telavancin and Cross-Infection

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

Telavancin (TLV) is a lipoglycopeptide derivative of vancomycin (VAN), which has activity against Gram-positive aerobic bacteria, and is especially effective against methicillin-resistant Staphylococcus aureus (MRSA) and Gram-positive bacteria resistant to VAN. Comparative clinical studies of TLV have demonstrated noninferiority compared with VAN in the treatment of hospital-acquired Gram-positive pneumonia, with high cure rates for TLV-treated patients with monomicrobial S. aureus infection, including isolates with reduced VAN susceptibility. The results based on the patients' clinical response were supported by supplemental post-hoc analyses of 28-day mortality. In Europe and the USA, TLV is approved as a useful alternative for patients with difficult-to-treat, hospital-acquired MRSA pneumonia when there are very few alternatives. The present article reviews TLV's pharmacological characteristics and clinical efficacy resulting from clinical trials giving a detailed picture of its properties and position in the management of hospital-acquired pneumonia.

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

Telavancin was the first marketed lipoglycopeptide. Although licensed in Europe in 2011 for the treatment of nosocomial pneumonia caused by meticillin-resistant Staphylococcus aureus (MRSA), it did not become clinically available until March 2014. Given the limited clinical experience with telavancin in Europe, this review provides an overview of its antimicrobial and clinical activity as well as its position among today's antimicrobials, with particular focus on the implications of its licensing requirements. Telavancin has potent in vitro activity against isolates of Gram-positive pathogens, including MRSA and glycopeptide-intermediate S. aureus strains. In addition, at clinically attainable doses telavancin inhibits Gram-positive isolates of antibiotic-resistant strains from biofilm models. The in vitro potency of telavancin has been corroborated in the clinical setting. Comparative clinical studies of telavancin demonstrate non-inferiority compared with vancomycin in the treatment of hospital-acquired Gram-positive pneumonia, with high cure rates for telavancin-treated patients with monomicrobial S. aureus infection, including isolates with reduced vancomycin susceptibility. These studies also demonstrate an overall similar safety profile for telavancin and vancomycin, although importantly, patients with moderate-to-severe renal impairment at baseline are at greater risk for mortality with telavancin and this feature must be taken into account when selecting patients for its usage. In Europe, telavancin is a useful alternative for patients with difficult-to-treat, hospital-acquired MRSA pneumonia when there are very few alternatives. For example, it should be considered in such patients when vancomycin and linezolid are not suitable and where renal function permits.

Topics: Aminoglycosides; Anti-Bacterial Agents; Cross Infection; Drug-Related Side Effects and Adverse Reactions; Europe; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Lipoglycopeptides

Hospital-acquired pneumonia (HAP) due to gram-positive pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) continues to be a major cause of morbid conditions and death. Telavancin is a lipoglycopeptide antibiotic with potent in vitro activity against a range of gram-positive pathogens, including MRSA, methicillin-susceptible S. aureus, and Streptococcus species. In 2 phase 3 clinical trials, telavancin was noninferior to vancomycin in patients with HAP due to gram-positive pathogens. Clinically evaluable patients with S. aureus as the sole pathogen or S. aureus with a vancomycin minimum inhibitory concentration >1 µg/mL, however, had higher cure rates with telavancin than with vancomycin. In patients with bacteremic HAP, telavancin resulted in clearance of blood cultures. It was associated with increased serum creatinine levels and higher mortality rates in patients with moderate to severe renal impairment at baseline; however, on subsequent analysis, the outcomes seemed to have been at least partially affected by the adequacy of empiric gram-negative antimicrobial therapy. Thus, clinicians need to consider the risk-benefit balance when choosing telavancin in patients with severe renal impairment at baseline. Overall, these data support the use of telavancin in the treatment of HAP due to S. aureus, including MRSA and strains with elevated vancomycin minimum inhibitory concentrations, but clinicians should always weigh the risks and benefits of various treatment options.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacteremia; Clinical Trials, Phase III as Topic; Cross Infection; Humans; Lipoglycopeptides; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Pneumonia, Ventilator-Associated; Staphylococcal Infections

Telavancin (Vibativ(®)), a lipoglycopeptide antibacterial agent, exhibits potent in vitro activity against Gram-positive bacteria associated with nosocomial pneumonia infections, including meticillin/oxacillin-resistant Staphylococcus aureus (MRSA) isolates and S. aureus isolates with reduced susceptibility to vancomycin. In two multinational trials in adult patients with nosocomial pneumonia caused by Gram-positive bacteria, including infections caused by MRSA isolates, a 1-h intravenous infusion of telavancin 10 mg/kg once daily was noninferior to intravenous vancomycin 1 g every 12 h in terms of clinical cure rates in the all-treated (AT) and clinically evaluable (CE) populations at the follow-up/test-of-cure (FU/TOC) visit. At this visit, clinical cure rates in the AT populations of both groups were approximately 60 %, with rates increasing to ≥80 % in the CE population. Pooled analyses of these trials also generally showed no significant between-group differences in clinical cure rates at the FU/TOC visit in the AT, CE and microbiologically evaluable (ME) populations. In the ME population, clinical cure rates were generally similar in the telavancin and vancomycin groups, irrespective of whether infections were mono- or polymicrobial, or caused by MRSA or methicillin/oxacillin-susceptible S. aureus isolates. Telavancin was generally well tolerated in patients with nosocomial pneumonia participating in clinical trials, with a tolerability profile that was generally similar to that of vancomycin. Telavancin offers an alternative treatment option in patients with nosocomial pneumonia caused by Gram-positive S. aureus, including those caused by MRSA and S. aureus isolates with reduced susceptibility to vancomycin.

Topics: Aminoglycosides; Anti-Bacterial Agents; Clinical Trials as Topic; Cross Infection; Humans; Lipoglycopeptides; Methicillin-Resistant Staphylococcus aureus; Pneumonia; Staphylococcal Infections

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

Hospital-acquired pneumonia is a common infection, associated with substantial mortality. Despite the increasing prevalence of nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA), approved treatment options for this pathogen are limited.. This article reviews the pharmacokinetics, dosing, preclinical studies and clinical efficacy, and safety of telavancin, with a particular focus on results from trials in nosocomial pneumonia. PubMed and Congress websites were searched for relevant articles published between 2003 and 2010.. Telavancin is a lipoglycopeptide antibiotic with rapid, bactericidal activity against MRSA, and may provide another option for the treatment of nosocomial pneumonia, owing to Gram-positive pathogens.

Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Cross Infection; Gram-Positive Bacterial Infections; Humans; Lipoglycopeptides; Methicillin-Resistant Staphylococcus aureus; Pneumonia, Staphylococcal; Skin Diseases, Bacterial

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

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.. 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.. The studies on microbiological activity, clinical efficacy and safety of telavancin were reviewed.. 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.

Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Cross Infection; Drug Resistance, Multiple, Bacterial; Humans; Lipoglycopeptides; Methicillin-Resistant Staphylococcus aureus; Staphylococcal Infections

When hospital-acquired or ventilator-associated bacterial pneumonia (HABP/VABP) is caused by gram-positive and gram-negative pathogens or both (mixed infections), the adequacy of gram-negative coverage (GNC) can confound the assessment of a gram-positive agent under study. This analysis examines the influence of gram-negative infections and the adequacy of GNC on clinical efficacy and all-cause mortality in the telavancin HABP/VABP phase 3 ATTAIN trials (Assessment of Telavancin for Treatment of Hospital-Acquired Pneumonia).. This post hoc analysis evaluated 3 patient groups from ATTAIN: (1) gram-positive-only infections, (2) gram-positive-only and mixed infections-adequate GNC, and (3) gram-negative-only infections and mixed infections with inadequate GNC. For each, clinical efficacy at test of cure and all-cause mortality at day 28 were compared for telavancin and vancomycin.. In the ATTAIN safety population there were 16 more deaths in the telavancin arms than in the vancomycin arms. Of these, 13 were in patients with gram-negative-only infections (n = 9) or with mixed infections and inadequate GNC (n = 4) and all had estimated baseline creatinine clearances of <30ml/min. Based on this analysis, clinical response and all-cause mortality could be confounded because there were more patients with gram-negative pathogens at baseline and more patients received inadequate treatment of these gram-negative infections in the telavancin groups.

Topics: Adult; Aminoglycosides; Anti-Bacterial Agents; Coinfection; Cross Infection; Double-Blind Method; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Hospital Mortality; Humans; Lipoglycopeptides; Male; Middle Aged; Pneumonia, Ventilator-Associated; Time Factors; Treatment Outcome; Vancomycin; Young Adult

Telavancin is approved in Europe for the treatment of nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus when other alternatives are not suitable. The approved European prescribing information contraindicates the use of telavancin in patients with severe renal impairment (creatinine clearance <30 mL/min, including patients on haemodialysis) and pre-existing acute renal failure owing to the higher observed mortality in these patients. Data from the ATTAIN studies were reanalysed, excluding patients with these contraindicating conditions at baseline. (At the time of submission of this article, the European marketing authorization of telavancin for the treatment of nosocomial pneumonia was suspended pending evidence of a new European Medicines Agency-approved supplier. Clinigen Healthcare Ltd, Theravance's commercialization partner for telavancin in Europe, is in the process of seeking approval of a new manufacturing source.). A post hoc analysis of data from two Phase 3 ATTAIN trials of telavancin for the treatment of Gram-positive nosocomial pneumonia assessing clinical outcomes and safety.. The all-treated population for this analysis represented 84.2% (1266/1503) of the ATTAIN all-treated population. The cure rates in the clinically evaluable population were similar in the telavancin (82.5%, 231/280) and vancomycin (81.3%, 243/299) groups [treatment difference (95% CI): 1.3% (-5.0% to 7.6%)], and were consistent with the overall ATTAIN study results. The cure rate was higher in the telavancin than the vancomycin treatment group in microbiologically evaluable patients with only Gram-positive pathogens isolated at baseline [85.0% (130/153) versus 75.2% (109/145), respectively; treatment difference (95% CI): 9.7% (0.6%-18.8%)]. The incidences of adverse events were similar between treatment groups and consistent with the overall findings of the ATTAIN study.. This analysis demonstrated that in the subset of patients without severe renal impairment or pre-existing acute renal failure, clinical and safety outcomes were similar in the telavancin and vancomycin treatment groups.

Topics: Aged; Aged, 80 and over; Aminoglycosides; Anti-Bacterial Agents; Cross Infection; Female; Humans; Lipoglycopeptides; Male; Pneumonia, Staphylococcal; Treatment Outcome

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

A population pharmacokinetic model of telavancin, a lipoglycopeptide antibiotic, was developed and used to identify sources of interindividual variability. Data were obtained from healthy subjects (seven phase 1 studies), patients with complicated skin and skin structure infections (cSSSI; two phase 2 and two phase 3 studies), and patients with hospital-acquired pneumonia (HAP; two phase 3 studies). A two-compartment open model with zero-order input best fit the telavancin data from healthy individuals and patients with cSSSI or HAP. Telavancin clearance was highly correlated with renal function and, to a lesser extent, with body weight. Other covariates were related to at least one parameter in cSSSI (gender, bacterial eradication, and surgery) or HAP (age of ≥ 75 years) but did not markedly affect exposure. These analyses support current dosing recommendations for telavancin based on patient weight and renal function.

Topics: Adult; Aged; Aged, 80 and over; Algorithms; Aminoglycosides; Anti-Bacterial Agents; Area Under Curve; Bacterial Infections; Bayes Theorem; Body Weight; Calibration; Cross Infection; Female; Humans; Lipoglycopeptides; Male; Middle Aged; Models, Statistical; Population; Sex Characteristics; Young Adult

Telavancin is a lipoglycopeptide bactericidal against gram-positive pathogens.. Two methodologically identical, double-blind studies (0015 and 0019) were conducted involving patients with hospital-acquired pneumonia (HAP) due to gram-positive pathogens, particularly methicillin-resistant Staphylococcus aureus (MRSA). Patients were randomized 1:1 to telavancin (10 mg/kg every 24 h) or vancomycin (1 g every 12 h) for 7-21 days. The primary end point was clinical response at follow-up/test-of-cure visit.. A total of 1503 patients were randomized and received study medication (the all-treated population). In the pooled all-treated population, cure rates with telavancin versus vancomycin were 58.9% versus 59.5% (95% confidence interval [CI] for the difference, -5.6% to 4.3%). In the pooled clinically evaluable population (n = 654), cure rates were 82.4% with telavancin and 80.7% with vancomycin (95% CI for the difference, -4.3% to 7.7%). Treatment with telavancin achieved higher cure rates in patients with monomicrobial S. aureus infection and comparable cure rates in patients with MRSA infection; in patients with mixed gram-positive/gram-negative infections, cure rates were higher in the vancomycin group. Incidence and types of adverse events were comparable between the treatment groups. Mortality rates for telavancin-treated versus vancomycin-treated patients were 21.5% versus 16.6% (95% CI for the difference, -0.7% to 10.6%) for study 0015 and 18.5% versus 20.6% (95% CI for the difference, -7.8% to 3.5%) for study 0019. Increases in serum creatinine level were more common in the telavancin group (16% vs 10%).. The primary end point of the studies was met, indicating that telavancin is noninferior to vancomycin on the basis of clinical response in the treatment of HAP due to gram-positive pathogens.

Topics: Adult; Aged; Aged, 80 and over; Aminoglycosides; Anti-Bacterial Agents; Cross Infection; Double-Blind Method; Female; Humans; Lipoglycopeptides; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Pneumonia, Staphylococcal; Treatment Outcome; Vancomycin

Clinicians and stewardship programs are challenged with positioning of novel, higher priced antibiotic agents for the treatment of clinical infections. We developed a decision-analytic model to describe costs, including drug, total treatment costs, and health care outcomes, associated with telavancin (TLV) compared with vancomycin (VAN) for patients with Staphylococcus aureus (SA) hospital-acquired bacterial pneumonia (HABP).. This decision-analytic model assessed the treatment of SA-HABP with TLV versus VAN. Data were obtained from the ATTAIN (Assessment of Telavancin for Treatment of Hospital-Acquired Pneumonia) clinical trials on the following: the probability of clinical cure; probability of nephrotoxicity; and prevalence of polymicrobial infection (30%), methicillin-resistant Staphylococcus aureus (MRSA) (68%), and SA with VAN MIC ≥1 µg/mL (85%). Data on length of stay for cure (10 days), failure (10 additional days), and nephrotoxicity (3.5 days) were based on literature. Cost per treated patient and incremental cost-effectiveness ratio (ICER) per additional cure were calculated for SA-HABP and for monomicrobial SA-HABP. One-way sensitivity analyses were performed.. Patients with SA-HABP were sub-grouped by methicillin susceptibility (n = 140, 32%) or resistance (n = 293, 68%), and occurrence of polymicrobial (n = 128, 30%) vs monomicrobial (n = 305, 70%) infections. Under the base case, hospital cost for patients with HABP treated with TLV was $42,564 and with VAN, it was $42,296. Telavancin was associated with higher drug ($2082) and nephrotoxicity ($467) costs and lower intensive care unit (-$1738) and ventilator (-$114) costs. ICER was $4156 per additional cure. ICER was sensitive to probabilities of cure, length of treatment in cures, intensive care unit cost, TLV cost, and additional length of stay due to failure. For monomicrobial SA-HABP, TLV was associated with a net cost savings of $907 per patient and yielded economic dominance.. Our decision-analytic model suggests that TLV for monomicrobial SA-HABP is associated with higher drug acquisition costs but a favorable ICER relative to VAN, provided that effective antimicrobial stewardship limits therapy to 7 days. Sensitivity analyses suggest a potential economic benefit of TLV treatment with appropriate patient selection. Antimicrobial stewardship programs may be able to reduce total costs through judicious use of novel antimicrobial agents. ClinicalTrials.gov identifiers: NCT00107952 and NCT00124020.

Topics: Aminoglycosides; Anti-Bacterial Agents; Antimicrobial Stewardship; Cost-Benefit Analysis; Cross Infection; Drug Costs; Humans; Lipoglycopeptides; Methicillin-Resistant Staphylococcus aureus; Pneumonia, Staphylococcal; Staphylococcus aureus; Vancomycin

The most common pathogen in pediatric cystic fibrosis (CF) patients is Staphylococcus aureus, and drug-resistant species are associated with negative outcomes. Methicillin-resistant Staphylococcus aureus (MRSA) is notoriously hard to treat because many antibiotics are not FDA approved for children and drug allergies or intolerances can prohibit the use of others. Telavancin is currently indicated for hospital-acquired pneumonia and ventilator-associated pneumonia caused by MRSA, but it has not been studied in patients with CF or in pediatrics. As a semi-synthetic derivative of vancomycin, it is unknown if cross-reactivity with telavancin occurs in patients with vancomycin hypersensitivity or intolerance. In this case series, we describe three adolescent patients with CF and previous intolerance to vancomycin who received telavancin for bronchopulmonary exacerbations.

Topics: Adolescent; Aminoglycosides; Anti-Bacterial Agents; Child; Cross Infection; Cystic Fibrosis; Drug Hypersensitivity; Female; Humans; Lipoglycopeptides; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Staphylococcal Infections; Treatment Outcome; Vancomycin

Telavancin had MIC50 and MIC90 values of 0.03 and 0.06 μg/ml (100.0% susceptible), respectively, against methicillin-resistant and -susceptible Staphylococcus aureus. Telavancin was active against vancomycin-susceptible Enterococcus faecalis (MIC50/90, 0.12/0.12 μg/ml; 100% susceptible) and Enterococcus faecium (MIC50/90, 0.03/0.06 μg/ml), while higher MIC values were obtained against vancomycin-resistant E. faecium (MIC50/90, 1/2 μg/ml) and E. faecalis (MIC50/90, >2/>2 μg/ml). Streptococci showed telavancin modal MIC results of ≤ 0.015 μg/ml, except against Streptococcus agalactiae (i.e., 0.03 μg/ml). This study reestablishes the telavancin spectrum of activity against isolates recovered from the United States (2011-2012) using the revised broth microdilution method.

Topics: Aminoglycosides; Anti-Bacterial Agents; Cross Infection; Drug Resistance, Bacterial; Enterococcus faecalis; Enterococcus faecium; Gram-Positive Bacterial Infections; Humans; Lipoglycopeptides; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Staphylococcal Infections; United States

U.S. Food and Drug Administration draft guidance for future antibiotic clinical trials of bacterial nosocomial pneumonia recommends the use of diagnostic criteria according to American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines and the use of a primary endpoint of 28-day all-cause mortality. The effect of applying these guidelines on outcomes of phase III nosocomial pneumonia studies of telavancin was evaluated in a post hoc analysis. ATS/IDSA criteria were applied in a blind fashion to the original all-treated (AT) group. Clinical cure rates at final follow-up were determined in the refined AT and clinically evaluable (CE) groups (ATS/IDSA-AT and ATS/IDSA-CE, respectively). The exploratory endpoint of 28-day survival was evaluated for the ATS/IDSA-AT group. Noninferiority of telavancin versus vancomycin was demonstrated, with similar cure rates in the ATS/IDSA-AT (59% versus 59%) and ATS/IDSA-CE (83% versus 80%) groups. Cure rates favored telavancin in ATS/IDSA-CE patients where Staphylococcus aureus was the sole pathogen (86% versus 75%). Overall, 28-day survival rates were similar in the telavancin (76%) and vancomycin (77%) groups but lower in telavancin-treated patients with preexisting moderate-to-severe renal impairment (creatinine clearance [CLCR] of <50 ml/min). Telavancin should be administered to patients with moderate-to-severe renal impairment only if treatment benefit outweighs the risk or if no suitable alternatives are available.

Topics: Adult; Aged; Aged, 80 and over; Aminoglycosides; Anti-Bacterial Agents; Cross Infection; Female; Humans; Lipoglycopeptides; Male; Middle Aged; Pneumonia; Staphylococcus aureus; United States; Vancomycin

Topics: Acetamides; Aminoglycosides; Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Cross Infection; Daptomycin; Humans; Linezolid; Lipoglycopeptides; Methicillin-Resistant Staphylococcus aureus; Minocycline; Oxazolidinones; Pneumonia, Staphylococcal; Tigecycline; Vancomycin; Virginiamycin

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

This study updates the activity of telavancin against Gram-positive pathogens collected from USA hospitals (2007-2009). Telavancin (MIC(50/90), 0.12/0.25 μg/mL) was active against coagulase-negative staphylococci and methicillin-resistant Staphylococcus aureus (100% susceptible), for which only daptomycin (MIC(50/90), 0.25/0.5 μg/mL; 99% susceptible) and quinupristin/dalfopristin (MIC(50/90), ≤ 0.25-0.5/0.5 μg/mL; 99% susceptible) exhibited similar activity. Telavancin (MIC(50/90), 0.25/0.5 μg/mL) inhibited 96.5% of Enterococcus faecalis at the Food and Drug Administration breakpoint (MIC, ≤ 1 μg/mL), where ampicillin (99.9% susceptible), daptomycin (99.9% susceptible), and linezolid (100% susceptible) also demonstrated high-level coverage. Telavancin inhibited, respectively, 100.0% and 91.7% of VanB-phenotype E. faecalis and E. faecium at ≤ 1 μg/mL, whereas it was less active against VanA strains. Telavancin was uniformly active against Streptococcus pneumoniae and resistant subsets, and demonstrated good potency (MIC(90), 0.06-0.12 μg/mL) against other streptococci, regardless of resistance to other drugs. This assessment reveals potent activity of telavancin against Gram-positive isolates collected from USA hospitals with no evidence of emergence of resistance.

Topics: Aminoglycosides; Anti-Bacterial Agents; Cross Infection; Daptomycin; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Hospitals; Humans; Lipoglycopeptides; Microbial Sensitivity Tests; United States; Virginiamycin

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

Telavancin is the first available lipoglycopeptide antibacterial agent. It is active against Gram-positive bacteria, including meticillin/oxacillin-resistant Staphylococcus aureus (MRSA) strains associated with complicated skin and skin structure infections (cSSSIs). In randomized, double-blind trials, intravenous telavancin 10 mg/kg once daily (administered as a 1-hour infusion) was effective in the treatment of adult patients with cSSSIs, including those with infections caused by MRSA, as shown by clinical cure rates in clinically evaluable, all-treated and microbiologically evaluable populations at the test-of-cure (TOC) visit. Telavancin 10 mg/kg once daily was noninferior to intravenous vancomycin 1 g every 12 hours, with clinical cure rates of 88% versus 87% at the TOC visit in pooled data from the clinically evaluable population (n = 1489) of two phase III trials. Pooled clinical cure rates in telavancin recipients at the TOC visit were also not significantly different from those in vancomycin recipients in the all-treated or microbiologically evaluable populations, including microbiologically evaluable subgroups with baseline infections caused by MRSA, meticillin-susceptible S. aureus or other Gram-positive pathogens. Telavancin was generally well tolerated in patients with cSSSIs, with most adverse events being of mild or moderate severity.

Topics: Adult; Aminoglycosides; Animals; Anti-Bacterial Agents; Cross Infection; Disease Models, Animal; Drug Administration Schedule; Drug Interactions; Drug Resistance, Multiple, Bacterial; Gram-Positive Bacteria; Humans; Lipoglycopeptides; Methicillin; Methicillin Resistance; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Oxacillin; Skin Diseases, Infectious; Staphylococcal Infections; Treatment Outcome; Vancomycin