CASE REPORT

Rothia dentocariosa Bacteremia in Children: Report of Two Cases and Review of the Literature Chin-Ying Yang,1 Po-Ren Hsueh,2 Chun-Yi Lu,3 Hsiu-Yuan Tsai,4 Ping-Ing Lee,3 Pei-Lan Shao,2 Chung-Yi Wang,3 Tsung-Zu Wu,4 Shih-Wei Chen,1 Li-Min Huang3*

Rothia dentocariosa, a pleomorphic, fastidious, Gram-positive rod, is a normal inhabitant of the orophar- ynx. It is a well-known causative agent of dental plaques and . Generally regarded as of low virulence to humans, R. dentocariosa has been increasingly recognized as a pathogen in adults and often associated with infective endocarditis. It should not necessarily be regarded as a contaminant when the isolate comes from areas other than the oropharynx, especially from the blood. We report two cases of R. dentocariosa bacteremia, including an 8-month-old boy with repaired transposition of the great arteries, and a healthy 20-month-old girl with herpangina. [J Formos Med Assoc 2007;106(3 Suppl): S33–S38]

Key Words: bacteremia, Rothia dentocariosa

Rothia dentocariosa is a filamentous, facultatively Case Reports anaerobic nonmotile, nonspore-forming, Gram- positive rod, which usually resides in the oral Case 1 cavity. Originally isolated from humans in 1949 An 8-month-old boy, who underwent an arterial by Onishi1 in carious dentine, it was known as switch procedure for d-transposition of the great dentocariosus. It was later reclassified arteries at 5 days of age, had frequent airway in- in the genus Norcardia because of its aerobic fections after the cardiac surgery. Ten days prior to growth requirement. In 1967, Georg and Brown this admission, he became febrile with cough and created the new genus Rothia because of its rhinorrhea. Symptomatic treatments and a 5-day unique cell wall composition.2 R. dentocariosa course of amoxicillin were given. Unfortunately, has rarely been isolated from clinical specimens his condition deteriorated. Severe cough, hoarse- and has generally been regarded as a low viru- ness, and tachypnea were noted when he presented lence organism. Bacteremia caused by R. dento- to the emergency department. His body temper- cariosa has rarely been described in children. Here, ature was 36.7°C, pulse rate was 144 beats/minute, we report Rothia bacteremia in two children and and respiratory rate was 64 breaths/minute. review the literature. His throat was infected. He was edentulous.

©2007 Elsevier & Formosan Medical Association ...... 1Youth Clinic, and Departments of 2Laboratory Medicine and Internal Medicine, and 3Pediatrics, National Taiwan University Hospital, and 4Department of Pediatrics, Taipei City Hospital, Taipei, Taiwan.

Received: August 31, 2005 *Correspondence to: Dr Li-Min Huang, Department of Pediatrics, National Taiwan University Hospital, 7 Revised: October 31, 2005 Chung-Shan South Road, Taipei 100, Taiwan. Accepted: January 10, 2006 E-mail: [email protected]

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No gingivitis was noted. Breathing sounds were coarse with diffuse wheezing and rhonchi. There were notable sub- and intercostal retractions. His heartbeats were regular with a grade III/VI systolic murmur along the left sternal border. The liver edge was 2 cm below the right costal margin and the spleen edge was 2 cm below the left costal mar- gin. These measurements were similar when com- pared to the findings at his previous examination 2 weeks before. The extremities were normal with- out cyanosis. No nail bed hemorrhage or abnormal Figure 1. Colonies of Rothia dentocariosa raised with rough skin lesions were detected. concentric radial ridges and irregular edges after incubation Laboratory studies showed the following val- for 72 hours. Isolate from case 1. ues: white blood cell (WBC) count of 8990/mm3 with 56.2% segmented neutrophils, 31.5% lym- phocytes, and 8.2% monocytes. His hemoglobin level was 9.6 g/dL and C-reactive protein was 1.99 mg/dL (normal, < 0.8 mg/dL). Serum elec- trolyte levels and liver function tests were within normal limits. His chest X-ray showed cardio- megaly and emphysematous changes in both lungs with a flattened diaphragm. Increased infiltration of the lower right lung field was noted. He was admitted under the impression of acute bronchi- olitis. Supportive treatments with intravenous fluids, inhalation of cool, humidified oxygen, Figure 2. Case 1: Gram stain smear of Rothia dentocariosa rd and chest hygiene care were given. On the 3 day from the culture shows pleomorphic Gram-positive branch- of hospitalization, the blood culture obtained at ing rods to cocci (1000×). the emergency room grew two Gram-positive bac- teria. Intravenous cephalothin (100 mg/kg/day) was given. These two were identified as of R. dentocariosa (accession number, AF543284). Streptococcus sanguis and R. dentocariosa using API We changed the cephalothin to G 32 STREP and API CORYNE (BioMerieux Vitek, (250,000 unit/kg/day) and gentamicin (7.5 mg/ Inc., Hazelwood, MO, USA), respectively. The kg/day). Antimicrobial susceptibility of R. dento- colonies of the R. dentocariosa isolate were raised cariosa was determined by the E-test (PDM, with rough concentric and irregular edges after Solna, Sweden) on Mueller-Hinton agar (BBL incubation for 72 hours (Figure 1). The Gram stain Microbiology Systems, Cockeysville, MD, USA). smear from the culture showed pleomorphic The minimal inhibitory concentration (MIC) Gram-positive branching rods to cocci (Figure 2). ranges (μg/mL) were as follows: penicillin 0.125, Sequence analysis of nearly complete 16S rRNA cephalothin 0.25, cefotaxime 0.38, gentamicin gene (1487 bp) for the R. dentocariosa isolate 2, amikacin 2, vancomycin 2, clindamycin 1, was also conducted using two primers (8FPL 0.023, and 1.5. and 1492).3 A blastn search was performed to The precordial echocardiogram showed mild compare the sequence of our isolate with those in stenosis of the neoaorta and mild regurgita- the GenBank and Ribosomal Project database. tion of neoaortic and pulmonary arteries. There Our isolate was compatible with the identification was no vegetation. Blood cultures obtained on

S34 J Formos Med Assoc | 2007 • Vol 106 • No 3 Suppl Rothia dentocariosa bacteremia in children the 3rd day of hospitalization before the use of Discussion cephalothin was negative. Parenteral were used for 5 days. The patient was discharged R. dentocariosa has been most frequently isolated on the 12th day of hospitalization after improve- from oropharyngeal secretions, sputum, and car- ment of his respiratory condition. No compli- ious teeth. Although it has also been isolated from cations developed during follow-up. blood, heart valves, ascitic fluid, CSF, urine, bone, pubic aspirate, eyes, and pleural and joint effu- Case 2 sions, the clinical significance of many of these A 20-month-old girl with no underlying disease isolates remains unclear. Kong et al,4 in a review of presented to our emergency department because specimens over 8 years from two reference labora- of fever and a seizure attack. At home, she had a tories in France, showed a total of 103 specimens, sudden loss of consciousness, upward gazing, and of which 69 were isolated from the respiratory tonic posturing of the extremities. This lasted for tract and were most likely contaminants. Only 5 minutes and she regained consciousness soon 19 cases had positive blood cultures and most of after. On physical examination, she appeared them were transient bacteremia. lethargic. Her body temperature was 38.8°C, However, in 1969, Roth and Flanagan5 exper- heart rate was 120 beats/minute, and respiration imentally induced abscess formation in mice, via rate was 34 breaths/minute. Her pupils were iso- local injections, thus demonstrating a pathogenic coric with prompt light reflex. There were multiple potential for R. dentocariosa. To date, 20 cases of vesicles over the soft palate and buccal mucosa. infectious endocarditis6–20 and 12 patients with There was no gingivitis or dental caries. Chest, extracardiac infection21–30 caused by R. dentocariosa cardiac, abdominal, integumentary, and neuro- have been reported in the English literature. Most logic examinations were unremarkable. Her WBC of them were immunocompromised adults or count was 10,430/mm3 with 65.3% segmented those with pre-existing cardiac disease (mitral valve neutrophils, 26.7% lymphocytes, and 5.9% prolapse, bicuspid aortic valve, rheumatic mitral monocytes. Her serum electrolyte levels, blood valvular disease, prosthetic valve) and poor oral glucose, and liver function tests were all within hygiene. Only five patients younger than 18 years normal limits. The result of her lumbar puncture of age have been reported (Table). In 1975, showed clear cerebrospinal fluid (CSF) with glu- Scharfen27 presented a 17-year-old girl with an cose concentration of 63 mg/dL, total protein infected pilonidal cyst, which required surgical concentration of 15 mg/dL, and no nucleated drainage. Recently, a 4-year-old, immunocompe- cells. She was admitted under the impression tent Japanese girl was reported to have severe acute of herpangina and possible febrile convulsion. tonsillitis with a pseudomembrane.30 Neither of She received intravenous fluids and antipyretics. the two had evidence of blood stream infection. No antibiotics were given. Her clinical condition The other three patients had infective endocardi- improved quickly and she was discharged 2 days tis; two of them were complicated with mycotic later. The blood culture obtained at the emergency aneurysms.9,12,20 room grew R. dentocariosa. Bacterial culture of We present two children with bacteremia her CSF was negative. Her follow-up electroen- caused by this rare pathogen, R. dentocariosa. In cephalography was normal. The seizure episode case 1, the isolated organisms, R. dentocariosa and at the emergency department was interpreted as S. sanguis, are commonly found as normal flora febrile convulsion. No further blood culture was in the oropharynx. In case 2, the mucosal damage obtained due to her good clinical condition on caused by herpangina might have provided the follow-up visits. No complication was detected. portal of entry for the bacteria. Although we did Initial isolate was lost for further antimicrobial not perform throat bacterial culture in either case, susceptibility testing. the bacteria probably invaded the blood through

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the injured oral mucosa. Both cases had benign clinical courses and complete recovery despite the fact that case 1 had a pre-existing complex congen- Cure Cure Cure Cure Cure Cure ital heart disease. The second blood culture in case 1 without using antimicrobial agent was al- ready negative. No antimicrobial agent was given in case 2. The clinical courses of the two cases were compatible with self-limited transient bacteremia by low virulent pathogen. Microbiologically, R. dentocariosa is a slow- growing (3–7 days) organism with an optimum growth temperature of 37°C. Its growth is best under aerobic conditions, but it is able to survive subarachnoid hemorrhages, aortic root subarachnoid mesenteric artery abscess requiring replacement abscess requiring None None microaerophilically. On 5% horse blood agar, white–gray, small (1 mm), smooth colonies with entire edges are seen after 24 hours of incubation. The colonies are raised with rough concentric, ra- dial ridges, and irregular edges after incubation for 72 hours. Gram stains from the culture vary from pleomorphic Gram-positive branching rods the abscess ceftriaxone cephalexin gentamicin

blood culture. to cocci. Biochemically, the isolates produce cata- = lase, reduce nitrate to nitrite, and hydrolyze esculin. Acid is produced by fermentation from glucose, maltose, sucrose, and trehalose. Negative reac- B/C amikacin Penicillin, mycotic aneurysms with Intracranial Cure B/C Imipenem-cilastatin None B/C Amoxicillin/clavulanate Aneurysm of superior tions include oxidase, urease, indole, and lactose. Microbiologically, similar laboratory characteris- tics are seen in , Arachnia, Actinomyces,

infective endocarditis; B/C = infective endocarditis; Corynebacterium, Oerskovia, and Propionibacterium. The growth rates, lack of partial acid fastness, ab- Infection Source Treatment Complication Outcome Pilonidal cyst Pilonidal cyst of drainage Surgical None Bacteremia B/C None Acute tonsillitis swab Throat Bacteremia Ampicillin B/C gentamicin Penicillin, None IE infection sence of aerial mycelium, and fermentation of sugars are helpful for distinguishing Rothia from Nocardia. The major glucose fermentation prod- ucts of Rothia are lactic and acetic acids, in contrast to succinate and propionic acid in Actinomyces and

Rothia dentocariosa Propionibacterium. Corynebacterium demonstrates stenosis and insufficiency primary tooth, VSD perimembranous whip handle-like forms on Gram stains. The API

d-transposition of the great arteries; IE of the great d-transposition CORYNE test strips are useful for identification = and typically yield codes 7050125 or 7052125.

6 yr/F Spontaneous loss of a IE 4 yr/F None Additional chemotaxonomic analyses (e.g. con- 17 yr/F Bicuspid aortic valve with IE 17 yr/F None 17 yr/M None 20 mo/F Herpangina Patient factors or Predisposing (age/sex) underlying disease tinuous flow analysis chromatography) may help

28 differentiate Rothia from other Gram-positive 20

12 rods. The application of 16S rRNA gene sequenc- 9 30 ing also provides good identification results. Summary of pediatric cases Although there are no National Committee for ventricular septal defect; d-TGA ventricular septal defect; d-TGA Clinical Laboratory Standard protocols for sus- Ohashi et al Lutwick & Rockhill Weersink et al Weersink Present reportsPresent 8 mo/M d-TGA Reference Boudewijns et al Braden et al Braden Table.

VSD = ceptibility testing of Rothia, most isolates from

S36 J Formos Med Assoc | 2007 • Vol 106 • No 3 Suppl Rothia dentocariosa bacteremia in children the literature are susceptible to , cepha- 8. Llopis F, Carratala J. Vertebral osteomyelitis complicating losporins, erythromycin, vancomycin, amino- Rothia dentocariosa endocarditis. Eur J Clin Microbiol Infect Dis 2000;19:562–3. glycosides, , chloramphenicol, and 9. Braden DS, Feldman S, Palmer AL. Rothia endocarditis in trimethoprim/sulfamethoxazole. Reported peni- a child. South Med J 1999;92:815–6. cillin MICs are low, ranging from < 0.016 mg/L to 10. Ferraz V, McCarthy K, Smith D, et al. Rothia dentocariosa 0.12 mg/L.10,11,15,17,19,24 Also, favorable outcome endocarditis and aortic root abscess. J Infect 1998;37: with penicillin therapy suggest in vivo suscepti- 292–5. 11. Binder D, Zbinden R, Widmer U, et al. Native and pros- bility. However, vancomycin treatment failure has thetic valve endocarditis caused by Rothia dentocariosa: 7,13 also been reported. diagnostic and therapeutic considerations. Infection 1997; In this report, we observed that R. dentocariosa 25:22–6. bacteremia could develop in immunocompetent 12. Weersink AJ, Rozenberg-Arska M, Westerhof PW, et al. children when oral mucosa is injured. The clinical Rothia dentocariosa endocarditis complicated by an ab- dominal aneurysm. Clin Infect Dis 1994;18:489–90. course is usually benign as transient bacteremia. 13. Sudduth EJ, Rozich JD, Farrar WE. Rothia dentocariosa But, since there were growing numbers of case endocarditis complicated by perivalvular abscess. Clin Infect reports of serious systemic infections caused by Dis 1993;17:772–5. R. dentocariosa,4,6–29 it should not necessarily be 14. Ruben SJ. Rothia dentocariosa endocarditis. West J Med regarded as a contaminant when the isolate comes 1993;159:690–1. 15. Isaacson JH, Grenko RT. Rothia dentocariosa endocarditis from areas other than the oropharynx. Penicillin, complicated by brain abscess. Am J Med 1988;84:352–4. the drug of choice, should be used once the blood 16. Schafer FJ, Wing EJ, Norden CW. Infectious endocarditis culture is positive. The duration of antimicrobial caused by Rothia dentocariosa. Ann Intern Med 1979;91: agent use depends on the following culture results. 747–8. In immunocompromised patients and those with 17. Broeren SA, Peel MM. Endocarditis caused by Rothia heart disease and poor dental hygiene, prompt iden- dentocariosa. J Clin Pathol 1984;37:1298–300. 18. Anderson MD, Kennedy CA, Walsh TP, et al. Prosthetic valve tification and antimicrobial susceptibility testing endocarditis due to Rothia dentocariosa. Clin Infect Dis are important to achieve good clinical response. 1993;17:945–6. 19. Pape J, Singer C, Kiehn TE, et al. Infective endocarditis caused by Rothia dentocariosa. Ann Intern Med 1979;91: References 746–7. 20. Boudewijns M, Magerman K, Verhaegen J, et al. Rothia dentocariosa, endocarditis and mycotic aneurysms: case 1. Onishi M. Study on the actinomyces isolated from the report and review of the literature. Clin Microbiol Infect deeper layers of carious dentine. Shikagaku Zasshi 1949;6: 2003;9:222–9. 273–318. 21. Wallet F, Perez T, Roussel-Delvallez M, et al. Rothia den- 2. Georg LK, Brown JM. Rothia, gen. nov., an aerobic genus of tocariosa: two new cases of pneumonia revealing lung the family Actinomycetaceae. Int J Syst Bacteriol 1967; cancer. Scand J Infect Dis 1997;29:419–20. 17:79–88. 22. Schiff MJ, Kaplan MH. Rothia dentocariosa pneumonia in 3. Chiang WC, Tsai JC, Chen SY, et al. Mycotic aneurysm an immunocompromised patient. Lung 1987;165:279–82. caused by Streptococcus constellatus subspecies constel- 23. Pers C, Kristiansen JE, Jonsson V, et al. Rothia dento- latus. J Clin Microbiol 2004;42:1826–8. cariosa septicemia in a patient with chronic lymphocytic 4. Kong R, Mebazaa A, Heitz B, et al. Case of triple endocardi- leukemia and toxic granulocytopenia. Dan Med Bull 1987; tis caused by Rothia dentocariosa and results of a survey in 34:322–3. France. J Clin Microbiol 1998;36:309–10. 24. Nivar-Aristy RA, Krajewski LP, Washington JA. Infection of 5. Roth GD, Flanagan V. The pathogenicity of Rothia den- an arteriovenous fistula with Rothia dentocariosa. Diagn tocariosa inoculated into mice. J Dent Res 1969;48: Microbiol Infect Dis 1991;14:167–9. 957–8. 25. Ergin C, Sezer MT, Agalar C, et al. A case of peritonitis due 6. Ricaurte JC, Klein O, LaBombardi V, et al. Rothia dento- to Rothia dentocariosa in a CAPD patient. Perit Dial Int cariosa endocarditis complicated by multiple intracranial 2000;20:242–3. hemorrhages. South Med J 2001;94:438–40. 26. Bibashi E, Kokolina E, Mitsopoulos E, et al. Peritonitis due 7. Shands JJ. Rothia dentocariosa endocarditis. Am J Med to Rothia dentocariosa in a patient receiving continuous am- 1988;85:280–1. bulatory peritoneal dialysis. Clin Infect Dis 1999;28:696.

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27. Scharfen J. Untraditional glucose fermenting actinomycetes 29. Suheil AS, Jorgen P. Three cases of Rothia dentocariosa as human pathogens. Part II: Rothia dentocariosa as a cause bacteremia: frequency in Denmark and a review. Scand J of abdominal actinomycosis and a pathogen for mice. Infect Dis 2002;34:153–7. Zentralbl Bakteriol [Orig A] 1975;233:80–92. 30. Ohashi M, Yoshikawa T, Akimoto S. Severe acute tonsillitis 28. Lutwick LI, Rockhill RC. Abscess associated with Rothia caused by Rothia dentocariosa in a healthy child Pediatr dentocariosa. J Clin Microbiol 1978;8:612–3. Infect Dis J 2005;24:466–7.

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