telavancin and Pneumonia--Bacterial

Telavancin is a novel lipoglycopeptide derivative of vancomycin that has activity against Gram-positive aerobic and anerobic bacteria, for the treatment of serious infections, including complicated skin and skin structure infections (cSSSI) and pneumonia.. This article was compiled through searches on telavancin up to December 2015 in the PubMed and the clinicaltrials.gov databases; the FDA and European Medicine Agency (EMA) websites. In our review, particular attention was paid to those articles that reviewed the pharmacokinetic characteristics of the drug and animal models of infection. We also searched for evidence of the efficacy of telavancin as demonstrated in clinical trials, safety and tolerability data and have compiled a summary of clinical trials on telavancin in pneumonia.. Telavancin is approved in Europe and the USA for the treatment of nosocomial pneumonia caused by methicillin resistant Staphylococcus aureus when other alternatives are not suitable.

Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Cross Infection; Disease Models, Animal; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Lipoglycopeptides; Methicillin-Resistant Staphylococcus aureus; Pneumonia, Bacterial; Pneumonia, Staphylococcal

Treatment options for hospital-acquired pneumonia caused by Gram-positive organisms are far from ideal. The increase in vancomycin MICs among methicillin-resistant Staphylococcus aureus (MRSA) isolates, and the slow bactericidal action and poor lung penetration of vancomycin have driven the search for an alternative agent. Telavancin, a once-daily lipoglycopeptide, displays strong bactericidal activity against S. aureus. Two large Phase III randomized trials have recently compared intravenous telavancin (10 mg/kg every 24 h) with vancomycin (1 g intravenously every 12 h) for 7-21 days for the treatment of hospital-acquired pneumonia caused by Gram positives. No significant differences were observed in the cure rates in the all-treated (n = 1503), the clinically evaluable (n = 654) and the microbiologically evaluable (n =480) populations. Telavancin performed better than vancomycin in patients with monomicrobial S. aureus pneumonia (84.2 vs 74.3%; 95% CI: 0.7-19.1), with MRSA (81.8 vs 74.1%; 95% CI: -3.5 to 19.3), and with strains having vancomycin MICs ≥1 µg/ml (87.1 vs 74.3; 95% CI: 0.5-23). The rate of adverse events, including serious adverse events, was similar in both groups, with a slightly higher rate of serum creatinine increase in the telavancin-treated group. Based on these results, telavancin (already approved for this indication by the EMA) could certainly be added to the current treatment options, particularly in patients with MRSA pneumonia.

Topics: Aminoglycosides; Anti-Bacterial Agents; Creatinine; Cross Infection; Drug Administration Schedule; Humans; Lipoglycopeptides; Microbial Sensitivity Tests; Pneumonia, Bacterial; Randomized Controlled Trials as Topic; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome; Vancomycin

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

Hospital-acquired bacterial pneumonia (HABP) is the second most common nosocomial infection in the USA and the leading cause of mortality among hospital-acquired infections. An increasing proportion of HABP cases are the result of infection with methicillin-resistant Staphylococcus aureus (MRSA). Telavancin is a once-daily injectable, semisynthetic lipoglycopeptide antimicrobial with bactericidal activity against susceptible Gram-positive pathogens, including MRSA. The two methodologically identical Phase III ATTAIN studies demonstrated that telavancin was noninferior to vancomycin for the treatment of HABP, including ventilator-associated bacterial pneumonia, due to S. aureus (including methicillin-sensitive S. aureus and MRSA). Telavancin showed a similar safety profile to vancomycin, except that in patients with moderate-to-severe renal impairment, there was increased mortality, which warrants caution when using telavancin in this population. Now approved in the USA for the treatment of HABP, including ventilator-associated bacterial pneumonia, caused by susceptible isolates of S. aureus when other alternatives are not suitable, telavancin offers another therapeutic option.

Topics: Adult; Aged; Aged, 80 and over; Aminoglycosides; Anti-Bacterial Agents; Cross Infection; Female; Humans; Lipoglycopeptides; Male; Middle Aged; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Treatment Outcome; Vancomycin

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacteremia; Cohort Studies; Drug Resistance, Bacterial; Hospitalization; Humans; Lipoglycopeptides; Microbial Sensitivity Tests; Pneumonia, Bacterial; Staphylococcal Skin Infections; Staphylococcus aureus; United States

When bacterial pneumonia contracted in hospital (nosocomial pneumonia) is thought to be due to a methicillin-resistant strain of S. aureus, the most commonly used antibiotics are vancomycin and teicoplanin (glycopeptides) or linezolid (an oxazolidinone). Telavancin, a glycopeptide derived from vancomycin, is active in vitro against methicillin-resistant S. aureus. It has been authorised in the European Union for second-line treatment of patients with nosocomial pneumonia caused by methicillin-resistant S. aureus. Telavancin has not been tested in nosocomial pneumonia resistant to first-line antibiotics. There is no evidence that its antibacterial efficacy is better than that of existing options. In two randomised trials including a total of 1532 patients with nosocomial pneumonia, telavancin and vancomycin yielded similar cure rates, including in cases due to methicillin-resistant S. aureus. Higher mortality rates were reported in the telavancin group, especially among patients with renal impairment. Telavancin causes more renal adverse effects and QT prolongation than vancomycin. The other known adverse effects of telavancin are shared by vancomycin. Cases of cross-allergy between the two drugs have been reported. Telavancin is both nephrotoxic and eliminated by the kidneys, creating a risk of interactions with other nephrotoxic drugs and accumulation in patients with renal impairment. Telavancin can interfere with some clotting tests. Telavancin was teratogenic in experimental animals. In practice, there is no evidence that telavancin is more effective than vancomycin, but it has more adverse effects. It is has not been shown to be effective on infections due to bacteria resistant to vancomycin, teicoplanin or linezolid. It is better not to use telavancin, but rather continue to use standard antibiotics appropriately.

Topics: Aminoglycosides; Anti-Bacterial Agents; Humans; Lipoglycopeptides; Pneumonia, Bacterial; Vancomycin

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacteremia; Cross Infection; Humans; Lipoglycopeptides; Pneumonia, Bacterial; Treatment Outcome; Vancomycin

Results of pharmacometric analyses influence high-level decisions such as clinical trial design, drug approval, and labeling. Key challenges for timely delivery of pharmacometric analyses are the data assembly process and tracking and documenting the modeling process and results. Since clinical efficacy and safety data typically reside in the biostatistics computing area, an integrated computing platform for pharmacometric and biostatistical analyses would be ideal. A case study is presented integrating a pharmacometric modeling platform into an existing statistical computing environment (SCE). The feasibility and specific configurations of running common PK/PD programs such as NONMEM and R inside of the SCE are provided. The case study provides an example of an integrated repository that facilitates efficient data assembly for pharmacometrics analyses. The proposed platform encourages a good pharmacometrics working practice to maintain transparency, traceability, and reproducibility of PK/PD models and associated data in supporting drug development and regulatory decisions.

Topics: Aminoglycosides; Anti-Bacterial Agents; Biostatistics; Computer Simulation; Cross Infection; Humans; Lipoglycopeptides; Models, Biological; Pharmacology, Clinical; Pneumonia, Bacterial; Software

Topics: Aminoglycosides; Anti-Bacterial Agents; Cross Infection; Gram-Positive Bacterial Infections; Humans; Lipoglycopeptides; Pneumonia, Bacterial; Treatment Outcome; Vancomycin

The antimicrobial activity of telavancin against 2279 clinical Gram-positive cocci obtained from patients with nosocomial pneumonia [NP; including those with ventilator-acquired pneumonia (VAP)] located in numerous medical centres worldwide was evaluated.. A contemporary collection of 2279 non-duplicate consecutive Gram-positive clinical isolates were submitted from 87 hospitals located in North America (913 isolates), Latin America (222 isolates), Europe (690 isolates), and the Asia-Pacific region (454 isolates) as part of the international telavancin surveillance programme for 2007-08. Isolates were tested for susceptibility by the reference broth microdilution method (with 2%-5% lysed horse blood added for testing of streptococci). Interpretive criteria were those from CLSI (M100-S20, 2010) except for telavancin, for which the susceptible breakpoints approved by the US FDA were applied.. Telavancin was highly active against Staphylococcus aureus (MIC(90), 0.25 mg/L; 100% susceptible), coagulase-negative staphylococci (MIC(90), 0.25 mg/L), Streptococcus pneumoniae (MIC(90), 0.03 mg/L), viridans group streptococci (MIC(90), 0.06 mg/L; 100% susceptible), β-haemolytic streptococci (MIC(90), 0.06 mg/L; 100% susceptible) and vancomycin-susceptible enterococci (MIC(90), 0.5 mg/L; 100% susceptible). Telavancin inhibited all staphylococci at ≤ 0.5 mg/L. Among enterococci non-susceptible to vancomycin (all Enterococcus faecium), telavancin was active against isolates exhibiting a VanB phenotype (MIC, 0.06-0.12 mg/L), but less potent against VanA strains (MIC, ≥ 2 mg/L).. Telavancin demonstrated equal or greater potency than the comparators (vancomycin, teicoplanin, daptomycin, linezolid and quinupristin/dalfopristin) against Gram-positive pathogens implicated in NP. Telavancin showed elevated MIC values only against enterococcus isolates showing a VanA phenotype. The continued appearance of multidrug-resistant pathogens among Gram-positive isolates, mainly S. aureus, necessitates the introduction of new agents and longitudinal surveillance to monitor for the potential emergence of resistance.

Topics: Aminoglycosides; Anti-Bacterial Agents; Asia; Cross Infection; Culture Media; Europe; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Latin America; Lipoglycopeptides; Microbial Sensitivity Tests; North America; Pacific Islands; Pneumonia, Bacterial; Respiratory System; United States