pharmd009

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Say you're writing the hospital guidelines for febrile neutropenia. Obviously you'd have to take into patient specific factors when selecting an agent for each patient, but if you had to choose between cefepime, zosyn, or a carbapenem as your recommended first line agent in your guidelines, which would you choose and why?
 

lord999

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Zosyn, has multiple treatment retreat options, more broad spectrum that cefepime (you really have to have a Pseudomonas problem around if you're immediately reaching for it), doesn't have the renal issues that the carbapenem has. (Is cheaper too).

Cefepime, I'm surprised your P&T chose that one for unknown as it's kind of infamous for being the high mortality option if you're wrong about its broad coverage.

If a carbapenem, not imipenem/cilastatin.

None of your choices have MRSA coverage as an option, which is not a good practice. Unknown cause febrile neutropenia should have Pseudomonal and MRSA coverage by default in an institutional setting.
 
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gwarm01

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Zosyn, has multiple treatment retreat options, more broad spectrum that cefepime (you really have to have a Pseudomonas problem around if you're immediately reaching for it), doesn't have the renal issues that the carbapenem has. (Is cheaper too).

Cefepime, I'm surprised your P&T chose that one for unknown as it's kind of infamous for being the high mortality option if you're wrong about its broad coverage.

If a carbapenem, not imipenem/cilastatin.

None of your choices have MRSA coverage as an option, which is not a good practice.
Why no Primaxin? I'll admit I'm not too familiar with it, so I'm not aware of any shortcoming. Most hospitals I've worked at have used meropenem, and my side job recent got rid of imipenem in favor of meropenem. I never bothered to look into it (side effect of being IT instead of clinical I suppose).
 

lord999

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Why no Primaxin? I'll admit I'm not too familiar with it, so I'm not aware of any shortcoming. Most hospitals I've worked at have used meropenem, and my side job recent got rid of imipenem in favor of meropenem. I never bothered to look into it (side effect of being IT instead of clinical I suppose).
What's the cilastatin for again is the answer (because a functioning kidney eliminates imipenem faster than you want)? Even with that, I've seen ARF and major hepatic ALT-AST elevation from that drug that it's just worth it to move to Merrem. When troubleshooting FUO issues, the last thing you want to do is cause associated ones like ARF or hepatic insufficiency as you then get stuck with the chicken-or-egg question of causation.

The point of picking drugs for FUO/neutropenia is to buy yourself time to figure out targeted therapy without causing ancillary damage (why aminoglycosides are avoided as part of FUO therapy as the side effect profile risk is too high to just use in general but are worth the profile if you know exactly what you're targeting).
 
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bacillus1

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Zosyn, has multiple treatment retreat options, more broad spectrum that cefepime (you really have to have a Pseudomonas problem around if you're immediately reaching for it), doesn't have the renal issues that the carbapenem has. (Is cheaper too).

Cefepime, I'm surprised your P&T chose that one for unknown as it's kind of infamous for being the high mortality option if you're wrong about its broad coverage.

If a carbapenem, not imipenem/cilastatin.

None of your choices have MRSA coverage as an option, which is not a good practice. Unknown cause febrile neutropenia should have Pseudomonal and MRSA coverage by default in an institutional setting.
Guidelines do not reommend vanc unless you have an additional indication for it (example: suspected source is SSTI). I would go with cefepime as well, as long as it is given at pseudomonal dosing. You don't want to make patients resistant in the future by exposing them to unnecessary therapy, especially if they continue having risk factors for neutropenic fever.
 
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lord999

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Guidelines do not reommend vanc unless you have an additional indication for it (example: suspected source is SSTI). I would go with cefepime as well, as long as it is given at pseudomonal dosing.
Of course we don't use vanc as the first line, but there are good MRSA options without vanc. I prefer FQs or SMX/TMP IV myself.

http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/2008 NewFever in Critically Ill.pdf

I still think these are out-of-date for what we know now about the narrower broad spectrum antibiotics (cefepime), and the changing profile of what's coming in nowadays. Not saying that cefepime sucks, but all of these agents makes for good conversation around the mortality numbers.

Then again, it's still a patient-by-patient decision. I would specifically attempt to cover MRSA and Pseudomonas if I knew nothing else about the patient including renal and hepatic status as if I need time, those two untreated get out of hand faster than I can get culture data back.
 
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Praziquantel86

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I thought I'd chime in here. First, to answer the original question, it is impossible to choose "one" agent for neutropenic fever among the anti-Pseudomonals, given different risks in different patients (prior ESBL colonization, MDR Pseudomonas colonization, allergies, prior antibiotic exposure - just a few things that come to mind). You can certainly offer guidance on when to use one agent over another, but having only one option just isn't possible.

To some of the other comments: the increased risk with cefepime in febrile neutropenia has been debunked and was mostly associated with inadequate dosing. The FDA did a nice followup with this. I'd imagine it's the first line agent in most institutions with a sizeable cancer population and it certainly is in mine. I would also say that cefepime is just about as far as you can get from a narrow spectrum agent, and the IDSA guidelines (updated in 2011) were completely aware of the Yahav meta analysis (published in 2007) when they were released. The NCCN guidelines, which are updated more frequently, still strongly recommend cefepime as first line monotherapy.

The aminoglycosides aren't recommended not because of their toxic profile (although that does factor in) but because they have been shown to be less effective in comparison to beta lactam agents for bacteremia and have additionally been shown to be less effective in neutropenic patients (the case with all antibiotics, but probably moreso with aminoglycosides than with the beta lactams). Aminoglycosides can still be quite useful though if the patient has a history of an MDR organism or is at high risk for such an infection, but they generally aren't recommended to be used front line.

Vancomycin, or MRSA coverage in general, is not recommended first line unless specific risk factors or present (indwelling line, prior colonization with MRSA, sepsis, etc.) or if the patient presents with a condition such as skin/soft tissue infection or healthcare-associated pneumonia that otherwise warrants coverage. Even here this is probably excessive and led to significant overuse of these drugs. Levofloxacin, to which MRSA rapidly develops resistance and has high baseline resistance, is not appropriate for MRSA and isn't recommended in any guideline I know of. Additionally, many of the highest risk patients are on quinolone prophylaxis to begin with (depending on your institution's usual practice). Bactrim is fine for non-invasive infections, but a great RCT comparing Bactrim to vancomycin for such infections showed that patients treated with bactrim had overall higher mortality. So that's probably not a great choice either if concerned for a serious MRSA infection in a neutropenic patient.

Imipenem isn't a terrible option, but it's somewhat less potent against Pseudomonas than meropenem and has generally fallen out of favor due to more complicated dosing and worse adverse event profile. It's also technically not correct to say that the kidneys "clear" imipenem faster, rather, dehydropeptidase which is found in renal tubules metabolizes imipenem. Hence the addition of cilastatin.

Long story short, cefepime, pip-tazo, and anti-Pseudomonal carbapenems are all appropriate front line options for monotherapy in febrile neutropenia, provided all are dosed at their maximal dosing and risks are taken into account. MRSA coverage isn't recommended in all cases, but is warranted in certain scenarios depending on patient risks.
 
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Rockinacoustic

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High dose Cefepime at my institution. We are very aggressive with dosing in renal dysfunction to maximize T > MIC. Also given our urban patient population (homeless, poor outpatient follow-up) we usually add Vanco on empirically for most patients as well.

Of course we don't use vanc as the first line, but there are good MRSA options without vanc. I prefer FQs or SMX/TMP IV myself.
Do you seriously use FQ's for MRSA?
 

Lnsean

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High dose Cefepime at my institution. We are very aggressive with dosing in renal dysfunction to maximize T > MIC. Also given our urban patient population (homeless, poor outpatient follow-up) we usually add Vanco on empirically for most patients as well.



Do you seriously use FQ's for MRSA?
get some of that avelox brahh
 

lord999

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High dose Cefepime at my institution. We are very aggressive with dosing in renal dysfunction to maximize T > MIC. Also given our urban patient population (homeless, poor outpatient follow-up) we usually add Vanco on empirically for most patients as well.



Do you seriously use FQ's for MRSA?
Yes, I know it's crazy, but those FQ's still work. More or less though, it's just a matter of time now until MRSA is completely replaced by VRSA.
 

KARM12

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The best agent depends on your antibiogram.... Most of these answers make me cringe (except prazi). Vanco is NOT recommended as standard empiric therapy for all patients.
 
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Yes, I know it's crazy, but those FQ's still work. More or less though, it's just a matter of time now until MRSA is completely replaced by VRSA.
Do you have any literature on use of FQ's for MRSA? I don't recall learning this in class and most of the literature I'm finding thus far is about MRSA rates associated with FQ use and one study regarding resistance rates of MRSA from a community in Cairo, Egypt.
 

PharmDBro2017

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Do you have any literature on use of FQ's for MRSA? I don't recall learning this in class and most of the literature I'm finding thus far is about MRSA rates associated with FQ use and one study regarding resistance rates of MRSA from a community in Cairo, Egypt.
AFAIK, per the MRSA guidelines in adults/children, FQs have no place treating MRSA... except if the patient is on long term suppressive antibiotics (bactrim/FQ/tetracycline) for device-related osteoarticular infections and then it's to be given in conjunction with rifampin (due to FQ resistance).
 
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AFAIK, per the MRSA guidelines in adults/children, FQs have no place treating MRSA... except if the patient is on long term suppressive antibiotics (bactrim/FQ/tetracycline) for device-related osteoarticular infections and then it's to be given in conjunction with rifampin (due to FQ resistance).

That's what I thought but I had no idea about the device-related osteoarticular infection long term use in conjunction with rifampin! Thank you very much!
 

KARM12

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FQ should not be used for Staph aureus...maybe in some odd ball case, but not as a general recommendation. Resistance is acquired quickly...
 
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Praziquantel86

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FQ should not be used for Staph aureus...maybe in some odd ball case, but not as a general recommendation. Resistance is acquired quickly...
Agreed. As mentioned, the only time this is appropriate (i.e., with some supporting literature) that I know of is as a combination with rifampin in orthopedic infections. Delafloxacin which is in development may have a role in these infections, but I'm very skeptical that that will pan out in real world data.

I think the onus is on anyone using FQs for S. aureus to prove that that is both effective and safe. Certainly any stewardship program using this as an avoidance strategy would need to do so.
 
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Agreed. As mentioned, the only time this is appropriate (i.e., with some supporting literature) that I know of is as a combination with rifampin in orthopedic infections. Delafloxacin which is in development may have a role in these infections, but I'm very skeptical that that will pan out in real world data.

I think the onus is on anyone using FQs for S. aureus to prove that that is both effective and safe. Certainly any stewardship program using this as an avoidance strategy would need to do so.
Do you mind sharing that literature? I'm not trying to call you out but I would love to read the studies some time.
 

Praziquantel86

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Do you mean on quinolones and rifampin? Should be able to find them pretty easily on Pubmed. If you don't have access I can send them to you.
 

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Our zosyn sensitivity for pseudomonas is abysmal, <70% in all units of the hospital. Meropenem is only 72% or so. So we give cefepime (85%) + amikacin (98%) only if hypotensive.