Clearance of Cellulosimicrobium cellulans Bacteremia in a Child without Central Venous Catheter Removal

Abstract

Cellulosimicrobium cellulans (formerly known as Oerskovia xanthineolytica) rarely causes human infection. Infections have been reported in immunocompromised hosts or in patients with foreign bodies, such as catheters, where treatment has generally involved removal of the foreign body. We report on a case in which the organism was isolated in multiple blood cultures from a 13-year-old male. After initial therapy failed, treatment with vancomycin and rifampin resulted in infection clearance without removal of the central venous catheter.

CASE REPORT

A 13-year-old male with a history of midgut volvulus and subsequent short-bowel syndrome, who had received total parenteral nutrition since shortly after birth, presented to the Emergency Department at the University of California—Los Angeles with fever of 39°C, malaise, and bilateral conjunctivitis. The patient had had numerous urinary tract infections and central venous catheter (CVC) line infections in the last few years with organisms such as Micrococcus, coagulase-negative Staphylococcus, Staphylococcus aureus, and Enterococcus species. In the emergency room, blood was drawn from the CVC and from a peripheral vein. Both specimens grew pleomorphic gram-positive rods in aerobic and anaerobic blood culture bottles that were identified as Cellulosimicrobium cellulans. The patient was hospitalized and initially treated with intravenous vancomycin and cefotaxime, which was changed 2 days later to vancomycin and gentamicin. After 3 days in the hospital, the patient became afebrile and was discharged home to continue intravenous vancomycin therapy. Blood cultures (drawn on hospital day 2) became positive for Cellulosimicrobium cellulans after 72 h. Because the patient had been discharged, he was readmitted even though he was afebrile. Due to the difficulty of finding another line of intravenous access for this patient, an attempt to preserve the CVC was made by adding oral rifampin to the treatment regimen. Once rifampin was begun, subsequent blood cultures (drawn 2, 3, and 5 days after readmission, respectively) were negative. The patient was discharged home to complete therapy of 3 weeks on intravenous vancomycin and oral rifampin. A repeat culture obtained 72 h after discontinuation of antibiotics was negative. The patient has not had any recurrent infections with this organism and continues to use the CVC line on a daily basis (1 year posttherapy).

Microbiology.

Aerobic and anaerobic BacT/Alert (SA and SN, respectively) blood culture bottles (BioMerieux, Durham, NC) were positive after 2 days of incubation. Pleomorphic, branching and filamentous, gram-positive bacilli were detected from both bottles; however, morphology from the agar plate culture was more coccobacillary when Gram stained (Fig. 1 and 2). The organism was easily decolorized on Gram staining and was acid fast negative. Aliquots from the positive blood bottles were plated onto 5% sheep blood agar and chocolate agar plates, incubated overnight at 35°C in 5% CO₂, and used for further biochemical analysis. On blood agar plates, 2-mm shiny yellow colonies were evident after overnight incubation; upon subsequent incubation (5 to 7 days), the colonies became fringed with some agar penetration (Fig. 3). In this case, the pigment production was a useful diagnostic, in addition to the following biochemical reactions: catalase positive, reduction of nitrate, and hydrolysis of gelatin and esculin (27). Cellulosimicrobium cellulans and bacteria of the related genus Oerskovia are aerobic or facultatively anaerobic and metabolize a range of carbohydrates fermentatively (including glucose, maltose, mannose, sucrose, and xylose). The API Coryne biochemical strip (BioMerieux) keyed out with the number 7572727, an excellent identification for “Oerskovia xanthineolytica,” which is now known as Cellulosimicrobium cellulans. The API Coryne strip has proved useful in identification of this species and other coryneforms (7) and was used for identification in many of the reports reviewed (4, 10, 14, 17, 19, 23). We attempted to confirm this identification with further tests which distinguish Cellulosimicrobium cellulans from Oerskovia turbata. The organism was nonmotile in semisolid motility medium, grew at 42°C, and tolerated 6% NaCl but did not hydrolyze xanthine as expected. Since hydrolysis of xanthine or hypoxanthine is a key distinguishing feature between these two species, 16S rRNA sequencing was carried out at Quest Diagnostics, Nichols Institute, San Clemente, CA, which identified the isolate as “Cellulosimicrobium cellulans.” Antimicrobial susceptibility tests were performed using our in-house broth microdilution microtiter panel, which was made and set up according to CLSI standard protocol (21, 22). The MICs, measured in micrograms/milliliter, were reported as follows: erythromycin, 2.0; penicillin, 2.0; vancomycin, 0.5; and rifampin, 1.0. In the absence of CLSI interpretive guidelines, the organism was presumed to be susceptible, due to the low MICs (8, 29).

FIG. 1.

Cellulosimicrobium cellulans Gram stain from positive aerobic blood culture bottle.

FIG. 2.

Cellulosimicrobium cellulans Gram stain from colony isolated on sheep blood agar.

FIG. 3.

Cellulosimicrobium cellulans growth on 5% sheep blood agar plate after 48 h of growth, 35°C, under aerobic conditions.

Discussion.

Cellulosimicrobium cellulans is a nocardia-like bacillum in the suborder Micrococcineae. Cellulosimicrobium cellulans is formerly of the genus Oerskovia/Cellulans, along with other cellulolytic species, such as Cellulomonas turbata, basonym Oerskovia turbata. The relationships within and around this genus have now been reclassified on the basis of phylogenetic evidence (including 16S rRNA sequences and DNA-DNA interactions) and chemotaxonomic status (including cell wall compositions and GC content) (2, 27, 31). Identification and drug susceptibilities for this gram-positive rod and others in this group are challenging. They are uncommon pathogens, and there has been much confusion over their classification. However, there are published guides for the identification of gram-positive rods and suggested antimicrobial resistance profiles (6-8). Confirmation by 16S rRNA sequencing is recommended.

We report a catheter-related bacteremia due to Cellulosimicrobium cellulans in a child with short-bowel syndrome. A review of the literature reveals a strong correlation with compromised immune status and the presence of a foreign body (Table 1). There have been 22 reports concerning Oerskovia infections in humans, 1 for Cellulosimicrobium cellulans (11), 15 for O. xanthineolytica (1, 4, 5, 8, 10, 12, 13, 17-19, 23, 26, 28, 32, 33), 4 for O. turbata (14, 16, 24, 25), 1 reported as “nonmotile Oerskovia” (3), and 1 reported as “Oerskovia species” (9). The types of infections were similar for all species described and included bacteremia, peritonitis, endocarditis, and joint, ocular, and soft-tissue infections. CVC-related bacteremia was a feature in five determined cases (4, 9, 14, 16, 18).

TABLE 1.

Summary of Oerskovia species (i.e., Cellulosimicrobium cellulans and Oerskovia turbata) infection case reports in the medical literature to date, in chronological order^a

Case report author (reference)	Patient's age (yr)/sex/other significance	Underlying condition	Cellulosimicrobium/ Oerskovia species	Infection	Foreign body/removal	Treatment regimenb	Reported resistancec	Laboratory identification method
Sottnekd (30)		Suspected infection; 35 cases	26 O. xanthineolytica isolates; 9 O. turbata isolates	8 O. xanthineolytica from blood (clinical significance unknown)	Unknown	Unknown	Unknown	Culture morphology, biochemical tests, and whole-cell analysis
Reller (25)	68/M/urban	Crohn's, ankylosing spondylitis	O. turbata	Endocarditis	Aortic heart valve/yes	SXT + AMP → + AMX	No single agent was highly active	Culture, biochemical tests
Cruickshank (3)	47/F/rural; farmer	Kidney trouble?	Nonmotile Oerskovia	Pyonephrosis	None	Nephrectomy, antibiotic regimen unknown	BEN, TET, ERY, KAN, SUL	Culture, biochemical tests
Hussain (12)	47/M/rural; farmer	None	O. xanthineolytica	Endophthalmitis	Machine metal/yes	AMB + GEN → PEN → + CFL	CLI, GEN	Culture, biochemical tests
Kailath (13)	38/F	VP shunt	O. xanthineolytica	Meningitis	VP shunt/yes	PEN + RIF		Culture, biochemical tests (hydrolysis of xanthine)
LeProwse (16)	3/M/camping	Acute myelogenous leukemia	O. turbata	CVC-related bacteremia	CVC/yes	AMK	β-Lactamase negative (I-PEN, AMP, ERY)	Culture, biochemical tests
Guss (9)	40/F	Crohn's, short bowel syndrome	Oerskovia species	Bacteremia (TPN contamination)	CVC/no	VAN + GEN + MET → VAN alone	OXA, CFZ	Culture, biochemical tests
Rihs (26)	70/M	ESRD	O. xanthineolytica	Peritonitis	Peritoneal catheter/yes	VAN + GEN	CTX, CRO DOX, CLI, GEN, ERY	Culture, biochemical tests
Reina (24)	23/M	AIDS	O. turbata	Axillary abscess	Unknown	Unknown	Unknown	Unknown
Truant (32)	40/M	Cirrhosis, Variceal hemorrhage	O. xanthineolytica	Bacteremia	None	CRO + CLI, → CRO + VAN → + GEN	GEN, CLI, ERY	Culture, biochemical tests
Funkee (5)	53/F/iatrogenic	Arthropathy in several joints	O. xanthineolytica	Soft tissue infection	‘Rumalon’, steroid injections	DOX	For both isolates CIP, CLI, ERY, GEN, PEN	Culture, biochemical tests (API + hydrolysis of xanthine)
	72/M/iatrogenic	Gall stones, jaundice	O. xanthineolytica	Probable bacteremia (Cholecystitis)	Cholangio-pancreatic endoscopy	Laparotomy, CFX
McDonald (19)	54/F	Metastatic breast cancer	O. xanthineolytica	Bacteremia Pneumonia?	CVC (role?)/no	CXM → VAN	PEN, OXA, AMP (I-CLI, ERY)	Culture, biochemical tests (API + hydrolysis of xanthine)
Maguire (18)	49/F	Metastatic colonic adeno carcinoma	O. xanthineolytica	CVC-related bacteremia	CVC/no	VAN	β-Lactamase positive	Culture
Borra (1)	59/F	Diabetes mellitus, ESRD	O. xanthineolytica	Peritonitis	Peritoneal catheter/No	VAN + TOB → DOX	PEN	Culture
Shah (28)	28/F	None	O. xanthineolytica	Keratitis	Soft contact lens/yes	CFZ + GEN drops	ERY, SXT	Culture
Harrington (10)	72/M	Heart bypass surgery, hypothyroidism, ethanol abuse, total left knee replacement	O. xanthineolytica	Prosthetic knee joint infection	Prosthetic knee joint/yes	VAN + SXT	CLI, PEN (I-ERY) (sendout tests at CDC found R to SXT, CIP, ERY)	Culture, biochemical tests (API + hydrolysis of xanthine)
Lair (14)	27/M/nosocomial	HIV	O. turbata	Nosocomial CVC-related bacteremia	CVC/Yes	IPM + AMK	CTX, NET	Culture, biochemical tests (API + hydrolysis)
Ellerbroek (4)	53/F	Non-Hodgkin's lymphoma (and BMT)	O. xanthineolytica	CVC-related bacteremia→ Endocarditis	CVC/Yes	DOX → CLI → MPM → SXT + AMX → PEN	CRO (I-PEN)	Culture, biochemical tests (API + hydrolysis)
Lujan-Zilbermann (17)	13/F	ESRD	O. xanthineolytica	Peritonitis	Peritoneal catheter/No	VAN	AMP, CRO, CLI, PEN, OXA, TOB	Culture, biochemical tests (API)
Niamut (23)	64/F	Immunocompromised	O. xanthineolytica	Bacteremia	None	TZP → + NET → NET + VAN → TZP again	PEN, NET, TET, ERY	Culture, biochemical tests (API), 16S rRNA sequencing
Urbina (33)	31/M	ESRD, renal transplant	O. xanthineolytica	Endocarditis (line related?)	Aortic heart valve/Yes	SAM + VAN	PEN, AMP, CRO, CLI	Culture
Heym (11)	48/M/urban	HIV	Cellulosimicrobium cellulans	Chronic tongue ulcer	None	PEN + AZI	None	The organism was not isolated; 16S rRNA sequencing
Present case	13/M/urban	Short-bowel syndrome	Cellulosimicrobium cellulans	CVC-related bacteremia	CVC/No	VAN → + RIF	CTX, CRO, CLI	Culture, biochemical tests (API), 16S rRNA sequencing

^aESRD, end-stage renal disease; BMT, bone marrow transplant; CVC, central venous catheter; HIV, human immunodeficiency virus; VP shunt, ventriculoperitoneal shunt; I, intermediate resistance; R, resistance. Antimicrobial agents used were amikacin (AMK), amoxicillin (AMX), amphotericin B (AMB), ampicillin (AMP), ampicllin-sulbactam (SAM), azithromycin (AZI), benzylpenicillin (BEN), cefazolin (CFZ), cefotaxime (CTX), cefoxitin (CFX), ceftriaxone (CRO), cefuroxime (CXM), cephalexin (CFL), ciprofloxacin (CIP), clindamycin (CLI), doxycycline (DOX), erythromycin (ERY), gentamicin (GEN), imipenem (IPM), kanamycin (KAN), meropenem (MPM), metronidazole (MET), netilmicin (NET), oxacillin (OXA), penicillin (PEN), piperacillin-tazobactam (TZP), rifampin (RIF), sulfonamide (SUL), tetracycline (TET), tobramycin (TOB), trimethoprim-sulfamethoxazole (SXT), and vancomycin (VAN).

^bAn arrow indicates a change or an addition to a treatment regimen.

^cResistance to antibacterial agents was tested by various previously reported methods, mainly the disk diffusion or microdilution method. However, with a few CLSI guidelines for Coryneform bacteria, susceptibility testing is not standardized.

^dA retrospective review of 35 diphtheroids submitted to CDC from 1957 to 1977.

^eFunke et al. also report on a third isolate that was thought to be a contaminant and is therefore not included here.

Treatment of Oerskovia infections varies, but in more than half of the reported cases, removal of the foreign body was necessary, because therapy with single- and multidrug combinations failed to eradicate the infection. Even when treated with an antibiotic to which the organisms was presumed susceptible in vitro, there are reports of recurrence and persistence of infections (4, 13, 16, 25, 26, 33). In cases where there was a foreign body, symptoms disappeared when the foreign body was removed. It is possible that antibiotics were unable to penetrate the infected area, perhaps inhibiting but not eradicating the organism (4, 20).

Oerskovia species are widely distributed in the environment and have been isolated from soil, water, and grass cuttings (15), and as with other environmental bacteria, these bacteria are fairly resistant to antimicrobial agents but do not appear to be particularly virulent; no deaths were attributed to the infections (29, 33). In vitro, they have exhibited resistance to a range of antimicrobials: penicillins, aminoglycosides, macrolides, and cephalosporins. They were reported as resistant (or intermediate) to erythromycin in many reports, although specific antibiotics and the methods by which resistance was assessed varied (3, 5, 10, 19, 23, 26, 28, 32). This is expected, since resistance to erythromycin and other macrolides is high among aerobic and facultative anaerobic, non-spore-forming gram-positive bacilli (29). These bacteria are considered vancomycin susceptible in vitro, and in most reports, this has been the antibiotic of choice. Although three cases involved catheter-related infection, intravenous vancomycin alone was enough to clear the infection without removal of the line (9, 17, 18). In the case reported by Truant et al., the patient was receiving vancomycin (to treat methicillin-resistant S. aureus) prior to isolating the organism from blood culture; the isolate was subsequently susceptible to vancomycin in vitro (32). Rihs et al. reported that despite prolonged treatment with vancomycin, it was not sufficient in clearing the infection until the line was removed (26). In the present case, vancomycin was also not adequate, and rifampin was added to clear infection without catheter removal.

The epidemiology and pathogenicity of Cellulosimicrobium cellulans (“Oerskovia xanthineolytica”) and Oerskovia turbata infections is of growing relevance in clinical microbiology. Oerskovia species have been isolated from the environment (and caused infections in both rural and urban patients), but in addition there have also been cases of nosocomial and iatrogenic infection, indicating their ubiquity in nature (5, 14). We should be aware of these opportunistic pathogens, as it is likely that there will be an increase in infections caused by them, related to the ever-increasing number of patients with immunocompromised status and the presence of long-term foreign bodies.