Trimethoprim displays greatest activity against methicillin-resistant Staphylococcus aureus

August 1, 2007

In vitro susceptibility patterns do not differentiate among the newer fluoroquinolones, (levofloxacin, moxifloxacin, and gatifloxacin). All have equal effectiveness against methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible S aureus (MSSA). With the exception of trimethoprim, a dihydrofolate reductase inhibitor, MRSA was highly resistant to all antibiotics tested by the TRUST (Tracking Resistance in the U.S. Today) Study. MSSA was highly susceptible to all antibiotics except polymyxin B, a polypeptide; penicillin, a ,b-lactam; and azithromycin, a macrolide. When treating patients with MRSA infections, the potential for failure of the antibiotics must be considered.

Key Points

"S aureus can cause potentially sight-threatening infections, including corneal ulcers and endophthalmitis. Broad-spectrum antibiotics such as the newer fluoroquinolones levofloxacin, gatifloxacin, and moxifloxacin are valued for their activity against a wide range of gram-positive and -negative pathogens, including S aureus. However, MRSA strains are often simultaneously resistant to multiple antibiotics, including the fluoroquinolones," he said.

"The increasing prevalence of MRSA in hospital- and community-acquired systemic infections as well as ocular infections has been reported. Longitudinal surveillance to detect changes in resistance can facilitate therapy selection," Dr. Ta said, highlighting the importance of this effort. About one in six S aureus ocular isolates are MRSA.

Isolates from eye infections were collected from October 2005 to June 2006 from seven eye hospitals and 28 community hospitals in 26 cites in 19 states. All isolates were tested by broth microdilution according to Clinical Laboratories Standards Institute (CLSI) methodology at a centralized independent laboratory. The minimal inhibitory concentrations were interpreted as susceptible, intermediate, or resistant according to 2006 CLSI criteria.

The antibiotics tested were the fluoroquinolones ciprofloxacin, gatifloxacin, levofloxacin, and moxifloxacin; azithromycin; penicillin; polymyxin B; tobramycin, an aminoglycoside; and trimethoprim.

The authors reported that 197 isolates were submitted for testing. Of these, 164 (83.2%) were MSSA and 33 (16.8%) were MRSA. "Most antimicrobials were active against MSSA, with the exception of penicillin and polymyxin B and, to a lesser extent, azithromycin. Tobramycin and trimethoprim displayed the greatest in vitro activity against MSSA, even greater than the fluoroquinolones. All fluoroquinolones tested had a similar antibiotic susceptibility pattern," Dr. Ta reported.

In contrast, the MRSA isolates were highly resistant to eight of the nine antimicrobials tested, except trimethoprim. Specifically, MSSA susceptibility testing indicated that 97.6% of isolates were susceptible to trimethoprim; 92.7% to tobramycin; 81.1% to the newer fluoroquinolones levofloxacin, gatifloxacin, and moxifloxacin; 79.9% to ciprofloxacin; 54.3% to azithromycin; and 9.8% to penicillin. No MSSA isolates were susceptible to polymyxin B.

MRSA susceptibility testing showed that 93.9% of isolates were susceptible to trimethoprim; 36.4% to tobramycin; 15.2% to ciprofloxacin, levofloxacin, gatifloxacin, and moxifloxacin; and 6.1% to azithromycin. No isolates were susceptible to penicillin or polymyxin B.

"The study demonstrated that trimethoprim is the most active agent against S aureus, displaying the greatest activity against MSSA and being the only agent to which MRSA is susceptible. Newer and older fluoroquinolones share nearly identical patterns of in vitro activity against S aureus, with MSSA displaying a relatively high degree of susceptibility but MRSA showing high-level resistance. MRSA cultured from ocular infections displays multi-drug resistance with high-level resistance to all agents except for trimethoprim," Dr. Ta commented.

Based on these results, he noted that when treating patients with MRSA infections, the potential for failure of the antibiotics must be considered.