By Chris Berrie
HELSINKI, Finland — May 20, 2009 — Monotherapy with quinolones should be reconsidered for patients with diabetic foot infections, due to low microbiological activities and high selection of resistant strains, according to research presented here at the 19th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID).
“The quinolones are the drugs that are used more frequently in … outpatients with diabetic foot infections — and these patients are treated at home with oral drugs, usually as monotherapies,” explained principal investigator Carlo Tascini, MD, Infectious Diseases Unit, Pisa University Hospital, Pisa, Italy, speaking here on May 18. The quinolones, however, show different levels of selection for resistant strains during antimicrobial therapy. Little information is available relating to the in vivo failure rates of quinolones and the emergence of resistant strains.
To add to the body of knowledge on quinolones and resistance, the research team reviewed the files of patients with diabetic foot infections, seeking comparisons of microbiological results following quinolone monotherapy. Specimen cultures were also reviewed, with healing defined as eradication of all bacteria after therapy. Failure, therefore, was related to the persistence of the same micro-organisms or appearance of new micro-organisms, in which cases quinolone susceptibility was studied.
Inclusion criteria were for patients with diabetic foot infections with severe lesions (Texas University Classification class 2 B-D and 3 B-D). The specimens taken included swabs, aspirates, or bone biopsies. Over the 3 years of the study, 709 patients were included who had been treated with monotherapies of levofloxacin (n = 373), moxifloxacin (n = 169), and ciprofloxacin (n = 167).
From a microbiological point of view, healing by eradication was achieved in 40%, 32%, and 22% of patients, for levofloxacin, moxifloxacin, and ciprofloxacin treatments, respectively.
The selection of resistant strains overall was significantly higher for levofloxacin (56%) over both moxifloxacin (43%; P = .03) and ciprofloxacin (40%; P = .02). “From the clinical point of view, this probably reflects the characteristics of these drugs, because ciprofloxacin has the best mutant-prevention concentration in vitro against Gram negatives, and moxifloxacin against Gram positives,” indicated Dr. Tascini. “Levofloxacin is in the middle.”
When examined in more detail for its resistance in Gram-positive bacteria, levofloxacin selection was significantly higher than for moxifloxacin (59% vs 41%; P = .03), with a trend over ciprofloxacin (42%). Similar findings were observed for resistance in Gram-negative bacteria, with levofloxacin selection significantly higher than ciprofloxacin (53% vs 39%; P = .01), with a trend over moxifloxacin (45%).
At the level of development of Staphylococcus aureus resistance, levofloxacin was again significantly higher than moxifloxacin (52% vs 34%; P < .05), with a trend over ciprofloxacin (46%). For Pseudomonas aeruginosa, however, the greatest selection was seen for moxifloxacin, which was significantly higher than ciprofloxacin (76% vs 36%; P = .01), with a trend over levofloxacin (60%).
While levofloxacin is the most effective molecule for eradication of bacteria associated with diabetic foot infections, Dr. Tascini concluded, it also provides a greater selection pressure for resistance to monotherapy.
“We say to be cautious about using monotherapy in these kinds of patients,” Dr. Tascini added.
[Presentation title: Quinolone Monotherapy in Diabetic Foot Infections (DFI): Rate of Failure and Selection for Resistant Strains. Abstract P1524]