

Table 1.

Chryseobacterium indologenes-related infections reported in the USA

Author	Year	Place	Age/gender	Predisposing factor	Clinical presentation	Treatment	Outcome
Green et al6	2001	Texas	77-year-old man	Treatment for squamous cell carcinoma of leg, swam in his pool	Cellulitis and bacteraemia	Levofloxacin	Recovered
Cone et al7	2007	California	57-year-old woman	Breast cancer central catheter	Sepsis due to an infected central catheter	Ciprofloxacin catheter was removed	Recovered
Al-Tatari et al8	2007	Michigan	13-year-old boy	Congenital hydrocephalus and LP shunt	LP shunt infection	Trimethoprim-sulfamethoxazole and rifampin LP shunt was removed	Recovered
Shah et al9	2012	New York	26-year-old woman	Liver transplant on immunosuppressive treatment; subcutaneous port	Worsening ascites, abdominal pain	Levofloxacin and trimethoprim-sulfamethoxazole port was removed	Recovered
Yasmin et al5	2013	Georgia	32-year-old woman	Metastatic breast cancer; on mechanical ventilation	Ventilator-associated pneumonia	Levofloxacin	Patient Died
Afshar et al4	2013	District Columbia	51-year-old man	End stage renal disease; on peritoneal dialysis	Peritonitis	Ceftazidime without catheter removal	Recovered
Monteen et al10	2013	Tennessee	66-year-old man	Critical accident; trapped under water and later intubated	Ventilator-associated pneumonia	Moxifloxacin and cefepime	Recovered
This study	2015	Michigan	63-year-old man	Indwelling Foley catheter; nursing home patient	UTI	Imipenem	Recovered

LP, lumboperitoneal; UTI, urinary tract infection.

We report a C. indologenes infection in a diabetic nursing home adult with an indwelling Foley catheter, in the USA.

Case presentation

A 63-year-old Caucasian man, a resident of an extended care facility, was brought to the hospital, with acute confusion that was preceded by dysuria, fever and diffuse cramping lower abdominal pain. He had a history of spinal stenosis and urinary retention treated with an indwelling Foley catheter of 2 months’ duration. Prior to admission, he had been treated empirically with nitrofurantoin 100 mg orally every 12 h for 5 days. Comorbid conditions included stable chronic obstructive pulmonary disease, coronary artery disease, diabetes mellitus, benign prostatic hypertrophy, atrial fibrillation, bipolar disorder and anaemia with haemoglobin of 7.7 g/dL. On physical examination, he was alert but oriented to neither time nor place; he had stable vital signs and some suprapubic tenderness.

Investigations

On the second hospital day, urine culture showed more than 100 000 colony-forming units of C. indologenes, which was resistant to almost all antimicrobials except imipenem-cilastatin. The patient had no leucocytosis and blood cultures were negative.

Treatment

Ceftriaxone 1 g was administered intravenously, which was later switched to vancomycin 1 g intravenously daily and piperacillin/tazobactam 3.375 g intravenously every 8 h, to provide broader empiric coverage. The source of infection was felt to be the indwelling Foley catheter, which was replaced and antibiotic therapy was changed to imipenem-cilastatin after consulting infectious disease.

Outcome and follow-up

Repeat urine culture was negative and the patient was discharged with resolution of symptoms after 7 days of hospitalisation.

Discussion

C. indologenes is ubiquitous in nature, mainly found in soil and water and may be perceived as a coloniser. However, in some patients, it may cause significant morbidity and mortality. It resists chlorination and can survive in municipal water supplies.² It is prevalent on wet or humid surfaces in hospitals and also in catheters containing fluids, such as feeding tubes, central venous catheters and tracheostomy tubes.¹⁵ The presence of contaminated medical devices in institutionalised and or immunocompromised patients, such as patients with diabetes mellitus, malignancies and neutropaenia and prolonged treatment with antibiotics, may result in serious infections.^{4 7 16–18} More than half of the reported cases have been among hospitalised, immunocompromised patients with mechanical ventilation or indwelling catheters.^{5 7 10 15} Although C. indologenes infections are nosocomial, device-related infections and, recently, non-catheter-related community-acquired C. indologenes bacteraemia in immunocompetent patients, have been reported.^{12 19 20}

It has also been reported that C. indologenes infection is more prevalent in the elderly.^20–23 However, there are only a few reports in octogenarians and/or nursing home patients. In addition to device-related risk in the elderly, other predisposing factors include immunocompromising conditions such as diabetes and long-term treatment with systemic steroids. Infections such as healthcare-associated pneumonia in an immunocompetent patient and polymicrobial urinary tract infections have been reported in this age group.^{20 21 24} Outcomes of the hospitalised elderly have been favourable.

The most common clinical presentations of C. indologenes infection are pneumonia, bacteraemia, cellulitis, surgical wound infections, urinary tract infections, ocular infections, meningitis due to central nervous system shunt, peritonitis due to peritoneal catheter dialysis, intra-abdominal and other catheter-related infections.^{4 6–8 25}

C. indologenes associated urinary tract infections have been recently reported worldwide^26–28 (table 2).

Table 2.

Urinary tract infections associated with Chryseobacterium indologenes: case reports

	Patient 1	Patient 2	Patient 3	Patient 4
Age (years)	19	86	42	21
Gender	Female	Female	Female	Female
Predisposing factor	Urinary catheter for 7 days after pyelolithotomy	Insulin-dependent type 2 diabetes	Chronic myeloid leukaemia	Urinary catheter for 24 h after induced labour for intrauterine fetal death
Clinical presentation	High-grade fever, burning micturition on fifth postoperative day	Hospitalised for decompensated congestive heart failure	High-grade fever	Fever spike
Treatment	Piperacillin-tazobactam	Levofloxacin	Ceftriaxone	Tigecycline
Outcome	Recovered	Recovered	Died with severe sepsis	Recovered
Year	2012	2013	2014	2015
Place	India	Spain	Senegal	India
Author	Bhuyar et al26	Acosta et al21	Omar et al27	Solanke et al28

The mortality rate of C. indologenes varies with different studies, however, in a 2011 study from Taiwan, which included 10 patients with C. indologenes with sepsis (mean age of 71.1 years), the mortality rate at 14 days was 40%.¹⁷ The analysis of 215 other C. indologenes cases, also from Taiwan, revealed that in-hospital mortality rates from bacteraemia were as high as 63.6% and from pneumonia, 35.25%.³

Although C. indologenes exhibits characteristics of low virulence, it may cause life-threatening infections due to its multidrug resistance.^{22 29 30} Its ability to produce biofilm on foreign materials and produce proteases, can cause several forms of infections and is responsible for its virulent character.³¹ One study mentioned the production of a metallo-β-lactamase, which allows the bacteria to hydrolyse the β lactam part of some drugs.³² It was sensitive to a limited number of antibiotics that include newer quinolones, in particular, garenoxacin, gatifloxacin and levofloxacin, rifampin, trimethoprim-sulfamethoxazole and piperacillin-tazobactam.²² The antibiotics commonly used to treat Gram-negative organisms, such as cephalosporins, aminoglycosides and imipenem, have—in an in vitro study—been reported to be ineffective against C. indologenes.³ In addition, it is now shown in this study that its resistance is rapidly evolving, with drastically limited antibiotics to which it is susceptible, namely, trimethoprim-sulfamethoxazole and cefoperazone-sulbactam.³

There is controversy regarding whether indwelling catheters should be removed when there is an associated C. indologenes infection. Reports vary on the effectiveness of antibiotic treatment with or without removal of the indwelling device.^{9 15 18 33–35} In general, when there is failure to respond to appropriate antibiotic treatment, indwelling catheters should be removed.¹⁵ If the indwelling catheter-related infection caused by C. indologenes does not cause rapid clinical deterioration, then the device does not require removal.^{15 18 36} However, in some immunocompromised patients, removal of a port or central catheter may hasten recovery.³⁷

Because of varying susceptibilities, it has been suggested that the treatment of the organism should be based on its sensitivity pattern. In our case, results of susceptibility testing differed from what has been previously reported. Our isolated pathogen was sensitive only to imipenem-cilastatin.

In summary, infection from C. indologenes was initially rarely reported outside Taiwan. It is important to keep C. indologenes in mind as a possible source of infection in patients with the appropriate risk factors. Because of varying susceptibilities to antimicrobials, empiric antibiotic treatment of the patient with possible C. indologenes infection needs to be tailored to its local susceptibilities until a confirmatory culture report is obtained. This may avoid delay in the recovery of the patient. In addition, removing the probable source of infection may also be an important consideration. Moreover, the multidrug resistance makes this organism an ominous emerging pathogen.

Learning points.

• In the elderly and people with advanced illness or indwelling catheters and institutionalised or frail nursing home residents, even an organism with low virulence, such as C. indologenes, may become a life-threatening pathogen.

• Nosocomial spread is possible, therefore in hospitals and nursing homes, universal precautions need to be observed to avoid spread of the infection.

• Because of varying susceptibilities to antimicrobials, empiric antibiotic treatment of the patient with possible C. indologenes infection needs to be tailored to its local susceptibilities until a confirmatory culture report is obtained.