Less-frequent antibiotics as effective as daily vancomycin for skin infections

Treatment with once-weekly dalbavancin and treatment with a one-time dose of oritavancin for acute bacterial skin and skin-structure infections had similar outcomes to conventional treatment with vancomycin, in studies reported in the June 5 issue of the New England Journal of Medicine.

In the noninferiority studies, the effects of treatment with the two long-acting intravenously administered antibiotics on methicillin-resistant Staphylococcus aureus (MRSA) infections were comparable to treatment with vancomycin, administered intravenously twice a day (followed by oral linezolid in the dalbavancin study).

Both dalbavancin, which was recently approved by the Food and Drug Administration, and oritavancin, which is being reviewed by the FDA, are lipoglycopeptide antibiotics with activity against gram-positive bacteria. Because of their prolonged half-lives, oritavancin can be administered as a single dose and dalbavancin can be administered once a week. The authors of both studies referred to the substantial medical costs associated with the inpatient treatment of acute bacterial skin and skin structure infections.

In the randomized double-blind, international study of oritavancin, the SOLO I trial, patients with acute bacterial skin and skin structure infections (cellulitis, wound infections, or an abscess), thought to be caused by a gram-positive pathogen were treated with a single intravenous dose of 1,200 mg of oritavancin (475 patients) or intravenous vancomycin twice a day for 7-10 days (479), at a dose of 1g or 15 mg/kg of body weight. Their mean age was 45 years, almost 9% were aged 65 years or older, more than half were white men, and about 34% were obese. Almost 20% had diabetes, and of the approximately 60% who had a pathogen isolated, almost all had a gram-positive pathogen known to cause acute bacterial skin and skin-structure infections, with S. aureus being the most common.

The primary endpoint, evaluated early in treatment (48-72 hours after the drug was administered) was a composite of the following: cessation of spreading or a reduction in the baseline lesion size, absence of fever, and no need for rescue antibiotic to be administered. This endpoint was met by 82.3% of those on oritavancin and 78.9% of those on vancomycin, which met the prespecified non-inferiority margin of 10%, reported the authors, led by Dr. G. Ralph Corey, professor of medicine, Duke University, Durham, NC. (N. Engl. J. Med. 2014;370:2180-90 [doi:10.1056/NEJMoa1310422]).

These results were similar when analyzed by body mass index, whether the patient had diabetes or MRSA infection, and by race, sex, or type of lesion. The investigator-assessed clinical cure rates 7-14 days after treatment ended were about 80% in both groups, and the proportion of patients with at least a 20% reduction in the area of the lesion 48-72 hours after treatment started was 86.9% among those on oritavancin vs. 82.9% of those on vancomycin. More patients on oritavancin experienced nausea; otherwise, the proportion of adverse events and serious adverse events were similar in the two treatment groups.

While the study had limitations, a single-dose treatment for acute bacterial skin and skin structure infections "that results in an early and sustained clinical response could have the potential to reduce the complications associated with multiple intravenous administrations in patients with these infections, improve adherence to treatment, improve quality of life, and reduce the utilization of health care resources," the authors concluded.

The dalbavancin studies, known as the Discover I and II studies, enrolled about 1,300 patients with cellulitis, a major abscess, or a wound infection; the median size of the infected area was 351cm² in one study and 336 cm² in the other. Patients were treated with dalbavancin (1g IV, followed by a 500 mg intravenous dose on day 8) or vancomycin (1 g or 15 mg/kg of body weight) every 12 hours for at least 3 days, with the option of changing to linezolid (600 mg) every 12 hours for a total of 10-14 days of treatment. Overall, 13% of the patients had diabetes, and more than 85% had a temperature over 38 degrees° C at baseline. The mean age was 49-50 years, almost 60% were male, almost 90% were white, and about half had systemic inflammatory response syndrome).

In a pooled analysis of the studies, 79.7% of those treated with dalbavancin and 79.8% of those treated with vancomycin-linezolid met the primary endpoint of an early clinical response (cessation of spread of infection-related erythema and absence of fever 48-72 hours after starting treatment).

The results were consistent at early and later time points, and results "were robust in patients with major abscess, cellulitis, or wound infection; in those with S. aureus, including MRSA, or Streptococcus pyogenes infection; and in those treated as an outpatient," reported the authors, led by Dr. Helen Boucher of Tufts University, Boston. (N. Engl. J. Med. 2014;370:2169-79 [doi:10.1056/NEJMoa1310480]).

Fewer patients on dalbavancin had adverse events (almost 33% vs. almost 38% of those on vancomycin-linezolid). The most common adverse events associated with treatment in both groups were nausea (almost 3% in both groups), diarrhea (0.8% among those on dalbavancin, vs. 2.5% among those on vancomycin-linezolid) and pruritus (0.6% vs. 2.3%).

The oritavancin study was funded by the Medicines Company, the drug’s manufacturer, and several authors are employees of the company. Dr. Corey’s disclosures include having received personal fees from the Medicines Company during the study. Other disclosures include fees paid to one author’s institution to conduct the study; other authors had no disclosures.

The dalbavancin study was funded by Durata Therapeutics, the drug’s manufacturer, and two of the six authors are Durata employees. Dr. Boucher disclosed having received fees for serving on advisory boards for Durata and other pharmaceutical companies. Disclosures of the remaining three authors included having received consulting and lecture fees and advisory board fees from various companies, including Durata. One author (not a Durata employee) also disclosed owning stock or stock options in several companies, including Durata.

In May, the FDA approved dalbavancin for the treatment of acute bacterial skin and skin structure infections; it is being marketed as Dalvance. In February, the Medicines Company announced that the application for approval of oritavancin for the treatment of skin and skin structure infections had been accepted by the FDA.

[email protected]

Treatment with once-weekly dalbavancin and treatment with a one-time dose of oritavancin for acute bacterial skin and skin-structure infections had similar outcomes to conventional treatment with vancomycin, in studies reported in the June 5 issue of the New England Journal of Medicine.

In the noninferiority studies, the effects of treatment with the two long-acting intravenously administered antibiotics on methicillin-resistant Staphylococcus aureus (MRSA) infections were comparable to treatment with vancomycin, administered intravenously twice a day (followed by oral linezolid in the dalbavancin study).

Both dalbavancin, which was recently approved by the Food and Drug Administration, and oritavancin, which is being reviewed by the FDA, are lipoglycopeptide antibiotics with activity against gram-positive bacteria. Because of their prolonged half-lives, oritavancin can be administered as a single dose and dalbavancin can be administered once a week. The authors of both studies referred to the substantial medical costs associated with the inpatient treatment of acute bacterial skin and skin structure infections.

In the randomized double-blind, international study of oritavancin, the SOLO I trial, patients with acute bacterial skin and skin structure infections (cellulitis, wound infections, or an abscess), thought to be caused by a gram-positive pathogen were treated with a single intravenous dose of 1,200 mg of oritavancin (475 patients) or intravenous vancomycin twice a day for 7-10 days (479), at a dose of 1g or 15 mg/kg of body weight. Their mean age was 45 years, almost 9% were aged 65 years or older, more than half were white men, and about 34% were obese. Almost 20% had diabetes, and of the approximately 60% who had a pathogen isolated, almost all had a gram-positive pathogen known to cause acute bacterial skin and skin-structure infections, with S. aureus being the most common.

The primary endpoint, evaluated early in treatment (48-72 hours after the drug was administered) was a composite of the following: cessation of spreading or a reduction in the baseline lesion size, absence of fever, and no need for rescue antibiotic to be administered. This endpoint was met by 82.3% of those on oritavancin and 78.9% of those on vancomycin, which met the prespecified non-inferiority margin of 10%, reported the authors, led by Dr. G. Ralph Corey, professor of medicine, Duke University, Durham, NC. (N. Engl. J. Med. 2014;370:2180-90 [doi:10.1056/NEJMoa1310422]).

These results were similar when analyzed by body mass index, whether the patient had diabetes or MRSA infection, and by race, sex, or type of lesion. The investigator-assessed clinical cure rates 7-14 days after treatment ended were about 80% in both groups, and the proportion of patients with at least a 20% reduction in the area of the lesion 48-72 hours after treatment started was 86.9% among those on oritavancin vs. 82.9% of those on vancomycin. More patients on oritavancin experienced nausea; otherwise, the proportion of adverse events and serious adverse events were similar in the two treatment groups.

While the study had limitations, a single-dose treatment for acute bacterial skin and skin structure infections "that results in an early and sustained clinical response could have the potential to reduce the complications associated with multiple intravenous administrations in patients with these infections, improve adherence to treatment, improve quality of life, and reduce the utilization of health care resources," the authors concluded.

The dalbavancin studies, known as the Discover I and II studies, enrolled about 1,300 patients with cellulitis, a major abscess, or a wound infection; the median size of the infected area was 351cm² in one study and 336 cm² in the other. Patients were treated with dalbavancin (1g IV, followed by a 500 mg intravenous dose on day 8) or vancomycin (1 g or 15 mg/kg of body weight) every 12 hours for at least 3 days, with the option of changing to linezolid (600 mg) every 12 hours for a total of 10-14 days of treatment. Overall, 13% of the patients had diabetes, and more than 85% had a temperature over 38 degrees° C at baseline. The mean age was 49-50 years, almost 60% were male, almost 90% were white, and about half had systemic inflammatory response syndrome).

In a pooled analysis of the studies, 79.7% of those treated with dalbavancin and 79.8% of those treated with vancomycin-linezolid met the primary endpoint of an early clinical response (cessation of spread of infection-related erythema and absence of fever 48-72 hours after starting treatment).

The results were consistent at early and later time points, and results "were robust in patients with major abscess, cellulitis, or wound infection; in those with S. aureus, including MRSA, or Streptococcus pyogenes infection; and in those treated as an outpatient," reported the authors, led by Dr. Helen Boucher of Tufts University, Boston. (N. Engl. J. Med. 2014;370:2169-79 [doi:10.1056/NEJMoa1310480]).

Fewer patients on dalbavancin had adverse events (almost 33% vs. almost 38% of those on vancomycin-linezolid). The most common adverse events associated with treatment in both groups were nausea (almost 3% in both groups), diarrhea (0.8% among those on dalbavancin, vs. 2.5% among those on vancomycin-linezolid) and pruritus (0.6% vs. 2.3%).

The oritavancin study was funded by the Medicines Company, the drug’s manufacturer, and several authors are employees of the company. Dr. Corey’s disclosures include having received personal fees from the Medicines Company during the study. Other disclosures include fees paid to one author’s institution to conduct the study; other authors had no disclosures.

The dalbavancin study was funded by Durata Therapeutics, the drug’s manufacturer, and two of the six authors are Durata employees. Dr. Boucher disclosed having received fees for serving on advisory boards for Durata and other pharmaceutical companies. Disclosures of the remaining three authors included having received consulting and lecture fees and advisory board fees from various companies, including Durata. One author (not a Durata employee) also disclosed owning stock or stock options in several companies, including Durata.

In May, the FDA approved dalbavancin for the treatment of acute bacterial skin and skin structure infections; it is being marketed as Dalvance. In February, the Medicines Company announced that the application for approval of oritavancin for the treatment of skin and skin structure infections had been accepted by the FDA.

[email protected]

Treatment with once-weekly dalbavancin and treatment with a one-time dose of oritavancin for acute bacterial skin and skin-structure infections had similar outcomes to conventional treatment with vancomycin, in studies reported in the June 5 issue of the New England Journal of Medicine.

In the noninferiority studies, the effects of treatment with the two long-acting intravenously administered antibiotics on methicillin-resistant Staphylococcus aureus (MRSA) infections were comparable to treatment with vancomycin, administered intravenously twice a day (followed by oral linezolid in the dalbavancin study).

Both dalbavancin, which was recently approved by the Food and Drug Administration, and oritavancin, which is being reviewed by the FDA, are lipoglycopeptide antibiotics with activity against gram-positive bacteria. Because of their prolonged half-lives, oritavancin can be administered as a single dose and dalbavancin can be administered once a week. The authors of both studies referred to the substantial medical costs associated with the inpatient treatment of acute bacterial skin and skin structure infections.

In the randomized double-blind, international study of oritavancin, the SOLO I trial, patients with acute bacterial skin and skin structure infections (cellulitis, wound infections, or an abscess), thought to be caused by a gram-positive pathogen were treated with a single intravenous dose of 1,200 mg of oritavancin (475 patients) or intravenous vancomycin twice a day for 7-10 days (479), at a dose of 1g or 15 mg/kg of body weight. Their mean age was 45 years, almost 9% were aged 65 years or older, more than half were white men, and about 34% were obese. Almost 20% had diabetes, and of the approximately 60% who had a pathogen isolated, almost all had a gram-positive pathogen known to cause acute bacterial skin and skin-structure infections, with S. aureus being the most common.

The primary endpoint, evaluated early in treatment (48-72 hours after the drug was administered) was a composite of the following: cessation of spreading or a reduction in the baseline lesion size, absence of fever, and no need for rescue antibiotic to be administered. This endpoint was met by 82.3% of those on oritavancin and 78.9% of those on vancomycin, which met the prespecified non-inferiority margin of 10%, reported the authors, led by Dr. G. Ralph Corey, professor of medicine, Duke University, Durham, NC. (N. Engl. J. Med. 2014;370:2180-90 [doi:10.1056/NEJMoa1310422]).

These results were similar when analyzed by body mass index, whether the patient had diabetes or MRSA infection, and by race, sex, or type of lesion. The investigator-assessed clinical cure rates 7-14 days after treatment ended were about 80% in both groups, and the proportion of patients with at least a 20% reduction in the area of the lesion 48-72 hours after treatment started was 86.9% among those on oritavancin vs. 82.9% of those on vancomycin. More patients on oritavancin experienced nausea; otherwise, the proportion of adverse events and serious adverse events were similar in the two treatment groups.

While the study had limitations, a single-dose treatment for acute bacterial skin and skin structure infections "that results in an early and sustained clinical response could have the potential to reduce the complications associated with multiple intravenous administrations in patients with these infections, improve adherence to treatment, improve quality of life, and reduce the utilization of health care resources," the authors concluded.

The dalbavancin studies, known as the Discover I and II studies, enrolled about 1,300 patients with cellulitis, a major abscess, or a wound infection; the median size of the infected area was 351cm² in one study and 336 cm² in the other. Patients were treated with dalbavancin (1g IV, followed by a 500 mg intravenous dose on day 8) or vancomycin (1 g or 15 mg/kg of body weight) every 12 hours for at least 3 days, with the option of changing to linezolid (600 mg) every 12 hours for a total of 10-14 days of treatment. Overall, 13% of the patients had diabetes, and more than 85% had a temperature over 38 degrees° C at baseline. The mean age was 49-50 years, almost 60% were male, almost 90% were white, and about half had systemic inflammatory response syndrome).

In a pooled analysis of the studies, 79.7% of those treated with dalbavancin and 79.8% of those treated with vancomycin-linezolid met the primary endpoint of an early clinical response (cessation of spread of infection-related erythema and absence of fever 48-72 hours after starting treatment).

The results were consistent at early and later time points, and results "were robust in patients with major abscess, cellulitis, or wound infection; in those with S. aureus, including MRSA, or Streptococcus pyogenes infection; and in those treated as an outpatient," reported the authors, led by Dr. Helen Boucher of Tufts University, Boston. (N. Engl. J. Med. 2014;370:2169-79 [doi:10.1056/NEJMoa1310480]).

Fewer patients on dalbavancin had adverse events (almost 33% vs. almost 38% of those on vancomycin-linezolid). The most common adverse events associated with treatment in both groups were nausea (almost 3% in both groups), diarrhea (0.8% among those on dalbavancin, vs. 2.5% among those on vancomycin-linezolid) and pruritus (0.6% vs. 2.3%).

The oritavancin study was funded by the Medicines Company, the drug’s manufacturer, and several authors are employees of the company. Dr. Corey’s disclosures include having received personal fees from the Medicines Company during the study. Other disclosures include fees paid to one author’s institution to conduct the study; other authors had no disclosures.

The dalbavancin study was funded by Durata Therapeutics, the drug’s manufacturer, and two of the six authors are Durata employees. Dr. Boucher disclosed having received fees for serving on advisory boards for Durata and other pharmaceutical companies. Disclosures of the remaining three authors included having received consulting and lecture fees and advisory board fees from various companies, including Durata. One author (not a Durata employee) also disclosed owning stock or stock options in several companies, including Durata.

In May, the FDA approved dalbavancin for the treatment of acute bacterial skin and skin structure infections; it is being marketed as Dalvance. In February, the Medicines Company announced that the application for approval of oritavancin for the treatment of skin and skin structure infections had been accepted by the FDA.

[email protected]