In vitro antimicrobial activity of moxifloxacin compared to other quinolones against recent clinical bacterial isolates from hospitalized and community-based cancer patients

Abstract

The in vitro spectrum of moxifloxacin (a C-8-methoxyquinolone) was compared to that of ciprofloxacin and levofloxacin against 924 recent clinical isolates from cancer patients. Moxifloxacin was more active than the comparator agents against Gram-positive pathogens, with potent activity against Aerococcus spp., Listeria monocytogenes, Micrococcus spp., Rhodococcus equi, and Stomatococcus mucilaginous, methicillin-susceptible Staphylococcus spp., all beta hemolytic streptococci, viridans streptococci and Streptococcus pneumoniae. It also had good to moderate activity against Bacillus spp., Corynebacterium spp., Enterococcus faecalis, and methicillin-resistant staphylococci. Although ciprofloxacin was the most active agent tested against the Enterobacteriaceae, moxifloxacin inhibited the majority of these isolates at ≤2.0 μg/ml. Moxifloxacin was the least active of the three agents tested against Pseudomonas aeruginosa, but had significant activity against other non-fermentative Gram-negative bacilli including Acinetobacter spp., Flavobacterium spp., Pseudomonas spp. other than P. aeruginosa, and Stenotrophomonas maltophilia. The overall broad spectrum of moxifloxacin, and its availability for both oral and parenteral administration, warrants its evaluation for the prevention and treatment of infections in cancer patients.

Introduction

Supportive care of the cancer patient has improved substantially over the past two decades resulting in improved outcomes among patients who develop infections, particularly when neutropenic (Hughes et al., 2002). The quinolones have played an important role in the overall management of cancer patients, both as prophylactic agents, and as the Gram-negative component of combination regimens used for empiric therapy in febrile neutropenic patients The GIMEMA Infection Program 1991, For the International Antimicrobial Therapy Cooperative, Group of the European Organization for Research and Treatment of Cancer et alFor the International Antimicrobial Therapy Cooperative, Group of the European Organization for Research and Treatment of Cancer et al 1999, Hughes et al 2002, Rolston 1999. The spectrum of bacterial infection in patients with chemotherapy induced neutropenia undergoes periodic changes. Currently, Gram-positive organisms outnumber Gram-negative bacilli as the predominant pathogens at most cancer treatment centers, including ours Koll and Brown 1993, Rolston and Bodey 2000, Zinner 1999. Although they are less frequent, Gram-negative bacilli are associated with greater morbidity and mortality, making Gram-negative activity an essential component of agents used for prophylaxis or empiric therapy. One of the drawbacks for continuing use of older generation quinolones (norfloxacin, ofloxacin, ciprofloxacin) in cancer patients is their lack of adequate Gram-positive activity. Some of these agents have even been considered to promote the acquisition of viridans streptococci, staphylococci, streptococci, and enterococci, when used for prophylaxis (Elting et al., 1992). The in vitro activity of newer generation quinolones (trovafloxacin, gatifloxacin) against isolates from cancer patients has been evaluated and their potential for use in such patients, demonstrated Diekema et al 1999, Jones et al 1998, Rolston et al 1997, Rolston et al 1999a, Rolston et al 1999b. Serious trovafloxacin related hepatotoxicity however, resulted in the withdrawal of this agent from clinical usage. Based on our in vitro data on gatifloxacin we have initiated pilot studies of prophylaxis and empiric monotherapy in low-risk patients with this agent.

Our interest in moxifloxacin, a relatively new 8-methoxyquinolone was limited until recently, because this agent was initially developed only for oral usage. Now that oral and parenteral formulations of moxifloxacin have become available, we wished to determine its potential utility in cancer patients. Consequently, we determined its in vitro activity against recent clinical isolates obtained from patients being treated at our institution—an NCI designated Comprehensive Cancer Center. Ciprofloxacin and levofloxacin were chosen as comparator agents since these are the two quinolones used most frequently at cancer treatment centers including ours. Our results form the basis of this report.