Background. Surveillance studies have shown that <0.1% of coagulase-negative staphylococci are linezolid resistant; however, at our institution, 4% of such organisms were found to be resistant. We ...investigated the risk factors for and the epidemiological profile of linezolid-resistant coagulase-negative staphylococci. Methods. Susceptibility testing and pulsed-field gel electrophoresis were performed to analyze the genetic relatedness of both linezolid-resistant and linezolid-susceptible isolates. Clinical data were retrieved from medical records, and a case-case-control study was performed to identify unique risk factors for linezolid resistance. Results. Isolates recovered from 25 patients with linezolid-resistant coagulase-negative staphylococci were examined; all but 1 of the isolates were identified as Staphylococcus epidermidis, and all but 1 had a minimum inhibitory concentration of linezolid of >256 µg/mL. Pulsed-field gel electrophoresis showed that 21 (84%) of 25 linezolid-resistant isolates exhibited genetic relatedness, whereas linezolid-susceptible isolates were of diverse clones. Unique, independent predictors of linezolid resistance included receipt of linezolid in the 3 months preceding isolation of the coagulase-negative staphylococci (odds ratio, 20.6; 95% confidence interval, 5.8–73.0). Conclusion. Linezolid-resistant coagulase-negative staphylococci have emerged at our institution and are predominately of a single clone. We believe that the most likely scenario to explain this emergence is that person-to-person spread of linezolid-resistant coagulase-negative staphylococci led to establishment of skin colonization with the strain. Subsequent use of linezolid was followed by selection of the linezolid-resistant strain, which then became the dominant skin flora. The potential for a parallel scenario involving clonal dissemination followed by selection of linezolid-resistant methicillin-resistant Staphylococcus aureus is a real possibility.
: Breakthrough invasive fungal infections among patients with hematologic malignancies receiving voriconazole are being reported with increasing frequency, with zygomycete infections predominating. ...We report a case of disseminated Scedosporium prolificans infection in a patient receiving voriconazole prophylaxis. Despite poor in vitro activity of voriconazole for this organism, synergy studies using the checkerboard method demonstrated synergy with the combination of voriconazole and terbinafine. This regimen, in conjunction with central venous line removal and intravitreal voriconazole, contributed to the recovery of the patient. S. prolificans is a life‐threatening mold that should be considered in patients with breakthrough invasive fungal infections while on voriconazole prophylaxis.
Current trends in primary medicine include the inappropriate prescription of unnecessary antibiotic treatments that raise drug resistance levels among certain strains of bacteria. It is necessary ...that efforts be made to curb this trend.
The first decade of the 20th century witnessed a surge in the incidence of infections due to several highly antimicrobial-resistant bacteria in hospitals worldwide. Acinetobacter baumannii is one ...such organism that turned from an occasional respiratory pathogen into a major nosocomial pathogen. An increasing number of A. baumannii genome sequences have broadened our understanding of the genetic makeup of these bacteria and highlighted the extent of horizontal transfer of DNA. Animal models of disease combined with bacterial mutagenesis have provided some valuable insights into mechanisms of A. baumannii pathogenesis. Bacterial factors known to be important for disease include outer membrane porins, surface structures including capsule and lipopolysaccharide, enzymes such as phospholipase D, iron acquisition systems, and regulatory proteins. A. baumannii has a propensity to accumulate resistance to various groups of antimicrobial agents. In particular, carbapenem resistance has become commonplace, accounting for the majority of A. baumannii strains in many hospitals today. Carbapenem-resistant strains are often resistant to all other routinely tested agents. Treatment of carbapenem-resistant A. baumannii infection therefore involves the use of combinations of last resort agents such as colistin and tigecycline, but the efficacy and safety of these approaches are yet to be defined. Antimicrobial-resistant A. baumannii has high potential to spread among ill patients in intensive care units. Early recognition and timely implementation of appropriate infection control measures is crucial in preventing outbreaks.
We describe the first emergence of carbapenem-resistant Acinetobacter baumannii in Australia. Ninety A. baumannii isolates recovered from cultures of blood specimens from 69 patients were analyzed. ...Overall, 58 isolates (64%) were resistant to meropenem. The chi 2 test for linear trend revealed that emergence of carbapenem resistance was statistically significant during the 32-month study period. Selected isolates were of the same clonal type, and no genes encoding carbapenemases were identified.
is a Gram negative opportunistic pathogen that has demonstrated a significant insurgence in the prevalence of infections over recent decades. With only a limited number of "traditional" virulence ...factors, the mechanisms underlying the success of this pathogen remain of great interest. Major advances have been made in the tools, reagents, and models to study
pathogenesis, and this has resulted in a substantial increase in knowledge. This article provides a comprehensive review of the bacterial virulence factors, the host immune responses, and animal models applicable for the study of this important human pathogen. Collating the most recent evidence characterizing bacterial virulence factors, their cellular targets and genetic regulation, we have encompassed numerous aspects important to the success of this pathogen, including membrane proteins and cell surface adaptations promoting immune evasion, mechanisms for nutrient acquisition and community interactions. The role of innate and adaptive immune responses is reviewed and areas of paucity in our understanding are highlighted. Finally, with the vast expansion of available animal models over recent years, we have evaluated those suitable for use in the study of
disease, discussing their advantages and limitations.
Daptomycin remains one of our last-line anti-staphylococcal agents. This study aims to characterize the genetic evolution to daptomycin resistance in S. aureus.
Whole genome sequencing was performed ...on a unique collection of isogenic, clinical (21 strains) and laboratory (12 strains) derived strains that had been exposed to daptomycin and developed daptomycin-nonsusceptibility. Electron microscopy (EM) and lipid membrane studies were performed on selected isolates.
On average, six coding region mutations were observed across the genome in the clinical daptomycin exposed strains, whereas only two mutations on average were seen in the laboratory exposed pairs. All daptomycin-nonsusceptible strains had a mutation in a phospholipid biosynthesis gene. This included mutations in the previously described mprF gene, but also in other phospholipid biosynthesis genes, including cardiolipin synthase (cls2) and CDP-diacylglycerol-glycerol-3-phosphate 3-phosphatidyltransferase (pgsA). EM and lipid membrane composition analyses on two clinical pairs showed that the daptomycin-nonsusceptible strains had a thicker cell wall and an increase in membrane lysyl-phosphatidylglycerol.
Point mutations in genes coding for membrane phospholipids are associated with the development of reduced susceptibility to daptomycin in S. aureus. Mutations in cls2 and pgsA appear to be new genetic mechanisms affecting daptomycin susceptibility in S. aureus.
Whether it is in the setting of disease or in a healthy state, the human body contains a diverse range of microorganisms, including bacteria and fungi. The interactions between these taxonomically ...diverse microorganisms are highly dynamic and dependent on a multitude of microorganism and host factors. Human disease can develop from an imbalance between commensal bacteria and fungi or from invasion of particular host niches by opportunistic bacterial and fungal pathogens. This Review describes the clinical and molecular characteristics of bacterial-fungal interactions that are relevant to human disease.
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