Diana Mahoney

MONTREAL — The potent respiratory fluoroquinolone moxifloxacin is as safe and effective as combination ampicillin/sulbactam therapy for the treatment of aspiration-associated pulmonary infections, Sebastian Ott, M.D., reported in a poster presentation at an international conference on community-acquired pneumonia.

To compare the efficacy, safety, and tolerability of moxifloxacin (Avelox) with that of ampicillin/sulbactam (Unasyn) for the treatment of aspiration pneumonia and primary lung abscess, Dr. Ott of the Helios Chest Hospital Heckeshorn in Berlin and his colleagues enrolled 139 patients diagnosed with either condition in a multicenter, open-label trial.

Nearly 65% of the patients in the study were diagnosed solely with aspiration pneumonia, and definite or presumptive pathogens were isolated in 45 subjects, he said.

Of the 139 patients, 96 were treated according to protocol: 48 were randomized to receive 400 mg of moxifloxacin given intravenously once daily followed by oral moxifloxacin for 7–14 days or until complete resolution of radiologic and clinical signs of infection, and 48 received 1.5–3.0 g of ampicillin/sulbactam intravenously twice daily followed by oral administration for the same duration.

At the end of treatment, the overall clinical response rate for both groups was 67%. In the moxifloxacin group, 59% of patients with aspiration pneumonia and 80% of those with primary lung abscess had responded to the antibiotic treatment.

Among those who received ampicillin/sulbactam, 64% of the aspiration pneumonia patients and 82% of the primary lung abscess patients responded to treatment.

Both of the regimens were well tolerated to a similar degree, “even after long-term administration,” Dr. Ott said. “The benefit of moxifloxacin is that its [once-daily] dosing is more convenient.”

The findings of this study provide clinicians with an important therapeutic option to add to their toolbox for treating aspiration-related pulmonary infections, which are rare but potentially life threatening.

MONTREAL — The potent respiratory fluoroquinolone moxifloxacin is as safe and effective as combination ampicillin/sulbactam therapy for the treatment of aspiration-associated pulmonary infections, Sebastian Ott, M.D., reported in a poster presentation at an international conference on community-acquired pneumonia.

To compare the efficacy, safety, and tolerability of moxifloxacin (Avelox) with that of ampicillin/sulbactam (Unasyn) for the treatment of aspiration pneumonia and primary lung abscess, Dr. Ott of the Helios Chest Hospital Heckeshorn in Berlin and his colleagues enrolled 139 patients diagnosed with either condition in a multicenter, open-label trial.

Nearly 65% of the patients in the study were diagnosed solely with aspiration pneumonia, and definite or presumptive pathogens were isolated in 45 subjects, he said.

Of the 139 patients, 96 were treated according to protocol: 48 were randomized to receive 400 mg of moxifloxacin given intravenously once daily followed by oral moxifloxacin for 7–14 days or until complete resolution of radiologic and clinical signs of infection, and 48 received 1.5–3.0 g of ampicillin/sulbactam intravenously twice daily followed by oral administration for the same duration.

At the end of treatment, the overall clinical response rate for both groups was 67%. In the moxifloxacin group, 59% of patients with aspiration pneumonia and 80% of those with primary lung abscess had responded to the antibiotic treatment.

Among those who received ampicillin/sulbactam, 64% of the aspiration pneumonia patients and 82% of the primary lung abscess patients responded to treatment.

Both of the regimens were well tolerated to a similar degree, “even after long-term administration,” Dr. Ott said. “The benefit of moxifloxacin is that its [once-daily] dosing is more convenient.”

The findings of this study provide clinicians with an important therapeutic option to add to their toolbox for treating aspiration-related pulmonary infections, which are rare but potentially life threatening.

MONTREAL — The potent respiratory fluoroquinolone moxifloxacin is as safe and effective as combination ampicillin/sulbactam therapy for the treatment of aspiration-associated pulmonary infections, Sebastian Ott, M.D., reported in a poster presentation at an international conference on community-acquired pneumonia.

To compare the efficacy, safety, and tolerability of moxifloxacin (Avelox) with that of ampicillin/sulbactam (Unasyn) for the treatment of aspiration pneumonia and primary lung abscess, Dr. Ott of the Helios Chest Hospital Heckeshorn in Berlin and his colleagues enrolled 139 patients diagnosed with either condition in a multicenter, open-label trial.

Nearly 65% of the patients in the study were diagnosed solely with aspiration pneumonia, and definite or presumptive pathogens were isolated in 45 subjects, he said.

Of the 139 patients, 96 were treated according to protocol: 48 were randomized to receive 400 mg of moxifloxacin given intravenously once daily followed by oral moxifloxacin for 7–14 days or until complete resolution of radiologic and clinical signs of infection, and 48 received 1.5–3.0 g of ampicillin/sulbactam intravenously twice daily followed by oral administration for the same duration.

At the end of treatment, the overall clinical response rate for both groups was 67%. In the moxifloxacin group, 59% of patients with aspiration pneumonia and 80% of those with primary lung abscess had responded to the antibiotic treatment.

Among those who received ampicillin/sulbactam, 64% of the aspiration pneumonia patients and 82% of the primary lung abscess patients responded to treatment.

Both of the regimens were well tolerated to a similar degree, “even after long-term administration,” Dr. Ott said. “The benefit of moxifloxacin is that its [once-daily] dosing is more convenient.”

The findings of this study provide clinicians with an important therapeutic option to add to their toolbox for treating aspiration-related pulmonary infections, which are rare but potentially life threatening.

MONTREAL — In vitro pneumococcal resistance continues to have a substantial role in guiding antibiotic choices and disease management plans for patients with community-acquired pneumonia, according to Michael S. Niederman, M.D.

Many surveillance studies have revealed an increasing global prevalence of in vitro drug resistance among pneumococcal isolates obtained from patients with community-acquired pneumonia. Updated treatment guidelines reflect these findings by stressing the need for clinicians to keep in mind local antibiotic resistance patterns as well as patient risk factors for infection with drug-resistant pathogens, Dr. Niederman said at the Second International Conference on Community Acquired Pneumonia.

“Drug-resistant pneumococcus is more likely in certain at-risk populations, including people older than 65 years and those with immune suppression, exposure to a child in daycare, or a history of alcoholism, multiple medical comorbidities, or therapy with a β-lactam in the past 3 months,” he said.

To minimize the opportunity for clinical failure of community-acquired pneumonia therapy related to antibiotic resistance, which can occur with any drug class, clinicians should be prepared to modify management approaches accordingly, stressed Dr. Niederman of the State University of New York at Stony Brook. One such consideration is to use focused instead of broad-spectrum therapy as appropriate, he said.

“Broad-spectrum agents such as quinolones are frequently used in situations where they are both not indicated and unnecessary,” he said. For example, in one study of 100 consecutive emergency department patients who were discharged on quinolone therapy, 81 of the patients had inappropriate indications for the drug, and of the 19 in whom quinolone therapy was appropriate, only 1 was given the correct dose for the correct duration, he said (Arch. Intern. Med. 2003;163:601–5).

“This is the type of behavior that drives more resistance and has to be avoided,” Dr. Niederman added.

Because recent prior therapy with β-lactams, macrolides, or quinolones predicts subsequent pneumococcal resistance to the agent that was used, “it is imperative that clinicians take a history of recent antibiotic usage and be prepared to choose an agent that differs from what was used previously,” Dr. Niederman said. “This form of patient-specific antibiotic rotation only works if we have choices, which requires an understanding of the acceptable options for therapy.”

For example, studies have shown that penicillin resistance probably has therapeutic significance only when MIC values are at least 4 mg/L.

“If β-lactam resistant pneumococcus is suspected, ceftriaxone [Rocephin] may be a reliable choice, while the cephalosporin cefuroxime [Ceftin] may be associated with increased mortality if used in the presence of in vitro resistance to this agent,” he said.

In general, when managing patients at risk for drug resistance, “clinicians should choose a highly active antipneumococcal agent to minimize selection pressure for more organisms emerging with higher levels of resistance,” Dr. Niederman said.

Patients not likely to have resistance should receive focused therapy with macrolides or ketolides, “reserving more potent agents for the appropriate setting,” he added.

Ketolide use in particular “can improve the management of community acquired pneumonia in this era of pneumococcal antibiotic resistance by adding another choice to the heterogeneity of options,” he said.

Studies have shown that telithromycin (Ketek)—the first ketolide available for clinical use—is an effective outpatient treatment for mild to moderate community-acquired pneumonia, even in older patients, those with higher pneumonia severity index scores, and those with bacteremia.

“The agent's rapid bactericidal effects appear to make short treatment durations feasible, and its mechanisms of action may avoid the induction of resistance, while maintaining good intrinsic activity against pneumococci, including those that are macrolide resistant,” Dr. Niederman said.

MONTREAL — In vitro pneumococcal resistance continues to have a substantial role in guiding antibiotic choices and disease management plans for patients with community-acquired pneumonia, according to Michael S. Niederman, M.D.

Many surveillance studies have revealed an increasing global prevalence of in vitro drug resistance among pneumococcal isolates obtained from patients with community-acquired pneumonia. Updated treatment guidelines reflect these findings by stressing the need for clinicians to keep in mind local antibiotic resistance patterns as well as patient risk factors for infection with drug-resistant pathogens, Dr. Niederman said at the Second International Conference on Community Acquired Pneumonia.

“Drug-resistant pneumococcus is more likely in certain at-risk populations, including people older than 65 years and those with immune suppression, exposure to a child in daycare, or a history of alcoholism, multiple medical comorbidities, or therapy with a β-lactam in the past 3 months,” he said.

To minimize the opportunity for clinical failure of community-acquired pneumonia therapy related to antibiotic resistance, which can occur with any drug class, clinicians should be prepared to modify management approaches accordingly, stressed Dr. Niederman of the State University of New York at Stony Brook. One such consideration is to use focused instead of broad-spectrum therapy as appropriate, he said.

“Broad-spectrum agents such as quinolones are frequently used in situations where they are both not indicated and unnecessary,” he said. For example, in one study of 100 consecutive emergency department patients who were discharged on quinolone therapy, 81 of the patients had inappropriate indications for the drug, and of the 19 in whom quinolone therapy was appropriate, only 1 was given the correct dose for the correct duration, he said (Arch. Intern. Med. 2003;163:601–5).

“This is the type of behavior that drives more resistance and has to be avoided,” Dr. Niederman added.

Because recent prior therapy with β-lactams, macrolides, or quinolones predicts subsequent pneumococcal resistance to the agent that was used, “it is imperative that clinicians take a history of recent antibiotic usage and be prepared to choose an agent that differs from what was used previously,” Dr. Niederman said. “This form of patient-specific antibiotic rotation only works if we have choices, which requires an understanding of the acceptable options for therapy.”

For example, studies have shown that penicillin resistance probably has therapeutic significance only when MIC values are at least 4 mg/L.

“If β-lactam resistant pneumococcus is suspected, ceftriaxone [Rocephin] may be a reliable choice, while the cephalosporin cefuroxime [Ceftin] may be associated with increased mortality if used in the presence of in vitro resistance to this agent,” he said.

In general, when managing patients at risk for drug resistance, “clinicians should choose a highly active antipneumococcal agent to minimize selection pressure for more organisms emerging with higher levels of resistance,” Dr. Niederman said.

Patients not likely to have resistance should receive focused therapy with macrolides or ketolides, “reserving more potent agents for the appropriate setting,” he added.

Ketolide use in particular “can improve the management of community acquired pneumonia in this era of pneumococcal antibiotic resistance by adding another choice to the heterogeneity of options,” he said.

Studies have shown that telithromycin (Ketek)—the first ketolide available for clinical use—is an effective outpatient treatment for mild to moderate community-acquired pneumonia, even in older patients, those with higher pneumonia severity index scores, and those with bacteremia.

“The agent's rapid bactericidal effects appear to make short treatment durations feasible, and its mechanisms of action may avoid the induction of resistance, while maintaining good intrinsic activity against pneumococci, including those that are macrolide resistant,” Dr. Niederman said.

MONTREAL — In vitro pneumococcal resistance continues to have a substantial role in guiding antibiotic choices and disease management plans for patients with community-acquired pneumonia, according to Michael S. Niederman, M.D.

Many surveillance studies have revealed an increasing global prevalence of in vitro drug resistance among pneumococcal isolates obtained from patients with community-acquired pneumonia. Updated treatment guidelines reflect these findings by stressing the need for clinicians to keep in mind local antibiotic resistance patterns as well as patient risk factors for infection with drug-resistant pathogens, Dr. Niederman said at the Second International Conference on Community Acquired Pneumonia.

“Drug-resistant pneumococcus is more likely in certain at-risk populations, including people older than 65 years and those with immune suppression, exposure to a child in daycare, or a history of alcoholism, multiple medical comorbidities, or therapy with a β-lactam in the past 3 months,” he said.

To minimize the opportunity for clinical failure of community-acquired pneumonia therapy related to antibiotic resistance, which can occur with any drug class, clinicians should be prepared to modify management approaches accordingly, stressed Dr. Niederman of the State University of New York at Stony Brook. One such consideration is to use focused instead of broad-spectrum therapy as appropriate, he said.

“Broad-spectrum agents such as quinolones are frequently used in situations where they are both not indicated and unnecessary,” he said. For example, in one study of 100 consecutive emergency department patients who were discharged on quinolone therapy, 81 of the patients had inappropriate indications for the drug, and of the 19 in whom quinolone therapy was appropriate, only 1 was given the correct dose for the correct duration, he said (Arch. Intern. Med. 2003;163:601–5).

“This is the type of behavior that drives more resistance and has to be avoided,” Dr. Niederman added.

Because recent prior therapy with β-lactams, macrolides, or quinolones predicts subsequent pneumococcal resistance to the agent that was used, “it is imperative that clinicians take a history of recent antibiotic usage and be prepared to choose an agent that differs from what was used previously,” Dr. Niederman said. “This form of patient-specific antibiotic rotation only works if we have choices, which requires an understanding of the acceptable options for therapy.”

For example, studies have shown that penicillin resistance probably has therapeutic significance only when MIC values are at least 4 mg/L.

“If β-lactam resistant pneumococcus is suspected, ceftriaxone [Rocephin] may be a reliable choice, while the cephalosporin cefuroxime [Ceftin] may be associated with increased mortality if used in the presence of in vitro resistance to this agent,” he said.

In general, when managing patients at risk for drug resistance, “clinicians should choose a highly active antipneumococcal agent to minimize selection pressure for more organisms emerging with higher levels of resistance,” Dr. Niederman said.

Patients not likely to have resistance should receive focused therapy with macrolides or ketolides, “reserving more potent agents for the appropriate setting,” he added.

Ketolide use in particular “can improve the management of community acquired pneumonia in this era of pneumococcal antibiotic resistance by adding another choice to the heterogeneity of options,” he said.

Studies have shown that telithromycin (Ketek)—the first ketolide available for clinical use—is an effective outpatient treatment for mild to moderate community-acquired pneumonia, even in older patients, those with higher pneumonia severity index scores, and those with bacteremia.

“The agent's rapid bactericidal effects appear to make short treatment durations feasible, and its mechanisms of action may avoid the induction of resistance, while maintaining good intrinsic activity against pneumococci, including those that are macrolide resistant,” Dr. Niederman said.

MONTREAL — In vitro pneumococcal resistance continues to have a substantial role in guiding antibiotic choices and disease management plans for patients with community-acquired pneumonia, according to Michael S. Niederman, M.D.

Many surveillance studies have revealed an increasing global prevalence of in vitro drug resistance among pneumococcal isolates obtained from patients with community-acquired pneumonia. Updated treatment guidelines reflect these findings by stressing the need for clinicians to keep in mind local antibiotic resistance patterns as well as patient risk factors for infection with drug-resistant pathogens, Dr. Niederman said at the Second International Conference on Community Acquired Pneumonia.

“Drug-resistant pneumococcus is more likely in certain at-risk populations, including people older than 65 years and those with immune suppression, exposure to a child in day care, or a history of alcoholism, multiple medical comorbidities, or therapy with a β-lactam in the past 3 months,” he said.

To minimize the opportunity for clinical failure of community-acquired pneumonia therapy related to antibiotic resistance, which can occur with any drug class, clinicians should be prepared to modify management approaches accordingly, stressed Dr. Niederman of the State University of New York at Stony Brook. One such consideration is to use focused instead of broad-spectrum therapy as appropriate, he said.

“Broad-spectrum agents, such as quinolones, are frequently used in situations where they are both not indicated and unnecessary,” he said. For example, in one study of 100 consecutive emergency department patients who were discharged on quinolone therapy, 81 of the patients had inappropriate indications for the drug, and of the 19 in whom quinolone therapy was appropriate, only 1 was given the correct dose for the correct duration, he said (Arch. Intern. Med. 2003;163:601–5).

“This is the type of behavior that drives more resistance and has to be avoided,” Dr. Niederman added.

Because recent prior therapy with β-lactams, macrolides, or quinolones predicts subsequent pneumococcal resistance to the agent that was used, “it is imperative that clinicians take a history of recent antibiotic usage and be prepared to choose an agent that differs from what was used previously,” Dr. Niederman said. “This form of patient-specific antibiotic rotation only works if we have choices, which requires an understanding of the acceptable options for therapy.”

For example, studies have shown that penicillin resistance probably has therapeutic significance only when MIC values are at least 4 mg/L. “If β-lactam resistant pneumococcus is suspected, ceftriaxone [Rocephin] may be a reliable choice, while the cephalosporin cefuroxime [Ceftin] may be associated with increased mortality if used in the presence of in vitro resistance to this agent,” he said.

In general, when managing patients at risk for drug resistance, “clinicians should choose a highly active antipneumococcal agent to minimize selection pressure for more organisms emerging with higher levels of resistance,” Dr. Niederman said. Patients not likely to have resistance should receive focused therapy with macrolides or ketolides, “reserving more potent agents for the appropriate setting.”

Ketolide use in particular “can improve the management of community-acquired pneumonia in this era of pneumococcal antibiotic resistance by adding another choice to the heterogeneity of options,” he said.

Studies have shown that telithromycin (Ketek)—the first ketolide available for clinical use—is an effective outpatient treatment for mild to moderate community-acquired pneumonia, even in older patients, those with higher pneumonia severity index scores, and those with bacteremia.

“The agent's rapid bactericidal effects appear to make short treatment durations feasible, and its mechanisms of action may avoid the induction of resistance, while maintaining good intrinsic activity against pneumococci, including those that are macrolide resistant,” Dr. Niederman said.

MONTREAL — In vitro pneumococcal resistance continues to have a substantial role in guiding antibiotic choices and disease management plans for patients with community-acquired pneumonia, according to Michael S. Niederman, M.D.

Many surveillance studies have revealed an increasing global prevalence of in vitro drug resistance among pneumococcal isolates obtained from patients with community-acquired pneumonia. Updated treatment guidelines reflect these findings by stressing the need for clinicians to keep in mind local antibiotic resistance patterns as well as patient risk factors for infection with drug-resistant pathogens, Dr. Niederman said at the Second International Conference on Community Acquired Pneumonia.

“Drug-resistant pneumococcus is more likely in certain at-risk populations, including people older than 65 years and those with immune suppression, exposure to a child in day care, or a history of alcoholism, multiple medical comorbidities, or therapy with a β-lactam in the past 3 months,” he said.

To minimize the opportunity for clinical failure of community-acquired pneumonia therapy related to antibiotic resistance, which can occur with any drug class, clinicians should be prepared to modify management approaches accordingly, stressed Dr. Niederman of the State University of New York at Stony Brook. One such consideration is to use focused instead of broad-spectrum therapy as appropriate, he said.

“Broad-spectrum agents, such as quinolones, are frequently used in situations where they are both not indicated and unnecessary,” he said. For example, in one study of 100 consecutive emergency department patients who were discharged on quinolone therapy, 81 of the patients had inappropriate indications for the drug, and of the 19 in whom quinolone therapy was appropriate, only 1 was given the correct dose for the correct duration, he said (Arch. Intern. Med. 2003;163:601–5).

“This is the type of behavior that drives more resistance and has to be avoided,” Dr. Niederman added.

Because recent prior therapy with β-lactams, macrolides, or quinolones predicts subsequent pneumococcal resistance to the agent that was used, “it is imperative that clinicians take a history of recent antibiotic usage and be prepared to choose an agent that differs from what was used previously,” Dr. Niederman said. “This form of patient-specific antibiotic rotation only works if we have choices, which requires an understanding of the acceptable options for therapy.”

For example, studies have shown that penicillin resistance probably has therapeutic significance only when MIC values are at least 4 mg/L. “If β-lactam resistant pneumococcus is suspected, ceftriaxone [Rocephin] may be a reliable choice, while the cephalosporin cefuroxime [Ceftin] may be associated with increased mortality if used in the presence of in vitro resistance to this agent,” he said.

In general, when managing patients at risk for drug resistance, “clinicians should choose a highly active antipneumococcal agent to minimize selection pressure for more organisms emerging with higher levels of resistance,” Dr. Niederman said. Patients not likely to have resistance should receive focused therapy with macrolides or ketolides, “reserving more potent agents for the appropriate setting.”

Ketolide use in particular “can improve the management of community-acquired pneumonia in this era of pneumococcal antibiotic resistance by adding another choice to the heterogeneity of options,” he said.

Studies have shown that telithromycin (Ketek)—the first ketolide available for clinical use—is an effective outpatient treatment for mild to moderate community-acquired pneumonia, even in older patients, those with higher pneumonia severity index scores, and those with bacteremia.

“The agent's rapid bactericidal effects appear to make short treatment durations feasible, and its mechanisms of action may avoid the induction of resistance, while maintaining good intrinsic activity against pneumococci, including those that are macrolide resistant,” Dr. Niederman said.

MONTREAL — In vitro pneumococcal resistance continues to have a substantial role in guiding antibiotic choices and disease management plans for patients with community-acquired pneumonia, according to Michael S. Niederman, M.D.

Many surveillance studies have revealed an increasing global prevalence of in vitro drug resistance among pneumococcal isolates obtained from patients with community-acquired pneumonia. Updated treatment guidelines reflect these findings by stressing the need for clinicians to keep in mind local antibiotic resistance patterns as well as patient risk factors for infection with drug-resistant pathogens, Dr. Niederman said at the Second International Conference on Community Acquired Pneumonia.

“Drug-resistant pneumococcus is more likely in certain at-risk populations, including people older than 65 years and those with immune suppression, exposure to a child in day care, or a history of alcoholism, multiple medical comorbidities, or therapy with a β-lactam in the past 3 months,” he said.

To minimize the opportunity for clinical failure of community-acquired pneumonia therapy related to antibiotic resistance, which can occur with any drug class, clinicians should be prepared to modify management approaches accordingly, stressed Dr. Niederman of the State University of New York at Stony Brook. One such consideration is to use focused instead of broad-spectrum therapy as appropriate, he said.

“Broad-spectrum agents, such as quinolones, are frequently used in situations where they are both not indicated and unnecessary,” he said. For example, in one study of 100 consecutive emergency department patients who were discharged on quinolone therapy, 81 of the patients had inappropriate indications for the drug, and of the 19 in whom quinolone therapy was appropriate, only 1 was given the correct dose for the correct duration, he said (Arch. Intern. Med. 2003;163:601–5).

“This is the type of behavior that drives more resistance and has to be avoided,” Dr. Niederman added.

Because recent prior therapy with β-lactams, macrolides, or quinolones predicts subsequent pneumococcal resistance to the agent that was used, “it is imperative that clinicians take a history of recent antibiotic usage and be prepared to choose an agent that differs from what was used previously,” Dr. Niederman said. “This form of patient-specific antibiotic rotation only works if we have choices, which requires an understanding of the acceptable options for therapy.”

For example, studies have shown that penicillin resistance probably has therapeutic significance only when MIC values are at least 4 mg/L. “If β-lactam resistant pneumococcus is suspected, ceftriaxone [Rocephin] may be a reliable choice, while the cephalosporin cefuroxime [Ceftin] may be associated with increased mortality if used in the presence of in vitro resistance to this agent,” he said.

In general, when managing patients at risk for drug resistance, “clinicians should choose a highly active antipneumococcal agent to minimize selection pressure for more organisms emerging with higher levels of resistance,” Dr. Niederman said. Patients not likely to have resistance should receive focused therapy with macrolides or ketolides, “reserving more potent agents for the appropriate setting.”

Ketolide use in particular “can improve the management of community-acquired pneumonia in this era of pneumococcal antibiotic resistance by adding another choice to the heterogeneity of options,” he said.

Studies have shown that telithromycin (Ketek)—the first ketolide available for clinical use—is an effective outpatient treatment for mild to moderate community-acquired pneumonia, even in older patients, those with higher pneumonia severity index scores, and those with bacteremia.

“The agent's rapid bactericidal effects appear to make short treatment durations feasible, and its mechanisms of action may avoid the induction of resistance, while maintaining good intrinsic activity against pneumococci, including those that are macrolide resistant,” Dr. Niederman said.

LOS ANGELES — Maternal exposure to clomiphene was independently associated with spinal neural tube defects in a case-control study nested within a live-birth cohort, Yvonne Wu, M.D., reported.

Although several studies have examined the possibility of a link between the ovulation-stimulating drug and neural tube defects, the results to date have been mixed, Dr. Wu said in a presentation at the annual meeting of the Child Neurology Society.

Dr. Wu stressed that her study is too limited in size and scope to make definitive statements about the association. “The data linking infertility treatment and neural tube defects have been inconsistent, and our results do not really shift the balance yet,” she said. “Our study was an offshoot of an existing [investigation] of cerebral palsy and was not even designed to look at this question.”

Given the study's limitations, the findings should not impact clinical decision-making. Instead, they should be the impetus for larger, better-defined studies, she said.

In the current study, Dr. Wu and colleagues from the University of California, San Francisco, electronically reviewed the medical charts of 110,624 mothers and their full-term singleton infants born at Kaiser Permanente Northern California between 1994 and 1997 to identify history of infertility exposure and cases of neural tube defects of the spine. For the purposes of the study, infertility exposure was defined as evaluation at an infertility clinic within Kaiser Permanente, physician diagnosis of infertility, or infertility medication prescribed within 60 days of conception. Information on infertility medication and diagnosis was obtained from electronic databases.

Of the full cohort, 18 infants were diagnosed with neural tube defects, including 12 with spina bifida cystica, 4 with tethered cord syndrome associated with sacral lipoma, and 2 with dermal sinus tracts.

Using multivariate logistic regression analysis, the investigators compared the 18 case mothers with 1,610 randomly selected controls from the same cohort. The mothers of babies born with neural tube defects were more likely to be Hispanic, have had a history of infertility, and have been prescribed clomiphene within 60 days of conception. After adjusting for maternal age, ethnicity, gestational age, and birth weight, exposure to clomiphene was the only independent association with neural tube defects of the spine, according to Dr. Wu.

To authoritatively confirm or dismiss the association between clomiphene and neural tube defects, “we need studies that include comprehensive infertility data on all cases of neural tube defects in a population, including those that resulted in pregnancy termination,” she said.

A better understanding of the underlying pathogenesis of neural tube defects and the mechanism of action of clomiphene, both of which are poorly understood, could provide important insight into the possible association between the two as well, Dr. Wu concluded.

LOS ANGELES — Maternal exposure to clomiphene was independently associated with spinal neural tube defects in a case-control study nested within a live-birth cohort, Yvonne Wu, M.D., reported.

Although several studies have examined the possibility of a link between the ovulation-stimulating drug and neural tube defects, the results to date have been mixed, Dr. Wu said in a presentation at the annual meeting of the Child Neurology Society.

Dr. Wu stressed that her study is too limited in size and scope to make definitive statements about the association. “The data linking infertility treatment and neural tube defects have been inconsistent, and our results do not really shift the balance yet,” she said. “Our study was an offshoot of an existing [investigation] of cerebral palsy and was not even designed to look at this question.”

Given the study's limitations, the findings should not impact clinical decision-making. Instead, they should be the impetus for larger, better-defined studies, she said.

In the current study, Dr. Wu and colleagues from the University of California, San Francisco, electronically reviewed the medical charts of 110,624 mothers and their full-term singleton infants born at Kaiser Permanente Northern California between 1994 and 1997 to identify history of infertility exposure and cases of neural tube defects of the spine. For the purposes of the study, infertility exposure was defined as evaluation at an infertility clinic within Kaiser Permanente, physician diagnosis of infertility, or infertility medication prescribed within 60 days of conception. Information on infertility medication and diagnosis was obtained from electronic databases.

Of the full cohort, 18 infants were diagnosed with neural tube defects, including 12 with spina bifida cystica, 4 with tethered cord syndrome associated with sacral lipoma, and 2 with dermal sinus tracts.

Using multivariate logistic regression analysis, the investigators compared the 18 case mothers with 1,610 randomly selected controls from the same cohort. The mothers of babies born with neural tube defects were more likely to be Hispanic, have had a history of infertility, and have been prescribed clomiphene within 60 days of conception. After adjusting for maternal age, ethnicity, gestational age, and birth weight, exposure to clomiphene was the only independent association with neural tube defects of the spine, according to Dr. Wu.

To authoritatively confirm or dismiss the association between clomiphene and neural tube defects, “we need studies that include comprehensive infertility data on all cases of neural tube defects in a population, including those that resulted in pregnancy termination,” she said.

A better understanding of the underlying pathogenesis of neural tube defects and the mechanism of action of clomiphene, both of which are poorly understood, could provide important insight into the possible association between the two as well, Dr. Wu concluded.

LOS ANGELES — Maternal exposure to clomiphene was independently associated with spinal neural tube defects in a case-control study nested within a live-birth cohort, Yvonne Wu, M.D., reported.

Although several studies have examined the possibility of a link between the ovulation-stimulating drug and neural tube defects, the results to date have been mixed, Dr. Wu said in a presentation at the annual meeting of the Child Neurology Society.

Dr. Wu stressed that her study is too limited in size and scope to make definitive statements about the association. “The data linking infertility treatment and neural tube defects have been inconsistent, and our results do not really shift the balance yet,” she said. “Our study was an offshoot of an existing [investigation] of cerebral palsy and was not even designed to look at this question.”

Given the study's limitations, the findings should not impact clinical decision-making. Instead, they should be the impetus for larger, better-defined studies, she said.

In the current study, Dr. Wu and colleagues from the University of California, San Francisco, electronically reviewed the medical charts of 110,624 mothers and their full-term singleton infants born at Kaiser Permanente Northern California between 1994 and 1997 to identify history of infertility exposure and cases of neural tube defects of the spine. For the purposes of the study, infertility exposure was defined as evaluation at an infertility clinic within Kaiser Permanente, physician diagnosis of infertility, or infertility medication prescribed within 60 days of conception. Information on infertility medication and diagnosis was obtained from electronic databases.

Of the full cohort, 18 infants were diagnosed with neural tube defects, including 12 with spina bifida cystica, 4 with tethered cord syndrome associated with sacral lipoma, and 2 with dermal sinus tracts.

Using multivariate logistic regression analysis, the investigators compared the 18 case mothers with 1,610 randomly selected controls from the same cohort. The mothers of babies born with neural tube defects were more likely to be Hispanic, have had a history of infertility, and have been prescribed clomiphene within 60 days of conception. After adjusting for maternal age, ethnicity, gestational age, and birth weight, exposure to clomiphene was the only independent association with neural tube defects of the spine, according to Dr. Wu.

To authoritatively confirm or dismiss the association between clomiphene and neural tube defects, “we need studies that include comprehensive infertility data on all cases of neural tube defects in a population, including those that resulted in pregnancy termination,” she said.

A better understanding of the underlying pathogenesis of neural tube defects and the mechanism of action of clomiphene, both of which are poorly understood, could provide important insight into the possible association between the two as well, Dr. Wu concluded.

Adolescents who engage in sex and drug behaviors are at risk for future depression, reported Denise D. Hallfors, Ph.D., and her colleagues at the University of North Carolina at Chapel Hill.

In their study, the association existed among youth of both sexes, but adolescent girls appear to be especially vulnerable to subsequent depression risk.

Although previous studies have associated adolescent depression with sex and drug use, the current study is among the first to provide insight into the causal relationship between the risky behaviors and depression, the authors wrote.

The findings appear to reject the frequent hypothesis that adolescents use sex and drugs to self-medicate depression, Dr. Hallfors and her associates said.

Using data from the National Longitudinal Study of Adolescent Health (Add Health)—a nationally representative sample of more than 13,000 7th- to 11th-grade adolescents who were first interviewed in 1995 and reinterviewed in 1996—investigators examined whether gender-specific patterns of substance use and sexual behavior predicted depression or whether depression predicted the gender-specific patterns of these risky behaviors (Am. J. Prev. Med. 2005;29:163–70).

In addition to sociodemographic measures, study data included self-reported information on adolescent risk behaviors, perceptions of physical maturity, and depression, measured using a version of the Center for Epidemiological Studies-Depression Scale (CES-D) modified for the study population to maximize sensitivity and specificity for detecting major depressive disorder in adolescents.

Compared with those adolescents who reported abstaining from risk behaviors in the initial interview, adolescents who engaged in risk behaviors were significantly more likely to meet the criteria for depression at the time of the second interview.

In particular, girls who fell into “experimental behavior” clusters at the initial interview—self-reported drinkers and those who reported experimenting with substances and sex—had a two- to threefold increase in depression compared with girls who abstained from such activities.

In contrast, boys in the experimental behavior clusters were no more depressed than were boys who abstained.

Similarly, girls in the high-risk behavior clusters—those with multiple sex partners and intravenous drug use—were significantly more likely than were abstainers to be depressed, while similar behavior patterns were not predictive of depression among boys.

In boys, binge drinking and frequent marijuana use were associated with a fourfold increase in depression compared with abstainers, while these patterns did not predict depression among girls.

In girls, depression at the first interview did not increase the likelihood of engaging in experimental behavior patterns, and it lowered the likelihood of engaging in high-risk behaviors.

In boys, depression was not predictive of engaging in either experimental or high-risk behaviors.

For girls who reported experimental behavior at baseline, depression did not predict further experimental behaviors, but it did predict movement to a high-risk behavior cluster. In boys who engaged in experimental behaviors, depression did not increase the likelihood of further experimentation or high-risk behaviors.

Given the gender-specific patterns in the relationship between risk behaviors and depression, screening and preventive interventions should be designed accordingly, the investigators said.

“Our findings indicate that patterns of substance abuse, especially binge drinking and frequent marijuana use, increase the likelihood of depression in boys by more than fourfold. Thus, boys who are heavy users should be counseled to reduce or stop use, and screened for depression,” they suggested. Boys who present with depression should be screened for substance abuse and addiction, which, if present, should be treated aggressively.

Among adolescent girls, those who engage in substance use or sex behaviors should be screened for depression “and provided with anticipatory guidance about the mental health risks of these behaviors,” the investigators said.

Treatment for adolescent girls with depression should include an assessment of risk behaviors, as well as appropriate substance use and sexual decision-making messages and counseling.

“Management plans for both boys and girls may also need to address issues related to sexually transmitted infections, HIV, unintended pregnancy, injury prevention, and depression and/or suicide risk,” Dr. Hallfors and her associates said.

Although temporal ordering of risky behavior and depression seen in this study suggests a cause-and-effect relationship, “these analyses cannot rule out unidentified predisposing factors that may cause both,” they pointed out, noting that more research is needed to identify the mechanisms of risk as well as to determine whether efforts to reduce risk-taking behaviors will have an impact on later depression risk.

Adolescents who engage in sex and drug behaviors are at risk for future depression, reported Denise D. Hallfors, Ph.D., and her colleagues at the University of North Carolina at Chapel Hill.

In their study, the association existed among youth of both sexes, but adolescent girls appear to be especially vulnerable to subsequent depression risk.

Although previous studies have associated adolescent depression with sex and drug use, the current study is among the first to provide insight into the causal relationship between the risky behaviors and depression, the authors wrote.

The findings appear to reject the frequent hypothesis that adolescents use sex and drugs to self-medicate depression, Dr. Hallfors and her associates said.

Using data from the National Longitudinal Study of Adolescent Health (Add Health)—a nationally representative sample of more than 13,000 7th- to 11th-grade adolescents who were first interviewed in 1995 and reinterviewed in 1996—investigators examined whether gender-specific patterns of substance use and sexual behavior predicted depression or whether depression predicted the gender-specific patterns of these risky behaviors (Am. J. Prev. Med. 2005;29:163–70).

In addition to sociodemographic measures, study data included self-reported information on adolescent risk behaviors, perceptions of physical maturity, and depression, measured using a version of the Center for Epidemiological Studies-Depression Scale (CES-D) modified for the study population to maximize sensitivity and specificity for detecting major depressive disorder in adolescents.

Compared with those adolescents who reported abstaining from risk behaviors in the initial interview, adolescents who engaged in risk behaviors were significantly more likely to meet the criteria for depression at the time of the second interview.

In particular, girls who fell into “experimental behavior” clusters at the initial interview—self-reported drinkers and those who reported experimenting with substances and sex—had a two- to threefold increase in depression compared with girls who abstained from such activities.

In contrast, boys in the experimental behavior clusters were no more depressed than were boys who abstained.

Similarly, girls in the high-risk behavior clusters—those with multiple sex partners and intravenous drug use—were significantly more likely than were abstainers to be depressed, while similar behavior patterns were not predictive of depression among boys.

In boys, binge drinking and frequent marijuana use were associated with a fourfold increase in depression compared with abstainers, while these patterns did not predict depression among girls.

In girls, depression at the first interview did not increase the likelihood of engaging in experimental behavior patterns, and it lowered the likelihood of engaging in high-risk behaviors.

In boys, depression was not predictive of engaging in either experimental or high-risk behaviors.

For girls who reported experimental behavior at baseline, depression did not predict further experimental behaviors, but it did predict movement to a high-risk behavior cluster. In boys who engaged in experimental behaviors, depression did not increase the likelihood of further experimentation or high-risk behaviors.

Given the gender-specific patterns in the relationship between risk behaviors and depression, screening and preventive interventions should be designed accordingly, the investigators said.

“Our findings indicate that patterns of substance abuse, especially binge drinking and frequent marijuana use, increase the likelihood of depression in boys by more than fourfold. Thus, boys who are heavy users should be counseled to reduce or stop use, and screened for depression,” they suggested. Boys who present with depression should be screened for substance abuse and addiction, which, if present, should be treated aggressively.

Among adolescent girls, those who engage in substance use or sex behaviors should be screened for depression “and provided with anticipatory guidance about the mental health risks of these behaviors,” the investigators said.

Treatment for adolescent girls with depression should include an assessment of risk behaviors, as well as appropriate substance use and sexual decision-making messages and counseling.

“Management plans for both boys and girls may also need to address issues related to sexually transmitted infections, HIV, unintended pregnancy, injury prevention, and depression and/or suicide risk,” Dr. Hallfors and her associates said.

Although temporal ordering of risky behavior and depression seen in this study suggests a cause-and-effect relationship, “these analyses cannot rule out unidentified predisposing factors that may cause both,” they pointed out, noting that more research is needed to identify the mechanisms of risk as well as to determine whether efforts to reduce risk-taking behaviors will have an impact on later depression risk.

Adolescents who engage in sex and drug behaviors are at risk for future depression, reported Denise D. Hallfors, Ph.D., and her colleagues at the University of North Carolina at Chapel Hill.

In their study, the association existed among youth of both sexes, but adolescent girls appear to be especially vulnerable to subsequent depression risk.

Although previous studies have associated adolescent depression with sex and drug use, the current study is among the first to provide insight into the causal relationship between the risky behaviors and depression, the authors wrote.

The findings appear to reject the frequent hypothesis that adolescents use sex and drugs to self-medicate depression, Dr. Hallfors and her associates said.

Using data from the National Longitudinal Study of Adolescent Health (Add Health)—a nationally representative sample of more than 13,000 7th- to 11th-grade adolescents who were first interviewed in 1995 and reinterviewed in 1996—investigators examined whether gender-specific patterns of substance use and sexual behavior predicted depression or whether depression predicted the gender-specific patterns of these risky behaviors (Am. J. Prev. Med. 2005;29:163–70).

In addition to sociodemographic measures, study data included self-reported information on adolescent risk behaviors, perceptions of physical maturity, and depression, measured using a version of the Center for Epidemiological Studies-Depression Scale (CES-D) modified for the study population to maximize sensitivity and specificity for detecting major depressive disorder in adolescents.

Compared with those adolescents who reported abstaining from risk behaviors in the initial interview, adolescents who engaged in risk behaviors were significantly more likely to meet the criteria for depression at the time of the second interview.

In particular, girls who fell into “experimental behavior” clusters at the initial interview—self-reported drinkers and those who reported experimenting with substances and sex—had a two- to threefold increase in depression compared with girls who abstained from such activities.

In contrast, boys in the experimental behavior clusters were no more depressed than were boys who abstained.

Similarly, girls in the high-risk behavior clusters—those with multiple sex partners and intravenous drug use—were significantly more likely than were abstainers to be depressed, while similar behavior patterns were not predictive of depression among boys.

In boys, binge drinking and frequent marijuana use were associated with a fourfold increase in depression compared with abstainers, while these patterns did not predict depression among girls.

In girls, depression at the first interview did not increase the likelihood of engaging in experimental behavior patterns, and it lowered the likelihood of engaging in high-risk behaviors.

In boys, depression was not predictive of engaging in either experimental or high-risk behaviors.

For girls who reported experimental behavior at baseline, depression did not predict further experimental behaviors, but it did predict movement to a high-risk behavior cluster. In boys who engaged in experimental behaviors, depression did not increase the likelihood of further experimentation or high-risk behaviors.

Given the gender-specific patterns in the relationship between risk behaviors and depression, screening and preventive interventions should be designed accordingly, the investigators said.

“Our findings indicate that patterns of substance abuse, especially binge drinking and frequent marijuana use, increase the likelihood of depression in boys by more than fourfold. Thus, boys who are heavy users should be counseled to reduce or stop use, and screened for depression,” they suggested. Boys who present with depression should be screened for substance abuse and addiction, which, if present, should be treated aggressively.

Among adolescent girls, those who engage in substance use or sex behaviors should be screened for depression “and provided with anticipatory guidance about the mental health risks of these behaviors,” the investigators said.

Treatment for adolescent girls with depression should include an assessment of risk behaviors, as well as appropriate substance use and sexual decision-making messages and counseling.

“Management plans for both boys and girls may also need to address issues related to sexually transmitted infections, HIV, unintended pregnancy, injury prevention, and depression and/or suicide risk,” Dr. Hallfors and her associates said.

Although temporal ordering of risky behavior and depression seen in this study suggests a cause-and-effect relationship, “these analyses cannot rule out unidentified predisposing factors that may cause both,” they pointed out, noting that more research is needed to identify the mechanisms of risk as well as to determine whether efforts to reduce risk-taking behaviors will have an impact on later depression risk.

MONTREAL — Recombinant human activated protein C can be a lifesaver for some of the sickest patients with community-acquired pneumonia, Gary E. Garber, M.D., said at an international conference on community-acquired pneumonia.

Yet despite evidence that the coagulation inhibitor reduces mortality in patients with severe sepsis and community-acquired pneumonia (CAP) as their infection source, clinicians have been slow to embrace activated protein C—or drotrecogin alfa (Xigris)—as an adjunctive therapy for this well-defined patient population, said Dr. Garber, head of the division of infectious diseases at the University of Ottawa and the Ottawa Hospital.

In the landmark 2001 Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) trial, activated protein C (APC) reduced mortality from severe sepsis by nearly 20% among the 850 patients who received the drug, compared with the 840 patients given the placebo (N. Engl. J. Med. 2001;344:699–709). The findings led to FDA approval of the drug for adult patients who have a high risk of death due to severe sepsis associated with acute organ dysfunction.

In a retrospective analysis of the investigation, Dr. Garber and his colleagues determined that more than 35% of the study participants had CAP as their infection source, and of these, 26% had Streptococcus pneumoniae identified as the pathogen (Crit. Care Med. 2005;33:952–61).

Those CAP patients treated with APC had a 28% relative reduction in mortality, compared with those who received placebo. In patients with confirmed S. pneumoniae infections, “mortality fell from an absolute mortality of 32.9% to 20% with APC treatment,” representing about a 40% relative reduction in mortality, he said.

The drug also had a significant effect on morbidity: Treated patients experienced faster resolution of cardiovascular and respiratory dysfunction and had more vasopressor- and ventilator-free days alive, compared with placebo patients, Dr. Garber said.

Because of its anticoagulant properties, APC is associated with an increased risk of serious bleeding, especially for patients with a preexisting risk for bleeding, such as those with central nervous system lesions or severe thrombocytopenia. This risk is one of the psychological barriers to wider usage of the drug, he noted.

In the PROWESS trial, 3.5% of the treated patients experienced bleeding-related complications, compared with 2% of patients on placebo. In both the treatment and placebo groups, the bleeding was usually related to an invasive procedure. However, Dr. Garber pointed out that “bleeding is a major risk associated with severe sepsis. If monitored, it is easily managed and is not a contraindication to using APC.”

The drug is contraindicated in situations in which bleeding cannot be easily monitored; in patients with intracranial trauma or increased intracranial pressure; and in those who have had a recent epidural catheter, he said.

“In reality, when weighed against the benefit of keeping these patients alive, the slightly increased bleeding risk becomes less relevant,” Dr. Garber said at the conference, which was sponsored by the International Society of Chemotherapy. Uncertainties about patient selection and drug cost are also barriers to clinician acceptance of APC, although neither concern is scientifically supported, he said.

“It is not that difficult to determine which patients should be treated with APC. Patients with pneumonia and systemic inflammation clearly benefit,” he said, alluding to the retrospective PROWESS analysis; these data indicated that levels of interleukin-6—a strong negative prognostic marker in sepsis—dropped rapidly with APC treatment in septic CAP patients.

Specifically, “patients admitted to the [intensive care unit] with community-acquired pneumonia who require ventilatory and inotropic support will likely benefit from adjunctive treatment,” Dr. Garber said. “These patients are at high risk of death, and experience tells us that the relative benefit of APC increases with increased mortality [risk] and severity of underlying coagulopathy and inflammation.”

In terms of cost, a therapeutic course of APC in prototypic CAP patients with severe sepsis is more than twice that of tissue plasminogen activator (TPA), but it can save 6 out of every 100 lives, compared with 1 in 1,000 for TPA. “Instead of debating the role of APC in severe sepsis, we should be asking why TPA is the standard of care,” he said.

Other obstacles to acceptance of APC include a poor understanding of and lack of standardized treatment protocols for sepsis, particularly severe sepsis, the condition for which the drug is approved, Dr. Garber hypothesized. He has served as an advisor for the drug's manufacturer, Eli Lilly & Co.

Perceived barriers notwithstanding, “in well-defined patient populations like CAP in the intensive care unit, APC should, without question, become a regular part of our treatment strategies,” he said.

Toward this end, clinicians need to be better educated ion the management of severe sepsis in community-acquired pneumonia, Dr. Garber said.

MONTREAL — Recombinant human activated protein C can be a lifesaver for some of the sickest patients with community-acquired pneumonia, Gary E. Garber, M.D., said at an international conference on community-acquired pneumonia.

Yet despite evidence that the coagulation inhibitor reduces mortality in patients with severe sepsis and community-acquired pneumonia (CAP) as their infection source, clinicians have been slow to embrace activated protein C—or drotrecogin alfa (Xigris)—as an adjunctive therapy for this well-defined patient population, said Dr. Garber, head of the division of infectious diseases at the University of Ottawa and the Ottawa Hospital.

In the landmark 2001 Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) trial, activated protein C (APC) reduced mortality from severe sepsis by nearly 20% among the 850 patients who received the drug, compared with the 840 patients given the placebo (N. Engl. J. Med. 2001;344:699–709). The findings led to FDA approval of the drug for adult patients who have a high risk of death due to severe sepsis associated with acute organ dysfunction.

In a retrospective analysis of the investigation, Dr. Garber and his colleagues determined that more than 35% of the study participants had CAP as their infection source, and of these, 26% had Streptococcus pneumoniae identified as the pathogen (Crit. Care Med. 2005;33:952–61).

Those CAP patients treated with APC had a 28% relative reduction in mortality, compared with those who received placebo. In patients with confirmed S. pneumoniae infections, “mortality fell from an absolute mortality of 32.9% to 20% with APC treatment,” representing about a 40% relative reduction in mortality, he said.

The drug also had a significant effect on morbidity: Treated patients experienced faster resolution of cardiovascular and respiratory dysfunction and had more vasopressor- and ventilator-free days alive, compared with placebo patients, Dr. Garber said.

Because of its anticoagulant properties, APC is associated with an increased risk of serious bleeding, especially for patients with a preexisting risk for bleeding, such as those with central nervous system lesions or severe thrombocytopenia. This risk is one of the psychological barriers to wider usage of the drug, he noted.

In the PROWESS trial, 3.5% of the treated patients experienced bleeding-related complications, compared with 2% of patients on placebo. In both the treatment and placebo groups, the bleeding was usually related to an invasive procedure. However, Dr. Garber pointed out that “bleeding is a major risk associated with severe sepsis. If monitored, it is easily managed and is not a contraindication to using APC.”

The drug is contraindicated in situations in which bleeding cannot be easily monitored; in patients with intracranial trauma or increased intracranial pressure; and in those who have had a recent epidural catheter, he said.

“In reality, when weighed against the benefit of keeping these patients alive, the slightly increased bleeding risk becomes less relevant,” Dr. Garber said at the conference, which was sponsored by the International Society of Chemotherapy. Uncertainties about patient selection and drug cost are also barriers to clinician acceptance of APC, although neither concern is scientifically supported, he said.

“It is not that difficult to determine which patients should be treated with APC. Patients with pneumonia and systemic inflammation clearly benefit,” he said, alluding to the retrospective PROWESS analysis; these data indicated that levels of interleukin-6—a strong negative prognostic marker in sepsis—dropped rapidly with APC treatment in septic CAP patients.

Specifically, “patients admitted to the [intensive care unit] with community-acquired pneumonia who require ventilatory and inotropic support will likely benefit from adjunctive treatment,” Dr. Garber said. “These patients are at high risk of death, and experience tells us that the relative benefit of APC increases with increased mortality [risk] and severity of underlying coagulopathy and inflammation.”

In terms of cost, a therapeutic course of APC in prototypic CAP patients with severe sepsis is more than twice that of tissue plasminogen activator (TPA), but it can save 6 out of every 100 lives, compared with 1 in 1,000 for TPA. “Instead of debating the role of APC in severe sepsis, we should be asking why TPA is the standard of care,” he said.

Other obstacles to acceptance of APC include a poor understanding of and lack of standardized treatment protocols for sepsis, particularly severe sepsis, the condition for which the drug is approved, Dr. Garber hypothesized. He has served as an advisor for the drug's manufacturer, Eli Lilly & Co.

Perceived barriers notwithstanding, “in well-defined patient populations like CAP in the intensive care unit, APC should, without question, become a regular part of our treatment strategies,” he said.

Toward this end, clinicians need to be better educated ion the management of severe sepsis in community-acquired pneumonia, Dr. Garber said.

MONTREAL — Recombinant human activated protein C can be a lifesaver for some of the sickest patients with community-acquired pneumonia, Gary E. Garber, M.D., said at an international conference on community-acquired pneumonia.

Yet despite evidence that the coagulation inhibitor reduces mortality in patients with severe sepsis and community-acquired pneumonia (CAP) as their infection source, clinicians have been slow to embrace activated protein C—or drotrecogin alfa (Xigris)—as an adjunctive therapy for this well-defined patient population, said Dr. Garber, head of the division of infectious diseases at the University of Ottawa and the Ottawa Hospital.

In the landmark 2001 Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) trial, activated protein C (APC) reduced mortality from severe sepsis by nearly 20% among the 850 patients who received the drug, compared with the 840 patients given the placebo (N. Engl. J. Med. 2001;344:699–709). The findings led to FDA approval of the drug for adult patients who have a high risk of death due to severe sepsis associated with acute organ dysfunction.

In a retrospective analysis of the investigation, Dr. Garber and his colleagues determined that more than 35% of the study participants had CAP as their infection source, and of these, 26% had Streptococcus pneumoniae identified as the pathogen (Crit. Care Med. 2005;33:952–61).

Those CAP patients treated with APC had a 28% relative reduction in mortality, compared with those who received placebo. In patients with confirmed S. pneumoniae infections, “mortality fell from an absolute mortality of 32.9% to 20% with APC treatment,” representing about a 40% relative reduction in mortality, he said.

The drug also had a significant effect on morbidity: Treated patients experienced faster resolution of cardiovascular and respiratory dysfunction and had more vasopressor- and ventilator-free days alive, compared with placebo patients, Dr. Garber said.

Because of its anticoagulant properties, APC is associated with an increased risk of serious bleeding, especially for patients with a preexisting risk for bleeding, such as those with central nervous system lesions or severe thrombocytopenia. This risk is one of the psychological barriers to wider usage of the drug, he noted.

In the PROWESS trial, 3.5% of the treated patients experienced bleeding-related complications, compared with 2% of patients on placebo. In both the treatment and placebo groups, the bleeding was usually related to an invasive procedure. However, Dr. Garber pointed out that “bleeding is a major risk associated with severe sepsis. If monitored, it is easily managed and is not a contraindication to using APC.”

The drug is contraindicated in situations in which bleeding cannot be easily monitored; in patients with intracranial trauma or increased intracranial pressure; and in those who have had a recent epidural catheter, he said.

“In reality, when weighed against the benefit of keeping these patients alive, the slightly increased bleeding risk becomes less relevant,” Dr. Garber said at the conference, which was sponsored by the International Society of Chemotherapy. Uncertainties about patient selection and drug cost are also barriers to clinician acceptance of APC, although neither concern is scientifically supported, he said.

“It is not that difficult to determine which patients should be treated with APC. Patients with pneumonia and systemic inflammation clearly benefit,” he said, alluding to the retrospective PROWESS analysis; these data indicated that levels of interleukin-6—a strong negative prognostic marker in sepsis—dropped rapidly with APC treatment in septic CAP patients.

Specifically, “patients admitted to the [intensive care unit] with community-acquired pneumonia who require ventilatory and inotropic support will likely benefit from adjunctive treatment,” Dr. Garber said. “These patients are at high risk of death, and experience tells us that the relative benefit of APC increases with increased mortality [risk] and severity of underlying coagulopathy and inflammation.”

In terms of cost, a therapeutic course of APC in prototypic CAP patients with severe sepsis is more than twice that of tissue plasminogen activator (TPA), but it can save 6 out of every 100 lives, compared with 1 in 1,000 for TPA. “Instead of debating the role of APC in severe sepsis, we should be asking why TPA is the standard of care,” he said.

Other obstacles to acceptance of APC include a poor understanding of and lack of standardized treatment protocols for sepsis, particularly severe sepsis, the condition for which the drug is approved, Dr. Garber hypothesized. He has served as an advisor for the drug's manufacturer, Eli Lilly & Co.

Perceived barriers notwithstanding, “in well-defined patient populations like CAP in the intensive care unit, APC should, without question, become a regular part of our treatment strategies,” he said.

Toward this end, clinicians need to be better educated ion the management of severe sepsis in community-acquired pneumonia, Dr. Garber said.

MONTREAL — Respiratory fluoroquinolones for the treatment of community-acquired pneumonia should generally be restricted to hospitalized patients to minimize the development of resistance to the drugs among respiratory pathogens as well as colonization by other pathogens, said Thomas M. File Jr., M.D.

“Outpatient studies have shown that many [community-acquired pneumonia] patients who are given quin-olones could have been given other agents as preferred first-line therapy, and investigators have identified incorrect dosing and duration patterns that could lead to the development of antibiotic resistance to quinolones,” Dr. File said at an international conference on community-acquired pneumonia.

Outpatient fluoroquinolone therapy should be considered only for patients at increased risk for drug-resistant Streptococcus pneumoniae, including those with comorbid conditions such as diabetes, chronic inflammatory lung disease, liver or renal insufficiency, malignancy, or congestive heart failure, and for patients who have been treated recently with antibacterial agents, said Dr. File, chief of the infectious disease service with Summa Health System in Akron, Ohio.

Since their introduction in the mid-1980s, fluoroquinolones have gained popularity because of their broad-spectrum coverage and high serum levels attained with oral administration—as well as increasing antibiotic resistance among pathogens. The approved agents, including gatifloxacin, gemifloxacin, levofloxacin, and moxifloxacin, are especially valuable for treating lower respiratory tract infections, given the growing prevalence of multiresistant pneumococci, Dr. File noted at the conference, sponsored by the International Society of Chemotherapy.

“The respiratory fluoroquinolones make excellent choices for therapy of community-acquired pneumonia because of their intrinsic activity against the key pathogens, including drug-resistant S. pneumoniae and the atypical organisms, and because of their excellent bioavailability and ability to penetrate well into pulmonary sites of infection,” he added. Another advantage is that the serum half-life is longer than that of other agents, including ciprofloxacin, allowing for once-daily dosing.

Numerous randomized trials have favored fluoroquinolones over standard therapy in terms of efficacy, and several have suggested that initial treatment with the respiratory fluoroquinolones can lead to a rapid clinical response, thus justifying shorter-course therapy for many patients and minimizing the possibility for noncompliance, Dr. File said.

For previously healthy outpatients with community-acquired pneumonia who have not received antimicrobial drugs within the prior 3 months, updated recommendations for empiric antimicrobial therapy suggest treatment with an extended-spectrum macrolide or doxycycline. For patients with comorbidities or recent antimicrobial therapy, therapeutic options include a respiratory fluoroquinolone, a ketolide alone in the absence of enteric gram-negative bacteria, or a combination of a β-lactam plus a macrolide, Dr. File said.

“Another possible option for outpatients with modifying factors is the use of parenteral intramuscular or intravenous ceftriaxone plus an oral macrolide or doxycycline,” he noted.

For inpatient therapy in the general hospital ward, recommended initial therapy includes monotherapy with one of the respiratory fluoroquinolones or a β-lactam plus a macrolide or doxycycline. “In some patients who don't have severe disease and have no risk factors for drug resistant S. pneumoniae or gram-negative pathogens, parenteral azithromycin monotherapy may be considered,” Dr. File said.

Initial treatment for patients in the ICU “who are more likely to be very ill and to have multiple risk factors for more resistant pathogens” should be more aggressive, covering for both atypical organisms and traditional bacterial pathogens. Combination therapy with a potent antipneumococcal β-lactam and an advanced macrolide or a respiratory fluoroquinolone is recommended when Pseudomonas infection is not a consideration, he noted.

“The role of the respiratory fluoroquinolones for severe community-acquired pneumonia patients in the intensive care unit has not been established, thus fluoroquinolone monotherapy is not recommended in these patients,” Dr. File added.

In the presence of risk factors for Pseudomonas infection, as with severe structural lung diseases, “therapy should include drugs that are effective against pneumococcus, Pseudomonas, and Legionella,” he said.

Such therapies include an antipneumococcal, antipseudomonal β-lactam plus ciprofloxacin or levofloxacin; an antipneumococcal, antipseudomonal β-lactam plus an aminoglycoside and an intravenous macrolide or an intravenous macrolide or an intravenous antipneumococcal quinolone; or, for patients with penicillin allergy, aztreonam plus levofloxacin or aztreonam plus moxifloxacin or gatifloxacin, with or without an aminoglycoside.

MONTREAL — Respiratory fluoroquinolones for the treatment of community-acquired pneumonia should generally be restricted to hospitalized patients to minimize the development of resistance to the drugs among respiratory pathogens as well as colonization by other pathogens, said Thomas M. File Jr., M.D.

“Outpatient studies have shown that many [community-acquired pneumonia] patients who are given quin-olones could have been given other agents as preferred first-line therapy, and investigators have identified incorrect dosing and duration patterns that could lead to the development of antibiotic resistance to quinolones,” Dr. File said at an international conference on community-acquired pneumonia.

Outpatient fluoroquinolone therapy should be considered only for patients at increased risk for drug-resistant Streptococcus pneumoniae, including those with comorbid conditions such as diabetes, chronic inflammatory lung disease, liver or renal insufficiency, malignancy, or congestive heart failure, and for patients who have been treated recently with antibacterial agents, said Dr. File, chief of the infectious disease service with Summa Health System in Akron, Ohio.

Since their introduction in the mid-1980s, fluoroquinolones have gained popularity because of their broad-spectrum coverage and high serum levels attained with oral administration—as well as increasing antibiotic resistance among pathogens. The approved agents, including gatifloxacin, gemifloxacin, levofloxacin, and moxifloxacin, are especially valuable for treating lower respiratory tract infections, given the growing prevalence of multiresistant pneumococci, Dr. File noted at the conference, sponsored by the International Society of Chemotherapy.

“The respiratory fluoroquinolones make excellent choices for therapy of community-acquired pneumonia because of their intrinsic activity against the key pathogens, including drug-resistant S. pneumoniae and the atypical organisms, and because of their excellent bioavailability and ability to penetrate well into pulmonary sites of infection,” he added. Another advantage is that the serum half-life is longer than that of other agents, including ciprofloxacin, allowing for once-daily dosing.

Numerous randomized trials have favored fluoroquinolones over standard therapy in terms of efficacy, and several have suggested that initial treatment with the respiratory fluoroquinolones can lead to a rapid clinical response, thus justifying shorter-course therapy for many patients and minimizing the possibility for noncompliance, Dr. File said.

For previously healthy outpatients with community-acquired pneumonia who have not received antimicrobial drugs within the prior 3 months, updated recommendations for empiric antimicrobial therapy suggest treatment with an extended-spectrum macrolide or doxycycline. For patients with comorbidities or recent antimicrobial therapy, therapeutic options include a respiratory fluoroquinolone, a ketolide alone in the absence of enteric gram-negative bacteria, or a combination of a β-lactam plus a macrolide, Dr. File said.

“Another possible option for outpatients with modifying factors is the use of parenteral intramuscular or intravenous ceftriaxone plus an oral macrolide or doxycycline,” he noted.

For inpatient therapy in the general hospital ward, recommended initial therapy includes monotherapy with one of the respiratory fluoroquinolones or a β-lactam plus a macrolide or doxycycline. “In some patients who don't have severe disease and have no risk factors for drug resistant S. pneumoniae or gram-negative pathogens, parenteral azithromycin monotherapy may be considered,” Dr. File said.

Initial treatment for patients in the ICU “who are more likely to be very ill and to have multiple risk factors for more resistant pathogens” should be more aggressive, covering for both atypical organisms and traditional bacterial pathogens. Combination therapy with a potent antipneumococcal β-lactam and an advanced macrolide or a respiratory fluoroquinolone is recommended when Pseudomonas infection is not a consideration, he noted.

“The role of the respiratory fluoroquinolones for severe community-acquired pneumonia patients in the intensive care unit has not been established, thus fluoroquinolone monotherapy is not recommended in these patients,” Dr. File added.

In the presence of risk factors for Pseudomonas infection, as with severe structural lung diseases, “therapy should include drugs that are effective against pneumococcus, Pseudomonas, and Legionella,” he said.

Such therapies include an antipneumococcal, antipseudomonal β-lactam plus ciprofloxacin or levofloxacin; an antipneumococcal, antipseudomonal β-lactam plus an aminoglycoside and an intravenous macrolide or an intravenous macrolide or an intravenous antipneumococcal quinolone; or, for patients with penicillin allergy, aztreonam plus levofloxacin or aztreonam plus moxifloxacin or gatifloxacin, with or without an aminoglycoside.

MONTREAL — Respiratory fluoroquinolones for the treatment of community-acquired pneumonia should generally be restricted to hospitalized patients to minimize the development of resistance to the drugs among respiratory pathogens as well as colonization by other pathogens, said Thomas M. File Jr., M.D.

“Outpatient studies have shown that many [community-acquired pneumonia] patients who are given quin-olones could have been given other agents as preferred first-line therapy, and investigators have identified incorrect dosing and duration patterns that could lead to the development of antibiotic resistance to quinolones,” Dr. File said at an international conference on community-acquired pneumonia.

Outpatient fluoroquinolone therapy should be considered only for patients at increased risk for drug-resistant Streptococcus pneumoniae, including those with comorbid conditions such as diabetes, chronic inflammatory lung disease, liver or renal insufficiency, malignancy, or congestive heart failure, and for patients who have been treated recently with antibacterial agents, said Dr. File, chief of the infectious disease service with Summa Health System in Akron, Ohio.

Since their introduction in the mid-1980s, fluoroquinolones have gained popularity because of their broad-spectrum coverage and high serum levels attained with oral administration—as well as increasing antibiotic resistance among pathogens. The approved agents, including gatifloxacin, gemifloxacin, levofloxacin, and moxifloxacin, are especially valuable for treating lower respiratory tract infections, given the growing prevalence of multiresistant pneumococci, Dr. File noted at the conference, sponsored by the International Society of Chemotherapy.

“The respiratory fluoroquinolones make excellent choices for therapy of community-acquired pneumonia because of their intrinsic activity against the key pathogens, including drug-resistant S. pneumoniae and the atypical organisms, and because of their excellent bioavailability and ability to penetrate well into pulmonary sites of infection,” he added. Another advantage is that the serum half-life is longer than that of other agents, including ciprofloxacin, allowing for once-daily dosing.

Numerous randomized trials have favored fluoroquinolones over standard therapy in terms of efficacy, and several have suggested that initial treatment with the respiratory fluoroquinolones can lead to a rapid clinical response, thus justifying shorter-course therapy for many patients and minimizing the possibility for noncompliance, Dr. File said.

For previously healthy outpatients with community-acquired pneumonia who have not received antimicrobial drugs within the prior 3 months, updated recommendations for empiric antimicrobial therapy suggest treatment with an extended-spectrum macrolide or doxycycline. For patients with comorbidities or recent antimicrobial therapy, therapeutic options include a respiratory fluoroquinolone, a ketolide alone in the absence of enteric gram-negative bacteria, or a combination of a β-lactam plus a macrolide, Dr. File said.

“Another possible option for outpatients with modifying factors is the use of parenteral intramuscular or intravenous ceftriaxone plus an oral macrolide or doxycycline,” he noted.

For inpatient therapy in the general hospital ward, recommended initial therapy includes monotherapy with one of the respiratory fluoroquinolones or a β-lactam plus a macrolide or doxycycline. “In some patients who don't have severe disease and have no risk factors for drug resistant S. pneumoniae or gram-negative pathogens, parenteral azithromycin monotherapy may be considered,” Dr. File said.

Initial treatment for patients in the ICU “who are more likely to be very ill and to have multiple risk factors for more resistant pathogens” should be more aggressive, covering for both atypical organisms and traditional bacterial pathogens. Combination therapy with a potent antipneumococcal β-lactam and an advanced macrolide or a respiratory fluoroquinolone is recommended when Pseudomonas infection is not a consideration, he noted.

“The role of the respiratory fluoroquinolones for severe community-acquired pneumonia patients in the intensive care unit has not been established, thus fluoroquinolone monotherapy is not recommended in these patients,” Dr. File added.

In the presence of risk factors for Pseudomonas infection, as with severe structural lung diseases, “therapy should include drugs that are effective against pneumococcus, Pseudomonas, and Legionella,” he said.

Such therapies include an antipneumococcal, antipseudomonal β-lactam plus ciprofloxacin or levofloxacin; an antipneumococcal, antipseudomonal β-lactam plus an aminoglycoside and an intravenous macrolide or an intravenous macrolide or an intravenous antipneumococcal quinolone; or, for patients with penicillin allergy, aztreonam plus levofloxacin or aztreonam plus moxifloxacin or gatifloxacin, with or without an aminoglycoside.

BOSTON — For acute heart failure patients with neither a history of coronary disease nor evidence of acute MI, myocardial contrast echocardiography can distinguish ischemic from nonischemic etiology, a study has shown.

The ability to identify underlying coronary artery disease in such patients has therapeutic and prognostic implications, reported Rajesh Janardhanan, M.D., in a poster presentation at the annual meeting of the American Society of Echocardiography.

A noninvasive bedside technique for evaluating acute coronary syndromes, myocardial contrast echocardiography (MCE) provides a simultaneous assessment of regional wall motion and myocardial perfusion using microbubble contrast agents.

To assess the sensitivity and specificity of the imaging tool in the evaluation of acute heart failure, Dr. Janardhanan of Brigham and Women's Hospital in Boston, and investigators at Northwick Park Hospital in Harrow, England, reviewed the imaging results from 52 consecutive patients with acute heart failure with no prior history of coronary artery disease (CAD) and no clinical evidence of acute MI on hospital admission.

All the patients in the study underwent echocardiography and MCE at rest and following dipyridamole stress.

Additionally, all patients underwent coronary arteriography prior to hospital discharge.

On coronary arteriography, 22 of the 52 patients had evidence of CAD, defined as more than 50% luminal diameter narrowing, Dr. Janardhanan said.

The sensitivity and specificity of MCE for detecting CAD in the 22 patients was 82% and 97%, respectively, with a positive predictive value of 95% and a negative predictive value of 88%.

Among the various markers of CAD, including MCE, clinical variables, ECG, biochemical measures, and resting echocardiographic results, MCE “was the only [statistically significant] independent predictor of CAD,” said Dr. Janardhanan.

Both myocardial blood flow reserve and myocardial blood velocity reserve decreased relative to increasing CAD severity, suggesting quantitative MCE data might be an effective tool for stratifying risk in patients with acute heart failure, Dr. Janardhanan concluded.

BOSTON — For acute heart failure patients with neither a history of coronary disease nor evidence of acute MI, myocardial contrast echocardiography can distinguish ischemic from nonischemic etiology, a study has shown.

The ability to identify underlying coronary artery disease in such patients has therapeutic and prognostic implications, reported Rajesh Janardhanan, M.D., in a poster presentation at the annual meeting of the American Society of Echocardiography.

A noninvasive bedside technique for evaluating acute coronary syndromes, myocardial contrast echocardiography (MCE) provides a simultaneous assessment of regional wall motion and myocardial perfusion using microbubble contrast agents.

To assess the sensitivity and specificity of the imaging tool in the evaluation of acute heart failure, Dr. Janardhanan of Brigham and Women's Hospital in Boston, and investigators at Northwick Park Hospital in Harrow, England, reviewed the imaging results from 52 consecutive patients with acute heart failure with no prior history of coronary artery disease (CAD) and no clinical evidence of acute MI on hospital admission.

All the patients in the study underwent echocardiography and MCE at rest and following dipyridamole stress.

Additionally, all patients underwent coronary arteriography prior to hospital discharge.

On coronary arteriography, 22 of the 52 patients had evidence of CAD, defined as more than 50% luminal diameter narrowing, Dr. Janardhanan said.

The sensitivity and specificity of MCE for detecting CAD in the 22 patients was 82% and 97%, respectively, with a positive predictive value of 95% and a negative predictive value of 88%.

Among the various markers of CAD, including MCE, clinical variables, ECG, biochemical measures, and resting echocardiographic results, MCE “was the only [statistically significant] independent predictor of CAD,” said Dr. Janardhanan.

Both myocardial blood flow reserve and myocardial blood velocity reserve decreased relative to increasing CAD severity, suggesting quantitative MCE data might be an effective tool for stratifying risk in patients with acute heart failure, Dr. Janardhanan concluded.

BOSTON — For acute heart failure patients with neither a history of coronary disease nor evidence of acute MI, myocardial contrast echocardiography can distinguish ischemic from nonischemic etiology, a study has shown.

The ability to identify underlying coronary artery disease in such patients has therapeutic and prognostic implications, reported Rajesh Janardhanan, M.D., in a poster presentation at the annual meeting of the American Society of Echocardiography.

A noninvasive bedside technique for evaluating acute coronary syndromes, myocardial contrast echocardiography (MCE) provides a simultaneous assessment of regional wall motion and myocardial perfusion using microbubble contrast agents.

To assess the sensitivity and specificity of the imaging tool in the evaluation of acute heart failure, Dr. Janardhanan of Brigham and Women's Hospital in Boston, and investigators at Northwick Park Hospital in Harrow, England, reviewed the imaging results from 52 consecutive patients with acute heart failure with no prior history of coronary artery disease (CAD) and no clinical evidence of acute MI on hospital admission.

All the patients in the study underwent echocardiography and MCE at rest and following dipyridamole stress.

Additionally, all patients underwent coronary arteriography prior to hospital discharge.

On coronary arteriography, 22 of the 52 patients had evidence of CAD, defined as more than 50% luminal diameter narrowing, Dr. Janardhanan said.

The sensitivity and specificity of MCE for detecting CAD in the 22 patients was 82% and 97%, respectively, with a positive predictive value of 95% and a negative predictive value of 88%.

Among the various markers of CAD, including MCE, clinical variables, ECG, biochemical measures, and resting echocardiographic results, MCE “was the only [statistically significant] independent predictor of CAD,” said Dr. Janardhanan.

Both myocardial blood flow reserve and myocardial blood velocity reserve decreased relative to increasing CAD severity, suggesting quantitative MCE data might be an effective tool for stratifying risk in patients with acute heart failure, Dr. Janardhanan concluded.

NEW ORLEANS — Fears and misconceptions about antidepressant medications contribute to older adults' reluctance to use pharmacologic treatment for depression, a qualitative study has shown.

“Depression is highly prevalent but undertreated in elderly primary care patients, despite the availability of effective medications,” Jane L. Givens, M.D., reported at the annual meeting of the Society of General Internal Medicine. Among the patient-level factors preventing appropriate treatment in this population are fear of addiction, concern about unnatural happiness or inability to feel grief and sadness, and fear of side effects.

Dr. Givens and her colleagues at the University of Pennsylvania in Philadelphia recruited a subsample of 68 older adults (mean age 75 years) with depression who participated in one of two qualitative, randomized treatment studies—the Prevention of Suicide in Primary Care Elderly: Collaborative Trial (PROSPECT) or the Primary Care Research in Substance Abuse and Mental Health for the Elderly (PRISM-E). Each of the patients participated in semistructured home-based interviews, which were audiotaped, transcribed, and entered into qualitative data analysis software for coding and analysis.

“Four themes emerged from this review,” Dr. Givens said. “Many expressed a fear of needing to take antidepressants for the rest of their lives or of becoming addicted. Some did not want to be unnaturally happy or to mute their capacity to feel sadness or to 'face reality.'”

Other patients resisted treating symptoms of sadness associated with the loss of a loved one, and some had previous histories of treatment with psychiatric medications, including tranquilizers, and were concerned about the side effects, particularly sedation, Dr. Givens noted.

Many studies have linked depression to excess morbidity and mortality in elderly patients because of insufficient screening and detection and inadequate treatment. The findings of this study suggest that identifying depressed patients and offering them pharmacologic therapy may not be enough. “There is a need for more patient education and dialogue about the characteristics of current antidepressant therapy,” she concluded.

NEW ORLEANS — Fears and misconceptions about antidepressant medications contribute to older adults' reluctance to use pharmacologic treatment for depression, a qualitative study has shown.

“Depression is highly prevalent but undertreated in elderly primary care patients, despite the availability of effective medications,” Jane L. Givens, M.D., reported at the annual meeting of the Society of General Internal Medicine. Among the patient-level factors preventing appropriate treatment in this population are fear of addiction, concern about unnatural happiness or inability to feel grief and sadness, and fear of side effects.

Dr. Givens and her colleagues at the University of Pennsylvania in Philadelphia recruited a subsample of 68 older adults (mean age 75 years) with depression who participated in one of two qualitative, randomized treatment studies—the Prevention of Suicide in Primary Care Elderly: Collaborative Trial (PROSPECT) or the Primary Care Research in Substance Abuse and Mental Health for the Elderly (PRISM-E). Each of the patients participated in semistructured home-based interviews, which were audiotaped, transcribed, and entered into qualitative data analysis software for coding and analysis.

“Four themes emerged from this review,” Dr. Givens said. “Many expressed a fear of needing to take antidepressants for the rest of their lives or of becoming addicted. Some did not want to be unnaturally happy or to mute their capacity to feel sadness or to 'face reality.'”

Other patients resisted treating symptoms of sadness associated with the loss of a loved one, and some had previous histories of treatment with psychiatric medications, including tranquilizers, and were concerned about the side effects, particularly sedation, Dr. Givens noted.

Many studies have linked depression to excess morbidity and mortality in elderly patients because of insufficient screening and detection and inadequate treatment. The findings of this study suggest that identifying depressed patients and offering them pharmacologic therapy may not be enough. “There is a need for more patient education and dialogue about the characteristics of current antidepressant therapy,” she concluded.

NEW ORLEANS — Fears and misconceptions about antidepressant medications contribute to older adults' reluctance to use pharmacologic treatment for depression, a qualitative study has shown.

“Depression is highly prevalent but undertreated in elderly primary care patients, despite the availability of effective medications,” Jane L. Givens, M.D., reported at the annual meeting of the Society of General Internal Medicine. Among the patient-level factors preventing appropriate treatment in this population are fear of addiction, concern about unnatural happiness or inability to feel grief and sadness, and fear of side effects.

Dr. Givens and her colleagues at the University of Pennsylvania in Philadelphia recruited a subsample of 68 older adults (mean age 75 years) with depression who participated in one of two qualitative, randomized treatment studies—the Prevention of Suicide in Primary Care Elderly: Collaborative Trial (PROSPECT) or the Primary Care Research in Substance Abuse and Mental Health for the Elderly (PRISM-E). Each of the patients participated in semistructured home-based interviews, which were audiotaped, transcribed, and entered into qualitative data analysis software for coding and analysis.

“Four themes emerged from this review,” Dr. Givens said. “Many expressed a fear of needing to take antidepressants for the rest of their lives or of becoming addicted. Some did not want to be unnaturally happy or to mute their capacity to feel sadness or to 'face reality.'”

Other patients resisted treating symptoms of sadness associated with the loss of a loved one, and some had previous histories of treatment with psychiatric medications, including tranquilizers, and were concerned about the side effects, particularly sedation, Dr. Givens noted.

Many studies have linked depression to excess morbidity and mortality in elderly patients because of insufficient screening and detection and inadequate treatment. The findings of this study suggest that identifying depressed patients and offering them pharmacologic therapy may not be enough. “There is a need for more patient education and dialogue about the characteristics of current antidepressant therapy,” she concluded.

BOSTON – Patients diagnosed with carpel tunnel syndrome are more likely to be anxious and depressed and to have lower levels of mental and physical health functioning and job satisfaction, compared with individuals without the common wrist condition, Jason Goodson said at the annual meeting of the Society of Behavioral Medicine.

Findings in a study suggest that brief assessments of psychosocial functioning when evaluating patients for carpel tunnel syndrome (CTS) might be useful for understanding and treating the condition, as well as for improving the prognosis, Mr. Goodson said at the annual meeting of the Society of Behavioral Medicine.

The case-control study compared the psychosocial functioning of 87 patients diagnosed with CTS (based on clinical symptoms and electrodiagnostic confirmation) with that of 74 gender-matched control patients from the same orthopedic clinic. All of the study participants completed self-report questionnaires that included measures of depression, anxiety, somatization, health locus of control, job satisfaction, and mental and physical functioning.

Univariate analyses showed that the CTS patients had significantly higher levels of anxiety, depression, and other health locus of control beliefs. They had significantly lower levels of job satisfaction and mental and physical health functioning, said Mr. Goodson of Utah State University, Logan.

Measures of job satisfaction and physical health functioning were statistically significant predictors of CTS in a multiple logistic regression analysis, with adjusted odds ratios of 0.92 and 0.70, respectively, noted Mr. Goodson, who conducted the study under the direction of M. Scott DeBerard, Ph.D.

Previous studies have identified biologic and work variables as risk factors for CTS, but potential psychosocial variables have received less attention, Mr. Goodson said. And those studies that do exist “have frequently used nonspecific measures of psychosocial functioning, such as general distress, rather than specific measures, such as anxiety, depression, and somatization, he said, noting that the specific measures have more relevance when it comes to designing interventions.

By assessing patients psychosocial functioning when evaluating CTS, clinicians can refer patients who are struggling emotionally for appropriate mental health care to enhance coping resources and improve their ability to understand and manage the associated pain and disability. Cognitive-behavioral therapy and stress management are among the techniques that have shown promise for mitigating the emotional pain of the condition, Mr. Goodson said.

BOSTON – Patients diagnosed with carpel tunnel syndrome are more likely to be anxious and depressed and to have lower levels of mental and physical health functioning and job satisfaction, compared with individuals without the common wrist condition, Jason Goodson said at the annual meeting of the Society of Behavioral Medicine.

Findings in a study suggest that brief assessments of psychosocial functioning when evaluating patients for carpel tunnel syndrome (CTS) might be useful for understanding and treating the condition, as well as for improving the prognosis, Mr. Goodson said at the annual meeting of the Society of Behavioral Medicine.

The case-control study compared the psychosocial functioning of 87 patients diagnosed with CTS (based on clinical symptoms and electrodiagnostic confirmation) with that of 74 gender-matched control patients from the same orthopedic clinic. All of the study participants completed self-report questionnaires that included measures of depression, anxiety, somatization, health locus of control, job satisfaction, and mental and physical functioning.

Univariate analyses showed that the CTS patients had significantly higher levels of anxiety, depression, and other health locus of control beliefs. They had significantly lower levels of job satisfaction and mental and physical health functioning, said Mr. Goodson of Utah State University, Logan.

Measures of job satisfaction and physical health functioning were statistically significant predictors of CTS in a multiple logistic regression analysis, with adjusted odds ratios of 0.92 and 0.70, respectively, noted Mr. Goodson, who conducted the study under the direction of M. Scott DeBerard, Ph.D.

Previous studies have identified biologic and work variables as risk factors for CTS, but potential psychosocial variables have received less attention, Mr. Goodson said. And those studies that do exist “have frequently used nonspecific measures of psychosocial functioning, such as general distress, rather than specific measures, such as anxiety, depression, and somatization, he said, noting that the specific measures have more relevance when it comes to designing interventions.

By assessing patients psychosocial functioning when evaluating CTS, clinicians can refer patients who are struggling emotionally for appropriate mental health care to enhance coping resources and improve their ability to understand and manage the associated pain and disability. Cognitive-behavioral therapy and stress management are among the techniques that have shown promise for mitigating the emotional pain of the condition, Mr. Goodson said.

BOSTON – Patients diagnosed with carpel tunnel syndrome are more likely to be anxious and depressed and to have lower levels of mental and physical health functioning and job satisfaction, compared with individuals without the common wrist condition, Jason Goodson said at the annual meeting of the Society of Behavioral Medicine.

Findings in a study suggest that brief assessments of psychosocial functioning when evaluating patients for carpel tunnel syndrome (CTS) might be useful for understanding and treating the condition, as well as for improving the prognosis, Mr. Goodson said at the annual meeting of the Society of Behavioral Medicine.

The case-control study compared the psychosocial functioning of 87 patients diagnosed with CTS (based on clinical symptoms and electrodiagnostic confirmation) with that of 74 gender-matched control patients from the same orthopedic clinic. All of the study participants completed self-report questionnaires that included measures of depression, anxiety, somatization, health locus of control, job satisfaction, and mental and physical functioning.

Univariate analyses showed that the CTS patients had significantly higher levels of anxiety, depression, and other health locus of control beliefs. They had significantly lower levels of job satisfaction and mental and physical health functioning, said Mr. Goodson of Utah State University, Logan.

Measures of job satisfaction and physical health functioning were statistically significant predictors of CTS in a multiple logistic regression analysis, with adjusted odds ratios of 0.92 and 0.70, respectively, noted Mr. Goodson, who conducted the study under the direction of M. Scott DeBerard, Ph.D.

Previous studies have identified biologic and work variables as risk factors for CTS, but potential psychosocial variables have received less attention, Mr. Goodson said. And those studies that do exist “have frequently used nonspecific measures of psychosocial functioning, such as general distress, rather than specific measures, such as anxiety, depression, and somatization, he said, noting that the specific measures have more relevance when it comes to designing interventions.

By assessing patients psychosocial functioning when evaluating CTS, clinicians can refer patients who are struggling emotionally for appropriate mental health care to enhance coping resources and improve their ability to understand and manage the associated pain and disability. Cognitive-behavioral therapy and stress management are among the techniques that have shown promise for mitigating the emotional pain of the condition, Mr. Goodson said.