- Email: [email protected]
Catheter-related blood stream infection caused by Dermacoccus barathri, representing the first case of Dermacoccus infection in humans
J Infect Chemother xxx (2015) 1e4
Contents lists available at ScienceDirect
Journal of Infection and Chemotherapy journal homepage: http://www.elsevier.com/locate/jic
Case report
Catheter-related blood stream infection caused by Dermacoccus barathri, representing the first case of Dermacoccus infection in humans Nobuhiro Takahashi a, Masayoshi Shinjoh b, *, Hirofumi Tomita a, Akihiro Fujino a, Kayoko Sugita c, Yasuhiro Katohno d, Tatsuo Kuroda a, Ken Kikuchi e, f a
Department of Pediatric Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan Department of Pediatrics, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan Center for Infectious Diseases and Infection Control, Keio University Hospital, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan d Central Clinical Laboratory, Keio University Hospital, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan e Department of Infection Control Science, Faculty of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan f Department of Infectious Diseases, Tokyo Women's Medical University, 8-1, Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan b c
a r t i c l e i n f o
a b s t r a c t
Article history: Received 9 February 2015 Received in revised form 9 April 2015 Accepted 10 April 2015 Available online xxx
A 7-year-old boy undergoing home parenteral nutrition with totally implantable central venous access device for chronic intestinal pseudo-obstruction experienced repeated episodes of fever with a temperature above 39.0 C despite the antibiotic treatment. The fever was considered to be catheter-related blood stream infections, as no other etiology could be justified. Repeated blood culture tests revealed negative after 1-week incubation, whereas some samples of blood collected from the central venous catheter yielded positive and gram-positive rods were detected. These bacteria were detected repeatedly, then the central venous access device was removed with consideration for the possibility of this bacteria being a pathogen. Thereafter, the fever did not recur and the blood culture tests were negative. The causative agent was identified as Dermacoccus barathri based on the 16S rRNA gene sequence and phylogenetic analysis of 6118-bp concatenated sequences of 4 housekeeping genes. Genus Dermacoccus are one form of Actinomycetes isolated from human skin and water, but human infection with Dermacoccus spp. has not been previously reported and the pathogenicity of the bacteria remains unclear. To our knowledge, this is the first reported case of Dermacoccus infection in humans. © 2015, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Keywords: Dermacoccus barathri Sepsis Catheter-related blood stream infection Chronic intestinal pseudo-obstruction Ethanol lock therapy
1. Introduction Parenteral nutrition is a life-saving, supportive intervention in patients with intestinal failure. However, long-term home parental nutrition is commonly associated with catheter-related blood stream infections (CRBSIs), which can be serious condition. In such cases, it is important to perform blood cultures and detect the causative pathogen to determine the appropriate treatment strategy. Coagulase-negative staphylococci, Staphylococcus aureus, aerobic gram-negative bacilli, and Candida albicans most commonly cause catheter-related blood stream infection [1] and these pathogens are usually detected within 1 week for blood cultures.
* Corresponding author. Tel.: þ81 3 5363 3816; fax: þ81 3 5379 1978. E-mail address: [email protected] (M. Shinjoh).
Genus Dermacoccus are one form of Actinomycetes isolated from human skin and water by Stackebrandt et al. in 1995 [2]. Thereafter, four species have been recognized: Dermacoccus nishinomiyaensis, Dermacoccus abyssi, Dermacoccus profundi, and Dermacoccus barathri and the latter three were first reported as bacteria isolated from the deep-sea mud of the Mariana trench [3,4]. Genus Dermacoccus are reported as gut-associated bacteria of invertebrate [5], but the pathogenicity of the bacteria remains unclear. Here, we report the first case of CRBSI caused by D. barathri. To our knowledge, this is the first case of Dermacoccus infection in humans. 2. Case report The patient was a 7-year-old boy, diagnosed with chronic intestinal pseudo-obstruction at the age of 1 year. Thereafter, he
http://dx.doi.org/10.1016/j.jiac.2015.04.007 1341-321X/© 2015, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Takahashi N, et al., Catheter-related blood stream infection caused by Dermacoccus barathri, representing the first case of Dermacoccus infection in humans, J Infect Chemother (2015), http://dx.doi.org/10.1016/j.jiac.2015.04.007
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N. Takahashi et al. / J Infect Chemother xxx (2015) 1e4
required daily home parental nutrition. At the age of 6 years, a totally implantable central venous access device (CVAD) (Slim port; Bard, Salt Lake City, UT, USA), which has single port and single lumen catheter, was surgically implanted through the right subclavian vein and gastrostomy was performed for intestinal decompression. At the age of 7 years, he experienced three episodes of fever with a temperature above 39.0 C in a single month. He visited a local hospital and antibiotics (ceftriaxone 90 mg/kg/ day) were prescribed. Despite antibiotic therapy, the fever continued to recur. Therefore, the patient visited our hospital. The patient had no history of travel or contact with animals. His height was 111 cm, and weight, 22 kg. At presentation, his body temperature was 39.0 C. The site of the implanted CVAD did not appear purulent or erythemic. The patient's abdomen was markedly distended with a girth of 66.5 cm because of the chronic intestinal pseudo-obstruction; this was not different from the usual girth. The results of laboratory tests, including a complete blood count, blood chemistry analysis, and urine analysis, were within normal limits, except that the serum C-reactive protein level was elevated (5.09 mg/dl). Chest radiography findings were unremarkable. The fever was considered to be catheter related, as no other etiology could be justified. The clinical course of the patient is depicted in Fig. 1a. CRBSI was suspected, and more than two blood samples were collected from the central venous catheter (CVC) and a peripheral vein for culture tests. The patient was then treated with antibiotics. Almost every time antibiotic treatment was discontinued, the fever relapsed within a few days. Ethanol
lock therapy was performed for 5 days, according to a previously documented method with some modifications (70% ethanol, 4 h/ day, 5 days) [6] in addition to antibiotic treatment, but the fever relapsed approximately 30 days later. Blood culture tests were performed repeatedly. The results were negative after 1-week incubation in BACTEC FX (Becton, Dickinson and Company, Franklin Lakes, NJ, USA) at 35 C (the usual protocol in our hospital), whereas 5 samples of blood collected from the CVC yielded positive blood culture results on incubation for a longer duration (10 days or more); gram-positive rod like Corynebacterium spp. were detected in all these cases (Fig. 1b). In particular, the organism only grew on subculturing in blood agar in 4 of the 5 positive cases. No bacteria were detected in culture bottles with blood from the peripheral vein or blood collected from the CVC during antibiotic treatment. At first, the bacteria detected on culturing for more than 1 week was considered to represent contamination rather than a pathogen. However, coryneform bacteria were detected repeatedly, and therefore, the possibility of this being a pathogen was considered. No other sites of origin, including the intestine, were plausible. Infective endocarditis was ruled out by echocardiography. The CVAD was removed and antibiotics were administered (ampicillin 200 mg/kg/day and oral clarithromycin 15 mg/kg/day for 2 weeks and 10 days, respectively). Thereafter, the fever did not recur and the blood culture tests were negative. The isolated strain was catalase positive, orange-yellow in color, and grew in smooth, glistening colonies (Fig. 1c). It showed lipase
Fig. 1. Clinical course of the patient and characteristics of the detected organism. (a) Clinical course of the patient. Days after first admission are plotted on the horizontal axis and the body temperature of the patient is plotted on the vertical axis. The antibiotics administered are indicated. Arrows represent the timing and the results of blood cultures. þ, positive. , negative. First four samples are the results of one-week incubation. A: admission, D: discharge, CTRX: ceftriaxone, CEZ: cefazolin, TEIC: teicoplanin, ABPC: ampicillin, CAM: clarithromycin, ELT: ethanol lock therapy. (b) Photograph of Gram staining (the Favor method) of D. barathri growing with the medium from the aerobic bottle. (c) Colony of Dermacoccus barathri on sheep blood agar after 72 h-capneic incubation. (d) Phylogenetic tree of Dermacoccus based on concatenated sequences of 4 housekeeping genes (16S rRNA gene: 1402 bp, groEL: 1598 bp, rpoB: 2659 bp, and recA: 459 bp). DN T: D. nishinomiyaensis JCM 11613T, DB T: D. barathri JCM 14588T, DP T: D. profundi JCM 14589T, DA T: D. abyssi JCM 14339T, 56025: a strain from this case.
Please cite this article in press as: Takahashi N, et al., Catheter-related blood stream infection caused by Dermacoccus barathri, representing the first case of Dermacoccus infection in humans, J Infect Chemother (2015), http://dx.doi.org/10.1016/j.jiac.2015.04.007
N. Takahashi et al. / J Infect Chemother xxx (2015) 1e4
and trypsin production, but no production of H2S, a-fucosidase, or b-glucosidase. Some of the colonies were tightly adherent to the blood agar plates and had a gummy appearance. The 16S rRNA gene sequence was identical to that of D. barathri MT2.1T for almost the entire length (1459/1459 bp). Although the 16S rRNA gene sequence of D. barathri shows 99% similarity with that of D. abyssi and D. profundi, D. barathri can be distinguished from the other species based on biochemical properties. Finally, the isolated organism was identified as D. barathri, based on phylogenetic analysis of 6118-bp concatenated sequences of 4 housekeeping genes (16S rRNA gene, groEL, rpoB, and recA) (Fig. 1d). The susceptibility data for the organism is shown in Online Resource 1. The identified organism was not detected in cultures from any other site (urine, stool, or gastric juice samples) during the clinical course. A colony of gram-positive rods was detected on right axillary skin culture, but the organism could not be identified. Environmental samples were not sent for culture tests. Removed CVAD were cultured and gram-positive coccui were detected but were not consistent with this organism. 3. Discussion Children with intestinal failure are often dependent on a CVC for nutritional support and the maintenance of the watereelectrolyte balance. However, these children with intestinal motility disorder are at risk of insufficient intestinal drainage, which increases the intestinal luminal pressure and results in translocation of intestinal bacteria. Thus, recurrent CVC-related sepsis is inevitable, and sepsis caused by multi-drug resistant bacteria is often seen in these patients, representing a life-threatening condition. To prevent such situations, CVC removal and replacement are generally essential, but this decreases the candidate venous access sites in children because the vessels of children in which the CVC is placed are very thin and hence easily occluded due to thrombus production, making CVC reinsertion impossible [7]. Intravenous access represents a lifeline for these patients, because the loss of vascular sites is considered an indication for intestinal transplantation. In patients with intestinal failure, CRBSIs typically arise from bacterial colonization of the internal surface of the intravascular catheter, often by migration of skin flora. Gastrostomy or enterostomy, often performed in these patients for intestinal decompression, may be the source of such infections. In addition, daily access for parenteral nutrition and fluid administration at home increases the likelihood of the catheter serving as a portal for infection. CRBSI in patients with intestinal failure is attributable to common intestinal flora in approximately 50% of cases [8]. Ethanol, not known to elicit bacterial resistance, is used to sterilize the hub [9] and the usefulness of ethanol locks for the treatment and prevention of CRBSI has been reported [6,10]. In contrast, ethanol lock therapy has been reported to be ineffective in a few cases, although the differences between the effective and ineffective cases are currently unknown. These may however be related to the type of CVC (e.g., Broviac, Hickman, and port type). In this case, incubation for more than 10 days was required to detect the causative pathogen in the blood cultures. The diagnosis of CRBSI could have been missed if incubation was not performed for this prolonged period. The possible reasons it took longer incubation to detect the bacteria are as follows. Positive blood cultures containing pathogens have been reported to be detected within the first 24 h of incubation in 87% of cases, although a four-fold longer incubation time is required for some pathogens such as Corynebacterium spp. [11]. The required incubation period for Dermacoccus spp. has not been reported, but considering that Corynebacterium spp. and Dermacoccus spp. belong to the order of Actinomycetales, they might have similar characteristics. Furthermore, in case of Staphylococcus
3
epidermidis, which is one of the major bacteria caused implanted biomaterial-associated infections like CRBSI due to producing large amounts of biofilm, its growth rate in biofilm is very slower than that in platonic culture [12]. The reason of this phenomenon is possibly explained as tricarboxylic acid cycle-dependent regulation of synthesis of polysaccharide intracellular adhesion, which is a major component of biofilm [13,14]. In this case, some colonies of D. barathri recovered from blood culture were quite adhesive on agar plates, which indicated these colonies formed extensive biofilm due to production of large amounts of extracellular polysaccharides like S. epidermidis. Although we referred to antibiotic susceptibility data for Dermacoccus spp. (Online Resource 1), the antibiotic susceptibility patterns have not been published. Furthermore, reports on the antibiotic susceptibility patterns of Kytococcus spp., the species most closely related to Dermacoccus spp., are also few [15]. In this case, because blood cultures turned negative during treatment with antibiotics, and at least TEIC, ABPC and CAM seemed sensitive from MIC data, these antibiotics were effective. However these antibiotics alone might not have been enough to eradicate the organisms for this patient with CRBSI. After ethanol lock therapy, the organism was not detected any more from any sites including blood at day 68 and inside or outside the CVAD. We judged ethanol lock therapy was effective for eradicating the organism, thus we could not prove that the organism adhered to the CVAD. Environmental samples were not collected and subjected to culture tests, and therefore, the source of the pathogen could not be identified. However, being a seemingly ubiquitous organism, it may be difficult to confirm its source. Further characterization of this organism will be invaluable in understanding it pathogenicity in humans. Here, we report the first case of human infection with D. barathri. Detection of this pathogen requires prolonged incubation periods for blood culture in patients with suspected CRBSI in a CVAD. Conflict of interest The authors state there are no conflicts of interests. Appendix A. Supplementary material Supplementary data related to this article can be found online at http://dx.doi.org/10.1016/j.jiac.2015.04.007. References [1] Mermel LA, Farr BM, Sherertz RJ, Raad II , O'Grady N, Harris JS, et al. Guidelines for the management of intravascular catheter-related infections. Clin Infect Dis 2001;32:1249e72. [2] Stackebrandt E, Koch C, Gvozdiak O, Schumann P. Taxonomic dissection of the genus Micrococcus: Kocuria gen. nov., Nesterenkonia gen. nov., Kytococcus gen. nov., Dermacoccus gen. nov., and Micrococcus Cohn 1872 gen. emend. Int J Syst Bacteriol 1995;45:682e92. [3] Pathom-Aree W, Nogi Y, Ward AC, Horikoshi K, Bull AT, Goodfellow M. Dermacoccus barathri sp. nov. and Dermacoccus profundi sp. nov., novel actinomycetes isolated from deep-sea mud of the Mariana Trench. Int J Syst Evol Microbiol 2006;56:2303e7. [4] Ruckmani A, Kaur I, Schumann P, Klenk HP, Mayilraj S. Calidifontibacter indicus gen. nov., sp. nov., a member of the family Dermacoccaceae isolated from a hot spring, and emended description of the family Dermacoccaceae. Int J Syst Evol Microbiol 2011;61:2419e24. [5] Gupta AK, Rastogi G, Nayduch D, Sawant SS, Bhonde RR, Shouche YS. Molecular phylogenetic profiling of gut-associated bacteria in larvae and adults of flesh flies. Med Vet Entomol 2014;28:345e54. [6] Broom J, Woods M, Allworth A, McCarthy J, Faoagali J, Macdonald S, et al. Ethanol lock therapy to treat tunnelled central venous catheter-associated blood stream infections: results from a prospective trial. Scand J Infect Dis 2008;40:399e406.
Please cite this article in press as: Takahashi N, et al., Catheter-related blood stream infection caused by Dermacoccus barathri, representing the first case of Dermacoccus infection in humans, J Infect Chemother (2015), http://dx.doi.org/10.1016/j.jiac.2015.04.007
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[7] Casey L, Lee KH, Rosychuk R, Turner J, Huynh HQ. 10-year review of pediatric intestinal failure: clinical factors associated with outcome. Nutr Clin Pract 2008;23:436e42. [8] Hull MA, Jones BA, Zurakowski D, Raphael B, Lo C, Jaksic T, et al. Low serum citrulline concentration correlates with catheter-related bloodstream infections in children with intestinal failure. J Parenter Enteral Nutr 2011;35: 181e7. [9] Metcalf SC, Chambers ST, Pithie AD. Use of ethanol locks to prevent recurrent central line sepsis. J Infect 2004;49:20e2. [10] Mouw E, Chessman K, Lesher A, Tagge E. Use of an ethanol lock to prevent catheter-related infections in children with short bowel syndrome. J Pediatr Surg 2008;43:1025e9. [11] McGowan KL, Foster JA, Coffin SE. Outpatient pediatric blood cultures: time to positivity. Pediatrics 2000;106:251e5.
[12] Evans E, Brown MR, Gilbert P. Iron chelator, exopolysaccharide and protease production in Staphylococcus epidermidis: a comparative study of the effects of specific growth rate in biofilm and planktonic culture. Microbiology 1994;140:153e7. [13] Vuong C, Kidder JB, Jacobson ER, Otto M, Proctor RA, Somerville GA. Staphylococcus epidermidis polysaccharide intercellular adhesin production significantly increases during tricarboxylic acid cycle stress. J Bacteriol 2005;187: 2967e73. [14] Sadykov MR, Olson ME, Halouska S, Zhu Y, Fey PD, Powers R, et al. Tricarboxylic acid cycle-dependent regulation of Staphylococcus epidermidis polysaccharide intercellular adhesin synthesis. J Bacteriol 2008;190:7621e32. [15] Chan JF, Wong SS, Leung SS, Fan RY, Ngan AH, To KK, et al. First report of chronic implant-related septic arthritis and osteomyelitis due to Kytococcus schroeteri and a review of human K. schroeteri infections. Infection 2012;40:567e73.
Please cite this article in press as: Takahashi N, et al., Catheter-related blood stream infection caused by Dermacoccus barathri, representing the first case of Dermacoccus infection in humans, J Infect Chemother (2015), http://dx.doi.org/10.1016/j.jiac.2015.04.007
Contents lists available at ScienceDirect
Journal of Infection and Chemotherapy journal homepage: http://www.elsevier.com/locate/jic
Case report
Catheter-related blood stream infection caused by Dermacoccus barathri, representing the first case of Dermacoccus infection in humans Nobuhiro Takahashi a, Masayoshi Shinjoh b, *, Hirofumi Tomita a, Akihiro Fujino a, Kayoko Sugita c, Yasuhiro Katohno d, Tatsuo Kuroda a, Ken Kikuchi e, f a
Department of Pediatric Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan Department of Pediatrics, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan Center for Infectious Diseases and Infection Control, Keio University Hospital, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan d Central Clinical Laboratory, Keio University Hospital, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan e Department of Infection Control Science, Faculty of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan f Department of Infectious Diseases, Tokyo Women's Medical University, 8-1, Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan b c
a r t i c l e i n f o
a b s t r a c t
Article history: Received 9 February 2015 Received in revised form 9 April 2015 Accepted 10 April 2015 Available online xxx
A 7-year-old boy undergoing home parenteral nutrition with totally implantable central venous access device for chronic intestinal pseudo-obstruction experienced repeated episodes of fever with a temperature above 39.0 C despite the antibiotic treatment. The fever was considered to be catheter-related blood stream infections, as no other etiology could be justified. Repeated blood culture tests revealed negative after 1-week incubation, whereas some samples of blood collected from the central venous catheter yielded positive and gram-positive rods were detected. These bacteria were detected repeatedly, then the central venous access device was removed with consideration for the possibility of this bacteria being a pathogen. Thereafter, the fever did not recur and the blood culture tests were negative. The causative agent was identified as Dermacoccus barathri based on the 16S rRNA gene sequence and phylogenetic analysis of 6118-bp concatenated sequences of 4 housekeeping genes. Genus Dermacoccus are one form of Actinomycetes isolated from human skin and water, but human infection with Dermacoccus spp. has not been previously reported and the pathogenicity of the bacteria remains unclear. To our knowledge, this is the first reported case of Dermacoccus infection in humans. © 2015, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Keywords: Dermacoccus barathri Sepsis Catheter-related blood stream infection Chronic intestinal pseudo-obstruction Ethanol lock therapy
1. Introduction Parenteral nutrition is a life-saving, supportive intervention in patients with intestinal failure. However, long-term home parental nutrition is commonly associated with catheter-related blood stream infections (CRBSIs), which can be serious condition. In such cases, it is important to perform blood cultures and detect the causative pathogen to determine the appropriate treatment strategy. Coagulase-negative staphylococci, Staphylococcus aureus, aerobic gram-negative bacilli, and Candida albicans most commonly cause catheter-related blood stream infection [1] and these pathogens are usually detected within 1 week for blood cultures.
* Corresponding author. Tel.: þ81 3 5363 3816; fax: þ81 3 5379 1978. E-mail address: [email protected] (M. Shinjoh).
Genus Dermacoccus are one form of Actinomycetes isolated from human skin and water by Stackebrandt et al. in 1995 [2]. Thereafter, four species have been recognized: Dermacoccus nishinomiyaensis, Dermacoccus abyssi, Dermacoccus profundi, and Dermacoccus barathri and the latter three were first reported as bacteria isolated from the deep-sea mud of the Mariana trench [3,4]. Genus Dermacoccus are reported as gut-associated bacteria of invertebrate [5], but the pathogenicity of the bacteria remains unclear. Here, we report the first case of CRBSI caused by D. barathri. To our knowledge, this is the first case of Dermacoccus infection in humans. 2. Case report The patient was a 7-year-old boy, diagnosed with chronic intestinal pseudo-obstruction at the age of 1 year. Thereafter, he
http://dx.doi.org/10.1016/j.jiac.2015.04.007 1341-321X/© 2015, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Takahashi N, et al., Catheter-related blood stream infection caused by Dermacoccus barathri, representing the first case of Dermacoccus infection in humans, J Infect Chemother (2015), http://dx.doi.org/10.1016/j.jiac.2015.04.007
2
N. Takahashi et al. / J Infect Chemother xxx (2015) 1e4
required daily home parental nutrition. At the age of 6 years, a totally implantable central venous access device (CVAD) (Slim port; Bard, Salt Lake City, UT, USA), which has single port and single lumen catheter, was surgically implanted through the right subclavian vein and gastrostomy was performed for intestinal decompression. At the age of 7 years, he experienced three episodes of fever with a temperature above 39.0 C in a single month. He visited a local hospital and antibiotics (ceftriaxone 90 mg/kg/ day) were prescribed. Despite antibiotic therapy, the fever continued to recur. Therefore, the patient visited our hospital. The patient had no history of travel or contact with animals. His height was 111 cm, and weight, 22 kg. At presentation, his body temperature was 39.0 C. The site of the implanted CVAD did not appear purulent or erythemic. The patient's abdomen was markedly distended with a girth of 66.5 cm because of the chronic intestinal pseudo-obstruction; this was not different from the usual girth. The results of laboratory tests, including a complete blood count, blood chemistry analysis, and urine analysis, were within normal limits, except that the serum C-reactive protein level was elevated (5.09 mg/dl). Chest radiography findings were unremarkable. The fever was considered to be catheter related, as no other etiology could be justified. The clinical course of the patient is depicted in Fig. 1a. CRBSI was suspected, and more than two blood samples were collected from the central venous catheter (CVC) and a peripheral vein for culture tests. The patient was then treated with antibiotics. Almost every time antibiotic treatment was discontinued, the fever relapsed within a few days. Ethanol
lock therapy was performed for 5 days, according to a previously documented method with some modifications (70% ethanol, 4 h/ day, 5 days) [6] in addition to antibiotic treatment, but the fever relapsed approximately 30 days later. Blood culture tests were performed repeatedly. The results were negative after 1-week incubation in BACTEC FX (Becton, Dickinson and Company, Franklin Lakes, NJ, USA) at 35 C (the usual protocol in our hospital), whereas 5 samples of blood collected from the CVC yielded positive blood culture results on incubation for a longer duration (10 days or more); gram-positive rod like Corynebacterium spp. were detected in all these cases (Fig. 1b). In particular, the organism only grew on subculturing in blood agar in 4 of the 5 positive cases. No bacteria were detected in culture bottles with blood from the peripheral vein or blood collected from the CVC during antibiotic treatment. At first, the bacteria detected on culturing for more than 1 week was considered to represent contamination rather than a pathogen. However, coryneform bacteria were detected repeatedly, and therefore, the possibility of this being a pathogen was considered. No other sites of origin, including the intestine, were plausible. Infective endocarditis was ruled out by echocardiography. The CVAD was removed and antibiotics were administered (ampicillin 200 mg/kg/day and oral clarithromycin 15 mg/kg/day for 2 weeks and 10 days, respectively). Thereafter, the fever did not recur and the blood culture tests were negative. The isolated strain was catalase positive, orange-yellow in color, and grew in smooth, glistening colonies (Fig. 1c). It showed lipase
Fig. 1. Clinical course of the patient and characteristics of the detected organism. (a) Clinical course of the patient. Days after first admission are plotted on the horizontal axis and the body temperature of the patient is plotted on the vertical axis. The antibiotics administered are indicated. Arrows represent the timing and the results of blood cultures. þ, positive. , negative. First four samples are the results of one-week incubation. A: admission, D: discharge, CTRX: ceftriaxone, CEZ: cefazolin, TEIC: teicoplanin, ABPC: ampicillin, CAM: clarithromycin, ELT: ethanol lock therapy. (b) Photograph of Gram staining (the Favor method) of D. barathri growing with the medium from the aerobic bottle. (c) Colony of Dermacoccus barathri on sheep blood agar after 72 h-capneic incubation. (d) Phylogenetic tree of Dermacoccus based on concatenated sequences of 4 housekeeping genes (16S rRNA gene: 1402 bp, groEL: 1598 bp, rpoB: 2659 bp, and recA: 459 bp). DN T: D. nishinomiyaensis JCM 11613T, DB T: D. barathri JCM 14588T, DP T: D. profundi JCM 14589T, DA T: D. abyssi JCM 14339T, 56025: a strain from this case.
Please cite this article in press as: Takahashi N, et al., Catheter-related blood stream infection caused by Dermacoccus barathri, representing the first case of Dermacoccus infection in humans, J Infect Chemother (2015), http://dx.doi.org/10.1016/j.jiac.2015.04.007
N. Takahashi et al. / J Infect Chemother xxx (2015) 1e4
and trypsin production, but no production of H2S, a-fucosidase, or b-glucosidase. Some of the colonies were tightly adherent to the blood agar plates and had a gummy appearance. The 16S rRNA gene sequence was identical to that of D. barathri MT2.1T for almost the entire length (1459/1459 bp). Although the 16S rRNA gene sequence of D. barathri shows 99% similarity with that of D. abyssi and D. profundi, D. barathri can be distinguished from the other species based on biochemical properties. Finally, the isolated organism was identified as D. barathri, based on phylogenetic analysis of 6118-bp concatenated sequences of 4 housekeeping genes (16S rRNA gene, groEL, rpoB, and recA) (Fig. 1d). The susceptibility data for the organism is shown in Online Resource 1. The identified organism was not detected in cultures from any other site (urine, stool, or gastric juice samples) during the clinical course. A colony of gram-positive rods was detected on right axillary skin culture, but the organism could not be identified. Environmental samples were not sent for culture tests. Removed CVAD were cultured and gram-positive coccui were detected but were not consistent with this organism. 3. Discussion Children with intestinal failure are often dependent on a CVC for nutritional support and the maintenance of the watereelectrolyte balance. However, these children with intestinal motility disorder are at risk of insufficient intestinal drainage, which increases the intestinal luminal pressure and results in translocation of intestinal bacteria. Thus, recurrent CVC-related sepsis is inevitable, and sepsis caused by multi-drug resistant bacteria is often seen in these patients, representing a life-threatening condition. To prevent such situations, CVC removal and replacement are generally essential, but this decreases the candidate venous access sites in children because the vessels of children in which the CVC is placed are very thin and hence easily occluded due to thrombus production, making CVC reinsertion impossible [7]. Intravenous access represents a lifeline for these patients, because the loss of vascular sites is considered an indication for intestinal transplantation. In patients with intestinal failure, CRBSIs typically arise from bacterial colonization of the internal surface of the intravascular catheter, often by migration of skin flora. Gastrostomy or enterostomy, often performed in these patients for intestinal decompression, may be the source of such infections. In addition, daily access for parenteral nutrition and fluid administration at home increases the likelihood of the catheter serving as a portal for infection. CRBSI in patients with intestinal failure is attributable to common intestinal flora in approximately 50% of cases [8]. Ethanol, not known to elicit bacterial resistance, is used to sterilize the hub [9] and the usefulness of ethanol locks for the treatment and prevention of CRBSI has been reported [6,10]. In contrast, ethanol lock therapy has been reported to be ineffective in a few cases, although the differences between the effective and ineffective cases are currently unknown. These may however be related to the type of CVC (e.g., Broviac, Hickman, and port type). In this case, incubation for more than 10 days was required to detect the causative pathogen in the blood cultures. The diagnosis of CRBSI could have been missed if incubation was not performed for this prolonged period. The possible reasons it took longer incubation to detect the bacteria are as follows. Positive blood cultures containing pathogens have been reported to be detected within the first 24 h of incubation in 87% of cases, although a four-fold longer incubation time is required for some pathogens such as Corynebacterium spp. [11]. The required incubation period for Dermacoccus spp. has not been reported, but considering that Corynebacterium spp. and Dermacoccus spp. belong to the order of Actinomycetales, they might have similar characteristics. Furthermore, in case of Staphylococcus
3
epidermidis, which is one of the major bacteria caused implanted biomaterial-associated infections like CRBSI due to producing large amounts of biofilm, its growth rate in biofilm is very slower than that in platonic culture [12]. The reason of this phenomenon is possibly explained as tricarboxylic acid cycle-dependent regulation of synthesis of polysaccharide intracellular adhesion, which is a major component of biofilm [13,14]. In this case, some colonies of D. barathri recovered from blood culture were quite adhesive on agar plates, which indicated these colonies formed extensive biofilm due to production of large amounts of extracellular polysaccharides like S. epidermidis. Although we referred to antibiotic susceptibility data for Dermacoccus spp. (Online Resource 1), the antibiotic susceptibility patterns have not been published. Furthermore, reports on the antibiotic susceptibility patterns of Kytococcus spp., the species most closely related to Dermacoccus spp., are also few [15]. In this case, because blood cultures turned negative during treatment with antibiotics, and at least TEIC, ABPC and CAM seemed sensitive from MIC data, these antibiotics were effective. However these antibiotics alone might not have been enough to eradicate the organisms for this patient with CRBSI. After ethanol lock therapy, the organism was not detected any more from any sites including blood at day 68 and inside or outside the CVAD. We judged ethanol lock therapy was effective for eradicating the organism, thus we could not prove that the organism adhered to the CVAD. Environmental samples were not collected and subjected to culture tests, and therefore, the source of the pathogen could not be identified. However, being a seemingly ubiquitous organism, it may be difficult to confirm its source. Further characterization of this organism will be invaluable in understanding it pathogenicity in humans. Here, we report the first case of human infection with D. barathri. Detection of this pathogen requires prolonged incubation periods for blood culture in patients with suspected CRBSI in a CVAD. Conflict of interest The authors state there are no conflicts of interests. Appendix A. Supplementary material Supplementary data related to this article can be found online at http://dx.doi.org/10.1016/j.jiac.2015.04.007. References [1] Mermel LA, Farr BM, Sherertz RJ, Raad II , O'Grady N, Harris JS, et al. Guidelines for the management of intravascular catheter-related infections. Clin Infect Dis 2001;32:1249e72. [2] Stackebrandt E, Koch C, Gvozdiak O, Schumann P. Taxonomic dissection of the genus Micrococcus: Kocuria gen. nov., Nesterenkonia gen. nov., Kytococcus gen. nov., Dermacoccus gen. nov., and Micrococcus Cohn 1872 gen. emend. Int J Syst Bacteriol 1995;45:682e92. [3] Pathom-Aree W, Nogi Y, Ward AC, Horikoshi K, Bull AT, Goodfellow M. Dermacoccus barathri sp. nov. and Dermacoccus profundi sp. nov., novel actinomycetes isolated from deep-sea mud of the Mariana Trench. Int J Syst Evol Microbiol 2006;56:2303e7. [4] Ruckmani A, Kaur I, Schumann P, Klenk HP, Mayilraj S. Calidifontibacter indicus gen. nov., sp. nov., a member of the family Dermacoccaceae isolated from a hot spring, and emended description of the family Dermacoccaceae. Int J Syst Evol Microbiol 2011;61:2419e24. [5] Gupta AK, Rastogi G, Nayduch D, Sawant SS, Bhonde RR, Shouche YS. Molecular phylogenetic profiling of gut-associated bacteria in larvae and adults of flesh flies. Med Vet Entomol 2014;28:345e54. [6] Broom J, Woods M, Allworth A, McCarthy J, Faoagali J, Macdonald S, et al. Ethanol lock therapy to treat tunnelled central venous catheter-associated blood stream infections: results from a prospective trial. Scand J Infect Dis 2008;40:399e406.
Please cite this article in press as: Takahashi N, et al., Catheter-related blood stream infection caused by Dermacoccus barathri, representing the first case of Dermacoccus infection in humans, J Infect Chemother (2015), http://dx.doi.org/10.1016/j.jiac.2015.04.007
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[7] Casey L, Lee KH, Rosychuk R, Turner J, Huynh HQ. 10-year review of pediatric intestinal failure: clinical factors associated with outcome. Nutr Clin Pract 2008;23:436e42. [8] Hull MA, Jones BA, Zurakowski D, Raphael B, Lo C, Jaksic T, et al. Low serum citrulline concentration correlates with catheter-related bloodstream infections in children with intestinal failure. J Parenter Enteral Nutr 2011;35: 181e7. [9] Metcalf SC, Chambers ST, Pithie AD. Use of ethanol locks to prevent recurrent central line sepsis. J Infect 2004;49:20e2. [10] Mouw E, Chessman K, Lesher A, Tagge E. Use of an ethanol lock to prevent catheter-related infections in children with short bowel syndrome. J Pediatr Surg 2008;43:1025e9. [11] McGowan KL, Foster JA, Coffin SE. Outpatient pediatric blood cultures: time to positivity. Pediatrics 2000;106:251e5.
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Please cite this article in press as: Takahashi N, et al., Catheter-related blood stream infection caused by Dermacoccus barathri, representing the first case of Dermacoccus infection in humans, J Infect Chemother (2015), http://dx.doi.org/10.1016/j.jiac.2015.04.007