In Vitro Activity of Newer Fluoroquinolones for Respiratory Tract Infections and Emerging Patterns of Antimicrobial Resistance: Data from the SENTRY Antimicrobial Surveillance Program

S16 In Vitro Activity of Newer Fluoroquinolones for Respiratory Tract Infections and Emerging Patterns of Antimicrobial Resistance: Data from the SENTRY Antimicrobial Surveillance Program Ronald N. Jones and Michael A. Pfaller University of Iowa College of Medicine, Iowa City, Iowa In 1997, an international surveillance program, SENTRY Antimicrobial Surveillance Program, was initiated with the aim of tracking the emergence of antimicrobial resistance worldwide. Results from reference antimicrobial susceptibility testing of bacterial pathogens (from bloodstream, inpatient and outpatient lower respiratory tract, urinary tract, and skin and soft-tissue infections) were included in an extensive database used to define antimicrobial resistance patterns throughout the world. On the basis of 1997–1999 test results from the Americas, fluoroquinolones continue to demonstrate potent in vitro activity against Enterobacteriaceae and important pathogens (Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, and atypicals) that cause community-acquired respiratory tract infections. At published breakpoint concentrations, gatifloxacin, levofloxacin, sparfloxacin, grepafloxacin, trovafloxacin, and ciprofloxacin inhibited ∼100% of H. influenzae isolates, including those that demonstrated resistance to b-lactams and macrolides. Fluoroquinolones were also active against numerous other gram-negative bacilli and demonstrated high activity against S. pneumoniae and b-hemolytic or viridans group streptococci. New fluoroquinolones maintain activity against penicillin-resistant strains of S. pneumoniae, with a low overall resistance in this species, even among the most recent (1999) clinical isolates. The SENTRY Antimicrobial Surveillance Program will continue to monitor the antibacterial activity of these newer agents throughout the world, to identify emerging resistant strains and to facilitate possible intervention strategies as these newer compounds are used in the clinic setting. The SENTRY Antimicrobial Surveillance Program was initiated in early 1997 with the purpose of monitoring patterns of antimicrobial resistance worldwide [1]. Currently, the program includes 180 medical centers in North America, South America, Europe, Australia, Asia, Africa, and the Middle East. In this program, pathogens collected from a number of infection sites (bloodstream, respiratory tract, urinary tract, and skin and soft tissue in both hospitalized and ambulatory patients) were forwarded to 1 of 3 regional coordinating and/or monitor centers (University of Iowa in Iowa City, IA; University Hospital in Utrecht, Netherlands; and Women’s and Children’s Hospital in Adelaide, Australia) to be tested by uniform standardized, reference microbiologic and molecular susceptibility methods [2–6]. The diverse geographic range and large number of tested pathogens (1100,000 isolates through 1999) provide a unique opportunity to document the frequency of occurrence of pathogens, as well as accurate patterns of antimicrobial resistance. These types of data are particularly important in understanding Reprints or correspondence: Dr. Ronald N. Jones, Medical Microbiology Division, C606 GH, Dept. of Pathology, University of Iowa College of Medicine, Iowa City, IA 52242 (). Clinical Infectious Diseases 2000; 31(Suppl 2):S16–23 q 2000 by the Infectious Diseases Society of America. All rights reserved. 1058-4838/2000/3102S2-0002$03.00 contemporary resistance problems in such developing regions, such as Latin America [1, 2, 4–6], where extensive surveillance studies have not been conducted previously. By documenting contemporary resistance levels in both hospital and community settings of developed and developing nations, SENTRY provides information necessary for establishing local public health and infection control strategies [7, 8]. In addition to monitoring resistance patterns, the SENTRY Program has provided an opportunity to assess the in vitro activity of 170 antimicrobial agents against a wide range of clinical isolates. Agents that have been tested by SENTRY include such newer fluoroquinolones as gatifloxacin, grepafloxacin, levofloxacin, sparfloxacin, and trovafloxacin [3, 9, 10], as well as investigational compounds (SB265805 and BMS 284756). Yet, other newer fluoroquinolones have also been developed (clinafloxacin and moxifloxacin) that have not been monitored by SENTRY [11, 12]. In the United States, use of this class of agents in the treatment of respiratory tract infections has increased dramatically over the last few years, as practitioners follow published treatment guidelines and the suggestions of experts in pulmonology and infectious disease [13–15]. The increase has been largely the result of the enhanced activity of many newer fluoroquinolones against clinically significant gram-positive organisms, particularly Streptococcus pneumoniae [3, 5, 11, 12, 16] and Staphylococcus aureus [2, 9, 12]. The following article reviews the 1997–1999 SENTRY data CID 2000;31 (Suppl 2) Fluoroquinolones and Respiratory Tract Infections for the activity of new fluoroquinolones and discusses these data within the context of changing epidemiologic patterns of resistance, especially as applied to respiratory tract infections [17]. In Vitro Activity of Fluoroquinolones against Gram-Positive Organisms S. pneumoniae is one of the leading causes of bacteremia, meningitis, and acute respiratory infections, including pneumonia, acute bacterial exacerbations of chronic bronchitis (ABECB), acute sinusitis, and otitis media. Pneumococci are usually associated with community-acquired infections and are among the most commonly reported pathogens in communityacquired pneumonia (CAP) [13, 14, 18]. According to a metaanalysis of CAP that reviewed studies from 1966 through 1985, S. pneumoniae accounted for 66% of cases for which a pathogen was documented [18]. Although S. pneumoniae has not been associated traditionally with nosocomial respiratory infections [19], some recent studies have listed it as an increasingly important cause of hospital-acquired lower respiratory tract infections [15, 20]. Consequently, changing patterns in the antimicrobial susceptibility of S. pneumoniae will probably affect both outpatient and hospital treatment practices of respiratory tract infections. Gatifloxacin is a new 8-methoxy fluoroquinolone that has demonstrated excellent activity against SENTRY isolates of S. pneumoniae [3, 4, 9]. In a SENTRY report that included study centers from the United States, Canada, and Latin America, gatifloxacin, levofloxacin, sparfloxacin, and ciprofloxacin were tested against 475 bloodstream isolates of S. pneumoniae [5]. Both gatifloxacin and sparfloxacin demonstrated excellent potency against these pneumococci; each had an MIC necessary to inhibit 90% of growth (MIC90) of 0.5 mg/mL. The activity of levofloxacin (MIC50 of 1 mg/mL) was the same as that of the older fluoroquinolone, ciprofloxaci (...truncated)