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Quadruple-Checkerboard: A Modification of the Three-Dimensional Checkerboard for Studying Drug Combinations
Published on: July 24, 2021
[Experience accumulated in hospital setting with levofloxacin, in monotherapy and in association therapy]
1UOC Infezioni Sistemiche e Immunodepressioni, Istituto Nazionale per le Malattie Infettive L Spallanzani, IRCCS, Roma, Italy.
Abstract:
Levofloxacin possesses a wide antimicrobial spectrum which encompasses Gram positive (also including penicillin-resistant Streptococcus pneumoniae) and Gram negative, and atypical respiratory pathogens Chlamydia pneumoniae, Legionella pneumophila and Mycoplasma pneumoniae) as well. Comparative clinical studies (macrolides, beta-lactams, and other fluoroquinolones), have evidenced bacteriological and clinical efficacy in community-acquired pneumonia (CAP), acute exacerbation of chronic bronchitis, urinary tract infections, and skin and soft tissue infections. In clinical practice, levofloxacin in sequential therapy allowed to reduce length of stay, the efficacy being maintained unaltered. In severe pneumonia, or when a pseudomonas aetiology is suspected, an association therapy is suggested, although a reliable body of clinical evidence is still lacking. Recent in vitro studies showed a synergism between levofloxacin and imipenem against multiresistant Pseudomonas aeruginosa strains. A recent Italian clinical study evidenced the good efficacy and tolerability profile of prophylactic use of levofloxacin in neutropenic patients with cancer. Such a prophylaxis reduced number of febrile episodes, at a statistically significant level, and mortality (although at a not statistically significant level).
Insights
Levofloxacin is effective against a broad range of bacteria, including resistant strains, for common infections like pneumonia and UTIs. It also shows promise in preventing infections in cancer patients undergoing chemotherapy.
Area of Science:
- Pharmacology and Microbiology
- Clinical Medicine
Context:
- Levofloxacin exhibits broad-spectrum antimicrobial activity against Gram-positive, Gram-negative, and atypical pathogens.
- Clinical studies confirm its efficacy in treating community-acquired pneumonia (CAP), chronic bronchitis exacerbations, UTIs, and skin infections.
Purpose:
- To review the clinical efficacy and applications of levofloxacin.
- To highlight its role in sequential therapy, combination therapy for severe infections, and prophylactic use.
Summary:
- Levofloxacin demonstrates bacteriological and clinical effectiveness across various infections, including penicillin-resistant Streptococcus pneumoniae.
- Sequential therapy with levofloxacin can reduce hospital stays without compromising efficacy.
- Combination therapy with imipenem shows in vitro synergy against multidrug-resistant Pseudomonas aeruginosa.
Impact:
- Levofloxacin offers a valuable therapeutic option for a wide array of bacterial infections.
- Prophylactic use in neutropenic cancer patients reduced febrile episodes and mortality.
- Further research is needed to establish evidence for combination therapy in severe Pseudomonas aeruginosa infections.
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