Evidence-based Medicine

Case Presentation

• 27 yo AA male presents to clinic with 3 days of pain and swelling in right leg

• First noted several spider bites on his leg – concerned they may be infected now

• Denies fever, chills, nausea, or other symptoms

Case Presentation

• PMH: HTN

• Meds: HCTZ, Adalat

• Allergies: NKDA

• Social: AD PO2 on shore duty at NI. Lives in Chula Vista with his wife.

• No recent antibiotics or hospital contacts

PE

• Vitals: BP - 132/82 P - 64 T - 98.1

• Gen: AAOX3, Appears well

• CV/Pulm: Unremarkable

• Right LE: Small, open pustule with surrounding edema, erythema. Scant thick, white discharge from lesion.

Diagnosis

• Uncomplicated cellulitis

Question

• What antibiotic is appropriate for uncomplicated cellulitis in an outpatient without risk factors for MRSA?

Choices…

• A) Any cephalosporin• B) vancomycin• C) linezolid• D) TMP-SMX• E) clindamycin• F) a fluoroquinolone• G) a tetracycline• H) An antistaphylococcal

PCN• I) Combination therapy

What bug is targeted?

a) MSSA

b) Streptococcus

c) MRSA

d) Pseudomonas

Is MRSA a concern?

• Emergence of CA-MRSA USA300 Clone as the Predominant Cause of Skin and Soft-Tissue Infections

• King, et al. Annals of Internal Medicine, 7 March 2006.

Background

• CA-MRSA known to be pathogen in select populations (prisons, military recruits)

• Is this an important community pathogen?

Methods

• Prospective study at single public inner-city hospital (Atlanta, GA) over 3.5 months in 2003.

• Retrospective review of records for all pts with S. aureus culture for HIV status, ESRD, hospitalization within 12 months, hx of MRSA, and cx within 72 hours of admission

• Reviewer was blinded to type of S. aureus infection

Genetic Analysis

• Pulse-field gel electrophoresis on most samples – compared to CDC samples

• Assessed for Panton-Valentine leukocidin gene by PCR

Statistical Analysis

• Univariate analysis of potential risk factors in MRSA USA 300/400 vs MSSA and MRSA USA 300/400 vs MRSA other.

• Then multivariate analysis of potential risk factors

Univariate Results

Multivariate Results

Discussion

• 72% of all S. aureus infections were caused by MRSA

• USA 300/400 clone accounted for 87% of ca-MRSA infections

Author’s conclusions

• MRSA coverage is essential to empiric coverage of skin and soft tissue infections

• I&D alone may be sufficient, but poor data

• USA 300 clone is usually sensitive to TMP-SMX, linezolid, tetracycline

• May have inducible clindamycin resistance

Study Weakness

• Only examined culture positive S. aureus infections, not all soft tissue infections

• All data from one hospital

• No evaluation of treatment

Surviving the New Killer Bug

• From Time Magazine; 26 June 2006

• “This is not bird flu or SARS or even the "flesh-eating bacteria" of tabloid fame. But it is every bit as dangerous, even if it goes by an uncommonly ungainly name: community-acquired methicillin-resistant Staphylococcus aureus (MRSA). Never heard of it? Neither have most doctors.”

CA-MRSA

• Typically USA 300 or USA 400 clone

• Normal resistance pattern includes resistance only to β-lactams and erythromycin

• Occasional resistance to levofloxacin, clindamycin, rifampin, and gentamycin

• Contains Panton-Valentine leukocidin gene (pvl) and SCCmec type IV gene

Panton-Valentine leukocidin gene

• Thought to be one of the major virulence factors for CA-MRSA

• Causes leukocyte destruction and tissue necrosis

Nosocomial MRSA

• Usually MDR

• Does not contain Panton-Valentine leukocidin gene

Is this applicable to our population?

• MRSA Infections among Patients in the Emergency Department

• Moran, et al. NEJM – 17 August 2006

Methods

• Prospective prevalence study

• Enrolled patients in 11 ERs with acute, purulent skin infections in August 2004

• Isolates typed with PFGE and PCR

Results

• S. aureus isolated in 76% of patients

• MRSA isolated in 59% of patients (78% of S. aureus cultures)

Results

Discussion

• 97% of MRSA was a USA 300 strain

• Susceptibilities: 100% TMP-SMX and rifampin; 95% clindamycin; 92% tetracycline

• Infectious organism resistant to antibiotic prescribed in 57% of patients (most common antibiotic was a β-lactam)

Discussion

• 59% of patients contacted for follow-up

• 96% of these patients reported the infection resolved or improved

• No association between antibiotic used and outcome in limited follow-up

Discussion

• 99% of MRSA had PFGE consistent with CA-MRSA, although 25% had risk factors for health-care associated MRSA

Study Weakness

• Poor follow-up – study not designed for treatment arm

• Only included purulent infections

• Only enrolled 42% of eligible patients

Question?

• What antibiotic is appropriate for uncomplicated cellulitis in an outpatient without risk factors for MRSA?

My Thoughts

• Treatment of any abscess requires drainage first

• Culture should always be performed on purulent infections

• Antibiotic coverage must include, at minimum, coverage for MRSA, MSSA, and group A streptococcus

My Thoughts

• A) Any cephalosporin – Will miss MRSA• B) vancomycin – Not appropriate for outpatient• C) linezolid – Very expensive; may induce resistance• D) TMP-SMX – Will likely miss streptococcus• E) clindamycin – May miss MRSA (inducible resistance)• F) A fluoroquinolone – Will miss MRSA, +/- vs strep• G) A tetracycline – Good coverage if tolerated• H) Antistaphylococcal PCN – Will miss MRSA• I) Combination therapy – More difficult, less compliance

My Thoughts

• Combination of TMP-SMX plus β-lactam until sensitivity results are available is appropriate empiric coverage

• Single coverage with a tetracycline is also appropriate

• Clindamycin not recommended as single therapy unless a “D-test” is performed

My Patient

• No culture performed

• Treated with clindamycin with full resolution of symptoms

Questions?

Sources• Fridkin, Scott, et al. MRSA Disease in Three Communities. NEJM

352;14• Graham, Philip, et al. A US Population-Based Survey of S. aureus

Colonization. Annals of Internal Medicine. 7MAR2006; 144:318-325• Grayson, M. The Treatment Triangle for Staphylococcal Infections.

NEJM; 355:724-726• King, Mark, et al. Emergence of CA-MRSA USA300 Clone as the

Predominant Cause of Skin and Soft-Tissue Infections. Annals of Internal Medicine. 7MAR2006; 144:309-317

• Moellering, Robert. The Growing Menace of CA-MRSA. Annals of Internal Medicine. 7MAR2006; 144:368-369

• Moran, G.J, et al. MRSA Infections among Patients in the Emergency Department. NEJM 355;7

• Pictures from: http://www.kcom.edu/faculty/chamberlain/