Transcript S aureus

Depresion, mental status testing,
addiction and skin and bone
infectrions
10/07/11
Which of the following is
the most common comorbidity
associated with nonresponse to
antidepressants?
A) Diabetes
B) Posttraumatic stress disorder
(PTSD)
C) Hypothyroidism
D) Substance abuse
Answer
• D) Substance abuse
Understanding antidepressant nonresponse
• since physicians diagnose depression on basis of
symptoms and history, many patients with other
illnesses meet diagnostic criteria
• (must rule out, eg, thyroid disease, unrecognized
diabetes, malignancies)
• medication selection—important
• since predicting responses not possible, iterative
trials required
• adherence—one-third of patients choose not to
refill prescriptions
• in Sequenced Treatment Alternatives to Relieve
Depression (STAR*D) trial, each treatment failure
resulted in loss of 10% to 20% of patients
According to data from the
Sequenced Treatment Alternatives to
Relieve Depression (STAR*D) trial,
two-thirds of patients who responded
to their treatments reported benefits
after:
A) 12 wk
B) 8 wk
C) 6 wk
D) 3 wk
Answer
• C) 6 wk
• Focus on improved methods of engaging,
preparing, and ensuring follow-through with
patients requiring continued treatment;duration—
guidelines recommend 8-wk trial, but speaker
argues that likelihood of response low if not seen
after first 2 wk
• disability, complexity, and comorbidities—
patients with poor natural history or prognosis
often have poor responses (10%-20% efficacy in
some groups) and may require different
framework of expectations or time course
• focus on establishing unit of symptom benefit (not
remission
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Common causes of nonresponse
Nonadherence
Unrecognized bipolarity—antidepressants show poor efficacy in patients with bipolar
disorder (BD) or bipolar spectrum features
unrecognized psychosis — late-life depression may present with delusions and
hallucinations
psychotic depression often accompanies severe recurrent illness in patients 60 to 70 yr
of age, but may occur earlier in life
psychosis plus depression in younger patients may indicate bipolarity
since patients may
mask delusions or hallucinations, watch for near-psychotic signs (eg, perplexity,
slippage, blocking, nonsequiters, confusing logic or reasoning)
dosages of antipsychotics used to augment antidepressants do not adequately treat
psychosis
unrecognized comorbidities—in studies, 5% to 10% of patients presenting with
apparently uncomplicated depression found to have 1 significant systemic medical
illness capable of affecting diagnosis or treatment outcomes
substance abuse most common comorbidity responsible for antidepressant failures
(often masked)
reassess for abuse at every stage of treatment
Adequate treatment trials
• 4- to 6-wk trials at full or maximum therapeutic dosage recommended
• however, may discontinue in patients with significant side effects and
no benefits at minimum dose
• always document rationale for early discontinuation
• speaker attempts trials with nutriceuticals, increased emphasis on
psychotherapy, or transcranial magnetic stimulation in patients with
history of intolerance to many (6-8) antidepressants
• patients with extremely poor tolerability to one medication typically
have similar responses to all agents in same class;
• remission vs response — although remission may be ideal, patients
showing significant improvement should continue current treatment
• attempt augmentation strategies to induce remission in patients with
partial response
• STAR*D data — two-thirds of responsive patients showed results by 6
wk
• speaker discourages 12-wk trails (without steady trend of improvement
with acceptable tolerability
In STAR*D, patients who failed one adequate
trial of an antidepressant showed:
A) Superior response rates when switched to
a multiple-action agent (eg, buproprion,
venlafaxine)
B) Superior response rates when switched to
a second selective serotonin reuptake inhibitor
(SSRI)
C) Comparable response rates when switched
to either multiple-action medications or SSRIs
Answer
• C) Comparable response rates when
switched to either multiple-action
medications or SSRIs
Strategies for stage I resistance
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switch within same class
switch across classes
adjunctive strategies
combining selected antidepressants
switching vs augmentation
Switching may be preferable (prevents costs
of second treatment and allows targeted
remediation of side effects
STAR*D data on medication
switch outcomes
• no statistically significant differences found
among patient groups switched from citalopram to
sertraline, bupropion, or venlafaxine
• authors found same-class switching viable option
(nearly as effective as switch to multiple-action
agents)
• nortriptyline and mirtazapine showed comparable
efficacy
• however, mirtazapine shows superior safety
profile and tolerability (no cardiography or blood
tests required for patients >40 yr of age
Benefits of augmentation strategies
• response more rapid
• No washout period needed
• easier implementation (eg, no issues with
cross-titration
Lithium has superior benefits as
an augmentative agent when used
with:
A) Tricyclic antidepressants
B) SSRIs
C) Serotonin and norepinephrine
reuptake inhibitors
D) Anxiolytics
Answer
• A) Tricyclic antidepressants
Best evidence-supported adjunctive therapies
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lithium — long history of use in enhancement of tricyclic antidepressants (TCAs)
requires blood level monitoring
significant side ef fects
less effective with modern antidepressants
has proven therapeutic efficacy
typically effective at 600 mg to 1200 mg daily (high blood levels not required)
thyroid augmentation — T3 hormone preferred (25-50 µg daily), since T4 not used for
brain activity
showed comparable efficacy to lithium augmentation in STAR*D, but with easier
implementation
One study linked efficacy to genetic polymorphisms affecting conversion of T4 to T3
(possible explanation for inconsistent results);
buspirone — nonhabit-forming anxiolytic (via partial agonism of serotonin receptor 1A)
appears to enhance or modify effects of selective serotonin reuptake inhibitors (SSRI)
potentially difficult to use (due to wide dosage range [5 mg bid to 20 mg tid] and side
effect burden); relieves anxiety and reverses sexual side effects when used with SSRI
_______ is recommended for use
in thyroid augmentation of
depression treatments, due to its
activity in the brain.
A) Monoiodothyronine
B) Diiodothyronine
C) T3 hormone
D) T4 hormone
Answer
• C) T3 hormone
According to STAR*D,
augmentation of an
antidepressant with _______ has
superior benefits in patients with
more severe anxiety.
A) Buspirone
B) Bupropion
C) Lithium
D) Lamotrigine
Answer
• B) Bupropion
Antidepressant combinations
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many agents have complementary effects
no washout required
efficacy remains understudied
citalopram augmented by bupropion vs
buspirone (STAR*D)
• combinations showed comparable efficacy
• bupropion showed superiority in patients
with greater anxiety and buspirone showed
superiority in patients with milder anxiety
Other options
• adjunctive benzodiazepines —show benefits only with
continuous use (ie, palliative but not curative)
• use caution when initiating for chronic complicating
anxiety due to high risk for long-term dependency
• monoamine oxidase inhibitors (MAOIs) —classically
effective agents with unique mechanisms of action
• particularly effective in early-onset chronic depression
with reversed vegetative features
• in STAR*D level 4, many physicians failed to prescribe
adequate dosages of MAOIs
• mirtazapine plus venlafaxine found more effective than
tranylcypromine (possibly due to relative ease of use
• DR Stahl calls it California rocket full
Responses to sequential treatment
in STAR*D
• after 4 failed medication trials, only 10% of
patients eventually achieve remission
• increasing treatment resistance also
increases risk for relapse after response
(close follow-up and monitoring required
Atypical antipsychotics show
proven efficacy in _______ of
patients with depression.
A) 55%
B) 35%
C) 20%
D) 10%
Answer
• C) 20%
Augmentation with atypical
antipsychotics (AAP)
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Proven effective (compared to placebo), but only in 20% of patients and in trials of 6 to
8 wk
guidelines for use undetermined
long-term use gradually increases risk for metabolic side effects and tardive dyskinesia
(in 1 yr follow-up of patients using adjunctive aripiprazole, several cases of reversible
acute onset dyskinesia occurred [<1% of patients])
Approved combinations — olanzapine plus fluoxetine
aripiprazole plus many antidepressants
quetiapine plus many antidepressants
risks —studies found olanzapine plus fluoxetine increased weight by average of 5.5 kg
over 8 wk
speaker’s conclusions — use only when justified by severity or urgency
keep baseline of weight and metabolic activity
record abnormal involuntary movement scores in patients undergoing long-term
treatmen
Augmentation with other mood
stabilizers
• lamotrigine most widely used
• shows “quelching” effect in patients with
history of posttraumatic stress disorder
(PTSD)
• covers subtle bipolar syndromes
• speaker prefers AAPs due to superior
clinical evidence
Modafinil and armodafinil
augmentation
• reduce symptoms of drowsiness and fatigue,
but do not improve mood, optimism, or
hedonic capacity
• costly and often not covered by insurance
• recommended only in patients reporting
persistent difficulties with sleepiness,
hypersomnolence, and fatigue
Dopaminergic options
• pramipexole — nonhabit-forming selective
dopamine agonist
• shows antidepressant effects in small
studies of treatment-resistant depression and
BD
• may cause drowsiness, lightheadedness, and
inappropriate alertness at night ( 20% of
patients discontinue
Conclusions
• outcome measuring, following adherence,
working through sequential treatment
hierarchies, retrials, and confident use of
TCAs, MAOIs, and electroconvulsive
therapy
• (and appropriate combinations of therapies),
• depression can be successfully resolved
within 1 yr in 90% of patients
_______ is shown to be
the most accurate psychologic screening
tool, but it requires more time than
competing forms of testing.
A) Mini-Mental State Examination
B) Mini-Cog Assessment
C) St. Louis University Mental Status
Examination
D) Montreal Cognitive Assessment
Answer
• D) Montreal Cognitive Assessment
NT vs Mini-Mental State
Examination (MMSE)
• does not replace thorough cognitive
assessment
• outdated; has high falsepositive rate in
patients >60 yr of age; fails to account for
baseline performance in patients with
above- or below-average level of education
Mini-Cog Assessment
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recommended for assessing dementia
requires only 2 to 3 min
public domain
patients required to retain memory of 3
words while drawing picture of clock set to
specific time
• can be performed by any caregiver
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Alternatives to MMSE
St. Louis University Mental Status
Examination— public domain
more difficult than MMSE
has higher expectations for healthy aging of brain
Brevity similar to that of MMSE, but yields far more
accurate results
Montreal Cognitive Assessment—most accurate cognitive
screening tool, but has slightly longer administration time
public domain
translated into >20 languages
easily score
Serial evaluation with NT should
ideally be spaced _______ apart.
A) 6 to 12 wk
B) 3 to 6 mo
C) 9 to 12 mo
D) 1 to 2 yr
Answer
• C) 9 to 12 mo
Nearly all forms of pleasure are
associated with dopamine release
in the:
A) Nucleus accumbens
B) Anterior insula
C) Cingulate gyrus
D) Brainstem
Answer
• A) Nucleus accumbens
Disulfram causes a toxic reaction
to alcohol by inhibiting the
metabolism of:
A) Ethyl glucuronide
B) Acetaldehyde
C) Acetic acid
D) Phosphatidyl ethanol
Answer
• B) Acetaldehyde
_______ is most effective in
patients with a strong family
history of alcoholism and an
early age of onset.
A) Disulfram
B) Naltrexone
C) Acamprosate
D) Baclofen
Answer
• B) Naltrexone
_______ has been shown to
prolong the time until relapse in
patients with stimulant
dependence.
A) Bupropion
B) Topiramate
C) Modafinil
D) Naltrexone
Answer
• A) Bupropion
Background on addiction
• brain disease characterized by compulsive
behavior, continued substance use despite
consequences, and persistent changes in brain
structure and functioning
• pathophysiology — all commonly abused
substances act at synaptic level
• synaptic effects cause cascade of intracellular
changes that affect long-term reactivity, gene
expression, and connectivity to other neurons
• reward pathways — nearly all forms of pleasure
coincide with dopamine release in nucleus
accumbens (NAcc), serotonin release in
brainstem, and activation of opioid receptors by
endogenous opiate peptides in NAc
Management of alcohol dependence
• Disulfiram: patients typically discontinue usage
before relapsing; causes toxic reaction to alcohol
by inhibiting metabolism of acetaldehyde
(secondary stage of ethanol metabolism)
• patient sensitivity varies (some report side effects
when ingesting vinegar)
• potential for severe hepatotoxicity (monitoring of
liver function tests [LFTs] required)
• has no effect on alcohol cravings
• recommended for patients with high motivation to
maintain sobriety, awareness of upcoming
triggers, and supportive individuals who can
witness patient's self-administratio
Naltrexone
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blocks rewarding effects of alcohol at opioid receptors
dosing —50 to 100 mg daily; LFTs required
Poor compliance causes poor outcomes
depot preparation— monthly intramuscular injection
slowly releases naltrexone into bloodstream at fixed rate
circumvents compliance issues efficacy— limited
reduction in cravings
blunts response to alcohol if relapse occurs
most effective in patients with strong family history and
early onset of alcoholism (possibly due to transcription
variations in µ-opioid receptors)
blockading opioid receptors on GABA neurons inhibits
dopamine release in NAc
Acamprosate
• chemically similar to GABA
• reduces glutamate transmission; mechanism of action— since alcohol
acts as
• substitute for GABA, endogenous production of GABA decreases with
repeated intoxication
• suppressed GABA results in compensatory increase of glutamate
(causing anxiety, tremors, and potential seizures if patient withdraws
from alcohol)
• acamprosate helps restore GABA-glutamate balance
• characteristics — few side effects; reduces cravings; may cause
gastrointestinal irritation (rarely affects adherence)
• requires large dose taken 3 times daily
• Excreted through kidneys; efficacy—speaker reports lackluster results
in United States (possibly due to different phenotypes of alcoholism
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Topiramate:
Gabapentin:
Topiramate 25 to 300 mg daily shown to improve overall well-being,
reduce some cravings, reduce harmful drinking consequences;
well-tolerated low-risk intervention (despite reports of cognitive
disturbances and “numbness”)
suppresses appetite in some patients
Gabapentin GABA analogue
can reduce cravings and anxiety and delay relapse; shown to improve
sleep initiation and maintenance in alcoholics during first 6 mo of
recovery
appears to increase endogenous GABA production; may be
started at high doses (eg, 600 mg before bed, 300 mg in morning),
since sedation not typically seen in patients with history of alcoholism
Others
• Baclofen: 30 mg daily shows impressive
rates of abstinence vs placebo in
randomized controlled trials (RCTs)
• Ondansetron: shows trend toward positive
results in patients biologically predisposed
to alcoholis
Management of opiate dependence
• Background: increasing in prevalence due to abuse of
synthetic medical opioids (eg, oxycodone);
• Symptomatic detoxification— performed from office
(outpatient); clonidine tapered over 3 to 6 days (speaker
recommends starting at 0.1 mg); always provide treatment
for diarrhea, stomach
• cramping, piloerection, and rhinorrhea (over-thecounterremedies typically suffice)
• trazodone or gabapentin may
• help sleep and anxiety issues
• causes of continued
• addiction —fear of withdrawal symptoms (often severe)
• long-term craving
Buprenorphine
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partial agonist of opioid receptors
Unlike full agonists, effects plateau at 32 mg daily (prevents respiratory
depression and euphoric effects)
Abolishes most withdrawal symptoms and blunts cravings (after acute
detoxification);
oral buprenorphine plus naloxone
(Suboxone) — patients must be clean of opiates for 24 hr
before starting therapy (prevents abrupt withdrawal symptoms); typically
induced at 2 to 4 mg daily
most patients show lasting effects at 12 to 16 mg daily
regulations — physicians must become federally registered prescribers
conclusions from study — buprenorphine has superiorsafety and lower abuse
potential than methadone but does not appear to reverse physical dependence
Preventing diversion — patients should consent to opiate contracts
and receive continuous education; treatment during
pregnancy — form without naloxone (Subutex) shown superior to methadone
in preventing neonatal abstinence syndrome Naltrexone
not effective as outpatient treatment; depot formulation (Vivitrol) recently
approve
Management of stimulant dependence
• Medications: no approved adjunct treatment
• several high quality open-label trials and small RCTs have assessed
bupropion, topiramate, modafinil, disulfiram (inhibits metabolism of
dopamine), and naltrexone
• Cocaine vaccine: currently under development
• primes body to remove cocaine from bloodstream before reaching
brain
• Depression and anxiety
• speaker recommends low threshold for use of selective serotonin
reuptake inhibitors (SSRIs; eg, citalopram, fluoxetine) for patients with
poor compliance; maximize usage of nonhabit-forming anxiolytics (eg,
• hydroxyzine, buspirone, propranolol, quetiapine [for racing thoughts
and avoidance of sleep])
• mindfulness meditation shows efficacy
• bupropion found to stave off relapse
Management of stress
• addictive substances induce intense
• acute stress states; hyperactive states
induced by substances
• make patients more attuned to cues
associated with cravings
• or relapse; treating heightened stress
responses (with, eg, SSRIs, beta-blockers)
can greatly improve quality of life in
substance-dependent patient
Which of the following is most
useful in the diagnosis of septic
arthritis?
A) Serum white blood cell
(WBC) count
B) Synovial fluid WBC count
C) Erythrocyte sedimentation rate
D) C-reactive protein level
Answer
• B) Synovial fluid WBC count
Septic joint
• most commonly affects hip, knee, and ankle joints
• multiple joints affected in 5% to 10% of cases
(usually asymmetric); microbiology—similar in
children (except neonates) and adults
• nearly 50% of infections due to Staphylococcus
aureus
• other causes include streptococci, gram-negative
bacilli, and Neisseria
• presentation —joint pain
• history of joint swelling in 80% of patients; fever
in 60% of patient
Serum LaboratoryValues
• white blood cell (WBC) count nonspecific and not
helpful
• erythrocyte sedimentation rate (ESR) <30 mm/hr
helpful
• C-reactive protein (CRP) >100 mg/L slightly
helpful
• synovial fluid studies —septic arthritis highly
likely in patients with WBC count >100,000/µL
(cut-off, 25,000-50,000/µL [ie, >25,000/µL highly
suggestive of septic arthritis])
• polymorphonuclear leukocytes (PMNs) >90%
(strong predictor)
• consider differential diagnosis
Management
• drainage of joint by arthrocentesis, arthroscopy, or
open drainage; duration of antimicrobial therapy
not welldefined, but 2 to 4 wk typical (gonococcal
infection can be treated for 7-10 days)
• for suspected gram-positive infection,
• use vancomycin (15-20 mg/kg every 8-12 hr;
empiric coverage in case of methicillin-resistant S
aureus [MRSA] Adjust as needed)
• Fluoroquinolones
• antipseudomonal Beta-lactams;
• carbapenems; for gram-negative infection, cover
for S aureus
Although not well defined,
typical duration of antimicrobial
therapy for treatment of septic
arthritis is _______.
A) 5 days
B) 1 wk
C) 2 to 4 wk
D) 4 to 6 wk
Answer
• C) 2 to 4 wk
Choose the correct statement about 3phase technetium bone scanning in the
diagnosis of osteomyelitis.
A) Shows uptake in phases 1 and 2, with
focal intense uptake in delayed images
B) Exposes patient to high-dose radiation
C) Not useful if multiple sites suspected
D) Sensitivity and specificity 90%
Answer
• A) Shows uptake in phases 1 and 2, with
focal intense uptake in delayed images
Conventional radiology
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sensitivity low
abnormal in 45% to 70% of cases
normal in 25% of cases
normal until 10 to21 days after infection
(not reliable in setting of acute disease)
• lytic changes not seen until >50% of bone
matrix destroyed; specificity low (25%);
early clues include soft tissue swelling,
periosteal thickening or elevation, or osteo
penia reflecting bony destruction; previous
abnormality (eg, fracture) major limitation
Magnetic resonance imaging (MRI)
• highly sensitive
• High resolution of periosteal bone, cortical
destruction, and joint damage
• sensitivity varies (60%-100%)
• specificity “quite good” in patients with no
previous bone destruction
• excellent anatomic resolution (of, eg,
associated abscess
Studies consistently show
intravenous (IV) metronidazole
more effective in the treatment of
osteomyelitis than oral
metronidazole.
A) True
B) False
Answer
• B) False
Treatment
IV antibiotics serum concentrations of Beta-lactams
(eg, nafcillin, cefazolin) 50 to 150 µg/mL (in bone, 5-15
µg/mL; minimum inhibitory concentration [MIC] <2
µg/mL)
bone penetration of daptomycin not as high due to high
protein binding, but MIC lower; oral antibiotics —difficult
to achieve high bone levels with traditional beta-lactams;
adequate serum concentrations can be achieved with
fluoroquinolones
metronidazole effective (IV or orally)
serum concentration of linezolid 10 to 20 µg/mL
good ratio with linezolid and trimethoprim-sulfamethoxazole
(TMP-SMZ)
good penetration with clindamycin and rifampin
Long courses of _______ are
associated with bone marrow and
nerve toxicity.
A) Trimethoprimsulfamethoxazole (TMP-SMZ)
B) Metronidazole
C) Linezolid
D) Rifampin
Answer
• C) Linezolid
Outpatient studies show that IV
vancomycin alone for treatment
of Staphylococcus aureus
infection leads to significantly
better outcomes than other drugs.
A) True
B) False
Answer
• B) False
According to guidelines from the
Infectious Diseases Society of
America, what is the primary
treatment of abscesses?
A) Incision and drainage (I&D)
B) I&D plus clindamycin
C) Rifampin
D) Combination of rifampin and
another antibiotic
Answer
• A) Incision and drainage (I&D)
Abscesses
• Abscesses: Infectious Diseases Society of America
guidelines incision and drainage (I&D) primary treatment
• benefit of addition of antibiotics unclear
• high (85%-90%) cure rates with or without active
antibiotic suggest I&D alone may be sufficient in most
cases
• consider antibiotic therapy for patients who present with
severe or extensive disease, signs or symptoms of systemic
• illness, associated comorbidities, immunosuppression,
extremes of age, abscess on area difficult to drain
completely (eg, hand, face, genitalia), or failure of
previous I&D
• study of patients with purulent infections, abscesses, and
cellulitis found most infections due to MRSA, suggesting
MRSA coverage indicate
Which of the following
antibiotics provides coverage of
methicillin-resistant S aureus,
methicillin-susceptible S aureus,
and group A streptococci?
A) TMP-SMZ
B) Doxycycline
C) Minocycline
D) Clindamycin
Answer
• D) Clindamycin
Oral antimicrobial options for CA-MRSA
• TMP-SMZ, doxycycline, and minocycline associated with low rates of
resistance, but unreliable for group A streptococci (GAS)
• clindamycin— covers MRSA, MSSA, and GAS
• excellent tissue and abscess penetration
• associated with risk for C difficile infection
• linezolid—indicated for complicated skin and soft tissue infections;
expensive; may lead to adverse events (primarily with long-term use)
• inducible clindamycin resistance —clindamycin therapy associated
with potential for selecting for resistance detected by specialized
testing (D-test)
• consider when laboratory report shows MRSA isolate resistant to
erythromycin and susceptible to clindamycin
• rates vary; unclear whether it leads to treatment failure; in some cases
(eg, mild or improving infection), may be reasonable to continue
clindamycin if patient
• does not respond to therapy or if patient has moderate to severe
infection, change antibiotics
Choose the correct statement about
decolonization regimens for recurrent skin
and soft tissue infections.
A) Mupirocin shown to prevent first-time skin
and soft tissue infection
B) Chlorhexidine appears to have transient
effect on colonization, but does not reduce
skin and soft tissue infection rates
C) Oral antimicrobial regimens routinely
recommended
D) Long-term use of rifampin-based regimens
recommended
Answer
• B) Chlorhexidine appears to have transient
effect on colonization, but does not reduce
skin and soft tissue infection rates
Decolonization regimens
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no clinical data suggest effectiveness in preventing recurrences
mupirocin—in recent study, application to nose twice daily for 5 to 10 days
resulted in reduced colonization, but did not prevent first-time skin and soft
tissue infection
mupirocin plus topical skin antiseptic (eg, chlorhexidine, dilute bleach)—
chlorhexidine alone appears to have transient effect on colonization, but does
not reduce skin and soft tissue infection rates
combination recently shown to reduce surgical site infection rates
oral antimicrobial regimens—not routinely recommended
may consider in combination with rifampin
Cochrane Review showed no benefit of systemic antibiotics for eradication of
hospital-acquired MRSA or reduction in infection rates
other systemic review found short-term reduction in S aureus colonization
with rifampin-based combination regimens, but no effect on infection rates
concerns include rifampin resistance and potential side effects
rifampin-based regimens recommended for short courses only
“if all else fails”—combination of TMP-SMZ and rifampin for 5 days, then
repeat every 6 wk for 8 cycles
add chlorhexidine and counsel about personal hygiene
vitamin C possibly beneficial (data limited)
Which of the following is the
most common cause of
monomicrobial necrotizing
fasciitis?
A) S aureus
B) Clostridia
C) β-hemolytic streptococci
D) Group A streptococci
Answer
• D) Group A streptococci