First EDition: News for and about the practice of Emergency Medicine

Drug-resistant shigellosis outbreak

BY DEEPAK CHITNIS
FROM MMWR

The United States is currently experiencing an outbreak of shigellosis caused by a strain of the Shigella sonnei bacteria that is resistant to ciprofloxacin, the most commonly prescribed antimicrobial treatment for shigellosis.

In its Morbidity and Mortality Weekly Report, the CDC revealed that 243 individuals in 32 states and the territory of Puerto Rico have come down with shigellosis between May 2014 and February 2015. Of those 243 cases, 126 isolates were tested and 109 (87%) of those were found to be nonsusceptible to ciprofloxacin. The largest clusters of the disease were found in Massachusetts (45 cases), California (25 cases), and Pennsylvania (18 cases).

Ninety-five of the cases associated with the current outbreak were traced back to the homeless population of San Francisco; about half of the remaining cases were attributed to international travelers – specifically, those visiting the Dominican Republic and India – who contracted the bacteria while abroad and unknowingly brought it to the United States. The disease is known to spread quickly in populations of children who attend child care facilities, homeless individuals, and men who have sex with men.

“These outbreaks show a troubling trend in Shigella infections in the United States,” Dr. Thomas Frieden, CDC director, said in a statement. “Drug-resistant infections are harder to treat and because Shigella spreads so easily between people, the potential for more – and larger – outbreaks is a real concern. We’re moving quickly to implement a national strategy to curb antibiotic resistance because we can’t take for granted that we’ll always have the drugs we need to fight common infections.”

Shigellosis causes an estimated 500,000 cases of diarrhea in the United States each year. To help curb the growing number of shigellosis cases, the CDC recommends that international travelers wash their hands meticulously while abroad, and follow strict dietary precautions, such as eating hot foods and drinking beverages only from sealed containers, especially when consuming water.

dchitnis@frontlinemedcom.com

Otherwise healthy patients over 80 benefit from aggressive treatment for MI

BY PATRICE WENDLING
AT ACC/CRF I2 SUMMIT

SAN DIEGO – Patients aged 80 years and older benefit from more invasive early treatment after non-ST-elevation myocardial infarction or unstable angina, the After Eighty Trial showed.

After a median follow-up of 1.5 years, an invasive strategy that included coronary angiography significantly reduced the primary endpoint of myocardial infarction (MI), need for urgent revascularization, stroke, and death from 61% with optimal medical treatment to 41%.

That drop was driven primarily by significantly fewer MIs (17% vs. 30%) and urgent revascularizations (2% vs. 11%), lead author Dr. Nicolai Tegn reported at the American College of Cardiology/Cardiovascular Research Foundation Innovation in Intervention Summit.

There were no significant differences between the invasive and conservative strategy groups in rates of stroke or all-cause death.

The composite of death and MI, however, significantly favored the invasive group (35% vs. 48%), he reported.

After Eighty randomly assigned 457 patients, aged 80 years or older, to either optimal medical therapy with no invasive treatments or coronary angiography at a percutaneous coronary intervention (PCI) center the day after inclusion, plus optimal medical therapy after about 4-5 hours if PCI was not performed or about 6-18 hours if it was. Of the 225 patients receiving angiography, 48% went on to balloon angioplasty and/or coronary stenting, and 3% had bypass surgery. The patients were selected from nearly 4,200 elderly patients at 17 community hospitals in Norway; over 3,700 of the patients were ineligible for the study because their life expectancy was less than 12 months because of a serious comorbidity; ongoing or recent bleeding; inability to comply with protocol; clinically unstable including ongoing ischemia; refusal to participate; logistic reasons; or other reasons.

After Eighty is a welcome study because of the under-representation of the elderly in clinical trials, Dr. David Kandzari, director of interventional cardiology at the Piedmont Heart Center in Atlanta, said during a press briefing at the meeting. But it raises the challenge of identifying patients in clinical practice with the same qualifying characteristics, he added, given that the study population represents only 10% of the entire screened population, “The coronary anatomy does not know the age of the patient, meaning that the findings of a benefit of an early invasive strategy seem consistent with previous studies we know across the management of patients with acute coronary syndromes,” Dr. Kandzari said.

pwendling@frontlinemedcom.com

FDA approves Anthrasil to treat inhalational anthrax

BY DEEPAK CHITNIS
FRONTLINE MEDICAL NEWS

The Food and Drug Administration has approved Anthrasil, Anthrax Immune Globulin Intravenous (Human), for treatment of inhalational anthrax when used with appropriate antibacterial drugs.

Inhalational anthrax is caused by breathing in Bacillus anthracis spores, which can occur after exposure to infected animals or contaminated animal products, or as a result of an intentional release of spores. In a statement, Dr. Karen Midthun – director of the FDA’s Center for Biologics Evaluation and Research – explained that Anthrasil “will be stored in U.S. Strategic National Stockpile to facilitate its availability in response to an anthrax emergency.”

Anthrasil was purchased by the U.S. Department of Health & Human Services’ Biomedical Advanced Research and Development Authority (BARDA) in 2011, but because it was not approved, its use prior to FDA approval would have required an emergency use authorization from the FDA.

The efficacy of Anthrasil was studied in animals because it was not feasible or ethical to conduct adequately controlled efficacy studies in humans, the FDA said. Monkeys and rabbits were exposed to Bacillus anthracis spores, and subsequently given either Anthrasil or a placebo. The survival rate for monkeys given Anthrasil was between 36% and 70%, with a trend toward increased survival at higher doses of Anthrasil. None of the monkeys given placebo survived. Rabbits had a 26% survival rate when given the drug, compared to 2% of those given placebo. A separate study exposed rabbits to Bacillus anthracis and treated them with either antibiotics or a combination of antibiotics and Anthrasil; survival rates were 71% for those treated with the combination and 25% for those treated with antibiotics only.

Safety was tested in 74 healthy human volunteers and the most commonly reported side effects were headache, back pain, nausea, and pain and swelling at the infusion site.

Anthrasil is manufactured by Cangene Corporation, based in Winnipeg, Canada, which developed the drug in collaboration with BARDA.

dchitnis@frontlinemedcom.com

FDA: Amiodarone plus some hepatitis C antivirals may result in bradycardia

BY ELIZABETH MECHCATIE
Frontline Medical News

Taking the antiarrythmic drug amiodarone with the hepatitis C antiviral drugs ledipasvir and sofosbuvir, or with sofosbuvir plus another direct-acting antiviral drug, has been associated with cases of symptomatic bradycardia – including a fatal cardiac arrest – according to the Food and Drug Administration.

Because of the reports, the antiviral drugs’ labels now recommend against using amiodarone with those hepatitis C drugs.

An FDA statement described the bradycardia cases as “serious and life-threatening.” Gilead Sciences markets the ledipasvir and sofosbuvir combination as Harvoni and markets sofosbuvir as Sovaldi to treat chronic hepatitis C virus (HCV) infection.

Gilead issued a “Dear Health Care Provider” letter that provides further details of the cases. There have been nine postmarketing reports of symptomatic bradycardia in patients who were taking amiodarone with Harvoni; amiodarone with Sovaldi plus another hepatitis C antiviral drug, simeprevir (Olysio); or amiodarone with an investigational hepatitis C antiviral drug, daclatasvir.

Of those cases, six occurred with in the first 24 hours of starting treatment with the antivirals, and three cases occurred within the first 2-12 days after antiviral therapy was started. A pacemaker was needed in three cases, and one case was a fatal cardiac arrest.

In three cases, a “rechallenge with HCV treatment in the setting of continued amiodarone therapy resulted in recurrence of symptomatic bradycardia,” according to the Gilead letter.

The effect of coadministration on the blood levels of the antiviral drugs is not known, nor is the mechanism behind the cardiac effect.

emechcatie@frontlinemedcom.com

Clindamycin, TMP-SMX are equally effective for skin infections

BY MARY ANN MOON
FROM THE NEW ENGLAND JOURNAL OF MEDICINE

Clindamycin and trimethoprim-sulfamethoxazole are similarly safe and effective for treating uncomplicated skin infections, including both cellulitis and abscesses, in ambulatory settings in regions where MRSA is endemic.

The data comparing these two agents in an ambulatory setting are limited, though both are commonly recommended as empirical therapy for skin infections in patients who present to clinics and emergency departments and have only minor or no coexisting conditions, said Dr. Loren G. Miller of the Los Angeles Biomedical Research Institute and the division of infectious diseases at Harbor-UCLA Medical Center, and his associates.

They performed a prospective double-blind randomized trial comparing clindamycin against TMP-SMX in 524 ethnically diverse adults and children who presented as outpatients with uncomplicated skin infections during a 2-year period in Chicago, San Francisco, Los Angeles, and Nashville – areas in which community-associated MRSA is endemic. The mean patient age was 27 years, and approximately 30% were pediatric patients. All the participants had cellulitis without abscesses (including erysipelas), one or more abscesses larger than 5 cm in diameter, or both conditions. A total of 264 were randomized to clindamycin and 260 to TMP-SMX daily for 10 days.

Cure rates did not differ significantly between the two study groups. At 7-10 days after completing therapy, the rates of cure in the intention-to-treat population were 80% for clindamycin and 78% for TMP-SMX, and in the evaluable population the rates were nearly 90% and 88%, respectively.

At 1 month follow-up, the cure rates in the evaluable population were 84% for clindamycin and 78% for TMP-SMX, the investigators said (N. Engl. J. Med. 2015;372:1093-103 [doi:10.1056/NEJMoa1403789]). Rates of adverse events were nearly identical between the two study groups at about 19%, and most were mild and resolved without sequelae. There were no treatment-associated serious adverse events, and the rates of treatment discontinuation were similar at nearly 9% between patients receiving clindamycin and those receiving TMP-SMX.

Stroke ambulances speed treatment to U.S. patients

BY MITCHEL L. ZOLER
AT THE INTERNATIONAL STROKE CONFERENCE

NASHVILLE, TENN. – Bringing a CT scanner and thrombolytic treatment directly to stroke patients in the field sped the time to thrombolysis, compared with waiting for the patient to arrive at the hospital.

Some U.S. stroke centers now send out a team that can immediately assess and start treating stroke patients in the community. In 2014, the first two U.S. mobile stroke-treatment units began operating, one in Houston and the second in Cleveland.

Initial reports show both programs were successful in cutting the time to deliver thrombolytic treatment with intravenous tissue plasminogen activator (TPA) to appropriate patients.

In Houston, the active phase of the program started in May 2014, and by October 2014, 47 acute ischemic stroke patients had been treated with TPA. The mobile-unit crews started 43% of eligible patients on thrombolysis within 60 minutes of their symptom onset and another 31% were treated starting 61-80 minutes after symptom onset, said Stephanie A. Parker at the International Stroke Conference.

The unit also treats patients diagnosed with hemorrhagic stroke with intravenous nicardipine for rapid blood pressure reduction, said Ms. Parker, a critical care and emergency medicine–trained registered nurse who is project manager for the Houston mobile unit.

The Cleveland program began in July 2014; of the first 100 stroke patients seen by the mobile unit 16 of 19 eligible patients received tPA, with an average time of 56 minutes from symptom onset to treatment. This compared with an average 94 minutes to tPA onset in patients brought conventionally last year to a Cleveland-area hospital, Dr. M. Shazam Hussain said in a report at the meeting, sponsored by the American Heart Association.

The clinical impact and cost effectiveness of the pilot programs using the mobile units have not yet been assessed from the data, Dr. Hussain and Ms. Parker emphasized. Funding for the Cleveland and Houston vehicles came from local donors; the Houston program also received equipment donations from manufacturers.

The two mobile units are standard 12-foot, box-shaped ambulances outfitted with a CT scanner, a point-of-care lab, and telemedicine components as well as more standard emergency-vehicle equipment. The Houston vehicle contains “all the diagnostic equipment that is in our emergency room,” Ms. Parker said.

The concept behind both the Cleveland unit, operated by the Cleveland Clinic, and the Houston unit, operated by the University of Texas, Houston, is that the mobile stroke unit arrives to a patient with a suspected stroke, the unit is stationary while a CT scan and other diagnostic tests are run, diagnosis occurs with telemedicine assistance. If the patient is cleared for TPA treatment, the infusion starts and the vehicle carries the patient to an appropriate stroke center.

Currently, the Houston unit goes out with a vascular neurologist and a telemedicine physician on board, but plans are in place to test the feasibility of relying entirely on telemedicine when making diagnostic and treatment decisions. The Cleveland mobile unit already operates in this fashion, with no physician on board, and was the first mobile stroke unit in the world to depend completely on telemedicine, according to Dr. Hussain, a neurologist and head of the stroke program at the Cleveland Clinic.

The world’s first mobile stroke unit began operating in Saarland, Germany, in 2008 (Lancet Neurology 2012;11:397-404), and a second unit began running in Berlin after that, Dr. Hussain noted. Because of limited funding, the service he directs in Cleveland has been operating from 8 a.m.-8 p.m., 7 days a week. The program plans to expand to 24-hour coverage. The Houston mobile unit operates 24/7; it averages two runs per day and administers TPA on 1 of every 10 runs, Ms. Parker said. Both the Houston and Cleveland units tie into the local 911 emergency activation systems for their respective regions.

mzoler@frontlinemedcom.com

Consider cephalosporin a safe alternative for patients with penicillin allergy

BY DEEPAK CHITNIS
AT THE 2015 AAAAI ANNUAL MEETING

HOUSTON – Given the low incidence of adverse drug reactions to cephalosporin antibiotics among nearly a million California health plan patients, patients with a history of penicillin allergy can safely be given cephalosporins, according to Dr. Eric M. Macy.

The recommendation is based on the findings of a retrospective, population-based analysis of the records of 949,323 Kaiser Permanente Southern California health plan members, which was presented by Dr. Macy, of the Kaiser Permanente Medical Center in San Diego, at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Dr. Macy and his colleagues examined the records of 622,456 health plan members who were given 901,908 regimens of oral cephalosporins and 326,867 members given 487,630 parenteral cephalosporin regimens between Jan. 1, 2010, and Dec. 31, 2012.

Clostridium difficile infection within 90 days, nephropathy within 30 days, and all-cause death within 1 day were the most common cephalosporin-associated adverse drug reactions (ADRs) reported by physicians, with rates of 0.91%, 0.15%, and 0.10%, respectively. Cephalosporin-associated anaphylaxis was documented by physicians a total of five times in oral patients and eight times in parenteral patients (P = .0761), while only three serious cutaneous adverse reactions (SCARs) were recorded. All of those SCARS were attributable to other antibiotics taken at the same time as the cephalosporins, according to Dr. Macy.

Patients who reported developing new cephalosporin allergies over the course of the study period were significantly more likely to be female than male: 0.56% vs. 0.43% (P < .0001). And patients with a history of penicillin allergy were more likely to report a new cephalosporin allergy within 30 days than patients with no drug allergy, another cephalosporin allergy, or a non–beta-lactam allergy.

dchitnis@frontlinemedcom.com

Drug-resistant shigellosis outbreak

BY DEEPAK CHITNIS
FROM MMWR

The United States is currently experiencing an outbreak of shigellosis caused by a strain of the Shigella sonnei bacteria that is resistant to ciprofloxacin, the most commonly prescribed antimicrobial treatment for shigellosis.

In its Morbidity and Mortality Weekly Report, the CDC revealed that 243 individuals in 32 states and the territory of Puerto Rico have come down with shigellosis between May 2014 and February 2015. Of those 243 cases, 126 isolates were tested and 109 (87%) of those were found to be nonsusceptible to ciprofloxacin. The largest clusters of the disease were found in Massachusetts (45 cases), California (25 cases), and Pennsylvania (18 cases).

Ninety-five of the cases associated with the current outbreak were traced back to the homeless population of San Francisco; about half of the remaining cases were attributed to international travelers – specifically, those visiting the Dominican Republic and India – who contracted the bacteria while abroad and unknowingly brought it to the United States. The disease is known to spread quickly in populations of children who attend child care facilities, homeless individuals, and men who have sex with men.

“These outbreaks show a troubling trend in Shigella infections in the United States,” Dr. Thomas Frieden, CDC director, said in a statement. “Drug-resistant infections are harder to treat and because Shigella spreads so easily between people, the potential for more – and larger – outbreaks is a real concern. We’re moving quickly to implement a national strategy to curb antibiotic resistance because we can’t take for granted that we’ll always have the drugs we need to fight common infections.”

Shigellosis causes an estimated 500,000 cases of diarrhea in the United States each year. To help curb the growing number of shigellosis cases, the CDC recommends that international travelers wash their hands meticulously while abroad, and follow strict dietary precautions, such as eating hot foods and drinking beverages only from sealed containers, especially when consuming water.

dchitnis@frontlinemedcom.com

Otherwise healthy patients over 80 benefit from aggressive treatment for MI

BY PATRICE WENDLING
AT ACC/CRF I2 SUMMIT

SAN DIEGO – Patients aged 80 years and older benefit from more invasive early treatment after non-ST-elevation myocardial infarction or unstable angina, the After Eighty Trial showed.

After a median follow-up of 1.5 years, an invasive strategy that included coronary angiography significantly reduced the primary endpoint of myocardial infarction (MI), need for urgent revascularization, stroke, and death from 61% with optimal medical treatment to 41%.

That drop was driven primarily by significantly fewer MIs (17% vs. 30%) and urgent revascularizations (2% vs. 11%), lead author Dr. Nicolai Tegn reported at the American College of Cardiology/Cardiovascular Research Foundation Innovation in Intervention Summit.

There were no significant differences between the invasive and conservative strategy groups in rates of stroke or all-cause death.

The composite of death and MI, however, significantly favored the invasive group (35% vs. 48%), he reported.

After Eighty randomly assigned 457 patients, aged 80 years or older, to either optimal medical therapy with no invasive treatments or coronary angiography at a percutaneous coronary intervention (PCI) center the day after inclusion, plus optimal medical therapy after about 4-5 hours if PCI was not performed or about 6-18 hours if it was. Of the 225 patients receiving angiography, 48% went on to balloon angioplasty and/or coronary stenting, and 3% had bypass surgery. The patients were selected from nearly 4,200 elderly patients at 17 community hospitals in Norway; over 3,700 of the patients were ineligible for the study because their life expectancy was less than 12 months because of a serious comorbidity; ongoing or recent bleeding; inability to comply with protocol; clinically unstable including ongoing ischemia; refusal to participate; logistic reasons; or other reasons.

After Eighty is a welcome study because of the under-representation of the elderly in clinical trials, Dr. David Kandzari, director of interventional cardiology at the Piedmont Heart Center in Atlanta, said during a press briefing at the meeting. But it raises the challenge of identifying patients in clinical practice with the same qualifying characteristics, he added, given that the study population represents only 10% of the entire screened population, “The coronary anatomy does not know the age of the patient, meaning that the findings of a benefit of an early invasive strategy seem consistent with previous studies we know across the management of patients with acute coronary syndromes,” Dr. Kandzari said.

pwendling@frontlinemedcom.com

FDA approves Anthrasil to treat inhalational anthrax

BY DEEPAK CHITNIS
FRONTLINE MEDICAL NEWS

The Food and Drug Administration has approved Anthrasil, Anthrax Immune Globulin Intravenous (Human), for treatment of inhalational anthrax when used with appropriate antibacterial drugs.

Inhalational anthrax is caused by breathing in Bacillus anthracis spores, which can occur after exposure to infected animals or contaminated animal products, or as a result of an intentional release of spores. In a statement, Dr. Karen Midthun – director of the FDA’s Center for Biologics Evaluation and Research – explained that Anthrasil “will be stored in U.S. Strategic National Stockpile to facilitate its availability in response to an anthrax emergency.”

Anthrasil was purchased by the U.S. Department of Health & Human Services’ Biomedical Advanced Research and Development Authority (BARDA) in 2011, but because it was not approved, its use prior to FDA approval would have required an emergency use authorization from the FDA.

The efficacy of Anthrasil was studied in animals because it was not feasible or ethical to conduct adequately controlled efficacy studies in humans, the FDA said. Monkeys and rabbits were exposed to Bacillus anthracis spores, and subsequently given either Anthrasil or a placebo. The survival rate for monkeys given Anthrasil was between 36% and 70%, with a trend toward increased survival at higher doses of Anthrasil. None of the monkeys given placebo survived. Rabbits had a 26% survival rate when given the drug, compared to 2% of those given placebo. A separate study exposed rabbits to Bacillus anthracis and treated them with either antibiotics or a combination of antibiotics and Anthrasil; survival rates were 71% for those treated with the combination and 25% for those treated with antibiotics only.

Safety was tested in 74 healthy human volunteers and the most commonly reported side effects were headache, back pain, nausea, and pain and swelling at the infusion site.

Anthrasil is manufactured by Cangene Corporation, based in Winnipeg, Canada, which developed the drug in collaboration with BARDA.

dchitnis@frontlinemedcom.com

FDA: Amiodarone plus some hepatitis C antivirals may result in bradycardia

BY ELIZABETH MECHCATIE
Frontline Medical News

Taking the antiarrythmic drug amiodarone with the hepatitis C antiviral drugs ledipasvir and sofosbuvir, or with sofosbuvir plus another direct-acting antiviral drug, has been associated with cases of symptomatic bradycardia – including a fatal cardiac arrest – according to the Food and Drug Administration.

Because of the reports, the antiviral drugs’ labels now recommend against using amiodarone with those hepatitis C drugs.

An FDA statement described the bradycardia cases as “serious and life-threatening.” Gilead Sciences markets the ledipasvir and sofosbuvir combination as Harvoni and markets sofosbuvir as Sovaldi to treat chronic hepatitis C virus (HCV) infection.

Gilead issued a “Dear Health Care Provider” letter that provides further details of the cases. There have been nine postmarketing reports of symptomatic bradycardia in patients who were taking amiodarone with Harvoni; amiodarone with Sovaldi plus another hepatitis C antiviral drug, simeprevir (Olysio); or amiodarone with an investigational hepatitis C antiviral drug, daclatasvir.

Of those cases, six occurred with in the first 24 hours of starting treatment with the antivirals, and three cases occurred within the first 2-12 days after antiviral therapy was started. A pacemaker was needed in three cases, and one case was a fatal cardiac arrest.

In three cases, a “rechallenge with HCV treatment in the setting of continued amiodarone therapy resulted in recurrence of symptomatic bradycardia,” according to the Gilead letter.

The effect of coadministration on the blood levels of the antiviral drugs is not known, nor is the mechanism behind the cardiac effect.

emechcatie@frontlinemedcom.com

Clindamycin, TMP-SMX are equally effective for skin infections

BY MARY ANN MOON
FROM THE NEW ENGLAND JOURNAL OF MEDICINE

Clindamycin and trimethoprim-sulfamethoxazole are similarly safe and effective for treating uncomplicated skin infections, including both cellulitis and abscesses, in ambulatory settings in regions where MRSA is endemic.

The data comparing these two agents in an ambulatory setting are limited, though both are commonly recommended as empirical therapy for skin infections in patients who present to clinics and emergency departments and have only minor or no coexisting conditions, said Dr. Loren G. Miller of the Los Angeles Biomedical Research Institute and the division of infectious diseases at Harbor-UCLA Medical Center, and his associates.

They performed a prospective double-blind randomized trial comparing clindamycin against TMP-SMX in 524 ethnically diverse adults and children who presented as outpatients with uncomplicated skin infections during a 2-year period in Chicago, San Francisco, Los Angeles, and Nashville – areas in which community-associated MRSA is endemic. The mean patient age was 27 years, and approximately 30% were pediatric patients. All the participants had cellulitis without abscesses (including erysipelas), one or more abscesses larger than 5 cm in diameter, or both conditions. A total of 264 were randomized to clindamycin and 260 to TMP-SMX daily for 10 days.

Cure rates did not differ significantly between the two study groups. At 7-10 days after completing therapy, the rates of cure in the intention-to-treat population were 80% for clindamycin and 78% for TMP-SMX, and in the evaluable population the rates were nearly 90% and 88%, respectively.

At 1 month follow-up, the cure rates in the evaluable population were 84% for clindamycin and 78% for TMP-SMX, the investigators said (N. Engl. J. Med. 2015;372:1093-103 [doi:10.1056/NEJMoa1403789]). Rates of adverse events were nearly identical between the two study groups at about 19%, and most were mild and resolved without sequelae. There were no treatment-associated serious adverse events, and the rates of treatment discontinuation were similar at nearly 9% between patients receiving clindamycin and those receiving TMP-SMX.

Stroke ambulances speed treatment to U.S. patients

BY MITCHEL L. ZOLER
AT THE INTERNATIONAL STROKE CONFERENCE

NASHVILLE, TENN. – Bringing a CT scanner and thrombolytic treatment directly to stroke patients in the field sped the time to thrombolysis, compared with waiting for the patient to arrive at the hospital.

Some U.S. stroke centers now send out a team that can immediately assess and start treating stroke patients in the community. In 2014, the first two U.S. mobile stroke-treatment units began operating, one in Houston and the second in Cleveland.

Initial reports show both programs were successful in cutting the time to deliver thrombolytic treatment with intravenous tissue plasminogen activator (TPA) to appropriate patients.

In Houston, the active phase of the program started in May 2014, and by October 2014, 47 acute ischemic stroke patients had been treated with TPA. The mobile-unit crews started 43% of eligible patients on thrombolysis within 60 minutes of their symptom onset and another 31% were treated starting 61-80 minutes after symptom onset, said Stephanie A. Parker at the International Stroke Conference.

The unit also treats patients diagnosed with hemorrhagic stroke with intravenous nicardipine for rapid blood pressure reduction, said Ms. Parker, a critical care and emergency medicine–trained registered nurse who is project manager for the Houston mobile unit.

The Cleveland program began in July 2014; of the first 100 stroke patients seen by the mobile unit 16 of 19 eligible patients received tPA, with an average time of 56 minutes from symptom onset to treatment. This compared with an average 94 minutes to tPA onset in patients brought conventionally last year to a Cleveland-area hospital, Dr. M. Shazam Hussain said in a report at the meeting, sponsored by the American Heart Association.

The clinical impact and cost effectiveness of the pilot programs using the mobile units have not yet been assessed from the data, Dr. Hussain and Ms. Parker emphasized. Funding for the Cleveland and Houston vehicles came from local donors; the Houston program also received equipment donations from manufacturers.

The two mobile units are standard 12-foot, box-shaped ambulances outfitted with a CT scanner, a point-of-care lab, and telemedicine components as well as more standard emergency-vehicle equipment. The Houston vehicle contains “all the diagnostic equipment that is in our emergency room,” Ms. Parker said.

The concept behind both the Cleveland unit, operated by the Cleveland Clinic, and the Houston unit, operated by the University of Texas, Houston, is that the mobile stroke unit arrives to a patient with a suspected stroke, the unit is stationary while a CT scan and other diagnostic tests are run, diagnosis occurs with telemedicine assistance. If the patient is cleared for TPA treatment, the infusion starts and the vehicle carries the patient to an appropriate stroke center.

Currently, the Houston unit goes out with a vascular neurologist and a telemedicine physician on board, but plans are in place to test the feasibility of relying entirely on telemedicine when making diagnostic and treatment decisions. The Cleveland mobile unit already operates in this fashion, with no physician on board, and was the first mobile stroke unit in the world to depend completely on telemedicine, according to Dr. Hussain, a neurologist and head of the stroke program at the Cleveland Clinic.

The world’s first mobile stroke unit began operating in Saarland, Germany, in 2008 (Lancet Neurology 2012;11:397-404), and a second unit began running in Berlin after that, Dr. Hussain noted. Because of limited funding, the service he directs in Cleveland has been operating from 8 a.m.-8 p.m., 7 days a week. The program plans to expand to 24-hour coverage. The Houston mobile unit operates 24/7; it averages two runs per day and administers TPA on 1 of every 10 runs, Ms. Parker said. Both the Houston and Cleveland units tie into the local 911 emergency activation systems for their respective regions.

mzoler@frontlinemedcom.com

Consider cephalosporin a safe alternative for patients with penicillin allergy

BY DEEPAK CHITNIS
AT THE 2015 AAAAI ANNUAL MEETING

HOUSTON – Given the low incidence of adverse drug reactions to cephalosporin antibiotics among nearly a million California health plan patients, patients with a history of penicillin allergy can safely be given cephalosporins, according to Dr. Eric M. Macy.

The recommendation is based on the findings of a retrospective, population-based analysis of the records of 949,323 Kaiser Permanente Southern California health plan members, which was presented by Dr. Macy, of the Kaiser Permanente Medical Center in San Diego, at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Dr. Macy and his colleagues examined the records of 622,456 health plan members who were given 901,908 regimens of oral cephalosporins and 326,867 members given 487,630 parenteral cephalosporin regimens between Jan. 1, 2010, and Dec. 31, 2012.

Clostridium difficile infection within 90 days, nephropathy within 30 days, and all-cause death within 1 day were the most common cephalosporin-associated adverse drug reactions (ADRs) reported by physicians, with rates of 0.91%, 0.15%, and 0.10%, respectively. Cephalosporin-associated anaphylaxis was documented by physicians a total of five times in oral patients and eight times in parenteral patients (P = .0761), while only three serious cutaneous adverse reactions (SCARs) were recorded. All of those SCARS were attributable to other antibiotics taken at the same time as the cephalosporins, according to Dr. Macy.

Patients who reported developing new cephalosporin allergies over the course of the study period were significantly more likely to be female than male: 0.56% vs. 0.43% (P < .0001). And patients with a history of penicillin allergy were more likely to report a new cephalosporin allergy within 30 days than patients with no drug allergy, another cephalosporin allergy, or a non–beta-lactam allergy.

dchitnis@frontlinemedcom.com

Drug-resistant shigellosis outbreak

BY DEEPAK CHITNIS
FROM MMWR

The United States is currently experiencing an outbreak of shigellosis caused by a strain of the Shigella sonnei bacteria that is resistant to ciprofloxacin, the most commonly prescribed antimicrobial treatment for shigellosis.

In its Morbidity and Mortality Weekly Report, the CDC revealed that 243 individuals in 32 states and the territory of Puerto Rico have come down with shigellosis between May 2014 and February 2015. Of those 243 cases, 126 isolates were tested and 109 (87%) of those were found to be nonsusceptible to ciprofloxacin. The largest clusters of the disease were found in Massachusetts (45 cases), California (25 cases), and Pennsylvania (18 cases).

Ninety-five of the cases associated with the current outbreak were traced back to the homeless population of San Francisco; about half of the remaining cases were attributed to international travelers – specifically, those visiting the Dominican Republic and India – who contracted the bacteria while abroad and unknowingly brought it to the United States. The disease is known to spread quickly in populations of children who attend child care facilities, homeless individuals, and men who have sex with men.

“These outbreaks show a troubling trend in Shigella infections in the United States,” Dr. Thomas Frieden, CDC director, said in a statement. “Drug-resistant infections are harder to treat and because Shigella spreads so easily between people, the potential for more – and larger – outbreaks is a real concern. We’re moving quickly to implement a national strategy to curb antibiotic resistance because we can’t take for granted that we’ll always have the drugs we need to fight common infections.”

Shigellosis causes an estimated 500,000 cases of diarrhea in the United States each year. To help curb the growing number of shigellosis cases, the CDC recommends that international travelers wash their hands meticulously while abroad, and follow strict dietary precautions, such as eating hot foods and drinking beverages only from sealed containers, especially when consuming water.

dchitnis@frontlinemedcom.com

Otherwise healthy patients over 80 benefit from aggressive treatment for MI

BY PATRICE WENDLING
AT ACC/CRF I2 SUMMIT

SAN DIEGO – Patients aged 80 years and older benefit from more invasive early treatment after non-ST-elevation myocardial infarction or unstable angina, the After Eighty Trial showed.

After a median follow-up of 1.5 years, an invasive strategy that included coronary angiography significantly reduced the primary endpoint of myocardial infarction (MI), need for urgent revascularization, stroke, and death from 61% with optimal medical treatment to 41%.

That drop was driven primarily by significantly fewer MIs (17% vs. 30%) and urgent revascularizations (2% vs. 11%), lead author Dr. Nicolai Tegn reported at the American College of Cardiology/Cardiovascular Research Foundation Innovation in Intervention Summit.

There were no significant differences between the invasive and conservative strategy groups in rates of stroke or all-cause death.

The composite of death and MI, however, significantly favored the invasive group (35% vs. 48%), he reported.

After Eighty randomly assigned 457 patients, aged 80 years or older, to either optimal medical therapy with no invasive treatments or coronary angiography at a percutaneous coronary intervention (PCI) center the day after inclusion, plus optimal medical therapy after about 4-5 hours if PCI was not performed or about 6-18 hours if it was. Of the 225 patients receiving angiography, 48% went on to balloon angioplasty and/or coronary stenting, and 3% had bypass surgery. The patients were selected from nearly 4,200 elderly patients at 17 community hospitals in Norway; over 3,700 of the patients were ineligible for the study because their life expectancy was less than 12 months because of a serious comorbidity; ongoing or recent bleeding; inability to comply with protocol; clinically unstable including ongoing ischemia; refusal to participate; logistic reasons; or other reasons.

After Eighty is a welcome study because of the under-representation of the elderly in clinical trials, Dr. David Kandzari, director of interventional cardiology at the Piedmont Heart Center in Atlanta, said during a press briefing at the meeting. But it raises the challenge of identifying patients in clinical practice with the same qualifying characteristics, he added, given that the study population represents only 10% of the entire screened population, “The coronary anatomy does not know the age of the patient, meaning that the findings of a benefit of an early invasive strategy seem consistent with previous studies we know across the management of patients with acute coronary syndromes,” Dr. Kandzari said.

pwendling@frontlinemedcom.com

FDA approves Anthrasil to treat inhalational anthrax

BY DEEPAK CHITNIS
FRONTLINE MEDICAL NEWS

The Food and Drug Administration has approved Anthrasil, Anthrax Immune Globulin Intravenous (Human), for treatment of inhalational anthrax when used with appropriate antibacterial drugs.

Inhalational anthrax is caused by breathing in Bacillus anthracis spores, which can occur after exposure to infected animals or contaminated animal products, or as a result of an intentional release of spores. In a statement, Dr. Karen Midthun – director of the FDA’s Center for Biologics Evaluation and Research – explained that Anthrasil “will be stored in U.S. Strategic National Stockpile to facilitate its availability in response to an anthrax emergency.”

Anthrasil was purchased by the U.S. Department of Health & Human Services’ Biomedical Advanced Research and Development Authority (BARDA) in 2011, but because it was not approved, its use prior to FDA approval would have required an emergency use authorization from the FDA.

The efficacy of Anthrasil was studied in animals because it was not feasible or ethical to conduct adequately controlled efficacy studies in humans, the FDA said. Monkeys and rabbits were exposed to Bacillus anthracis spores, and subsequently given either Anthrasil or a placebo. The survival rate for monkeys given Anthrasil was between 36% and 70%, with a trend toward increased survival at higher doses of Anthrasil. None of the monkeys given placebo survived. Rabbits had a 26% survival rate when given the drug, compared to 2% of those given placebo. A separate study exposed rabbits to Bacillus anthracis and treated them with either antibiotics or a combination of antibiotics and Anthrasil; survival rates were 71% for those treated with the combination and 25% for those treated with antibiotics only.

Safety was tested in 74 healthy human volunteers and the most commonly reported side effects were headache, back pain, nausea, and pain and swelling at the infusion site.

Anthrasil is manufactured by Cangene Corporation, based in Winnipeg, Canada, which developed the drug in collaboration with BARDA.

dchitnis@frontlinemedcom.com

FDA: Amiodarone plus some hepatitis C antivirals may result in bradycardia

BY ELIZABETH MECHCATIE
Frontline Medical News

Taking the antiarrythmic drug amiodarone with the hepatitis C antiviral drugs ledipasvir and sofosbuvir, or with sofosbuvir plus another direct-acting antiviral drug, has been associated with cases of symptomatic bradycardia – including a fatal cardiac arrest – according to the Food and Drug Administration.

Because of the reports, the antiviral drugs’ labels now recommend against using amiodarone with those hepatitis C drugs.

An FDA statement described the bradycardia cases as “serious and life-threatening.” Gilead Sciences markets the ledipasvir and sofosbuvir combination as Harvoni and markets sofosbuvir as Sovaldi to treat chronic hepatitis C virus (HCV) infection.

Gilead issued a “Dear Health Care Provider” letter that provides further details of the cases. There have been nine postmarketing reports of symptomatic bradycardia in patients who were taking amiodarone with Harvoni; amiodarone with Sovaldi plus another hepatitis C antiviral drug, simeprevir (Olysio); or amiodarone with an investigational hepatitis C antiviral drug, daclatasvir.

Of those cases, six occurred with in the first 24 hours of starting treatment with the antivirals, and three cases occurred within the first 2-12 days after antiviral therapy was started. A pacemaker was needed in three cases, and one case was a fatal cardiac arrest.

In three cases, a “rechallenge with HCV treatment in the setting of continued amiodarone therapy resulted in recurrence of symptomatic bradycardia,” according to the Gilead letter.

The effect of coadministration on the blood levels of the antiviral drugs is not known, nor is the mechanism behind the cardiac effect.

emechcatie@frontlinemedcom.com

Clindamycin, TMP-SMX are equally effective for skin infections

BY MARY ANN MOON
FROM THE NEW ENGLAND JOURNAL OF MEDICINE

Clindamycin and trimethoprim-sulfamethoxazole are similarly safe and effective for treating uncomplicated skin infections, including both cellulitis and abscesses, in ambulatory settings in regions where MRSA is endemic.

The data comparing these two agents in an ambulatory setting are limited, though both are commonly recommended as empirical therapy for skin infections in patients who present to clinics and emergency departments and have only minor or no coexisting conditions, said Dr. Loren G. Miller of the Los Angeles Biomedical Research Institute and the division of infectious diseases at Harbor-UCLA Medical Center, and his associates.

They performed a prospective double-blind randomized trial comparing clindamycin against TMP-SMX in 524 ethnically diverse adults and children who presented as outpatients with uncomplicated skin infections during a 2-year period in Chicago, San Francisco, Los Angeles, and Nashville – areas in which community-associated MRSA is endemic. The mean patient age was 27 years, and approximately 30% were pediatric patients. All the participants had cellulitis without abscesses (including erysipelas), one or more abscesses larger than 5 cm in diameter, or both conditions. A total of 264 were randomized to clindamycin and 260 to TMP-SMX daily for 10 days.

Cure rates did not differ significantly between the two study groups. At 7-10 days after completing therapy, the rates of cure in the intention-to-treat population were 80% for clindamycin and 78% for TMP-SMX, and in the evaluable population the rates were nearly 90% and 88%, respectively.

At 1 month follow-up, the cure rates in the evaluable population were 84% for clindamycin and 78% for TMP-SMX, the investigators said (N. Engl. J. Med. 2015;372:1093-103 [doi:10.1056/NEJMoa1403789]). Rates of adverse events were nearly identical between the two study groups at about 19%, and most were mild and resolved without sequelae. There were no treatment-associated serious adverse events, and the rates of treatment discontinuation were similar at nearly 9% between patients receiving clindamycin and those receiving TMP-SMX.

Stroke ambulances speed treatment to U.S. patients

BY MITCHEL L. ZOLER
AT THE INTERNATIONAL STROKE CONFERENCE

NASHVILLE, TENN. – Bringing a CT scanner and thrombolytic treatment directly to stroke patients in the field sped the time to thrombolysis, compared with waiting for the patient to arrive at the hospital.

Some U.S. stroke centers now send out a team that can immediately assess and start treating stroke patients in the community. In 2014, the first two U.S. mobile stroke-treatment units began operating, one in Houston and the second in Cleveland.

Initial reports show both programs were successful in cutting the time to deliver thrombolytic treatment with intravenous tissue plasminogen activator (TPA) to appropriate patients.

In Houston, the active phase of the program started in May 2014, and by October 2014, 47 acute ischemic stroke patients had been treated with TPA. The mobile-unit crews started 43% of eligible patients on thrombolysis within 60 minutes of their symptom onset and another 31% were treated starting 61-80 minutes after symptom onset, said Stephanie A. Parker at the International Stroke Conference.

The unit also treats patients diagnosed with hemorrhagic stroke with intravenous nicardipine for rapid blood pressure reduction, said Ms. Parker, a critical care and emergency medicine–trained registered nurse who is project manager for the Houston mobile unit.

The Cleveland program began in July 2014; of the first 100 stroke patients seen by the mobile unit 16 of 19 eligible patients received tPA, with an average time of 56 minutes from symptom onset to treatment. This compared with an average 94 minutes to tPA onset in patients brought conventionally last year to a Cleveland-area hospital, Dr. M. Shazam Hussain said in a report at the meeting, sponsored by the American Heart Association.

The clinical impact and cost effectiveness of the pilot programs using the mobile units have not yet been assessed from the data, Dr. Hussain and Ms. Parker emphasized. Funding for the Cleveland and Houston vehicles came from local donors; the Houston program also received equipment donations from manufacturers.

The two mobile units are standard 12-foot, box-shaped ambulances outfitted with a CT scanner, a point-of-care lab, and telemedicine components as well as more standard emergency-vehicle equipment. The Houston vehicle contains “all the diagnostic equipment that is in our emergency room,” Ms. Parker said.

The concept behind both the Cleveland unit, operated by the Cleveland Clinic, and the Houston unit, operated by the University of Texas, Houston, is that the mobile stroke unit arrives to a patient with a suspected stroke, the unit is stationary while a CT scan and other diagnostic tests are run, diagnosis occurs with telemedicine assistance. If the patient is cleared for TPA treatment, the infusion starts and the vehicle carries the patient to an appropriate stroke center.

Currently, the Houston unit goes out with a vascular neurologist and a telemedicine physician on board, but plans are in place to test the feasibility of relying entirely on telemedicine when making diagnostic and treatment decisions. The Cleveland mobile unit already operates in this fashion, with no physician on board, and was the first mobile stroke unit in the world to depend completely on telemedicine, according to Dr. Hussain, a neurologist and head of the stroke program at the Cleveland Clinic.

The world’s first mobile stroke unit began operating in Saarland, Germany, in 2008 (Lancet Neurology 2012;11:397-404), and a second unit began running in Berlin after that, Dr. Hussain noted. Because of limited funding, the service he directs in Cleveland has been operating from 8 a.m.-8 p.m., 7 days a week. The program plans to expand to 24-hour coverage. The Houston mobile unit operates 24/7; it averages two runs per day and administers TPA on 1 of every 10 runs, Ms. Parker said. Both the Houston and Cleveland units tie into the local 911 emergency activation systems for their respective regions.

mzoler@frontlinemedcom.com

Consider cephalosporin a safe alternative for patients with penicillin allergy

BY DEEPAK CHITNIS
AT THE 2015 AAAAI ANNUAL MEETING

HOUSTON – Given the low incidence of adverse drug reactions to cephalosporin antibiotics among nearly a million California health plan patients, patients with a history of penicillin allergy can safely be given cephalosporins, according to Dr. Eric M. Macy.

The recommendation is based on the findings of a retrospective, population-based analysis of the records of 949,323 Kaiser Permanente Southern California health plan members, which was presented by Dr. Macy, of the Kaiser Permanente Medical Center in San Diego, at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Dr. Macy and his colleagues examined the records of 622,456 health plan members who were given 901,908 regimens of oral cephalosporins and 326,867 members given 487,630 parenteral cephalosporin regimens between Jan. 1, 2010, and Dec. 31, 2012.

Clostridium difficile infection within 90 days, nephropathy within 30 days, and all-cause death within 1 day were the most common cephalosporin-associated adverse drug reactions (ADRs) reported by physicians, with rates of 0.91%, 0.15%, and 0.10%, respectively. Cephalosporin-associated anaphylaxis was documented by physicians a total of five times in oral patients and eight times in parenteral patients (P = .0761), while only three serious cutaneous adverse reactions (SCARs) were recorded. All of those SCARS were attributable to other antibiotics taken at the same time as the cephalosporins, according to Dr. Macy.

Patients who reported developing new cephalosporin allergies over the course of the study period were significantly more likely to be female than male: 0.56% vs. 0.43% (P < .0001). And patients with a history of penicillin allergy were more likely to report a new cephalosporin allergy within 30 days than patients with no drug allergy, another cephalosporin allergy, or a non–beta-lactam allergy.

dchitnis@frontlinemedcom.com