Curtobacterium albidum/citreum bacteremia in an intensive care unit patient: The first case report

Abstract

A 70-year-old man was admitted to a local hospital complaining of fever for 3 days. After 8 days of hospitalization, his platelet count began to decrease, his respiratory rate increased, and he was transferred to the intensive care unit of our hospital. His vital signs upon admission were as follows: Glasgow Coma Scale score, 10 (E3V1M6); pulse, 118 bpm; blood pressure, 119/68 mmHg; respiratory rate, 26/min; peripheral capillary oxygen saturation, 99% on 5 L/min of oxygen; as well as generalized jaundice. Blood cultures obtained on day one were negative, and the patient’s general condition gradually improved. However, on day 20, gram-positive rods were isolated from two of the four blood cultures obtained (aerobic bottles only). Vancomycin was initiated, and the following day the infecting organism was identified as Curtobacterium albidum/citreum. However, a second blood culture obtained on day 22 was still positive. Bone marrow examination confirmed a diagnosis of diffuse large B-cell lymphoma, and chemotherapy was initiated on day 25; however, the patient’s general condition deteriorated, and he died on day 26. 16S rRNA analysis revealed a 99% match with C. citreum, a Corynebacterium-like gram-positive rod that colonizes rice and other crops. However, only a few human infections have been reported, including one previous report of possible catheter-related bacteremia based on recovery from a single aerobic bottle. To our knowledge, no prior case of probable clinically significant Curtobacterium bacteremia supported by repeated recovery from separate blood-culture collections has been documented. The number of reports is likely to increase as the use of matrix-assisted laser desorption ionization time-of-flight mass spectrometry becomes more widespread. C. albidum/citreum can cause nosocomial infections in immunocompromised patients, and further studies are required to determine the optimal therapeutic agents.

Key Clinical Message

Curtobacterium albidum/citreum is a plant-associated pathogen that can cause fatal bacteremia in immunocompromised patients. Monotherapy with antibiotics may be insufficient for effective treatment.

Introduction

Curtobacterium albidum/citreum (C. albidum/citreum) is a plant pathogenic bacterium rarely encountered in human clinical settings. Herein, we present, to our knowledge, the first reported case of probable clinically significant Curtobacterium bacteremia supported by repeated recovery from separate blood-culture collections in an intensive care unit (ICU) patient. This case report highlights the potential of C. albidum/citreum to cause nosocomial infections, and underscores the need for accurate identification and appropriate therapeutic interventions.

Case presentation

Case history

A 70-year-old man fell and received a laceration on his forehead that required suturing. The attending surgeon prescribed a daily cefdinir regimen of 300 mg. The patient complained of malaise and fever, and the following day, his hepatobiliary enzyme levels increased. Further evaluation of the patient’s condition revealed worsening malaise, and he was admitted to a local hospital on the fourth day. Blood cultures were obtained, and a regimen of cefoperazone/sulbactam (1 g q12h) was initiated. However, due to persistent inflammation, the regimen was switched to tazobactam/piperacillin on day four of admission. Subsequently, the patient was transferred to our facility on day nine following his initial admission due to thrombocytopenia and tachypnea. Upon admission, his vital signs were as follows: heart rate, 118 bpm; blood pressure, 119/68 mmHg; respiratory rate, 26/min; and, peripheral capillary oxygen saturation (SpO2), 99% on 5 L/min of oxygen. Physical examination revealed jaundice, conjunctival icterus, clear lung sounds, and a benign abdomen. No abnormalities were observed in the patient's extremities.

Differential diagnosis and investigations

Chest CT revealed bilateral pleural effusion. Minimal ascites was also noted. Laboratory tests revealed elevated aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, γ-glutamyl transpeptidase and blood urea nitrogen levels. Additionally, creatinine and potassium levels were slightly elevated (Table 1). Complete blood count revealed 0.5% atypical lymphocytes. However, contrast-enhanced CT showed no evidence of lymph node enlargement; therefore, a careful watchful waiting approach was adopted. Following transfer, the patient was intubated due to hypotension, and was admitted to the ICU. The results of a lumbar puncture and abdominocentesis were unremarkable. On day six of hospitalization, bone marrow biopsy revealed hemophagocytosis, supporting a diagnosis of diffuse large B-cell lymphoma (DLBCL). Biopsy was prompted due to elevated ferritin levels, thrombocytopenia, splenomegaly, and the suspicion of lymphoma.

Table 1.

Blood test results on the day of admission (9th day).

pH	7.491		AST	87	U/L	BUN	42	mg/dL
PaO2	162	Torr	ALT	31	U/L	Creatinine	0.94	mg/dL
PaCO2	30.1	Torr	LDH	589	U/L	Na	141	mmol/L
HCO3-	23	mEq/L	ALP	283	U/L	K	5.1	mmol/L
Base excess	0.1	mEq/L	γ-GTP	86	U/L	Cl	110	mmol/L
lactate	4.3	mEq/L	TP	5.3	g/dL
			albumin	1.7	g/dL	PT-%	104	%
RBC	3.32	× 106/μL	T.Bill	10.1	mg/dL	APTT	46.9	sec
Hb	9.8	g/dL	D.Bill	8.2	mg/dL	fibrinogen	427	mg/dL
Hct	29	%	CK	31	U/L	FDP	36	μg/mL
WBC	7.8	× 103/μL	CRP	32.7	mg/dL	D-dimer	20.6	μg/mL
neutrophil	69	%	PCT	7.75	ng/mL	AT-Ⅲ	39	%
atypical lymphocytes	0.5	%	IL-6	351	pg/mL	TAT	23.6	ng/mL
plt	23	× 103/μL

PaO₂, partial pressure of arterial oxygen; PaCO₂, partial pressure of arterial carbon dioxide; RBC, red blood cell count; Hb, hemoglobin; Hct, hematocrit; WBC, white blood cell count; plt, platelet count; AST, aspartate aminotransferase; ALT, alanine aminotransferase; LDH, lactate dehydrogenase; ALP, alkaline phosphatase; γ-GTP, γ-glutamyl transpeptidase; TP, total protein; T. Bill, total bilirubin; D. Bill, direct bilirubin; CK, creatine kinase; CRP, C-reactive protein; PCT, procalcitonin; IL-6, interleukin-6; BUN, blood urea nitrogen; Na, sodium; K, potassium; Cl, chloride; PT, prothrombin time; APTT, activated partial thromboplastin time; FDP, fibrin/fibrinogen degradation products; ATIII, antithrombin III; TAT, thrombin antithrombin III complex

Blood cultures obtained on the first day of admission showed no bacterial growth; however, gram-positive rods (GPR) were isolated from two aerobic bottles of four blood cultures obtained on the 19th day. The isolated GPR were presumed to be Corynebacterium spp. based on morphology, and vancomycin (VCM) was initiated. Incubation of BD BACTEC™ Plus Aerobic/F and BD BACTEC™ Plus Anaerobic/F media using the BD BACTEC™ FX blood culture system resulted in positive signals at an average of 26.27 h. Growth on AccuRate™ Sheep Blood Agar (Shimadzu Diagnostics Corporation) revealed yellow-orange colonies (Fig. 1) identified as C. albidum/citreum by Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI TOF/MS). Identification was performed using a MALDI Biotyper Smart (Bruker Daltonics) with the MALDI Biotyper Reference Library (version 11.0, 10,833 MSPs). The antimicrobial susceptibility of Curtobacterium sp. isolates was determined using the broth microdilution method based on the Clinical & Laboratory Standards Institute (CLSI) guidelines for susceptibility testing of Corynebacterium sp. The VCM regimen was continued based on drug sensitivity results (Table 2), and the patient was weaned from the ventilator on day 11 22. C. albidum/citreum was also isolated from blood cultures obtained on the same day, and the central venous catheter that had been inserted at admission was removed. The catheter tip culture was not submitted, and the site of blood culture collection was unclear; therefore, a diagnosis of catheter-related bloodstream infection (CRBSI) based on differential time to positivity was not established.

Fig. 1.

Image of the gram stained colonies from the blood culture. (A) Gram-stained image of the positive bottle. Corynebacterium-like GPR. (B) Colonies cultured aerobically for 48 hr on sheep blood agar. Yellow-orange color.

Table 2.

Drug sensitivity test results.

Antimicrobial agent	MIC(μg/mL)
PCG	1
ABPC	2
A/S	≦ 2
CTRX	≦ 1
P/T	32
MNZ	> 16
MINO	≦ 0.5
CLDM	2
VCM	≦ 0.5
LVFX	≦ 0.5
LZD	≦ 2
AMK	≦ 4
MEPM	≦ 0.12
ST	≦ 0.5

PCG, penicillin G; ABPC, ampicillin; A/S, ampicillin/sulbactam; CTRX, ceftriaxone; P/T, piperacillin/tazobactam; MNZ, metronidazole; MINO, minocycline; CLDM, clindamycin; VCM, vancomycin; LVFX, levofloxacin; LZD, linezolid; AMK, amikacin; MEPM, meropenem; ST, sulfamethoxazole/trimethoprim

Outcome and follow-up

Although rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) therapy was initiated on day 25, the patient's general condition deteriorated, and he died on day 26. However, a pathological autopsy could not be performed. The patient's clinical course is presented in Fig. 2.

Fig. 2.

Clinical course C. albidum/citreum was isolated from blood cultures at 19 and 22 days, and the patient died at 26 days.

BLASTN analysis (BLAST version 2.16.0, https://blast.ncbi.nlm.nih.gov/Blast.cgi) of the individual quality-trimmed reads consistently showed Curtobacterium citreum NR_026156.1 as the top type-strain match, with 99.19–99.73% identity and 99–100% query coverage. However, separation from the closest non-citreum Curtobacterium type-strain sequence was only 0.27–0.31%; therefore, 16S rRNA gene sequencing supported identification as Curtobacterium sp. most closely related to C. citreum, but did not independently resolve the isolate at the species level. This isolate was catalase positive, urease negative, and strongly hydrolyzed esculin.

Discussion

C. albidum/citreum is a gram-positive bacillus with a Corynebacterium-like morphology that belongs to the order Micrococcales [1]. It is a motile plant pathogen, formerly classified as Corynebacterium [2]. The genus Curtobacterium is found in plants and in the soil, and includes C. albidum, C. citreum, C. luteum, C. pusillum, C. flaccumfaciens, C. herbarum, and C. ammoniagenes. In Latin, Curtus means “short”, therefore, Curtobacterium refers to short rod-shaped bacteria. These bacteria form yellowish-orange colonies and have an optimal growth temperature of 30 ℃. This applies to members such as C. albidum, C. flaccumfaciens, and C. herbarum; however, C. citreum, C. luteum, C. plantarum, and C. pusillum demonstrate optimal growth at both temperatures of 30 and 37 ℃ [3]. In the present case, MALDI-TOF MS assigned the isolate to C. albidum/citreum, whereas 16S rRNA gene sequencing supported identification only as Curtobacterium sp. most closely related to C. citreum. Accordingly, species-level attribution was not made.

The portal of entry in the current case is unclear; and the wound on the patient’s forehead healed by day 12, which was the time of the patient's presentation to our hospital, showing no signs of infection. The patient was a farmer who cultivated tomatoes and other crops; environmental exposure was therefore possible but unproven. C. albidum/citreum was not isolated through nasal surveillance culture at the time of ICU admission or from specimens other than blood. We considered whether the blood culture findings could represent contamination. Clinical significance was supported by recovery from two bottles on day 19 and again from a separate blood culture collection on day 22 despite ongoing VCM, together with the absence of another clinically evident focus. Recovery on separate days is less compatible with a single contamination event. Nevertheless, contamination cannot be excluded with certainty because the collection sites were not documented, the catheter tip was not cultured, and differential time to positivity was unavailable. We therefore interpreted the findings as clinically significant bacteremia while acknowledging that the source remained unconfirmed. Although a definitive diagnosis of CRBSI was not established, central line-associated bloodstream infection (CLABSI) was suspected as no other sites of infection were clinically evident [4]. The National Healthcare Safety Network (NHSN) defines CLABSI as a laboratory-confirmed bloodstream infection in a patient with a central line in place for over 48 h and no other source of infection identified [5]. Although malignant lymphoma induces cellular immunodeficiency, the impact of C. albidum/citreum on bacteremia remains unclear as it is not an intracellular pathogen. Although a central venous catheter was required, unnecessary long-term catheter placement should be avoided.

The results of an extensive review of the literature for reported cases of Curtobacterium infection in humans are listed in Table 3. Viana-Niero et al. [6] reported a 2-year-old child with leukemia and a central venous catheter in whom Curtobacterium sp. was recovered from a single aerobic bottle drawn through the catheter. The authors described possible catheter-related bacteremia but did not establish causality. In contrast, the present case showed repeated recovery from separate blood-culture collections on days 19 and 22. On this basis, to our knowledge, this is the first reported case of probable clinically significant Curtobacterium bacteremia supported by repeated recovery from separate collections. Rivera et al. [7] reported a case of an epidural abscess that developed following resection and radiation chemotherapy for a brain tumor (pathological diagnosis: glioblastoma multiforme). However, no specific reports of plant contact could be found in the literature. The portal of entry for the present case remains unknown; and the case presented by Rivera was similar to the present one in that the infection was caused by C. citreum, occurring in a hospital setting. Additionally, Francis et al. [8] reported bacterial arthritis caused by C. flaccumfaciens, which infected a knee joint punctured by plant spines. Moreover, Mallick [1] reported bacterial keratitis caused by banana sap, which suggests an association with C. flaccumfaciens. Although a limited number of reports do not allow for a definitive conclusion, C. citreum is a known pathogen that can cause nosocomial infections. Additional case reports are expected, as previously undiagnosed cases can now be identified due to the widespread use of MALDI-TOF MS.

Table 3.

Previously reported Curtobacterium infections in humans.

Age	Sex	Diagnosis	Strain type and taxon	Specimen	Treatment	Comorbidity	Prognosis
54 [3]	Female	respiratory distress	Curtobacterium sp.	sputum	Unknown	Unknown	Unknown
76 [3]	Male	chronic bronchitis	Curtobacterium sp.	sputum	Unknown	Unknown	Unknown
70 [3]	Male	soft tissue infection	Curtobacterium sp.	wound	Unknown	Unknown	Unknown
34 [3]	Female	conjunctivitis	Curtobacterium sp.	eye discharge	Unknown	Unknown	Unknown
41 [3]	Male	lymphadenopathy	Curtobacterium sp.	lymph node tissue	Unknown	Unknown	Unknown
2 [6]	Male	possible catheter-related bacteremia (unproven)	Curtobacterium sp.	blood drawn through Hickman catheter (one aerobic bottle)	CTRX + CAM → CFPM	juvenile chronic myelomonocytic leukemia after transplantation	recovery catheter retained
7 [8]	Male	bacterial arthritis	Curtobacterium flaccumfaciens	synovial fluid and knee tissue	TIPC/CVA→AMPC	none	a full recovery
64 [7]	Female	right frontal lobe epidural abscess	Curtobacterium citreum Curtobacterium flaccumfaciens	epidural abscess	VCM + GM→LZD + MEPM →AZM + MINO	temperomandibular joint syndrome hydrocodone/acetaminophen was used	survived
24 [1]	Male	bacterial keratitis	Curtobacterium flaccumfaciens	corneal scraping	topical CPFX	none	recovery

To our knowledge, this is the first reported probable clinically significant bacteremia supported by repeated recovery from separate blood-culture collections. TIPC/CVA, ticarcillin/clavulanic acid; AMPC, amoxicillin; GM, gentamycin; AZM, azithromycin; CPFX, ciprofloxacin

Reported treatment options include various antimicrobials such as β-lactamase-inhibitor combinations, VCM, linezolid, and quinolone ophthalmic drops. Based on the susceptibility profile of this isolate, we initiated VCM therapy, taking into account both the low minimum inhibitory concentrations (MICs) and Corynebacterium-like morphology. Although all previously reported cases with known prognoses survived, suggesting that C. albidum/citreum has low pathogenicity, the patient in the present case developed persistent bacteremia and died without achieving clearance of blood cultures. Potential contributing factors to the persistent bacteremia include a VCM trough level on day three, which was below the recommended range of 15–20 μg/mL for critically ill patients; delayed catheter removal; and immunodeficiency due to DLBCL. In retrospect, a two-drug combination could have been considered as reported by Rivera et al. [7]. Funke et al. [3] reported low MICs for amikacin, gentamicin, VCM, and teicoplanin against C. albidum/citreum.

Conclusions

To our knowledge, this is the first reported case of probable clinically significant Curtobacterium bacteremia supported by repeated recovery from separate blood-culture collections in an ICU patient. Further case reports and research on the pathogenesis and optimal treatment of C. albidum/citreum infections are required as the number of reported cases is expected to increase as the use of MALDI-TOF MS becomes more common. Additionally, it is suggested that single-agent antimicrobial therapy might not be sufficient for managing confirmed bacteremia.

CRediT authorship contribution statement

Mikinori Kannae: Writing – review & editing, Writing – original draft, Visualization, Software, Resources, Project administration, Investigation, Data curation, Conceptualization. Kenji Gotoh: Visualization, Resources, Data curation, Conceptualization. Kazuya Kunitake: Visualization, Resources, Data curation, Conceptualization. Nobuhisa Hirayu: Visualization, Resources, Data curation, Conceptualization. Masakazu Nabeta: Visualization, Resources, Data curation, Conceptualization. Naotaka Tashiro: Visualization, Resources, Data curation, Conceptualization. Hiroshi Watanabe: Validation, Supervision. Osamu Takasu: Validation, Supervision.

Ethics declaration

Written informed consent to take part in the study and to publish the article has been obtained from all participants or their legal representatives. The privacy rights of participants have been observed.

This study was performed in compliance with relevant laws, regulatory frameworks and guidelines where the research took place. Ethics committee approval was not required under relevant laws and institutional guidelines. This study is a case report of a single patient and does not require ethical approval according to institutional guidelines.

Patient consent statement

Written informed consent was obtained from the patient’s next of kin for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Declaration of Generative AI and AI-assisted technologies in the writing process

During the preparation of this manuscript, the authors used Codex (OpenAI) to assist with English-language editing, clarity and readability, and literature/reference consistency. The authors independently verified all citations and references and reviewed the complete output. No generative AI or AI-assisted technology was used for data analysis or for the generation or alteration of figures or images. After using this tool, the authors reviewed and edited the manuscript as needed and take full responsibility for the content of the publication.

Funding

The authors did not receive any grants from funding agencies in the public, commercial, or non-profit sectors.

Case reports

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Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.