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.
Blalock-Taussig Shunt

The left subclavian artery is divided and

connected to the left pulmonary artery. This
allows blood to flow to the lungs to pick up
oxygen.

View illustration at:

http://images.healthcentersonline.com/heart/images/article/i14Blalock.jpg
Social/Family History

Lives with 1 year-old daughter and fianc.

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

Home medications:
Furosemide 20 mg po daily
Lisinopril 5 mg po daily
Digoxin 0.125 mg po daily
Metoprolol ER 12.5 mg po daily
ASA 81 mg po daily
Allergies:
Penicillin rash. Has tolerated cephalosporins
and vancomycin in the past. Question of
ceftriaxone-induced rash at Wake.
ROS

Denies neck soreness/pain, sinus pain, sore

throat, dysuria, hematuria, back pain, recent
dental work, abdominal pain, arthralgias, skin
infections, cough, altered mental status. Has
had some palpitations.
Physical Exam

Vital Signs: Tm 103.4, HR 111-168, RR 18-20,

BP 110-126/38-57, O2 68-89% on non-
rebreather mask.
General: Awake, alert, in distress, struggling to
breathe.
HEENT: Sclerae anicteric, PERRL, EOMI,
oropharynx without erythema or exudates, clear
nares.
Neck: No masses, nontender, full ROM, no JVD.
Physical Exam continued

Lymph: No cervical, supraclavicular, or axillary

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

MSK: Normal tone and strength.

Neuro: Full sensory and motor function,
cranial nerves 2-12 intact. No focal deficits.
Skin: No rashes or lesions, + cyanosis of
hands and feet. No splinter hemorrhages,
Janeway lesions, Oslers nodes.
Psych: Oriented x 3 with normal mental
status. Appropriate mood and affect.
Admission Labs

WBC 10.3, Hgb 18.2, Hct 54, Plt 133

Na 134, K 3.2, Cl 106, Bicarb 20, BUN 14, Cr 0.9, Gluc 109, Ca
8.6
Urine pregnancy negative
U/A 13 RBCs, 6 WBCs, nitrite neg, leuk esterase neg, 2+
bacteria
Albumin 2.5, tot. protein 5.8, t bili 4.7, ALT 54, AST 67, alk phos
78
CK 337, MB 2.2, trop I 0.05

CXR: moderate cardiomegaly, no acute changes, no opacities

in lungs, + evidence of prior median sternotomy
Management

Given ceftriaxone and vancomycin in the ED

and admitted to Wake MICU on 10/4.
Treated there with vancomycin, ceftriaxone
(discontinued after a rash appeared),
aztreonam, and levofloxacin.
Transferred here from Wake at patients
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)
Nutritionally Variant Streptococci

First described in 1961 as fastidious gram-positive

bacteria that grow as satellite colonies around other
bacteria, particularly Staph aureus.
Found as normal flora of the upper respiratory,
urogenital, and gastrointestinal tracts of humans.
Like other bacterial residents of the oral cavity, NVS
have been identified as an important cause of
endocarditis.
NVS can also cause primary bacteremia, particularly
for neutropenic patients and patients with underlying
hematological malignancies.
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
A little history

On the basis of DNA-DNA hybridization studies, it

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

Streptococcus adjacens and S. defectivus

Abiotrophia adiacens and A. defectiva
A. defectiva stays the same, everything else
goes to genus Granulicatella.
NVS and Endocarditis

Nutritionallyvariant streptococci cause

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

Vegetations are comparatively small, but

commonly embolize (33% vs. 11% for other
oral species).

Two dimensional echocardiography

visualizes vegetations in 64% of patients.
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%).
The higher infectivity of G. adiacens and A. defectiva
has been attributed to their capacity to bind to
cardiac valvular tissue.
G. adiacens is the NVS found in the greatest
numbers in the oropharynx (ratio is 11:1:1 for G.
adiacens: G. elegans: A. defectiva).
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.
For NVS and viridans streptococci
endocarditis, mortality rates have been
reported as 14% and 5% respectively.
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 -hemolytic on blood agar.
Micro lab continued

In subculture, solid media must be

supplemented with 0.001% pyridoxal or
0.01% l-cysteine to sustain growth.
Alternatively, the subculture plate can be
cross-streaked with S. aureus to provide
these factors and permit growth as satellite
colonies.
Pick your treatment!
Difficulties in treating NVS

Relapse rates are approximately 17%, and

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

The growth rate of NVS is significantly slower

than viridans, so longer treatment durations
are suggested.
NVS are less susceptible in vitro to penicillin
than are other streptococci. Approximately
33% to 65% of strains are relatively resistant,
and some isolates are highly resistant.
Treatment

Synergy between penicillin or vancomycin in

combination with an aminoglycoside is
observed both in vitro and in experimental
animal models of endocarditis.
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 continued

Aminoglycosides show variable in vitro

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

In vitro antimicrobial susceptibility testing of

NVS is beyond the scope of many routine
clinical laboratories.
It is recommended that all patients with NVS
endocarditis be treated with long-term
combination therapy for 4 to 6 weeks. Even
with this regimen, however, the rates of
bacteriologic failure and relapse are high.
Our treatment selection

Antibiotics
we picked: Gentamicin,
Vancomycin, and Rifampin
This triple combination has been indicated as
being the most synergistic in animal models, and
was used successfully in case reports.
Hospital Course for our patient

Respiratorystatus improved while here, and

she remained afebrile.

TEE results: large ASD, perimembranous

VSD, degenerative mitral valve disease,
trivial MR, mild TR, atretic appearing
tricuspid and pulmonic valves. No
vegetations or abscesses were noted.
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.
Discharge Plan

The patient will be discharged on

vancomycin, rifampin, and gentamicin for
treatment of bacteremia/endovascular
infection.
She will follow up with ID clinic in 2 weeks, at
which time sensitivities of the Wake
specimen are likely to be ready.
Shes doing well!
Resources

Jeng A, et al. Prosthetic valve endocarditis from Granulicatella

adiacens (nutritionally variant streptococci). Journal of
Infection (2005)51, e125-e129.
Mandell, Bennett, & Dolin: Principles and Practice of Infectious
Diseases, 6th ed. Book available online via the UNC-CH Libraries
Perkins A, et al. A case of endocarditis due to Granulicatella
adiacens. Clinical Microbiology and Infection (2003)9(6), 576
577.
Ruoff KL. Nutritionally variant streptococci. Clinical
Microbiology Review. 1991 Apr;4(2):184-90.
Senn L, et al. Bloodstream and endovascular infections due to
Abiotrophia defectiva and Granulicatella species. BMC
Infectious Diseases 2006, 6:9.
Search PubMed

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