Fluoroquinolones and the Risk for Methicillin-resistant Staphylococcus aureus in Hospitalized Patients

Stephen G. Weber, Howard S. Gold, David C. Hooper, A.W. Karchmer, Yehuda Carmeli


Emerging Infectious Diseases. 2003;9(11) 

In This Article

Abstract and Introduction

To determine whether fluoroquinolone exposure is a risk factor for the isolation of Staphylococcus aureus and whether the effect is different for methicillin-resistant S. aureus (MRSA) versus methicillin-susceptible S. aureus (MSSA), we studied two case groups. The first case group included 222 patients with nosocomially acquired MRSA. The second case group included 163 patients with nosocomially acquired MSSA. A total of 343 patients admitted concurrently served as controls. Outcome measures were the adjusted odds ratio (OR) for isolation of MRSA and MSSA after fluoroquinolone exposure. Exposure to both levofloxacin (OR 5.4; p < 0.0001) and ciprofloxacin (OR 2.2; p < 0.003) was associated with isolation of MRSA but not MSSA. After adjustment for multiple variables, both drugs remained risk factors for MRSA (levofloxacin OR 3.4; p < 0.0001; ciprofloxacin OR 2.5; p = 0.005) but not MSSA. Exposure to levofloxacin or ciprofloxacin is a significant risk factor for the isolation of MRSA, but not MSSA.

Methicillin-resistant Staphylococcus aureus (MRSA) has been implicated as a pathogen in hospital-acquired infections since the 1960s.[1] During the 1990s, the proportion of nosocomial infections caused by MRSA increased substantially, and MRSA is now a leading cause of such infections in the United States.[2] According to data from the SENTRY Antimicrobial Surveillance Program, approximately 40% of S. aureus isolates recovered in intensive care units (ICU) are resistant to methicillin.[3] Recently, MRSA infections acquired in the community have been identified as emerging pathogens responsible for substantial disease and death.[4,5] While no satisfactory explanation exists for the recent proliferation of MRSA, expanded use of antimicrobial drugs in sites outside the hospital has been suggested as a major contributor to emerging resistance in the community.[6]

Fluoroquinolones are among the most commonly prescribed classes of antimicrobial drugs in both the hospital and in the community. Ciprofloxacin, one of the first fluoroquinolones to gain extensive clinical use, was originally heralded for its activity against a broad range of pathogens, including MRSA.[7] However, by the early 1990s, many MRSA isolates from clinical specimens were found to be resistant to ciprofloxacin.[8] The next generation of fluoroquinolones, including levofloxacin, was introduced during the second part of the 1990s and promised improved activity against gram-positive pathogens. Unfortunately, screening of large numbers of staphylococcal bloodstream isolates as part of the SENTRY Antimicrobial Surveillance Program demonstrated resistance to many of the newest fluoroquinolones as well.[9]

Several recent investigations offer preliminary evidence that suggests that the fluoroquinolones themselves may actually predispose patients to infection with or carriage of MRSA. A comparison of microbiology laboratory data with antimicrobial reimbursement reports found a significant correlation between ciprofloxacin prescriptions and the isolation of MRSA.[10] Two case-control studies examining risk factors for MRSA have found a significant association between fluoroquinolone exposure and MRSA isolation or infection.[11,12] Preliminary analysis from one also suggested a difference in risk between members of the class. Additionally, a prospective study examining the impact of nasally administered mupirocin ointment on MRSA carriage also identified fluoroquinolone exposure as a risk factor for MRSA carriage.[13] However, none of these studies was designed specifically to examine the risk associated with fluoroquinolones. Moreover, the design of the prior case-control investigations, as a result of the inappropriate use of patients colonized or infected with sensitive strains for controls, may have yielded biased results. Thus, the association between fluoroquinolone exposure and MRSA remains to be confirmed.

This study was specifically designed to determine whether exposure to fluoroquinolones is a risk factor for the subsequent isolation of S. aureus, and whether the effect is different for MRSA versus methicillin-susceptible S. aureus (MSSA). In addition, we sought to preliminarily explore any difference in risk between levofloxacin and ciprofloxacin.

1This study was presented in part at the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, California, September 2002.