New treatments for bacterial keratitis.

2012

Wong RL, Gangwani RA, Yu LW, Lai JS.

Source

Eye Institute, The University of Hong Kong, Room 301, Level 3, Block B, 100 Cyberport Road, Cyberport 4, Hong Kong.

Abstract

Purpose. 

To review the newer treatments for bacterial keratitis. 

Data Sources. 

PubMed literature search up to April 2012. Study Selection. Key words used for literature search: "infectious keratitis", "microbial keratitis", "infective keratitis", "new treatments for infectious keratitis", "fourth generation fluoroquinolones", "moxifloxacin", "gatifloxacin", "collagen cross-linking", and "photodynamic therapy". 

Data Extraction. 

Over 2400 articles were retrieved. Large scale studies or publications at more recent dates were selected. 

Data Synthesis. 

Broad spectrum antibiotics have been the main stay of treatment for bacterial keratitis but with the emergence of bacterial resistance; there is a need for newer antimicrobial agents and treatment methods. Fourth-generation fluoroquinolones and corneal collagen cross-linking are amongst the new treatments. In vitro studies and prospective clinical trials have shown that fourth-generation fluoroquinolones are better than the older generation fluoroquinolones and are as potent as combined fortified antibiotics against common pathogens that cause bacterial keratitis. Collagen cross-linking was shown to improve healing of infectious corneal ulcer in treatment-resistant cases or as an adjunct to antibiotics treatment. 

Conclusion. 

Fourth-generation fluoroquinolones are good alternatives to standard treatment of bacterial keratitis using combined fortified topical antibiotics. Collagen cross-linking may be considered in treatment-resistant infectious keratitis or as an adjunct to antibiotics therapy.

PubMed

Antibiotics as immunomodulant agents in COPD.

Feb 2012

Blasi F, Mantero M, Aliberti S.

Source

Respiratory Medicine Section, Dipartimento Toraco-Polmonare e Cardiocircolatorio, University of Milan, IRCCS Fondazione Cà Granda Ospedale Maggiore, Milan, Italy.

Abstract

It is widely accepted that some antibiotics have activities beyond their direct antibacterial effects. Macrolide is the antibiotic class with more convincing studies and evidence on its immunomodulatory and anti-inflammatory activities. Different clinical studies have shown that macrolide prophylaxis in patients with moderate-severe chronic obstructive pulmonary disease (COPD) can have a significant impact on the exacerbation rate reducing morbidity and, potentially, mortality of the disease. Other antibiotics, such as fluoroquinolones, demonstrate a variety of immunomodulatory effects but only few clinical data are available in COPD. New macrolide derivatives devoid of antibacterial activity have been synthetized. This review analyses the relevance of immunomodulatory and anti-inflammatory effects of antibiotics in the management of COPD.

PubMed

Rational antibiotic therapy of urinary tract infections

Rational antibiotic therapy of urinary tract infections

Med Monatsschr Pharm. 2008 Oct

Wagenlehner FM, Naber KG, Weidner W.
Klinik und Poliklinik für Urologie und Kinderurologie, Justus-Liebig-Universität Giessen, Rudolf-Buchheim-Str. 7, 35385 Giessen. Wagenlehner@AOL.com

Rational antibiotic therapy of urinary tract infections Urinary tract infections (UTI) are frequent infections in the outpatient and nosocomial setting. Generally UTI can be stratified into uncomplicated and complicated infections with respect to treatment options. Uncomplicated UTI are mainly caused by E. coli, whereas complicated UTI exhibit a broader bacterial spectrum with a higher rate of multiresistant uropathogens. On the other hand increasing resistance rates are also found in uncomplicated UTI, e.g. against aminopenicillins, Co-trimoxazol and increasingly also fluoroquinolones. This fact has to be considered in the empirical therapy. Recurrent UTI are frequently found in young, sexually active women, and postmenopausal women. In complicated UTI the complicating factors have to be diagnosed and treated additionally to the antibiotic treatment. If not treated, a severe UTI and urosepsis can develop.

PMID: 18972869 [PubMed - in process]

Emergence and maintenance of resistance to fluoroquinolones and coumarins in Staphylococcus aureus: predictions from in vitro studies.

Emergence and maintenance of resistance to fluoroquinolones and coumarins in Staphylococcus aureus: predictions from in vitro studies.

J Antimicrob Chemother. 2007 Jun 7

Vickers AA, O'neill AJ, Chopra I.
Antimicrobial Research Centre and Research Institute of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK.

Objectives: Fluoroquinolones and coumarins interfere with the activity of bacterial type II topoisomerase enzymes. We examined the development of resistance to these agents in Staphylococcus aureus and determined the effect of simultaneous topoisomerase IV and DNA gyrase mutations on the biological fitness of the organism.

This work aimed to gain insight into how such mutants might arise and survive in the clinical environment. Methods Spontaneous mutants resistant to fluoroquinolones and coumarins were selected in S. aureus. Resistance mutations were identified by DNA sequencing of PCR amplicons corresponding to the genes encoding topoisomerase IV and DNA gyrase. In vitro fitness of resistant mutants was compared with the antibiotic-susceptible progenitor strain using pair-wise competition assays.

Results: Mutants simultaneously resistant to both a fluoroquinolone and either of the coumarins, novobiocin or coumermycin A1, could not be recovered following a single-step selection. However, mutants concurrently resistant to both classes of antimicrobial could be generated by step-wise selections. These mutants demonstrated reductions in competitive fitness of up to 36%.

Conclusions: Dual-targeting of topoisomerase IV and DNA gyrase enzymes, for example with the combination of a fluoroquinolone and a coumarin agent, could minimize the emergence of resistance to these drugs in S. aureus. However, resistance-associated fitness costs may not be sufficient to limit the survival of mutants with dual resistance, if they arose in the clinical setting.

Antimicrobial Chemotherapy