Daptomycin Studied for Bone, Joint Infections : The drug's off-label use may be less likely to cause drug resistance due to long-term therapy.

BOSTON — Daptomycin may effectively treat gram-positive bone and joint infections and may be less likely than standard antimicrobials to cause drug resistance as a consequence of long-term therapy, Michael S. Finney, M.D., said at the annual meeting of the Infectious Diseases Society of America.

In a retrospective medical record study, daptomycin (Cubicin) successfully eradicated infections in 9 of 10 patients diagnosed with gram-positive osteomyelitis, septic joint infection, septic arthritis infection, and/or bacteremia. The patients were treated at two medical centers between November 2003 and April 2004, Dr. Finney said.

“Eight of the patients were infected with methicillin-resistant Staphylococcus aureus [MRSA], and enterococcus and streptococcus were isolated from two patients,” said Dr. Finney of Fountain Valley (Calif.) Regional Hospital, where six of the patients were treated. The remaining four patients were treated at Rush University Medical Center in Chicago.

Daptomycin was effective in treating seven of eight MRSA-infected patients and both of the non-MRSA patients. Of the 10 patients, 4 had a diagnosis of osteomyelitis only and 6 had some combination of osteomyelitis, septic joint infection, septic arthritis infection, and/or bacteremia.

Nine had undergone prior unsuccessful treatment with one or more antibiotics: Eight received vancomycin, three received linezolid, and three received quinupristin/dalfopristin. Among the patients successfully treated with daptomycin were seven who had failed or could not tolerate vancomycin, which is often a first-line treatment for osteomyelitis.

The daptomycin treatment duration averaged 30 days, ranging from 21 to 42 days. “In general, the therapy was well tolerated, even for the longer treatment durations,” Dr. Finney said. No patients had severe adverse effects; one stopped therapy at 3 weeks because of nausea, and another had a mild elevation in CPK levels but not enough to warrant discontinuing therapy.

The one patient in the case series whose infection was not resolved had a relapse during daptomycin therapy, “possibly as a result of underdosing,” Dr. Finney said. Because of renal insufficiency, the septic arthritis patient was started on alternate-day vs. daily dosing and was not adjusted to daily dosing once renal function improved. During the course of therapy, the patient developed an epidural abscess from MRSA with reduced susceptibility to daptomycin.

Bone and joint infections are notoriously difficult to resolve, require prolonged treatment, and are associated with a high risk of recurrence. “Effective treatment requires the antibiotic to penetrate the site of infection at an adequate concentration to effectively kill the causative pathogen,” Dr. Finney noted. Because gram-positive organisms, particularly S. aureus, are the predominant cause of these infections, the possibility of drug resistance further complicates treatment.

Vancomycin is a standard treatment for bone and joint infections, but it is not highly active against some gram-positive organisms, including S. aureus. In fact, Dr. Finney said, “studies have shown an increased risk of recurrence with vancomycin treatment for S. aureus osteomyelitis.” It is possible that bacteriostatic antimicrobials such as vancomycin, which merely inhibit the growth of bacteria, have a higher risk of causing drug resistance during therapy than do bactericidal agents such as daptomycin, he said.

Currently, daptomycin is approved for the treatment of complicated skin and skin structure infections. The findings from this case series suggest that further studies are warranted to determine the agent's role in treating gram-positive bone and joint infections as well as to determine optimal dosing, “to improve clinical outcomes and to reduce the risk of resistance,” Dr. Finney said.

He and his colleagues in this investigation reported that they have no financial interest in the manufacturer of daptomycin, Cubist Pharmaceuticals Inc.

BOSTON — Daptomycin may effectively treat gram-positive bone and joint infections and may be less likely than standard antimicrobials to cause drug resistance as a consequence of long-term therapy, Michael S. Finney, M.D., said at the annual meeting of the Infectious Diseases Society of America.

In a retrospective medical record study, daptomycin (Cubicin) successfully eradicated infections in 9 of 10 patients diagnosed with gram-positive osteomyelitis, septic joint infection, septic arthritis infection, and/or bacteremia. The patients were treated at two medical centers between November 2003 and April 2004, Dr. Finney said.

“Eight of the patients were infected with methicillin-resistant Staphylococcus aureus [MRSA], and enterococcus and streptococcus were isolated from two patients,” said Dr. Finney of Fountain Valley (Calif.) Regional Hospital, where six of the patients were treated. The remaining four patients were treated at Rush University Medical Center in Chicago.

Daptomycin was effective in treating seven of eight MRSA-infected patients and both of the non-MRSA patients. Of the 10 patients, 4 had a diagnosis of osteomyelitis only and 6 had some combination of osteomyelitis, septic joint infection, septic arthritis infection, and/or bacteremia.

Nine had undergone prior unsuccessful treatment with one or more antibiotics: Eight received vancomycin, three received linezolid, and three received quinupristin/dalfopristin. Among the patients successfully treated with daptomycin were seven who had failed or could not tolerate vancomycin, which is often a first-line treatment for osteomyelitis.

The daptomycin treatment duration averaged 30 days, ranging from 21 to 42 days. “In general, the therapy was well tolerated, even for the longer treatment durations,” Dr. Finney said. No patients had severe adverse effects; one stopped therapy at 3 weeks because of nausea, and another had a mild elevation in CPK levels but not enough to warrant discontinuing therapy.

The one patient in the case series whose infection was not resolved had a relapse during daptomycin therapy, “possibly as a result of underdosing,” Dr. Finney said. Because of renal insufficiency, the septic arthritis patient was started on alternate-day vs. daily dosing and was not adjusted to daily dosing once renal function improved. During the course of therapy, the patient developed an epidural abscess from MRSA with reduced susceptibility to daptomycin.

Bone and joint infections are notoriously difficult to resolve, require prolonged treatment, and are associated with a high risk of recurrence. “Effective treatment requires the antibiotic to penetrate the site of infection at an adequate concentration to effectively kill the causative pathogen,” Dr. Finney noted. Because gram-positive organisms, particularly S. aureus, are the predominant cause of these infections, the possibility of drug resistance further complicates treatment.

Vancomycin is a standard treatment for bone and joint infections, but it is not highly active against some gram-positive organisms, including S. aureus. In fact, Dr. Finney said, “studies have shown an increased risk of recurrence with vancomycin treatment for S. aureus osteomyelitis.” It is possible that bacteriostatic antimicrobials such as vancomycin, which merely inhibit the growth of bacteria, have a higher risk of causing drug resistance during therapy than do bactericidal agents such as daptomycin, he said.

Currently, daptomycin is approved for the treatment of complicated skin and skin structure infections. The findings from this case series suggest that further studies are warranted to determine the agent's role in treating gram-positive bone and joint infections as well as to determine optimal dosing, “to improve clinical outcomes and to reduce the risk of resistance,” Dr. Finney said.

He and his colleagues in this investigation reported that they have no financial interest in the manufacturer of daptomycin, Cubist Pharmaceuticals Inc.

BOSTON — Daptomycin may effectively treat gram-positive bone and joint infections and may be less likely than standard antimicrobials to cause drug resistance as a consequence of long-term therapy, Michael S. Finney, M.D., said at the annual meeting of the Infectious Diseases Society of America.

In a retrospective medical record study, daptomycin (Cubicin) successfully eradicated infections in 9 of 10 patients diagnosed with gram-positive osteomyelitis, septic joint infection, septic arthritis infection, and/or bacteremia. The patients were treated at two medical centers between November 2003 and April 2004, Dr. Finney said.

“Eight of the patients were infected with methicillin-resistant Staphylococcus aureus [MRSA], and enterococcus and streptococcus were isolated from two patients,” said Dr. Finney of Fountain Valley (Calif.) Regional Hospital, where six of the patients were treated. The remaining four patients were treated at Rush University Medical Center in Chicago.

Daptomycin was effective in treating seven of eight MRSA-infected patients and both of the non-MRSA patients. Of the 10 patients, 4 had a diagnosis of osteomyelitis only and 6 had some combination of osteomyelitis, septic joint infection, septic arthritis infection, and/or bacteremia.

Nine had undergone prior unsuccessful treatment with one or more antibiotics: Eight received vancomycin, three received linezolid, and three received quinupristin/dalfopristin. Among the patients successfully treated with daptomycin were seven who had failed or could not tolerate vancomycin, which is often a first-line treatment for osteomyelitis.

The daptomycin treatment duration averaged 30 days, ranging from 21 to 42 days. “In general, the therapy was well tolerated, even for the longer treatment durations,” Dr. Finney said. No patients had severe adverse effects; one stopped therapy at 3 weeks because of nausea, and another had a mild elevation in CPK levels but not enough to warrant discontinuing therapy.

The one patient in the case series whose infection was not resolved had a relapse during daptomycin therapy, “possibly as a result of underdosing,” Dr. Finney said. Because of renal insufficiency, the septic arthritis patient was started on alternate-day vs. daily dosing and was not adjusted to daily dosing once renal function improved. During the course of therapy, the patient developed an epidural abscess from MRSA with reduced susceptibility to daptomycin.

Bone and joint infections are notoriously difficult to resolve, require prolonged treatment, and are associated with a high risk of recurrence. “Effective treatment requires the antibiotic to penetrate the site of infection at an adequate concentration to effectively kill the causative pathogen,” Dr. Finney noted. Because gram-positive organisms, particularly S. aureus, are the predominant cause of these infections, the possibility of drug resistance further complicates treatment.

Vancomycin is a standard treatment for bone and joint infections, but it is not highly active against some gram-positive organisms, including S. aureus. In fact, Dr. Finney said, “studies have shown an increased risk of recurrence with vancomycin treatment for S. aureus osteomyelitis.” It is possible that bacteriostatic antimicrobials such as vancomycin, which merely inhibit the growth of bacteria, have a higher risk of causing drug resistance during therapy than do bactericidal agents such as daptomycin, he said.

Currently, daptomycin is approved for the treatment of complicated skin and skin structure infections. The findings from this case series suggest that further studies are warranted to determine the agent's role in treating gram-positive bone and joint infections as well as to determine optimal dosing, “to improve clinical outcomes and to reduce the risk of resistance,” Dr. Finney said.

He and his colleagues in this investigation reported that they have no financial interest in the manufacturer of daptomycin, Cubist Pharmaceuticals Inc.