ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Dec. 2005, p. 5189 0066-4804/05/$08.00⫹0 doi:10.1128/AAC.49.12.5189.2005 Copyright © 2005, American Society for Microbiology. All Rights Reserved.
Vol. 49, No. 12
Letters to the Editor Levofloxacin and Moxifloxacin Increase Human Gut Colonization by Candida Species The human gut is the natural habitat of many bacterial species. The normal bacterial microflora of the gut, especially the zillions of anaerobes, prevent colonization by pathogenic bacteria (2). The use of antimicrobials is the main reason for the loss of the normal flora and its replacement by potentially pathogenic microorganisms, such as gram-negative aerobic bacilli and Candida species. Colonization by Candida species is an independent risk factor for invasive disease (7). Quinolones are currently among the main classes of antibiotics used worldwide. Among them, the newer fluoroquinolones levofloxacin and moxifloxacin have enhanced activity against respiratory and anaerobic pathogens (1, 3). No studies have examined the role of these two antimicrobial agents on the gut colonization of humans by Candida species. Therefore, we evaluated the effect of levofloxacin and moxifloxacin on the human gastrointestinal tract colonization by Candida species in 30 patients who received levofloxacin or moxifloxacin for 8 to 10 days as monotherapy for the treatment of a variety of infections. Fifteen patients received levofloxacin at 500 mg/day, and 15 patients received moxifloxacin at 400 mg/day. Quantitative stool cultures for Candida species were performed immediately before, at the end, and 1 week after the end of antibiotic treatment. Stool specimens were collected in sterile plastic containers. Each gram of stool was mixed with 9 ml of sterile normal saline and emulsified in a vortex mixer. Subsequently, 10-fold serial dilutions with saline were performed, and 0.1 ml of each dilution was inoculated onto Sabouraud dextrose agar. Candida colonies were counted after incubation at 37°C for 48 h. Identification of the isolates was done with the use of the API 20C AUX system (BioMe´rieux, Marcy l’ Etoile, France). Twelve patients in the levofloxacin group and 14 in the moxifloxacin group had baseline cultures positive for Candida species. Both antibiotics increased intestinal colonization by the yeast. Levofloxacin caused a greater increase (1.8 log10 CFU/g of stool) compared to moxifloxacin (1.2 log10 CFU/g of stool) (Table 1). These increases were statistically significant (P ⬍ 0.001) compared to pretreatment values. A persistent and statistically significant increase in the gastrointestinal Candida concentration was also seen by quantitative stool cultures 1 week after the end of therapy in both groups (P ⬍ 0.005 for levofloxacin and P ⬍ 0.008 for moxifloxacin). In the past, we and others have shown that other quinolones, such as ciprofloxacin, norfloxacin, and ofloxacin, caused smaller increases in the human gut colonization by Candida species (4–6). Our results can be explained by the increased in vitro potency of levofloxacin and moxifloxacin against anaerobes (3), although this activity in vivo has been questioned (1). It is of interest that 1 week after discontinuation of antibiotic therapy, the median concentration of Candida organisms in the stools, although decreased, did not return to baseline levels, as previously seen with ciprofloxacin, norfloxacin, and ofloxacin. In conclusion,
TABLE 1. Median concentration of Candida species before treatment, on the last day of treatment, and 1 week after the end of treatment Median yeast concn (range) (log10 CFU/g of stool) Before treatment
Last day of treatment
1 wk after end of treatment
4.5 (0–6.3) 4.2 (0–6.0)
5.95 (2.0–8.2) 5.6 (2.0–7.3)
5.0 (2.0–7.7) 4.7 (0–6.7)
Antibiotic
Levofloxacin Moxifloxacin
we showed that levofloxacin and moxifloxacin can significantly increase the concentration of Candida species in the human gut. Hence, these agents should be used with caution in patients at risk for systemic fungal infections. REFERENCES 1. Edlund, C., and C. E. Nord. 1999. Effect of quinolones on intestinal ecology. Drugs 58(Suppl. 2):65–70. 2. Guarner, F., and J. R. Malagelada. 2003. Gut flora in health and disease. Lancet 361:512–519. 3. Hooper, D. C.2005. Quinolones, p. 451–473. In G. L. Mandell, R. G. Douglas, and J. E. Bennet (ed.), Principles and practice of infectious diseases, 6th ed. Churchill Livingstone, New York, N.Y. 4. Mavromanolakis, E., S. Maraki, A. Cranidis, Y. Tselentis, D. P. Kontoyiannis, and G. Samonis. 2001. The impact of norfloxacin, ciprofloxacin and ofloxacin on human gut colonization by Candida albicans. Scand. J. Infect. Dis. 33:477–478. 5. Samonis, G., A. Gikas, P. Toloudis, S. Maraki, G. Vrentzos, Y. Tselentis, N. Tsaparas, and G. P. Bodey. 1994. Prospective evaluation of the impact of broad-spectrum antibiotics on the yeast flora of the human gut. Eur. J. Clin. Microbiol. Infect. Dis. 13:665–667. 6. Scully, B. E., K. Jules, N. X. Chin, and H. C. Neu. 1987. Effect of ciprofloxacin on fecal flora of patients with cystic fibrosis and other patients treated with oral ciprofloxacin. Am. J. Med. 82:336–338. 7. Wey, S. B., M. Mori, M. A. Pfaller, R. F. Woolson, and R. P. Wenzel. 1989. Risk factors for hospital-acquired candidemia: a matched case-control study. Arch. Intern. Med. 149:2349–2353.
George Samonis* Diamantis P. Kofteridis Sofia Maraki Dimitrios Alegakis Elpis Mantadakis John A. Papadakis Achilleas H. Gikas The University of Crete Division of Medicine Heraklion, Crete, Greece Matthew Falagas Alfa Institute of Biomedical Sciences Athens, Greece *Phone: 30-2810-392426 Fax: 30-2810-392802 E-mail:
[email protected]
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