Johns Hopkins Antibiotic (ABX) Guide

Pathogens
Bacteria

Staphylococcus aureus
Sara E. Cosgrove, M.D., M.S.; Paul G. Auwaerter, M.D.

MICROBIOLOGY

Gram-positive cocci, usually seen in clusters.

Easily grown on blood agar or other conventional media.

o

Coagulase positive and thermonuclease positive.

Antimicrobial resistance: rare isolates remain penicillin susceptible. In many areas,

MRSA > MSSA.
o

Penicillin resistance (MSSA) conferred by penicillinase production which can be

overcome by the addition of a beta-lactamase inhibitor
(e.g., amoxicillin/clavulanate, ampicillin/sulbactam) or use of a penicillinaseresistant penicillin (e.g., oxacillin, nafcillin).

Methicillin resistance (MRSA) conferred by presence of mecA gene that

encodes penicillin binding protein 2a, an enzyme that has low affinity for
beta-lactams and thus leads to resistance to methicillin, oxacillin, nafcillin,
and cephalosporins.

Community-acquired MRSA (CA-MRSA) isolates (strains include USA 300 as

most common in US, also USA 500, USA1000): often maintain susceptibility
to tetracyclines (tetracycline, doxycycline, minocycline, tigecycline)
and TMP/SMX.

Clindamycin susceptibilities vary geographically. If isolate

is erythromycin resistant, must confirm clindamycin susceptibility with
D-test.

CLINICAL

Carried in anterior nares by 20-30% of population.

o

Higher carriage rates seen in diabetics, injection drug users (IDU), HIV or
dialysis pts.

Carriers have > risk of subsequent infection.

Risk factors: skin disease, venous catheters, other foreign bodies (e.g., prosthetic
joints, pacemakers), IDU, hemodialysis, recent surgical procedure.

Methicillin resistance increasing. MRSA traditionally associated w/ healthcare system

interaction; CA-MRSA has emerged as significant pathogen, especially in children,
prisoners, IDUs (although rates also increased in adults with no clear risk factors).
o

CA-MRSA mostly causes skin/soft tissue infections; these are relatively benign
with good response to I&D antibiotics, although recurrent disease can
occur. Rarely, serious disease with or necrotizing fasciitis may occur.

CA-MRSA also a cause of necrotizing pneumonia. Consider diagnosis in a

severe pneumonia with evidence of cavitation/necrosis, particularly after
influenza-like illness.

Probably not a frequent cause of cellulitis in the absence of purulence

(abscess) or wound[1].

Dx: positive cx from sterile site (blood, joint, CSF), abscess or wound.
o

Positive cx from nares = colonization, not infection.

Staphylococcal toxic shock syndrome (see separate module) caused by TSST-1 or

other enterotoxin producing strains. Constellation of fever, low BP, red rash &
multiorgan failure. Risks: tampon use, nasal packing, surgical wounds.

Diarrhea: ingestion of preformed Staphylococcal enterotoxin causes acute, self-limited

gastroenteritis. Incubation 2-6h.

Severe MRSA infections with vancomycin MIC 1.5-2.0 not responding to therapy,
consider alternative agent (e.g., daptomycin). Several studies have worse clinical
outcomes with vancomycin in these settings.

SITES OF INFECTION

Bloodstream: primary risk is presence of intravascular catheter, which should be

removed.
o

May occur without apparent focus or entry site.

Evaluate if without focus for endocarditis (TTE/TEE), mycotic aneurysms or

vertebral infection (discitis, osteomyelitis, epidural abscess)

Skin/soft tissues:folliculitis, cellulitis, furuncle, carbuncle, abscess, impetigo (may

occur in combination with Streptococcus pyogenes). Breast:mastitis.

Abscesses: spleen, kidney, epidural space; visceral or deep abscesses occur almost
always due to hematogenous seeding from bacteremia.

Cardiac: endocarditis, occurs in 6-25% of S. aureus bacteremia; afflicts both native

and prosthetic valves.

Bone: osteomyelitis (S. aureus leading cause, most common is vertebral osteomyelitis
secondary to bacteremia/discitis).

Prosthetic devices: e.g., pacemaker leads and pocket, prosthetic joints.

Lung: nosocomial pneumonia or following influenza.

o

Septic pulmonary emboli: associated with right-sided endocarditis.

Mucosal surfaces: related to release of TSST-1 and subsequent toxic shock syndrome.

GI: toxin-associated gastroenteritis.

CNS: post-operative meningitis, meningitis or cerebritis associated with

bacteremia/endocarditis

TREATMENT
Bacteremia

Perform detailed history and physical to detect source and if metastatic spread has
occurred. Infectious diseases consultation recommended in most cases.
o

Remove foci of infection whenever possible; remove implicated venous

catheter if present.

May occur without apparent focus or entry site.

Evaluate if without focus for endocarditis (TTE/TEE), mycotic aneurysms or

vertebral infection (discitis, osteomyelitis, epidural abscess).

Rule out endocarditis with echocardiography (TEE preferred).

Treatment:

MSSA: superiority of -lactams make clear favorite over using vancomycin.

Preferred: oxacillin or nafcillin 2g IV q4h.

Alternative for non-life threatening PCN allergy: cefazolin 2g IV

q8h. Cefazolin can be given to hemodialysis patients: 2 gm after
dialysis if next dialysis in 2 days and 3 gm after dialysis if next dialysis
in 3 days.

Consider oxacillin/nafcillin desensitization for life-threatening Type

1 PCN allergy (hives/anaphylaxis).

MRSA or life-threatening PCN allergy:

Preferred: vancomycin 15-20mg/kg q 12h. Consider loading dose for

severe infections: guidelines recommend 25-30 mg/kg, although at
Johns Hopkins, favor 20-25 mg/kg, particularly in patients with any
baseline renal dysfunction.

Alternatives: for severe allergy or treatment failure, consider

infectious diseases consultation. Little robust data to guide choices.
Unclear if monotherapy or combination therapy needed for salvage
therapy.

Daptomycin 6mg/kg IV daily (FDA approved for S.

aureus bacteremia and right-sided endocarditis, preferred in
most instances); some experts recommend higher doses 8-10
mg/kg daily for severe infections.

Linezolid 600mg IV/PO q12h (not FDA approved for S.

aureus bacteremia)

Quinupristin/dalfopristin 7.5mg/kg IV q12h. (not FDA

approved for S. aureus bacteremia

TMP/SMX 5 mg/kg IV q8-12h (not FDA approved for S.

aureus bacteremia).

Ceftaroline 600mg IV q12h (not FDA approved for S.

aureus bacteremia).

Telavancin 10mg/kg IV once daily (not FDA approved for S.

aureus bacteremia).

o
o

Duration of therapy:

Bacteremia: 28d is the standard course of therapy

Short course therapy, 14d only if following criteria met:

Endocarditis is ruled out by transesophageal echocardiography

No implanted prostheses (e.g., prosthetic valves, cardiac

devices, or arthroplasties)

Blood cultures drawn 2-4 days after the initial cultures were
negative, the patient defervesces within 72 hours of
appropriate therapy

No evidence of metastatic infection

Endocarditis or epidural abscess: 42d minimum.

Endocarditis, native valve

Perform detailed history and physical to detect source and metastatic spread.

Diagnostic and therapeutic considerations:

o

Remove or drain foci of infection whenever possible.

Obtain brain & CNS vessel imaging if neurologic symptoms or persistent

headache present.

Consult cardiac surgery if patient has persistently positive blood cultures,

evidence of heart failure or ongoing embolic disease.

Evaluation especially recommended if vegetation > 10mm, new heart

block, persistent fevers.

Obtain MRI w/ contrasts spine imaging if back pain present to assess for
discitis, verterbral osteomyelitis or epidural abscess.

Echocardiography recommended, TEE favored over TTE.

Treatment:
o

MSSA, native valve, left-sided:

Preferred: oxacillin or nafcillin 2g IV q4h for 4-6 weeks with optional

addition of gentamicin 1 mg/kg IV q8h for 1st 3-5 days.

Alternative for non-life threatening PCN allergy: cefazolin 2g IV q8h

with optional addition of gentamicin 1 mg/kg IV q8h for 1st 3-5 days.
Use of synergistic gentamicin does not decrease mortality and is
associated with nephrotoxicity--avoid in patients with baseline
decreased CrCl, diabetes, advanced age.

Many clinicians no longer employ gentamicin.

MSSA, native valve, right-sided involvement ONLY: pt w/o AIDS, vascular

prosthesis or embolic dz other than septic pulmonary emboli.

Preferred: oxacillin or nafcillin 2g IV q4h gentamicin 1 mg/kg IV

q8h for 14d.

Use of synergistic gentamicin does not decrease mortality and

is associated with nephrotoxicity--avoid in patients with
baseline decreased CrCl, diabetes, advanced age.

IDSA MRSA endocarditis recommendations no longer favor

gentamicin for native valve infection.

Alternate oral regimen: only for IDU, TV MSSA endocarditis.

Ciprofloxacin 750 mg PO twice daily PLUS rifampin 300 mg PO twice

daily for 28 days, if isolate proven susceptible to both agents.

Alternate, if life-threatening penicillin allergy:

Desensitize to oxacillin/nafcillin (preferred).

Vancomycin 15-20 mg/kg IV q12h (consider loading dose; guidelines

recommend 25-30 mg/kg, although at Johns Hopkins favor 20-25
mg/kg, particularly in patients with any baseline renal dysfunction).

MRSA, native valve, right or left sided involvement:

Preferred: vancomycin 15-20 mg/kg IV q12h for 4-6 wks.

Alternative: daptomycin 6 mg/kg IV daily for 4-6 weeks; some

experts recommend higher doses 8-12 mg/kg daily.

Endocarditis, prosthetic valve

TEE recommended for all cases to evaluate for significant perivalvular abscess, leak or
if other valves involved.

Early evaluation for potential valve replacement suggested.

See diagnostic and therapeutic considerations listed above.

MSSA, prosthetic valve:

o

Oxacillin or nafcillin 2g IV q4h for 6 weeks PLUS gentamicin 1 mg/kg IV q8h

for 1st 2 weeks PLUS rifampin 300 mg PO q8h for 6 weeks after blood
cultures have cleared; confirm susceptibility to all agents.

MRSA, prosthetic valve:

o

Vancomycin 15-20 mg/kg IV q12h for 6 weeks (consider loading dose of 2530 mg/kg) PLUS gentamicin 1 mg/kg IV q8h for 1st 2 weeks
PLUS rifampin 300 mg PO q8h for 6 weeks after blood cultures have cleared;
confirm susceptibility to all agents.

Soft tissue infections

Surgical drainage for any collection. For cutaneous abscess, I & D may be sufficient.

For non-purulent cellulitis, this usually is due to -hemolytic streptococci rather than
CA-MRSA.

Antibiotics indicated for severe/rapidly progressive infections, signs and symptoms of

systemic illness, diabetes or other significant immunosuppression, advanced age,
location of abscess in an area where complete drainage is difficult, lack of response to
initial I&D (also assess for need for additional I&D), extensive abscess-associated
cellulitis.

If antibiotics employed, obtaining cultures recommended to help guide therapy.

Treatment:
o

Parenteral: IV antibiotics generally not needed unless severe infection,

concomitant bacteremia or systemic toxicity.

If using parenteral abx,choices the same as listed above for

bacteremia, exceptions:

Vancomycin 1g q12h IV (if routine infections), 15mg/kg IV

q12h (severe infections)

Daptomycin dose is 4mg/kg IV daily

Oral regimens:

MSSA:

Cephalexin 500mg PO four times a day

Dicloxacillin 500mg PO four times a day

Clindamycin 300-450mg PO three times a day

Amoxicillin/clavulanate 875mg PO twice daily

MRSA: check susceptibilities, includes options for CA-MRSA

with TMP/SMX and tetracyclines most likely susceptible.

Clindamycin 300-450mg PO three times a day

TMP/SMX 1-2 DS tabs PO twice daily

Doxycycline 100mg PO twice daily

Minocycline 100mg PO twice daily

Linezolid 600mg PO twice daily

Duration of therapy: depends on extent of disease, usual range 5-10 days.

o

Recurrent soft tissue infections: education regarding hand

hygiene and personal hygiene (e.g., regular bathing, no
sharing of personal items, clean personal sporting equipment,
avoid shaving).

Clean high touch areas in contact with bare skin (e.g., counters, sinks, door
knobs, tubs, toilet seats, etc) with commercial cleaners

Indications for decolonization include recurrent infection despite optimal

hygeine or household transmission. Evaluate contacts for evidence of S.
aureus infection. Routine screening cultures of nares not recommended.

Consider decolonization for recurrent soft tissue infections: potential

approaches include (both index patient contacts/household)

Mupirocin 2% ointment to nares twice daily for 5-10 days. Some

repeat for a period of months, e.g, first five days of each month.

Mupirocin 2% as above + chlorhexidine (Hibiclens) washes daily for 514d or dilute bleach bath (1 tsp/gallon, cup per 13 gallons) twice
weekly x ~3 months.

Oral antibiotics not usually recommended. Some use if above

measures fail. Typically choose one drug from oral MRSA regimen
above plus rifampin (e.g., doxycycline 100mg twice daily
+ rifampin 600mg daily x 7-10d).
o

Some clinicians add rifampin to oral agents for MRSA for

patients with recurrent soft tissue infections; rifampin should
NEVER be used as monotherapy; efficacy of this strategy is
unproven and rifampin is associated with significant drug
interactions so we do not recommend it in most cases.

Pneumonia

Consider MRSA pneumonia in any patient with severe CAP (e.g., ICU admission,
necrotizing/cavitary disease, empyema) pending sputum or blood culture results.

Treatment: use susceptibilities to help guide final choice. Linezolid may have better
PK/PD data in lung compared to vancomycin; recent study shows better initial clinical
success than vancomycin, but similar 60d mortality[2].

Vancomycin 15mg/kg IV q12h

Linezolid 600mg IV/PO q12h

Clindamycin 600mg IV or 300-450mg PO q8h

Daptomycin cannot be used for pulmonary infections because it is inactivated by

surfactant.

Drain or proceed with thoracic surgical consultation for empyema.

Duration of therapy: 7-21d course, depending on severity; many cases of ventilator

associated pneumonia can be treated for 8d; necrotizing pneumonia usually requires
longer courses 14d; bacteremic pneumonia, at least 14d.

Bone/joint infections

Osteomyelitis (OM)

MRI with gadolinium often best study to employ to diagnose infection in

verterbral bones or feet.

Drainage and debridement of devitalized bone should be done if possible.

No clear data to suggest preference regarding parenteral or oral route of

antibiotic.

Treatment:

MSSA: select from bacteremia choices above.

MRSA:

Vancomycin 15mg/kg IV q12h

Daptomycin 6mg/kg IV q 24h

TMP/SMX 4mg/kg (TMP component) twice daily

rifampin 600mg once daily

Linezolid 600mg PO/IV q 12h

Clindamycin 600mg IV q8h

Some add rifampin to any of the above dosing as 600mg once daily or 300450mg PO twice daily. If patient bacteremic, only addrifampin after
bacteremia clear to avoid emergence of resistance.

Duration: unclear best course, many choose 6-8 wks. Some treat for
additional 4-12 wks especially if OM of longstanding nature or if complete
debridement not achieved. ESR/CRP may be used to follow response.

Potential oral combinations include monotherapy

using TMP/SMX, doxycycline, minocycline, clindamycin or moxifloxacin
OR combination therapy using abx + rifampin.

Septic arthritis
o

Always drain or debride joint.

Repeat closed drainage as needed.

No clear preference for closed or open drainage.

Consult orthopedics for open drainage

Treatment: select from MSSA or MRSA choices as above.

Prosthetic joint infection: see module for additional details.

o

Early (< 2 mos post-op) or acute hematogenous infection w/ stable joint <
3wks symptoms:

Debride/washout joint and retain.

Select abx from OM choices above + rifampin 600mg or 300-450mg

PO twice daily x 2 weeks. Follow by TMP/SMX,
fluoroquinolone, tetracycline or clindamycin + rifampin x 3-6 months.

Late (> 2 mos post-op): or if unstable, later-onset infection or > 3wks

symptoms--remove hardware and administer abx as above.

CNS

Meningitis
o

MSSA: nafcillin or oxacillin 2g IV q4h.

MRSA:

Preferred: vancomycin 15-20 mg/kg IV 12h (consider loading dose;

guidelines recommend 25-30 mg/kg, although we favor 20-25 mg/kg,

particularly in patients with any baseline renal dysfunction). Strive for

trough level ~20 g/mL.

Alternatives:

Linezolid 600mg IV q12h (limited data for meningitis but has

good CNS penetration).

TMP/SMX 5mg/kg (trimethoprim component) q8-12h.

Some add rifampin 600mg PO/IV q24 or 300-450mg IV/PO q12h.

Refractory infection: consider intrathecal vancomycin, 5-20mg daily.

Duration: 14d.

CNS shunt infection: remove device. Replace only when CSF cultures
repeatedly sterile.
o

Brain abscess, subdural empyema, epidural abscess

Consult neurosurgery urgently for drainage.

MSSA or MRSA: choices as above.

Duration: 4-6 wks.

Toxic Shock Syndrome

See Staphylococcal TSS module for details.

Remove focus of staphylococcal colonization or infection.

Stabilize blood pressure w/ aggressive hydration +/- pressors.

MSSA: oxacillin or nafcillin 2g IV q4h PLUS clindamycin 600mg IV q8h.

MRSA: vancomycin 15-20 mg/kg IV q12h PLUS clindamycin 600mg IV q8h (if
susceptible) or linezolid 600 mg IV/PO q12h.

Consider intravenous immunoglobulin infusions.

Selected Drug Comments

Drug

Recommendation

Amoxicillin/clavulanate

Good activity against MSSA and other Gram + organisms (not

MRSA). Useful for skin and skin structure infections when some
Gram (-) and anaerobic coverage is also desirable (bite, mixed
abscess). Not recommended for S. aureus bacteremia
or endocarditis.

Ampicillin/sulbactam

Good activity against MSSA and other Gram + organisms (not

MRSA). Useful for skin and skin structure infections when some
Gram (-) and anaerobic coverage is also desirable (bite, mixed
abscess). Not recommended for S. aureus bacteremia
or endocarditis.

Cefazolin

First generation cephalosporin antibiotic with excellent general

Gram + activity except for enterococci and MRSA. A practical
alternative for S. aureus endocarditis or bacteremia therapy
when CNS involvement is not suspected (only 1-4% penetration
into CSF)

Clindamycin

A good choice for skin and skin structure infections due to S.

aureus, particularly CA-MRSA. CA-MRSA susceptibilities
to clindamycin vary by geographic
location. Erythromycin resistance predicts
inducibleclindamycin resistance in many isolates; thus, the
microbiology lab should perform a D-test to assess
forclindamycin susceptibility. Excellent oral absorption, although
GI intolerance (including C. difficile) is more likely with higher

doses. Not recommended for S. aureus bacteremia

or endocarditis.
Minocycline

A good choice for skin and skin structure infections due to S.

aureus, particularly CA-MRSA; poor anti-streptococcal activity.
Has the best in vitro Gram + activity of the tetracyclines. Side
effects include photosensitivity, reversible vestibular
dysfunction, and blue skin discoloration. Often used for longterm suppressive therapy in orthopedic infections, sometimes in
combination with rifampin. Not recommended forS.
aureus bacteremia or endocarditis.

Nafcillin

Well-established agent for serious systemic S. aureus infections

(not MRSA). No dose adjustment for renal failure. Main toxicity
is neutropenia. Agent is administered intravenously q4h or by
pump for home therapy.

Oxacillin

Well-established agent for serious systemic S. aureus infections

(not MRSA). No dose adjustment for renal failure. Main toxicity
is elevation of hepatic enzymes. Agent is administered
intravenously q4h or by pump for home therapy.

Piperacillin/tazobactam

Good activity against MSSA and other Gram + organisms (not

MRSA) as well as most Gram (-) organisms. Useful for broad
spectrum empiric therapy when MSSA,
streptococcus, enterococcus, Gram (-), and anaerobic coverage
is desirable. Not recommended for S. aureus bacteremia
or endocarditis.

Quinupristin/dalfopristin

Combination streptogramin antibiotic active against MRSA

and Vancomycin resistant Enterococcus faecium.E. faecalis is
intrinsically resistant. Not FDA approved for S.
aureus bacteremia. Must be given IV via a central line because
of phlebitis risk. Other side effects are severe arthralgia and
myalgia. Has a variety of drug-drug interactions mediated via
the cytochrome P450 system. No dose adjustment is required
for renal or hepatic insufficiency.

Rifampin

Excellent bactericidal agent against S. aureus but SHOULD

NEVER BE USED AS MONOTHERAPY because of rapid
development of resistance. Can be used in combination with
fluoroquinolones, TMP/SMX, clindamycin, or minocycline after a
course of appropriate IV therapy for complicated bone and joint
infections requiring long-term therapy/suppression. Also used
as part of combination therapy for PVE. No robust studies have
proven beneficial role independently, and some have suggested
use equates with poorer outcomes.

Trimethoprim/sulfamethoxazol
e

A good choice for skin and skin structure infections due to S.

aureus, particularly CA-MRSA; poor anti-streptococcal activity .
Use compared to vancomycin has been studied in a cohort of
injection drug users with MSSA and MRSA infections with good
clinical results, particularly with MRSA. Not recommended for S.
aureus bacteremia or endocarditis except in salvage situations
in conjunction with infectious diseases consultation.

Vancomycin

Active against MRSA and MSSA (but less effective

so if MSSA, prefer beta-lactam therapy for serious
infections).
o

Clinical failure rate is higher for

staphylococcal endocarditis treated with
vancomycin than with alternate beta-

lactam agents. Use is thus reserved for

MRSA or for patients with documented
severe beta-lactam allergy.

Must be given IV (no oral absorption).

When using this agent it is prudent to follow serum

trough levels (aiming for a trough of 15-20 mcg/ml
for serious infections). No single dose should
exceed 2g. Loading dose should be considered in
patients who are critically ill.

Trough concentrations are most accurate method to

guide dosing; obtain after steady state likely
following 4th or 5th dose. For routine SSTI infections,
1g q12h dosing should be adequate.

Linezolid

An oxazolidinone antibiotic available both orally and

intravenously with activity against both MSSA and
MRSA as well as VRE. No dose alteration required
in renal or hepatic insufficiency.

Not FDA approved for S. aureus bacteremia.

Side effects include thrombocytopenia, anemia,

neutropenia as well as optic neuritis and
irreversible peripheral neuropathy. Side effects are
more common in patients receiving the drug for >
3 weeks.

Because it is a monoamine oxidase inhibitor (MAOI), it should not be used with MAO-Is and should be
used with caution with serotonergic drugs (SSRIs)
given case reports of serotonin syndrome. Patient
on both drugs should be monitored for mental
status changes, myoclonus, diaphoresis and other
symptoms of serotonin syndrome.

Daptomycin

A lipopeptide antibiotic FDA approved for MSSA and

MRSA bacteremia and right-sided endocarditisand
complicated skin and skin structure infections due
to MSSA, MRSA, GAS, and VSE.

It is inactivated by pulmonary surfactant and

cannot be used for pneumonia.

Dose is 6 mg/kg/day when used for S.

aureus bacteremia or endocarditis and 4
mg/kg/day when used for skin infections. Some
experts recommend higher doses (8-12 mg/kg
daily) for MRSA bacteremia and endocarditis. Dose
reduction required for CrCl < 30mL/min (same
doses but administered every other day).

Main side effect is myopathy; CK must be checked

at least weekly.

Cases of emergence of resistance during therapy

have been reported, particularly in patients without
source control who have received
prior vancomycin; monitor for recurrent positive
blood cultures during therapy.

Doxycycline

A good choice for skin and skin structure infections due to S.

aureus, particularly CA-MRSA but has poor anti-streptococcal
activity. Side effects include photosensitivity (patients should be
warned to avoid the sun). Often used for long-term suppressive
therapy in orthopedic infections, sometimes in combination
withrifampin . Not recommended for S. aureus bacteremia
or endocarditis.

Tigecycline

FDA approved for skin and soft tissue infections. Low serum
levels make this a drug not typically employed for bacteremia.
FDA warning issued based on review of clinical trials warned of
increased mortality with its use.

Telavancin

Lipoglycopeptide that was initially FDA approved for

SSTI on the basis of non-inferiority studies
compared to vancomycin. Unclear if lower MRSA
MIC of telavancin compared to vancomycin has
clinical significance.

May cause red man syndrome and should not be

used in pregnancy.

May be slightly more nephrotoxic than vancomycin.

After an absence, drug is now again available in

US.

In 2013 FDA approved drug to be used for HAP but

only when other alternatives are not suitable, i.e.,
not a first line agent. Concern with the drug is that
studies have suggested a substantially higher rate
of mortality in patients with diabetes or renal
failure compared to those treated with vancomycin.

Ceftaroline

New generation cephalosporin with MRSA activity as well as

Gram negative spectrum similar to ceftriaxone. FDA approved
for CAP and SSTIs, but some clinicians using off label with
success in the treatment of difficult MRSA infections including
persistent bacteremia (typically dosed 600mg IV q 8 +/another agent [e.g., TMP/SMX] in salvage situations).

FOLLOW UP

For patients with bacteremia or endocarditis, follow up blood cultures should be

obtained to document clearance of bacteremia while on therapy.

Endocarditis treatment failure or persistent bacteremia: typically occurs

on vancomycin therapy. Select an alternative antibiotic regimen as for bacteremia; ID
and cardiac surgery consults recommended.
o

Always search for focus of infection or removal of any devices.

Salvage regimens not well studied, but options include both changing therapy
and using combination therapy. Use susceptibilities to guide.

Daptomycin 10mg/kg with another agent (gentamicin 1mg/kg IV

q8h, rifampin 600mg PO/IV daily, linezolid 600mg twice
daily, TMP/SMX 5mg/kg twice daily or beta-lactam antibiotic
[e.g, oxacillin or nafcillin[3]].

Ceftaroline 600mg IV q 12h (alone or in combination, no FDA

indication for bacteremia)

If organism with reduced susceptibility to daptomycin or vancomycin:

consider use of the following agents, in combination.

Quinupristin/dalfopristin 7.5mg/kg IV q8h

TMP/SMX 5mg/kg q 12h

Linezolid 600mg q12h

Telavancin 10mg/kg IV once daily

Ceftaroline 600mg IV q12h

For patients with serious S. aureus infections treated

with vancomycin, trough levels should be 15-20 mcg/ml (20
mcg/ml for CNS infection and severe pneumonia).

OTHER INFORMATION

Mortality associated with S. aureus bacteremia is 20-40%.

S. aureus bacteremia is associated with heart valve involvement in 25% when studied
with transesophageal echo (TEE). Clinicians must rule out endocarditis before
treating S. aureus bacteremia with short (i.e. 2 week) course antibiotics.

All patients with S. aureus bacteremia should undergo at least a good quality
transthoracic echo (TTE). TEE is preferred for patients with prosthetic valves or with
inadequate TTE.

Be alert for the development of metastatic abscess formation w/ any S.

aureus bacteremia. S. aureus in urine cx should alert to the possibility of associated
bacteremia.

Patients with MRSA colonization or infection should be placed on contact precautions.