Current Concepts:

Methicillin resistant staphylococcus aureus

Andrew BernhardKent State University College of Podiatric Medicine

Department of Podiatry, Medical StudentBeth Israel Deaconess Medical Center

Harvard Medical School

Boston, MA

A teaching hospital of

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Methicillin Resistant Staph. Aureus

• Methicillin was first produced in 1959

• During the 1960s, infrequent MRSA outbreaks occurred in Europe and Australia.

• In 1968, Boston City Hospital reported the first case in America.

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MRSA Considerations

• S. aureus is traditionally sensitive to beta-lactam antibiotics.

• These antibiotics inhibit cell wall synthesis, which results in bacteriocidal performance.

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β-Lactam Resistance

• The key to MRSA virulence is its resistance, which can be due to production of hydrolytic enzymes, like β-Lactamase and penicillinase, or altered penicillin binding proteins.

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Resistance Mechanisms

Figure 1, above, depicts the conversion of penicillin to penicilloic acid, an inactive compound.

Figure 2, right, depicts mecA encoded PBPs, which do not bind β-Lactam antibiotics.

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What does this mean?

• MRSA rates are generally considered to have been increasing.

• Large, generalized population studies are rare, but studies specifically show increased incidence in the following:

• High school athletes• Dutch animal farmers• Young Ohioans• Hospitalized patients• Nursing home workers• College students

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Further statistics

• According to the CDC: – 79 million Americans are

colonized with staph aureus

– 4.1 million are colonized with MRSA

– The prevalence of MRSA has increased from 2% of staph infections in 1974 to

64% in 2004.

Thankfully, some newer research shows a decrease in MRSA rates

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Why the downward trend?

• Needles with safety features and antimicrobial coated catheters have offered minimal infection control.

• Improvements in hospital staff behavior have proven more effective.

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What about contact precautions?

• We are all familiar with them but what does the research say?

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Contact Precaution Efficacy on MRSA

• Few prospective studies exist.

• The good news is that several studies show a correlation between contact precautions and decreased MRSA transmission, most notably Jernigan in 1996.

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On the down side,

• There are many studies which also demonstrate non-superiority of contact precautions, though they are older.

• More commonly, current literature speaks to adverse effects.

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• From Morgan’s comprehensive literature review

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How does this affect MRSA?

• Most patients under contact precautions are there because they are MRSA colonizers.

• Active surveillance cultures are a great tool for identifying these patients.

• But what new treatments are in the pipeline?

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Ceftobiprole

• New 5th generation cephalosporin

• Broad spectrum and bacteriocidal

• No safety concerns

• Efficacy trials were potentially biased

• Currently only available in Switzerland

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Oritavancin• A glycopeptide

antibiotic, like Vanco• Seemingly bacteriocidal

against MRSA, VRE, C. diff, and Anthrax

• Has had less ADRs then comparable drugs, but studies were not powerful enough for FDA.

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Iclaprim

• Diaminopyrimidine dihydrofolate reductase inhibitor

• Similar to trimethoprim, but active against MRSA, VRSA, S. pneumonia, and gram –

• Has been granted fast-track FDA status

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The State of Antibiotic Research

• Most sources say that antibiotic development is currently very underfunded.

• New classes of drugs are more likely to be successful than newer versions of older drugs.

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New Drug Targets

• Yoneyama and Katsumata offer a review of potential new drug targets: – Peptide deformylase– Non-mevalonate pathway– Bacterial fatty acid

synthesis– Bacterial virulence

factors

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Any Questions?

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(2008) 8(5), 289-301.

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