RESUMO
A hallmark of airways in patients with cystic fibrosis (CF) is highly refractory, chronic infections by several opportunistic bacterial pathogens. A recent study demonstrated that acidified sodium nitrite (A-NO(2)(-)) killed the highly refractory mucoid form of Pseudomonas aeruginosa, a pathogen that significantly compromises lung function in CF patients (S. S. Yoon et al., J. Clin. Invest. 116:436-446, 2006). Therefore, the microbicidal activity of A-NO(2)(-) (pH 6.5) against the following three major CF pathogens was assessed: P. aeruginosa (a mucoid, mucA22 mutant and a sequenced nonmucoid strain, PAO1), Staphylococcus aureus USA300 (methicillin resistant), and Burkholderia cepacia, a notoriously antibiotic-resistant organism. Under planktonic, anaerobic conditions, growth of all strains except for P. aeruginosa PAO1 was inhibited by 7.24 mM (512 µg ml(-1) NO(2)(-)). B. cepacia was particularly sensitive to low concentrations of A-NO(2)(-) (1.81 mM) under planktonic conditions. In antibiotic-resistant communities known as biofilms, which are reminiscent of end-stage CF airway disease, A-NO(2)(-) killed mucoid P. aeruginosa, S. aureus, and B. cepacia; 1 to 2 logs of cells were killed after a 2-day incubation with a single dose of â¼15 mM A-NO(2)(-). Animal toxicology and phase I human trials indicate that these bactericidal levels of A-NO(2)(-) can be easily attained by aerosolization. Thus, in summary, we demonstrate that A-NO(2)(-) is very effective at killing these important CF pathogens and could be effective in other infectious settings, particularly under anaerobic conditions where bacterial defenses against the reduction product of A-NO(2)(-), nitric oxide (NO), are dramatically reduced.
Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Burkholderia cepacia/efeitos dos fármacos , Fibrose Cística/microbiologia , Plâncton/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Nitrito de Sódio/farmacologia , Anaerobiose , Testes de Sensibilidade Microbiana , Microscopia ConfocalAssuntos
Antibacterianos/farmacologia , Infecções Meningocócicas/epidemiologia , Infecções Meningocócicas/microbiologia , Neisseria meningitidis/efeitos dos fármacos , Neisseria meningitidis/isolamento & purificação , Farmacorresistência Bacteriana , Humanos , Indiana/epidemiologia , Kentucky/epidemiologia , Testes de Sensibilidade Microbiana , Ohio/epidemiologia , Vigilância da PopulaçãoRESUMO
Routine bacterial cultures of corneal scrapings from seven cats with either ulcerative feline keratitis, keratomalacia, or both yielded colonies which were identified by 16S rRNA gene sequencing as Mycoplasma felis (six cases) and Mycoplasma gateae (one case). Identification of the pathogens allowed the use of less empirical and more organism-specific therapy.