Fluoroquinolones and anaerobes.
ABSTRACT The usefulness of fluoroquinolones for the treatment of mixed aerobic and anaerobic infections has been investigated since these agents started being used in clinical practice. Newer compounds have increased in vitro activity against anaerobes, but clinically relevant susceptibility breakpoints for these bacteria have not been established. Pharmacodynamic analyses and corroboration by new data from clinical trials have enhanced our knowledge concerning the use of fluoroquinolones to treat selective anaerobic pathogens. These studies suggest that newer agents could be useful in the treatment of several types of mixed aerobic and anaerobic infections, including skin and soft-tissue, intra-abdominal, and respiratory infections. The major concerns with expanding the use of fluoroquinolones to treat anaerobic infections have been reports of increasing resistance in Bacteroides group isolates and the impact of these antibiotics on the incidence of Clostridium difficile-associated disease.
Article: Enhanced production of phospholipase C and perfringolysin O (alpha and theta toxins) in a gatifloxacin-resistant strain of Clostridium perfringens.[show abstract] [hide abstract]
ABSTRACT: Clostridium perfringens-induced gas gangrene is mediated by potent extracellular toxins, especially alpha toxin (a phospholipase C [PLC]) and theta toxin (perfringolysin O [PFO], a thiol-activated cytolysin); and antibiotic-induced suppression of toxin synthesis is an important clinical goal. The production of PLC and PFO by a gatifloxacin-induced, fluoroquinolone-resistant mutant strain of C. perfringens, strain 10G, carrying a stable mutation in DNA gyrase was compared with that of the wild-type (WT) parent strain. Zymography (with sheep red blood cell and egg yolk overlays) and time course analysis [with hydrolysis of egg yolk lecithin and O-(4 nitrophenyl-phosphoryl)choline] demonstrated that strain 10G produced more PLC and PFO than the WT strain. Increased toxin production in strain 10G was not related either to differences in growth characteristics between the wild-type and the mutant strain or to nonsynonymous polymorphisms in PLC, PFO, or their known regulatory proteins. Increased PLC and PFO production by strain 10G was associated with increased cytotoxic activity for HT-29 human adenocarcinoma cells and with increased platelet-neutrophil aggregate formation. Four other gatifloxacin-induced gyrase mutants did not show increased toxin production, suggesting that gatifloxacin resistance was not always associated with increased toxin production in all strains of C. perfringens. This is the first report of increased toxin production in a fluoroquinolone-resistant strain of C. perfringens.Antimicrobial Agents and Chemotherapy 04/2008; 52(3):895-900. · 4.84 Impact Factor
Article: Clinical update on the use of moxifloxacin in the treatment of community-acquired complicated intraabdominal infections.[show abstract] [hide abstract]
ABSTRACT: Community-acquired complicated intraabdominal infections (cIAIs) present problems for clinicians and have substantial impact on hospital resources. Because of the polymicrobial nature of these infections, successful management of cIAIs depends on timely and appropriate use of antisepsis and antiinfective strategies. The literature pertinent to this article was reviewed. The Surgical Infection Society and the Infectious Disease Society of America guidelines recommend a variety of single and combined antimicrobial therapies, including fluoroquinolone therapy, for prophylactic and definitive treatment of cIAIs with different severities. Moxifloxacin, a fluoroquinolone, demonstrates a broad spectrum of antimicrobial (including anaerobic) activity, good tissue penetration into the gastrointestinal tract, and a good tolerability profile. Clinical data also have demonstrated that moxifloxacin is effective as monotherapy for patients with cIAIs. This review identifies the clinical issues impacting antimicrobial selection in cIAI and discusses data on the role of moxifloxacin in light of the current guidelines for management of these patients. Moxifloxacin provides clinicians with a convenient monotherapy option for the treatment of mild-to-moderate cIAIs.Surgical Infections 10/2010; 11(5):487-94. · 1.80 Impact Factor