Infectious Disease Consult Service

Case Presentation

October 10, 2007
Sarah Hubbell, MS4

History

 30-year-old African American female, with
PMH significant for congenital heart disease
and previous episodes of endocarditis,
presents with four day history of chills, fevers
up to 103 F, myalgias, and dyspnea
(increased over baseline).

History continued

 On the day prior to admission, she had
emesis x 1, diarrhea x 2, nausea, and clear
rhinorrhea. Admits to mild frontal headaches
that worsen with chills, and occasional sharp
pain over her sternum. The sternal pain
seems to resolve with resolution of chills.
She took Tylenol and TheraFlu with some
relief.

Past Medical History

 Congenital cyanotic heart disease (ASD, VSD,
pulmonary atresia), s/p Waterston shunt as a
neonate, and Blalock Taussig shunt at age 12. Most
recent echo (3/2006) showed EF 45-50%.
 Right basal ganglia abscess in 2005, s/p drainage.
Culture negative.
 Streptococcus viridans endocarditis x 3, last episode
in 2003.
 Paroxysmal atrial fibrillation since 1997.
 CVA, 1999 – related to line infection. No residual
defects.

.Brief cardiac detour…  Waterston shunt: creation of a narrow opening between the ascending aorta and subjacent right pulmonary artery to increase pulmonary circulation.  Blalock Taussig shunt: anastomosis of right or left subclavian artery to the right or left pulmonary artery – directing blood from the systemic circulation to the lungs.

jpg .Blalock-Taussig Shunt  The left subclavian artery is divided and connected to the left pulmonary artery. View illustration at: http://images.com/heart/images/article/i14Blalock.healthcentersonline. This allows blood to flow to the lungs to pick up oxygen.

lung. Denies tobacco. Aunt with enlarged heart. though her daughter did develop a dry cough after her illness began. leukemia. alcohol. including breast. She stays at home. or drug use. No recent travel or sick contacts.Social/Family History  Lives with 1 year-old daughter and fiancé. HIV negative in 2005.  Father and aunt have HTN. Family history of multiple cancers. melanoma. .

Has tolerated cephalosporins and vancomycin in the past.5 mg po daily – ASA 81 mg po daily  Allergies: – Penicillin  rash.Medications  Home medications: – Furosemide 20 mg po daily – Lisinopril 5 mg po daily – Digoxin 0. Question of ceftriaxone-induced rash at Wake. .125 mg po daily – Metoprolol ER 12.

hematuria. sinus pain. arthralgias. cough. altered mental status. dysuria. back pain. sore throat. skin infections. .ROS  Denies neck soreness/pain. abdominal pain. recent dental work. Has had some palpitations.

RR 18-20. HR 111-168. O2 68-89% on non- rebreather mask. clear nares.  HEENT: Sclerae anicteric. nontender. full ROM. no JVD. PERRL. BP 110-126/38-57. EOMI.4. .  General: Awake. struggling to breathe.Physical Exam  Vital Signs: Tm 103. in distress. oropharynx without erythema or exudates. alert.  Neck: No masses.

 CV: Irregularly irregular.  Respiratory: Decreased breath sounds. III/VI systolic murmur best heard on left sternal border. Scattered mild rales and rhonchi. . Normoactive bowel sounds. particularly on the left. tachycardic. or axillary adenopathy.  Abdomen: Soft. increased work of breathing. supraclavicular. no masses. non-distended.Physical Exam continued  Lymph: No cervical. non-tender.

 Psych: Oriented x 3 with normal mental status.  Skin: No rashes or lesions. cranial nerves 2-12 intact.Physical Exam continued  MSK: Normal tone and strength. Osler’s nodes. Appropriate mood and affect. Janeway lesions. No splinter hemorrhages. + cyanosis of hands and feet. No focal deficits.  Neuro: Full sensory and motor function. .

6  Urine pregnancy negative  U/A 13 RBC’s.9.8. nitrite neg. 6 WBC’s.3. AST 67.2.5. tot. leuk esterase neg.Admission Labs  WBC 10. Hct 54. no acute changes. 2+ bacteria  Albumin 2. BUN 14. alk phos 78  CK 337.2.2. t bili 4. MB 2. Plt 133  Na 134. Hgb 18. K 3. ALT 54.05  CXR: moderate cardiomegaly. trop I 0.7. Gluc 109. no opacities in lungs. Bicarb 20. Cr 0. Ca 8. protein 5. + evidence of prior median sternotomy . Cl 106.

Treated there with vancomycin. and levofloxacin. aztreonam. ceftriaxone (discontinued after a rash appeared). .Management  Given ceftriaxone and vancomycin in the ED and admitted to Wake MICU on 10/4.  Transferred here from Wake at patient’s request. as her primary cardiologist is at UNC.

Discussion .

And the blood cultures grew out…  Gram positive cocci in chains .

Granulicatella adiacens Nutritionally Variant Streptococci (NVS) .

.  Found as normal flora of the upper respiratory. particularly Staph aureus.Nutritionally Variant Streptococci  First described in 1961 as fastidious gram-positive bacteria that grow as satellite colonies around other bacteria. particularly for neutropenic patients and patients with underlying hematological malignancies.  NVS can also cause primary bacteremia.  Like other bacterial residents of the oral cavity. and gastrointestinal tracts of humans. NVS have been identified as an important cause of endocarditis. urogenital.

Other infections  There are reports of NVS being isolated from patients with: – Osteomyelitis – Otitis media – Wound infections – Brain abscesses – Septic arthritis – Endophthalmitis – Meningitis. – Pancreatic abscess .

defectiva.  In 1995. . defectivus were proposed as new designations in 1989. studies using 16S ribosomal RNA sequence analysis showed that these two species were actually not related to other members of the Streptococcus genus. adiacens and A. as A. defectiva to the new genus Granulicatella. the genus Abiotrophia was taxonomically revised. it was found that NVS fit the genus description of Streptococcus but were taxonomically unrelated to other viridans group organisms.  In 2000. adjacens and S. They were placed in a new genus Abiotrophia. reclassifying all species except A.A little history…  On the basis of DNA-DNA hybridization studies. The names S.

defectiva   A.For the medical student…  Streptococcus adjacens and S. . everything else goes to genus Granulicatella. defectivus  Abiotrophia adiacens and A. defectiva stays the same.

. NVS is believed to have accounted for most cases of culture- negative endocarditis. Historically.NVS and Endocarditis  Nutritionallyvariant streptococci cause approximately 5% of cases of bacterial endocarditis. primarily occurring in the setting of valvular disease and progressing indolently.  NVS endocarditis resembles that of viridans.

. but commonly embolize (33% vs. 11% for other oral species).  Two dimensional echocardiography visualizes vegetations in 64% of patients.NVS and Endocarditis  Vegetations are comparatively small.

 G. . defectiva).  The higher infectivity of G. elegans: A. defectiva has been attributed to their capacity to bind to cardiac valvular tissue. adiacens: G.NVS and Endocarditis  Granulicatella adiacens and Abiotrophia defectiva comprise the vast majority of NVS causing endocarditis (57% and 41% respectively) with Granulicatella elegans causing a small number (2%). adiacens and A. adiacens is the NVS found in the greatest numbers in the oropharynx (ratio is 11:1:1 for G.

. mortality rates have been reported as 14% and 5% respectively.  For NVS and viridans streptococci endocarditis.NVS and Endocarditis  A comparison between patients with NVS endocarditis and patients with infection caused by other oral species revealed a higher mortality rate and more frequent complications of embolization for NVS.

In the micro lab…  NVS are recognized by their requirement for pyridoxal or thiol group supplementation for growth.  Colonies of NVS are small and are either non-hemolytic or α-hemolytic on blood agar. .

 Alternatively.Micro lab continued  In subculture.001% pyridoxal or 0. the subculture plate can be cross-streaked with S. solid media must be supplemented with 0. . aureus to provide these factors and permit growth as satellite colonies.01% l-cysteine to sustain growth.

Pick your treatment! .

due to increased length of time required to isolate and identify these bacteria. – Failure rate has been attributed in part to delay in starting therapy. and bacteriological failure rates of 41% have been noted.Difficulties in treating NVS  Relapse rates are approximately 17%. .

. Approximately 33% to 65% of strains are relatively resistant.  NVS are less susceptible in vitro to penicillin than are other streptococci. and some isolates are highly resistant.Difficulties in treating NVS  The growth rate of NVS is significantly slower than viridans. so longer treatment durations are suggested.

 NVS has demonstrated 100% sensitivity to both vancomycin and rifampin.  Rifampin has been observed to produce synergistic bactericidal activity when given in combination with vancomycin in time-kill studies. .Treatment  Synergy between penicillin or vancomycin in combination with an aminoglycoside is observed both in vitro and in experimental animal models of endocarditis.

. chloramphenicol.  Most NVS are also susceptible to clindamycin. and erythromycin  The activity of the cephalosporins and tetracyclines are variable.Treatment continued  Aminoglycosides show variable in vitro activity against NVS. High-level resistance has not been reported.

Even with this regimen.  It is recommended that all patients with NVS endocarditis be treated with long-term combination therapy for 4 to 6 weeks. however. the rates of bacteriologic failure and relapse are high.Treatment continued  In vitro antimicrobial susceptibility testing of NVS is beyond the scope of many routine clinical laboratories. .

and was used successfully in case reports. Vancomycin. .Our treatment selection  Antibiotics we picked: Gentamicin. and Rifampin – This triple combination has been indicated as being the most synergistic in animal models.

 TEE results: large ASD. . atretic appearing tricuspid and pulmonic valves. perimembranous VSD. and she remained afebrile. degenerative mitral valve disease.Hospital Course for our patient  Respiratorystatus improved while here. No vegetations or abscesses were noted. mild TR. trivial MR.

Hospital Course continued  Cardiac MRI for Morphology revealed: – Low normal LV systolic function – Functional Waterston' s shunt with flow from the ascending thoracic aorta to the right pulmonary artery – Probable left pulmonary artery atresia – Atrial septal defect – Left subclavian artery atresia with recanalization within the axilla via subcostal arterial network – No evidence for myocardial scar or infiltration – The Blalock-Taussig shunt could not be identified .

.Hospital Course continued  Blood cultures drawn here have remained negative.  Isolate of NVS from Wake is being prepared for shipping to our lab for sensitivity testing.

 She will follow up with ID clinic in 2 weeks. at which time sensitivities of the Wake specimen are likely to be ready.  She’s doing well! . rifampin.Discharge Plan  The patient will be discharged on vancomycin. and gentamicin for treatment of bacteremia/endovascular infection.

Prosthetic valve endocarditis from Granulicatella adiacens (nutritionally variant streptococci). Nutritionally variant streptococci.  Mandell. A case of endocarditis due to Granulicatella adiacens. & Dolin: Principles and Practice of Infectious Diseases. Journal of Infection (2005)51.Resources  Jeng A.  Ruoff KL. Clinical Microbiology and Infection (2003)9(6). Bennett.  Senn L. Book available online via the UNC-CH Libraries  Perkins A. Bloodstream and endovascular infections due to Abiotrophia defectiva and Granulicatella species. . e125-e129. et al. Clinical Microbiology Review. 1991 Apr. 576– 577. et al. 6th ed. et al. BMC Infectious Diseases 2006.4(2):184-90. 6:9.

Search PubMed  Nutritionally Variant Streptococci – Case Reports – Reviews – Differential Diagnosis – Drug Therapy .