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Antimicrobial Agents and Chemotherapy, March 2004, p. 1012-1016, Vol. 48, No. 3
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.3.1012-1016.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

In Vitro Activities of Moxifloxacin against 900 Aerobic and Anaerobic Surgical Isolates from Patients with Intra-Abdominal and Diabetic Foot Infections

Charles E. Edmiston,^1* Candace J. Krepel,¹ Gary R. Seabrook,¹ Lewis R. Somberg,² Atilla Nakeeb,³ Robert A. Cambria,¹ and Jonathan B. Towne¹

Divisions of Vascular Surgery,¹ Trauma and Critical Care,² Pancreatobiliary Surgery, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin³

Received 2 July 2003/ Returned for modification 24 August 2003/ Accepted 12 November 2003

Top Abstract Introduction References

 
The in vitro activities of moxifloxacin, ciprofloxacin, levofloxacin, gatifloxacin, imipenem, piperacillin-tazobactam, clindamycin, and metronidazole against 900 surgical isolates were determined using NCCLS testing methods. Moxifloxacin exhibited good to excellent antimicrobial activity against most aerobic (90.8%) and anaerobic (97.1%) microorganisms, suggesting that it may be effective for the treatment of polymicrobial surgical infections.

Top Abstract Introduction References

 
Infections of the abdominal-pelvic vaults and diabetic limbs involve a mixed microbial flora, often characterized by a high level of antimicrobial resistance (5-7). In addition to appropriate antimicrobial spectrum, the ideal antimicrobial agent must also have extensive tissue distribution, as many surgical infections occur in sites where there is significant disruption of tissue plains and vascular supply (7, 17, 22). Since the introduction of ciprofloxacin in the late 1980s, the fluoroquinolones have been viewed as potent antimicrobials for the treatment of serious gram-negative infections. Newer quinolones have improved in vitro activity against anaerobes, with trovafloxacin, moxifloxacin, and gatifloxacin having more potent activities than levofloxacin and ciprofloxacin (1, 3). Unfortunately, safety and toxicity concerns have limited the potential therapeutic usefulness of many of these agents (11, 14, 15, 21). The present study was undertaken to investigate the in vitro activity of moxifloxacin against aerobic and anaerobic clinical isolates recently obtained from surgical patients with diabetic foot and intra-abdominal infections.

Nine hundred sequential, nonduplicated clinical isolates (350 aerobic and 550 anaerobic strains) were collected over a 3-year period (1999 to 2002) from patients with intra-abdominal and diabetic foot infections in a tertiary care medical center in Milwaukee, Wis. (three surgical services: vascular surgery, trauma and critical care, and pancreatobiliary surgery). NCCLS-recommended reference broth and agar dilution methods were used for aerobic and anaerobic susceptibility testing, respectively (18, 19). Microbroth and agar dilution plates were prepared on the day of testing and incubated at 35°C for 24 h (aerobes) and 48 h (anaerobes), respectively. Gram-positive and gram-negative aerobic-facultative isolates were tested in Mueller-Hinton broth. Anaerobic strains were tested within an anaerobic chamber on brucella blood agar plates supplemented with 5 µg of hemin, 1 µg of vitamin K₁ per ml, and 5% lysed sheep blood. The agar dilution plates were inoculated (10⁵ CFU/spot) using a 32-prong Steers replicator device. Antimicrobial standard powders (ciprofloxacin and moxifloxacin [Bayer Corp., West Haven, Conn.], gatifloxacin [Bristol-Myers Squibb, Princeton, N.J.], levofloxacin [Ortho-McNeil Pharmaceuticals, Raritan, N.J.], imipenem [Merck & Co., Inc., Rahway, N.J.], piperacillin-tazobactam [Wyeth-Ayerst, St. Davids, Pa.], clindamycin [Pharmacia-Upjohn, Kalamazoo, Mich.], and metronidazole [SCS, Chicago, Ill.]) were reconstituted according to the manufacturers' instructions, serially diluted, and added to appropriate media for testing. Control strains included Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25922, Bacteroides fragilis ATCC 25285, Bacteroides thetaiotaomicron ATCC 29741, and Eubacterium lentum ATCC 4305.

The susceptibilities of the aerobic isolates, listed by species, are shown in Table 1. The results are expressed as the MICs at which 50 and 90% of strains were inhibited (MIC₅₀ and MIC₉₀, respectively) and the ranges for all strains. While moxifloxacin, gatifloxacin, and imipenem demonstrated good activity against methicillin-susceptible S. aureus, E. faecalis, and Streptococcus spp., all agents tested failed to provide reliable in vitro activity (based on MIC₉₀s) against methicillin-resistant S. aureus, Staphylococcus epidermidis, and Enterococcus faecium. All four fluoroquinolones tested demonstrated excellent activity against gram-negative aerobic isolates. Imipenem also demonstrated excellent activity against all gram-negative aerobic isolates (MIC₉₀ 0.5 mg/liter). Piperacillin-tazobactam was active against E. coli, Klebsiella spp., Proteus mirabilis, and Morganella morganii (MIC₉₀ 8.0 mg/liter). However, for Citrobacter spp. and Enterobacter spp., the percent susceptibility to piperacillin-tazobactam was highly variable (range, 70 to 83.3%). Overall, 90.8% of aerobic gram-positive and gram-negative surgical isolates were susceptible to moxifloxacin.

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TABLE 1. Activities of moxifloxacin and other agents against 350 gram-positive and gram-negative aerobic-facultative isolates from surgical patients

Among the 550 gram-positive and gram-negative anaerobes tested, Bacteroides was the most common genus (n = 310), comprising 56.3% of the total number of isolates (Table 2), followed by Clostridium spp. (n = 72; 13%) and Peptostreptococcus spp. (n = 65; 12%). Against B. fragilis, moxifloxacin exhibited excellent in vitro activity, based on an MIC₉₀ of 1 mg/liter (Table 2). Comparing the percent susceptibilities for B. fragilis, metronidazole, imipenem, and piperacillin-tazobactam demonstrated similar in vitro efficacies, while less than 85% of B. fragilis isolates were sensitive to clindamycin. The percent susceptibility of B. fragilis group isolates (B. thetaiotaomicron, B. ovatus, B. vulgatus, and B. distasonis) to moxifloxacin based on a proposed breakpoint (4 mg/liter) was similar to the values reported for imipenem, metronidazole, and piperacillin-tazobactam. In general, clindamycin activity against B. fragilis and non-fragilis strains was poor compared to the other test compounds. Moxifloxacin demonstrated excellent activity against Clostridium perfringens (MIC₉₀ = 2 mg/liter) and other clostridial isolates (MIC₉₀ = 1 mg/liter). Against C. perfringens, imipenem and piperacillin-tazobactam demonstrated the most potent in vitro activity (MIC₉₀ = 0.25 mg/liter for both) and clindamycin demonstrated the least (MIC₉₀ = 8 mg/liter), while both clindamycin (MIC₉₀ = 16) and piperacillin-tazobactam (MIC₉₀ = 32) exhibited the weakest activity against other miscellaneous clostridial isolates. Moxifloxacin exhibited excellent activity against all three species of anaerobic streptococci (Peptostreptococcus anaerobius, Peptostreptococcus magnus, and Peptostreptococcus micros) recovered from surgical patients (MIC₉₀ 1 mg/liter). The activities of the other agents tested against these strains were highly variable depending on the species, although imipenem was the most active overall (MIC₉₀ = 0.12 mg/liter) and metronidazole was the least active (MIC₉₀ ranged from 1 to 4 mg/liter) of all agents tested. Moxifloxacin exhibited excellent activity against Fusobacterium mortiferum and F. nucleatum (MIC₉₀ 1 mg/liter), although some uncommon strains (specifically F. varium and F. russii) demonstrated resistance. Clindamycin, imipenem, and metronidazole were the most potent agents tested against F. mortiferum and F. nucleatum (MIC₉₀ 0.5 mg/liter). Against Porphyromonas and Prevotella species, moxifloxacin demonstrated good activity (MIC₉₀ 2 mg/liter); however, clindamycin, imipenem, and piperacillin-tazobactam demonstrated more potent in vitro activity (MIC₉₀ 0.25 mg/liter). Both imipenem and moxifloxacin exhibited similar in vitro activities against Eubacterium lentum (MIC₉₀ 0.5 mg/liter). Overall, by using a breakpoint of 4 mg/liter, 97.1% of anaerobic strains were found to be susceptible to moxifloxacin.

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TABLE 2. Activities of moxifloxacin and other agents against 550 gram-positive and gram-negative anaerobic isolates from surgical patients

Moxifloxacin demonstrates broad-spectrum in vitro activity against both gram-positive and gram-negative aerobic and anaerobic surgical isolates compared to other anti-infectives commonly used in the treatment of surgical infections. Empirical therapy of mixed, aerobic, and anaerobic infections remains challenging because of the rising resistance rates of surgical pathogens, such as E. coli and B. fragilis. Data collected from 1987 to 1999 revealed that 22% of B. fragilis isolates from bloodstream infections were resistant to clindamycin (2). In the same surveillance study, however, 96% of B. fragilis strains were susceptible to imipenem, metronidazole, and trovafloxacin (the only quinolone tested). Inappropriate therapy for serious anaerobic infections (e.g., bacteremic complications of peritonitis) has been associated with at least a twofold-increased mortality rate (16, 20) as well as significantly increased rates of clinical and bacteriologic failure (20).

In the present study, moxifloxacin demonstrated good to excellent activity against over 19 species of anaerobic bacteria. These data support the results of previous studies that found moxifloxacin to be highly active against clinical isolates of B. fragilis (4, 10, 13). However, a recent in vitro study has suggested that quinolone resistance among members of the B. fragilis group may be increasing, possibly limiting the therapeutic utility of selective agents (23). It should be noted that the NCCLS has not yet adopted a susceptibility breakpoint for moxifloxacin against the B. fragilis group, and therapeutic speculation relative to interpretation of in vitro susceptibility data is at best preliminary. Not unexpectedly, many B. fragilis isolates were nonsusceptible to clindamycin based on an MIC₉₀ of 4 mg/liter (NCCLS-recommended susceptible breakpoint is 2 mg/liter). This high degree of resistance to clindamycin confirms the findings of at least one other recent report wherein only 78% of B. fragilis isolates were susceptible to clindamycin (2). Moxifloxacin also demonstrated good to excellent in vitro activity against Clostridium spp. and Fusobacterium spp. isolates from infections involving the peritoneal cavity. In addition, all anaerobic streptococcal isolates from diabetic foot and intra-abdominal infections were susceptible to moxifloxacin.

Selection of an effective antimicrobial agent for a surgical infection requires knowledge of the potential microbial pathogens, an understanding of the pathophysiology of the infectious process, and an understanding of the pharmacology and pharmacokinetics of the intended therapeutic agent (7, 8). Quinolones have been effective in the treatment of selected surgical infections in part because of their excellent activity against aerobic gram-negative bacteria and tissue penetration (9). However, the extended-spectrum and broad-spectrum quinolones do not exhibit potent antianaerobic activity and as such must be used in combination with other therapeutic (antianaerobic) agents. The present study suggests that moxifloxacin exhibits potent activity against both aerobes and anaerobes and may be an effective agent for the treatment of both community- or hospital-acquired intra-abdominal infection and diabetic foot infection, both of which involve a complexed polymicrobial flora (12, 17, 22).

 
We thank Brian Shearer and Mary Connolly for their technical assistance in developing this manuscript.

This work was supported in part by an unrestricted research grant from Bayer Corp., Pharmaceutical Division, West Haven, Conn.

 
* Corresponding author. Mailing address: Department of Surgery, Medical College of Wisconsin, 9200 W. Wisconsin Ave., Milwaukee, WI 53226. Phone: (414) 805-5739. Fax: (414) 805-0152. E-mail: edmiston{at}mcw.edu.

Top Abstract Introduction References

 

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Antimicrobial Agents and Chemotherapy, March 2004, p. 1012-1016, Vol. 48, No. 3
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.3.1012-1016.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Edmiston, C. E. Articles by Towne, J. B. Search for Related Content PubMed PubMed Citation Articles by Edmiston, C. E. Articles by Towne, J. B.