Sherry Boschert

SAN FRANCISCO — Drug resistance was a common cause of treatment failure in 26 patients with community-acquired pneumonia who developed bacteremia while being treated with macrolide antibiotics, Dr. Gavin Bayan Grant said at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Of the 26 patients who developed bacteremia while on erythromycin, clarithromycin, or azithromycin therapy, 21 (81%) had resistant organisms, compared with 15 (44%) of 34 patients who developed bacteremia after recent use of one of the macrolides (defined as 16–90 days before the bacteremia diagnosis) and 14% of 721 patients who had not been taking any antibiotics and developed bacteremia.

Macrolide antibiotics are standard therapy for outpatient treatment of pneumonia, and evidence that significant macrolide resistance occurs has been inconclusive, said Dr. Grant of the Centers for Disease Control and Prevention, Atlanta. The current findings provide further evidence that resistance can lead to treatment failure with macrolides, which may inform clinical decisions to change antibiotics in some patients, he said at the meeting, sponsored by the American Society for Microbiology.

Dr. Grant has no association with the companies that make macrolides.

After patient age, immunosuppression, chronic comorbidities, and residence in a long-term care facility were controlled for, patients failing macrolide therapy were 5 times more likely to have resistant organisms, compared with patients who developed bacteremia after recent macrolide use, and 26 times more likely to have resistance than patients with bacteremia who had not been taking antibiotics.

The study also found that clinicians who define macrolide resistance using a cutoff of a minimum inhibitory concentration (MIC) of at least 16 mcg/mL will miss a significant percentage of the treatment failures. “Failures often occur at macrolide MICs less than 16 mcg/mL,” he said.

The laboratory-defined cutoff for pneumococcal resistance to erythromycin is 1 mcg/mL, but some researchers advocate the 16 mcg/mL cutoff as more likely to result in breakthrough bacteremia, he explained.

Comparison of isolates from all three patient groups found that breakthrough bacteremia occurred at a broad range of MIC values above 1 mcg/mL, not just at the higher levels of resistance, Dr. Grant said.

Among the patients who had MICs of 1 mcg/mL or greater, the distribution of MICs did not differ significantly between groups. An MIC of 16 mcg/mL or greater was seen in 39% of the group failing macrolide therapy and 6% of patients who developed bacteremia after recent macrolide therapy or not taking antibiotics.

SAN FRANCISCO — Drug resistance was a common cause of treatment failure in 26 patients with community-acquired pneumonia who developed bacteremia while being treated with macrolide antibiotics, Dr. Gavin Bayan Grant said at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Of the 26 patients who developed bacteremia while on erythromycin, clarithromycin, or azithromycin therapy, 21 (81%) had resistant organisms, compared with 15 (44%) of 34 patients who developed bacteremia after recent use of one of the macrolides (defined as 16–90 days before the bacteremia diagnosis) and 14% of 721 patients who had not been taking any antibiotics and developed bacteremia.

Macrolide antibiotics are standard therapy for outpatient treatment of pneumonia, and evidence that significant macrolide resistance occurs has been inconclusive, said Dr. Grant of the Centers for Disease Control and Prevention, Atlanta. The current findings provide further evidence that resistance can lead to treatment failure with macrolides, which may inform clinical decisions to change antibiotics in some patients, he said at the meeting, sponsored by the American Society for Microbiology.

Dr. Grant has no association with the companies that make macrolides.

After patient age, immunosuppression, chronic comorbidities, and residence in a long-term care facility were controlled for, patients failing macrolide therapy were 5 times more likely to have resistant organisms, compared with patients who developed bacteremia after recent macrolide use, and 26 times more likely to have resistance than patients with bacteremia who had not been taking antibiotics.

The study also found that clinicians who define macrolide resistance using a cutoff of a minimum inhibitory concentration (MIC) of at least 16 mcg/mL will miss a significant percentage of the treatment failures. “Failures often occur at macrolide MICs less than 16 mcg/mL,” he said.

The laboratory-defined cutoff for pneumococcal resistance to erythromycin is 1 mcg/mL, but some researchers advocate the 16 mcg/mL cutoff as more likely to result in breakthrough bacteremia, he explained.

Comparison of isolates from all three patient groups found that breakthrough bacteremia occurred at a broad range of MIC values above 1 mcg/mL, not just at the higher levels of resistance, Dr. Grant said.

Among the patients who had MICs of 1 mcg/mL or greater, the distribution of MICs did not differ significantly between groups. An MIC of 16 mcg/mL or greater was seen in 39% of the group failing macrolide therapy and 6% of patients who developed bacteremia after recent macrolide therapy or not taking antibiotics.

SAN FRANCISCO — Drug resistance was a common cause of treatment failure in 26 patients with community-acquired pneumonia who developed bacteremia while being treated with macrolide antibiotics, Dr. Gavin Bayan Grant said at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Of the 26 patients who developed bacteremia while on erythromycin, clarithromycin, or azithromycin therapy, 21 (81%) had resistant organisms, compared with 15 (44%) of 34 patients who developed bacteremia after recent use of one of the macrolides (defined as 16–90 days before the bacteremia diagnosis) and 14% of 721 patients who had not been taking any antibiotics and developed bacteremia.

Macrolide antibiotics are standard therapy for outpatient treatment of pneumonia, and evidence that significant macrolide resistance occurs has been inconclusive, said Dr. Grant of the Centers for Disease Control and Prevention, Atlanta. The current findings provide further evidence that resistance can lead to treatment failure with macrolides, which may inform clinical decisions to change antibiotics in some patients, he said at the meeting, sponsored by the American Society for Microbiology.

Dr. Grant has no association with the companies that make macrolides.

After patient age, immunosuppression, chronic comorbidities, and residence in a long-term care facility were controlled for, patients failing macrolide therapy were 5 times more likely to have resistant organisms, compared with patients who developed bacteremia after recent macrolide use, and 26 times more likely to have resistance than patients with bacteremia who had not been taking antibiotics.

The study also found that clinicians who define macrolide resistance using a cutoff of a minimum inhibitory concentration (MIC) of at least 16 mcg/mL will miss a significant percentage of the treatment failures. “Failures often occur at macrolide MICs less than 16 mcg/mL,” he said.

The laboratory-defined cutoff for pneumococcal resistance to erythromycin is 1 mcg/mL, but some researchers advocate the 16 mcg/mL cutoff as more likely to result in breakthrough bacteremia, he explained.

Comparison of isolates from all three patient groups found that breakthrough bacteremia occurred at a broad range of MIC values above 1 mcg/mL, not just at the higher levels of resistance, Dr. Grant said.

Among the patients who had MICs of 1 mcg/mL or greater, the distribution of MICs did not differ significantly between groups. An MIC of 16 mcg/mL or greater was seen in 39% of the group failing macrolide therapy and 6% of patients who developed bacteremia after recent macrolide therapy or not taking antibiotics.

SAN DIEGO — Thinking of weight gain simply as the sum of “calories in minus calories out” doesn't cover a minority of obese patients whose dietary records show reasonable caloric balance but who can't seem to lose weight, Dr. Scott R. Rigden said.

These patients may show dietary records reflecting an intake of 1,800–1,900 calories per day, and often say they're tired of health care providers thinking that they're lying in their food diaries because they haven't lost weight, he said at a symposium on obesity sponsored by the American Society of Bariatric Physicians.

“I really think there are a lot of people with special issues, with switched-off metabolisms, that don't fit that model” of calories in/calories out, said Dr. Rigden, a family physician in Chandler, Ariz. who also has practiced bariatrics since 1976. “What has shut down their metabolism, and how do we turn it back on?”

To help these patients, think in terms of the following five subcategories, and tailor dietary and lifestyle recommendations accordingly, he suggested.

▸ Carbohydrate sensitivity. Dr. Rigden defined a patient with carbohydrate sensitivity as one whose genetic makeup produces a rapid spike of glucose after consuming simple carbohydrates and sugars. That glucose spike in turn triggers a spike in insulin and associated metabolic cellular messengers that tell the body to store fat, not burn it. The insulin spike also causes a rapid and uncomfortable drop in glucose that motivates the person to seek more carbohydrates and sugars to remedy the discomfort.

These patients do not yet meet criteria for metabolic syndrome. They have normal fasting insulin and glucose levels and are not hypertensive. “They often have stellar labs, yet a terrible lifelong obesity issue,” Dr. Rigden said. He has devised a nine-item questionnaire focusing on eating and exercise habits to identify this subgroup.

A four-step treatment plan starts with behavior modification to change the patient's relationship with food and an exercise program with at least 150 minutes of moderate aerobic exercise weekly. The third step emphasizes adequate water intake of at least 64 ounces per day—“perhaps the most overlooked part of a weight management program,” he added.

Dietary intervention is the fourth step, starting with a soy protein powder meal replacement plan and switching to a low glycemic diet (which he also called a modified Mediterranean diet) after the patient loses 5%–10% of initial weight.

▸ Metabolic syndrome. Diagnostic criteria for metabolic syndrome include an elevated waist circumference, triglyceride level above 150 mg/dL, an HDL level less than 40 mg/dL for males or less than 50 mg/dL for females, blood pressure above 130/85 mmHg, and fasting blood sugar above 100 mg/dL.

In these patients, foods that have a high glycemic index cause blood sugar levels to plummet, boosting cravings for more high-glycemic foods such as sugars and fat, Dr. Rigden said. He recommends what he calls a “caveman or cavewoman” diet of low-fat, nonstarchy foods that he spells out for patients. After losing 10% of body weight, they switch to the low glycemic diet.

He also recommends nutraceutical medical food with slow-release, amylose-resistant starch, and soluble fiber in the form of 15 g per day of guar gum. Micronutrient support may be the most undervalued component of therapy for these patients, he added.

▸ Hormonal imbalances. Questionnaires and physical exams will help identify the endocrine problems contributing to recalcitrant obesity in these patients, Dr. Rigden said. Most will be due to clinical or subclinical hypothyroidism. “This is probably the No. 1 hormonal imbalance that I see in people who have switched metabolism,” he said.

Polycystic ovarian syndrome or a sex hormone imbalance with estrogen dominance are other problems to consider. Tailor treatment to the particular problem, he said.

▸ Food hypersensitivity. These are not true allergies but hypersensitivities that can lead to switched metabolism, Dr. Rigden said. Wheat and milk are the most common reactors, with delayed physical findings—such as boggy nasal mucosa or urticaria—appearing 24–72 hours after ingestion. IgG levels may help identify offending foods.

He said he has no conflict of interest with regard to the products he discussed.

SAN DIEGO — Thinking of weight gain simply as the sum of “calories in minus calories out” doesn't cover a minority of obese patients whose dietary records show reasonable caloric balance but who can't seem to lose weight, Dr. Scott R. Rigden said.

These patients may show dietary records reflecting an intake of 1,800–1,900 calories per day, and often say they're tired of health care providers thinking that they're lying in their food diaries because they haven't lost weight, he said at a symposium on obesity sponsored by the American Society of Bariatric Physicians.

“I really think there are a lot of people with special issues, with switched-off metabolisms, that don't fit that model” of calories in/calories out, said Dr. Rigden, a family physician in Chandler, Ariz. who also has practiced bariatrics since 1976. “What has shut down their metabolism, and how do we turn it back on?”

To help these patients, think in terms of the following five subcategories, and tailor dietary and lifestyle recommendations accordingly, he suggested.

▸ Carbohydrate sensitivity. Dr. Rigden defined a patient with carbohydrate sensitivity as one whose genetic makeup produces a rapid spike of glucose after consuming simple carbohydrates and sugars. That glucose spike in turn triggers a spike in insulin and associated metabolic cellular messengers that tell the body to store fat, not burn it. The insulin spike also causes a rapid and uncomfortable drop in glucose that motivates the person to seek more carbohydrates and sugars to remedy the discomfort.

These patients do not yet meet criteria for metabolic syndrome. They have normal fasting insulin and glucose levels and are not hypertensive. “They often have stellar labs, yet a terrible lifelong obesity issue,” Dr. Rigden said. He has devised a nine-item questionnaire focusing on eating and exercise habits to identify this subgroup.

A four-step treatment plan starts with behavior modification to change the patient's relationship with food and an exercise program with at least 150 minutes of moderate aerobic exercise weekly. The third step emphasizes adequate water intake of at least 64 ounces per day—“perhaps the most overlooked part of a weight management program,” he added.

Dietary intervention is the fourth step, starting with a soy protein powder meal replacement plan and switching to a low glycemic diet (which he also called a modified Mediterranean diet) after the patient loses 5%–10% of initial weight.

▸ Metabolic syndrome. Diagnostic criteria for metabolic syndrome include an elevated waist circumference, triglyceride level above 150 mg/dL, an HDL level less than 40 mg/dL for males or less than 50 mg/dL for females, blood pressure above 130/85 mmHg, and fasting blood sugar above 100 mg/dL.

In these patients, foods that have a high glycemic index cause blood sugar levels to plummet, boosting cravings for more high-glycemic foods such as sugars and fat, Dr. Rigden said. He recommends what he calls a “caveman or cavewoman” diet of low-fat, nonstarchy foods that he spells out for patients. After losing 10% of body weight, they switch to the low glycemic diet.

He also recommends nutraceutical medical food with slow-release, amylose-resistant starch, and soluble fiber in the form of 15 g per day of guar gum. Micronutrient support may be the most undervalued component of therapy for these patients, he added.

▸ Hormonal imbalances. Questionnaires and physical exams will help identify the endocrine problems contributing to recalcitrant obesity in these patients, Dr. Rigden said. Most will be due to clinical or subclinical hypothyroidism. “This is probably the No. 1 hormonal imbalance that I see in people who have switched metabolism,” he said.

Polycystic ovarian syndrome or a sex hormone imbalance with estrogen dominance are other problems to consider. Tailor treatment to the particular problem, he said.

▸ Food hypersensitivity. These are not true allergies but hypersensitivities that can lead to switched metabolism, Dr. Rigden said. Wheat and milk are the most common reactors, with delayed physical findings—such as boggy nasal mucosa or urticaria—appearing 24–72 hours after ingestion. IgG levels may help identify offending foods.

He said he has no conflict of interest with regard to the products he discussed.

SAN DIEGO — Thinking of weight gain simply as the sum of “calories in minus calories out” doesn't cover a minority of obese patients whose dietary records show reasonable caloric balance but who can't seem to lose weight, Dr. Scott R. Rigden said.

These patients may show dietary records reflecting an intake of 1,800–1,900 calories per day, and often say they're tired of health care providers thinking that they're lying in their food diaries because they haven't lost weight, he said at a symposium on obesity sponsored by the American Society of Bariatric Physicians.

“I really think there are a lot of people with special issues, with switched-off metabolisms, that don't fit that model” of calories in/calories out, said Dr. Rigden, a family physician in Chandler, Ariz. who also has practiced bariatrics since 1976. “What has shut down their metabolism, and how do we turn it back on?”

To help these patients, think in terms of the following five subcategories, and tailor dietary and lifestyle recommendations accordingly, he suggested.

▸ Carbohydrate sensitivity. Dr. Rigden defined a patient with carbohydrate sensitivity as one whose genetic makeup produces a rapid spike of glucose after consuming simple carbohydrates and sugars. That glucose spike in turn triggers a spike in insulin and associated metabolic cellular messengers that tell the body to store fat, not burn it. The insulin spike also causes a rapid and uncomfortable drop in glucose that motivates the person to seek more carbohydrates and sugars to remedy the discomfort.

These patients do not yet meet criteria for metabolic syndrome. They have normal fasting insulin and glucose levels and are not hypertensive. “They often have stellar labs, yet a terrible lifelong obesity issue,” Dr. Rigden said. He has devised a nine-item questionnaire focusing on eating and exercise habits to identify this subgroup.

A four-step treatment plan starts with behavior modification to change the patient's relationship with food and an exercise program with at least 150 minutes of moderate aerobic exercise weekly. The third step emphasizes adequate water intake of at least 64 ounces per day—“perhaps the most overlooked part of a weight management program,” he added.

Dietary intervention is the fourth step, starting with a soy protein powder meal replacement plan and switching to a low glycemic diet (which he also called a modified Mediterranean diet) after the patient loses 5%–10% of initial weight.

▸ Metabolic syndrome. Diagnostic criteria for metabolic syndrome include an elevated waist circumference, triglyceride level above 150 mg/dL, an HDL level less than 40 mg/dL for males or less than 50 mg/dL for females, blood pressure above 130/85 mmHg, and fasting blood sugar above 100 mg/dL.

In these patients, foods that have a high glycemic index cause blood sugar levels to plummet, boosting cravings for more high-glycemic foods such as sugars and fat, Dr. Rigden said. He recommends what he calls a “caveman or cavewoman” diet of low-fat, nonstarchy foods that he spells out for patients. After losing 10% of body weight, they switch to the low glycemic diet.

He also recommends nutraceutical medical food with slow-release, amylose-resistant starch, and soluble fiber in the form of 15 g per day of guar gum. Micronutrient support may be the most undervalued component of therapy for these patients, he added.

▸ Hormonal imbalances. Questionnaires and physical exams will help identify the endocrine problems contributing to recalcitrant obesity in these patients, Dr. Rigden said. Most will be due to clinical or subclinical hypothyroidism. “This is probably the No. 1 hormonal imbalance that I see in people who have switched metabolism,” he said.

Polycystic ovarian syndrome or a sex hormone imbalance with estrogen dominance are other problems to consider. Tailor treatment to the particular problem, he said.

▸ Food hypersensitivity. These are not true allergies but hypersensitivities that can lead to switched metabolism, Dr. Rigden said. Wheat and milk are the most common reactors, with delayed physical findings—such as boggy nasal mucosa or urticaria—appearing 24–72 hours after ingestion. IgG levels may help identify offending foods.

He said he has no conflict of interest with regard to the products he discussed.

SEATTLE — A heart rate of 90 beats per minute was detrimental in a study of pacemaker-dependent patients with heart failure, Krishnamurti Rao reported at the annual meeting of the Heart Failure Society of America.

Thirteen patients in a crossover study spent 2 months with the heart rate set at 60, 75, or 90 beats per minute (bpm), then were randomized to 2 months at one of the other settings, and then 2 months at the third of the three settings. At 90 bpm, patients had significantly lower ejection fractions and reduced exercise tolerance as measured by maximal oxygen consumption (peak VO₂) and walked significantly shorter distances on 6-minute walk tests, compared with the periods when heart rates were set to 75 or 60 bpm.

“These findings suggest that a mild tachycardia of even 90 [bpm], when chronic, can lead to left ventricular dysfunction,” said Mr. Rao, who conducted the study with associates on the faculty of the University of Maryland, Baltimore, and currently is a student at Boston University. He has no affiliation with the companies that make pacemakers or heart medications.

Patients also fared worse clinically at a setting of 90 bpm, compared with the other two settings. Clinical deterioration caused four patients in the 90-bpm period and one patient in the 60-bpm period to discontinue that setting before the end of the 2 months. Symptoms worsened in some patients immediately upon starting the 90-bpm rate and in others several weeks after changing rates, he noted. Two patients had their rates turned down to 85 or 80 bpm 3–4 weeks into the 90-bpm period.

The study could not determine the optimal heart rate. Based on the data available, the investigators suggest that pacemaker rates should not be set at more than 75 bpm.

Mean peak VO₂ at 60 bpm was 11 mL/kg per minute, at 75 bpm was 11.3 mL/kg per minute, and at 90 bpm was 9.5 mL/kg per minute. The exercise tolerance findings may even underestimate the negative effect of the 90 bpm, because one patient who deteriorated clinically was unable to exercise, he said.

Mean ejection fractions at 60 bpm were 33%, at 75 bpm were 30%, and at 90 bpm were 25%. On the 6-minute walk test, the mean distance was 938 feet at 60 bpm, 996 feet at 75 bpm, and 888 feet at 90 bpm.

Chronic use of β-blockers is known to improve cardiac function, though it has not been clear whether the benefits derive from their effects on heart rate or from other actions, he said.

SEATTLE — A heart rate of 90 beats per minute was detrimental in a study of pacemaker-dependent patients with heart failure, Krishnamurti Rao reported at the annual meeting of the Heart Failure Society of America.

Thirteen patients in a crossover study spent 2 months with the heart rate set at 60, 75, or 90 beats per minute (bpm), then were randomized to 2 months at one of the other settings, and then 2 months at the third of the three settings. At 90 bpm, patients had significantly lower ejection fractions and reduced exercise tolerance as measured by maximal oxygen consumption (peak VO₂) and walked significantly shorter distances on 6-minute walk tests, compared with the periods when heart rates were set to 75 or 60 bpm.

“These findings suggest that a mild tachycardia of even 90 [bpm], when chronic, can lead to left ventricular dysfunction,” said Mr. Rao, who conducted the study with associates on the faculty of the University of Maryland, Baltimore, and currently is a student at Boston University. He has no affiliation with the companies that make pacemakers or heart medications.

Patients also fared worse clinically at a setting of 90 bpm, compared with the other two settings. Clinical deterioration caused four patients in the 90-bpm period and one patient in the 60-bpm period to discontinue that setting before the end of the 2 months. Symptoms worsened in some patients immediately upon starting the 90-bpm rate and in others several weeks after changing rates, he noted. Two patients had their rates turned down to 85 or 80 bpm 3–4 weeks into the 90-bpm period.

The study could not determine the optimal heart rate. Based on the data available, the investigators suggest that pacemaker rates should not be set at more than 75 bpm.

Mean peak VO₂ at 60 bpm was 11 mL/kg per minute, at 75 bpm was 11.3 mL/kg per minute, and at 90 bpm was 9.5 mL/kg per minute. The exercise tolerance findings may even underestimate the negative effect of the 90 bpm, because one patient who deteriorated clinically was unable to exercise, he said.

Mean ejection fractions at 60 bpm were 33%, at 75 bpm were 30%, and at 90 bpm were 25%. On the 6-minute walk test, the mean distance was 938 feet at 60 bpm, 996 feet at 75 bpm, and 888 feet at 90 bpm.

Chronic use of β-blockers is known to improve cardiac function, though it has not been clear whether the benefits derive from their effects on heart rate or from other actions, he said.

SEATTLE — A heart rate of 90 beats per minute was detrimental in a study of pacemaker-dependent patients with heart failure, Krishnamurti Rao reported at the annual meeting of the Heart Failure Society of America.

Thirteen patients in a crossover study spent 2 months with the heart rate set at 60, 75, or 90 beats per minute (bpm), then were randomized to 2 months at one of the other settings, and then 2 months at the third of the three settings. At 90 bpm, patients had significantly lower ejection fractions and reduced exercise tolerance as measured by maximal oxygen consumption (peak VO₂) and walked significantly shorter distances on 6-minute walk tests, compared with the periods when heart rates were set to 75 or 60 bpm.

“These findings suggest that a mild tachycardia of even 90 [bpm], when chronic, can lead to left ventricular dysfunction,” said Mr. Rao, who conducted the study with associates on the faculty of the University of Maryland, Baltimore, and currently is a student at Boston University. He has no affiliation with the companies that make pacemakers or heart medications.

Patients also fared worse clinically at a setting of 90 bpm, compared with the other two settings. Clinical deterioration caused four patients in the 90-bpm period and one patient in the 60-bpm period to discontinue that setting before the end of the 2 months. Symptoms worsened in some patients immediately upon starting the 90-bpm rate and in others several weeks after changing rates, he noted. Two patients had their rates turned down to 85 or 80 bpm 3–4 weeks into the 90-bpm period.

The study could not determine the optimal heart rate. Based on the data available, the investigators suggest that pacemaker rates should not be set at more than 75 bpm.

Mean peak VO₂ at 60 bpm was 11 mL/kg per minute, at 75 bpm was 11.3 mL/kg per minute, and at 90 bpm was 9.5 mL/kg per minute. The exercise tolerance findings may even underestimate the negative effect of the 90 bpm, because one patient who deteriorated clinically was unable to exercise, he said.

Mean ejection fractions at 60 bpm were 33%, at 75 bpm were 30%, and at 90 bpm were 25%. On the 6-minute walk test, the mean distance was 938 feet at 60 bpm, 996 feet at 75 bpm, and 888 feet at 90 bpm.

Chronic use of β-blockers is known to improve cardiac function, though it has not been clear whether the benefits derive from their effects on heart rate or from other actions, he said.

SEATTLE — Adding an angiotensin receptor blocker to ACE inhibitor therapy in patients with heart failure significantly increased the risk of hypotension and renal failure, with a trend toward an increased risk for hyperkalemia, compared with ACE inhibitor therapy alone, in a meta-analysis of randomized, controlled trials, Dr. Rachid Lakhdar reported.

A previous meta-analysis of randomized, controlled studies found that combination therapy with an angiotensin receptor blocker (ARB) and an ACE inhibitor reduced hospitalizations in patients with heart failure but provided no survival benefit, he said in poster presentation at the annual meeting of the Heart Failure Society of America. The earlier meta-analysis did not analyze the safety of this drug combination.

Dr. Lakhdar and his coinvestigator, Dr. Mouaz H. Al-Mallah, both of Henry Ford Hospital, Detroit, searched the medical literature and abstracts from medical meetings and analyzed safety data from nine studies including 18,160 patients with heart failure. The incidence of side effects was low but was 25% higher in the combination therapy arms, compared with ACE inhibitor therapy alone, they reported.

Patients on combined therapy were 54% more likely to develop hypotension and twice as likely to develop worsened renal function, compared with patients on an ACE inhibitor alone. A 2.5-fold increase in risk for hyperkalemia was not statistically significant.

“Those side effects—hypotension, hyperkalemia, and renal failure—are related directly or indirectly to reduced angiotensin II formation,” the investigators noted. The rates of cough and angioedema did not differ significantly between groups.

Not all the studies showed a significant increase in side effects with the combination therapy, perhaps owing to small sample size, short follow-up, or the characteristics of different drugs and doses. The longer trials found more side effects than shorter trials did, so it may be that some adverse events associated with the combination therapy would have shown up over time, Dr. Lakhdar and Dr. Al-Mallah suggested. “The presence of this excess risk, lack of a definitive survival benefit of this strategy, and the availability of other agents with proven survival benefit in heart failure in combination with ACE inhibitors suggests that the addition of an ARB to ACE inhibitor therapy should be discouraged,” they said.

The investigators reported that they have no associations with the companies that make the drugs.

SEATTLE — Adding an angiotensin receptor blocker to ACE inhibitor therapy in patients with heart failure significantly increased the risk of hypotension and renal failure, with a trend toward an increased risk for hyperkalemia, compared with ACE inhibitor therapy alone, in a meta-analysis of randomized, controlled trials, Dr. Rachid Lakhdar reported.

A previous meta-analysis of randomized, controlled studies found that combination therapy with an angiotensin receptor blocker (ARB) and an ACE inhibitor reduced hospitalizations in patients with heart failure but provided no survival benefit, he said in poster presentation at the annual meeting of the Heart Failure Society of America. The earlier meta-analysis did not analyze the safety of this drug combination.

Dr. Lakhdar and his coinvestigator, Dr. Mouaz H. Al-Mallah, both of Henry Ford Hospital, Detroit, searched the medical literature and abstracts from medical meetings and analyzed safety data from nine studies including 18,160 patients with heart failure. The incidence of side effects was low but was 25% higher in the combination therapy arms, compared with ACE inhibitor therapy alone, they reported.

Patients on combined therapy were 54% more likely to develop hypotension and twice as likely to develop worsened renal function, compared with patients on an ACE inhibitor alone. A 2.5-fold increase in risk for hyperkalemia was not statistically significant.

“Those side effects—hypotension, hyperkalemia, and renal failure—are related directly or indirectly to reduced angiotensin II formation,” the investigators noted. The rates of cough and angioedema did not differ significantly between groups.

Not all the studies showed a significant increase in side effects with the combination therapy, perhaps owing to small sample size, short follow-up, or the characteristics of different drugs and doses. The longer trials found more side effects than shorter trials did, so it may be that some adverse events associated with the combination therapy would have shown up over time, Dr. Lakhdar and Dr. Al-Mallah suggested. “The presence of this excess risk, lack of a definitive survival benefit of this strategy, and the availability of other agents with proven survival benefit in heart failure in combination with ACE inhibitors suggests that the addition of an ARB to ACE inhibitor therapy should be discouraged,” they said.

The investigators reported that they have no associations with the companies that make the drugs.

SEATTLE — Adding an angiotensin receptor blocker to ACE inhibitor therapy in patients with heart failure significantly increased the risk of hypotension and renal failure, with a trend toward an increased risk for hyperkalemia, compared with ACE inhibitor therapy alone, in a meta-analysis of randomized, controlled trials, Dr. Rachid Lakhdar reported.

A previous meta-analysis of randomized, controlled studies found that combination therapy with an angiotensin receptor blocker (ARB) and an ACE inhibitor reduced hospitalizations in patients with heart failure but provided no survival benefit, he said in poster presentation at the annual meeting of the Heart Failure Society of America. The earlier meta-analysis did not analyze the safety of this drug combination.

Dr. Lakhdar and his coinvestigator, Dr. Mouaz H. Al-Mallah, both of Henry Ford Hospital, Detroit, searched the medical literature and abstracts from medical meetings and analyzed safety data from nine studies including 18,160 patients with heart failure. The incidence of side effects was low but was 25% higher in the combination therapy arms, compared with ACE inhibitor therapy alone, they reported.

Patients on combined therapy were 54% more likely to develop hypotension and twice as likely to develop worsened renal function, compared with patients on an ACE inhibitor alone. A 2.5-fold increase in risk for hyperkalemia was not statistically significant.

“Those side effects—hypotension, hyperkalemia, and renal failure—are related directly or indirectly to reduced angiotensin II formation,” the investigators noted. The rates of cough and angioedema did not differ significantly between groups.

Not all the studies showed a significant increase in side effects with the combination therapy, perhaps owing to small sample size, short follow-up, or the characteristics of different drugs and doses. The longer trials found more side effects than shorter trials did, so it may be that some adverse events associated with the combination therapy would have shown up over time, Dr. Lakhdar and Dr. Al-Mallah suggested. “The presence of this excess risk, lack of a definitive survival benefit of this strategy, and the availability of other agents with proven survival benefit in heart failure in combination with ACE inhibitors suggests that the addition of an ARB to ACE inhibitor therapy should be discouraged,” they said.

The investigators reported that they have no associations with the companies that make the drugs.

SAN FRANCISCO — Several factors can help guide empiric therapy for acute otitis media by flagging patients at higher risk for infection with multiple organisms or resistant organisms, Dr. Mendel E. Singer said in a poster presentation at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Patients with bilateral infection, those with a history of acute otitis media, or patients infected in the fourth quarter of the year may warrant high-dose aminopenicillin therapy rather than low doses, said Dr. Singer, an epidemiologist at Case Western Reserve University, Cleveland.

He and associates retrospectively analyzed pooled data from 14 studies of patients aged 3–36 months treated at Soroka University Medical Center, Beer Sheva, Israel, for acute otitis media from 1994 to 2004. Among 967 patients, 23% were infected with multiple pathogens.

The 63% of patients with bilateral ear infections were 53% more likely to have multiple pathogens than patients with unilateral infections, he said at the meeting, sponsored by the American Society for Microbiology.

Analysis of drug resistance in a subset of 333 patients infected with Streptococcus pneumoniae found that 33% had organisms resistant to the treatment drug. Data showed high rates of resistance to trimethoprim-sulfamethoxazole (in 67% of patients treated with these drugs) and to the cephalosporins cefdinir, cefaclor, or cefuroxime (in 59% of patients treated with these). There was moderate resistance to azithromycin (in 23%) and to low-dose regimens of the aminopenicillins amoxicillin or amoxicillin clavulanate (in 16% of patients given these drugs). Only 1% of isolates treated with high-dose aminopenicillins were resistant to therapy.

S. pneumoniae was 32% more likely to be drug-resistant in girls than in boys. A history of prior acute otitis media nearly tripled the risk for resistant S. pneumoniae. Infection in the fourth quarter of the year doubled the risk for resistance.

The study suggests that patients with any of these risk factors might best be treated empirically with high-dose amoxicillin or amoxicillin-clavulanate, Dr. Singer said. Patients without these characteristics may respond sufficiently to low doses of these drugs or to treatment with the other medications used in the study.

Dr. Singer has no affiliations with the companies that market the drugs discussed.

Besides S. pneumoniae, infection with Haemophilus influenzae was common, found in nearly half of patients, the physician said.

SAN FRANCISCO — Several factors can help guide empiric therapy for acute otitis media by flagging patients at higher risk for infection with multiple organisms or resistant organisms, Dr. Mendel E. Singer said in a poster presentation at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Patients with bilateral infection, those with a history of acute otitis media, or patients infected in the fourth quarter of the year may warrant high-dose aminopenicillin therapy rather than low doses, said Dr. Singer, an epidemiologist at Case Western Reserve University, Cleveland.

He and associates retrospectively analyzed pooled data from 14 studies of patients aged 3–36 months treated at Soroka University Medical Center, Beer Sheva, Israel, for acute otitis media from 1994 to 2004. Among 967 patients, 23% were infected with multiple pathogens.

The 63% of patients with bilateral ear infections were 53% more likely to have multiple pathogens than patients with unilateral infections, he said at the meeting, sponsored by the American Society for Microbiology.

Analysis of drug resistance in a subset of 333 patients infected with Streptococcus pneumoniae found that 33% had organisms resistant to the treatment drug. Data showed high rates of resistance to trimethoprim-sulfamethoxazole (in 67% of patients treated with these drugs) and to the cephalosporins cefdinir, cefaclor, or cefuroxime (in 59% of patients treated with these). There was moderate resistance to azithromycin (in 23%) and to low-dose regimens of the aminopenicillins amoxicillin or amoxicillin clavulanate (in 16% of patients given these drugs). Only 1% of isolates treated with high-dose aminopenicillins were resistant to therapy.

S. pneumoniae was 32% more likely to be drug-resistant in girls than in boys. A history of prior acute otitis media nearly tripled the risk for resistant S. pneumoniae. Infection in the fourth quarter of the year doubled the risk for resistance.

The study suggests that patients with any of these risk factors might best be treated empirically with high-dose amoxicillin or amoxicillin-clavulanate, Dr. Singer said. Patients without these characteristics may respond sufficiently to low doses of these drugs or to treatment with the other medications used in the study.

Dr. Singer has no affiliations with the companies that market the drugs discussed.

Besides S. pneumoniae, infection with Haemophilus influenzae was common, found in nearly half of patients, the physician said.

SAN FRANCISCO — Several factors can help guide empiric therapy for acute otitis media by flagging patients at higher risk for infection with multiple organisms or resistant organisms, Dr. Mendel E. Singer said in a poster presentation at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Patients with bilateral infection, those with a history of acute otitis media, or patients infected in the fourth quarter of the year may warrant high-dose aminopenicillin therapy rather than low doses, said Dr. Singer, an epidemiologist at Case Western Reserve University, Cleveland.

He and associates retrospectively analyzed pooled data from 14 studies of patients aged 3–36 months treated at Soroka University Medical Center, Beer Sheva, Israel, for acute otitis media from 1994 to 2004. Among 967 patients, 23% were infected with multiple pathogens.

The 63% of patients with bilateral ear infections were 53% more likely to have multiple pathogens than patients with unilateral infections, he said at the meeting, sponsored by the American Society for Microbiology.

Analysis of drug resistance in a subset of 333 patients infected with Streptococcus pneumoniae found that 33% had organisms resistant to the treatment drug. Data showed high rates of resistance to trimethoprim-sulfamethoxazole (in 67% of patients treated with these drugs) and to the cephalosporins cefdinir, cefaclor, or cefuroxime (in 59% of patients treated with these). There was moderate resistance to azithromycin (in 23%) and to low-dose regimens of the aminopenicillins amoxicillin or amoxicillin clavulanate (in 16% of patients given these drugs). Only 1% of isolates treated with high-dose aminopenicillins were resistant to therapy.

S. pneumoniae was 32% more likely to be drug-resistant in girls than in boys. A history of prior acute otitis media nearly tripled the risk for resistant S. pneumoniae. Infection in the fourth quarter of the year doubled the risk for resistance.

The study suggests that patients with any of these risk factors might best be treated empirically with high-dose amoxicillin or amoxicillin-clavulanate, Dr. Singer said. Patients without these characteristics may respond sufficiently to low doses of these drugs or to treatment with the other medications used in the study.

Dr. Singer has no affiliations with the companies that market the drugs discussed.

Besides S. pneumoniae, infection with Haemophilus influenzae was common, found in nearly half of patients, the physician said.

SAN FRANCISCO — Children with respiratory tract infection and their parents generally preferred treatment with clarithromycin granules sipped through a strawlike device than with conventional clarithromycin suspension syrup, Dr. Dieter Adam reported.

A randomized, open-label study in 263 children aged 2–12 years treated for 7–10 days found no significant difference in efficacy after completion of the therapy, with the bacterial organism eradicated in 93% by either formulation.

In the sipping group, however, 23% had clinical symptoms resolve in 3–5 days compared with 13% in the suspension group, he said in a poster presentation at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Parents assessed the sipped formulation as easier to administer and better tasting to the child, compared with the suspension form.

Rates of adherence to therapy were significantly higher with the sipped form than with the suspension in the first 5 days of therapy (92% vs. 38%) and at the end of treatment (94% vs. 86%), said Dr. Adam, a pediatrician at the University of Munich, Germany, and his associates.

The study was funded by Grünenthal GmbH, which markets the Siptechnology formulation in Latin America and some European countries. The company is pursuing U.S. approval, said Dr. Adam, who has no other affiliation with the company.

The Siptechnology consists of a plastic strawlike device loaded with a dose of drug granules with a film coating to mask the taste. The study randomized patients in a 2:1 ratio to the Siptechnology or suspension syrup. Children in the Siptechnology group used the device to sip their preferred soft drink through a liquid-permeable controller on the end of the “straw,” ingesting both the soda and drug granules.

Both regimens delivered 15 mg/kg per day divided into two equal doses. Patients were treated for acute otitis media in 20% of cases, tonsillitis in 25%, pharyngitis in 30%, and acute bronchitis in 42%. (Some children had more than one infection.)

“Normally, clarithromycin has a bitter taste” that may interfere with adherence and might reduce cure rates in the real world compared with the Siptechnology, although efficacy was comparable in this trial setting, Dr. Adam said at the conference, sponsored by the American Society for Microbiology.

Patients or their parents reported the taste was good or very good in 62% of the Siptechnology group compared with 36% of the suspension group. Patients ingested the drug without resistance or resentment in 88% of doses in the Siptechnology group and 67% of doses in the suspension group.

SAN FRANCISCO — Children with respiratory tract infection and their parents generally preferred treatment with clarithromycin granules sipped through a strawlike device than with conventional clarithromycin suspension syrup, Dr. Dieter Adam reported.

A randomized, open-label study in 263 children aged 2–12 years treated for 7–10 days found no significant difference in efficacy after completion of the therapy, with the bacterial organism eradicated in 93% by either formulation.

In the sipping group, however, 23% had clinical symptoms resolve in 3–5 days compared with 13% in the suspension group, he said in a poster presentation at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Parents assessed the sipped formulation as easier to administer and better tasting to the child, compared with the suspension form.

Rates of adherence to therapy were significantly higher with the sipped form than with the suspension in the first 5 days of therapy (92% vs. 38%) and at the end of treatment (94% vs. 86%), said Dr. Adam, a pediatrician at the University of Munich, Germany, and his associates.

The study was funded by Grünenthal GmbH, which markets the Siptechnology formulation in Latin America and some European countries. The company is pursuing U.S. approval, said Dr. Adam, who has no other affiliation with the company.

The Siptechnology consists of a plastic strawlike device loaded with a dose of drug granules with a film coating to mask the taste. The study randomized patients in a 2:1 ratio to the Siptechnology or suspension syrup. Children in the Siptechnology group used the device to sip their preferred soft drink through a liquid-permeable controller on the end of the “straw,” ingesting both the soda and drug granules.

Both regimens delivered 15 mg/kg per day divided into two equal doses. Patients were treated for acute otitis media in 20% of cases, tonsillitis in 25%, pharyngitis in 30%, and acute bronchitis in 42%. (Some children had more than one infection.)

“Normally, clarithromycin has a bitter taste” that may interfere with adherence and might reduce cure rates in the real world compared with the Siptechnology, although efficacy was comparable in this trial setting, Dr. Adam said at the conference, sponsored by the American Society for Microbiology.

Patients or their parents reported the taste was good or very good in 62% of the Siptechnology group compared with 36% of the suspension group. Patients ingested the drug without resistance or resentment in 88% of doses in the Siptechnology group and 67% of doses in the suspension group.

SAN FRANCISCO — Children with respiratory tract infection and their parents generally preferred treatment with clarithromycin granules sipped through a strawlike device than with conventional clarithromycin suspension syrup, Dr. Dieter Adam reported.

A randomized, open-label study in 263 children aged 2–12 years treated for 7–10 days found no significant difference in efficacy after completion of the therapy, with the bacterial organism eradicated in 93% by either formulation.

In the sipping group, however, 23% had clinical symptoms resolve in 3–5 days compared with 13% in the suspension group, he said in a poster presentation at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Parents assessed the sipped formulation as easier to administer and better tasting to the child, compared with the suspension form.

Rates of adherence to therapy were significantly higher with the sipped form than with the suspension in the first 5 days of therapy (92% vs. 38%) and at the end of treatment (94% vs. 86%), said Dr. Adam, a pediatrician at the University of Munich, Germany, and his associates.

The study was funded by Grünenthal GmbH, which markets the Siptechnology formulation in Latin America and some European countries. The company is pursuing U.S. approval, said Dr. Adam, who has no other affiliation with the company.

The Siptechnology consists of a plastic strawlike device loaded with a dose of drug granules with a film coating to mask the taste. The study randomized patients in a 2:1 ratio to the Siptechnology or suspension syrup. Children in the Siptechnology group used the device to sip their preferred soft drink through a liquid-permeable controller on the end of the “straw,” ingesting both the soda and drug granules.

Both regimens delivered 15 mg/kg per day divided into two equal doses. Patients were treated for acute otitis media in 20% of cases, tonsillitis in 25%, pharyngitis in 30%, and acute bronchitis in 42%. (Some children had more than one infection.)

“Normally, clarithromycin has a bitter taste” that may interfere with adherence and might reduce cure rates in the real world compared with the Siptechnology, although efficacy was comparable in this trial setting, Dr. Adam said at the conference, sponsored by the American Society for Microbiology.

Patients or their parents reported the taste was good or very good in 62% of the Siptechnology group compared with 36% of the suspension group. Patients ingested the drug without resistance or resentment in 88% of doses in the Siptechnology group and 67% of doses in the suspension group.

SAN DIEGO — A hormonal imbalance may be the reason that some obese patients fail to lose weight despite appropriate efforts to do so, Dr. Neil W. Hirschenbein said at a symposium on obesity sponsored by the American Society of Bariatric Physicians.

About 90% of people will lose weight if they eat a balanced, whole-foods diet, supplement that with nutrients as needed (vitamins, minerals, fish oils, etc.), engage in cross-training exercise, and maintain a healthy lifestyle. Perhaps 10% of overweight people will not lose weight even on this regimen, however, because of “damaged metabolisms,” said Dr. Hirschenbein, an internist and gastroenterologist and medical director for the La Jolla (Calif.) Institute of Comprehensive Medicine.

He described some of the more common hormonal imbalances that contribute to recalcitrant obesity:

▸ Hypothyroidism. Undiagnosed hypothyroidism is a problem in many patients who seek help for obesity after being told by an endocrinologist that their thyroid-stimulating hormone (TSH) levels are just outside the normal range, but not to worry about it. If clinicians could improve their ability to combine clinical symptoms with near-normal TSH results, “we would find more hypothyroidism.”

Getting lab tests to check for thyroid disorders is essential, he added. “I have lots of patients coming in to deal with their thyroid problems because their physicians have refused to even order the tests,” he said.

▸ Cortisol. Stress-induced cortisol imbalance is a major factor in weight loss resistance, Dr. Hirschenbein said. He asks patients to rate their level of stress on a scale of 1–10, with 10 being the worst, and frequently they rate it a 12. “Having good stress can be as hard on your adrenal glands as bad stress,” with stress hormones released by both crises and welcome events.

Stress releases the “fight or flight” hormones epinephrine and norepinephrine, which later return to normal levels, and the stress hormone cortisol, which can remain elevated for longer periods or even persistently with chronic stress. The effects of cortisol stimulate appetite. High cortisol levels, which favor fat deposition and a higher set point for body fat, are associated with central obesity. Stress management techniques can help these patients.

▸ Insulin resistance. Both fasting insulin and fasting glucose levels should be measured in patients resistant to weight loss, he advised. Insulin resistance is associated with excess weight and metabolic syndrome.

“A patient may have a good sugar level but a very high insulin level. If all you're doing is looking at sugars, you'll miss some of these problems until later,” he said.

▸ Sleep deprivation. Inadequate sleep may lead to the development of insulin resistance, and is associated with weight gain even in people with excellent diets who exercise regularly. In one study, when sleep was decreased from 8 hours to 4 hours each night, the resulting alterations in glucose metabolism in some cases resembled those of patients with type 2 diabetes, he said.

The results of another study found that people who sleep 2–4 hours per night are 73% more likely to be obese than normal sleepers who get 8–10 hours per night. Patients sleeping only 5 hours per night were 50% more likely to be obese than normal sleepers.

Lack of sleep increases levels of ghrelin, a hunger hormone, and decreases levels of leptin, a satiety hormone. The result: overeating and weight gain.

Dr. Hirschenbein advised asking patients very specific questions such as what time they go to bed, how quickly they fall asleep, how long they sleep, what time they wake up, and whether an alarm is needed to wake up.

He added that techniques such as keeping the room quiet, dark, and cool; limiting fluids before sleep; avoiding stimulating activities right before bedtime; and allowing enough sleep time might help patients obtain adequate rest.

About 10% of overweight people on a diet regimen will not lose weight because of 'damaged metabolisms.' DR. HIRSCHENBEIN

SAN DIEGO — A hormonal imbalance may be the reason that some obese patients fail to lose weight despite appropriate efforts to do so, Dr. Neil W. Hirschenbein said at a symposium on obesity sponsored by the American Society of Bariatric Physicians.

About 90% of people will lose weight if they eat a balanced, whole-foods diet, supplement that with nutrients as needed (vitamins, minerals, fish oils, etc.), engage in cross-training exercise, and maintain a healthy lifestyle. Perhaps 10% of overweight people will not lose weight even on this regimen, however, because of “damaged metabolisms,” said Dr. Hirschenbein, an internist and gastroenterologist and medical director for the La Jolla (Calif.) Institute of Comprehensive Medicine.

He described some of the more common hormonal imbalances that contribute to recalcitrant obesity:

▸ Hypothyroidism. Undiagnosed hypothyroidism is a problem in many patients who seek help for obesity after being told by an endocrinologist that their thyroid-stimulating hormone (TSH) levels are just outside the normal range, but not to worry about it. If clinicians could improve their ability to combine clinical symptoms with near-normal TSH results, “we would find more hypothyroidism.”

Getting lab tests to check for thyroid disorders is essential, he added. “I have lots of patients coming in to deal with their thyroid problems because their physicians have refused to even order the tests,” he said.

▸ Cortisol. Stress-induced cortisol imbalance is a major factor in weight loss resistance, Dr. Hirschenbein said. He asks patients to rate their level of stress on a scale of 1–10, with 10 being the worst, and frequently they rate it a 12. “Having good stress can be as hard on your adrenal glands as bad stress,” with stress hormones released by both crises and welcome events.

Stress releases the “fight or flight” hormones epinephrine and norepinephrine, which later return to normal levels, and the stress hormone cortisol, which can remain elevated for longer periods or even persistently with chronic stress. The effects of cortisol stimulate appetite. High cortisol levels, which favor fat deposition and a higher set point for body fat, are associated with central obesity. Stress management techniques can help these patients.

▸ Insulin resistance. Both fasting insulin and fasting glucose levels should be measured in patients resistant to weight loss, he advised. Insulin resistance is associated with excess weight and metabolic syndrome.

“A patient may have a good sugar level but a very high insulin level. If all you're doing is looking at sugars, you'll miss some of these problems until later,” he said.

▸ Sleep deprivation. Inadequate sleep may lead to the development of insulin resistance, and is associated with weight gain even in people with excellent diets who exercise regularly. In one study, when sleep was decreased from 8 hours to 4 hours each night, the resulting alterations in glucose metabolism in some cases resembled those of patients with type 2 diabetes, he said.

The results of another study found that people who sleep 2–4 hours per night are 73% more likely to be obese than normal sleepers who get 8–10 hours per night. Patients sleeping only 5 hours per night were 50% more likely to be obese than normal sleepers.

Lack of sleep increases levels of ghrelin, a hunger hormone, and decreases levels of leptin, a satiety hormone. The result: overeating and weight gain.

Dr. Hirschenbein advised asking patients very specific questions such as what time they go to bed, how quickly they fall asleep, how long they sleep, what time they wake up, and whether an alarm is needed to wake up.

He added that techniques such as keeping the room quiet, dark, and cool; limiting fluids before sleep; avoiding stimulating activities right before bedtime; and allowing enough sleep time might help patients obtain adequate rest.

About 10% of overweight people on a diet regimen will not lose weight because of 'damaged metabolisms.' DR. HIRSCHENBEIN

SAN DIEGO — A hormonal imbalance may be the reason that some obese patients fail to lose weight despite appropriate efforts to do so, Dr. Neil W. Hirschenbein said at a symposium on obesity sponsored by the American Society of Bariatric Physicians.

About 90% of people will lose weight if they eat a balanced, whole-foods diet, supplement that with nutrients as needed (vitamins, minerals, fish oils, etc.), engage in cross-training exercise, and maintain a healthy lifestyle. Perhaps 10% of overweight people will not lose weight even on this regimen, however, because of “damaged metabolisms,” said Dr. Hirschenbein, an internist and gastroenterologist and medical director for the La Jolla (Calif.) Institute of Comprehensive Medicine.

He described some of the more common hormonal imbalances that contribute to recalcitrant obesity:

▸ Hypothyroidism. Undiagnosed hypothyroidism is a problem in many patients who seek help for obesity after being told by an endocrinologist that their thyroid-stimulating hormone (TSH) levels are just outside the normal range, but not to worry about it. If clinicians could improve their ability to combine clinical symptoms with near-normal TSH results, “we would find more hypothyroidism.”

Getting lab tests to check for thyroid disorders is essential, he added. “I have lots of patients coming in to deal with their thyroid problems because their physicians have refused to even order the tests,” he said.

▸ Cortisol. Stress-induced cortisol imbalance is a major factor in weight loss resistance, Dr. Hirschenbein said. He asks patients to rate their level of stress on a scale of 1–10, with 10 being the worst, and frequently they rate it a 12. “Having good stress can be as hard on your adrenal glands as bad stress,” with stress hormones released by both crises and welcome events.

Stress releases the “fight or flight” hormones epinephrine and norepinephrine, which later return to normal levels, and the stress hormone cortisol, which can remain elevated for longer periods or even persistently with chronic stress. The effects of cortisol stimulate appetite. High cortisol levels, which favor fat deposition and a higher set point for body fat, are associated with central obesity. Stress management techniques can help these patients.

▸ Insulin resistance. Both fasting insulin and fasting glucose levels should be measured in patients resistant to weight loss, he advised. Insulin resistance is associated with excess weight and metabolic syndrome.

“A patient may have a good sugar level but a very high insulin level. If all you're doing is looking at sugars, you'll miss some of these problems until later,” he said.

▸ Sleep deprivation. Inadequate sleep may lead to the development of insulin resistance, and is associated with weight gain even in people with excellent diets who exercise regularly. In one study, when sleep was decreased from 8 hours to 4 hours each night, the resulting alterations in glucose metabolism in some cases resembled those of patients with type 2 diabetes, he said.

The results of another study found that people who sleep 2–4 hours per night are 73% more likely to be obese than normal sleepers who get 8–10 hours per night. Patients sleeping only 5 hours per night were 50% more likely to be obese than normal sleepers.

Lack of sleep increases levels of ghrelin, a hunger hormone, and decreases levels of leptin, a satiety hormone. The result: overeating and weight gain.

Dr. Hirschenbein advised asking patients very specific questions such as what time they go to bed, how quickly they fall asleep, how long they sleep, what time they wake up, and whether an alarm is needed to wake up.

He added that techniques such as keeping the room quiet, dark, and cool; limiting fluids before sleep; avoiding stimulating activities right before bedtime; and allowing enough sleep time might help patients obtain adequate rest.

About 10% of overweight people on a diet regimen will not lose weight because of 'damaged metabolisms.' DR. HIRSCHENBEIN

SAN FRANCISCO — An experimental fluoroquinolone compared favorably with amoxicillin or ceftriaxone for treating community-acquired pneumonia in two phase III trials, researchers reported in poster presentations at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

One study of 308 outpatients in Europe and Russia with mild to moderate community-acquired pneumonia (CAP) showed similar response rates in patients given 5 days of oral garenoxacin or 10 days of oral amoxicillin, reported Dr. Hetty Waskin of Schering-Plough Research Institute, Kenilworth, N.J. The company is developing garenoxacin and funded the study. The lead investigator in the study was Dr. N. Mogulkoc of Ege University, Izmir, Turkey.

Evaluations 7–14 days after completing therapy showed clinical responses in 91% of patients randomized to once-daily doses of 400 mg garenoxacin and in 87% of patients given amoxicillin 1 g t.i.d. Bacterial eradication was achieved in 88% of the garenoxacin group and 91% of the amoxicillin group. Drug-related adverse events—most commonly diarrhea, headache, abdominal pain, and nausea—were seen in 13% of patients in the garenoxacin group and 12% of those in the amoxicillin group.

The second study of 406 hospitalized patients with CAP showed an 88% clinical cure rate in 328 evaluable patients regardless of treatment group. Patients were randomized to either IV garenoxacin 400 mg/day with possible step-down to oral garenoxacin 400 mg/day or IV ceftriaxone 1–2 g/day with possible step-down to oral clarithromycin 500 mg b.i.d. If atypical pneumonia was suspected, the ceftriaxone patients also could receive IV erythromycin 0.5–1 g every 6 hours.

Patients were treated for 7–14 days and evaluated for cure 7–14 days after completing therapy, said Dr. Mark E. Dowell of Casper, Wyo., the primary investigator. He has no other relationship with Schering-Plough except that the company funded the study and a company employee (Dr. Waskin) was a coinvestigator.

SAN FRANCISCO — An experimental fluoroquinolone compared favorably with amoxicillin or ceftriaxone for treating community-acquired pneumonia in two phase III trials, researchers reported in poster presentations at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

One study of 308 outpatients in Europe and Russia with mild to moderate community-acquired pneumonia (CAP) showed similar response rates in patients given 5 days of oral garenoxacin or 10 days of oral amoxicillin, reported Dr. Hetty Waskin of Schering-Plough Research Institute, Kenilworth, N.J. The company is developing garenoxacin and funded the study. The lead investigator in the study was Dr. N. Mogulkoc of Ege University, Izmir, Turkey.

Evaluations 7–14 days after completing therapy showed clinical responses in 91% of patients randomized to once-daily doses of 400 mg garenoxacin and in 87% of patients given amoxicillin 1 g t.i.d. Bacterial eradication was achieved in 88% of the garenoxacin group and 91% of the amoxicillin group. Drug-related adverse events—most commonly diarrhea, headache, abdominal pain, and nausea—were seen in 13% of patients in the garenoxacin group and 12% of those in the amoxicillin group.

The second study of 406 hospitalized patients with CAP showed an 88% clinical cure rate in 328 evaluable patients regardless of treatment group. Patients were randomized to either IV garenoxacin 400 mg/day with possible step-down to oral garenoxacin 400 mg/day or IV ceftriaxone 1–2 g/day with possible step-down to oral clarithromycin 500 mg b.i.d. If atypical pneumonia was suspected, the ceftriaxone patients also could receive IV erythromycin 0.5–1 g every 6 hours.

Patients were treated for 7–14 days and evaluated for cure 7–14 days after completing therapy, said Dr. Mark E. Dowell of Casper, Wyo., the primary investigator. He has no other relationship with Schering-Plough except that the company funded the study and a company employee (Dr. Waskin) was a coinvestigator.

SAN FRANCISCO — An experimental fluoroquinolone compared favorably with amoxicillin or ceftriaxone for treating community-acquired pneumonia in two phase III trials, researchers reported in poster presentations at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

One study of 308 outpatients in Europe and Russia with mild to moderate community-acquired pneumonia (CAP) showed similar response rates in patients given 5 days of oral garenoxacin or 10 days of oral amoxicillin, reported Dr. Hetty Waskin of Schering-Plough Research Institute, Kenilworth, N.J. The company is developing garenoxacin and funded the study. The lead investigator in the study was Dr. N. Mogulkoc of Ege University, Izmir, Turkey.

Evaluations 7–14 days after completing therapy showed clinical responses in 91% of patients randomized to once-daily doses of 400 mg garenoxacin and in 87% of patients given amoxicillin 1 g t.i.d. Bacterial eradication was achieved in 88% of the garenoxacin group and 91% of the amoxicillin group. Drug-related adverse events—most commonly diarrhea, headache, abdominal pain, and nausea—were seen in 13% of patients in the garenoxacin group and 12% of those in the amoxicillin group.

The second study of 406 hospitalized patients with CAP showed an 88% clinical cure rate in 328 evaluable patients regardless of treatment group. Patients were randomized to either IV garenoxacin 400 mg/day with possible step-down to oral garenoxacin 400 mg/day or IV ceftriaxone 1–2 g/day with possible step-down to oral clarithromycin 500 mg b.i.d. If atypical pneumonia was suspected, the ceftriaxone patients also could receive IV erythromycin 0.5–1 g every 6 hours.

Patients were treated for 7–14 days and evaluated for cure 7–14 days after completing therapy, said Dr. Mark E. Dowell of Casper, Wyo., the primary investigator. He has no other relationship with Schering-Plough except that the company funded the study and a company employee (Dr. Waskin) was a coinvestigator.

SAN FRANCISCO — Drug resistance was a common cause of treatment failure in 26 patients with community-acquired pneumonia who developed bacteremia while being treated with macrolide antibiotics, Dr. Gavin Bayan Grant said at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Of the 26 patients who developed bacteremia while on erythromycin, clarithromycin, or azithromycin therapy, 21 (81%) had resistant organisms, compared with 15 (44%) of 34 patients who developed bacteremia after recent use of one of the macrolides (defined as 16–90 days before the bacteremia diagnosis) and 14% of 721 patients who had not been taking any antibiotics and developed bacteremia.

Macrolide antibiotics are standard therapy for outpatient treatment of pneumonia, and evidence that significant macrolide resistance occurs has been inconclusive, said Dr. Grant of the Centers for Disease Control and Prevention, Atlanta. The current findings provide further evidence that resistance can lead to treatment failure with macrolides, which may inform clinical decisions to change antibiotics in some patients, he said at the meeting, sponsored by the American Society for Microbiology.

Dr. Grant has no association with the companies that make macrolides.

After controlling for patient age, immunosuppression, chronic comorbidities, and residence in a long-term care facility, patients failing macrolide therapy were 5 times more likely to have resistant organisms, compared with patients who developed bacteremia after recent macrolide use, and 26 times more likely to have resistance than patients with bacteremia who had not been taking antibiotics.

The study also found that clinicians who define macrolide resistance using a cutoff of a minimum inhibitory concentration (MIC) of at least 16 mcg/mL will miss a significant percentage of the treatment failures. “Failures often occur at macrolide MICs less than 16 mcg/mL,” he said.

SAN FRANCISCO — Drug resistance was a common cause of treatment failure in 26 patients with community-acquired pneumonia who developed bacteremia while being treated with macrolide antibiotics, Dr. Gavin Bayan Grant said at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Of the 26 patients who developed bacteremia while on erythromycin, clarithromycin, or azithromycin therapy, 21 (81%) had resistant organisms, compared with 15 (44%) of 34 patients who developed bacteremia after recent use of one of the macrolides (defined as 16–90 days before the bacteremia diagnosis) and 14% of 721 patients who had not been taking any antibiotics and developed bacteremia.

Macrolide antibiotics are standard therapy for outpatient treatment of pneumonia, and evidence that significant macrolide resistance occurs has been inconclusive, said Dr. Grant of the Centers for Disease Control and Prevention, Atlanta. The current findings provide further evidence that resistance can lead to treatment failure with macrolides, which may inform clinical decisions to change antibiotics in some patients, he said at the meeting, sponsored by the American Society for Microbiology.

Dr. Grant has no association with the companies that make macrolides.

After controlling for patient age, immunosuppression, chronic comorbidities, and residence in a long-term care facility, patients failing macrolide therapy were 5 times more likely to have resistant organisms, compared with patients who developed bacteremia after recent macrolide use, and 26 times more likely to have resistance than patients with bacteremia who had not been taking antibiotics.

The study also found that clinicians who define macrolide resistance using a cutoff of a minimum inhibitory concentration (MIC) of at least 16 mcg/mL will miss a significant percentage of the treatment failures. “Failures often occur at macrolide MICs less than 16 mcg/mL,” he said.

SAN FRANCISCO — Drug resistance was a common cause of treatment failure in 26 patients with community-acquired pneumonia who developed bacteremia while being treated with macrolide antibiotics, Dr. Gavin Bayan Grant said at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Of the 26 patients who developed bacteremia while on erythromycin, clarithromycin, or azithromycin therapy, 21 (81%) had resistant organisms, compared with 15 (44%) of 34 patients who developed bacteremia after recent use of one of the macrolides (defined as 16–90 days before the bacteremia diagnosis) and 14% of 721 patients who had not been taking any antibiotics and developed bacteremia.

Macrolide antibiotics are standard therapy for outpatient treatment of pneumonia, and evidence that significant macrolide resistance occurs has been inconclusive, said Dr. Grant of the Centers for Disease Control and Prevention, Atlanta. The current findings provide further evidence that resistance can lead to treatment failure with macrolides, which may inform clinical decisions to change antibiotics in some patients, he said at the meeting, sponsored by the American Society for Microbiology.

Dr. Grant has no association with the companies that make macrolides.

After controlling for patient age, immunosuppression, chronic comorbidities, and residence in a long-term care facility, patients failing macrolide therapy were 5 times more likely to have resistant organisms, compared with patients who developed bacteremia after recent macrolide use, and 26 times more likely to have resistance than patients with bacteremia who had not been taking antibiotics.

The study also found that clinicians who define macrolide resistance using a cutoff of a minimum inhibitory concentration (MIC) of at least 16 mcg/mL will miss a significant percentage of the treatment failures. “Failures often occur at macrolide MICs less than 16 mcg/mL,” he said.

SAN FRANCISCO — Two simple new tools may help predict which patients with community-acquired pneumonia are likely to die or to need ICU care, investigators reported in separate presentations at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The tools could help clinicians flag some patients for more intensive treatment and monitoring, whereas others could be managed as outpatients. Adults with community-acquired pneumonia (CAP) and any of four clinical predictors had an increased risk of death within 30 days in a study of 1,525 patients, Maylee Chen, Pharm.D., said at the meeting, which was sponsored by the American Society for Microbiology.

The odds for 30-day mortality nearly tripled in patients with cerebrovascular disease or hypoxemia (defined as partial pressure of arterial oxygen less than 60 mm Hg, ratio of partial pressure of arterial oxygen to fractional inspiratory oxygen less than 300, or oxygen saturation less than 90% by oximetry). The odds for 30-day mortality doubled in patients with coexisting neoplasm or uremia (defined as a BUN of at least 30 mg/dL), said Dr. Chen, who led the study while a fellow at the University of Louisville (Ky.), and now practices at the Queen's Medical Center, Honolulu.

The 30-day mortality rate in the cohort overall was 16%. Without any of the four predictors, 6% of patients with CAP died within 30 days. Death rates within 30 days ranged from 23% to 55% for patients with one of the four clinical predictors.

Cerebrovascular disease, hypoxemia, neoplasm, and uremia are among 20 criteria used in the Pneumonia Severity Index to predict risk. The study validates use of the simplified model for predicting risk of death from CAP, Dr. Chen said. Patients with the highest risk by the Pneumonia Severity Index (rated class V) were the most likely to die and the most likely to have one or more of the four clinical predictors of death.

Patient data came from the multinational Community-Acquired Pneumonia Organization study. Dr. Chen and her associates also performed a secondary analysis that included 982 patients whose 30-day mortality was unknown—assuming that any patient with an unknown outcome survived—in addition to the 1,525 patients with known outcomes. Each of the four clinical variables remained a significant predictor of 30-day mortality, she said.

In a separate presentation, Dr. Patrick G. P. Charles of Austin Hospital, Heidelberg, Victoria, Australia, described another assessment tool that may predict the need for ICU care of patients with CAP if a planned prospective study validates preliminary findings.

The SMARTCOP assessment tool gauges risk for ICU care by assigning points to patients based on these characteristics:

▸ Systolic blood pressure less than 90 mm Hg.

▸ Multilobar chest x-ray involvement.

▸ Albumin less than 3.5 g/dL.

▸ Respiratory rate (at least 30 breaths per minute in patients aged 40 years or older, at least 25 breaths per minute if younger).

▸ Tachycardia of 125 beats per minute, or higher.

▸ Confusion.

▸ Poor oxygenation.

▸ pH below 7.35.

Early data from a study of 849 patients showed the SMARTCOP tool (and an abbreviated version, SMRT-CP) was simpler and as accurate as two tools already used in predicting the need for ICU care, said Dr. Charles and his associates, who compared SMARTCOP and SMRT-CP with the Pneumonia Severity Index and CURB-65. The latter assesses CAP risk based on the presence of confusion, urea nitrogen levels, respiratory rate, blood pressure, and age of 65 years or older.

Overall, 10% of the patients needed ICU care, and 5% died within 30 days. The study excluded patients who were likely to die within 12–24 hours and were admitted for palliative care, so mortality was lower than might be expected.

SMARTCOP was simpler and as accurate as two tools already used in predicting the need for ICU care. DR. CHARLES

SAN FRANCISCO — Two simple new tools may help predict which patients with community-acquired pneumonia are likely to die or to need ICU care, investigators reported in separate presentations at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The tools could help clinicians flag some patients for more intensive treatment and monitoring, whereas others could be managed as outpatients. Adults with community-acquired pneumonia (CAP) and any of four clinical predictors had an increased risk of death within 30 days in a study of 1,525 patients, Maylee Chen, Pharm.D., said at the meeting, which was sponsored by the American Society for Microbiology.

The odds for 30-day mortality nearly tripled in patients with cerebrovascular disease or hypoxemia (defined as partial pressure of arterial oxygen less than 60 mm Hg, ratio of partial pressure of arterial oxygen to fractional inspiratory oxygen less than 300, or oxygen saturation less than 90% by oximetry). The odds for 30-day mortality doubled in patients with coexisting neoplasm or uremia (defined as a BUN of at least 30 mg/dL), said Dr. Chen, who led the study while a fellow at the University of Louisville (Ky.), and now practices at the Queen's Medical Center, Honolulu.

The 30-day mortality rate in the cohort overall was 16%. Without any of the four predictors, 6% of patients with CAP died within 30 days. Death rates within 30 days ranged from 23% to 55% for patients with one of the four clinical predictors.

Cerebrovascular disease, hypoxemia, neoplasm, and uremia are among 20 criteria used in the Pneumonia Severity Index to predict risk. The study validates use of the simplified model for predicting risk of death from CAP, Dr. Chen said. Patients with the highest risk by the Pneumonia Severity Index (rated class V) were the most likely to die and the most likely to have one or more of the four clinical predictors of death.

Patient data came from the multinational Community-Acquired Pneumonia Organization study. Dr. Chen and her associates also performed a secondary analysis that included 982 patients whose 30-day mortality was unknown—assuming that any patient with an unknown outcome survived—in addition to the 1,525 patients with known outcomes. Each of the four clinical variables remained a significant predictor of 30-day mortality, she said.

In a separate presentation, Dr. Patrick G. P. Charles of Austin Hospital, Heidelberg, Victoria, Australia, described another assessment tool that may predict the need for ICU care of patients with CAP if a planned prospective study validates preliminary findings.

The SMARTCOP assessment tool gauges risk for ICU care by assigning points to patients based on these characteristics:

▸ Systolic blood pressure less than 90 mm Hg.

▸ Multilobar chest x-ray involvement.

▸ Albumin less than 3.5 g/dL.

▸ Respiratory rate (at least 30 breaths per minute in patients aged 40 years or older, at least 25 breaths per minute if younger).

▸ Tachycardia of 125 beats per minute, or higher.

▸ Confusion.

▸ Poor oxygenation.

▸ pH below 7.35.

Early data from a study of 849 patients showed the SMARTCOP tool (and an abbreviated version, SMRT-CP) was simpler and as accurate as two tools already used in predicting the need for ICU care, said Dr. Charles and his associates, who compared SMARTCOP and SMRT-CP with the Pneumonia Severity Index and CURB-65. The latter assesses CAP risk based on the presence of confusion, urea nitrogen levels, respiratory rate, blood pressure, and age of 65 years or older.

Overall, 10% of the patients needed ICU care, and 5% died within 30 days. The study excluded patients who were likely to die within 12–24 hours and were admitted for palliative care, so mortality was lower than might be expected.

SMARTCOP was simpler and as accurate as two tools already used in predicting the need for ICU care. DR. CHARLES

SAN FRANCISCO — Two simple new tools may help predict which patients with community-acquired pneumonia are likely to die or to need ICU care, investigators reported in separate presentations at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The tools could help clinicians flag some patients for more intensive treatment and monitoring, whereas others could be managed as outpatients. Adults with community-acquired pneumonia (CAP) and any of four clinical predictors had an increased risk of death within 30 days in a study of 1,525 patients, Maylee Chen, Pharm.D., said at the meeting, which was sponsored by the American Society for Microbiology.

The odds for 30-day mortality nearly tripled in patients with cerebrovascular disease or hypoxemia (defined as partial pressure of arterial oxygen less than 60 mm Hg, ratio of partial pressure of arterial oxygen to fractional inspiratory oxygen less than 300, or oxygen saturation less than 90% by oximetry). The odds for 30-day mortality doubled in patients with coexisting neoplasm or uremia (defined as a BUN of at least 30 mg/dL), said Dr. Chen, who led the study while a fellow at the University of Louisville (Ky.), and now practices at the Queen's Medical Center, Honolulu.

The 30-day mortality rate in the cohort overall was 16%. Without any of the four predictors, 6% of patients with CAP died within 30 days. Death rates within 30 days ranged from 23% to 55% for patients with one of the four clinical predictors.

Cerebrovascular disease, hypoxemia, neoplasm, and uremia are among 20 criteria used in the Pneumonia Severity Index to predict risk. The study validates use of the simplified model for predicting risk of death from CAP, Dr. Chen said. Patients with the highest risk by the Pneumonia Severity Index (rated class V) were the most likely to die and the most likely to have one or more of the four clinical predictors of death.

Patient data came from the multinational Community-Acquired Pneumonia Organization study. Dr. Chen and her associates also performed a secondary analysis that included 982 patients whose 30-day mortality was unknown—assuming that any patient with an unknown outcome survived—in addition to the 1,525 patients with known outcomes. Each of the four clinical variables remained a significant predictor of 30-day mortality, she said.

In a separate presentation, Dr. Patrick G. P. Charles of Austin Hospital, Heidelberg, Victoria, Australia, described another assessment tool that may predict the need for ICU care of patients with CAP if a planned prospective study validates preliminary findings.

The SMARTCOP assessment tool gauges risk for ICU care by assigning points to patients based on these characteristics:

▸ Systolic blood pressure less than 90 mm Hg.

▸ Multilobar chest x-ray involvement.

▸ Albumin less than 3.5 g/dL.

▸ Respiratory rate (at least 30 breaths per minute in patients aged 40 years or older, at least 25 breaths per minute if younger).

▸ Tachycardia of 125 beats per minute, or higher.

▸ Confusion.

▸ Poor oxygenation.

▸ pH below 7.35.

Early data from a study of 849 patients showed the SMARTCOP tool (and an abbreviated version, SMRT-CP) was simpler and as accurate as two tools already used in predicting the need for ICU care, said Dr. Charles and his associates, who compared SMARTCOP and SMRT-CP with the Pneumonia Severity Index and CURB-65. The latter assesses CAP risk based on the presence of confusion, urea nitrogen levels, respiratory rate, blood pressure, and age of 65 years or older.

Overall, 10% of the patients needed ICU care, and 5% died within 30 days. The study excluded patients who were likely to die within 12–24 hours and were admitted for palliative care, so mortality was lower than might be expected.

SMARTCOP was simpler and as accurate as two tools already used in predicting the need for ICU care. DR. CHARLES