Mutant prevention concentration of ozenoxacin for quinolone-susceptible or -resistant Staphylococcus aureus and Staphylococcus epidermidis

Ozenoxacin (OZN) belongs to a new generation of non-fluorinated quinolones for the topical treatment of skin infections which has shown to be effective in the treatment of susceptible and resistant Gram-positive cocci. The mutant prevention concentration (MPC) of ozenoxacin, levofloxacin and ciprofloxacin was determined in quinolone-susceptible and -resistant strains including methicillin-susceptible S. aureus, methicillin-resistant S. aureus, methicillin-susceptible S. epidermidis and methicillin-resistant S. epidermidis with different profile of mutation in the quinolone resistance determining regions (QRDR). The MPC value of OZN for the methicillin-susceptible S. aureus strain susceptible to quinolones, without mutations in QRDR, was 0.05 mg/L, being 280-fold lower than that observed with ciprofloxacin and levofloxacin. In methicillin-susceptible and-resistant S. aureus strains with mutations in the gyrA or/and grlA genes the MPC of OZN went from 0.1 to 6 mg/L, whereas the MPC of levofloxacin and ciprofloxacin was > 50 mg/L for the same strains. For methicillin-susceptible and-resistant S. epidermidis the results were similar to those abovementioned for S. aureus. According to our results, the MPC of OZN was far below the quantity of ozenoxacin achieved in the epidermal layer, suggesting that the in vivo selection of mutants, if it occurs, will take place at low frequency. Ozenoxacin is an excellent candidate for the treatment of bacterial infections caused by susceptible and quinolone-resistant staphylococci isolated usually from skin infections

Analysis of the population structure of Plasmodium falciparum-infected erythrocytes

Preprin

Microbiological profile of ozenoxacin

Aim: To explore the antibacterial spectrum of ozenoxacin and compare its in vitro activity with that of other antibacterial agents. Materials & methods: In 2010, 10,054 isolates were collected from 128 centers worldwide. Minimum inhibitory concentrations against Gram-positive and Gram-negative isolates were determined for 23 and 13 antibacterial agents, respectively. Results: Ozenoxacin exhibited high in vitro activity against susceptible, and methicillin- or levofloxacin-resistant, Gram-positive bacteria. Ozenoxacin was one or two dilutions less active against Enterobacteriaceae isolates, except for Escherichia coli, than other quinolones. Conclusion: Ozenoxacin is a potent antimicrobial agent mainly against susceptible and resistant strains of Gram-positive isolates (staphylococci and streptococci), and shows activity against some Gram-negative isolates

Comparative in vitro antibacterial activity of ozenoxacin against Gram-positive clinical isolates

AIM: To compare the in vitro activity of the anti-impetigo agent, ozenoxacin, and other antimicrobial agents against Gram-positive clinical isolates from skin and soft tissue infections. MATERIALS & METHODS: Isolates were collected in two studies: 1097 isolates from 49 centers during 2009-2010 and 1031 isolates from ten centers during 2014. Minimum inhibitory concentrations were determined for 18 and 11 antimicrobials in these studies, respectively, using standard broth microdilution methods. Isolates were stratified by species and methicillin susceptibility/resistance and/or levofloxacin susceptibility/nonsusceptibility status. RESULTS: Ozenoxacin exhibited high in vitro activity against Staphylococcus aureus and coagulase-negative staphylococci isolates in both studies. Ozenoxacin was also highly active against Streptococcus pyogenes and Streptococcus agalactiae isolates. CONCLUSION: Ozenoxacin is a potent antimicrobial agent against staphylococci and streptococci

Thermodynamic Concepts in the Study of Microbial Populations: Age Structure in Plasmodium falciparum Infected Red Blood Cells

Variability is a hallmark of microbial systems. On the one hand, microbes are subject to environmental heterogeneity and undergo changeable conditions in their immediate surroundings. On the other hand, microbial populations exhibit high cellular diversity. The relation between microbial diversity and variability of population dynamics is difficult to assess. This connection can be quantitatively studied from a perspective that combines in silico models and thermodynamic methods and interpretations. The infection process of Plasmodium falciparum parasitizing human red blood cells under laboratory cultivation conditions is used to illustrate the potential of Individual-based models in the context of predictive microbiology and parasitology. Experimental data from several in vitro cultures are compared to the outcome of an individual-based model and analysed from a thermodynamic perspective. This approach allows distinguishing between intrinsic and external constraints that give rise to the diversity in the infection forms, and it provides a criterion to quantitatively define transient and stationary regimes in the culture. Increasing the ability of models to discriminate between different states of microbial populations enhances their predictive capability which finally leads to a better the control over culture systems. The strategy here presented is of general application and it can substantially improve modelling of other types of microbial communities

A Murine Model of falciparum-Malaria by In Vivo Selection of Competent Strains in Non-Myelodepleted Mice Engrafted with Human Erythrocytes

To counter the global threat caused by Plasmodium falciparum malaria, new drugs and vaccines are urgently needed. However, there are no practical animal models because P. falciparum infects human erythrocytes almost exclusively. Here we describe a reliable falciparum murine model of malaria by generating strains of P. falciparum in vivo that can infect immunodeficient mice engrafted with human erythrocytes. We infected NODscid/β2m−/− mice engrafted with human erythrocytes with P. falciparum obtained from in vitro cultures. After apparent clearance, we obtained isolates of P. falciparum able to grow in peripheral blood of engrafted NODscid/β2m−/− mice. Of the isolates obtained, we expanded in vivo and established the isolate Pf3D70087/N9 as a reference strain for model development. Pf3D70087/N9 caused productive persistent infections in 100% of engrafted mice infected intravenously. The infection caused a relative anemia due to selective elimination of human erythrocytes by a mechanism dependent on parasite density in peripheral blood. Using this model, we implemented and validated a reproducible assay of antimalarial activity useful for drug discovery. Thus, our results demonstrate that P. falciparum contains clones able to grow reproducibly in mice engrafted with human erythrocytes without the use of myeloablative methods

Numerical analysis of electroforetic periplasmic protein patterns, a possible marker system for epidemiological studies

The whole-cell and periplasmic protein (PP) compositions of 22 Serratia marcescens isolates were examined. Numerical analysis of whole-cell protein patterns was not a useful procedure for measuring relationships between organisms at the subspecific level. However, there was a very good correlation between electrophoretic PP pattern results and those obtained previously from multilocus enzyme electrophoresis (electrophoretic type) and biotype (D. Gargallo-Viola, J. Clin. Microbiol. 27:860-868, 1989). Clustering of isolates by using PP patterns compared by coefficients based on peak position (Dice coefficient) gave more precise information than that obtained by correlation coefficients. PP patterns appeared to be a useful tool that may be of value for epidemiologic studies.Postprint (published version

Numerical analysis of electroforetic periplasmic protein patterns, a possible marker system for epidemiological studies

The whole-cell and periplasmic protein (PP) compositions of 22 Serratia marcescens isolates were examined. Numerical analysis of whole-cell protein patterns was not a useful procedure for measuring relationships between organisms at the subspecific level. However, there was a very good correlation between electrophoretic PP pattern results and those obtained previously from multilocus enzyme electrophoresis (electrophoretic type) and biotype (D. Gargallo-Viola, J. Clin. Microbiol. 27:860-868, 1989). Clustering of isolates by using PP patterns compared by coefficients based on peak position (Dice coefficient) gave more precise information than that obtained by correlation coefficients. PP patterns appeared to be a useful tool that may be of value for epidemiologic studies

Numerical analysis of electroforetic periplasmic protein patterns, a possible marker system for epidemiological studies

The whole-cell and periplasmic protein (PP) compositions of 22 Serratia marcescens isolates were examined. Numerical analysis of whole-cell protein patterns was not a useful procedure for measuring relationships between organisms at the subspecific level. However, there was a very good correlation between electrophoretic PP pattern results and those obtained previously from multilocus enzyme electrophoresis (electrophoretic type) and biotype (D. Gargallo-Viola, J. Clin. Microbiol. 27:860-868, 1989). Clustering of isolates by using PP patterns compared by coefficients based on peak position (Dice coefficient) gave more precise information than that obtained by correlation coefficients. PP patterns appeared to be a useful tool that may be of value for epidemiologic studies