How Can Nafcillin Treat Beta-Lactamase–Producing Staphylococcus aureus?

• If beta-lactamase destroys beta-lactam antibiotics, how can a beta-lactam like nafcillin treat the organism?
  • The reason comes down to the structure of the antibiotic—specifically, the side chain attached to the beta-lactam ring
• Does beta-lactamase production make Staphylococcus aureus resistant to beta-lactam antibiotics?
  • To some but not all
• Can you use nafcillin, a beta lactam antibiotic, to treat beta lactamase producing staph aureus?
  • Yes

Let’s take a closer look at why nafcillin remains effective against methicillin-susceptible Staphylococcus aureus (MSSA) despite production of the beta-lactamase enzyme.

What is a Beta Lactam Antibiotic?

Quite simply, any antibiotic that has a beta lactam ring is a beta lactam antibiotic. The beta lactam “ring” looks more like a square.

Beta Lactam antibiotics refer to a broad classification that includes a number of smaller and distinct antibiotics subgroups. This includes penicillins, cephalosporins, monobactams and carbapenems.

What is Beta Lactamase?

Beta lactamase is an enzyme produced by some bacteria. This enzyme disrupts the beta lactam ring on the antibiotics rendering them ineffective. The beta lactam structure has to be intact for the antibiotic to be effective.

How Some Penicillins Avoid Penicillinase

While all penicillins share the presence of a beta lactam ring what gives them unique properties is the difference in the side chains attached to the ring.

Some antibiotics have a bulky side chain that physically blocks access to the site where beta lactamase has to bind in order to disrupt the beta lactam ring. For nafcillin this bulky side chain is called the naphthyl group.

Nafcillin is available an intravenous infusion. It is most commonly dosed 2g every 4 to 6 hours. It can also be administered as a continuous infusion.

Another available penicillin that maintains its bactericidal activity in the presence of the beta lactamase enzyme is dicloxacillin. Dicloxacillin is an oral antibiotic typically dosed 500mg to 1000mg every 6 hours.

Clinical Significance

Penicillin antibiotics are still the preferred agent to treat MSSA. The Infectious Disease Society of America (IDSA) infective endocarditis guidelines recommend nafcillin as a preferred agent for treatment of MSSA native-valve endocarditis.

Penicillins are bactericidal and have low toxicity. These qualities are especially important when patients require extended durations of treatment. This includes cases of endocarditis, osteomyelitis and meningitis. Nafcillin is an excellent antimicrobial when the infecting organism is MSSA.

Common Pit Falls

Culture and sensitivity reports can often be misinterpreted when beta lactamase is detected.

1. The presence of beta lactamase does not exclude the use of all beta lactam antibiotics
2. An MIC indicating sensitivity to a beta lactamase producing staph species not always mean that it is an appropriate choice.

Here is a sample of what the culture and sensitivity report may look like:

The above culture and sensitivity report shows susceptibility of staph aureus to oxacillin making is MSSA with susceptibility to ampicillin/sulbactam. However, the detection of beta-lactamase with penicillin should eliminate ampicillin/sulbactam as an option. A positive beta lactamase result overrules the MIC for beta lactams that are not beta lactamase resistant.

Why Can’t Lab Report Resistance When Beta Lactamase of Detetcted?

Clinical and Laboratory Standards Institute (CLSI) requires that antibiotic susceptibility be reported based on MIC only. This is why culture and sensitivity reports must not simply be read but interpreted.

The current recommendation by CLSI is that all penicillin susceptible MSSA should be tested for beta lactamase production.

Production of penicillinase is coded by BlaZ, which can be detected by PCR. It is also commonly detected by the Cloverleaf Test.

If want to learn more about how to analyze culture and sensitivity reports check out my post: How to Analyze Antimicrobial Culture and Sensitivity Reports

Hope this helps!

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