Damian McNamara

MIAMI — Approval of micafungin by the Food and Drug Administration in March added another option for combatting infections caused by Candida or Aspergillus species John R. Perfect, M.D., said at a meeting on fungal infections sponsored by Imedex.

Micafungin (Mycamine), an echinocandin antifungal agent, is indicated for prophylaxis of Candida infections in patients undergoing hematopoietic stem cell transplantation and for treatment of esophageal candidiasis. The echinocandin class also includes caspofungin (Cancidas), approved in 2001. Two more drugs in this class, anidulafungin and aminocandin, are in development.

“My suspicion is, [drugs in this class] will have a significant impact on how we manage patients,” said Dr. Perfect, professor of medicine at Duke University Medical Center, Durham, N.C. Yet “candins lack any significantly good data for any fungal infections outside Candida or Aspergillus.”

A possible drawback is that the echinocandins are available only for intravenous infusion. Other considerations are the low urinary and brain concentrations achieved by these drugs, but “these things are not necessarily bad,” he added.

Dr. Perfect disclosed an affiliation with PLIVA, a company that manufactures generic fluconazole, ketoconazole, and metronidazole.

Both caspofungin and micafungin are effective in treating esophageal candidiasis. The echinocandins also have a long half-life and low toxicity, and require little dosage adjustment for patients with renal or liver dysfunction. And the agents have a low potential for drug interactions, which means they can be used in patients taking many other drugs, he said.

Although prevention of Aspergillus infections would be an off-label use of micafungin, the drug does have activity against these organisms, said Dr. Perfect. He predicted that the echinocandins would have a role in preventing Aspergillus infections in the future. “Candins for aspergillosis are trendy in combination, but no one has any data to support that today.”

The “paradigm-changing study” for the echinocandins, Dr. Perfect said, was a randomized, double-blind, multicenter comparison between caspofungin and amphotericin B for patients with invasive candidiasis (N. Engl. J. Med. 2002;347:2020-9). The patients were stratified by neutropenic status and Apache score, and there was no difference between the two drugs in outcome. The study design was practical, he added, because after 10 days of intravenous therapy, patients were switched to oral fluconazole. Intravenous therapy is very expensive, he noted.

He and his colleagues examined caspofungin efficacy for 109 episodes of invasive candidiasis at Duke University Medical Center. The clinical cure rate was 83% (55/66) for bloodstream infections and 88% (23/26) for intraabdominal infections. “This drug performed very, very well with intraabdominal infections.” The failure rate for invasive candidiasis decreased from 26% in 2001 to 11% in 2003. “In this population, there are few ways you are going to improve on that success rate,” he said.

Some people point out that echinocandins are very expensive, compared with the azoles, which are available as generics in many cases, Dr. Perfect said. “But there are a number of candins coming out, so hopefully the market will help with that.”

MIAMI — Approval of micafungin by the Food and Drug Administration in March added another option for combatting infections caused by Candida or Aspergillus species John R. Perfect, M.D., said at a meeting on fungal infections sponsored by Imedex.

Micafungin (Mycamine), an echinocandin antifungal agent, is indicated for prophylaxis of Candida infections in patients undergoing hematopoietic stem cell transplantation and for treatment of esophageal candidiasis. The echinocandin class also includes caspofungin (Cancidas), approved in 2001. Two more drugs in this class, anidulafungin and aminocandin, are in development.

“My suspicion is, [drugs in this class] will have a significant impact on how we manage patients,” said Dr. Perfect, professor of medicine at Duke University Medical Center, Durham, N.C. Yet “candins lack any significantly good data for any fungal infections outside Candida or Aspergillus.”

A possible drawback is that the echinocandins are available only for intravenous infusion. Other considerations are the low urinary and brain concentrations achieved by these drugs, but “these things are not necessarily bad,” he added.

Dr. Perfect disclosed an affiliation with PLIVA, a company that manufactures generic fluconazole, ketoconazole, and metronidazole.

Both caspofungin and micafungin are effective in treating esophageal candidiasis. The echinocandins also have a long half-life and low toxicity, and require little dosage adjustment for patients with renal or liver dysfunction. And the agents have a low potential for drug interactions, which means they can be used in patients taking many other drugs, he said.

Although prevention of Aspergillus infections would be an off-label use of micafungin, the drug does have activity against these organisms, said Dr. Perfect. He predicted that the echinocandins would have a role in preventing Aspergillus infections in the future. “Candins for aspergillosis are trendy in combination, but no one has any data to support that today.”

The “paradigm-changing study” for the echinocandins, Dr. Perfect said, was a randomized, double-blind, multicenter comparison between caspofungin and amphotericin B for patients with invasive candidiasis (N. Engl. J. Med. 2002;347:2020-9). The patients were stratified by neutropenic status and Apache score, and there was no difference between the two drugs in outcome. The study design was practical, he added, because after 10 days of intravenous therapy, patients were switched to oral fluconazole. Intravenous therapy is very expensive, he noted.

He and his colleagues examined caspofungin efficacy for 109 episodes of invasive candidiasis at Duke University Medical Center. The clinical cure rate was 83% (55/66) for bloodstream infections and 88% (23/26) for intraabdominal infections. “This drug performed very, very well with intraabdominal infections.” The failure rate for invasive candidiasis decreased from 26% in 2001 to 11% in 2003. “In this population, there are few ways you are going to improve on that success rate,” he said.

Some people point out that echinocandins are very expensive, compared with the azoles, which are available as generics in many cases, Dr. Perfect said. “But there are a number of candins coming out, so hopefully the market will help with that.”

MIAMI — Approval of micafungin by the Food and Drug Administration in March added another option for combatting infections caused by Candida or Aspergillus species John R. Perfect, M.D., said at a meeting on fungal infections sponsored by Imedex.

Micafungin (Mycamine), an echinocandin antifungal agent, is indicated for prophylaxis of Candida infections in patients undergoing hematopoietic stem cell transplantation and for treatment of esophageal candidiasis. The echinocandin class also includes caspofungin (Cancidas), approved in 2001. Two more drugs in this class, anidulafungin and aminocandin, are in development.

“My suspicion is, [drugs in this class] will have a significant impact on how we manage patients,” said Dr. Perfect, professor of medicine at Duke University Medical Center, Durham, N.C. Yet “candins lack any significantly good data for any fungal infections outside Candida or Aspergillus.”

A possible drawback is that the echinocandins are available only for intravenous infusion. Other considerations are the low urinary and brain concentrations achieved by these drugs, but “these things are not necessarily bad,” he added.

Dr. Perfect disclosed an affiliation with PLIVA, a company that manufactures generic fluconazole, ketoconazole, and metronidazole.

Both caspofungin and micafungin are effective in treating esophageal candidiasis. The echinocandins also have a long half-life and low toxicity, and require little dosage adjustment for patients with renal or liver dysfunction. And the agents have a low potential for drug interactions, which means they can be used in patients taking many other drugs, he said.

Although prevention of Aspergillus infections would be an off-label use of micafungin, the drug does have activity against these organisms, said Dr. Perfect. He predicted that the echinocandins would have a role in preventing Aspergillus infections in the future. “Candins for aspergillosis are trendy in combination, but no one has any data to support that today.”

The “paradigm-changing study” for the echinocandins, Dr. Perfect said, was a randomized, double-blind, multicenter comparison between caspofungin and amphotericin B for patients with invasive candidiasis (N. Engl. J. Med. 2002;347:2020-9). The patients were stratified by neutropenic status and Apache score, and there was no difference between the two drugs in outcome. The study design was practical, he added, because after 10 days of intravenous therapy, patients were switched to oral fluconazole. Intravenous therapy is very expensive, he noted.

He and his colleagues examined caspofungin efficacy for 109 episodes of invasive candidiasis at Duke University Medical Center. The clinical cure rate was 83% (55/66) for bloodstream infections and 88% (23/26) for intraabdominal infections. “This drug performed very, very well with intraabdominal infections.” The failure rate for invasive candidiasis decreased from 26% in 2001 to 11% in 2003. “In this population, there are few ways you are going to improve on that success rate,” he said.

Some people point out that echinocandins are very expensive, compared with the azoles, which are available as generics in many cases, Dr. Perfect said. “But there are a number of candins coming out, so hopefully the market will help with that.”

MARCO ISLAND, FLA. — Posttraumatic stress disorder is not uncommon after moderate-to-severe traumatic brain injury, Jesse R. Fann, M.D., said at the annual meeting of the Academy of Psychosomatic Medicine.

Many people experience anxiety after moderate-to-severe traumatic brain injury. Because both brain injury and dissociation from posttraumatic stress disorder (PTSD) can impair declarative memory, the true occurrence of PTSD remains controversial, noted Dr. Fann, director of the psychiatry and psychology consultation service at the Seattle Cancer Care Alliance.

In a 6-month prospective follow-up study, the researchers assessed 124 patients admitted to Harborview Medical Center in Seattle following traumatic brain injury to determine the incidence of PTSD, the risk factors, and how PTSD symptoms manifest in this population.

Researchers did monthly assessments with the PTSD Checklist- Civilian Version, the Patient Health Questionnaire, and the Self-Reported Health Status (SF-1) instruments. The first month had the highest incidence of PTSD, about 13%. “A lot of the PTSD may not be prolonged, lasting 1–3 months,” he said.

Patients with lower levels of education and those injured in an assault were significantly more likely to meet criteria for the disorder. Participants who met PTSD criteria most commonly reported feeling sad when recalling aspects of the event and feeling cut off from others, jumpy, hypervigilant, and irritable. Sleep disturbances were common.

The investigators looked at PTSD symptom clusters and found arousal symptoms present in 23% of assessments over the 6 months. They also found intrusive symptoms in 20%, and avoidance and numbing in 8%.

“There is a significant overlap of other comorbid psychiatric disorders, such as anxiety and depression, that can present a diagnostic challenge,” Dr. Fann said. “There is also overlap of PTSD and traumatic brain injury symptoms.”

The researchers also assessed patients for major depressive disorder, panic disorder, and other anxiety disorders. PTSD was significantly associated with current major depression, any other anxiety disorder, a blood alcohol level greater than 0.08, and a psychiatric history, according to a univariate analysis. A logistic regression analysis showed that people with a history of PTSD reported significantly increased functional impairment compared with those without PTSD. There also was a trend toward poorer self-reported health status among participants with PTSD.

The study was funded by NIH's National Center for Medical Rehabilitation Research.

MARCO ISLAND, FLA. — Posttraumatic stress disorder is not uncommon after moderate-to-severe traumatic brain injury, Jesse R. Fann, M.D., said at the annual meeting of the Academy of Psychosomatic Medicine.

Many people experience anxiety after moderate-to-severe traumatic brain injury. Because both brain injury and dissociation from posttraumatic stress disorder (PTSD) can impair declarative memory, the true occurrence of PTSD remains controversial, noted Dr. Fann, director of the psychiatry and psychology consultation service at the Seattle Cancer Care Alliance.

In a 6-month prospective follow-up study, the researchers assessed 124 patients admitted to Harborview Medical Center in Seattle following traumatic brain injury to determine the incidence of PTSD, the risk factors, and how PTSD symptoms manifest in this population.

Researchers did monthly assessments with the PTSD Checklist- Civilian Version, the Patient Health Questionnaire, and the Self-Reported Health Status (SF-1) instruments. The first month had the highest incidence of PTSD, about 13%. “A lot of the PTSD may not be prolonged, lasting 1–3 months,” he said.

Patients with lower levels of education and those injured in an assault were significantly more likely to meet criteria for the disorder. Participants who met PTSD criteria most commonly reported feeling sad when recalling aspects of the event and feeling cut off from others, jumpy, hypervigilant, and irritable. Sleep disturbances were common.

The investigators looked at PTSD symptom clusters and found arousal symptoms present in 23% of assessments over the 6 months. They also found intrusive symptoms in 20%, and avoidance and numbing in 8%.

“There is a significant overlap of other comorbid psychiatric disorders, such as anxiety and depression, that can present a diagnostic challenge,” Dr. Fann said. “There is also overlap of PTSD and traumatic brain injury symptoms.”

The researchers also assessed patients for major depressive disorder, panic disorder, and other anxiety disorders. PTSD was significantly associated with current major depression, any other anxiety disorder, a blood alcohol level greater than 0.08, and a psychiatric history, according to a univariate analysis. A logistic regression analysis showed that people with a history of PTSD reported significantly increased functional impairment compared with those without PTSD. There also was a trend toward poorer self-reported health status among participants with PTSD.

The study was funded by NIH's National Center for Medical Rehabilitation Research.

MARCO ISLAND, FLA. — Posttraumatic stress disorder is not uncommon after moderate-to-severe traumatic brain injury, Jesse R. Fann, M.D., said at the annual meeting of the Academy of Psychosomatic Medicine.

Many people experience anxiety after moderate-to-severe traumatic brain injury. Because both brain injury and dissociation from posttraumatic stress disorder (PTSD) can impair declarative memory, the true occurrence of PTSD remains controversial, noted Dr. Fann, director of the psychiatry and psychology consultation service at the Seattle Cancer Care Alliance.

In a 6-month prospective follow-up study, the researchers assessed 124 patients admitted to Harborview Medical Center in Seattle following traumatic brain injury to determine the incidence of PTSD, the risk factors, and how PTSD symptoms manifest in this population.

Researchers did monthly assessments with the PTSD Checklist- Civilian Version, the Patient Health Questionnaire, and the Self-Reported Health Status (SF-1) instruments. The first month had the highest incidence of PTSD, about 13%. “A lot of the PTSD may not be prolonged, lasting 1–3 months,” he said.

Patients with lower levels of education and those injured in an assault were significantly more likely to meet criteria for the disorder. Participants who met PTSD criteria most commonly reported feeling sad when recalling aspects of the event and feeling cut off from others, jumpy, hypervigilant, and irritable. Sleep disturbances were common.

The investigators looked at PTSD symptom clusters and found arousal symptoms present in 23% of assessments over the 6 months. They also found intrusive symptoms in 20%, and avoidance and numbing in 8%.

“There is a significant overlap of other comorbid psychiatric disorders, such as anxiety and depression, that can present a diagnostic challenge,” Dr. Fann said. “There is also overlap of PTSD and traumatic brain injury symptoms.”

The researchers also assessed patients for major depressive disorder, panic disorder, and other anxiety disorders. PTSD was significantly associated with current major depression, any other anxiety disorder, a blood alcohol level greater than 0.08, and a psychiatric history, according to a univariate analysis. A logistic regression analysis showed that people with a history of PTSD reported significantly increased functional impairment compared with those without PTSD. There also was a trend toward poorer self-reported health status among participants with PTSD.

The study was funded by NIH's National Center for Medical Rehabilitation Research.

MIAMI — Resistance to Candida species is rare in high-risk nurseries in the United States, according to a study from the Centers for Disease Control and Prevention presented in a poster at a meeting on fungal infections sponsored by Imedex.

Scott Fridkin, M.D., and colleagues also found the overall rate of invasive candidiasis in very-low-birth-weight infants has decreased since 2000—although they are unsure why.

Candida bloodstream infections are the third most common cause of late-onset sepsis in the neonatal intensive care unit. Infection incidence and resistance information could help target azole antifungal prophylaxis in this population.

The CDC investigators reviewed all cases of invasive candidiasis in neonates registered in the high-risk nursery section of the National Nosocomial Infections Surveillance System from January 1995 to December 2004. A total of 129 high-risk nurseries contributed information on 130,523 patients.

Dr. Fridkin, medical officer in the Division of Bacterial and Mycotic Diseases at the CDC's National Center for Infectious Diseases in Atlanta, and his associates assessed the incidence of invasive candidiasis among infants admitted to intensive care by birth weight, as well as the incidence of Candida blood stream infections associated with central venous catheter use.

They also looked for rates of resistance to different Candida species.

“The big take-home message is the [low] number of invasive candidiasis infections,” Dr. Fridkin said in an interview at the meeting.

The rate of disease in very-low-birth-weight infants decreased considerably since 2000. (See chart.)

Although the decrease could be a result of antifungal prophylaxis or improved use of catheters, “why it went down is pure conjecture,” said Dr. Fridkin.

Dr. Fridkin and his colleagues identified 1,997 neonates (1.5%) with invasive candidiasis. Most of these cases of invasive candidiasis (1,472 [74%]) occurred in infants with a birth weight less than 1,000 g.

The incidence of invasive candidiasis varied by species, with 58% attributed to C. albicans, 34% to C. parapsilosis, 4% to C. glabrata, 2% to C. tropicalis, 2% to C. lusitaniae, and 0.2% to C. krusei.

Incidence of invasive candidiasis among infants with birth weight less than 1,000 g varied greatly between individual high-risk nurseries, the researchers noted—as did incidence density (the number of Candida blood stream infections per 1,000 central venous catheter days).

The researchers looked for resistance in C. glabrata and C. krusei, species commonly resistant to azole treatment. They wrote, “Although invasive candidiasis is a serious problem among neonates less than 1,000 g, invasive candidiasis due to species commonly resistant to azoles were extremely rare.”

Dr. Fridkin said, “Despite all the fear about antifungal resistance in the NICU, these data say, right now in the U.S., there is almost no resistance to yeast. It's a real solid finding.”

KEVIN FOLEY, RESEARCH/ANGIE RIES, DESIGN

MIAMI — Resistance to Candida species is rare in high-risk nurseries in the United States, according to a study from the Centers for Disease Control and Prevention presented in a poster at a meeting on fungal infections sponsored by Imedex.

Scott Fridkin, M.D., and colleagues also found the overall rate of invasive candidiasis in very-low-birth-weight infants has decreased since 2000—although they are unsure why.

Candida bloodstream infections are the third most common cause of late-onset sepsis in the neonatal intensive care unit. Infection incidence and resistance information could help target azole antifungal prophylaxis in this population.

The CDC investigators reviewed all cases of invasive candidiasis in neonates registered in the high-risk nursery section of the National Nosocomial Infections Surveillance System from January 1995 to December 2004. A total of 129 high-risk nurseries contributed information on 130,523 patients.

Dr. Fridkin, medical officer in the Division of Bacterial and Mycotic Diseases at the CDC's National Center for Infectious Diseases in Atlanta, and his associates assessed the incidence of invasive candidiasis among infants admitted to intensive care by birth weight, as well as the incidence of Candida blood stream infections associated with central venous catheter use.

They also looked for rates of resistance to different Candida species.

“The big take-home message is the [low] number of invasive candidiasis infections,” Dr. Fridkin said in an interview at the meeting.

The rate of disease in very-low-birth-weight infants decreased considerably since 2000. (See chart.)

Although the decrease could be a result of antifungal prophylaxis or improved use of catheters, “why it went down is pure conjecture,” said Dr. Fridkin.

Dr. Fridkin and his colleagues identified 1,997 neonates (1.5%) with invasive candidiasis. Most of these cases of invasive candidiasis (1,472 [74%]) occurred in infants with a birth weight less than 1,000 g.

The incidence of invasive candidiasis varied by species, with 58% attributed to C. albicans, 34% to C. parapsilosis, 4% to C. glabrata, 2% to C. tropicalis, 2% to C. lusitaniae, and 0.2% to C. krusei.

Incidence of invasive candidiasis among infants with birth weight less than 1,000 g varied greatly between individual high-risk nurseries, the researchers noted—as did incidence density (the number of Candida blood stream infections per 1,000 central venous catheter days).

The researchers looked for resistance in C. glabrata and C. krusei, species commonly resistant to azole treatment. They wrote, “Although invasive candidiasis is a serious problem among neonates less than 1,000 g, invasive candidiasis due to species commonly resistant to azoles were extremely rare.”

Dr. Fridkin said, “Despite all the fear about antifungal resistance in the NICU, these data say, right now in the U.S., there is almost no resistance to yeast. It's a real solid finding.”

KEVIN FOLEY, RESEARCH/ANGIE RIES, DESIGN

MIAMI — Resistance to Candida species is rare in high-risk nurseries in the United States, according to a study from the Centers for Disease Control and Prevention presented in a poster at a meeting on fungal infections sponsored by Imedex.

Scott Fridkin, M.D., and colleagues also found the overall rate of invasive candidiasis in very-low-birth-weight infants has decreased since 2000—although they are unsure why.

Candida bloodstream infections are the third most common cause of late-onset sepsis in the neonatal intensive care unit. Infection incidence and resistance information could help target azole antifungal prophylaxis in this population.

The CDC investigators reviewed all cases of invasive candidiasis in neonates registered in the high-risk nursery section of the National Nosocomial Infections Surveillance System from January 1995 to December 2004. A total of 129 high-risk nurseries contributed information on 130,523 patients.

Dr. Fridkin, medical officer in the Division of Bacterial and Mycotic Diseases at the CDC's National Center for Infectious Diseases in Atlanta, and his associates assessed the incidence of invasive candidiasis among infants admitted to intensive care by birth weight, as well as the incidence of Candida blood stream infections associated with central venous catheter use.

They also looked for rates of resistance to different Candida species.

“The big take-home message is the [low] number of invasive candidiasis infections,” Dr. Fridkin said in an interview at the meeting.

The rate of disease in very-low-birth-weight infants decreased considerably since 2000. (See chart.)

Although the decrease could be a result of antifungal prophylaxis or improved use of catheters, “why it went down is pure conjecture,” said Dr. Fridkin.

Dr. Fridkin and his colleagues identified 1,997 neonates (1.5%) with invasive candidiasis. Most of these cases of invasive candidiasis (1,472 [74%]) occurred in infants with a birth weight less than 1,000 g.

The incidence of invasive candidiasis varied by species, with 58% attributed to C. albicans, 34% to C. parapsilosis, 4% to C. glabrata, 2% to C. tropicalis, 2% to C. lusitaniae, and 0.2% to C. krusei.

Incidence of invasive candidiasis among infants with birth weight less than 1,000 g varied greatly between individual high-risk nurseries, the researchers noted—as did incidence density (the number of Candida blood stream infections per 1,000 central venous catheter days).

The researchers looked for resistance in C. glabrata and C. krusei, species commonly resistant to azole treatment. They wrote, “Although invasive candidiasis is a serious problem among neonates less than 1,000 g, invasive candidiasis due to species commonly resistant to azoles were extremely rare.”

Dr. Fridkin said, “Despite all the fear about antifungal resistance in the NICU, these data say, right now in the U.S., there is almost no resistance to yeast. It's a real solid finding.”

KEVIN FOLEY, RESEARCH/ANGIE RIES, DESIGN

KEY BISCAYNE, FLA. — Laboratory tests indicated the patient had diabetes insipidus. A bone scan was negative. MRI of his head showed pituitary stalk infiltration and plaques typical of multiple sclerosis. A chest CT scan revealed multiple pulmonary nodules. Both biopsies indicated Langerhans cell histiocytosis (LCH). The patient was diagnosed with stage III LCH with skin, lung, and CNS involvement.

Assess hematologic, pulmonary, hepatic, renal, and skeletal systems to determine extent of disease, Paul A. Krusinski, M.D., suggested at the annual meeting of the Noah Worcester Dermatological Society. Treatment is guided by extent of disease and number of systems involved, added Dr. Krusinski, professor of medicine at the University of Vermont in Burlington.

In cases of single-system skin disease, treatment options include topical steroids, psoralen-ultraviolet-light treatment, and topical nitrogen mustard.

With multisystem involvement, combination therapy with vinblastine and a steroid is most common. Vinblastine plus etoposide, prednisone, and mercaptopurine is more effective than monotherapy. A failure to respond to therapy by 6 weeks indicates a poorer prognosis.

The patient was treated with desmopressin acetate for his diabetes insipidus. He also received six monthly cycles of 2-chlorodeoxyadenosine (cladribine) for the histiocytosis. Cladribine destroys resting and dividing lymphocytes and is approved for treatment of hairy cell leukemia. Cladribine trials for LCH are ongoing; it may be effective at blocking the clonal proliferation of Langerhans cells responsible for the disease. Principal toxicity is from myelosuppression, but long-term malignancy effects are unknown. Another potential treatment is imatinib mesylate.

With single-system disease, 5-year survival is 100%. With multisystem involvement, 5-year survival is 92%. If there is lung disease, 5-year survival drops to 87%.

KEY BISCAYNE, FLA. — Laboratory tests indicated the patient had diabetes insipidus. A bone scan was negative. MRI of his head showed pituitary stalk infiltration and plaques typical of multiple sclerosis. A chest CT scan revealed multiple pulmonary nodules. Both biopsies indicated Langerhans cell histiocytosis (LCH). The patient was diagnosed with stage III LCH with skin, lung, and CNS involvement.

Assess hematologic, pulmonary, hepatic, renal, and skeletal systems to determine extent of disease, Paul A. Krusinski, M.D., suggested at the annual meeting of the Noah Worcester Dermatological Society. Treatment is guided by extent of disease and number of systems involved, added Dr. Krusinski, professor of medicine at the University of Vermont in Burlington.

In cases of single-system skin disease, treatment options include topical steroids, psoralen-ultraviolet-light treatment, and topical nitrogen mustard.

With multisystem involvement, combination therapy with vinblastine and a steroid is most common. Vinblastine plus etoposide, prednisone, and mercaptopurine is more effective than monotherapy. A failure to respond to therapy by 6 weeks indicates a poorer prognosis.

The patient was treated with desmopressin acetate for his diabetes insipidus. He also received six monthly cycles of 2-chlorodeoxyadenosine (cladribine) for the histiocytosis. Cladribine destroys resting and dividing lymphocytes and is approved for treatment of hairy cell leukemia. Cladribine trials for LCH are ongoing; it may be effective at blocking the clonal proliferation of Langerhans cells responsible for the disease. Principal toxicity is from myelosuppression, but long-term malignancy effects are unknown. Another potential treatment is imatinib mesylate.

With single-system disease, 5-year survival is 100%. With multisystem involvement, 5-year survival is 92%. If there is lung disease, 5-year survival drops to 87%.

KEY BISCAYNE, FLA. — Laboratory tests indicated the patient had diabetes insipidus. A bone scan was negative. MRI of his head showed pituitary stalk infiltration and plaques typical of multiple sclerosis. A chest CT scan revealed multiple pulmonary nodules. Both biopsies indicated Langerhans cell histiocytosis (LCH). The patient was diagnosed with stage III LCH with skin, lung, and CNS involvement.

Assess hematologic, pulmonary, hepatic, renal, and skeletal systems to determine extent of disease, Paul A. Krusinski, M.D., suggested at the annual meeting of the Noah Worcester Dermatological Society. Treatment is guided by extent of disease and number of systems involved, added Dr. Krusinski, professor of medicine at the University of Vermont in Burlington.

In cases of single-system skin disease, treatment options include topical steroids, psoralen-ultraviolet-light treatment, and topical nitrogen mustard.

With multisystem involvement, combination therapy with vinblastine and a steroid is most common. Vinblastine plus etoposide, prednisone, and mercaptopurine is more effective than monotherapy. A failure to respond to therapy by 6 weeks indicates a poorer prognosis.

The patient was treated with desmopressin acetate for his diabetes insipidus. He also received six monthly cycles of 2-chlorodeoxyadenosine (cladribine) for the histiocytosis. Cladribine destroys resting and dividing lymphocytes and is approved for treatment of hairy cell leukemia. Cladribine trials for LCH are ongoing; it may be effective at blocking the clonal proliferation of Langerhans cells responsible for the disease. Principal toxicity is from myelosuppression, but long-term malignancy effects are unknown. Another potential treatment is imatinib mesylate.

With single-system disease, 5-year survival is 100%. With multisystem involvement, 5-year survival is 92%. If there is lung disease, 5-year survival drops to 87%.

MIAMI BEACH — There are many options for antibiotic treatment of uncomplicated and complicated skin infections, each with its own advantages and disadvantages, according to a presentation by Richard K. Scher, M.D., at a symposium sponsored by the Florida Society of Dermatology and Dermatologic Surgery.

Uncomplicated infections affect superficial skin tissue and include furuncles, cellulites, folliculitis, simple abscesses, and impetiginous lesions. Complicated infections affect deeper soft tissue or require significant surgery, such as infected ulcers, burns, or major abscesses. Infections are also complicated in the presence of significant underlying disease or if the affected site carries a higher risk for anaerobic or gram-negative infection, such as the rectal area.

Patients with severe atopic dermatitis, poorly controlled diabetes, or kidney failure may be predisposed to skin infections. Other risk factors include leukemia or lymphoma; malnutrition and low serum iron; alcohol abuse; intravenous drug use; and medications including systemic steroids, cytotoxic agents, and immunosuppressants.

Dr. Scher, professor of clinical dermatology at Columbia University, New York, discussed options for treatment of uncomplicated skin and skin structure infections:

▸ Cephalosporins. These drugs have good tolerability and good sensitivity. The risk of hypersensitivity is low, probably less than 2%, for a patient with a history of nonanaphylactic penicillin allergy.

First-generation drugs in this class include cephalexin and cefadroxil. They have good activity against S. pyogenes and methicillin-resistant S. aureus. Dosing is t.i.d. to q.i.d.

Second-generation agents include cefaclor and cefuroxime. These drugs feature expanded activity against gram-negative bacteria and have a longer half-life than the first-generation drugs. Dosing is b.i.d.

Third-generation cephalosporins include cefixime and ceftibuten. They are good for gram-negative organisms but not as effective for gram-positive bacteria, Dr. Scher noted. Dosing is once daily or b.i.d.

Extended-spectrum cephalosporins include cefdinir and cefpodoxime. These agents have good activity against both gram-negative and gram-positive bacteria. Cefdinir is administered b.i.d.

▸ Penicillins. S. pyogenes is always sensitive to treatment with penicillins, but because of cross resistance from MRSA, S. aureus is no longer sensitive. Drugs in this class that are β-lactamase stable exhibit good antistaphylococcal activity. Most dosing is t.i.d. or q.i.d.

▸ Macrolides. These medications include erythromycin, clarithromycin, and azithromycin. They are less likely to be used because of concerns about resistance, Dr. Scher said. Increasing resistance to S. pyogenes and S. aureus has been reported.

▸ Tetracyclines. The tetracyclines have some coverage for community-acquired MRSA. However, there are some resistance issues, and these agents can cause tooth discoloration in children and photosensitivity in some patients.

▸ Fluoroquinolones. Advantages of drugs in this class include a long half-life and the suggestion in early studies that fluoroquinolones are as efficacious as β-lactams for erysipelas, cellulites, impetigo, surgical wounds, and diabetic foot infections. However, resistance is increasing because of widespread use. Possible adverse effects include tendonitis and tendon rupture in adults. The fluoroquinolones are contraindicated in pediatric patients.

▸ Lincosamides. Clindamycin has good activity against S. pyogenes and methicillin-susceptible strains of S. aureus. It is also active against some MRSA strains. Resistance to erythromycin could signal inducible resistance to clindamycin, Dr. Scher said. There is an increased risk of pseudomembranous colitis associated with Clostridium difficile. Dosing is t.i.d.

▸ Trimethoprim-sulfamethoxazole. This drug combination covers some community-acquired MRSA infections. There is some resistance among staphylococci and no coverage for streptococci. Possible adverse reactions include rash and photosensitivity.

Factors that may alter antimicrobial decision making include emerging macrolide resistance among the β-hemolytic or viridans-group streptococci, Dr. Scher noted. He added that patients with community-acquired MRSA might also be resistant to β-lactams, macrolides, and quinolones, further limiting therapeutic choices.

MIAMI BEACH — There are many options for antibiotic treatment of uncomplicated and complicated skin infections, each with its own advantages and disadvantages, according to a presentation by Richard K. Scher, M.D., at a symposium sponsored by the Florida Society of Dermatology and Dermatologic Surgery.

Uncomplicated infections affect superficial skin tissue and include furuncles, cellulites, folliculitis, simple abscesses, and impetiginous lesions. Complicated infections affect deeper soft tissue or require significant surgery, such as infected ulcers, burns, or major abscesses. Infections are also complicated in the presence of significant underlying disease or if the affected site carries a higher risk for anaerobic or gram-negative infection, such as the rectal area.

Patients with severe atopic dermatitis, poorly controlled diabetes, or kidney failure may be predisposed to skin infections. Other risk factors include leukemia or lymphoma; malnutrition and low serum iron; alcohol abuse; intravenous drug use; and medications including systemic steroids, cytotoxic agents, and immunosuppressants.

Dr. Scher, professor of clinical dermatology at Columbia University, New York, discussed options for treatment of uncomplicated skin and skin structure infections:

▸ Cephalosporins. These drugs have good tolerability and good sensitivity. The risk of hypersensitivity is low, probably less than 2%, for a patient with a history of nonanaphylactic penicillin allergy.

First-generation drugs in this class include cephalexin and cefadroxil. They have good activity against S. pyogenes and methicillin-resistant S. aureus. Dosing is t.i.d. to q.i.d.

Second-generation agents include cefaclor and cefuroxime. These drugs feature expanded activity against gram-negative bacteria and have a longer half-life than the first-generation drugs. Dosing is b.i.d.

Third-generation cephalosporins include cefixime and ceftibuten. They are good for gram-negative organisms but not as effective for gram-positive bacteria, Dr. Scher noted. Dosing is once daily or b.i.d.

Extended-spectrum cephalosporins include cefdinir and cefpodoxime. These agents have good activity against both gram-negative and gram-positive bacteria. Cefdinir is administered b.i.d.

▸ Penicillins. S. pyogenes is always sensitive to treatment with penicillins, but because of cross resistance from MRSA, S. aureus is no longer sensitive. Drugs in this class that are β-lactamase stable exhibit good antistaphylococcal activity. Most dosing is t.i.d. or q.i.d.

▸ Macrolides. These medications include erythromycin, clarithromycin, and azithromycin. They are less likely to be used because of concerns about resistance, Dr. Scher said. Increasing resistance to S. pyogenes and S. aureus has been reported.

▸ Tetracyclines. The tetracyclines have some coverage for community-acquired MRSA. However, there are some resistance issues, and these agents can cause tooth discoloration in children and photosensitivity in some patients.

▸ Fluoroquinolones. Advantages of drugs in this class include a long half-life and the suggestion in early studies that fluoroquinolones are as efficacious as β-lactams for erysipelas, cellulites, impetigo, surgical wounds, and diabetic foot infections. However, resistance is increasing because of widespread use. Possible adverse effects include tendonitis and tendon rupture in adults. The fluoroquinolones are contraindicated in pediatric patients.

▸ Lincosamides. Clindamycin has good activity against S. pyogenes and methicillin-susceptible strains of S. aureus. It is also active against some MRSA strains. Resistance to erythromycin could signal inducible resistance to clindamycin, Dr. Scher said. There is an increased risk of pseudomembranous colitis associated with Clostridium difficile. Dosing is t.i.d.

▸ Trimethoprim-sulfamethoxazole. This drug combination covers some community-acquired MRSA infections. There is some resistance among staphylococci and no coverage for streptococci. Possible adverse reactions include rash and photosensitivity.

Factors that may alter antimicrobial decision making include emerging macrolide resistance among the β-hemolytic or viridans-group streptococci, Dr. Scher noted. He added that patients with community-acquired MRSA might also be resistant to β-lactams, macrolides, and quinolones, further limiting therapeutic choices.

MIAMI BEACH — There are many options for antibiotic treatment of uncomplicated and complicated skin infections, each with its own advantages and disadvantages, according to a presentation by Richard K. Scher, M.D., at a symposium sponsored by the Florida Society of Dermatology and Dermatologic Surgery.

Uncomplicated infections affect superficial skin tissue and include furuncles, cellulites, folliculitis, simple abscesses, and impetiginous lesions. Complicated infections affect deeper soft tissue or require significant surgery, such as infected ulcers, burns, or major abscesses. Infections are also complicated in the presence of significant underlying disease or if the affected site carries a higher risk for anaerobic or gram-negative infection, such as the rectal area.

Patients with severe atopic dermatitis, poorly controlled diabetes, or kidney failure may be predisposed to skin infections. Other risk factors include leukemia or lymphoma; malnutrition and low serum iron; alcohol abuse; intravenous drug use; and medications including systemic steroids, cytotoxic agents, and immunosuppressants.

Dr. Scher, professor of clinical dermatology at Columbia University, New York, discussed options for treatment of uncomplicated skin and skin structure infections:

▸ Cephalosporins. These drugs have good tolerability and good sensitivity. The risk of hypersensitivity is low, probably less than 2%, for a patient with a history of nonanaphylactic penicillin allergy.

First-generation drugs in this class include cephalexin and cefadroxil. They have good activity against S. pyogenes and methicillin-resistant S. aureus. Dosing is t.i.d. to q.i.d.

Second-generation agents include cefaclor and cefuroxime. These drugs feature expanded activity against gram-negative bacteria and have a longer half-life than the first-generation drugs. Dosing is b.i.d.

Third-generation cephalosporins include cefixime and ceftibuten. They are good for gram-negative organisms but not as effective for gram-positive bacteria, Dr. Scher noted. Dosing is once daily or b.i.d.

Extended-spectrum cephalosporins include cefdinir and cefpodoxime. These agents have good activity against both gram-negative and gram-positive bacteria. Cefdinir is administered b.i.d.

▸ Penicillins. S. pyogenes is always sensitive to treatment with penicillins, but because of cross resistance from MRSA, S. aureus is no longer sensitive. Drugs in this class that are β-lactamase stable exhibit good antistaphylococcal activity. Most dosing is t.i.d. or q.i.d.

▸ Macrolides. These medications include erythromycin, clarithromycin, and azithromycin. They are less likely to be used because of concerns about resistance, Dr. Scher said. Increasing resistance to S. pyogenes and S. aureus has been reported.

▸ Tetracyclines. The tetracyclines have some coverage for community-acquired MRSA. However, there are some resistance issues, and these agents can cause tooth discoloration in children and photosensitivity in some patients.

▸ Fluoroquinolones. Advantages of drugs in this class include a long half-life and the suggestion in early studies that fluoroquinolones are as efficacious as β-lactams for erysipelas, cellulites, impetigo, surgical wounds, and diabetic foot infections. However, resistance is increasing because of widespread use. Possible adverse effects include tendonitis and tendon rupture in adults. The fluoroquinolones are contraindicated in pediatric patients.

▸ Lincosamides. Clindamycin has good activity against S. pyogenes and methicillin-susceptible strains of S. aureus. It is also active against some MRSA strains. Resistance to erythromycin could signal inducible resistance to clindamycin, Dr. Scher said. There is an increased risk of pseudomembranous colitis associated with Clostridium difficile. Dosing is t.i.d.

▸ Trimethoprim-sulfamethoxazole. This drug combination covers some community-acquired MRSA infections. There is some resistance among staphylococci and no coverage for streptococci. Possible adverse reactions include rash and photosensitivity.

Factors that may alter antimicrobial decision making include emerging macrolide resistance among the β-hemolytic or viridans-group streptococci, Dr. Scher noted. He added that patients with community-acquired MRSA might also be resistant to β-lactams, macrolides, and quinolones, further limiting therapeutic choices.

MIAMI — Approval of micafungin by the Food and Drug Administration in March added another option for combatting infections caused by Candida or Aspergillus species, John R. Perfect, M.D., said at a meeting on fungal infections sponsored by Imedex.

Micafungin (Mycamine), an echinocandin antifungal agent, is indicated for prophylaxis of Candida infections in patients undergoing hematopoietic stem cell transplantation and for treatment of esophageal candidiasis. The echinocandin class also includes caspofungin (Cancidas), approved in 2001. Two more drugs in this class, anidulafungin and aminocandin, are in development.

“My suspicion is, [drugs in this class] will have a significant impact on how we manage patients,” said Dr. Perfect, professor of medicine at Duke University Medical Center, Durham, N.C.

However, “candins lack any significantly good data for any fungal infections outside Candida or Aspergillus,” he added.

One possible drawback is that the echinocandins are available only for intravenous infusion. Other considerations are the low urinary and brain concentrations achieved by these drugs, but Dr. Perfect added that “these things are not necessarily bad.”

Dr. Perfect disclosed an affiliation with PLIVA, a company that manufactures generic fluconazole, ketoconazole, and metronidazole.

Both caspofungin and micafungin are effective in treating esophageal candidiasis. The echinocandins also have a long half-life and low toxicity, and require little dosage adjustment for patients with renal or liver dysfunction. And the agents have a low potential for drug interactions, which means they can be used in patients taking many other drugs, he said.

Although prevention of Aspergillus infections would be an off-label use of micafungin, the drug does have activity against these organisms, said Dr. Perfect. He predicted that the echinocandins would have a role in preventing Aspergillus infections in the future. “Candins for aspergillosis are trendy in combination, but no one has any data to support that today.”

The “paradigm-changing study” for the echinocandins, Dr. Perfect said, was a randomized, double-blind, multicenter comparison between caspofungin and amphotericin B for patients with invasive candidiasis (N. Engl. J. Med. 2002; 347:2020-9). The patients were stratified by neutropenic status and Apache score, and there was no difference between the two drugs in outcome. The study design was practical, he added, because after 10 days of intravenous therapy, patients were switched to oral fluconazole. Intravenous therapy is very expensive, he noted.

Dr. Perfect and his colleagues examined caspofungin efficacy for 109 episodes of invasive candidiasis at Duke University Medical Center. The clinical cure rate was 83% (55/66) for bloodstream infections and 88% (23/26) for intraabdominal infections. “This drug performed very, very well with intraabdominal infections.”

The failure rate for invasive candidiasis at Duke decreased from 26% in 2001 to 11% in 2003. “In this population, there are few ways you are going to improve on that success rate,” he said.

Some people point out that echinocandins are very expensive, compared with the azoles, which are available as generics in many cases, Dr. Perfect said. “But there are a number of candins coming out, so hopefully the market will help with that.

“You have to look at your patient population and the flora you have in your hospital to see what is best,” he said. For example, he would prescribe caspofungin if he had four patients with breakthrough Candida glabrata infections while on azole therapy.

MIAMI — Approval of micafungin by the Food and Drug Administration in March added another option for combatting infections caused by Candida or Aspergillus species, John R. Perfect, M.D., said at a meeting on fungal infections sponsored by Imedex.

Micafungin (Mycamine), an echinocandin antifungal agent, is indicated for prophylaxis of Candida infections in patients undergoing hematopoietic stem cell transplantation and for treatment of esophageal candidiasis. The echinocandin class also includes caspofungin (Cancidas), approved in 2001. Two more drugs in this class, anidulafungin and aminocandin, are in development.

“My suspicion is, [drugs in this class] will have a significant impact on how we manage patients,” said Dr. Perfect, professor of medicine at Duke University Medical Center, Durham, N.C.

However, “candins lack any significantly good data for any fungal infections outside Candida or Aspergillus,” he added.

One possible drawback is that the echinocandins are available only for intravenous infusion. Other considerations are the low urinary and brain concentrations achieved by these drugs, but Dr. Perfect added that “these things are not necessarily bad.”

Dr. Perfect disclosed an affiliation with PLIVA, a company that manufactures generic fluconazole, ketoconazole, and metronidazole.

Both caspofungin and micafungin are effective in treating esophageal candidiasis. The echinocandins also have a long half-life and low toxicity, and require little dosage adjustment for patients with renal or liver dysfunction. And the agents have a low potential for drug interactions, which means they can be used in patients taking many other drugs, he said.

Although prevention of Aspergillus infections would be an off-label use of micafungin, the drug does have activity against these organisms, said Dr. Perfect. He predicted that the echinocandins would have a role in preventing Aspergillus infections in the future. “Candins for aspergillosis are trendy in combination, but no one has any data to support that today.”

The “paradigm-changing study” for the echinocandins, Dr. Perfect said, was a randomized, double-blind, multicenter comparison between caspofungin and amphotericin B for patients with invasive candidiasis (N. Engl. J. Med. 2002; 347:2020-9). The patients were stratified by neutropenic status and Apache score, and there was no difference between the two drugs in outcome. The study design was practical, he added, because after 10 days of intravenous therapy, patients were switched to oral fluconazole. Intravenous therapy is very expensive, he noted.

Dr. Perfect and his colleagues examined caspofungin efficacy for 109 episodes of invasive candidiasis at Duke University Medical Center. The clinical cure rate was 83% (55/66) for bloodstream infections and 88% (23/26) for intraabdominal infections. “This drug performed very, very well with intraabdominal infections.”

The failure rate for invasive candidiasis at Duke decreased from 26% in 2001 to 11% in 2003. “In this population, there are few ways you are going to improve on that success rate,” he said.

Some people point out that echinocandins are very expensive, compared with the azoles, which are available as generics in many cases, Dr. Perfect said. “But there are a number of candins coming out, so hopefully the market will help with that.

“You have to look at your patient population and the flora you have in your hospital to see what is best,” he said. For example, he would prescribe caspofungin if he had four patients with breakthrough Candida glabrata infections while on azole therapy.

MIAMI — Approval of micafungin by the Food and Drug Administration in March added another option for combatting infections caused by Candida or Aspergillus species, John R. Perfect, M.D., said at a meeting on fungal infections sponsored by Imedex.

Micafungin (Mycamine), an echinocandin antifungal agent, is indicated for prophylaxis of Candida infections in patients undergoing hematopoietic stem cell transplantation and for treatment of esophageal candidiasis. The echinocandin class also includes caspofungin (Cancidas), approved in 2001. Two more drugs in this class, anidulafungin and aminocandin, are in development.

“My suspicion is, [drugs in this class] will have a significant impact on how we manage patients,” said Dr. Perfect, professor of medicine at Duke University Medical Center, Durham, N.C.

However, “candins lack any significantly good data for any fungal infections outside Candida or Aspergillus,” he added.

One possible drawback is that the echinocandins are available only for intravenous infusion. Other considerations are the low urinary and brain concentrations achieved by these drugs, but Dr. Perfect added that “these things are not necessarily bad.”

Dr. Perfect disclosed an affiliation with PLIVA, a company that manufactures generic fluconazole, ketoconazole, and metronidazole.

Both caspofungin and micafungin are effective in treating esophageal candidiasis. The echinocandins also have a long half-life and low toxicity, and require little dosage adjustment for patients with renal or liver dysfunction. And the agents have a low potential for drug interactions, which means they can be used in patients taking many other drugs, he said.

Although prevention of Aspergillus infections would be an off-label use of micafungin, the drug does have activity against these organisms, said Dr. Perfect. He predicted that the echinocandins would have a role in preventing Aspergillus infections in the future. “Candins for aspergillosis are trendy in combination, but no one has any data to support that today.”

The “paradigm-changing study” for the echinocandins, Dr. Perfect said, was a randomized, double-blind, multicenter comparison between caspofungin and amphotericin B for patients with invasive candidiasis (N. Engl. J. Med. 2002; 347:2020-9). The patients were stratified by neutropenic status and Apache score, and there was no difference between the two drugs in outcome. The study design was practical, he added, because after 10 days of intravenous therapy, patients were switched to oral fluconazole. Intravenous therapy is very expensive, he noted.

Dr. Perfect and his colleagues examined caspofungin efficacy for 109 episodes of invasive candidiasis at Duke University Medical Center. The clinical cure rate was 83% (55/66) for bloodstream infections and 88% (23/26) for intraabdominal infections. “This drug performed very, very well with intraabdominal infections.”

The failure rate for invasive candidiasis at Duke decreased from 26% in 2001 to 11% in 2003. “In this population, there are few ways you are going to improve on that success rate,” he said.

Some people point out that echinocandins are very expensive, compared with the azoles, which are available as generics in many cases, Dr. Perfect said. “But there are a number of candins coming out, so hopefully the market will help with that.

“You have to look at your patient population and the flora you have in your hospital to see what is best,” he said. For example, he would prescribe caspofungin if he had four patients with breakthrough Candida glabrata infections while on azole therapy.

MIAMI — The echinocandin antifungal agents appear to have little significant toxicity and may ultimately prove to be safer than the azoles or amphotericin B in terms of potential interactions, according to Paul O. Gubbins, Pharm.D.

“Echinocandins are an exciting new class. To date, there are few significant drug-drug interactions,” Dr. Gubbins said at a meeting on fungal infections sponsored by Imedex.

The echinocandin caspofungin (Cancidas) has “no significant interaction” with cytochrome P-450 (CYP450) metabolism or P-glycoprotein, according to product labeling. The most abundant enzyme in the CYP450 system, CYP3A4, metabolizes about 50%-60% of all medicines.

In addition, the recently approved echinocandin micafungin (see accompanying story) is not a substrate or inhibitor for P-glycoprotein, a transmembrane efflux pump in the liver, intestine, kidneys, and blood-brain barrier.

With a lower potential for interactions, the echinocandins may be ideal for combination therapy, said Dr. Gubbins, chair of the department of pharmacy practice, University of Arkansas, Little Rock.

Toxicity is another important consideration, and it can relate to drug interactions. Traditional formulations of amphotericin B have renal toxicity that can produce additive drug interactions. “We're all familiar with the toxicities of amphotericin B. They are subtle and, in most cases, unavoidable. Consider renal-sparing alternatives” such as lipid amphotericin B or caspofungin, he suggested.

When prescribing traditional amphotericin B, monitor serum levels of drugs that have a narrow therapeutic index and are eliminated by the kidneys. Examples include aminoglycosides and 5-flucytosine.

Physicians are much more aware of drug interactions now than they used to be, and not just for antifungals, but for all drug classes, Dr. Gubbins said in response to a meeting attendee's question.

Some patients, such as organ transplant recipients, require closer monitoring. They often use drugs they cannot avoid, such as immunosuppressants, which increase the risk of fungal infections, he added.

The azoles have a complicated set of interactions. They can interact through multiple mechanisms, including CYP450 metabolism, gastric pH-dependent effects, and P-glycoprotein activity. “Interactions can be managed with alternative drugs in the affected class or by switching agents,” Dr. Gubbins said.

Itraconazole leads the azole class in terms of p otential interactions. The antifungal interacts through the CYP450 system with statins, especially lovastatin, simvastatin, and atorvastatin (Lipitor), and this can lead to skeletal muscle toxicity. Other affected agents include benzodiazepines, anxiolytics, immunosuppressants, and corticosteroids. With corticosteroids, he said, “The key is, it doesn't matter if you give these orally or IV, or if they're inhaled, you can get interactions.”

Itraconazole can also have significant pH interactions. Dissolution depends on gastric pH, meal composition, and gastric emptying. Dr. Gubbins suggested that patients take the tablets with a high-fat meal that is dense in calories in order to slow gastric emptying or with a meal that contains enough protein to buffer the stomach contents. Other techniques for reducing pH interactions include spacing the administration of tablets, considering itraconazole oral solution, or switching to another agent. P-glycoprotein interactions are significant only for itraconazole, not for voriconazole (Vfend), or fluconazole, Dr. Gubbins said.

Although several agents lower serum levels of itraconazole, including phenytoin, phenobarbital, rifampin, and rifabutin (Mycobutin), “remember that itraconazole affects other medications more than other medications affect itraconazole,” he said. “The ones we're worried about are the ones with a narrow therapeutic index, such as digoxin.”

Fluconazole affects more CYP450 enzymes than does itraconazole. “It's a whole different ball game,” Dr. Gubbins said. Interactions depend largely on fluconazole concentration and are typically seen with doses greater than 200 mg.

Of particular concern are interactions between fluconazole and phenytoin or warfarin. “With phenytoin, if you do not see a response, it could be that [phenytoin] is inhibiting fluconazole.”

“We also worry about the anticoagulant warfarin. … This interaction is almost guaranteed.” Decreasing the warfarin dose might help, but “you almost always need to move to another antifungal.”

Three CYP450 enzymes metabolize voriconazole extensively. Two have genetic polymorphisms that make interactions more likely in certain populations. For example, a CYP2C19 polymorphism is present in 2%-5% of whites, 12%-23% of Asians, and 38%-79% of South Pacific populations.

Drugs that affect voriconazole include phenytoin, rifampin, and rifabutin. Other potential interactions include carbamazepine, protease inhibitors, nonnucleoside reverse transcriptase inhibitors, benzodiazepines, and statins.

“How do we get around this? There are drugs we just don't use with voriconazole, such as rifampin or rifabutin,” Dr. Gubbins said. He also suggested increasing the voriconazole dosage cautiously with phenytoin and monitoring patients taking warfarin closely.

MIAMI — The echinocandin antifungal agents appear to have little significant toxicity and may ultimately prove to be safer than the azoles or amphotericin B in terms of potential interactions, according to Paul O. Gubbins, Pharm.D.

“Echinocandins are an exciting new class. To date, there are few significant drug-drug interactions,” Dr. Gubbins said at a meeting on fungal infections sponsored by Imedex.

The echinocandin caspofungin (Cancidas) has “no significant interaction” with cytochrome P-450 (CYP450) metabolism or P-glycoprotein, according to product labeling. The most abundant enzyme in the CYP450 system, CYP3A4, metabolizes about 50%-60% of all medicines.

In addition, the recently approved echinocandin micafungin (see accompanying story) is not a substrate or inhibitor for P-glycoprotein, a transmembrane efflux pump in the liver, intestine, kidneys, and blood-brain barrier.

With a lower potential for interactions, the echinocandins may be ideal for combination therapy, said Dr. Gubbins, chair of the department of pharmacy practice, University of Arkansas, Little Rock.

Toxicity is another important consideration, and it can relate to drug interactions. Traditional formulations of amphotericin B have renal toxicity that can produce additive drug interactions. “We're all familiar with the toxicities of amphotericin B. They are subtle and, in most cases, unavoidable. Consider renal-sparing alternatives” such as lipid amphotericin B or caspofungin, he suggested.

When prescribing traditional amphotericin B, monitor serum levels of drugs that have a narrow therapeutic index and are eliminated by the kidneys. Examples include aminoglycosides and 5-flucytosine.

Physicians are much more aware of drug interactions now than they used to be, and not just for antifungals, but for all drug classes, Dr. Gubbins said in response to a meeting attendee's question.

Some patients, such as organ transplant recipients, require closer monitoring. They often use drugs they cannot avoid, such as immunosuppressants, which increase the risk of fungal infections, he added.

The azoles have a complicated set of interactions. They can interact through multiple mechanisms, including CYP450 metabolism, gastric pH-dependent effects, and P-glycoprotein activity. “Interactions can be managed with alternative drugs in the affected class or by switching agents,” Dr. Gubbins said.

Itraconazole leads the azole class in terms of p otential interactions. The antifungal interacts through the CYP450 system with statins, especially lovastatin, simvastatin, and atorvastatin (Lipitor), and this can lead to skeletal muscle toxicity. Other affected agents include benzodiazepines, anxiolytics, immunosuppressants, and corticosteroids. With corticosteroids, he said, “The key is, it doesn't matter if you give these orally or IV, or if they're inhaled, you can get interactions.”

Itraconazole can also have significant pH interactions. Dissolution depends on gastric pH, meal composition, and gastric emptying. Dr. Gubbins suggested that patients take the tablets with a high-fat meal that is dense in calories in order to slow gastric emptying or with a meal that contains enough protein to buffer the stomach contents. Other techniques for reducing pH interactions include spacing the administration of tablets, considering itraconazole oral solution, or switching to another agent. P-glycoprotein interactions are significant only for itraconazole, not for voriconazole (Vfend), or fluconazole, Dr. Gubbins said.

Although several agents lower serum levels of itraconazole, including phenytoin, phenobarbital, rifampin, and rifabutin (Mycobutin), “remember that itraconazole affects other medications more than other medications affect itraconazole,” he said. “The ones we're worried about are the ones with a narrow therapeutic index, such as digoxin.”

Fluconazole affects more CYP450 enzymes than does itraconazole. “It's a whole different ball game,” Dr. Gubbins said. Interactions depend largely on fluconazole concentration and are typically seen with doses greater than 200 mg.

Of particular concern are interactions between fluconazole and phenytoin or warfarin. “With phenytoin, if you do not see a response, it could be that [phenytoin] is inhibiting fluconazole.”

“We also worry about the anticoagulant warfarin. … This interaction is almost guaranteed.” Decreasing the warfarin dose might help, but “you almost always need to move to another antifungal.”

Three CYP450 enzymes metabolize voriconazole extensively. Two have genetic polymorphisms that make interactions more likely in certain populations. For example, a CYP2C19 polymorphism is present in 2%-5% of whites, 12%-23% of Asians, and 38%-79% of South Pacific populations.

Drugs that affect voriconazole include phenytoin, rifampin, and rifabutin. Other potential interactions include carbamazepine, protease inhibitors, nonnucleoside reverse transcriptase inhibitors, benzodiazepines, and statins.

“How do we get around this? There are drugs we just don't use with voriconazole, such as rifampin or rifabutin,” Dr. Gubbins said. He also suggested increasing the voriconazole dosage cautiously with phenytoin and monitoring patients taking warfarin closely.

MIAMI — The echinocandin antifungal agents appear to have little significant toxicity and may ultimately prove to be safer than the azoles or amphotericin B in terms of potential interactions, according to Paul O. Gubbins, Pharm.D.

“Echinocandins are an exciting new class. To date, there are few significant drug-drug interactions,” Dr. Gubbins said at a meeting on fungal infections sponsored by Imedex.

The echinocandin caspofungin (Cancidas) has “no significant interaction” with cytochrome P-450 (CYP450) metabolism or P-glycoprotein, according to product labeling. The most abundant enzyme in the CYP450 system, CYP3A4, metabolizes about 50%-60% of all medicines.

In addition, the recently approved echinocandin micafungin (see accompanying story) is not a substrate or inhibitor for P-glycoprotein, a transmembrane efflux pump in the liver, intestine, kidneys, and blood-brain barrier.

With a lower potential for interactions, the echinocandins may be ideal for combination therapy, said Dr. Gubbins, chair of the department of pharmacy practice, University of Arkansas, Little Rock.

Toxicity is another important consideration, and it can relate to drug interactions. Traditional formulations of amphotericin B have renal toxicity that can produce additive drug interactions. “We're all familiar with the toxicities of amphotericin B. They are subtle and, in most cases, unavoidable. Consider renal-sparing alternatives” such as lipid amphotericin B or caspofungin, he suggested.

When prescribing traditional amphotericin B, monitor serum levels of drugs that have a narrow therapeutic index and are eliminated by the kidneys. Examples include aminoglycosides and 5-flucytosine.

Physicians are much more aware of drug interactions now than they used to be, and not just for antifungals, but for all drug classes, Dr. Gubbins said in response to a meeting attendee's question.

Some patients, such as organ transplant recipients, require closer monitoring. They often use drugs they cannot avoid, such as immunosuppressants, which increase the risk of fungal infections, he added.

The azoles have a complicated set of interactions. They can interact through multiple mechanisms, including CYP450 metabolism, gastric pH-dependent effects, and P-glycoprotein activity. “Interactions can be managed with alternative drugs in the affected class or by switching agents,” Dr. Gubbins said.

Itraconazole leads the azole class in terms of p otential interactions. The antifungal interacts through the CYP450 system with statins, especially lovastatin, simvastatin, and atorvastatin (Lipitor), and this can lead to skeletal muscle toxicity. Other affected agents include benzodiazepines, anxiolytics, immunosuppressants, and corticosteroids. With corticosteroids, he said, “The key is, it doesn't matter if you give these orally or IV, or if they're inhaled, you can get interactions.”

Itraconazole can also have significant pH interactions. Dissolution depends on gastric pH, meal composition, and gastric emptying. Dr. Gubbins suggested that patients take the tablets with a high-fat meal that is dense in calories in order to slow gastric emptying or with a meal that contains enough protein to buffer the stomach contents. Other techniques for reducing pH interactions include spacing the administration of tablets, considering itraconazole oral solution, or switching to another agent. P-glycoprotein interactions are significant only for itraconazole, not for voriconazole (Vfend), or fluconazole, Dr. Gubbins said.

Although several agents lower serum levels of itraconazole, including phenytoin, phenobarbital, rifampin, and rifabutin (Mycobutin), “remember that itraconazole affects other medications more than other medications affect itraconazole,” he said. “The ones we're worried about are the ones with a narrow therapeutic index, such as digoxin.”

Fluconazole affects more CYP450 enzymes than does itraconazole. “It's a whole different ball game,” Dr. Gubbins said. Interactions depend largely on fluconazole concentration and are typically seen with doses greater than 200 mg.

Of particular concern are interactions between fluconazole and phenytoin or warfarin. “With phenytoin, if you do not see a response, it could be that [phenytoin] is inhibiting fluconazole.”

“We also worry about the anticoagulant warfarin. … This interaction is almost guaranteed.” Decreasing the warfarin dose might help, but “you almost always need to move to another antifungal.”

Three CYP450 enzymes metabolize voriconazole extensively. Two have genetic polymorphisms that make interactions more likely in certain populations. For example, a CYP2C19 polymorphism is present in 2%-5% of whites, 12%-23% of Asians, and 38%-79% of South Pacific populations.

Drugs that affect voriconazole include phenytoin, rifampin, and rifabutin. Other potential interactions include carbamazepine, protease inhibitors, nonnucleoside reverse transcriptase inhibitors, benzodiazepines, and statins.

“How do we get around this? There are drugs we just don't use with voriconazole, such as rifampin or rifabutin,” Dr. Gubbins said. He also suggested increasing the voriconazole dosage cautiously with phenytoin and monitoring patients taking warfarin closely.

SAN JUAN, P.R. – Just as with major depressive disorder, bipolar disorder, and schizophrenia, substance use disorders occur at a high rate in patients with psychotic major depressive disorder, according to a study presented at the annual meeting of the American Academy of Addiction Psychiatry.

For that reason, it is very important to assess those patients who have psychotic major depressive disorder (PMDD) for any co-occurring substance use disorders, John D. Matthews, M.D., said in a follow-up interview to his poster presentation.

Over the last 20 years, more evidence has emerged to suggest that major depressive disorder with psychotic features is a separate disorder and not just a more severe form of major depressive disorder, as it was previously considered.

It has a lot of symptoms in common with major depressive disorder, but with PMDD, there is also delusional thinking, hallucinations, or both, he said.

About one-quarter to one-third of the people who enter hospitals or programs because of major depressive disorder also have psychotic symptoms, he noted.

“It's actually as common as schizophrenia or bipolar disorder–about 1% of the general population,” said Dr. Matthews, who is director of inpatient research and training for the depression and clinical research program at Massachusetts General Hospital in Boston.

Dr. Matthews and his colleagues studied 52 inpatients and outpatients with PMDD to determine predictors for substance use disorders. They assessed severity of depression, number of depressive episodes, family history of depression, gender, age, and total number of Axis I diagnoses. The mean age of participants was 36 years, and 58% were women.

Family history of depression significantly predicted who would develop substance use disorder in this population, according to a logistic regression analysis.

“What we didn't predict was that the total number of Axis I diagnoses was a negative predictor,” Dr. Matthews said. “I don't have a good explanation for that.”

Together, these two predictors achieved an 84% correct classification for substance use disorder among people with PMDD.

Assessment of comorbidity was another aim of the study. “One thing missing in understanding the illness is what are the comorbid disorders, such as panic disorder or bipolar disorder. We know addictions frequently occur with those as well,” he said.

The researchers found that 17% of participants met criteria for a lifetime alcohol use disorder. In addition, 38% met criteria for a lifetime substance use disorder.

“We probably underestimated the number because they were involved in pharmacologic trials, and we had excluded those with a 6-month or less history of substance use disorder,” Dr. Matthews explained.

The substance use assessment was a secondary, ad hoc analysis of a pharmacologic intervention trial.

A prospective study is planned to assess substance use disorders in patients with PMDD without restricting the exclusion criteria.

SAN JUAN, P.R. – Just as with major depressive disorder, bipolar disorder, and schizophrenia, substance use disorders occur at a high rate in patients with psychotic major depressive disorder, according to a study presented at the annual meeting of the American Academy of Addiction Psychiatry.

For that reason, it is very important to assess those patients who have psychotic major depressive disorder (PMDD) for any co-occurring substance use disorders, John D. Matthews, M.D., said in a follow-up interview to his poster presentation.

Over the last 20 years, more evidence has emerged to suggest that major depressive disorder with psychotic features is a separate disorder and not just a more severe form of major depressive disorder, as it was previously considered.

It has a lot of symptoms in common with major depressive disorder, but with PMDD, there is also delusional thinking, hallucinations, or both, he said.

About one-quarter to one-third of the people who enter hospitals or programs because of major depressive disorder also have psychotic symptoms, he noted.

“It's actually as common as schizophrenia or bipolar disorder–about 1% of the general population,” said Dr. Matthews, who is director of inpatient research and training for the depression and clinical research program at Massachusetts General Hospital in Boston.

Dr. Matthews and his colleagues studied 52 inpatients and outpatients with PMDD to determine predictors for substance use disorders. They assessed severity of depression, number of depressive episodes, family history of depression, gender, age, and total number of Axis I diagnoses. The mean age of participants was 36 years, and 58% were women.

Family history of depression significantly predicted who would develop substance use disorder in this population, according to a logistic regression analysis.

“What we didn't predict was that the total number of Axis I diagnoses was a negative predictor,” Dr. Matthews said. “I don't have a good explanation for that.”

Together, these two predictors achieved an 84% correct classification for substance use disorder among people with PMDD.

Assessment of comorbidity was another aim of the study. “One thing missing in understanding the illness is what are the comorbid disorders, such as panic disorder or bipolar disorder. We know addictions frequently occur with those as well,” he said.

The researchers found that 17% of participants met criteria for a lifetime alcohol use disorder. In addition, 38% met criteria for a lifetime substance use disorder.

“We probably underestimated the number because they were involved in pharmacologic trials, and we had excluded those with a 6-month or less history of substance use disorder,” Dr. Matthews explained.

The substance use assessment was a secondary, ad hoc analysis of a pharmacologic intervention trial.

A prospective study is planned to assess substance use disorders in patients with PMDD without restricting the exclusion criteria.

SAN JUAN, P.R. – Just as with major depressive disorder, bipolar disorder, and schizophrenia, substance use disorders occur at a high rate in patients with psychotic major depressive disorder, according to a study presented at the annual meeting of the American Academy of Addiction Psychiatry.

For that reason, it is very important to assess those patients who have psychotic major depressive disorder (PMDD) for any co-occurring substance use disorders, John D. Matthews, M.D., said in a follow-up interview to his poster presentation.

Over the last 20 years, more evidence has emerged to suggest that major depressive disorder with psychotic features is a separate disorder and not just a more severe form of major depressive disorder, as it was previously considered.

It has a lot of symptoms in common with major depressive disorder, but with PMDD, there is also delusional thinking, hallucinations, or both, he said.

About one-quarter to one-third of the people who enter hospitals or programs because of major depressive disorder also have psychotic symptoms, he noted.

“It's actually as common as schizophrenia or bipolar disorder–about 1% of the general population,” said Dr. Matthews, who is director of inpatient research and training for the depression and clinical research program at Massachusetts General Hospital in Boston.

Dr. Matthews and his colleagues studied 52 inpatients and outpatients with PMDD to determine predictors for substance use disorders. They assessed severity of depression, number of depressive episodes, family history of depression, gender, age, and total number of Axis I diagnoses. The mean age of participants was 36 years, and 58% were women.

Family history of depression significantly predicted who would develop substance use disorder in this population, according to a logistic regression analysis.

“What we didn't predict was that the total number of Axis I diagnoses was a negative predictor,” Dr. Matthews said. “I don't have a good explanation for that.”

Together, these two predictors achieved an 84% correct classification for substance use disorder among people with PMDD.

Assessment of comorbidity was another aim of the study. “One thing missing in understanding the illness is what are the comorbid disorders, such as panic disorder or bipolar disorder. We know addictions frequently occur with those as well,” he said.

The researchers found that 17% of participants met criteria for a lifetime alcohol use disorder. In addition, 38% met criteria for a lifetime substance use disorder.

“We probably underestimated the number because they were involved in pharmacologic trials, and we had excluded those with a 6-month or less history of substance use disorder,” Dr. Matthews explained.

The substance use assessment was a secondary, ad hoc analysis of a pharmacologic intervention trial.

A prospective study is planned to assess substance use disorders in patients with PMDD without restricting the exclusion criteria.

SAN JUAN, P.R. – Depression was not significantly associated with heroin or cocaine use for methadone maintenance patients infected with hepatitis C, according to a study presented at the annual meeting of the American Academy of Addiction Psychiatry.

“Depression has been associated with increased substance use in some previous studies of drug users, but patients with hepatitis C infection may be somewhat different,” Steven L. Batki, M.D., said in an interview. Neuropsychiatric effects of the disease itself are a possible explanation.

“The bottom line is that in our sample, past or current depression was not significantly correlated with substance use over the past year,” he said.

The only significant association noted in the study was lower alcohol use in the previous 12 months for participants who met criteria for current major depression or who reported a history of depression.

Patients with substance use disorders are a difficult population for whom to provide hepatitis C treatment. “Substance abuse is often a barrier to access to medical care for hepatitis C. Better treatment for mental disorders in patients with substance use problems would likely increase access and adherence to hepatitis C treatment,” said Dr. Batki, professor of psychiatry at the State University of New York, Syracuse, where he is also director of the Veterans Affairs Center for Integrated Healthcare.

About 80% of injection drug users in the Syracuse area are infected with the hepatitis C virus. The 82 patients interviewed for the study in 2001 and 2003 in central New York reported “considerable recent substance use,” Dr. Batki said.

More than 60% of hepatitis C patients in methadone treatment reported heroin and/or cocaine use during the previous year, and more than 50% reported alcohol use. In addition, nearly 50% met DSM-IV diagnostic criteria for a major depressive disorder.

The mean age of study participants was 42 years: 62% of participants were male, and 62% were white. A total of 72% reported mental health problems. At the time of the survey, 55% were being treated for depression, and 55% had a Beck Depression Inventory score greater than 15. In addition, 66% reported a history of depression, including 31% who had been hospitalized for depression at some point. The National Institute on Drug Abuse funded the study.

Methadone patients come to treatment for months or years but often do not have consistent medical or psychiatric care. Substance users have often had hepatitis C for many years and therefore are at high risk for long-term morbidity from infection, cirrhosis, and liver failure. “When you find hepatitis C infected patients in a substance abuse program, these are people in their 40s, usually infected for 20 years or more,” he said.

Historically, patients with substance use and psychiatric disorders were systematically barred from hepatitis C treatment, Dr. Batki said.

Although 2002 guidelines from a National Institutes of Health Consensus Development Conference removed the strict rules against offering hepatitis C treatment to these patients, “there has not yet been any widespread change in practice,” he said.

“My concern, as with HIV and tuberculosis, is that too little is being done to bring the medical treatment to where the patients are,” Dr. Batki said.

With that in mind, he is now performing a National Institute on Drug Abuse-funded randomized controlled trial to see whether hepatitis C treatment offered on site in methadone programs improves outcomes compared with routine care in community GI clinics.

The study also seeks to assess the sustained virologic response after initiation of hepatitis C treatment and to follow the development of any neuropsychiatric symptoms before, during, and after treatment.

SAN JUAN, P.R. – Depression was not significantly associated with heroin or cocaine use for methadone maintenance patients infected with hepatitis C, according to a study presented at the annual meeting of the American Academy of Addiction Psychiatry.

“Depression has been associated with increased substance use in some previous studies of drug users, but patients with hepatitis C infection may be somewhat different,” Steven L. Batki, M.D., said in an interview. Neuropsychiatric effects of the disease itself are a possible explanation.

“The bottom line is that in our sample, past or current depression was not significantly correlated with substance use over the past year,” he said.

The only significant association noted in the study was lower alcohol use in the previous 12 months for participants who met criteria for current major depression or who reported a history of depression.

Patients with substance use disorders are a difficult population for whom to provide hepatitis C treatment. “Substance abuse is often a barrier to access to medical care for hepatitis C. Better treatment for mental disorders in patients with substance use problems would likely increase access and adherence to hepatitis C treatment,” said Dr. Batki, professor of psychiatry at the State University of New York, Syracuse, where he is also director of the Veterans Affairs Center for Integrated Healthcare.

About 80% of injection drug users in the Syracuse area are infected with the hepatitis C virus. The 82 patients interviewed for the study in 2001 and 2003 in central New York reported “considerable recent substance use,” Dr. Batki said.

More than 60% of hepatitis C patients in methadone treatment reported heroin and/or cocaine use during the previous year, and more than 50% reported alcohol use. In addition, nearly 50% met DSM-IV diagnostic criteria for a major depressive disorder.

The mean age of study participants was 42 years: 62% of participants were male, and 62% were white. A total of 72% reported mental health problems. At the time of the survey, 55% were being treated for depression, and 55% had a Beck Depression Inventory score greater than 15. In addition, 66% reported a history of depression, including 31% who had been hospitalized for depression at some point. The National Institute on Drug Abuse funded the study.

Methadone patients come to treatment for months or years but often do not have consistent medical or psychiatric care. Substance users have often had hepatitis C for many years and therefore are at high risk for long-term morbidity from infection, cirrhosis, and liver failure. “When you find hepatitis C infected patients in a substance abuse program, these are people in their 40s, usually infected for 20 years or more,” he said.

Historically, patients with substance use and psychiatric disorders were systematically barred from hepatitis C treatment, Dr. Batki said.

Although 2002 guidelines from a National Institutes of Health Consensus Development Conference removed the strict rules against offering hepatitis C treatment to these patients, “there has not yet been any widespread change in practice,” he said.

“My concern, as with HIV and tuberculosis, is that too little is being done to bring the medical treatment to where the patients are,” Dr. Batki said.

With that in mind, he is now performing a National Institute on Drug Abuse-funded randomized controlled trial to see whether hepatitis C treatment offered on site in methadone programs improves outcomes compared with routine care in community GI clinics.

The study also seeks to assess the sustained virologic response after initiation of hepatitis C treatment and to follow the development of any neuropsychiatric symptoms before, during, and after treatment.

SAN JUAN, P.R. – Depression was not significantly associated with heroin or cocaine use for methadone maintenance patients infected with hepatitis C, according to a study presented at the annual meeting of the American Academy of Addiction Psychiatry.

“Depression has been associated with increased substance use in some previous studies of drug users, but patients with hepatitis C infection may be somewhat different,” Steven L. Batki, M.D., said in an interview. Neuropsychiatric effects of the disease itself are a possible explanation.

“The bottom line is that in our sample, past or current depression was not significantly correlated with substance use over the past year,” he said.

The only significant association noted in the study was lower alcohol use in the previous 12 months for participants who met criteria for current major depression or who reported a history of depression.

Patients with substance use disorders are a difficult population for whom to provide hepatitis C treatment. “Substance abuse is often a barrier to access to medical care for hepatitis C. Better treatment for mental disorders in patients with substance use problems would likely increase access and adherence to hepatitis C treatment,” said Dr. Batki, professor of psychiatry at the State University of New York, Syracuse, where he is also director of the Veterans Affairs Center for Integrated Healthcare.

About 80% of injection drug users in the Syracuse area are infected with the hepatitis C virus. The 82 patients interviewed for the study in 2001 and 2003 in central New York reported “considerable recent substance use,” Dr. Batki said.

More than 60% of hepatitis C patients in methadone treatment reported heroin and/or cocaine use during the previous year, and more than 50% reported alcohol use. In addition, nearly 50% met DSM-IV diagnostic criteria for a major depressive disorder.

The mean age of study participants was 42 years: 62% of participants were male, and 62% were white. A total of 72% reported mental health problems. At the time of the survey, 55% were being treated for depression, and 55% had a Beck Depression Inventory score greater than 15. In addition, 66% reported a history of depression, including 31% who had been hospitalized for depression at some point. The National Institute on Drug Abuse funded the study.

Methadone patients come to treatment for months or years but often do not have consistent medical or psychiatric care. Substance users have often had hepatitis C for many years and therefore are at high risk for long-term morbidity from infection, cirrhosis, and liver failure. “When you find hepatitis C infected patients in a substance abuse program, these are people in their 40s, usually infected for 20 years or more,” he said.

Historically, patients with substance use and psychiatric disorders were systematically barred from hepatitis C treatment, Dr. Batki said.

Although 2002 guidelines from a National Institutes of Health Consensus Development Conference removed the strict rules against offering hepatitis C treatment to these patients, “there has not yet been any widespread change in practice,” he said.

“My concern, as with HIV and tuberculosis, is that too little is being done to bring the medical treatment to where the patients are,” Dr. Batki said.

With that in mind, he is now performing a National Institute on Drug Abuse-funded randomized controlled trial to see whether hepatitis C treatment offered on site in methadone programs improves outcomes compared with routine care in community GI clinics.

The study also seeks to assess the sustained virologic response after initiation of hepatitis C treatment and to follow the development of any neuropsychiatric symptoms before, during, and after treatment.

MIAMI BEACH — Modern-day hair transplantation yields high patient satisfaction and a low risk of side effects, according to a presentation at a symposium sponsored by the Florida Society of Dermatology and Dermatologic Surgery.

Dermatologists who offer hair transplantation must battle the legacy of poor techniques and suboptimal outcomes from previous techniques. With more advances in technology, donor hair density is the only limiting factor, said Marc R. Avram, M.D., of the department of dermatology, Weill Cornell Medical Center, New York.

Even though consistent, natural-looking results are now the rule rather than the exception, practical tips can help optimize outcomes. Dr. Avram recommends using polarized light with magnification for both donor and recipient zones. Other keys to success include thorough staff training and good office ergonomics because the work is labor intensive. Dr. Avram said it takes three to five assistants 40-60 minutes to create 1,000-1,500 follicular grafts. Each graft unit consists of one to four hair follicles.

Physicians employ elliptical donor harvesting for more than 95% of patients. An elliptical donor strip of hair is taken from the back of the scalp. The width of the ellipse should be no greater than 1 cm and should be longer rather than wider, Dr. Avram said. Exercise care when working on the area behind the ears and below the occipital protuberance because of higher risk of broad or hypertrophy scarring. Place the blade into subcutaneous tissue and check the angle of the blade every 2-3 cm to monitor transaction of hair follicles; the angle of hair follicles can change across the back of the scalp, he added. Undermine the graft only if necessary.

Less common is 1.25-1.5 mm punch harvesting. Fewer than 5% of patients are potential candidates. People with limited hair loss in the recipient site (from a trauma or scar) or those with limited donor tissue because of a history of multiple surgeries are typical candidates for this technique.

Patients can resume normal activities immediately after the procedure but should avoid heavy exercise for 1 week. Patients are instructed to wear an overnight dressing and take oral antibiotics for 5 days. Dr. Avram also prescribes Tylenol 3, one to two tablets every 4-6 hours as needed and instructs patients to call if pain or discomfort persists beyond the first night. He also typically prescribes prednisone 40 mg to be taken for 3 consecutive days.

Special considerations for women undergoing hair transplantation include an increased risk of telogen effluvium and a more unpredictable donor region. All three hairlines—the frontal, temporal, and posterior—generally remain intact in women. So the goal of hair transplantation in this population is to increase hair density within these stable hairlines.

The future of hair transplantation will feature improved instrumentation, robotics, and cloning, Dr. Avram said. For example, lasers will be able to separate one to three hair grafts with zero transection. Robotics may assist implantation. And if hair cloning becomes a reality, it will alleviate the limiting factor of donor hair density.

MIAMI BEACH — Modern-day hair transplantation yields high patient satisfaction and a low risk of side effects, according to a presentation at a symposium sponsored by the Florida Society of Dermatology and Dermatologic Surgery.

Dermatologists who offer hair transplantation must battle the legacy of poor techniques and suboptimal outcomes from previous techniques. With more advances in technology, donor hair density is the only limiting factor, said Marc R. Avram, M.D., of the department of dermatology, Weill Cornell Medical Center, New York.

Even though consistent, natural-looking results are now the rule rather than the exception, practical tips can help optimize outcomes. Dr. Avram recommends using polarized light with magnification for both donor and recipient zones. Other keys to success include thorough staff training and good office ergonomics because the work is labor intensive. Dr. Avram said it takes three to five assistants 40-60 minutes to create 1,000-1,500 follicular grafts. Each graft unit consists of one to four hair follicles.

Physicians employ elliptical donor harvesting for more than 95% of patients. An elliptical donor strip of hair is taken from the back of the scalp. The width of the ellipse should be no greater than 1 cm and should be longer rather than wider, Dr. Avram said. Exercise care when working on the area behind the ears and below the occipital protuberance because of higher risk of broad or hypertrophy scarring. Place the blade into subcutaneous tissue and check the angle of the blade every 2-3 cm to monitor transaction of hair follicles; the angle of hair follicles can change across the back of the scalp, he added. Undermine the graft only if necessary.

Less common is 1.25-1.5 mm punch harvesting. Fewer than 5% of patients are potential candidates. People with limited hair loss in the recipient site (from a trauma or scar) or those with limited donor tissue because of a history of multiple surgeries are typical candidates for this technique.

Patients can resume normal activities immediately after the procedure but should avoid heavy exercise for 1 week. Patients are instructed to wear an overnight dressing and take oral antibiotics for 5 days. Dr. Avram also prescribes Tylenol 3, one to two tablets every 4-6 hours as needed and instructs patients to call if pain or discomfort persists beyond the first night. He also typically prescribes prednisone 40 mg to be taken for 3 consecutive days.

Special considerations for women undergoing hair transplantation include an increased risk of telogen effluvium and a more unpredictable donor region. All three hairlines—the frontal, temporal, and posterior—generally remain intact in women. So the goal of hair transplantation in this population is to increase hair density within these stable hairlines.

The future of hair transplantation will feature improved instrumentation, robotics, and cloning, Dr. Avram said. For example, lasers will be able to separate one to three hair grafts with zero transection. Robotics may assist implantation. And if hair cloning becomes a reality, it will alleviate the limiting factor of donor hair density.

MIAMI BEACH — Modern-day hair transplantation yields high patient satisfaction and a low risk of side effects, according to a presentation at a symposium sponsored by the Florida Society of Dermatology and Dermatologic Surgery.

Dermatologists who offer hair transplantation must battle the legacy of poor techniques and suboptimal outcomes from previous techniques. With more advances in technology, donor hair density is the only limiting factor, said Marc R. Avram, M.D., of the department of dermatology, Weill Cornell Medical Center, New York.

Even though consistent, natural-looking results are now the rule rather than the exception, practical tips can help optimize outcomes. Dr. Avram recommends using polarized light with magnification for both donor and recipient zones. Other keys to success include thorough staff training and good office ergonomics because the work is labor intensive. Dr. Avram said it takes three to five assistants 40-60 minutes to create 1,000-1,500 follicular grafts. Each graft unit consists of one to four hair follicles.

Physicians employ elliptical donor harvesting for more than 95% of patients. An elliptical donor strip of hair is taken from the back of the scalp. The width of the ellipse should be no greater than 1 cm and should be longer rather than wider, Dr. Avram said. Exercise care when working on the area behind the ears and below the occipital protuberance because of higher risk of broad or hypertrophy scarring. Place the blade into subcutaneous tissue and check the angle of the blade every 2-3 cm to monitor transaction of hair follicles; the angle of hair follicles can change across the back of the scalp, he added. Undermine the graft only if necessary.

Less common is 1.25-1.5 mm punch harvesting. Fewer than 5% of patients are potential candidates. People with limited hair loss in the recipient site (from a trauma or scar) or those with limited donor tissue because of a history of multiple surgeries are typical candidates for this technique.

Patients can resume normal activities immediately after the procedure but should avoid heavy exercise for 1 week. Patients are instructed to wear an overnight dressing and take oral antibiotics for 5 days. Dr. Avram also prescribes Tylenol 3, one to two tablets every 4-6 hours as needed and instructs patients to call if pain or discomfort persists beyond the first night. He also typically prescribes prednisone 40 mg to be taken for 3 consecutive days.

Special considerations for women undergoing hair transplantation include an increased risk of telogen effluvium and a more unpredictable donor region. All three hairlines—the frontal, temporal, and posterior—generally remain intact in women. So the goal of hair transplantation in this population is to increase hair density within these stable hairlines.

The future of hair transplantation will feature improved instrumentation, robotics, and cloning, Dr. Avram said. For example, lasers will be able to separate one to three hair grafts with zero transection. Robotics may assist implantation. And if hair cloning becomes a reality, it will alleviate the limiting factor of donor hair density.