Download Bacteremia and Endocarditis

Bacteremia and
Endocarditis
September 26th, 2005
Blood Cultures
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2 sets, >15 minutes apart
Now continuous monitoring
No entry of bacteria for
monitoring
lysis-centrifugation system
(Isolator) used for either routine
bacteria, fungi, mycobacteria, or
fastidious organisms such as
Bartonella or Brucella
 Labor intensive
 More contamination
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Technique
 70% alcohol, followed by
tincture of iodine (1 minute) or
povidone iodine (2 minutes).
 septum of the culture bottle or
tube need only be wiped with
70% alcohol
 transported to the laboratory
promptly
 volume of blood cultured and
the number of sets drawn are
particularly important
 current recommendations for
adults are to draw at least two
separate blood cultures totaling
30 to 40 ml of blood.
 Separate venipunctures should
be performed to help interpret
cultures that contain skin flora
Classification of Bacteremia
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Community-acquired
Nosocomial
Healthcare-associated Bacteremia
indwelling catheters
 HD
 receiving other outpatient therapy
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Wound care
nursing home residents
Friedman: Ann Intern Med, Volume
137(10).November 19, 2002.791-797
Martin: N Engl J Med, Volume 348(16).April 17, 2003.1546-1554
Infectious Endocarditis (IE)
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Traditional risk factor of RHD decreasing, newer factors increasing
Emergence of enterococci and Staph, particularly MRSA and VRE, also
VISA and VRSA
Viridans Strep now emerging MDR strains
Subtypes
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native value IE
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prosthetic valve IE
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RHD
MVP (10-100 fold increased risk if regurgitant)
Degenerative/inherited valve disorders
Early (Staph epi, Staph aureus)
Late (Strep, HACEK)
IE in intravenous drug users
Healthcare-associated IE
nosocomial IE
Microbiologic Etiology
in 1779 Patients With
Definite Endocarditis
From: Fowler: JAMA, Volume
293(24).June 22/29, 2005.3012–3021
Trends in Age- and Sex-Adjusted Incidence Rates of Infective Endocarditis Caused by Staphylococcus
aureus and Viridans Group Streptococci From 1970 to 2000 in Olmsted County, Minnesota
From: Tleyjeh: JAMA, Volume 293(24).June 22/29, 2005.3022–3028
IDU-associated IE
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median age 30 and 40 yrs
up to 40% of cases of IE in San Francisco
tricuspid valve > 50% of cases, aortic in 25%, mitral in
20%, mixed right- and left-sided IE unusual.
injections of impure drugs and particulates might
produce microtrauma to the tricuspid leaflets,
facilitating microbial colonization
20–40% of IDU with IE have pre-existing cardiac
lesions
Bacteria often originate from the skin
streptococci and others also seen
Pseudomonas aeruginosa and fungi may produce severe IE.
mortality of IE higher in patients who have AIDS
Nosocomial IE
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The incidence is increasing.
Many patients have other debilitating underlying
< 50% had obvious cardiac predisposing factors
In most circumstances a potential source of bacteremia could be
identified, (lines, procedures)
staphylococci and enterococci most common
other organisms-Gram-negative bacteria and fungi.
Right-sided IE is increasingly recognized in association with
central venous lines, pulmonary artery catheters and pacemakers.
procedures that produce transient bacteremia represent risk in
hospitalized patients, especially when the circulating organism is
S. aureus.
mortality of nosocomial IE is greater than 50%.
Culture-negative IE
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HACEK
Haemophilus spp.
 Actinobacillus actinomycetemcomitans
 Cardiobacterium hominis
 Eikenella corrodens
 Kingella kingae
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Nutritionally-deficient Strep spp.
Fastidious GNR
Culture-negative IE
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Coxiella burnetii (Q fever)
Brucella
Bartonella quintana
Chlamydia
Tropheryma whippelii
Pathogenesis
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Basic lesion is endothelial
damage
IE pathogens possess surface
ligands that mediate
attachment to extracellular
matrix proteins of the host
(MSCRAMMs)
direct invasion of endothelial
cells may also occur
Transient bacteremias occur
during chewing,
toothbrushing and other
normal activities, and from
more invasive procedures
Microscopic appearance of a vegetation from a patient suffering
mitral valve infective endocarditis due to Streptococcus sanguis.
The purple area represents clusters of streptococci packed within a
fibrin-platelet meshwork. Professional phagocytes are essentially
absent from the lesion.
IE Prophylaxis
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Goals:
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No controlled studies
Regimens used in humans are based upon their proven efficacy in animal models of IE
successful prophylaxis does not require bactericidal antibiotics
Antiseptic mouth rinses applied immediately prior to dental procedures may reduce
the incidence or magnitude of bacteremia
Cover most probable pathogens circulating in the blood during a given procedure
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identification of patients at risk;
determination of the procedures or circumstances that may result in bacteremias;
choice of an appropriate antimicrobial regimen; and
balancing of the known risks against the possible benefits of intervention.
oropharyngeal manipulation-streptococci
gastrointestinal or urogenital manipulations, it should be aimed at enterococci (plus results
of a preprocedure urine culture)
skin or other infected lesions-staphylococci
If already on antibiotics, choose another class.
Cardiac Conditions Associated With Endocarditis
Endocarditis prophylaxis recommended
High-risk category
Prosthetic cardiac valves, including bioprosthetic
and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease (eg,
single ventricle states, transposition of the great
arteries, tetralogy of Fallot)
Surgically constructed systemic pulmonary shunts
or conduits
Moderate-risk category
Most other congenital cardiac malformations (other
than above and below)
Acquired valvar dysfunction (eg, rheumatic heart
disease)
Hypertrophic cardiomyopathy
Mitral valve prolapse with valvar regurgitation
and/or thickened leaflets1
Endocarditis prophylaxis not recommended
Negligible-risk category (no greater risk than the
general population)
Isolated secundum atrial septal defect
Surgical repair of atrial septal defect, ventricular
septal defect, or patent ductus arteriosus (without
residua beyond 6 mo)
Previous coronary artery bypass graft surgery
Mitral valve prolapse without valvar regurgitation
(risk only increased if prolapse and regurg)
Physiologic, functional, or innocent heart murmurs1
Previous Kawasaki disease without valvar
dysfunction
Previous rheumatic fever without valvar
dysfunction
Cardiac pacemakers (intravascular and epicardial)
and implanted defibrillators
AHA, 1997
Diagnosis
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Duke criteria
Classic exam/lab findings
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Osler nodes
Splenomegaly
Janeway lesions
Microscopic hematuria
Elevated ESR and CRP
Septic pulmonary emboli (right)
Classic findings may be absent
Repeating TEE 7 to 10 days after an initial "negative" result may
be advisable
Posttreatment echocardiography is recommended
Peripheral Stigmata of IE
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Osler node=small, raised,
tender cutaneous lesion,
usually on the pads of fingers
or toes (vasculitic)
Janeway lesion=flat, painless
small hemorrhages with a
slightly nodular appearance
that occur on the palms and
soles (septic emboli)
Splinter hemorrhages
Petechiae
Roth spots=hemorrhage in
the retina with a white center
Definite infective endocarditis
Pathological criteria
Microorganisms demonstrated by culture or histological
examination of a vegetation, a vegetation that has embolized, or an
intracardiac abscess specimen
Pathological lesions; vegetation or intracardiac abscess confirmed
by histological examination showing active endocarditis
Clinical criteria
2 major criteria; or
1 major criterion and 3 minor criteria; or
5 minor criteria
Possible IE
1 major criterion and 1 minor criterion; or
3 minor criteria
Rejected
Firm alternative diagnosis explaining evidence of IE; or
Resolution of IE syndrome with antibiotic therapy for <4 days; or
No pathological evidence of IE at surgery or autopsy, with antibiotic
therapy for <4 days; or
Does not meet criteria for possible IE as above
Major criteria
Blood culture positive for IE
Typical microorganisms consistent with IE from 2
separate blood cultures: Viridans streptococci, Streptococcus
bovis, HACEK group, Staphylococcus aureus; or communityacquired enterococci in the absence of a primary focus; or
Microorganisms consistent with IE from persistently
positive blood cultures defined as follows: At least 2 positive
cultures of blood samples drawn >12 h apart; or all of 3 or a
majority of 4 separate cultures of blood (with first and last
sample drawn at least 1 h apart)
Single positive blood culture for Coxiella burnetii or
anti–phase 1 IgG antibody titer >1:800
Evidence of endocardial involvement
Echocardiogram positive for IE: defined as follows:
oscillating intracardiac mass on valve or supporting
structures, in the path of regurgitant jets, or on implanted
material in the absence of an alternative anatomic
explanation; or abscess; or new partial dehiscence of
prosthetic valve; new valvular regurgitation (worsening or
changing or preexisting murmur not sufficient)
Minor criteria
Predisposition, predisposing heart condition, or IDU
Fever, temperature >38°C
Vascular phenomena, major arterial emboli, septic
pulmonary infarcts, mycotic aneurysm, intracranial
hemorrhage, conjunctival hemorrhages, and Janeway’s
lesions
Immunologic phenomena: glomerulonephritis, Osler’s
nodes, Roth’s spots, and rheumatoid factor
Microbiological evidence: positive blood culture but does
not meet a major criterion as noted above* or serological
evidence of active infection with organism consistent with IE
Echocardiographic minor criteria eliminated
Surgery
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Indication
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Severe CHF (reduced mortality with surgery)
Persistent bacteremia
Certain pathogens (fungal, GNR)
Embolic events
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Large vegetation on mitral valve highest risk
Valve abscess/dehiscence
Timing
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7-fold higher risk of recurrent IE if valve replaced during
active infection
Treatment
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If using synergistic agents give them together
Day 1 is first day documented negative blood
cultures
postoperative treatment regimen should be one
that is recommended for prosthetic valve
treatment rather than one that is recommended
for native valve treatment
Start over if cultures positive
Viridans Strep
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community-acquired native valve
endocarditis in patients who are not
intravenous drug users (IDUs).
-hemolytic
S sanguis, S oralis (mitis), S salivarius, S mutans,
and Gemella morbillorum (formerly called S
morbillorum).
S anginosus group (S intermedius, anginosus, and
constellatus) aka S milleri group
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have nutritional deficiencies that hinder their growth
Gemella (morbillorum, bergeriae, sanguinis,
and hemolysans)
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tends to form abscesses and cause
hematogenously disseminated infection (eg,
myocardial and visceral abscesses, septic
arthritis, vertebral osteomyelitis).
S intermedius usually is sensitive to penicillin,
but some strains may exhibit variable
penicillin resistance.
Abiotrophia defectiva and Granulicatella species
(G elegans, G adiacens, G paraadiacens, and G
balaenopterae; formerly known as nutritionally
variant streptococci),
share some physiological
characteristics with nutritionally variant
streptococci
should be treated with more aggressive
combination therapy
S bovis expresses the group D antigen,
but it can be distinguished from group
D Enterococcus by appropriate
biochemical tests.
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should undergo colonoscopy
Treatment
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Native valve, highly susceptible viridans Strep or
Strep bovis (MIC <.12)
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Aq Pen G x 4 wks
Rocephin x 4 wks
Aq Pen G + gent x 2 wks (synergy)
Rocephin + gent x 2 wks
Vanc x 4 wks
Viridans Group Streptococci and S bovis With
Penicillin MIC >0.12 to 0.5 µg/ml
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Aq pen or Rocephin x 4 wks + gent 1st 2 wks (single daily
dose)
vancomycin
Treatment
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A defectiva, Granulicatella species, and Gemella species and a microorganism with
an MIC to penicillin >0.5 µg/mL should be treated with a regimen that is
recommended for enterococcal endocarditis
prosthetic valves should receive 6 weeks of therapy with penicillin or
ceftriaxone with or without gentamicin for the first 2 weeks
S pneumoniae, S pyogenes, and Groups B, C, and G Streptococci
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highly penicillin-susceptible S pneumoniae should receive 4 weeks of antimicrobial
therapy with penicillin, cefazolin, or ceftriaxone
High-dose penicillin or a third-generation cephalosporin can be used in patients
with penicillin-resistant infection and without meningitis
If the isolate is resistant (MIC 2 µg/mL) to cefotaxime, then the addition of
vancomycin and rifampin should be considered.
Consider gentamicin for at least the first 2 weeks of a 4- to 6-week course of
antimicrobial therapy for group B, C, and G strep (relatively pen res)
Aq pen G for Gp A
Coagulase-negative Staph (CoNS)
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Usually associated with
PVE
Occasionally native valve,
usually damaged
More indolent than
Staph aureus
Staph lugdinensis more
virulent
Staph aureus endocarditis
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Nosocomial bacteremia
previously thought to be
lower risk for endocarditis
health care–associated
infection was the single most
common form of S aureus IE
health care–associated IE is
distinguished by a relative
infrequency of classic clinical
stigmata of IE
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S aureus bacteremia
associated with health care
has increased among
hospitalized patients and
among those receiving
outpatient medical therapy
MRSA in both hospital and
community increased
dramatically
implanted medical devices
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prosthetic heart valves
grafts
hemodialysis catheters
pacemakers
Endocarditis
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Factors associated with Staph aureus SBE:
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Native valve
Hemodialysis
Invasive procedures
Other chronic disease
Multiple pulmonary emboli
Intravascular device source
Tricuspid
Healthcare-associated
IDU-associated
Persistent bacteremia, emboli requiring surgery
Complications including stroke, other emboli, death
Factors associated with non-Staph aureus SBE
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Aortic valve
Prosthetic valve
Congenital heart disease
Dental work
Symptoms >1 month
International Collaboration on Endocarditis-Prospective Cohort Study from June 2000 to December 2003.
Figure. In-Hospital Mortality Rates Among Patients With Health Care–Associated
Staphylococcus aureus Endocarditis. Includes both nosocomial and nonnosocomial
health care–associated infections, community-acquired injection drug use–associated
S aureus endocarditis, and community-acquired noninjection drug use–associated S
aureus endocarditis by geographic region.
From: Fowler: JAMA, Volume 293(24).June 22/29, 2005.3012–3021
Table 4. Clinical Characteristics and Outcomes of 424 Prospectively Identified Patients With Definite Endocarditis Due to
Methicillin-Susceptible and Methicillin-Resistant Staphylococcus aureus*
From: Fowler: JAMA, Volume 293(24).June 22/29, 2005.3012–3021
Treatment
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Staph aureus IDU (right)
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parenteral ß-lactam +/- gent x 2 wks (uncomplicated)
Oral also effective (Cipro + rifampin x 4 wks)
Vancomycin requires 4 wks
Staph aureus non-IDU
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Beta lactam x 4-6wks, gent 1st few days if fulminant
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Faster clearance of bacteremia
Not better mortality
Vanc only if anaphylactoid history to PEN
Clinda not recommended, high relapse rate
Consider desensitizing or daptomycin.
PVE add gentamicin for 2 wks, plus rifampin full 6 wks
Treatment
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MRSA
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Vancomycin (same gent caveats, plus possible increased
ototox)
Linezolid
Synercid
Daptomycin
PVE add gentamicin for 2 wks, plus rifampin full 6 wks
CoNS
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Assume meth-resistant
Vancomycin for 6 wks
PVE add gentamicin for 2 wks, plus rifampin full 6 wks
Enterococci
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Group D
test MICs to penicillin and vancomycin and for high-level resistance to
gentamicin and streptomycin
trough antibiotic concentration in serum must be maintained above the
MIC.
relatively resistant to penicillin, ampicillin, and vancomycin.
requires the synergistic action of penicillin, ampicillin, or vancomycin
in combination with either gentamicin or streptomycin.
relatively impermeable to aminoglycosides.
cell wall–active agents raise the permeability of the enterococcal cell so
that a bactericidal effect can be achieved
If resistant to high concentrations of an aminoglycoside (500 µg/mL
of gentamicin or 1000 µg/mL of streptomycin), then the combination
of an aminoglycoside with the cell wall–active agent will not result in
bactericidal activity, nor will it predictably produce a microbiological
cure.
<3 months’ duration of symptoms 4 weeks; >3 months’ duration of
symptoms 6 weeks
PVE 6 wks
Enterococci
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Beta lactam resistant-vancomycin
VRE
vancomycin-resistant E faecalis and E
gallinarum/casseliflavus usually are penicillin susceptible
 Linezolid
 Daptomycin
 Synercid (faecium only)
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HACEK
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fastidious Gram-negative
bacilli (grow slowly )
Haemophilus parainfluenzae, H
aphrophilus, H paraphrophilus,
H influenzae, Actinobacillus
actinomycetemcomitans,
Cardiobacterium hominis,
Eikenella corrodens, Kingella
kingae, and K denitrificans
5%-10% of native valve
community-acquired IE in
non IDUs
hold blood cultures for 2
wks in patients suspected of
having IE.
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ß-lactamase–producing
strains increasing
should be considered
ampicillin resistant
susceptible to ceftriaxone,
ampicillin-sulbactam, and
fluoroquinolones.
limited published clinical data
duration of therapy for
native valve infection should
be 4 weeks
prosthetic valve 6 weeks
bacteremia caused by
HACEK is highly suggestive
of endocarditis
Other Gram-negatives
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IDU, prosthetic valve, and cirrhosis are
risk factors
Enterobacteriaceae
 Salmonella species have an affinity
for abnormal cardiac valves
 Valvular perforation, atrial
thrombi, myocarditis, and
pericarditis are common
 Salmonellae also may produce
endarteritis in aneurysms of major
vessels. Other Enterobacteriaceae,
including
 E coli and Serratia marcescens, may
rarely cause endocarditis
 S marcescens endocarditis typically
develops in IDUs.
 Left-sided disease, large
vegetations, and involvement
of normal valves
 mortality rates are 70%.
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Cardiac surgery is a
cornerstone of treatment
Combinations of pens/cephs
and aminoglycosides have been
shown to be synergistic
E. coli or Proteus mirabilis, a
combination of either
ampicillin or penicillin or a
broad-spectrum ceph +
aminoglycoside, usually gent
Endovascular Salmonella
infections also may respond to
third-generation
cephalosporins.
combination of a thirdgeneration cephalosporin and
an aminoglycoside (either
gentamicin or amikacin) is
recommended for Klebsiella
endocarditis.
Pseudomonas
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Nearly all IDUs
Associated with tripelennamine and
pentazocine ("T’s and blues")
mean age 30 years
affects normal valves
Major embolic phenomena, inability to
sterilize valves, neurol complications
(53%), ring and annular abscesses,
splenic abscesses, bacteremic relapses,
and rapidly progressive CHF are
common.
many authorities recommend early
surgery for left-sided Pseudomonas
endocarditis
High-dose regimens of
antipseudomonal penicillins combined
with aminoglycosides are used
minimum 6 weeks
Medical therapy works in P aeruginosa
IE involving the right side of the heart
in 50% to 75%
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partial tricuspid valvulectomy or
"vegetectomy“ if failure
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quinolones (in combination with
an aminoglycoside) appear
promising, based on favorable
results in animal models and
humans, but development of
stepwise resistance during therapy
may limit the efficacy
ceftazidime-tobramycin is
preferred over aztreonamtobramycin
7 cases of P aeruginosa endocarditis
have been successfully treated with
imipenem plus an aminoglycoside
potential for the development of
resistance exists with any of these
regimens.
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Culture-negative IE
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Why?
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Antibiotics prior
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Fastidious organism (Rocephin + gent +doxy)
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Cover your bases i.e. Staph, Strep, enterococcus
Bartonella
Brucella
Q fever
Whipple’s
Chlamydia
Not infectious
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Marantic
Autoimmune
Neoplastic
Fungal IE
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often a complication of medical
and surgical advances
usually have multiple predisposing
conditions (cardiovascular devices,
prosthetic cardiac valves and
central venous catheters)
mortality rates for fungal
endocarditis are very high.
survival rate for patients with
mold-related endocarditis is <20%.
Candida and Aspergillus species
account for the large majority
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Historically, is an indication for
surgical replacement of an infected
valve.
amphotericin B, a fungicidal agent,
is the drug of choice
antifungal therapy usually is given
for 6 weeks.
long-term (lifelong) suppressive
therapy with an oral azole
Predisposing Conditions in FE
From: Pierrotti: Chest, Volume 122(1).July 2002.302-310
Complications of FE
From: Pierrotti: Chest, Volume 122(1).July 2002.302-310
Complications of IE
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Cardiovascular
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CHF
MI
Mycotic aneurysms
Embolic
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CVA
Peripheral
Organ
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Bowel
Peripheral arteries
spleen