Ceftobiprole, novel broad spectrum cephalosporin

[ZpackSux]

has coverage against nosocomial MRSA and Pseudomonas.

Discuss.

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[psychoandy]

Interesting. Had to google it because lexi comp and johns hopkins abx didn't have anything. The questions I have in my limited student knowedge base is how much money and any special considerations. From the little bit of scanning that I did it didn't seem that much more effective. Sure, vanco has red man and kidneys are of concern, but it's dirt cheap compared to Zyvox. Of course, another 1st/2nd line agent is always good to have.

PS: I just found out my hospital has Xopenex nebs on formulary...but the only time I ever see it dispensed is b/c that's what the pt is on at home. But we're non profit so I doubt it matters as much.

 

[ZpackSux]

J and J is expecting to release the drug at $160 per day....about equal to Zyvox... I can give more info as we discuss in depth.

 

[GatorRxGirl]

Ask again in 6 months when maybe I'll know what I'm talking about.

 

[ZpackSux]

Ask again in 6 months when maybe I'll know what I'm talking about.

I wanna know what you think about it now..... not in 6 months..

 

[GravyRPH]

But we're non profit so I doubt it matters as much.

What does that mean? Most hospitals wether you're non-profit or not are struggling to keep afloat with increasing health care costs and ever decreasing reimbursement. I work for a non-profit and still have to keep a strict control on formulary and prescribing to keep us less in the red than we already are.

They'd have to crawl over my dead body to add Xopenex to the formulary.

 

[GravyRPH]

Oh ya, the topic, Ceftiboprole. Too hard to say. I think I'll hold out until we get at least 3 free lunches from the J&J rep.

 

[ZpackSux]

Oh ya, the topic, Ceftiboprole. Too hard to say. I think I'll hold out until we get at least 3 free lunches from the J&J rep.

Spoken like a true seasoned hospital pharmacist.

 

[GravyRPH]

Heheh. Yes. And not even 5 minutes after spouting off how tightly I control the formulary.

I do really...really...like sushi though.


(They do know I'm kidding, right?)

 

[ZpackSux]

Heheh. Yes. And not even 5 minutes after spouting off how tightly I control the formulary.

I do really...really...like sushi though.


(They do know I'm kidding, right?)

Do they know you're kidding? I'm not so sure... there are quite a few uptight pharmacy students out there...

 

[ZpackSux]

Ceftobiprole is a novel cephalosporin because it's the first in class to cover MRSA. The phase III trial which compared ceftobiprole 500mg BID to Vancomycin 1gram Q12h in CSSI pts show similar clinical cure rate.

Then again, I'm not impressed with Vanc 1gram Q12h..because an average male patient with average renal fxn will only attain levels of 6-28 mcg/ml...which I do not consider as an efficacious regimen.

Ceftobiprole also has a farily good coverage against gram neg organisms including Pseudomonas species. This sounds great.

However, what benefit do we gain by having Ceftobiprole on board? Vancomycin has been a very durable antibiotic with less than 10 documented cases of VRSA...

 

[pharmboy30]

what is cover gram negatives?

edit: nevermind, you mentioned that.......

 

[ZpackSux]

what is cover gram negatives?

eh?

 

[pharmboy30]

eh?

or I read it speficically targets the penicillin resistance mechanisms?
i don't know, i'm tired and work sucks, short staffed........
that, or I just ate a big burrito...

 

[Hernandez]

Is this one of the new beta-lactams which is targeting Penicillin binding site 2?

 

[Hernandez]

Sure, vanco has red man and kidneys are of concern, but it's dirt cheap compared to Zyvox.

Vanc also sucks against soft tissue infections, so as long as it has great skin bio-availability, it'll have a niche.

 

[ZpackSux]

Vanc also sucks against soft tissue infections, so as long as it has great skin bio-availability, it'll have a niche.

Well...then that's too bad..because when Ceftobiprole was compared to Vanc in SSI, the curate rates were equivalent.

Vanco does not "suck" against soft tissue infection. You may be referring to Vancomycin's lack of penetration to soft tissues.. obviously since Vanc is a very big molecule. But this doesn't always translate to clinical failure.

Studies pitting Zyvox against Vanco in CSSI shows slightly advantage of Zyvox over Vanco.. which just proves Vanco was underdosed at 1 gram q12h which could mean very low peak and trough...below MIC.

 

[Hernandez]

Vanco does not "suck" against soft tissue infection. You may be referring to Vancomycin's lack of penetration to soft tissues.. obviously since Vanc is a very big molecule. But this doesn't always translate to clinical failure.

No, but it more than emphasizes that the most common presentation of MRSA infections does not lend itself to the use of an IV drug which has lower concentrations in the area which you need to treat. But if they're sick enough to be in the hospital secondarily to a MRSA skin infection, they're .not going to be put on Vanc alone

Studies pitting Zyvox against Vanco in CSSI shows slightly advantage of Zyvox over Vanco.. which just proves Vanco was underdosed at 1 gram q12h which could mean very low peak and trough...below MIC.

Until you pharmacists start giving us data which support the higher doses and gives physicians data to show that the peak levels we have now are somewhat artificial, then nothing is going to change. I frequently have seen 1 gm q12 put peak levels higher than 15, and if for some reason they were to develop oto- or nephrotoxicity, that's just asking to be bent over in court

Well...then that's too bad..because when Ceftobiprole was compared to Vanc in SSI, the curate rates were equivalent.

SSI? surgical site infections?

 

[ZpackSux]

Clinda is added often due to its' skin penetration ability. But nosocomial MRSA skin infection (different from community acquired MRSA which is susceptible to many other ABX) is still treated primarily with Vanco.

1 gram q12h and peak of 15 is about right on a larger and young patient. Except, in 2 half lives, the trough is 3.5 ug/ml which is below MIC and subtherapeutic. No wonder you have to add other antibiotics. Vanco is a durable ABX but the MICs of different bugs have crept up... now we like to keep the trough at 15 to 20 for serious infections. Which means we're seeing peak of 40+.

The irreversible ototoxicity is a concern at levels above 80 and even though reversible ototoxicities have occured at therapeutic levels, they were more prevalent when Vanco was called the Mississippi Mud.. when it had impurities. Vancomyicn today is very purified...

Vanco nephrotoxicity and lawsuits? LOL...


SSI = skin structure infection.

 

[ZpackSux]

btw, Vancomycin is a time dependent bacteriocidal abx..which means the therapeutic peak level is less of a concern than keeping the level above MIC.

Concentration dependent ABX such as aminoglycosides is more cidal at higher level about 10 X MIC... which does not cause the toxicity rather low but sustained trough causes the nephrotoxicity. AG is nephrotoxic for sure. Vanco on the other hand is very safe.

 

[ZpackSux]

Is this one of the new beta-lactams which is targeting Penicillin binding site 2?

It readily binds to the PCN Binding protein 2.

 

[Hernandez]

1 gram q12h and peak of 15 is about right on a larger and young patient. Except, in 2 half lives, the trough is 3.5 ug/ml which is below MIC and subtherapeutic. No wonder you have to add other antibiotics. Vanco is a durable ABX but the MICs of different bugs have crept up...

Unless you have a better way of calculating Vanc dosing for various pts, that's kinda what we're stuck with as a starting dose, so if that first trough is <4, we decrease the time interval between dosing, but at the moment, I have little way to accurately predict who is going to have a low trough.

now we like to keep the trough at 15 to 20 for serious infections. Which means we're seeing peak of 40+.

can ya point in me in the direction of some lit on this? If there are times where I can justify higher dosing, I'd like to know.

The irreversible ototoxicity is a concern at levels above 80 and even though reversible ototoxicities have occured at therapeutic levels,

Do you have any pharmaceutical lit on this? I specifically tried to research (in the medical lit) peak levels and toxicities a month ago, but the literature I found consistently stated that there were no peak levels shown to have consistent toxicities and then all seemed to universally agree on peak levels somewhere between 12-20, and if you can point me in the right direction on some data which gives me some better data than the "there is no peak level which has shown to consistently cause toxicities" line which I've got, then I'd greatly appreciate it. It'd definitively put my mind at ease if I knew that there was some backing that irreversible toxicities are rare at lower peaks

Vanco nephrotoxicity and lawsuits? LOL...

I mistyped, it was ototoxicity not nephrotoxicity, there was 1 such lawsuit at my schools teaching hospital ~8-10 years ago and they plaintiff won since no one had ever checked a peak or trough.

 

[npage148]

slap em all on continous vanco infusions!

 

[ZpackSux]

Unless you have a better way of calculating Vanc dosing for various pts, that's kinda what we're stuck with as a starting dose, so if that first trough is <4, we decrease the time interval between dosing, but at the moment, I have little way to accurately predict who is going to have a low trough.

Volume of distribution of Vanco is 0.7L/kg. So for a patient with dosing weight of 80kg, the VancVd = 56Liters. 1000mg in 56 Liter will give you an absolute peak of 17.85ug/ml. Dosing wt isn't always the IBW or ABW. So you can predict the peak by calculating the Volume of Distribution. Therefore, I would load this particular patient with 1.75grams to get the peak of 30+ug/ml. Or ask your pharmacist to dose it for you.

http://jcm.asm.org/cgi/content/abstract/44/11/3883

This describes the increasing MIC trends of MRSA.

can ya point in me in the direction of some lit on this? If there are times where I can justify higher dosing, I'd like to know.

http://www.ucsf.edu/idmp/adult_guide/vanco_dosing.htm

UCSF is very reputable in the clinical pharmacy arena. Here is the recommendation of troughs. In order to attain those troughs, peak needs to be be 30 to 40ug/ml or higher.

Do you have any pharmaceutical lit on this? I specifically tried to research (in the medical lit) peak levels and toxicities a month ago, but the literature I found consistently stated that there were no peak levels shown to have consistent toxicities and then all seemed to universally agree on peak levels somewhere between 12-20, and if you can point me in the right direction on some data which gives me some better data than the "there is no peak level which has shown to consistently cause toxicities" line which I've got, then I'd greatly appreciate it. It'd definitively put my mind at ease if I knew that there was some backing that irreversible toxicities are rare at lower peaks

Peak of 12-20 will give you a trough of 3 to 5. Sub therapeutic.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3057327&dopt=Abstract

http://www.baylorhealth.edu/proceedings/14_2/14_2_gurk-turner.html read "Toxicity" section for your peace of mind.

I mistyped, it was ototoxicity not nephrotoxicity, there was 1 such lawsuit at my schools teaching hospital ~8-10 years ago and they plaintiff won since no one had ever checked a peak or trough.

Ask your pharmacist to dose it for you. Simply write:

Vancomycin per pharmacy. Please dose to Peak of 40ug/ml and trough of 10ug/ml. Hernandez, MD.

Next time, ask your pharmacy buddies for the info. All these should be in their "Vanco" file.

 

[ZpackSux]

slap em all on continous vanco infusions!

Not a bad idea...but it ties up a valuable IV access..and every time the patient gets something else IV, there are concerns of incompatibilities etc. And can you imagine the patient having the Red Man Syndrome all day long?

Fun Fun!

 

[ZpackSux]

Amazing...SDN hasn't responded on this thread....

 

[GravyRPH]

Unless you have a better way of calculating Vanc dosing for various pts, that's kinda what we're stuck with as a starting dose, so if that first trough is <4, we decrease the time interval between dosing, but at the moment, I have little way to accurately predict who is going to have a low trough.

"Us pharmacists" have great ways to predict levels based on specific patient parameters involving all these neat pharmacokinetic equations. Most (all?) institutions have Vanco protocols per pharmacy. You normally don't even have to specify what peak and trough you want because even an average pharmacist should be able to get you where you want to be.

can ya point in me in the direction of some lit on this? If there are times where I can justify higher dosing, I'd like to know.

Check the current ATS/IDSA guidelines. It's all in there.