Chryseobacterium indologenes Bacteremia : Clinical and Microbiological Characteristics of an Emerging Infection

Purpose: Since Chryseobacterium indologenes (C. indologenes) is a rare human pathogen, its clinical significance has not yet been fully established. C. indologenes contamination of medical devices involving fluids and of surgical implants has led to an increasing number of serious infectious reported in recent years, mainly in patients in extremes ages and an immunocompromised state. In this study, we describe the clinical and microbiological characteristics of seven adult patients with C. indologenes bacteremia treated in a tertiary medical center in Israel over a six-year period. Methods: Adult patients hospitalized in Rabin Medical Center, Israel, with a blood culture positive for C. indologenes during the period 2009-2014 were identified retrospectively and their medical records were reviewed. Results: Seven episodes of C. indologenes bacteremia in seven patients were identified during the study period. Five patients were females; the mean age was 76.8 years (41 92). Serious underlying conditions were present in all patients. All patients but one, presented after a recent invasive healthcare related intervention. Two patients required mechanical ventilation. Two patients died. All but one isolates were susceptible to ciprofloxacin. Conclusions: Despite our limited number of cases, to the best of our knowledge, our study serves as the largest cohort of adult patients with C. indologenes bacteremia reported in recent years.


Introduction
Chryseobacterium indologenes is a non-fermentative, oxidase-catalase-and indole-positive, non-motile bacillus that belongs to the genius of Chryseobacterium (previously known as Flavobacterium CDC group IIb) [1].It is widely found in nature, on soil, water and plants and only rarely causes human disease [2].Since the organism can survive in chlorine treated water, it can colonize water supplies, thus creating potential reservoirs for infections in hospital settings [3].Therefore, although not present in human microflora, contamination of medical devices involving fluids and of surgical implants has led to an increasing number of serious infectious reported in recent years.These include cases of pneumonia [4], indwelling device associated infections [5], peritonitis [6], ocular infections [7] and bacteremia [8].Other reported infections included pyelonephritis, biliary tract infections, neurosurgical shunt infections and wound infections [9] [10].Case series conducted mostly in Taiwan have demonstrated extremes of age and an immunocompromised state to be common risk factors [8].
The highly active proteases of C. indologenes as well as its biofilm production capacity are both responsible for its virulence [11].C. indologenes is known to exhibit natural resistance to a wide variety of broad spectrum antibiotics, including aminoglycosides, tetracyclines, chloramphenicol, macolides, clindamycin and teicoplanin as well as to extended spectrum penicillins, first and second generation cephalosporins, aztreonam, ticarcillin-clavulanate and the carbapenems.Piperacillin-tazobactam, ceftazidime, minocycline, rifampicin, trimethoprim-sulfamethoxazole and quinolones usually remain effective [3].
Since C. indologenes is a rare human pathogen, its clinical significance has not yet been fully established.To the best of our knowledge, the latest case series published described six cases of C. indologenes infections, 2012-2015, all in pediatric patients [12].
We thus aimed in this study to describe the clinical and microbiological characteristics of seven adult patients with C. indologenes bacteremia in our institution over a six-year period (2009-2014).

Methods
The Rabin medical center is a 1000 bed, teaching, tertiary care facility located in central Israel.It serves a population of over 500,000 people and includes, among other services, advanced transplantation and oncology services.
Study population: All adult patients with a blood culture positive for C. indologenes in the study period (2009)(2010)(2011)(2012)(2013)(2014) were identified retrospectively and their medical records were reviewed.There were no other inclusion or exclusion criteria.
An episode of clinical infection was defined by at least one blood culture positive for C. indologenes together with clinical sepsis.Recent surgery was defined by a procedure performed within the previous month.Empirical appropriate antibiotic therapy was defined as the use of at least one antibiotic to which the or- Death was considered related to the bacteremia if the patient died within a week after its onset.
Blood culture samples were processed using BACTEC-FX (Becton Dickinson, USA).Positive cultures following Gram staining were subcultured on blood agar, chocolate agar and MacConkey agar plates.
The Brucker MALDI-TOF (Brucker, USA) system was used for C. indologenes identification.MIC values for C. indologenes isolates were determined by direct sensitivity using the disc diffusion method.The MICs for susceptibility were determined according to the CLSI standards.
The study was approved by Rabin Medical Center's Ethics Committee.
Female patients constructed the majority of our patient population (71%).The mean age was 76.8 years (41 -92).Serious underlying conditions, such as chronic renal failure, diabetes and dementia were present in all patients.All patients but one, presented after a recent invasive healthcare related intervention: drainage of an intracranial epidural hematoma, complicated coronary artery Four patients were treated empirically with appropriate antibiotics, of these, three patients survived.In all these cases, the agent given to which the isolate was susceptible was ciprofloxacin.
Among the three patients who were treated empirically with inappropriate antibiotics, only two survived.

Antimicrobial Resistance
The susceptibility and resistance results of all C. indologenes are presented in Table 2.
All isolated were susceptible to minocycline and to piperacillin-tazobactam.All but one isolates were susceptible to quinolones, trimethoprim-sulfamethoxazole and ceftazidime.

Discussion
Chryseobacterium indologenes is a non fermentative Gram negative bacillus widely distributed in nature [1].Although a rare human pathogen, serious infections caused by C. indologenes have been increasingly reported in recent years [5] [12] [13] [14].Most of the reported infections occurred in immunocompromised patients or in patients with invasive devices during their hospital stay [15] [16] where it can persist on wet surfaces and in fluid containing apparatuses [17].Most isolates reported are from clinical specimens other than blood [3], limited data is available on characteristics, treatment and outcome of patients with C. indologenes bacteremia.We present a cohort of seven patients who had C. indologenes bacteremia over a period of six-year in a large tertiary medical center.As reported in previous publications, all patients had severe underlying conditions, such as diabetes, end stage renal disease, pneumonia necessitating mechanical ventilation, heart failure and intracranial bleeding.All patients were, to a different extent, immunocompromised: either due to age related immunosenescence, diabetes or immunosuppressant medications.All but one of the patients had undergone a recent invasive procedure in a hospital: Drainage of an epidural hematoma, a coronary percutaneous intervention with complications, the formation of an arteriovenous fistula, drainage of a transplanted kidney abscess, the correction of a diaphragmatic hernia and debridement of an abscess complicating a surgical amputation wound.The mean age of our patients was 76 years, but four of them were above the age of 80 years, which is older than in previous reports [8] [18] [19].In contrast to previous reports, females were predominant in our study [8] [18].Also in contrast to previous reports, most of our patients had not received previous, prolonged courses of antibiotics [8].We therefore suggest that C. indologenes is a pathogen that might cause bacteremia in elderly patients with multiple co-morbidities who have undergone various hospital procedures, most probably as a result of a breach in infection control practices.
C. indologenes is inherently resistant to many antimicrobial agents [3], with a nearly uniform resistance to extended spectrum penicillins, cephalosporins (other than ceftazidime, cefepime), aztreonam, ticarcillin-clavulanate, the carbapenems, macrolides, aminoglycosydes and macrolides and chloramphenicol has been reported.C. indologenes remains susceptible, in most reports, to minocycline, ceftazidime, piperacillin-tazobactam, rifampin, the quinolones and trimethoprim-sulfamethoxazole [20].In our study, the resistance and susceptibility patterns, as determined by the disc diffusion method, were consistent with

D.
Alon et al.DOI: 10.4236/ijcm.2018.96045522 International Journal of Clinical Medicine ganism was susceptible prior its identification by the microbiological laboratory.
[18] et al.Both these patients were elderly, had dementia and resided in chronic care facilities.The attributable mortality of C. indologenes as suggested in previous literature is around 17%[2][18].Although the calculated mortality in our study (two out of seven patients, 28%) was higher than previously reported, the two patients who died were both elderly, with advanced dementia and residing in chronic care facilities, for which appropriate treatment did not confer a survival benefit, just as inappropriate treatment was not associated with a higher mortality rate.Therefore, our results are in agreement with the literature published thus far, according to which C. indologenes bacteremia is not necessarily associated with an unfavorable outcome.We believe patients' outcome is mainly driven by host factors rather than bacterial virulence factors.Despite our limited number of cases, to the best of our knowledge, our study serves as the largest cohort of adult patients with C. indologenes bacteremia reported in recent years.Risk factors repeatedly reported for C. indologenes bacteremia include advanced age, immunosuppression, and previous invasive procedures.Although the optimal antibiotic choice remains to be determined, quinolones as well as trimethoprim-sulfamethoxazole seem to provide appropriate antimicrobial coverage.Further surveillance programs are necessary to fully elucidate the clinical importance of this rare pathogen and to inform recommended antibiotic therapies.