Staphylococcus aureus bacteremia

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Staphylococcus aureus bacteremia

• Sumathi Nambiar MD MPH
• Medical Team Leader
• Division of Anti-Infective Drug Products
• US Food and Drug Administration

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• Micrococcus, which when limited in its extent
  and activity, causes acute suppurative
  inflammation, produces, when more extensive and
  intense in its action on the human system, the
  most virulent forms of septicaemia and pyaemia

Ogston A. Micrococcus poisoning. J Anat
18821724-58.
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Epidemiology

• S.aureus is an important cause of bacteremia in
  both US and non-US hospitals.
• SCOPE project
• 1995-1998 Second most common bloodstream
  isolate 16 of hospital-acquired (HA)
  bacteremias.
• 1995-2001 9 of HA bacteremias in pediatric
  patients.
• 7-year study from a single institution in
  Switzerland 14 of all bacteremias.
• Incidence of S.aureus community-acquired (CA)
  bacteremia in Connecticut was 17/100, 000
  persons.

Edmond MB et al. CID 199929239-44
Wisplinghoff H et al. PIDJ 200322686-91
Lautenschlager S et al. CID 199316567-73
Morin CA et al. JID 20011841029-34
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Epidemiology

• Increasing incidence of S.aureus bacteremia (SAB)
  paralleled by increase in incidence of S.aureus
  infective endocarditis (IE).
• 25-40 of native valve endocarditis caused by
  S.aureus.
• 329 patients with IE at a tertiary care facility
  from 1993-1999
• 132/329 (40) due to S.aureus.
• Frequency of S.aureus IE increased from 3/30
  (10) in 1993 to 26/38 (68) in 1999.

Cabell CH et al. Arch Intern Med 200216290-94
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What makes SAB different

• Wide spectrum of clinical manifestations.
• Complications are common and often difficult to
  identify or predict.
• Difficult to standardize extent of diagnostic
  procedures.
• Overlap with infective endocarditis often
  difficult to differentiate clinically.
• Mortality remains high.
• Treatment issues
• Resistance
• Optimum length of therapy

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Risk factors for SAB

• Intravascular catheters
• Hemodialysis
• Intravenous drug use
• Underlying illnesses
• Diabetes mellitus
• Immunosuppression

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Classification of SAB

• Community vs. Hospital acquired
• Primary vs. Secondary
• Complicated vs. Uncomplicated

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Source of SAB

• Frequency of identification of a primary focus
  for SAB varies among studies.
• depends upon type of investigations done
• presence or absence of an intravascular catheter
• population of IVDU versus non-IVDU.
• Community vs. hospital acquired
• On an average no focus is identified in about 20
  of cases.

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Jensen AG. Journal Hospital Infection
20025229-36
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Community vs. Hospital acquired

• Retrospective study of 105 cases with SAB two
  distinct populations described

Group 1 (n63) Group 2 (n42)
Apparent primary focus No apparent primary focus
Hospital-acquired disease Community-acquired disease
Older Younger
Significant underlying illnesses IVDU
Secondary foci less likely 2 had IE Secondary foci more likely 24 had IE
Nolan CM, Beaty HN. Am J Med 1976 60495-500
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Community-acquired SAB

• Patients with CA-SAB are more likely to have
• Unknown portal of entry
• Metastatic disease
• Poorer prognosis
• Frequency of CA-SAB differs between studies.
• Positive culture within 48 hours some have used
  72-96 hours.
• 48h cut off 131/278 (47) CA-SAB.
• Prior contact with healthcare system.
• 120/192 (62) patients with CA-SAB had prior
  healthcare contact.

Jensen AG et al. Arch Intern Med
200216225-32 Morin CA et al. JID
20011841029-34
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Complicated vs. Uncomplicated SAB

• Definitions of complicated SAB
• Focus of infection not identified/non-removable.
• Metastasis, deep-seated infections or
  complications.
• Attributable mortality, infection extension or
  metastasis, embolic stroke, or recurrent S.aureus
  infection
• Risk factors for complicated SAB
• Positive blood culture at 48-96 hours
• Community acquisition
• Skin findings suggesting acute systemic infection
  
• Persistent fever at 72 hours

Fowler et al. Arch Intern Med 20031632066-72
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SAB and Catheters

• Hospital and CA-SAB increasingly associated with
  intravascular catheters.
• Catheter usually considered the focus
• No evidence of alternate source and
• Evidence of inflammation/infection at the
  catheter insertion site or
• Catheter tip culture positive for S.aureus
• In the absence of catheter microbiologic
  criteria, often a diagnosis of exclusion.

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SAB and Catheters

• SAB from 1980-83 and 1990-93 compared
• 1980-83 25 of HA-SAB were intravascular
  device-related. No documented catheter-related
  CA-SAB.
• 1990-93 56 of HA-SAB and 22 of CA-SAB
  associated with intravascular devices.
• 1994-1999Intravenous catheter was focus in
  363/724 (50) patients with SAB.

Steinberg et al. CID199623255-9 Fowler et al.
Arch Intern Med 20031632066-72
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SAB and Infective Endocarditis

• Incidence of IE in SAB patients varies from
  6-64 depends on population and extent of
  evaluation.
• Predicted by clinical characteristics
• Community-acquired disease
• Absence of a primary focus of infection
• Evidence of metastatic disease
• IE can occur in patients with HA-SAB, presence of
  primary focus, and in non IVDU.
• Of 59 patients with S.aureus IE, 46 had HA-SAB.
• 76 non-IVDU SAB patients 59 had portal of
  entry, 13/59 (22) had IE.

Fowler et al. CID 199928106-114 Miriamanoff
et al. Arch Intern Med 19821421311-1313
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SAB and Infective Endocarditis

• IE is often missed based on clinical findings
  only.
• A 10-year study from Denmark found that IE was
  missed clinically in over half of the 152
  pathologically confirmed IE due to S.aureus.
• Among 103 patients with SAB, 26 had IE
• Clinical evidence was seen in only 7 patients
  five had peripheral emboli and two had new
  murmurs.
• TEE identified vegetations in 22 patients,
  abscess in 2, perforation and new regurgitation
  in one each.

Røder et al. Arch Intern Med 1999159462-469 Fo
wler et al. JACC 1997301072-8
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Risk factors for S.aureus IE

• Native valve disease
• Rheumatic heart disease
• Structural abnormalities such as mitral valve
  prolapse, bicuspid aortic valve
• Degenerative disease such as aortic valve
  sclerosis
• Congenital heart disease
• Prosthetic valve
• Intravenous drug use
• History of prior IE
• Community acquisition

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Metastatic Disease

• Frequency of metastatic complications varies.
• Retrospective study of 281 patients with SAB
• 27 developed metastasis.
• Joints (36), kidneys (29), CNS (28), skin
  (16), and intervertebral disc (15).
• 50 had more than one metastatic site.
• 4-year prospective study of 68 patients with
  SAB
• 53 had metastatic foci.
• Comprehensive diagnostic monitoring including
  x-ray, echocardiography, bone/leukocyte
  scintigraphy.

Lautenschlager S et al. CID 199316 567-73
Ringberg H et al. Infection 200028132-6
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Metastatic Disease Risk factors

• Community-acquired bacteremia
• Primary SAB
• Underlying cardiac valvular disease
• Presence of prosthetic devices
• Persistent bacteremia
• Of 104 patients with SAB, metastasis developed in
  59 with positive blood culture gt 24 hours after
  starting effective therapy versus 17 in those
  without sustained bacteremia.

Lesens O et al. J Infect 200448245-52
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Metastatic Disease

• Time to development of metastases
• 207 patients with left-sided IE
• Rate of embolic events decreased from 13/1000
  patient days during the 1st week of therapy to
  less than 1.2/ 1000 patient days after completion
  of the second week of therapy.
• 39 patients with SAB
• 9 developed metastatic complications 8 after the
  first week of positive blood culture.

Steckelberg JM et al. Annals of Intern Med
1991114635-640 Libman H et al. Arch Intern
Med 1984144 541-5
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Length of therapy

• Depends on extent of disease and host risk
  factors.
• Complicated infections such as IE, deep tissue
  abscesses often need 4-6 weeks of therapy.
• Appropriate length of therapy for patients with
  uncomplicated disease still unclear.
• Some propose 14 days of therapy.
• Others propose longer duration based on higher
  complication rates seen with shorter therapy.

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Outcomes

• Acute systemic complications ARDS, DIC, and
  septic shock usually occur within 48 hours.
• Mortality
• 1930s 40s 71 - 82
• 1980s - 2000s 16 - 34
• Risk factors Severity of illness at onset of
  SAB, unknown source, older age, non-eradicable
  foci.
• Recurrence develops in 12-15
• Persistent bacteremia
• Retained intravascular device
• Non- eradicable foci

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Challenges with SAB

• Clinical characteristics
• Community-acquired vs. hospital acquired
• Presence or absence of an apparent primary focus
• Overlap with IE
• Need for echocardiographic evaluation
• Metastatic disease
• Extent of diagnostic procedures, lack of drug
  effect
• Role of intravascular catheters
• Diagnosis of exclusion or laboratory criteria
• Treatment
• Need to initiate empiric therapy
• Choice of initial therapy
• Short versus long course therapy