How To Choose Antibiotics For Staph Aureus Infections

By Mark Kosinski, DPM

The common thread shared by virtually all antibiotics relevant to podiatry is their activity against S. aureus. After all, S. aureus is by far the predominant infecting organism in lower extremity skin and skin structure infections. The rationale behind choosing an appropriate anti-staphylococcal drug is a daunting task given the ever-changing resistance pattern of this formidable organism. Today, virtually all strains of S. aureus found in lower extremity infections produce beta-lactamase. Beta-lactamase (also known as penicillinase) is an enzyme that cleaves the beta-lactam ring and inactivates the antibiotic. Therefore, empiric therapy for suspected Staph infections should always include a beta-lactamase stable antibiotic. For this reason, it is useful to categorize antibiotics as being either beta-lactamase stable or beta-lactamase susceptible. Drugs such as amoxicillin and ampicillin are beta-lactamase susceptible and should not be relied upon to treat lower extremity Staph infections. Patients will often begin self-treatment with these agents as they may have a few capsules left over from an ear or dental infection. However, they have minimal usefulness in the foot. To overcome bacterial resistance, some drugs combine a beta-lactam antibiotic and a beta-lactamase inhibitor, thus creating a stable, new compound (such as amoxicillin/clavulanate, ampicillin/sulbactam, piperacillin/tazobactam and ticarcillin/clavulanate) with good activity against Staph. A useful side benefit of these additions is the extension of the drug’s spectrum to include B. fragilis, which makes the antibiotics attractive choices when anaerobic bacteria is an issue. Nafcillin, oxacillin, dicloxacillin and, of course, methicillin, also known as the semisynthetic or penicillinase resistant penicillins, are all beta-lactamase stable as are the cephalosporins and carbapenems. Historically, methicillin was one of the first drugs developed to combat the growing number of beta-lactamase producing S. aureus infections. However, methicillin is no longer used due to adverse reactions. The primary reason to be familiar with the drug is because organisms resistant to the entire class have become known as “methicillin resistant.” Other antibiotics are beta-lactamase stable and active against Staph by virtue of the fact that they are not beta-lactam compounds and thus do not contain a beta-lactam ring (see “Other Agents” in “Differentiating Antibiotic Categories” below). Although they have varying degrees of activity against S. aureus, they are often used to help treat patients who have a history of a penicillin allergy. Understanding The Origin And Impact Of MRSA Shortly after its introduction, strains of S. aureus resistant to methicillin began to emerge. Currently, rates of nosocomial methicillin resistant Staph aureus (MRSA) approach 60 percent in many ICUs. Rates of MRSA in the community have likewise been increasing with a recent study putting the number at close to 40 percent. In early reports, community isolates of MRSA had largely affected people with known risk factors for colonization. These risk factors included patients who have been in acute or long term care facilities, individuals who have recently undergone antibiotic therapy and those in proximity to patients infected or colonized with MRSA. However, recent reports describe colonization and transmission in populations lacking risk factors. To understand why some drugs are active against MRSA and others are not, it is helpful to look at the mechanism of resistance. Methicillin resistance is associated with penicillin binding protein 2a (PBP2a). Encoded by the mec A gene, PBP2a has low binding affinity for beta-lactam antibiotics. Therefore, by definition, MRSA is resistant to all currently available beta-lactam antibiotics. Over the years, oxacillin has replaced methicillin on culture and sensitivity reports as the antibiotic one looks to for identifying MRSA. Oxacillin is a more stable drug and is more resistant to degradation in storage. Oxacillin is also more likely to detect heteroresistant strains. Indeed, methicillin has fallen out of use and is no longer commercially available in the United States. The acronym MRSA is still used to describe these isolates because of its historic role.

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