Part of a Perfect Microbial Storm
Alana Arnold, PharmD
Associate Director-Clinical Coordinator
Infectious Disease Specialist
Part of a Perfect Microbial Storm
The family tree
Methicillin sensitive s.aureus (MSSA)
Methicillin resistant s.aureus (MRSA)
– Healthcare-associated MRSA (HC-MRSA)
– (h/o surgery, dialysis, LTC within 12 months)
– Community-acquired MRSA (CA-MRSA)
Where do we usually see it?
Staph Scalded Skin Syndrome
Toxic Shock Syndrome
4 Swartz MN. In Mandell GL et al. Principles of Infection Dis. 2000;1037-1057.
Other concerning infection sites
Bacteremia and sepsis
– Osteo, meningitis, endocarditis, etc
Surgical site infections
Catheter associated infections
Infections of prosthetic devices
5 Waldvogel FA. In Mandell GL et al> Principals and practice of Infect. Dis. 2000; 2069-2092.
The adaptive potential of the microbial world
is such that for each new antibiotic that is
introduced, several escape mechanisms are
The action of antibiotics and resistance are
linked like light and shadow: one does not
exist without the other.
6 Waldevogel, NEJM, 1999
Methicillin-resistant Staphylococcus aureus
First described: 1961
Definition: MRSA is a bacterium responsible for difficult-to-treat
infections in humans. MRSA is a strain of Staphylococcus
aureus that is resistant to a large group of antibiotics called the
beta-lactams, which include the penicillins and the
Resistance: The mecA gene (the gene responsible for methicillin
resistance) is part of a mobile genetic element found in all
MRSA strains. Katayama et al. demonstrated that mecA is part
of a genomic island designated staphylococcal cassette
chromosome mec (SCCmec).
Hospital–associated strains of S. aureus Courtesy of the CDC
still cause about 85% of all MRSA cases. Large numbers of
Staphylococcus aureus bacteria,
Hospital patients with S. aureus which were found on the inside
surface of a catheter. The sticky-
infections are five times more likely to die looking substance woven
between the round cocci bacteria
than are patients without the infection. is known as a “biofilm”.
Biofilms help to protect the
Multi-drug resistant (MDR) – resistant to bacteria.
beta-lactams UNLIKE MSSA !
Vancomycin - one treatment option for
HA-MRSA, but is often no longer
effective due to rising MICs.
From HA and CA-MRSA
Until recently, most MRSA infections started in
hospitals, especially among surgical and
immunocompromised patients. (HA-MRSA)
In the early 1980s, new strains of MRSA began to
strike healthy people in community settings – first
identified in Detroit. (CA-MRSA)
Community MRSA that was NOT MDR !
Direct person to person contact
Sharing of towels or personal hygiene items
Drug use equipment
Prevalence is increasing!!
HA-MRSA in ICU patients
1989 = 27%
2005 = 60%
Some areas report > 10% incidence in ER skin infection visits
– antibiogram to assess prevalence in community.
– risk factors for MRSA
Prevalence - August 2004
Add chart – ER incidence
Morgan gj et al NEJM 2006; 355:666-74
12 Moran, et al. NEJM 2006;355:666-674
Staphyloccal bacteria that have become Courtesy of the CDC
resistant to beta-lactam antibiotics but
NOT multi-drug resistant (MDR).
Several antibiotics remain effective
against CA–MRSA, but it is an
aggressive and rapidly evolving form of
S. aureus. Cutaneous abscess
caused by methicillin–
Usually appears as a skin infection, but resistant
it can spread quickly to a bloodstream Staphylococcus aureus
infection or a very serious form of bacteria.
HA-MRSA and CA-MRSA
Mean Age Old Young
SSTI % 35% 75%
Resistance gene SCCmec type I,II,III SCCmec type IV,V
Strain Type USA 100 and USA 200 USA 300 and USA 400
PVL Toxin Gene Rare 5% Almost 100%
Susceptibility Vancomycin, Linezolid Usually susceptible to Bactrim,
Synercid, Daptomycin doxycycline, clindamycin, rifampin
Risk Factors Recent hospitalization or -Close contact-childcare centers,
surgery, recurrent abscesses, nursing homes, prisons.
Long term care, IV drug user, -Certain populations (Pacific
indwelling catheters, medical Islanders, Native Americans), Contact
conditions such as diabetes, sports (football, wrestling)
14 HIV, renal failure -Sharing of towels, equipment
Strain Type – USA300
Staphylococcus aureus (CA-MRSA) infections are
caused primarily by a single strain — USA300 — of
an evolving bacterium that has spread with
"extraordinary transmissibility" throughout the United
States during the past five years, according to a new
study led by National Institutes of Health (NIH)
scientists. CA-MRSA, an emerging public health
concern, typically causes readily treatable soft-tissue
infections such as boils, but also can lead to life-
threatening conditions that are difficult to treat.
Monday, January 21, 2008 -5:00 p.m. EST NIH News
Panton–Valentine Leukocidin (PVL)
Described in 1932
Gene common among CA-MRSA strains resulting in
increased virulence (enhances inflammation and
– Lysis of WBCs
– Dermal Necrosis
Associated with necrotizing pneumonia (destruction of
healthy lung tissue), fasciitis
Commonly complain of infected pimples, spider
bites, or sores.
Usually minor carbuncles, furuncles, abscesses.
Can be more extensive cellulitis, deep-seated
abscesses, septic arthritis, pneumonia and sepsis.
Should be considered in the DDX of all SSTIs.
Aerobic cultures should be obtained on all open
lesions/ draining abscesses.
Some S. aureus infections can be treated
without antibiotics by surgically draining the
wound. Local incision and drainage and hot Cultured Staphylococcus
packs are first-line therapy for skin infections. aureus on agar plate.
Before prescribing an antibiotic, a doctor must
determine if MRSA bacteria are present.
Using the wrong drug delays treatment and
encourages the development of more resistant
Bactrim (PO + IV)
Clindamycin (PO + IV)
Linezolid (PO + IV)
Fluoroquinolones (PO + IV)
CA-MRSA can demonstrate in vitro sensitivity
– 76% Susceptibility
– Strong consideration for treatment
MSSA isolates rarely develop methicillin resistance and
typically remain susceptible
Overuse of fluoroquinolones may cause:
– MSSA colonization replaced by MRSA post-exposure
– Increased expression of adherence factors promote host
colonization via over-expression of fibronectin-binding protein
Weber SG Emerg Infect Dis 2003 Nov; 9: 1415-22. LeBlanc L Emerg Infect Dis 2006 Sep; 12: 1398-
20 405. Bisognano C Antimicrob Agents Chemother. 1997 May; 41: 906-13.
LaPlante KL, Rybak MJ, Amjad M, Kaatz GW. Pharmacotherapy. 2007 Jan;27(1):3-10
95% CA-MRSA isolates are susceptible
Excellent bioavailability and distribution
Poor activity against Streptococcus species
(GAS and Beta hemolytic)
Dosage & Dosage Forms
Not recommended for use in patients <2 mos.
Dosage: TRIMETHOPRIM component
– PO: 6 to12 mg/kg/day divided BID-TID
– Usual max dosing of 160-320 mg PO BID-TID
– Suspension: Trimethoprim 40 mg sulfamethoxazole 200 mg
and per 5 mL
– Single strength: Trimethoprim 80 mg and sulfamethoxazole
– Double strength: Trimethoprim 160 mg and
sulfamethoxazole 800 mg
Coverage for Staphylococcal and Streptococcal
Excellent bioavailability and distribution
Suppresses PVL production of CA-MRSA
Potential for emergence of resistance with high
inoculum infections caused by strains inducibly
resistant to erythromycin
– D-zone test should be performed to identify inducible
clindamycin resistance in S. aureus determined clindamycin
susceptible via MIC method
LaPlante K. Antimicrobial Agents Chemotherapy. 2008;52:14
Activity against Staphylococcal and
Like clindamycin, linezolid also suppresses
PVL production in CA-MRSA
Drug-Drug & Drug-Food Interactions
Serotonin syndrome possible with concomitant
– Tyramine rich foods
– Serotonergic medications (SSRIs, MAOIs)
Foods high in tyramine:
– Aged, fermented, pickled, smoked
Cheese, pepperoni, soy sauce, red wines, beer,
Minocycline and Doxycycline
Susceptibility >90% for CA-MRSA
Potential, but unreliable coverage for Group
Not indicated for children <8 yrs of age
– Tooth enamel hypoplasia
– Tooth discoloration
Moran G NEJM. 2006;7:666-74.
Four Pediatric Deaths from Community-Acquired
Methicillin-Resistant Staphylococcus aureus -- Minnesota
and North Dakota, 1997-1999 (MMWR Vol.48/No.32)
– Cases of community-acquired MRSA infection in patients without established
Community Acquired Methicillin-Resistant Staphylococcus
aureus in a Rural American Indian Community
Methicillin-Resistant Staphylococcus aureus Infections in
correctional facilities – Georgia, California and Texas,
The Perfect Microbial Storm
December 6, 2003
Ricky Lannetti presented to ER due to rapidly
worsening pneumonia and died within
12hrs. He also had influenza infection during same time period.
PMH: healthy star wide receiver for Lycoming College
Autopsy: Death result of MRSA infection
CDC Analysis: Staph-USA300
During same flu season: 4 similar deaths in Baltimore
ID specialist John Francis (John Hopkins) led team of investigators
who made the link between USA300 and influenza.
―When this strain of staph ends up in the same body as the influenza
virus,‖ says Francis, ―the result is the perfect storm, a one-two
28 punch to the immune system.‖
Necrotizing pneumonia associated with PVL toxin is a recent
described clinical entity. It mainly occurs in children and young
adults (median age 15 years), is fatal in 75% of cases, and is
associated with a median survival time of 4 days.
Necrotizing pneumonia is mainly associated with PVL-positive
methicillin-susceptible and methicillin-resistant Staphylococcus
Necrotizing pneumonia is often preceded by a viral-like illness.
Viruses such as the influenza A virus have been isolated
concomitantly with the PVL-positive S. aureus.
Garnier F, Tristan A, François B, Etienne J, Delage-Corre M, Martin C, et al. Pneumonia and new
29 methicillin-resistant Staphylococcus aureus clone. Emerg Infect Dis. 2006 Mar.
Predicting the future…..
CA-MRSA rapidly increasing in prevalence
Increase in antibiotic resistance as CA-MRSA moves
into healthcare setting
Increase in CA-MRSA bacteremia due to
colonization in hospitals
CA and HA-MRSA distinction blurring
Increase in necrotizing pneumonia associated with
the looming influenza pandemic infection
Isolation and Contact Precautions within health
Wash hands frequently and thoroughly.
Use hand sanitizer if soap/water are not available.
Keep skin cuts clean and covered.
Don’t touch another person’s wound or bandage.
Avoid sharing personal items (towels, razors,etc)
Routine cleaning of athletic equipment
Routine disinfection of countertops, exam tables or
other treatable surfaces.
All open wounds should be covered.
Get immunized !!