Think ‘ceftaroline’ in suspected drug-resistant CAP

ESTES PARK, COLO. – For primary care physicians, ceftaroline is hands-down the most exciting and important of the four systemic antibacterial agents to reach the U.S. market since the great 7-year drought in approvals ended in 2008, an infectious disease expert observed.

Ceftaroline (Teflaro) is a novel cephalosporin with unique binding to penicillin-binding proteins, including the altered versions that confer resistance in methicillin-resistant Staphylococcus aureus and penicillin- and cephalosporin-resistant Streptococcus pneumoniae. Thus, ceftaroline is a potent and effective drug in the increasingly common situation of beta-lactam-resistant community-acquired pneumonia (CAP) or complicated skin and soft tissue infections, noted Dr. Mary T. Bessesen, chief of the infectious diseases section at Denver V.A. Medical Center.

In the pivotal FOCUS 1 and FOCUS 2 trials conducted in patients with CAP not due to MRSA, ceftaroline proved noninferior overall to ceftriaxone (Rocephin). Of note, in the 14% of FOCUS participants with CAP due to S. aureus, ceftaroline proved to be significantly more effective than ceftriaxone. Importantly, the same was true among the one-third of FOCUS participants in whom S. pneumoniae was isolated (Clin. Infect. Dis. 2010;51:1395-405).

"I think if you’re going to impact mortality in CAP, pneumococcus has to be the primary target. Ceftaroline is a good alternative when penicillin-resistant S. pneumoniae is suspected or proven," Dr. Bessesen said at a conference on internal medicine sponsored by the University of Colorado.

Other common pathogens in CAP that are sensitive to ceftaroline are Hemophilus influenza and Moraxella catarrhalis. The Gram-negative pathogens E. coli, Klebsiella pneumoniae, and Enterobacter cloacae are also ceftaroline sensitive, with activity similar to ceftriaxone and ceftazidime (Fortaz).

Not only is MRSA sensitive to ceftaroline, so are methicillin-sensitive S. aureus, vancomycin-intermediate S. aureus, vancomycin-resistant S. aureus, linezolid (Zyvox)-resistant S. aureus, and daptomycin (Cubicin)-nonsusceptible S. aureus.

Ceftaroline does not cover the atypical pneumonia pathogens Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumoniae, nor does it cover Pseudomonas aeruginosa or extended-spectrum beta-lactamase-producing Enterobacteriaceae, stressed Dr. Bessesen.

The current CAP guidelines don’t include recommendations for ceftaroline, because the drug received Food and Drug Administration approval for treatment of CAP and complicated skin and soft tissue infections after the guidelines were issued.

Clinical trials investigating ceftaroline in CAP caused by MRSA would be welcome, Dr. Bessesen noted, because the current CAP guidelines don’t include any recommendations for CAP pneumonia.

"It really leaves us wondering in high-risk cases what’s best to do," she said. "There’s been some controversy about vancomycin versus linezolid when you suspect MRSA pneumonia. Ceftaroline would be a nice way to get around all of that."

Ceftaroline is administered intravenously twice daily, with dose adjustment for renal function. The drug’s pharmacokinetics are favorable for intramuscular injection, but there are limited clinical data for this route, and it is not FDA approved.

Ceftaroline costs about $84 per day, or four times more than ceftriaxone, Dr. Bessesen said. As a result, formulary committees are reluctant to put ceftaroline on the list.

That makes Dr. Bessesen see red.

"I’ve never been on a drug company speakers bureau. I’ve never had any research money from drug companies. I speak only as someone who’s interested in us being able to continue to treat bacterial infections when I say we’ve got to change our attitude. We have to be willing to pay something for these antibiotics," she asserted.

The antibiotic development pipeline has failed as pharmaceutical companies have abandoned the field, Dr. Bessesen continued. There are three reasons for this. One is that all the easy drugs have already been discovered. Another is that the FDA regulatory approval system for antibacterial agents is seriously outdated; the European Medicines Agency is much more forward thinking in this area and would be a useful model for FDA modernization, she noted.

But the biggest reason for the broken pipeline is that antibiotics are not a good financial investment for pharmaceutical companies. "It’s much more profitable for them to develop a drug like lovastatin that you’re going to take every day for the rest of your life than to develop an antibiotic you’re going to prescribe for a week or two. And society expects antibiotics to be cheap," Dr. Bessesen observed.

Contrast the roughly $1,600 cost of 4 weeks of ceftriaxone for S. viridans endocarditis – a serious infection – with the $54,000 price tag for 1 year of trastuzumab for breast cancer or $240,000 for a course of induction therapy with ipilimumab for melanoma, Dr. Bessesen noted.

"I’m not saying drugs should cost that much. I’m simply pointing out how society looks differently at these," she said.

With regard to the other three systemic antibiotics approved by the FDA in the 5 years since the 7-year drought ended, bedaquiline (Sirturo) is the most important globally, because it is indicated for multidrug-resistant tuberculosis. However, few U.S. physicians will have occasion to prescribe it.

Fidaxomicin (Dificid) is an effective drug for Clostridium difficile diarrhea; it’s eight times more potent than vancomycin against C. difficile, has minimal systemic absorption, and offers the major advantage of producing little negative impact on favorable gut flora. Telavancin (Vibativ) is a once-daily agent for hospital-acquired and ventilator-associated bacterial pneumonia.

Dr. Bessesen reported having no conflicts of interest.

bjancin@frontlinemedcom.com

ESTES PARK, COLO. – For primary care physicians, ceftaroline is hands-down the most exciting and important of the four systemic antibacterial agents to reach the U.S. market since the great 7-year drought in approvals ended in 2008, an infectious disease expert observed.

Ceftaroline (Teflaro) is a novel cephalosporin with unique binding to penicillin-binding proteins, including the altered versions that confer resistance in methicillin-resistant Staphylococcus aureus and penicillin- and cephalosporin-resistant Streptococcus pneumoniae. Thus, ceftaroline is a potent and effective drug in the increasingly common situation of beta-lactam-resistant community-acquired pneumonia (CAP) or complicated skin and soft tissue infections, noted Dr. Mary T. Bessesen, chief of the infectious diseases section at Denver V.A. Medical Center.

In the pivotal FOCUS 1 and FOCUS 2 trials conducted in patients with CAP not due to MRSA, ceftaroline proved noninferior overall to ceftriaxone (Rocephin). Of note, in the 14% of FOCUS participants with CAP due to S. aureus, ceftaroline proved to be significantly more effective than ceftriaxone. Importantly, the same was true among the one-third of FOCUS participants in whom S. pneumoniae was isolated (Clin. Infect. Dis. 2010;51:1395-405).

"I think if you’re going to impact mortality in CAP, pneumococcus has to be the primary target. Ceftaroline is a good alternative when penicillin-resistant S. pneumoniae is suspected or proven," Dr. Bessesen said at a conference on internal medicine sponsored by the University of Colorado.

Other common pathogens in CAP that are sensitive to ceftaroline are Hemophilus influenza and Moraxella catarrhalis. The Gram-negative pathogens E. coli, Klebsiella pneumoniae, and Enterobacter cloacae are also ceftaroline sensitive, with activity similar to ceftriaxone and ceftazidime (Fortaz).

Not only is MRSA sensitive to ceftaroline, so are methicillin-sensitive S. aureus, vancomycin-intermediate S. aureus, vancomycin-resistant S. aureus, linezolid (Zyvox)-resistant S. aureus, and daptomycin (Cubicin)-nonsusceptible S. aureus.

Ceftaroline does not cover the atypical pneumonia pathogens Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumoniae, nor does it cover Pseudomonas aeruginosa or extended-spectrum beta-lactamase-producing Enterobacteriaceae, stressed Dr. Bessesen.

The current CAP guidelines don’t include recommendations for ceftaroline, because the drug received Food and Drug Administration approval for treatment of CAP and complicated skin and soft tissue infections after the guidelines were issued.

Clinical trials investigating ceftaroline in CAP caused by MRSA would be welcome, Dr. Bessesen noted, because the current CAP guidelines don’t include any recommendations for CAP pneumonia.

"It really leaves us wondering in high-risk cases what’s best to do," she said. "There’s been some controversy about vancomycin versus linezolid when you suspect MRSA pneumonia. Ceftaroline would be a nice way to get around all of that."

Ceftaroline is administered intravenously twice daily, with dose adjustment for renal function. The drug’s pharmacokinetics are favorable for intramuscular injection, but there are limited clinical data for this route, and it is not FDA approved.

Ceftaroline costs about $84 per day, or four times more than ceftriaxone, Dr. Bessesen said. As a result, formulary committees are reluctant to put ceftaroline on the list.

That makes Dr. Bessesen see red.

"I’ve never been on a drug company speakers bureau. I’ve never had any research money from drug companies. I speak only as someone who’s interested in us being able to continue to treat bacterial infections when I say we’ve got to change our attitude. We have to be willing to pay something for these antibiotics," she asserted.

The antibiotic development pipeline has failed as pharmaceutical companies have abandoned the field, Dr. Bessesen continued. There are three reasons for this. One is that all the easy drugs have already been discovered. Another is that the FDA regulatory approval system for antibacterial agents is seriously outdated; the European Medicines Agency is much more forward thinking in this area and would be a useful model for FDA modernization, she noted.

But the biggest reason for the broken pipeline is that antibiotics are not a good financial investment for pharmaceutical companies. "It’s much more profitable for them to develop a drug like lovastatin that you’re going to take every day for the rest of your life than to develop an antibiotic you’re going to prescribe for a week or two. And society expects antibiotics to be cheap," Dr. Bessesen observed.

Contrast the roughly $1,600 cost of 4 weeks of ceftriaxone for S. viridans endocarditis – a serious infection – with the $54,000 price tag for 1 year of trastuzumab for breast cancer or $240,000 for a course of induction therapy with ipilimumab for melanoma, Dr. Bessesen noted.

"I’m not saying drugs should cost that much. I’m simply pointing out how society looks differently at these," she said.

With regard to the other three systemic antibiotics approved by the FDA in the 5 years since the 7-year drought ended, bedaquiline (Sirturo) is the most important globally, because it is indicated for multidrug-resistant tuberculosis. However, few U.S. physicians will have occasion to prescribe it.

Fidaxomicin (Dificid) is an effective drug for Clostridium difficile diarrhea; it’s eight times more potent than vancomycin against C. difficile, has minimal systemic absorption, and offers the major advantage of producing little negative impact on favorable gut flora. Telavancin (Vibativ) is a once-daily agent for hospital-acquired and ventilator-associated bacterial pneumonia.

Dr. Bessesen reported having no conflicts of interest.

bjancin@frontlinemedcom.com

ESTES PARK, COLO. – For primary care physicians, ceftaroline is hands-down the most exciting and important of the four systemic antibacterial agents to reach the U.S. market since the great 7-year drought in approvals ended in 2008, an infectious disease expert observed.

Ceftaroline (Teflaro) is a novel cephalosporin with unique binding to penicillin-binding proteins, including the altered versions that confer resistance in methicillin-resistant Staphylococcus aureus and penicillin- and cephalosporin-resistant Streptococcus pneumoniae. Thus, ceftaroline is a potent and effective drug in the increasingly common situation of beta-lactam-resistant community-acquired pneumonia (CAP) or complicated skin and soft tissue infections, noted Dr. Mary T. Bessesen, chief of the infectious diseases section at Denver V.A. Medical Center.

In the pivotal FOCUS 1 and FOCUS 2 trials conducted in patients with CAP not due to MRSA, ceftaroline proved noninferior overall to ceftriaxone (Rocephin). Of note, in the 14% of FOCUS participants with CAP due to S. aureus, ceftaroline proved to be significantly more effective than ceftriaxone. Importantly, the same was true among the one-third of FOCUS participants in whom S. pneumoniae was isolated (Clin. Infect. Dis. 2010;51:1395-405).

"I think if you’re going to impact mortality in CAP, pneumococcus has to be the primary target. Ceftaroline is a good alternative when penicillin-resistant S. pneumoniae is suspected or proven," Dr. Bessesen said at a conference on internal medicine sponsored by the University of Colorado.

Other common pathogens in CAP that are sensitive to ceftaroline are Hemophilus influenza and Moraxella catarrhalis. The Gram-negative pathogens E. coli, Klebsiella pneumoniae, and Enterobacter cloacae are also ceftaroline sensitive, with activity similar to ceftriaxone and ceftazidime (Fortaz).

Not only is MRSA sensitive to ceftaroline, so are methicillin-sensitive S. aureus, vancomycin-intermediate S. aureus, vancomycin-resistant S. aureus, linezolid (Zyvox)-resistant S. aureus, and daptomycin (Cubicin)-nonsusceptible S. aureus.

Ceftaroline does not cover the atypical pneumonia pathogens Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumoniae, nor does it cover Pseudomonas aeruginosa or extended-spectrum beta-lactamase-producing Enterobacteriaceae, stressed Dr. Bessesen.

The current CAP guidelines don’t include recommendations for ceftaroline, because the drug received Food and Drug Administration approval for treatment of CAP and complicated skin and soft tissue infections after the guidelines were issued.

Clinical trials investigating ceftaroline in CAP caused by MRSA would be welcome, Dr. Bessesen noted, because the current CAP guidelines don’t include any recommendations for CAP pneumonia.

"It really leaves us wondering in high-risk cases what’s best to do," she said. "There’s been some controversy about vancomycin versus linezolid when you suspect MRSA pneumonia. Ceftaroline would be a nice way to get around all of that."

Ceftaroline is administered intravenously twice daily, with dose adjustment for renal function. The drug’s pharmacokinetics are favorable for intramuscular injection, but there are limited clinical data for this route, and it is not FDA approved.

Ceftaroline costs about $84 per day, or four times more than ceftriaxone, Dr. Bessesen said. As a result, formulary committees are reluctant to put ceftaroline on the list.

That makes Dr. Bessesen see red.

"I’ve never been on a drug company speakers bureau. I’ve never had any research money from drug companies. I speak only as someone who’s interested in us being able to continue to treat bacterial infections when I say we’ve got to change our attitude. We have to be willing to pay something for these antibiotics," she asserted.

The antibiotic development pipeline has failed as pharmaceutical companies have abandoned the field, Dr. Bessesen continued. There are three reasons for this. One is that all the easy drugs have already been discovered. Another is that the FDA regulatory approval system for antibacterial agents is seriously outdated; the European Medicines Agency is much more forward thinking in this area and would be a useful model for FDA modernization, she noted.

But the biggest reason for the broken pipeline is that antibiotics are not a good financial investment for pharmaceutical companies. "It’s much more profitable for them to develop a drug like lovastatin that you’re going to take every day for the rest of your life than to develop an antibiotic you’re going to prescribe for a week or two. And society expects antibiotics to be cheap," Dr. Bessesen observed.

Contrast the roughly $1,600 cost of 4 weeks of ceftriaxone for S. viridans endocarditis – a serious infection – with the $54,000 price tag for 1 year of trastuzumab for breast cancer or $240,000 for a course of induction therapy with ipilimumab for melanoma, Dr. Bessesen noted.

"I’m not saying drugs should cost that much. I’m simply pointing out how society looks differently at these," she said.

With regard to the other three systemic antibiotics approved by the FDA in the 5 years since the 7-year drought ended, bedaquiline (Sirturo) is the most important globally, because it is indicated for multidrug-resistant tuberculosis. However, few U.S. physicians will have occasion to prescribe it.

Fidaxomicin (Dificid) is an effective drug for Clostridium difficile diarrhea; it’s eight times more potent than vancomycin against C. difficile, has minimal systemic absorption, and offers the major advantage of producing little negative impact on favorable gut flora. Telavancin (Vibativ) is a once-daily agent for hospital-acquired and ventilator-associated bacterial pneumonia.

Dr. Bessesen reported having no conflicts of interest.

bjancin@frontlinemedcom.com