treating-habp

Treating HABP/VABP

Early appropriate therapy is critical in patients with HABP/VABP

Waiting to treat HABP/VABP patients with appropriate therapy adds unnecessary risks and costs1

Patients who received inadequate therapy required longer hospital stays to achieve clinical resolution, with increased time and costs1-3

Higher mortality accompanied delays in initiation of appropriate therapy for patients with HABP/VABP.

In patients with HABP, more than 41% did not receive appropriate therapy and had higher mortality rates compared with patients receiving adequate therapy2

bahp-chart1

With a P value of 0.056, this comparison did not reach statistical significance.

In patients with VABP, more than 25% did not receive appropriate therapy until after 24 hours of diagnosis and had higher mortality rates compared with patients receiving adequate therapy3

attain

attain trials

In the ATTAIN trials, VIBATIV demonstrated similar efficacy rates when compared with vancomycin in HABP/VABP populations4,5

Cure rates

Cure rates for VIBATIV were significantly greater than for vancomycin in HABP/VABP patients with a single Gram-positive pathogen. The VIBATIV cure rate was numerically higher than that for vancomycin in HABP/VABP patients with MRSA and with S. aureus that had a vancomycin MIC ≥1 μg/mL.4,5

tissue-penetration

tissue penetration

VIBATIV demonstrates tissue penetration into infection sites

VIBATIV concentrations in epithelial lining fluid and alveolar macrophages exceeded the MIC90 for S. aureus for at least 24 hours following dosing5

Unlike daptomycin, VIBATIV is not affected by the presence of pulmonary surfactant5

Mean concentrations of VIBATIV 10 mg/kg IV over 24 hours in plasma, epithelial lining fluid (ELF), and alveolar macrophages (AMs)5

treating-habp

For patients with HABP/VABP
and baseline bacteremia,

VIBATIV offers comparable efficacy to vancomycin in a
difficult-to-treat patient population5,6

As part of a phase 3 clinical trial, VIBATIV was studied in a subset of patients with HABP/VABP and concurrent S. aureus bacteremia5,6

Clinical cure rates at test of cure (TOC) (MAT population)

Of the 797 patients in the Modified All Treated (MAT) population with at least 1 Gram-positive respiratory pathogen at baseline:

  • 73 patients had concurrent S. aureus bacteremia at baseline
    • 35 (8.5%) were treated with VIBATIV (21 for MRSA)
    • 38 (9.8%) were treated with vancomycin (24 for MRSA)
  • Clinical cure rates in these patients were 54.3% with VIBATIV and 47.4% with vancomycin
  • Given the limited sample size in this subgroup, the interpretation of these results is limited
tissue-penetration

vibativ in subgroups

VIBATIV has proven efficacy in clinically meaningful subgroups of patients with HABP/VABP due to S. aureus:

VABP

Concomitant bacteremia

Age ≥65 years

Baseline CPIS score >6

APACHE II ≥20

References: 1. Kollef MH, Morrow LE, Niederman MS, et al. Clinical characteristics and treatment patterns among patients with ventilator-associated pneumonia. Chest. 2006;129:1210-1218. 2. Piskin N, Aydemir H, Oztoprak N, et al. Inadequate treatment of ventilator-associated and hospital-acquired pneumonia: risk factors and impact on outcomes. BMC Infect Dis. 2012;12:268. 3. Iregui M, Ward S, Sherman C, et al. Clinical importance of delays in the initiation of appropriate antibiotic treatment for ventilator-associated pneumonia. Chest. 2002;122:262-268. 4. Rubinstein E, Lalani T, Corey GR, et al; for the ATTAIN Study Group. Telavancin versus vancomycin for hospital-acquired pneumonia due to Gram-positive pathogens. Clin Infect Dis. 2011;52(1):31-40. 5. VIBATIV® (telavancin) Prescribing Information. Theravance Biopharma Antibiotics, Inc. May 2016. 6. Data on file. Theravance Biopharma Antibiotics, Inc. 7. Gotfried MH, Shaw J-P, Benton BM, et al. Intrapulmonary distribution of intravenous telavancin in healthy subjects and effect of pulmonary surfactant on in vitro activities of telavancin and other antibiotics. Antimicrob Agents Chemother. 2008;52(1):92-97.

Indication

HABP/VABP

VIBATIV is indicated for the treatment of adult patients with hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP), caused by susceptible isolates of Staphylococcus aureus (including methicillin-susceptible and -resistant isolates). VIBATIV should be reserved for use when alternative treatments are not suitable.

cSSSI

VIBATIV is indicated for the treatment of adult patients with complicated skin and skin structure infections (cSSSI) caused by susceptible isolates of the following Gram-positive microorganisms:

  • Staphylococcus aureus (including methicillin-susceptible and -resistant isolates)
  • Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus anginosus group (includes S. anginosus, S. intermedius, and S. constellatus), or
  • Enterococcus faecalis (vancomycin-susceptible isolates only)

Combination therapy may be clinically indicated if the documented or presumed pathogens include Gram-negative organisms.

Appropriate specimens for bacteriological examination should be obtained in order to isolate and identify the causative pathogens and to determine their susceptibility to telavancin. VIBATIV may be initiated as empiric therapy before results of these tests are known. To reduce the development of drug-resistant bacteria and maintain the effectiveness of VIBATIV and other antibacterial drugs, VIBATIV should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Important Safety Information

Mortality

Patients with pre-existing moderate/severe renal impairment (CrCl ≤50 mL/min) who were treated with VIBATIV for hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia had increased mortality observed versus vancomycin. Use of VIBATIV in patients with pre-existing moderate/severe renal impairment (CrCl ≤50 mL/min) should be considered only when the anticipated benefit to the patient outweighs the potential risk.

Nephrotoxicity

New onset or worsening renal impairment occurred in patients who received VIBATIV. Renal adverse events were more likely to occur in patients with baseline comorbidities known to predispose patients to kidney dysfunction and in patients who received concomitant medications known to affect kidney function. Monitor renal function in all patients receiving VIBATIV prior to initiation of treatment, during treatment, and at the end of therapy. If renal function decreases, the benefit of continuing VIBATIV versus discontinuing and initiating therapy with an alternative agent should be assessed.

Fetal Risk

Women of childbearing potential should have a serum pregnancy test prior to administration of VIBATIV. Avoid use of VIBATIV during pregnancy unless the potential benefit to the patient outweighs the potential risk to the fetus. Adverse developmental outcomes observed in three animal species at clinically relevant doses raise concerns about potential adverse developmental outcomes in humans. If not already pregnant, women of childbearing potential should use effective contraception during VIBATIV treatment.

Contraindication

Intravenous unfractionated heparin sodium is contraindicated with VIBATIV administration due to artificially prolonged activated partial thromboplastin time (aPTT) test results for up to 18 hours after VIBATIV administration.

VIBATIV is contraindicated in patients with a known hypersensitivity to the drug.

Hypersensitivity Reactions

Serious and potentially fatal hypersensitivity reactions, including anaphylactic reactions, may occur after first or subsequent doses. VIBATIV should be used with caution in patients with known hypersensitivity to vancomycin.

Geriatric Use

Telavancin is substantially excreted by the kidney, and the risk of adverse reactions may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection in this age group.

Infusion Related Reactions

VIBATIV is a lipoglycopeptide antibacterial agent and should be administered over a period of 60 minutes to reduce the risk of infusion-related reactions. Rapid intravenous infusions of the glycopeptide class of antimicrobial agents can cause “Red-man Syndrome” like reactions including: flushing of the upper body, urticaria, pruritus, or rash.

QTc Prolongation

Caution is warranted when prescribing VIBATIV to patients taking drugs known to prolong the QT interval. In a study involving healthy volunteers, VIBATIV prolonged the QTc interval. Use of VIBATIV should be avoided in patients with congenital long QT syndrome, known prolongation of the QTc interval, uncompensated heart failure, or severe left ventricular hypertrophy.

Most Common Adverse Reactions

The most common adverse reactions (greater than or equal to 10% of patients treated with VIBATIV) were diarrhea, taste disturbance, nausea, vomiting, and foamy urine.

Please see full Prescribing Information including Boxed Warning and Medication Guide.