A case series and literature review of infections due to Myroides spp.: identification of contributing factors and emerging antibiotic susceptibility trends

Abstract

Introduction.

Infections forby Myroides spp. can lead to significant morbidity and mortality, particularly in immunocompromised patients with underlying co-morbidities. Recent reports have highlighted its intrinsic and acquired drug resistance, making it a particularly challenging infectious agent to combat.

Methods.

Myroides spp. isolated and reported in clinically significant urine samples were considered for the study. Identification of the organism was done via the VITEK 2C system. Antibiotic susceptibility testing was done using both manual and automated methods following Clinical and Laboratory Standards Institute (CLSI) guidelines. Existing literature was searched on MEDLINE using PubMed.

Results.

We present a series of five catheter-associated urinary tract infections due to Myroides odoratimimus , with sensitivity to only minocycline. This is the first case from Western India, and the third case in the existing literature that shows Myroides sensitivity only to minocycline. Our literature review is the first to systematically describe contributory factors to infection, allowing us to devise a clinically relevant tool that delineates contributory factors and efficacious drugs in Myroides spp. infection.

Conclusion.

Myroides spp. infections, previously considered rare and opportunistic, need cognizance and diagnostic suspicion especially in particular associated conditions.

Data Summary

Anonymized individual participant data and other study documents can be requested for further research by contacting the corresponding author.

Introduction

The genus Myroides belongs to the family Flavobacteriaceae and is present ubiquitously in the environment [1]. Clinically relevant species include Myroides odoratus [2–15], M. odoratimimus [16–30], M. injenensis [31, 32] and M. phaeus [33]. Previously considered ‘low-grade’ and not highly pathogenic, infections by Myroides spp. can lead to significant morbidity and mortality, particularly in immunocompromised patients with underlying co-morbidities [32]. These opportunistic pathogens have been implicated in both hospital- and community-acquired infections and affect a variety of sites (Table 1) [34]. Clinicians need to be aware of this pathogen, which is now being detected at a greater frequency possibly due to widespread availability of automated technologies. Recent reports have highlighted its intrinsic and acquired drug resistance, making it a particularly challenging infectious agent to combat [15, 25, 28, 30, 35–37]. Of particular interest is in the intensive care setting, where the likelihood of both infection and drug resistance is higher. Here we present a case series of five patients with extensively drug-resistant M. odoratimimus infection encountered at a tertiary care centre. We also review available literature on this subject, and this paper provides the first systematic description of possible contributory factors to infection along with trends in antibiotic susceptibility.

Table 1.

Review of existing literature

Reference/year	Myroides species	No. of cases	Clinical infection	Possible contributory factors	Immune status*	Sensitive drugs on AST
Holmes/1979	odoratum	5	1. Stump infection, 2. Indwelling catheter infection, 3. Foot gangrene, cellulitis, 4 and 5. Recurrent UTI	1. Ischaemic lower limb disease, 2. Indwelling catheter, 3. Frostbite, 4. Bladder carcinoma, 5. CKD	na	S: sulfamethoxazole, cotrimoxazole, cephaloridine and nalidixic acid
Davis/1979	odoratum	1	Foot gangrene	Chronic alcoholic, possibly cirrhotic	na	S: chloramphenicol
MacFarlane/1985	odoratum	1	Ventriculitis	Prolonged hospitalization, multiple invasive procedures	na	S: cefotaxime
Hsueh/1995	odoratum	1	Bacteraemia, necrotizing fasciitis	Chronic HBV cirrhosis	−	S: aztreonam, imipenem, chloramphenicol, vancomycin, ofloxacin, ciprofloxacin
Ferrer/1995	odoratum	1	Bacterial endocarditis	CKD on chronic haemodialysis, invasive procedure	−	S: netilmicin, ceftazidime
Bachman/1996	odoratum	1	Cellulitis, bacteraemia	Chronic steroid use, unsanitary water exposure	−	S: ceftriaxone, cotrimoxazole, piperacillin, imipenem
Spanik/1998	odoratum	4	Bacteraemia	3 blood cancers with neutropenia, 1 solid cancer; 4 indwelling central venous catheter	3−, 1+	S: gentamicin, amikacin, ofloxacin, ciprofloxacin, netilmicin, tobramycin, azlocillin; only one patient was resistant to third-generation cephalosporins
Yağci/2000	odoratimimus	13	Pyuria	4 urinary tract neoplasia, 9 urinary calculi, 13 indwelling urinary catheter	+	R: amikacin, aztreonam, cefoperazone, ceftazidime, ceftriaxone, ciprofloxacin, gentamicin, imipenem, piperacillin, tetracycline, tobramycin and cotrimoxazole
Green/2001	odoratus	1	Recurrent cellulitis, bacteraemia,	Unsanitary water exposure	+	S: cotrimoxazole, piperacillin/tazobactam, ciprofloxacin and levofloxacin
Motwani/2004	odoratum	1	Cellulitis, septic shock	Diabetes mellitus, peripheral vascular disease	+	S: cotrimoxazole and fluoroquinolones
Thomas/2007	Myroides spp.	1	Acalculous cholecystitis	−	+	na
Bachmeyer/2008	odoratimimus	1	Cellulitis	Trauma; chronic alcoholic, possibly cirrhotic	−	S: ciprofloxacin, rifampicin
Benedetti/2011	odoratimimus	1	Septic shock, pneumonia, soft tissue infection	Trauma, environmental exposure, prolonged hospitalization, multiple invasive procedures	+	S: imipenem, meropenem, piperacillin/tazobactam, and ticarcillin/clavulanate
Ktari/2012	odoratimimus	7	4 UTI, 3 bladder colonization	4 indwelling D-J stent; 7 prolonged hospitalization, postoperative	+	Pan-drug resistant
Maraki/2012	odoratimimus	1	Cellulitis	Animal bite	+	S: levofloxacin, gatifloxacin, moxifloxacin, ofloxacin, cotrimoxazole, chloramphenicol, and amoxicillin/clavulanic acid
Kim/2012	injenensis	1	UTI	Multiple surgical procedures (radical hysterectomy and percutaneous nephrostomy), cervical cancer, CKD	+	na
Deepa/2014	odoratus	1	Pneumonia (secondary)	Diabetic, pulmonary tuberculosis	−	S: ciprofloxacin, levofloxacin, cotrimoxazole, amikacin, tobramycin, imipenem, meropenem and piperacillin/tazobactam
Crum-cianflone/2014	odoratus	1	Necrotizing fascitis	Chronic HCV cirrhosis	−	S: meropenem
Endicott-Yazdani/2015	odoratimimus	1	Bacteraemia	Exposure to unsanitary water, trauma, diabetic foot ulcer	+	na
Prateek/2015	odoratus	1	Pericardial effusion	CKD on haemodialysis	−	Pan-drug resistant
Ali/2015	Myroides spp.	1	Canaliculitis	None	+	R: beta lactams and monobactams
Lahmer/2016	odoratus	1	Necrotizing pancreatitis, septic shock, multiorgan failure	Chronic alcoholic, possibly cirrhotic	+	S: cotrimoxazole and ciprofloxacin
Willems/2016	odoratimimus	1	Erysipelas and sepsis	Dog scratch,	−	S: levofloxacin, clindamycin, meropenem, tigecycline
Beharrysingh/2017	Myroides spp.	1	Bacteraemia and cellulitis	Diabetes, H/O bilateral toe amputations, indwelling left chest wall catheter, unsanitary water exposure	−	S: meropenem, cotrimoxazole
Pompilio/2017	odoratimimus	1	Recurrent calcaneal ulcer	Trauma, diabetes, H/O skin graft at same site	−	S: imipenem
Licker/2018	odoratimimus	4	UTI	1 Post-renal transplant on immunosuppression with urinary catheter; 1 DKA with urinary catheter; 1 COPD on long-term steroids, H/O TURP with urinary catheter; 1 post-cancer-surgery with ureterostomy tube	3−, 1+	S: minocycline
Ahamed/2018	odoratimimus	1	UTI	ESRD on haemodialysis	+	Pan-drug resistant
Lorenzin/2018	odoratimimus	1	Recurrent macroscopic haematuria	ESRD on haemodialysis, diabetes, indwelling urinary catheter	−	S: cotrimoxazole
LaVergne/2019	injenensis	1	Cellulitis	Alcoholic cirrhosis	+	S: ampicillin/sulbactam, piperacillin/tazobactam, ciprofloxacin, levofloxacin, meropenem
Meyer/2019	Myroides spp.	1	Cellulitis and bacteraemia	Diabetes mellitus, COPD on long-term steroids, trauma, animal exposure to wounds	−	S: ciprofloxacin, levofloxacin, piperacillin/tazobactam, imipenem
Mohapatra/2019	Myroides spp.	1	Empyema due to ruptured liver abscess	Chronic alcoholic, possibly cirrhotic	−	S: amoxiclav, piperacillin/tazobactam, carbapenems and ciprofloxacin
Lu/2020	odoratimimus	1	Catheter related bloodstream infection	Indwelling catheter,	+	S: cefoperazone/sulbactam
Foo/2020	Myroides spp.	1	Septic shock	Diabetes, foot ulcer, exposure to soil	−	S: meropenem
Perez-Lazo/2020	phaeus	1	Bacteraemia	CKD on haemodialysis, multiple myeloma on chemotherapy, indwelling catheter	−	S: Piperacillin/tazobactam
Kutlu/2020	odoratimimus	6	3 UTI, 3 bladder colonization	6 indwelling urinary catheter and diabetes; 1 COPD on long-term steroids, 1 ESRD	−	Pan-drug resistant
Yang/2020	odoratimimus	22	4 Bacteraemia; 18 incidental	22 prolonged hospitalization, post-operative, urinary catheterization	−	S: fluoroquinolones
Vempuluru/2021	Myroides spp.	1	Canaliculitis	na	+	S: chloramphenicol
Mahendran/2021	Myroides spp.	1	UTI	DKA	−	S: minocycline
Beathard/2021	Myroides spp.	1	Cellulitis and bacteraemia	CKD, diabetes	−	S: ciprofloxacin, meropenem
O'Neal/2022	odoratus	2	1 VAP, 1 bacteraemia	1 prolonged hospitalization, invasive procedures, indwelling catheters; 1 postoperative, prolonged hospitalization, indwelling catheters	+	S: minocycline, ceftazidime/avibactam
Faraz/2022	Myroides spp.	1	Recurrent UTI	Diabetes, post-renal transplant, repeated self-catheterization due to neurogenic bladder	−	Pan-drug resistant
Kurt/2022	odoratimimus	1	Bacteraemia	Indwelling catheters, Covid 19 pneumonia	−	Pan-drug resistant

AST, antimicrobial susceptibility testing; CKD, chronic kidney disease; HBV, hepatitis B virus; HCV, hepatitis C virus; UTI, urinary tract infection; na, not applicable; D-J stent, double J stent; H/O, history of; DKA, diabetic ketoacidosis; COPD, chronic obstructive pulmonary disease; TURP, transurethral resection of prostate; ESRD, end-stage renal disease; VAP, ventilator associated pneumonia.

Case presentation

All urine samples received in the department of microbiology having significant bacteriuria for Myroides spp. were included in the study. For all cases, identification of the organism was done via the VITEK 2C system (bioMérieux). Antibiotic susceptibility testing was done using both manual (Kirby Bauer for disc diffusion and E-test for MICs) and automated (VITEK 2C) methods, following Clinical and Laboratory Standards Institute (CLSI) guidelines. Each isolate was sent to a reference laboratory for species identification using the matrix-assisted laser desorption ionization – time of flight (MALDI-TOF) Biotyper Sirius system (Bruker Daltonics). Sample size calculation using a power analysis was not done since this is a prospective observational study.

Case 1

A 48-year-old male presented to the emergency department in an unconscious and intubated condition with a suspected brain injury. He was a known case of hypertension with type 2 diabetes mellitus and was on regular medications for the last 2 years. Magnetic resonance imaging of the brain revealed intracranial bleeding, following which he was immediately taken in for craniotomy. Requisite pre-operative preparation, including urinary catheter placement, was carried out. On the fourth day of the surgery, the patient experienced bouts of fever and increased white blood cell (WBC) counts. A urine culture was sent to the microbiology laboratory before empirical therapy was begun with intravenous ceftriaxone. Cultures reported Myroides spp. sensitive only to minocycline, and species identification yielded M. odoratimimus as the causative organism. Administration of minocycline resulted in an improvement in WBC counts, and urine cultures sent on the seventh day of surgery returned negative. This was our index case of Myroides spp. The patient’s condition worsened and eventually proved fatal, although not attributed to Myroides infection.

Case 2

A 29-year-old female who was a case of post-partum haemorrhage (PPH) and gestational diabetes was brought into our centre in an intubated condition. The patient developed abdominal pain with oliguria and altered sensorium 4 days after her normal vaginal delivery, following which she was transferred to our hospital and catheterized on admission. Based on abnormal baseline laboratory parameters on arrival, the patient was immediately moved to the intensive care unit (ICU). An emergent abdominal computed tomography (CT) scan revealed abdominal wall cellulitis with cystitis, and empiric therapy with intravensour piperacillin-tazobactam was begun for the same. Cultures on day 0 and 6 revealed no growth. On day 9 of her hospital stay, a fever spike was noted for which investigations were requested, with urine microscopy revealing pyuria. A urine culture was sent to the microbiology laboratory for further evaluation, revealing extensively drug-resistant Myroides spp. growth with sensitivity to only minocycline. The antibiotic minocycline was added to ongoing treatment for 7 days and counts resolved to within normal limits.

Case 3

A 41-year-old haemodynamically unstable diabetic male patient was referred to our hospital after having undergone multiple procedures including placement of a double-J (D-J) stent for a previous ureteric stricture and an emergent tracheal tube insertion. He presented with right-sided pleural effusion and was a known case of tuberculosis receiving modified anti-tubercular therapy, due to altered liver and kidney function. On admission, initial laboratory investigations revealed raised procalcitonin values, and a provisional diagnosis of sepsis and tubercular empyema was made. He was then moved to the ICU and catheterized for monitoring of kidney function. The patient had a fever spike on the eighth day, with urine microscopy revealing pyuria. A urine culture was sent to the laboratory and extensively drug-resistant Myroides spp. were isolated which were only sensitive to minocycline. Urine infection subsided by day 7 of minocycline administration and repeat cultures showed no further growth after cessation of treatment.

Case 4

A 55-year-old male was referred to our centre, having been admitted for breathlessness of sudden onset for 3 days. He arrived in an intubated and unconscious condition and was catheterized on ICU admission, revealing an oliguric state. He was a known case of type 2 diabetes mellitus for 7 years and hypertension for 2 years treated with insulin and antihypertensive medications. On initial workup and examination, a diagnosis of acute chronic kidney disease, lower respiratory tract infection, cardiogenic shock and multiorgan failure was made. Emergent treatment was begun. Ultrasonography of the abdomen revealed right-sided pleural effusion and bilaterally raised renal echogenicity. Initial blood and urine culture reports yielded no growth. On day 8 of admission, a fever spike was noted with raised WBC counts and pus cells on urine microscopy. Urine cultures were sent to guide empiric therapy and Myroides spp. were reported with susceptibility only to minocycline. The treatment plan was updated, and minocycline was administered for 7 days. Repeat cultures reported no growth and counts returned to normal. However, the condition of the patient deteriorated, and he died due to complications not attributable to the infection.

Case 5

A 69-year-old male was admitted to the emergency department with oliguria for the past 20 days and recent onset of disorientation and appetite loss over the previous 24 h. He was a known case of hypertension, type 2 diabetes, and chronic kidney disease for the last 5 years with a D-J stent in place. The patient was primarily managed in the emergency department where he was intubated, catheterized and then moved to the ICU. After further evaluation, a provisional diagnosis of acute liver failure and acute kidney injury with obstructive uropathy was made. Within 2 days of catheterization, the patient had a fever spike and raised WBC counts. Samples were sent for urine culture, which reported multi-drug resistant Myroides spp. Susceptibility was noted only to minocycline, similar to all our other cases. After administration of minocycline for 7 days, repeat cultures revealed no growth.

Literature review

We conducted a literature search on PubMed using a mix of controlled terms and free text searching, with the string ‘((Flavobacteriaceae Infections) AND Myroides) OR (Myroides AND Infections)’ which yielded 72 results. Papers of English language that presented clinical Myroides spp. infection were considered for inclusion. Forty-two papers describing a total of 97 cases were included (Table 1).

Discussion

Our study is the latest in a series of recent studies that have found Myroides spp. to be almost pan-drug resistant [13, 15, 24, 25, 28, 30, 35–37]. This is the first case from Western India, and the third case worldwide that shows Myroides sensitivity only to minocycline [24, 35]. Analysis of the trends behind the occurrence of Myroides infection revealed a wide swathe of possible causes, but a trend emerged with infections occurring in hospitalized patients. Our case series (Table 2) is similar to other cases [16, 19] in that there was a cluster of healthcare-associated urinary tract infections in patients with multiple comorbidities. All five cases had an indwelling device and were diabetic, pointing to these two being possible contributory factors to infection. Further investigation of contributory factors in the pre-existing literature revealed similar aetiologies in numerous cases. We elucidate this in Table 3, a clinically useful tool that portrays, at a glance, the risk factors for Myroides infection and drug classes most likely to be effective in treatment. This can help guide clinicians to suspect Myroides infection and initiate appropriate antibiotic therapy while keeping in mind local sensitivity patterns.

Table 2.

Summary of case series

Case no./age (Years)/sex	Location of admission	Collection date (of positive sample)	Possible contributory factors	Immune status	Presence of indwelling device	Infection	Treatment	Outcome
C1/48/M	SICU	Day 4	Diabetes, invasive procedure	–	Urinary catheter, endotracheal tube	UTI	Minocycline	Fatal (unrelated to infection)
C2/29/F	SICU	Day 9	Gestational diabetes, prolonged hospitalization	–	Urinary catheter, endotracheal tube	UTI	Minocycline	Cured
C3/41/M	CCMICU	Day 8	Diabetes, CKD, tubercular empyema, prolonged hospitalization, invasive procedure	–	D-J stent, tracheal tube, urinary catheter, intracranial drain	UTI	Minocycline	Cured
C4/55/M	CCMICU	Day 8	Diabetes, CKD, multiorgan failure, prolonged hospitalization	–	Urinary catheter, endotracheal tube, central line	UTI	Minocycline	Fatal (unrelated to infection)
C5/69/M	SICU	Day 2	Diabetes, CKD, hydronephrosis with ureteric stricture, sepsis, prolonged hospitalization	–	D-J stent, tracheal tube, urinary catheter	UTI	Minocycline	Cured

CKD, chronic kidney disease; SICU, surgical intensive care unit CCMICU, critical care medicine intensive care unit; UTI, urinary tract infection; D-J stend, double J stent.

Table 3.

Clinical support tool

Risk factors for infection	Targeted therapeutic options*
Indwelling catheters/devices Prolonged hospitalization Invasive/surgical procedures Diabetes CKD	Chloramphenicol Levofloxacin Cotrimoxazole Meropenem Minocycline

*Sensitive in >50 % of cases in the existing literature.

CKD, chronic kidney disease.

Myroides has classically been considered a ubiquitous organism and an opportunistic pathogen associated with infection only in immunocompromised patients (Table 1) or those having multiple comorbidities [34]. Cases due to animal exposure have been reported [20, 22] and unsanitary environmental exposure via water or soil has been suspected as a contaminant [7, 9, 18, 21, 34, 38–40]. Yet, attempts at identifying the source of this infection in nosocomial settings have been largely unsuccessful [16, 19]. Of note is that infections in immunocompetent individuals are increasingly appearing in the literature [8–10, 14–16, 18–21, 24, 25, 27, 31, 32, 41, 42]. This throws into question the clinical presumption that Myroides infection is always opportunistic, and due diligence needs to be given to this emerging extensively drug-resistant pathogen.

Initiating appropriate treatment for Myroides infection is challenging due to resistance to commonly used antimicrobial agents. Myroides can auto-aggregate and co-aggregate to form biofilms and have strong adherence and hydrophobicity [23, 26]. These properties along with chromosomally encoded beta-lactamases are hypothesized to confer drug resistance to most Myroides species [43]. More research is needed to elucidate the exact mechanisms of resistance in this organism [44, 45]. Antibiotic susceptibility testing on our isolates using the VITEK 2C system revealed resistance to penicillins, cephalosporins, norfloxacin, ciprofloxacin, aztreonam, amikacin, gentamicin, imipenem, meropenem, colistin and polymyxin. Susceptibility only to minocycline was seen.

The emergence of such extensive drug resistance led us to analyse the existing literature for trends in risk factors and antimicrobial sensitivity, which resulted in the development of the clinical tool presented (Table 3). All papers retrieved through the literature search were used to mine data, and this gave startling results. The five most likely risk factors – indwelling catheters/devices, prolonged hospitalization, invasive/surgical procedures, diabetes and chronic kidney disease – were present in 56, 36, 35, 21 and 12 % of cases respectively. This finding underlines the high chance of infection that these risk factors confer on patients. Targeted therapeutic options were selected if they were sensitive in at least 50 % of the studies in which they were reported. Antibiotics that were not reported in at least three papers were not included, and intermediate sensitivity was not factored into the analysis. This led us to elucidate the top five therapeutic options that are useful in Myroides infections. Minocycline, though having the highest sensitivity percentage of 100 %, was placed at the end of the table since it was reported in just four studies, in contrast to the average of 10 studies for other antibiotic choices. More case reports which include minocycline in their antimicrobial susceptibility testing are required before it can be recognized as the drug of choice. Spanik et al. [8] found that source removal via changing catheters led to the resolution of Myroides infection without specific antimicrobial therapy. This therapeutic modality can be explored in subsequent studies. Timely and appropriate identification of Myroides , through antimicrobial testing and antibiotic susceptibility testing to better guide therapeutic decisions and interventions, is imperative, given their potential to cause outbreaks, non-healing of wounds and prolonged duration of hospital stay.

There are a few limitations of the present study. While conducting the literature review, we restricted our search to only MEDLINE. Expanding the scope of the search will yield additional cases, yet were beyond the scope of this study. A significant number of cases retrieved were of urinary tract infections, including our own, which could explain the high prevalence of catheterization and its subsequent association with Myroides infection. Future research in this area should aim to systematically review all available reports to glean information existing in different databases.