Activity of tedizolid against gram-positive clinical isolates causing infections in Europe and surrounding areas (2014–2015)

Activities of tedizolid and comparators were evaluated against gram-positive isolates responsible for skin and skin structure infections, pneumonia, and bloodstream infections. Non-duplicate gram-positive isolates (8011) were collected from 20 European countries/regions.

Tedizolid (0.12?mg/L) showed similar results of minimum inhibitory concentration required to inhibit the growth of 50% of organisms (MIC₅₀) regardless of pathogen/group or infection type, except for coagulase-negative staphylococci, Enterococcus faecalis, and viridans group streptococci (VGS), against which tedizolid had MIC₅₀ values of 0.06, 0.25, and 0.06?mg/L, respectively. Similar results of tedizolid MIC₅₀ and minimum inhibitory concentration required to inhibit the growth of 90% of organisms (MIC₉₀) (MIC_50/90, 0.12/0.12?mg/L) were obtained against methicillin-resistant Staphylococcus aureus and methicillin-susceptible S. aureus. Tedizolid, linezolid, and daptomycin were active against enterococci. Tedizolid (MIC₉₀, 0.12–0.25?mg/L), ceftaroline (MIC₉₀, 0.12?mg/L), and vancomycin (MIC₉₀, 0.25–0.5?mg/L) had the lowest MIC₉₀ values against Streptococcus pneumoniae and VGS, whereas ceftaroline (MIC₉₀, ≤0.015?mg/L), penicillin (MIC₉₀, ≤0.06?mg/L), ceftriaxone (MIC₉₀, ≤0.06–0.12?mg/L), and tedizolid (MIC₉₀, 0.12?mg/L) were the most potent against β-haemolytic streptococci.

Tedizolid displayed potent activity against gram-positive isolates from Europe, regardless of infection type.     

The role of telavancin in the treatment of MRSA infections in hospital

Background: Serious infections caused by Gram-positive bacteria, particularly multi-drug resistant, are an important cause of morbidity and mortality in patients admitted to intensive care units. Thus, new antibiotics covering these pathogens are urgently needed. Objective: To review characteristics of telavancin, a novel antibiotic intended to use for treating infections caused by difficult Gram-positive bacteria, such as Staphylococcus aureus, resistant to meticillin or vancomycin, multi-drug-resistant Streptococcus pneumoniae or glycopeptide-resistant enterococci. Methods: The studies on microbiological activity, clinical efficacy and safety of telavancin were reviewed. Results/conclusion: Telavancin is a lipoglycopeptide administered intravenously once-daily and excreted with urine. It proved to be microbiologically active against numerous Gram-positive pathogens including drug-resistant staphylococci, enterococci and pneumococci. Large randomized Phase II and III clinical trials on efficacy and safety of telavancin in treating complicated skin and skin structure infections reported telavancin to be non-inferior to standard treatment (mostly vancomycin). Preliminary data on telavancin in hospital-acquired pneumonia, including ventilator-associated pneumonia, documented that telavancin was efficacious for this indication. Overall incidence of adverse events was similar for telavancin and the comparator arms. Mild and transient disgeusia, nausea and vomiting resulted to be more frequent in telavancin group. Increase in creatinine values was also observed in telavancin arm.     

Current and prospective treatments for multidrug-resistant gram-positive infections

Introduction: Staphylococcus aureus and Enterococcus spp. are two of the most common organisms causing nosocomial infections today; and are consistently associated with high mortality rates (approximately 20 and 44%, respectively). Resistance among these pathogens to first line agents such as methicillin and vancomycin continues to rise while isolates with reduced susceptibility to newer agents including linezolid and daptomycin continue to emerge, representing a serious concern for clinicians.

Areas covered: Mechanisms of action and resistance as well as in vitro and clinical experience in the treatment of resistant staphylococci and enterococci with currently available agents are discussed. Additionally, novel combination regimens showing enhanced efficacy and available data pertaining to prospective therapies including solithromycin, tedizolid, dalbavancin and oritavancin will be covered.

Expert opinion: With an increase in organisms displaying reduced susceptibility to vancomycin and the associated treatment failures, the significance of alternative therapies such as daptomycin, linezolid, ceftaroline, and prospective anti-gram-positive agents is on the rise. As our understanding of antimicrobial pharmacokinetic-pharmacodynamics principles continues to evolve, the selection of highly effective agents and optimization of dosages may lead to improved patient outcomes and delay the development of resistance.     

Failure of daptomycin β-Lactam combination therapy to prevent resistance emergence in Enterococcus faecium

Daptomycin β-Lactam combination therapy offers “protection” against daptomycin non-susceptibility (DNS) development in Enterococcus faecium. We report failure of this strategy and the importance of source control. Mutations were detected in the LiaF and cls genes in DNS isolates. A single DNS isolate contained an unrecognized mutation, which requires confirmation.     

Clinical relevance of the ESKAPE pathogens

In recent years, the Infectious Diseases Society of America has highlighted a faction of antibiotic-resistant bacteria (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) – acronymically dubbed ‘the ESKAPE pathogens’ – capable of ‘escaping’ the biocidal action of antibiotics and mutually representing new paradigms in pathogenesis, transmission and resistance. This review aims to consolidate clinically relevant background information on the ESKAPE pathogens and provide a contemporary summary of bacterial resistance, alongside pertinent microbiological considerations necessary to face the mounting threat of antimicrobial resistance.     

Investigational treatments for postoperative surgical site infections

Surgical site infections rank third among nosocomial infections, representing a global threat, associated with the emergence of multi-drug-resistant bacteria. The pharmaceutical industry has recently curtailed developmental programmes; however, the need for new compounds is extremely important. This article reviews new antimicrobials and immunointerventional targets for their potential to treat surgical site infections in comparison with recently licensed compounds. Daptomycin, dalbavancin, oritavancin, telavancin, iclaprim and ranbezolid seem to be promising agents against infections caused by Gram-positive pathogens and effectively address the present problems of multi-resistance in Gram-positive infections. Peptide deformylase inhibitors and immunostimulating agents open new perspectives in this field; however, very few compounds targeting Gram-negative problematic pathogens are in the pipeline of the future. Tigecycline (recently marketed) ceftobiprole, ceftaroline and doripenem seem to possess an extended anti-Gram-positive and -negative spectrum. Among these compounds, only doripenem demonstrates activity against Pseudomonas aeruginosa, for which there is a clear unmet need for new compounds, focusing on new targets.     

Killing of VRE Enterococcus faecalis by commensal strains: Evidence for evolution and accumulation of mobile elements in the absence of competition

Enterococci are members of the gastrointestinal tract of humans and most animals that, over the past 3 decades, have emerged as leading causes of multidrug resistant hospital acquired infection (HAI). In addition to their general hardiness, many traits have entered enterococcal lineages through horizontal gene transfer, which has led to the evolution of pathogenic hospital-associated lineages uniquely adapted for survival and proliferation in the antibiotic perturbed ecology of the gastrointestinal tract. We recently observed that the accretion of mobile genetic elements in the prototype vancomycin resistant E. faecalis, clinical isolate V583, renders it unable to co-exist with native enterococci in healthy human fecal flora. In this addendum, we discuss how these findings inform our understanding of how multidrug resistant enterococci evolve, and the implications for the development of treatments that limit colonization and spread of highly antibiotic refractory microbes of this type.     

Colonization of residents and staff of a long-term-care facility and adjacent acute-care hospital geriatric unit by multiresistant bacteria

Long-term-care facilities (LTCFs) are reservoirs of resistant bacteria. We undertook a point-prevalence survey and risk factor analysis for specific resistance types among residents and staff of a Bolzano LTCF and among geriatric unit patients in the associated acute-care hospital. Urine samples and rectal, inguinal, oropharyngeal and nasal swabs were plated on chromogenic agar; isolates were typed by pulsed-field gel electrophoresis; resistance genes and links to insertion sequences were sought by PCR; plasmids were analysed by PCR, restriction fragment length polymorphism and incompatibility grouping. Demographic data were collected. Of the LTCF residents, 74.8% were colonized with ≥1 resistant organism, 64% with extended-spectrum β-lactamase (ESBL) producers, 38.7% with methicillin-resistant Staphylococcus aureus (MRSA), 6.3% with metallo-β-lactamase (MBL) producers, and 2.7% with vancomycin-resistant enterococci. Corresponding rates for LTCF staff were 27.5%, 14.5%, 14.5%, 1.5% and 0%, respectively. Colonization frequencies for geriatric unit patients were lower than for those in the LTCF. Both clonal spread and plasmid transfer were implicated in the dissemination of MBL producers that harboured IncN plasmids bearing bla_VIM-1, qnrS, and bla_SHV-12. Most (44/45) ESBL-producing Escherichia coli isolates had bla_CTX-M genes of group 1; a few had bla_CTX-M genes of group 9 or bla_SHV-5; those with bla_CTX-M-15 or bla_SHV-5 were clonal. Risk factors for colonization of LTCF residents with resistant bacteria included age ≥86 years, antibiotic treatment in the previous 3 months, indwelling devices, chronic obstructive pulmonary disease, physical disability, and the particular LTCF unit; those for geriatric unit patients were age and dementia. In conclusion, ESBL-producing and MBL-producing Enterobacteriaceae and MRSA were prevalent among the LTCF residents and staff, but less so in the hospital geriatric unit. Education of LTCF employees and better infection control are proposed to minimize the spread of resistant bacteria in the facility.