Safety and Efficacy of Gatifloxacin Therapy for Children with Recurrent Acute Otitis Media (AOM) and/or AOM Treatment Failure

Background. Because of concerns about arthrotoxicity, fluoroquinolones are restricted for use in children. This study describes the safety and efficacy of gatifloxacin when used for treatment of children with recurrent acute otitis media (ROM) or acute otitis media (AOM) treatment failure (AOMTF). Methods. We performed an analysis of 867 children included in 4 clinical trials who had ROM and/or AOMTF and were treated with gatifloxacin (10 mg/kg once daily for 10 days). Results. Gatifloxacin had adverse event rates that were similar overall to those of a comparator antibiotic (amoxicillin-clavulanate), except for increased diarrhea in children !2 years old receiving amoxicillin-clavulanate. There was no evidence of arthrotoxicity, hepatotoxicity, alteration of glucose homeostasis, or central nervous system toxicity acutely or during 1 year follow-up in any child. Regarding efficacy, in 2 noncomparative trials, the gatifloxacin cure rate of AOM was 89% (95% confidence interval [CI], 83%-95%) at the test of cure (TOC) visit, 3-10 days after completion of therapy. In 2 comparative trials of gatifloxacin versus amoxicillin-clavulanate, the efficacy of gatifloxacin was 88% (95% CI, 82%-94%). Gatifloxacin led to better clinical outcomes than amoxicillinclavulanate for AOMTF (91% vs. 81%; ), for AOMTF and age !2 years old (89% vs. 69%; ), P p .029 P p .009 and for severe AOM in children !2 years old (90% vs. 75%; ). Among children with AOMTF previously P p .012 treated with amoxicillin-clavulanate or ceftriaxone injections, gatifloxacin cure rates were high (88% and 75%, respectively). Conclusions. Gatifloxacin appears to be safe for children, with no evidence of producing arthrotoxicity in 867 children exposed to the antibiotic when used as treatment for ROM and AOMTF

Prevalence of Avian-Pathogenic Escherichia coli Strain O1 Genomic Islands among Extraintestinal and Commensal E. coli Isolates

Escherichia coli strains that cause disease outside the intestine are known as extraintestinal pathogenic E. coli (ExPEC) and include pathogens of humans and animals. Previously, the genome of avian-pathogenic E. coli (APEC) O1:K1:H7 strain O1, from ST95, was sequenced and compared to those of several other E. coli strains, identifying 43 genomic islands. Here, the genomic islands of APEC O1 were compared to those of other sequenced E. coli strains, and the distribution of 81 genes belonging to 12 APEC O1 genomic islands among 828 human and avian ExPEC and commensal E. coli isolates was determined. Multiple islands were highly prevalent among isolates belonging to the O1 and O18 serogroups within phylogenetic group B2, which are implicated in human neonatal meningitis. Because of the extensive genomic similarities between APEC O1 and other human ExPEC strains belonging to the ST95 phylogenetic lineage, its ability to cause disease in a rat model of sepsis and meningitis was assessed. Unlike other ST95 lineage strains, APEC O1 was unable to cause bacteremia or meningitis in the neonatal rat model and was significantly less virulent than uropathogenic E. coli (UPEC) CFT073 in a mouse sepsis model, despite carrying multiple neonatal meningitis E. coli (NMEC) virulence factors and belonging to the ST95 phylogenetic lineage. These results suggest that host adaptation or genome modifications have occurred either in APEC O1 or in highly virulent ExPEC isolates, resulting in differences in pathogenicity. Overall, the genomic islands examined provide targets for further discrimination of the different ExPEC subpathotypes, serogroups, phylogenetic types, and sequence types

Modification of cell surface properties of Pseudomonas alcaligenes S22 during hydrocarbon biodegradation

Biodegradation of water insoluble hydrocarbons can be significantly increased by the addition of natural surfactants one. Very promising option is the use of saponins. The obtained results indicated that in this system, after 21 days, 92% biodegradation of diesel oil could be achieved using Pseudomonas alcaligenes. No positive effect on the biodegradation process was observed using synthetic surfactant Triton X-100. The kind of carbon source influences the cell surface properties of microorganisms. Modification of the surface cell could be observed by control of the sedimentation profile. This analytical method is a new approach in microbiological analysis

Indexing the Pseudomonas specialized metabolome enabled the discovery of poaeamide B and the bananamides

Pseudomonads are cosmopolitan microorganisms able to produce a wide array of specialized metabolites. These molecules allow Pseudomonas to scavenge nutrients, sense population density and enhance or inhibit growth of competing microorganisms. However, these valuable metabolites are typically characterized one-molecule–one-microbe at a time, instead of being inventoried in large numbers. To index and map the diversity of molecules detected from these organisms, 260 strains of ecologically diverse origins were subjected to mass-spectrometry-based molecular networking. Molecular networking not only enables dereplication of molecules, but also sheds light on their structural relationships. Moreover, it accelerates the discovery of new molecules. Here, by indexing the Pseudomonas specialized metabolome, we report the molecular-networking-based discovery of four molecules and their evolutionary relationships: a poaeamide analogue and a molecular subfamily of cyclic lipopeptides, bananamides 1, 2 and 3. Analysis of their biosynthetic gene cluster shows that it constitutes a distinct evolutionary branch of the Pseudomonas cyclic lipopeptides. Through analysis of an additional 370 extracts of wheat-associated Pseudomonas, we demonstrate how the detailed knowledge from our reference index can be efficiently propagated to annotate complex metabolomic data from other studies, akin to the way in which newly generated genomic information can be compared to data from public databases

Universality of Thermodynamic Constants Governing Biological Growth Rates

Background: Mathematical models exist that quantify the effect of temperature on poikilotherm growth rate. One family of such models assumes a single rate-limiting ‘master reaction ’ using terms describing the temperature-dependent denaturation of the reaction’s enzyme. We consider whether such a model can describe growth in each domain of life. Methodology/Principal Findings: A new model based on this assumption and using a hierarchical Bayesian approach fits simultaneously 95 data sets for temperature-related growth rates of diverse microorganisms from all three domains of life, Bacteria, Archaea and Eukarya. Remarkably, the model produces credible estimates of fundamental thermodynamic parameters describing protein thermal stability predicted over 20 years ago. Conclusions/Significance: The analysis lends support to the concept of universal thermodynamic limits to microbial growth rate dictated by protein thermal stability that in turn govern biological rates. This suggests that the thermal stability of proteins is a unifying property in the evolution and adaptation of life on earth. The fundamental nature of this conclusion has importance for many fields of study including microbiology, protein chemistry, thermal biology, and ecological theory including, for example, the influence of the vast microbial biomass and activity in the biosphere that is poorly described in current climate models

Translocations as Experiments in the Ecological Resilience of an Asocial Mega-Herbivore

Species translocations are remarkable experiments in evolutionary ecology, and increasingly critical to biodiversity conservation. Elaborate socio-ecological hypotheses for translocation success, based on theoretical fitness relationships, are untested and lead to complex uncertainty rather than parsimonious solutions. We used an extraordinary 89 reintroduction and 102 restocking events releasing 682 black rhinoceros (Diceros bicornis) to 81 reserves in southern Africa (1981–2005) to test the influence of interacting socio-ecological and individual characters on post-release survival. We predicted that the socio-ecological context should feature more prominently after restocking than reintroduction because released rhinoceros interact with resident conspecifics. Instead, an interaction between release cohort size and habitat quality explained reintroduction success but only individuals' ages explained restocking outcomes. Achieving translocation success for many species may not be as complicated as theory suggests. Black rhino, and similarly asocial generalist herbivores without substantial predators, are likely to be resilient to ecological challenges and robust candidates for crisis management in a changing world

Effect of Fructooligosaccharide Metabolism on Chicken Colonization by an Extra-Intestinal Pathogenic Escherichia coli Strain

Extra-intestinal pathogenic Escherichia coli (ExPEC) strains cause many diseases in humans and animals. While remaining asymptomatic, they can colonize the intestine for subsequent extra-intestinal infection and dissemination in the environment. We have previously identified the fos locus, a gene cluster within a pathogenicity island of the avian ExPEC strain BEN2908, involved in the metabolism of short-chain fructooligosaccharides (scFOS). It is assumed that these sugars are metabolized by the probiotic bacteria of the microbiota present in the intestine, leading to a decrease in the pathogenic bacterial population. However, we have previously shown that scFOS metabolism helps BEN2908 to colonize the intestine, its reservoir. As the fos locus is located on a pathogenicity island, one aim of this study was to investigate a possible role of this locus in the virulence of the strain for chicken. We thus analysed fos gene expression in extracts of target organs of avian colibacillosis and performed a virulence assay in chickens. Moreover, in order to understand the involvement of the fos locus in intestinal colonization, we monitored the expression of fos genes and their implication in the growth ability of the strain in intestinal extracts of chicken. We also performed intestinal colonization assays in axenic and Specific Pathogen-Free (SPF) chickens. We demonstrated that the fos locus is not involved in the virulence of BEN2908 for chickens and is strongly involved in axenic chicken cecal colonization both in vitro and in vivo. However, even if the presence of a microbiota does not inhibit the growth advantage of BEN2908 in ceca in vitro, overall, growth of the strain is not favoured in the ceca of SPF chickens. These findings indicate that scFOS metabolism by an ExPEC strain can contribute to its fitness in ceca but this benefit is fully dependent on the bacteria present in the microbiota