oritavancin and Cross-Infection

Health care-associated infections, especially those caused by multidrug-resistant gram-positive organisms, such as methicillin-resistant Staphylococcus aureus (MRSA), are a growing public health threat. In 2014, the U.S. Food and Drug Administration approved two new lipoglycopeptides, oritavancin and dalbavancin, for the treatment of acute bacterial skin and skin structure infections. The rationale for the development of these antimicrobials was partly to aid in the battle against vancomycin resistance in both Staphylococcus and Enterococcus. Considered a subclass of the glycopeptide antibiotics, the new lipoglycopeptides have similar mechanisms of action of binding to the carboxyl terminal d-alanyl-d-alanine residue of the growing peptide chains but differ from their parent glycopeptides by the addition of lipophilic tails. This addition allows for these agents to have prolonged half-lives, giving them unique dosing profiles. In addition, by concentrating at the site of action, they have increased potency against MRSA compared with vancomycin, the current mainstay of therapy. In this review, we focus on comparing and contrasting these two new agents with regard to their pharmacology, mechanisms of action, spectrum of activity, safety profiles, dosage and administration, and drug and laboratory interactions, and we review the clinical trials evaluating their use.

Topics: Animals; Anti-Bacterial Agents; Cross Infection; Drug Interactions; Glycopeptides; Gram-Positive Bacterial Infections; Half-Life; Humans; Lipoglycopeptides; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Randomized Controlled Trials as Topic; Skin Diseases, Bacterial; Teicoplanin; United States; Vancomycin Resistance

Current antibiotics available for the treatment of healthcare-associated pneumonia (HCAP) may result in clinical failure due to resistance development, side effect intolerance, or poor pharmacokinetic-pharmacodynamic profiles. New agents active against common HCAP pathogens are needed. The mechanism of action, spectrum of activity, pharmacokinetics, adverse effects, and clinical efficacy of seven new agents in clinical development or recently approved with either methicillin-resistant Staphylococcus aureus (MRSA) or pseudomonal activity are reviewed. They include doripenem, a new antipseudomonal carbapenem; ceftobiprole and ceftaroline, two anti-MRSA cephalosporins; iclaprim, a selective dihydrofolate reductase antagonist; and three glycopeptides, dalbavancin, telavancin, and oritavancin.

Topics: Aminoglycosides; Anti-Bacterial Agents; Carbapenems; Ceftaroline; Cephalosporins; Cross Infection; Doripenem; Glycopeptides; Lipoglycopeptides; Methicillin-Resistant Staphylococcus aureus; Pneumonia, Bacterial; Pseudomonas Infections; Pyrimidines; Staphylococcal Infections; Teicoplanin

Ten analogues of a teicoplanin pseudoaglycon derivative have been synthesized with the aim of optimizing the in vitro activity of the compound against VanA type vancomycin resistant enterococci (VRE) isolated from hospitalized patients. Teicoplanin, vancomycin, and oritavancin were used as reference antibiotics for the antibacterial evaluations. One of the new derivatives exhibited far superior activity than the original compound. The in vitro MICs measured were comparable to that of oritavancin against the investigated VRE strains.

Topics: Anti-Bacterial Agents; Cross Infection; Drug Resistance, Bacterial; Gram-Positive Bacteria; Lipoglycopeptides; Microbial Sensitivity Tests; Teicoplanin; Vancomycin-Resistant Enterococci

Topics: Anti-Bacterial Agents; Bacteremia; Cross Infection; Europe; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Hospitals; Humans; Lipoglycopeptides; United States

Topics: Anti-Bacterial Agents; Cross Infection; Enterococcus; Enterococcus faecalis; Glycopeptides; Gram-Positive Bacterial Infections; Humans; Lipoglycopeptides; Microbial Sensitivity Tests; Vancomycin; Vancomycin Resistance

Topics: Anti-Bacterial Agents; Community-Acquired Infections; Cross Infection; Glycopeptides; Humans; Lipoglycopeptides; Microbial Sensitivity Tests; Staphylococcal Infections; Staphylococcus aureus; United States

To assess oritavancin activity in vitro against clinically relevant Gram-positive pathogens causing skin and soft-tissue infections (SSTIs) in European and US hospitals.. 13 262 consecutive and unique isolates deemed to be responsible for SSTIs were included. Isolates originated from 36 and 27 institutions in Europe (Israel included) and the USA, respectively, between 2010 and 2013.. Oritavancin (98.8% susceptible) showed modal MIC, MIC50 and MIC90 results of 0.03, 0.03 and 0.06 mg/L, respectively, for Staphylococcus aureus. CoNS from the USA (MIC50, 0.015 mg/L) demonstrated an MIC50 value of oritavancin slightly lower than those from Europe (MIC50, 0.03 mg/L). Overall, vancomycin-resistant (VanA-phenotype) Enterococcus faecalis had oritavancin MICs (MIC50/90, 0.25/0.5 mg/L) that were 16-fold higher than those obtained for vancomycin-susceptible isolates (MIC50/90, 0.015/0.03 mg/L; 99.2%-99.8% susceptible); nevertheless, oritavancin inhibited all VanA E. faecalis at ≤0.5 mg/L. Equivalent oritavancin MICs (MIC50/90, 0.004/0.008 mg/L) were noted for all VanB and vancomycin-susceptible Enterococcus faecium, while higher MICs (MIC50/90, 0.03/0.12 mg/L) were obtained for VanA strains. Oritavancin had low MICs against the overall populations of Streptococcus pyogenes (MIC50/90, 0.03/0.12 mg/L; 98.4%-98.6% susceptible), Streptococcus agalactiae (MIC50/90, 0.03/0.06 mg/L; 97.9%-98.0% susceptible) and the Streptococcus anginosus group (MIC50/90, 0.008/0.015 mg/L; 100.0% susceptible), with slightly higher MICs for Streptococcus dysgalactiae (MIC50/90, 0.06/0.25 mg/L; ≥98.3% susceptible).. Oritavancin had potent activity in vitro against this contemporary collection of European and US isolates causing SSTIs. These results describe oritavancin activity against Gram-positive pathogens collected shortly prior to its regulatory approval in the USA.

Topics: Anti-Bacterial Agents; Cross Infection; Drug Resistance, Bacterial; Europe; Glycopeptides; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Lipoglycopeptides; Microbial Sensitivity Tests; Public Health Surveillance; Skin Diseases, Bacterial; Soft Tissue Infections; United States

To assess the oritavancin spectrum and activity against 2811 rarer species of coagulase-negative staphylococci (CoNS), streptococci and other Gram-positive species.. A total of 2057 CoNS (14 species), 674 streptococci (7 groups) and 80 other Gram-positive species (3 genera) collected over a 5 year period as part of the SENTRY Program (2008-12) were included. Isolates were primarily identified by the participating laboratory and identification was confirmed by the reference monitoring laboratory (JMI Laboratories, North Liberty, IA, USA). Isolates were tested for susceptibility by broth microdilution following the CLSI M07-A9 and M100-S23 documents.. Overall, oritavancin was active against all CoNS (MIC50/MIC90, 0.015/0.06 mg/L), with MIC50 values of ≤0.008-0.03 mg/L. Streptococci exhibited oritavancin MIC50 results of ≤0.008 mg/L, except for the Streptococcus bovis (0.03 mg/L), Streptococcus dysgalactiae (0.06 mg/L) and Streptococcus salivarius/vestibularis (0.06 mg/L) groups. Micrococcus spp., Listeria monocytogenes and Corynebacterium spp. had oritavancin MIC50 results of ≤0.008 mg/L.. This study expands the oritavancin in vitro data against several species of Gram-positive organisms.

Topics: Anti-Bacterial Agents; Cross Infection; Global Health; Glycopeptides; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Hospitals; Humans; Inhibitory Concentration 50; Lipoglycopeptides; Microbial Sensitivity Tests; Staphylococcus; Streptococcus

In vitro resistance of community-acquired and nosocomial strains of Enterococcus faecalis isolated in Badajoz (Spain) were determined by a microdilution method. The isolates were identified with conventional MicroScan Pos Combo 4 I dehydrated panels. No resistance to glycopeptides was found, but LY333328 was 2-4 times more active than vancomycin. In the nosocomial strains, high-level resistance to streptomycin (HLRS) was 54.7%, and high-level resistance to gentamicin (HLRG) was 38.1%. Resistance to ciprofloxacin and trovafloxacin was 45.3 and 38.9%, respectively. In the community-acquired isolates, HLRS, HLRG, resistance to ciprofloxacin and resistance to trovafloxacin were 44.2, 17.3, 15.4 and 13.5%, respectively. Trovafloxacin was 2-4 times more active than ciprofloxacin against both groups of strains. An association between high-level resistance to aminoglycosides and resistance to fluoroquinolones was noted. The resistance to aminoglycosides did not influence the activity of vancomycin and LY333328.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Ciprofloxacin; Community-Acquired Infections; Cross Infection; Drug Resistance, Bacterial; Enterococcus faecalis; Fluoroquinolones; Gentamicins; Glycopeptides; Gram-Positive Bacterial Infections; Humans; Incidence; Lipoglycopeptides; Microbial Sensitivity Tests; Naphthyridines; Spain; Streptomycin; Vancomycin

The in vitro activity of LY333328 was evaluated for 1,479 nosocomial gram-positive pathogens isolated in 12 countries during 1997. LY333328 MICs at which 90% of the isolates tested were inhibited for Enterococcus faecalis (n = 351), Enterococcus faecium (n = 100), Staphylococcus aureus (n = 593), coagulase-negative Staphylococcus species (n = 325), and Streptococcus pneumoniae (n = 110) were 1, 1, 2, 2, and 0.015 microg/ml, respectively. LY333328 demonstrated potent activity against isolates of vancomycin-resistant enterococci, oxacillin-resistant staphylococci, and penicillin-resistant pneumococci.

Topics: Anti-Bacterial Agents; Cross Infection; Glycopeptides; Gram-Positive Bacteria; Humans; Lipoglycopeptides; Microbial Sensitivity Tests; Penicillin Resistance; Vancomycin Resistance