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by Candida spp.; S. aureus and entercocci are also commonly associated. Tsukamurella species are quite rare
Tsukamurella
Named for Tsukamura, the Japanese microbiologist well-known for his studies of Gordona spp. in lung disease
in the 1970s ADDIN EN.CITE Tsukamura19712041099266811971SepProposal of a new genus, Gordona, for slightly acid-fast organisms occurring in sputa of patients with pulmonary disease and in soil15-26Tsukamura, M.J Gen MicrobiolAcids/biosynthesisAerobiosisAmines/metabolismAnimalsBacteria/*classification/enzymology/growth & development/isolation &purification/metabolism/pathogenicityBronchiectasis/*microbiologyCatalase/metabolismChickensGlucose/metabolismGuinea PigsHumansMannose/metabolismMiceMycobacterium/classificationNitrates/metabolismNocardia/classificationOxidation-ReductionRabbits*Soil MicrobiologySputum/*microbiologyStaining and LabelingSucrose/metabolismSulfatases/metabolismTuberculosis, Pulmonary/*microbiologyhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=41099267, Tsukamurella were first classed as a separate genus by Collins et al. in the late 1980s after they discovered strong sequence homology between organisms previously classed as both Corynebacterium
paurometabola and Rhodococcus aurantiacus ADDIN EN.CITE Collins198830Collins, M.D.Smida, J.Dorsh, M.Stackebrandt, E.1988Tsukamurella gen.
nov. harboring Corynebacterium paurometabolum and Rhodococcus aurantiacus.Int J Syst Bacteriol38385-918. Individual species of Tsukamurella associated with disease
include T. paurometabola, T. inchonensis, T. pulmonis, T. tyrosinosolvens, and T. wratislaviensis.
Tsukamurella are obligately aerobic, gram-positive organisms that now fall within the order Actinomycetales
along with Nocardia, Gordonia, Streptomyces, and Rhodococcus. They are bacilli that form branching
hyphae-like structures, and are partially acid fast. Like Mycobacterium, Corynebacterium, Nocardia, and
Rhodococcus, the Tsukanurella cell wall is high in mycolic acid content. Tsukamurella are found in soil
and grow quickly in culture when compared to many mycobacteria. When grown on agar, the tan-to-grey
colonies appear dry and may look rough with rhizoid edges after time.
Differentiation of Tsukanurella from similar staining organisms at the genus level (i.e., from Nocardia and Rhodococcus genera) relies on gas-liquid chromatography or HPLC. Pattern recognition programs have
been applied for automating identification once the chromatography result is generated ADDIN EN.CITE Glickman19945081953873231994MarRapid identification of mycolic acid patterns of mycobacteria by high-performance liquid chromatography using pattern recognition software and a Mycobacterium library740-5Division of Bacterial and Mycotic Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333.Glickman, S. E.Kilburn, J. O.Butler, W. R.Ramos, L. S.J Clin MicrobiolAlgorithmsBacterial Typing Techniques/statistics & numerical data*Bacteriological Techniques/statistics & numerical data*Chromatography, High Pressure Liquid/statistics & numerical dataEvaluation StudiesHumansMycobacterium/*chemistry/*classification/isolation & purificationMycolic Acids/*analysisPattern Recognition, AutomatedSoftwareSpecies Specificityhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=81953879. In addition to
this classic methodology, molecular approaches are being developed which facilitate identification of
Tsukamurella and differentiation from other genera. These include 16S rRNA sequencing ADDIN EN.CITE Laurent19999098540713711999JanRapid identification of clinically relevant Nocardia species to genus level by 16S rRNA gene PCR99-102Institut Pasteur, Unite de Mycologie, Centre National de Reference des Mycoses Humaines, des Antifongiques et des Actinomycetes, 75724 Paris Cedex 15, France. laurent@lyon-sud.univ-lyon1.frLaurent, F. J.Provost, F.Boiron, P.J Clin MicrobiolBacteriological TechniquesBase SequenceComparative StudyHumansMolecular Sequence DataNocardia/genetics/*isolation & purificationPolymerase Chain Reaction/*methodsRNA, Bacterial/*analysisRNA, Ribosomal, 16S/*analysisSensitivity and SpecificitySequence AlignmentSpecies Specificityhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=985407110, which can
be used for Tsukamurella identification to the species level, and restriction fragment length polymorphism
(RFLP) analysis of a 439bp PCR amplicon of the 65kDa heat shock protein gene ADDIN EN.CITE Steingrube19978091571343541997AprRapid identification of clinically significant species and taxa of aerobic actinomycetes, including Actinomadura, Gordona, Nocardia, Rhodococcus, Streptomyces, and Tsukamurella isolates, by DNA amplification and restriction endonuclease analysis817-22Department of Microbiology University of Texas Health Center at Tyler 75710-2003, USA.Steingrube, V. A.Wilson, R. W.Brown, B. A.Jost, K. C., Jr.Blacklock, Z.Gibson, J. L.Wallace, R. J., Jr.J Clin MicrobiolActinomyces/classification/*isolation & purificationBacterial Typing TechniquesDNA, Bacterial/*analysisPolymerase Chain ReactionPolymorphism, Restriction Fragment LengthResearch Support, Non-U.S. Gov'thttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=915713411.
Clinically, Tsukamurella may be considered an opportunistic infection, with most cases being caused in
the immunecompromised. Collections of Tsukamurella cases have been published for patients with indwelling
central venous catheters; in a recent report of six such cases ADDIN EN.CITE Schwartz2002110122288393572002Oct 1Central venous catheter-related bacteremia due to Tsukamurella species in the immunocompromised host: a case series and review of the literaturee72-7Department of Medicine, Division of Infectious Diseases, University of Washington, Seattle, WA, USA. margot.schwartz@vmmc.orgSchwartz, M. A.Tabet, S. R.Collier, A. C.Wallis, C. K.Carlson, L. C.Nguyen, T. T.Kattar, M. M.Coyle, M. B.Clin Infect DisActinomycetales/*isolation & purificationAdolescentAdultAgedBacteremia/*microbiologyCatheterization, Central Venous/*adverse effectsChildChild, PreschoolFemaleHumans*Immunocompromised HostInfantMaleMiddle AgedProsthesis-Related Infections/*microbiologyhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=122288394 five were markedly immunocompromized because
of inherited severe combined immunodeficiency (SCID), leukemia, a myelodysplastic bone marrow pathology,
or immunosuppressive chemotherapy for treatment of metastatic cancer or graft-verses-host disease (GVHD)
after bone marrow transplant. One of the patients had only chronic renal failure from IgA nephropathy and may
be though of as similar to our case in terms of predisposing factors.
References:
ADDIN EN.REFLIST 1. Shapiro CL, Haft RF, Gantz NM, et al. Tsukamurella paurometabolum: a novel pathogen causing catheter-related bacteremia in patients with cancer. Clin Infect Dis 1992; 14:200-3.
2. Lai KK. A cancer patient with central venous catheter-related sepsis caused by Tsukamurella paurometabolum (Gordona aurantiaca). Clin Infect Dis 1993; 17:285-7.
3. Maertens J, Wattiau P, Verhaegen J, Boogaerts M, Verbist L, Wauters G. Catheter-related bacteremia due to Tsukamurella pulmonis. Clin Microbiol Infect 1998; 4:51-53.
4. Schwartz MA, Tabet SR, Collier AC, et al. Central venous catheter-related bacteremia due to Tsukamurella species in the immunocompromised host: a case series and review of the literature. Clin Infect Dis 2002; 35:e72-7.
5. Sheridan EA, Warwick S, Chan A, Antonia MD, Koliou M, Sefton A. Tsukamurella tyrosinosolvens intravascular catheter infection identified using 16S ribosomal DNA sequencing. Clin Infect Dis 2003; 36:e69-70.
6. Shaer AJ, Gadegbeku CA. Tsukamurella peritonitis associated with continuous ambulatory peritoneal dialysis. Clin Nephrol 2001; 56:241-6.
7. Tsukamura M. Proposal of a new genus, Gordona, for slightly acid-fast organisms occurring in sputa of patients with pulmonary disease and in soil. J Gen Microbiol 1971; 68:15-26.
8. Collins MD, Smida J, Dorsh M, Stackebrandt E. Tsukamurella gen. nov. harboring Corynebacterium paurometabolum and Rhodococcus aurantiacus. Int J Syst Bacteriol 1988; 38:385-91.
9. Glickman SE, Kilburn JO, Butler WR, Ramos LS. Rapid identification of mycolic acid patterns of mycobacteria by high-performance liquid chromatography using pattern recognition software and a Mycobacterium library. J Clin Microbiol 1994; 32:740-5.
10. Laurent FJ, Provost F, Boiron P. Rapid identification of clinically relevant Nocardia species to genus level by 16S rRNA gene PCR. J Clin Microbiol 1999; 37:99-102.
11. Steingrube VA, Wilson RW, Brown BA, et al. Rapid identification of clinically significant species and taxa of aerobic actinomycetes, including Actinomadura, Gordona, Nocardia, Rhodococcus, Streptomyces, and Tsukamurella isolates, by DNA amplification and restriction endonuclease analysis. J Clin Microbiol 1997; 35:817-22.
THE JOHNS HOPKINS MICROBIOLOGY NEWSLETTER Vol. 24, No. 10
Tuesday, March 8, 2005
A. Provided by Sharon Wallace, Division of Outbreak Investigation, Maryland Department
of Health and Mental Hygiene.
7 outbreaks were reported to DHMH during MMWR Week 9 (February 27 March 5):
3 Respiratory Outbreaks
2 outbreaks of INFLUENZA LIKE ILLNESS associated with Nursing Homes in Garrett Co. and Calvert Co.
1 outbreak of MRSA associated with a Detention Center in Howard Co.
3 Gastroenteritis Outbreaks
2 outbreaks of GASTROENTERITIS associated with a Nursing Homes in Worcester Co. and Baltimore City.
1 outbreak of GASTROENTERITIS associated with a Hospital in Calvert Co.
1 Other Outbreak
1 outbreak of CONJUNCTIVITIS associated with a school in Howard Co.
B. The Johns Hopkins Hospital, Department of Pathology, Information provided by,
Kathleen Burns, M.D., Ph. D
The Clinical Case
A 45-year-old African American woman with ischemic nephropathy and end stage renal disease presented with
a history of fevers over the preceding few days. She denied other symptoms. The patient undergoes hemodialysis
three times weekly with circulatory access by a Davol catheter.She was admitted to the Johns Hopkins Hospital
with temperatures nearing 40oC for management of a probable catheter infection. White blood cell count was
within normal limits at 5470, but with a neutrophil predominance of 83.9%. Blood cultures were sent to the
microbiology laboratory. She began a course of vancomycin and was given a single dose of gentamicin.
The Laboratory Diagnosis
Four separate blood cultures drawn on admission and over the following two days all were positive for growth
at one day with pleomorphic, clumped and branching Gram-positive bacilli. The technician reviewing Gram
stain morphology proceeded to perform an acid fast stain, which showed the organism was acid fast positive.
Upon referral for gas-liquid chromatography identification, findings were diagnostic of Tsukamurella species.
The Clinical Outcome
Gentamicin was discontinued, and the patient continued on vancomycin.The patient was discharged still
transiently febrile, but feeling well and with instructions to return with any changes. She followed up on the
second day for replacement of the Davol catheter at which time cultures were sent again. She said she no
longer had fevers. This culture exhibits no growth for one week at the time this is written.
Clinical Comment
This patient has a number of factors that put her at risk for infectious diseases, given her renal condition and
the need for circulatory access through an indwelling catheter. Catheter-related infections are common. Leading
the organisms associated with sepsis in patients with catheters are the coagulase-negative staphylococci, followed
in comparison, but case reports continue to be published ADDIN EN.CITE Shapiro199212015714301411992JanTsukamurella paurometabolum: a novel pathogen causing catheter-related bacteremia in patients with cancer200-3Division of Clinical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.Shapiro, C. L.Haft, R. F.Gantz, N. M.Doern, G. V.Christenson, J. C.O'Brien, R.Overall, J. C.Brown, B. A.Wallace, R. J., Jr.Clin Infect DisActinomycetales/*isolation & purificationActinomycetales Infections/etiology/*microbiologyAdolescentAgedBacteremia/etiology/*microbiologyBreast Neoplasms/complications/drug therapy*Catheterization, Central VenousFemaleHumansLeukemia, Lymphocytic, Acute/complications/drug therapyMaleMiddle AgedNeoplasms/*complications/drug therapyPelvic Neoplasms/complications/drug therapyResearch Support, U.S. Gov't, P.H.S.Sarcoma, Ewing's/complications/drug therapyhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1571430Lai19934083998861721993AugA cancer patient with central venous catheter-related sepsis caused by Tsukamurella paurometabolum (Gordona aurantiaca)285-7Lai, K. K.Clin Infect DisActinomycetales Infections/*etiologyAgedCatheterization, Central Venous/*adverse effectsFemaleHumans*Immunocompromised HostLeukemia, Lymphocytic, Acute/drug therapyMethotrexate/therapeutic useMicrobial Sensitivity Tests*Rhodococcushttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=83998861, 2 ADDIN EN.CITE Maertens199810011864235411998JanCatheter-related bacteremia due to Tsukamurella pulmonis51-53Department of Internal Medicine, Haematology, University Hospitals Leuven, Leuven, Belgium.Maertens, J.Wattiau, P.Verhaegen, J.Boogaerts, M.Verbist, L.Wauters, G.Clin Microbiol Infecthttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=118642353 ADDIN EN.CITE Schwartz2002110122288393572002Oct 1Central venous catheter-related bacteremia due to Tsukamurella species in the immunocompromised host: a case series and review of the literaturee72-7Department of Medicine, Division of Infectious Diseases, University of Washington, Seattle, WA, USA. margot.schwartz@vmmc.orgSchwartz, M. A.Tabet, S. R.Collier, A. C.Wallis, C. K.Carlson, L. C.Nguyen, T. T.Kattar, M. M.Coyle, M. B.Clin Infect DisActinomycetales/*isolation & purificationAdolescentAdultAgedBacteremia/*microbiologyCatheterization, Central Venous/*adverse effectsChildChild, PreschoolFemaleHumans*Immunocompromised HostInfantMaleMiddle AgedProsthesis-Related Infections/*microbiologyhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=122288394 ADDIN EN.CITE Sheridan2003140125946573652003Mar 1Tsukamurella tyrosinosolvens intravascular catheter infection identified using 16S ribosomal DNA sequencinge69-70Department of Medical Microbiology, St. Bartholomew's and the Royal London Hospitals, London, United Kingdom. drlizsheridan@yahoo.co.ukSheridan, E. A.Warwick, S.Chan, A.Antonia, M. D.Koliou, M.Sefton, A.Clin Infect DisActinomycetales/genetics/*isolation & purificationAdultCatheters, Indwelling/*microbiologyHumansMaleProsthesis-Related Infections/*microbiologyRNA, Ribosomal, 16S/*analysis/geneticshttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=125946575. Tsukamurella has also been associated with
peritonitis in the setting of peritoneal dialysis ADDIN EN.CITE Shaer2001130115970405632001SepTsukamurella peritonitis associated with continuous ambulatory peritoneal dialysis241-6Division of Nephrology, Medical University of South Carolina, Charleston 29425, USA. shaeraj@musc.eduShaer, A. J.Gadegbeku, C. A.Clin NephrolActinomycetales/drug effectsActinomycetales Infections/diagnosis/drug therapy/*etiologyAdultFemaleHumansMicrobial Sensitivity TestsPeritoneal Dialysis, Continuous Ambulatory/*adverse effectsPeritonitis/diagnosis/drug therapy/*etiology/microbiologyhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=115970406.
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1 T a b l e ) W o r d D o c u m e n t S u m m a r y I n f o r m a t i o n ( D o c u m e n t S u m m a r y I n f o r m a t i o n 8 C o m p O b j j
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Gregory Clark, M.D.
Dr Clark’s research focuses on pancreatic development and regeneration and cellular therapies for diabetes. His research investigates both adult and embryonic stem cells for their ability to repair or replace insulin producing beta cells that are destroyed in type 1 diabetes. Dr Clark has also developed a program for transitioning patients with diabetes from the pediatric to adult clinic and is studying the effects of this program on health outcomes.
