Vancomycin goal levels

[nafcillin]

can you give me a list of your goal levels?

---

Members don't see this ad.

 

[dingerx]

can you give me a list of your goal levels?

SSTI is typically 10-15
Osteo 15-20 (sometimes 25 if they have DMII and are looking at amputation)

 

[WVUPharm2007]

link

 

[xiphoid2010]

can you give me a list of your goal levels?

The way I memorized the ones needing trough of 15-20 is "bbb, heart & lung".

Bbb = blood (bacteremia), brain (meningitis), bone (osteomyelitis)
Heart = endocarditis
Lung = pneumonia

although I think recently MRSA csssi also got the thumbs up for it.

 

[spacecowgirl]

15-20 regardless of indication. Although in our facility the indication is almost always DM-related osteo cSSTI.

 

[Praziquantel86]

I've always aimed for 15-20 for all indications, although we're sometimes less aggressive getting there when it's an uncomplicated SSTI.

 

[pharmboycu]

I've always aimed for 15-20 for all indications, although we're sometimes less aggressive getting there when it's an uncomplicated SSTI.

+1. 15-20 mg/L. If they're improving and the trough is low then I don't worry about it much as long as it's above 10 or so. If it's CNS or DM cellulitis that isn't improving I'll carefully watch it and let the troughs run a little higher, up to about.

John

 

[xiphoid2010]

trough of 15-20 is not indicated for all infections. The guideline clearly states which specific infections calls for that trough. Otherwise 10-15 is the goal (unless you live in a areas where staph MIC is typically >1)

 

[Its Z]

Maybe y'all should be discussing the reason why trough needs to be above 15mcg/ml for certain diagnosis... such as AUC/MIC ratio.

 

[Sparda29]

i've always aimed for 15-20 for all indications, although we're sometimes less aggressive getting there when it's an uncomplicated ssti.

+1.

What's the absolute maximum dose that can be given at a single time? The places I've rotated at are always very hesitant at going above 2 gm for a single dose, when I've been told that you can be safe with a 4 gm maximum. Also, it seems that physicians prefer low dose-high frequency compared to high dose-low frequency.

 

[rxlea]

We have gone as high as 2.5 in obese patients.

 

[nafcillin]

I've done 2500gm for obese people as well. as long as it falls in line with 15-20mg/kg

 

[Praziquantel86]

trough of 15-20 is not indicated for all infections. The guideline clearly states which specific infections calls for that trough. Otherwise 10-15 is the goal (unless you live in a areas where staph MIC is typically >1)

There is definitely a weak evidence base for vancomycin levels in most infections when you consider hard clinical data. However, the PK data show that lower levels do not come close to achieving the optimal AUC/MIC ratios. Unless I'm presented with evidence to the contrary, aiming for a trough of 15-20 seems reasonable for most, if not all, infections. If these trough values are unachievable (getting over the 4g/day limit or using impractical frequencies), then you can and should reconsider on a per patient basis.

As far as the MIC > 1 issue goes, I don't think vancomycin is a drug that should be used in that case, especially for serious infections. That's where I've seen the bulk of therapeutic failures, and given the PK data, it seems like a foregone conclusion. Daptomycin or linezolid would be the better options in those cases.

 

[spacecowgirl]

We max at 2 grams/dose.

 

[Its Z]

I know the guidelines recommend 2gram max but only evidenced by expert opinion only. I do not agree with this. The rationale for the max dose stems from being gun shy about potential renal toxicity due to having to clear large amount of Vancomycin. However, as a self claimed expert, I believe it's more critical to get a level high from the first dose and never fall below 15mcg/ml throughout the entire regimen. I have thrown out the 2 gram max idea but do recommend 25mg/kg loading dose based on "Dosing" weight. Incredible Hulk with very low adipose tissue would probably receive 3 gram loading dose.

 

[Its Z]

As far as the MIC > 1 issue goes, I don't think vancomycin is a drug that should be used in that case, especially for serious infections. That's where I've seen the bulk of therapeutic failures, and given the PK data, it seems like a foregone conclusion. Daptomycin or linezolid would be the better options in those cases.

What kind of failure rates are reported in Linezolid and Dapto studies?

 

[Praziquantel86]

What kind of failure rates are reported in Linezolid and Dapto studies?

Can't think of daptomycin off the top of my head, I believe around a 40% success rate for staph bacteremia. Linezolid is in the mid-40s for success in pneumonia patients. Vancomycin is about the same, but the vast majority of patients studied on a large scale have MIC < 1.

The hVISA strains are almost always reported as therapeutic vanc failures, so anything would be better than nothing.

 

[Its Z]

Can't think of daptomycin off the top of my head, I believe around a 40% success rate for staph bacteremia. Linezolid is in the mid-40s for success in pneumonia patients. Vancomycin is about the same, but the vast majority of patients studied on a large scale have MIC < 1.

The hVISA strains are almost always reported as therapeutic vanc failures, so anything would be better than nothing.

Dapto study is questionable anyways.

Here's the issue. Despite MIC < 1, as you mentioned, the failure rate is very high for all drugs. So many believe Vanco doesn't work and just jump right to Zyvox or Dapto.... I don't think they realize the high failure rate of those drugs either. Also, there are error issues with MIC methodology with Microscan.

 

[Praziquantel86]

Dapto study is questionable anyways.

Here's the issue. Despite MIC < 1, as you mentioned, the failure rate is very high for all drugs. So many believe Vanco doesn't work and just jump right to Zyvox or Dapto.... I don't think they realize the high failure rate of those drugs either. Also, there are error issues with MIC methodology with Microscan.

Absolutely. We definitely need better drugs for MRSA, but we also need to optimize use of the drugs that we have. A lot of it comes with proper education and a lot of it comes with better initial management of septic patients. Neither one is very easy.

 

[xiphoid2010]

However, the PK data show that lower levels do not come close to achieving the optimal AUC/MIC ratios.

Please present data.

AUC/MIC >400 is hard to achieve only if (1) MIC>1, (2) vanc has poor penetration.

It's mainly the poor penetration that is the reason for higher troughs in pneumonia. For example, vanc concentration in lung vs. plasma is 1:6. So a trough of 10 in the plasma will only 1.67 in the lung tissue. The same poor penetration also applies for bone and meningitis. Hence the need for higher tough of 15-20. Bacteremia/sepsis and endocarditis calls for higher troughs for emergent reasons.

In well penetrated tissue, AUC/MIC >400 is not a problem with a trough of 10-15. It only becomes somewhat of a problem if the bug has MIC >1. So just going around hosing every infection with troughs of 15-20 is unnecessary.

 

[sosoo]

if i remember correctly, the new guideline specified 15-20 for all indications.

 

[xiphoid2010]

if i remember correctly, the new guideline specified 15-20 for all indications.

You are probably thinking about IDSA's new MRSA guideline, but it does NOT say 15-20 for everything. It still lists the same 5 infections that need 15-20, but with the MRSA csssi (specifically necrotising fascitis) I mentioned earlier added to the "bbb heart & lung". So now there are technically 6 infections that calls for trough of 15-20, the rest are still 10-15 trough goal.

 

[PharmDstudent]

15-20, and only being used for MRSA from what I've seen

 

[Hpower12]

+1.

What's the absolute maximum dose that can be given at a single time? The places I've rotated at are always very hesitant at going above 2 gm for a single dose, when I've been told that you can be safe with a 4 gm maximum. Also, it seems that physicians prefer low dose-high frequency compared to high dose-low frequency.

15-20 for more serious infections
10-15 for less serious

I have also seen physicians order for higher trough levels in some infections.

We have done doses of 5 Grams before in obese patients, as loading doses.

 

[Praziquantel86]

Please present data.

AUC/MIC >400 is hard to achieve only if (1) MIC>1, (2) vanc has poor penetration.

It's mainly the poor penetration that is the reason for higher troughs in pneumonia. For example, vanc concentration in lung vs. plasma is 1:6. So a trough of 10 in the plasma will only 1.67 in the lung tissue. The same poor penetration also applies for bone and meningitis. Hence the need for higher tough of 15-20. Bacteremia/sepsis and endocarditis calls for higher troughs for emergent reasons.

In well penetrated tissue, AUC/MIC >400 is not a problem with a trough of 10-15. It only becomes somewhat of a problem if the bug has MIC >1. So just going around hosing every infection with troughs of 15-20 is unnecessary.

Sure! The citation below links to a review article, which in turn cites an abstract from ICAAC in 2006, authored by Dr. Craig out of Wisconsin. Their study determined that the optimal vancomycin fAUC/MIC is 100-250 (corresponding to a total AUC/MIC ratio of 200 - 500). This is where the recommendation comes from. Nowhere is tissue penetration mentioned, in fact, these parameters were determined in a murine thigh model.

If you'll remember, vancomycin doesn't penetrate terribly well into skin, and has even worse penetration into diabetic skin. For the same reasons that you use higher concentrations in meningeal or cardiac infections, lower tissue penetration, those are also issues in skin infections.

Clin Infect Dis. 2008 Jun 1;46 Suppl 5:S360-7.
Increasing antibiotic resistance among methicillin-resistant Staphylococcus aureus strains.

Sakoulas G, Moellering RC Jr.
Source

Division of Infectious Diseases, Department of Medicine, Westchester Medical Center and New York Medical College, Valhalla, New York, USA.

Abstract

Vancomycin use has increased dramatically worldwide since the mid-1980s, largely as a result of empirical and directed therapy against burgeoning methicillin-resistant Staphylococcus aureus (MRSA) infections. With limited choices, clinicians have traditionally relied on vancomycin alone in the management of serious MRSA infections and have enjoyed a significant period free of vancomycin resistance in S. aureus. Even now, 5 decades after its introduction, vancomycin resistance among S. aureus strains, as currently defined microbiologically, remains rare. Yet it is becoming clear that vancomycin is losing potency against S. aureus, including MRSA. Serious infections due to MRSA defined as susceptible in the laboratory are not responding well to vancomycin. This is demonstrated by increased mortality seen in patients with MRSA infection and markedly attenuated vancomycin efficacy caused by vancomycin heteroresistance in S. aureus. Therefore, it appears that our definition of vancomycin susceptibility requires further scrutiny as applied to serious MRSA infections, such as bacteremia and pneumonia.

 

[xiphoid2010]

Sure! The citation below links to a review article, which in turn cites an abstract from ICAAC in 2006, authored by Dr. Craig out of Wisconsin. Their study determined that the optimal vancomycin fAUC/MIC is 100-250 (corresponding to a total AUC/MIC ratio of 200 - 500). This is where the recommendation comes from. Nowhere is tissue penetration mentioned, in fact, these parameters were determined in a murine thigh model.

Your article in fact is echoing the IDSA/ASHP guideline, mentioning 15-20 for the 5 specific infections, noting HCAP and MIC >1 specifically. Nowhere does it tell say to use 15-20 for all infections. This is exactly the same as the IDSA guideline.

Also, the murine thigh model by Dr. Craig has been incorporated and referenced in the 2009 IDSA/ASHP guideline, and in conclusion the guideline recommend 15-20 only for the 5 severe infections only using this evidence. So I think the issue has been settled. Goal trough of 15-20 for the specific 5 (now 6 with the new IDSA MRSA guideline) severe infections, and 10-15 trough for other infections.

 

[Praziquantel86]

Your article in fact is echoing the IDSA/ASHP guideline, mentioning 15-20 for the 5 specific infections, noting HCAP and MIC >1 specifically. Nowhere does it tell say to use 15-20 for all infections. This is exactly the same as the IDSA guideline.

Also, the murine thigh model by Dr. Craig has been incorporated and referenced in the 2009 IDSA/ASHP guideline, and in conclusion the guideline recommend 15-20 only for the 5 severe infections only using this evidence. So I think the issue has been settled. Goal trough of 15-20 for the specific 5 (now 6 with the new IDSA MRSA guideline) severe infections, and 10-15 trough for other infections.

I posted the article more for the citation than the content. I don't think the issue has been settled at all. The stated goal AUC/MIC ratio is >400 for all infections. AUC is a PK parameter independent of infection type, so, by my reasoning (and apparently that of quite a few others), the goal trough should be independent of infection type.

If you are advocating a lower AUC for other infection types, please present data stating that is a reasonable thing to do.

EDIT: By the way, this reasoning also includes prevention of the development of resistance to vancomycin. That is a stated goal within the guidelines as well.

 

[xiphoid2010]

If you are advocating a lower AUC for other infection types, please present data stating that is a reasonable thing to do.

The data are all sited in the IDSA/ASHP guideline. The data you presented has been evaluated and incorporated into the guideline, with the conclusion that 10-15 are the goal except for the specific infections mentioned. You are trying to extrapolate a different conclusion from a research which the author himself stated 15-20 are only for specific infections.

If you have other data that the IDSA failed to consider, or you have credential above the physicans and clinical pharmacist on the panel, then please present them.

 

[Praziquantel86]

The data are all sited in the IDSA/ASHP guideline. The data you presented has been evaluated and incorporated into the guideline, with the conclusion that 10-15 are the goal except for the specific infections mentioned. You are trying to extrapolate a different conclusion from a research which the author himself stated 15-20 are only for specific infections.

If you have other data that the IDSA failed to consider, or you have credential above the physicans and clinical pharmacist on the panel, then please present them.

There are two goals specifically mentioned in the IDSA guidelines: AUC/MIC > 400 and trough values of 15 - 20 for serious infections. It also mentions that troughs should at no point fall below the 10mg/mL mark in order to prevent the creation of VISA-like strains. I may have missed where it says 10 - 15 for all other infections, but I don't think I did.

I don't consider myself more qualified than any of the members on the panel, however, the area we're talking about is a grey area still requiring a lot of research. These are simply my opinions based on the data at hand. You and I are drawing different conclusions from the same data, which is not unusual or unexpected. That's why I love this field, it's as much an art as it is science.

 

[xiphoid2010]

I may have missed where it says 10 - 15 for all other infections, but I don't think I did.

I don't consider myself more qualified than any of the members on the panel, however, the area we're talking about is a grey area still requiring a lot of research. These are simply my opinions based on the data at hand. You and I are drawing different conclusions from the same data, which is not unusual or unexpected. That's why I love this field, it's as much an art as it is science.

Copied and pasted from the IDSA guideline: Summary table 2.

"Optimal trough concentration: Minimum serum vancomycin trough concentrations should always be maintained above 10 mg/L to avoid development of resistance. For a pathogen with an MIC of 1 mg/L, the
minimum trough concentration would have to be at least 15 mg/L to generate the target AUC:MIC of 400."

Meaning, trough goal of >10 is optimal tough except when your patient has more resistant staph (MIC of 1 or higher). Trough >10 is enough to avoid development of resistance.

"Optimal trough concentration&#8212;complicated infections (bacteremia, endocarditis, osteomyelitis, meningitis,and hospital-acquired pneumonia caused by Staphylococcus aureus): Vancomycin serum trough concentrations of 15&#8211;20 mg/L are recommended to improve penetration, increase the probability of obtaining optimal target serum concentrations, and improve clinical outcomes."

Meaning, for the 5 complicated infections specified, optimal trough goal is 15-20. This is due to poor penetration, hence the need for the higher trough to achieve goal.

Now, you could argue that the guideline is gray enough to interpret >10 implies it's not wrong to go 15-20 on every infections. But "15-20 for everything" is clearly not what it said. Furthermore, I would argue that IDSA's 2nd optimal goal spelling out which of the 5 complicated infections should go for 15-20 indicates that other "uncomplicated infections" goal should be 10-15.

Also note, higher trough is not without cost. It increase drug cost, increase infusion time, ties up lines, increase nursing/pharmacy time, increased side effect and toxicity specially when combined with AG. So when an infection is just as effective treated using trough of 10-15, you should use go that route.

 

[Praziquantel86]

Copied and pasted from the IDSA guideline: Summary table 2.

"Optimal trough concentration: Minimum serum vancomycin trough concentrations should always be maintained above 10 mg/L to avoid development of resistance. For a pathogen with an MIC of 1 mg/L, the
minimum trough concentration would have to be at least 15 mg/L to generate the target AUC:MIC of 400."

Meaning, trough goal of >10 is optimal tough except when your patient has more resistant staph (MIC of 1 or higher). Trough >10 is enough to avoid development of resistance.

"Optimal trough concentration—complicated infections (bacteremia, endocarditis, osteomyelitis, meningitis,and hospital-acquired pneumonia caused by Staphylococcus aureus): Vancomycin serum trough concentrations of 15–20 mg/L are recommended to improve penetration, increase the probability of obtaining optimal target serum concentrations, and improve clinical outcomes."

Meaning, for the 5 complicated infections specified, optimal trough goal is 15-20. This is due to poor penetration, hence the need for the higher trough to achieve goal.

Now, you could argue that the guideline is gray enough to interpret >10 implies it's not wrong to go 15-20 on every infections. But "15-20 for everything" is clearly not what it said. Furthermore, I would argue that IDSA's 2nd optimal goal spelling out which of the 5 complicated infections should go for 15-20 indicates that other "uncomplicated infections" goal should be 10-15.

Also note, higher trough is not without cost. It increase drug cost, increase infusion time, ties up lines, increase nursing/pharmacy time, increased side effect and toxicity specially when combined with AG. So when an infection is just as effective treated using trough of 10-15, you should use go that route.

That is the main point as I see it. It's something that I personally think is worthwhile, as the goal of correct antimicrobial therapy is to treat disease and prevent the development of resistance. However, if a patient is getting better with an SSTI and a trough of 12, I'm not going to push the issue. It's a flexible target for me, but I'd much rather be towards the 20 end of the spectrum than the 10.

To me, the omission of stating a goal for non-serious infections is an acknowledgement of the lack of good data rather than an implication that a trough of 10 - 15 should be targeted. I personally believe the AUC/MIC ratio should remain over 400 (with a surrogate trough of 15 - 20), although the matter is much more pressing in serious infections.

I don't disagree with your point that it is not always practical or a good choice to maintain a trough at that level, and I don't view it as a hard an fast rule. Simply a goalpost to shoot for.

Definitely a debate worth having though, I wish this dialogue happened more frequently among providers. Everyone wins.

 

[xiphoid2010]

To me, the omission of stating a goal for non-serious infections is an acknowledgement of the lack of good data rather than an implication that a trough of 10 - 15 should be targeted. I personally believe the AUC/MIC ratio should remain over 400 (with a surrogate trough of 15 - 20), although the matter is much more pressing in serious infections.

While stating a trough goal of 15-20 for everything may be not strictly wrong. But it certainly isn't right either, as it clearly isn't what the guideline and evidence on which it is based stated.

I agree that AUC/MIC needs to be >400. The issue is that trough >10 will produce AUC/MIC >400 except when MIC is above 1 (and the complicated infections w/ poor penetrations). This is spelled out in the guideline, and is backed up by plenty of data based on monte carlo simulations using models based on actual PK parameters.

So to summarize what the guideline states specifically. Any trough >10 is a good goal unless: (a) MIC of 1 or higher and (b) the 5 specific infections, for which 15-20 is the goal.

Did I back off on vanc every time a celluitis patient's trough came back 15-20 during my residency? Of course not, by the time it's due to draw another SS trough, the pt would likely be discharged on bactrim plus keflex already. But I certainly wouldn't shoot for 15-20 to begin with, as that just would just increases the risk of ADE without any therapeutic benefits.

 

[sosoo]

i didnt go back to read the guideline, but im thinking for argument sake why go for 10-15 for possibility of raising resistant and not reach AUC:MIC >400 when we could go for trough 15-20? thats having two risk factors, not killing at high enough concentration and also raising resistant. on the other hand, vanco toxicity that is most concerned is nephrotoxic, but this toxicity is only when used in combination with other nephrotoxic drugs. so like beta lactams, vanco is very well tolerated.

 

[xiphoid2010]

i didnt go back to read the guideline, but im thinking for argument sake why go for 10-15 for possibility of raising resistant and not reach AUC:MIC >400 when we could go for trough 15-20? thats having two risk factors, not killing at high enough concentration and also raising resistant. on the other hand, vanco toxicity that is most concerned is nephrotoxic, but this toxicity is only when used in combination with other nephrotoxic drugs. so like beta lactams, vanco is very well tolerated.

The evidence out there is that achieving a trough of >10 does not cause increase resistance, <10 does. So there is no reason to go for a higher trough of 15-20 for that purpose.

AUC/MIC >400 again, is not an issue once trough is 10 or above (except for the poorly penetrated sites listed). It only becomes is an issue if the bug is also semi-resistant (MIC >1). So you need to look at your antibiogram at your hospital, if S.aureus MIC50 (or is it MIC90?) is >1, then it would be prudent to dose empirically to a trough of 15-20. But if it is not, then again, no good reason to target that high.

When comes to using drugs, you don't go by "the drug is pretty harmless, so why not use the max dose." Otherwise, all patients would be getting ceftriaxone 2 grams instead of 1gram for CAP, omeprezole 40 bid instead of 20 daily for GERD. That's just bad non-evidence based medicine, and we are here to prevent that.

 

[Praziquantel86]

The evidence out there is that achieving a trough of >10 does not cause increase resistance, <10 does. So there is no reason to go for a higher trough of 15-20 for that purpose.

AUC/MIC >400 again, is not an issue once trough is 10 or above (except for the poorly penetrated sites listed). It only becomes is an issue if the bug is also semi-resistant (MIC >1). So you need to look at your antibiogram at your hospital, if S.aureus MIC50 (or is it MIC90?) is >1, then it would be prudent to dose empirically to a trough of 15-20. But if it is not, then again, no good reason to target that high.

When comes to using drugs, you don't go by "the drug is pretty harmless, so why not use the max dose." Otherwise, all patients would be getting ceftriaxone 2 grams instead of 1gram for CAP, omeprezole 40 bid instead of 20 daily for GERD. That's just bad non-evidence based medicine, and we are here to prevent that.

I disagree. AUC is a kinetic parameter that is independent of tissue penetration. The Monte Carlo simulations took total body distribution and MIC into account, none utilized tissue-specific data that I'm aware of. I agree that achieving the target parameters is probably more important in infections at sites that are poorly penetrated, but nowhere in my reading am I led to believe that it is a different goal for well-penetrated sites (skin isn't even necessarily one of these anyways).

 

[xiphoid2010]

I disagree. AUC is a kinetic parameter that is independent of tissue penetration. The Monte Carlo simulations took total body distribution and MIC into account, none utilized tissue-specific data that I'm aware of. I agree that achieving the target parameters is probably more important in infections at sites that are poorly penetrated, but nowhere in my reading am I led to believe that it is a different goal for well-penetrated sites (skin isn't even necessarily one of these anyways).

Correect, the AUC is measured from the serum concentration, not the tissue. So AUC/MIC>400 is a number derived from serum vanco level, hence directly correlated to vanc trough level.

As you are well aware, the MIC in the AUC/MIC stands for minimum inhibitory concentration. If you don't have that concentration, you are not inhibiting anything. So to make AUC/MIC a relevant paremeter, you need to meet the MIC. If I recall correction, studies have show that lung tissue has serum to tissue concentration of ~6:1. You wouldn't even be meeting the MIC for some of the bugs with a trough of 10, hence the rational for trough of 15-20. This is why the guideline specifically included higher trough for the specified infections.

Skin penetration, (1) I don't recall study data showing vanc has poor penetration in celluitits (2) drug penetration is increased at the site of inflammation (3) lower illness severity could be used to justify more conservative treatment intensity.

 

[Praziquantel86]

Correect, the AUC is measured from the serum concentration, not the tissue. So AUC/MIC>400 is a number derived from serum vanco level, hence directly correlated to vanc trough level.

As you are well aware, the MIC in the AUC/MIC stands for minimum inhibitory concentration. If you don't have that concentration, you are not inhibiting anything. So to make AUC/MIC a relevant paremeter, you need to meet the MIC. If I recall correction, studies have show that lung tissue has serum to tissue concentration of ~6:1. You wouldn't even be meeting the MIC for some of the bugs with a trough of 10, hence the rational for trough of 15-20. This is why the guideline specifically included higher trough for the specified infections.

Skin penetration, (1) I don't recall study data showing vanc has poor penetration in celluitits (2) drug penetration is increased at the site of inflammation (3) lower illness severity could be used to justify more conservative treatment intensity.

I'd agree with your logic if the efficacy of vancomycin were correlated to time above MIC, like a beta-lactam. However, the parameter of interest is AUC/MIC, with a value of >400 being targeted. This information was specifically derived from a murine thigh infection model, which is in a higher-penetration area.

From what I recall (based on textbooks), vancomycin has relatively poor skin penetration, down to about 10% of serum concentrations in diabetic patients. I do agree with points 2 and 3, however. I don't think the trough values are as critical with minor infections as they are with serious infections, but I still think we should strive to meet the AUC/MIC goal in these patients.

 

[pharmboycu]

The evidence out there is that achieving a trough of >10 does not cause increase resistance, <10 does. So there is no reason to go for a higher trough of 15-20 for that purpose.

AUC/MIC >400 again, is not an issue once trough is 10 or above (except for the poorly penetrated sites listed). It only becomes is an issue if the bug is also semi-resistant (MIC >1). So you need to look at your antibiogram at your hospital, if S.aureus MIC50 (or is it MIC90?) is >1, then it would be prudent to dose empirically to a trough of 15-20. But if it is not, then again, no good reason to target that high.

When comes to using drugs, you don't go by "the drug is pretty harmless, so why not use the max dose." Otherwise, all patients would be getting ceftriaxone 2 grams instead of 1gram for CAP, omeprezole 40 bid instead of 20 daily for GERD. That's just bad non-evidence based medicine, and we are here to prevent that.

I'm all for evidence based medicine, but guidelines and evidence are no substitute for common sense and clinical judgement. MIC's and identification of MRSA take longer to return than an initial result of "Gm + cocci in clusters." Until the lab comes back that says the MIC is low enough to use a target of 10-15 mg/L, the most logical thing to do is to temporarily assume MRSA, temporarily assume it has a high MIC, treat accordingly, and lower the dose if the MIC proves to be low or de-escalate therapy if it turns out to be MSSA. I wouldn't want to waste 3 days waiting for a MIC to come back only to find out that I should have been treating more aggressively. You can always de-escalate but if you wait to escalate you can cause serious damage.

Do you have GERD? I would assume not if you're suggesting starting out at 20 mg omeprazole daily. Trust me-- you'd want the max dose for a few days and then reduce to 20 qday once the acid isn't running back up into your throat at night.

John

 

[xiphoid2010]

I'm all for evidence based medicine, but guidelines and evidence are no substitute for common sense and clinical judgement.

Empiric treatment is based on local culture and sensitivity. You should be looking at your antibiogram. Empiric treatment is not meant to cover everything, just the most likely ones. If your local s. aureus MIC90 is less than 1, dosing every cellulitis patient that comes in to a trough of 15-20 would be NOT use common sense or clinical judgement. Also note the guideline already accounted for time sensitive complicated infections to be dosed empirically to 15-20, eg. endocarditis and bacteremia. I'm sure all those IDSA and ASHP folks are known for lack of common sense and writing guidelines that fly in the face of clinical judgement.

Do you have GERD? I would assume not if you're suggesting starting out at 20 mg omeprazole daily. Trust me-- you'd want the max dose for a few days and then reduce to 20 qday once the acid isn't running back up into your throat at night.

John

I actually have GERD, had it for for the last 5 years, result of hiatal hernia. And physician indeed started me on omeprazole at 20 daily, and still is to this day. Hell, I was actually started on ranitidine. So I'm sorry that I don't trust you on this.

 

[pharmboycu]

Empiric treatment is based on local culture and sensitivity. You should be looking at your antibiogram. Empiric treatment is not meant to cover everything, just the most likely ones. If your local s. aureus MIC90 is less than 1, dosing every cellulitis patient that comes in to a trough of 15-20 would be not use common sense or clinical judgement. Also note the guideline already accounted for time sensitive complicated infections to be dosed empirically to 15-20, eg. endocarditis and bacteremia.

I actually have GERD, had it for for the last 5 years, result of hiatal hernia. And physician indeed started on omeprazole 20 daily. Hell, I was actually started on ranitidine. So I'm sorry that I don't trust you on this.

I'm sorry if I don't quite follow or agree with you here. In one post you say we should be using guidelines but in this post you say it's based on local data. This is what I mean. Common sense and clinical judgement means realizing the guidelines are just that-- guidelines-- and may not be appropriate for every patient.

MRSA isn't an "innocent until proven guilty" pathogen. It's guilty until proven innocent. All I can say is that God forbid I have MRSA and get admitted for it, if ya'll dose me, empirically treat for 15-20 until the MIC's prove otherwise and continue 15-20 (despite what the guidelines or antibiogram say) if I'm not clinically improving. I wouldn't want to lose an appendage because someone was following the guidelines or antibiogram to the letter. That's common sense. 🙂

John

 

[KARM12]

::Shakes head::

Some bad ID stewardship going on here...

 

[pharmboycu]

::Shakes head::

Some bad ID stewardship going on here...

I could agree that it's not ideal, but it is a pragmatic approach to a problem with potentially devastating consequences if we don't treat for the worst case scenario and then de-escalate if we are presented with something better.

John

 

[xiphoid2010]

I'm sorry if I don't quite follow or agree with you here. In one post you say we should be using guidelines but in this post you say it's based on local data. This is what I mean. Common sense and clinical judgement means realizing the guidelines are just that-- guidelines-- and may not be appropriate for every patient.

The guidelines made room for local data. There are many IDSA guidelines stating that you should take local susceptibility into account. This vanc guideline also said to use 15-20 if MIC is >1, meaning look at the MIC of your local bugs.

MRSA isn't an "innocent until proven guilty" pathogen. It's guilty until proven innocent. All I can say is that God forbid I have MRSA and get admitted for it, if ya'll dose me, empirically treat for 15-20 until the MIC's prove otherwise and continue 15-20 (despite what the guidelines or antibiogram say) if I'm not clinically improving. I wouldn't want to lose an appendage because someone was following the guidelines or antibiogram to the letter. That's common sense. 🙂

John

You are asking for certainty of MIC yet doing vanc empirically? Emperic treatment's goal is to cover the most likely (80-90% of the susceptible) organisms. It's never going to be 100%. To do that, you would have to load up vanc and linezolid and dapto, and we haven't even started gram negative coverages yet.

 

[Praziquantel86]

::Shakes head::

Some bad ID stewardship going on here...

I'm curious what your approach is to this.

 

[pharmboycu]

The guidelines made room for local data. There are many IDSA guidelines stating that you should take local susceptibility into account. This vanc guideline also said to use 10-15 if MIC is >1, meaning look at the MIC of your local bugs.



You are asking for certainty of MIC yet doing vanc empirically? Emperic treatment's goal is to cover the most likely (80-90% of the susceptible) organisms. It's never going to be 100%. To do that, you would have to load up vanc and linezolid and dapto, and we haven't even started gram negative coverages yet.

Actually, yes, and perhaps "empiric" was the wrong word choice. In a typical scenario, we already have an idea that it's at least S. aureus but do not yet know if it's MSSA or MRSA, so "initial" treatment might have been more appropriate.

Our primary results are usually reported quickly in the form of a single line-- "Gm+ cocci in clusters." If the patient meets the "common sense" test for MRSA (is it a nursing home patient, has the patient been here for any length of time, etc.), then we can usually conclude it's most likely MRSA, in accordance with local data as well as guidelines. At that point, I suggest that if Vancomycin is to be started (usually by a hospitalist with I.D. consult to follow) we go for a trough of 15-20 mg/L. The identification and sensitivity usually comes a day or two later and will either report MSSA or presumptive MRSA. At this point, we're usually 3 days into therapy and still don't have an MIC. A couple of days later, the MIC's will usually be back and tell us what we're dealing with. Once we have that number then I can safely say whether or not 10-15 or 15-20 will be needed. If we're at 15-20 already, great-- we can lower the dose if the MIC's are sufficient to use 10-15 or even de-escalate to other drugs if the sensitivities dictate. If the MIC's indicate 15-20 is needed then we haven't missed the boat by 5 days but if we shot for 10-15 and needed 15-20, we *have* missed the boat by 5 days.

If you have a lab where MIC's don't take as long to come back it may be more practical to start lower. The time frame in our case doesn't necessarily lend itself to this. I hope that helps put it into better context and perspective.

John

 

[xiphoid2010]

Actually, yes, and perhaps "empiric" was the wrong word choice. In a typical scenario, we already have an idea that it's at least S. aureus but do not yet know if it's MSSA or MRSA, so "initial" treatment might have been more appropriate.

Our primary results are usually reported quickly in the form of a single line-- "Gm+ cocci in clusters." If the patient meets the "common sense" test for MRSA (is it a nursing home patient, has the patient been here for any length of time, etc.), then we can usually conclude it's most likely MRSA, in accordance with local data as well as guidelines. At that point, I suggest that if Vancomycin is to be started (usually by a hospitalist with I.D. consult to follow) we go for a trough of 15-20 mg/L. The identification and sensitivity usually comes a day or two later and will either report MSSA or presumptive MRSA. At this point, we're usually 3 days into therapy and still don't have an MIC. A couple of days later, the MIC's will usually be back and tell us what we're dealing with. Once we have that number then I can safely say whether or not 10-15 or 15-20 will be needed. If we're at 15-20 already, great-- we can lower the dose if the MIC's are sufficient to use 10-15 or even de-escalate to other drugs if the sensitivities dictate. If the MIC's indicate 15-20 is needed then we haven't missed the boat by 5 days but if we shot for 10-15 and needed 15-20, we *have* missed the boat by 5 days.

If you have a lab where MIC's don't take as long to come back it may be more practical to start lower. The time frame in our case doesn't necessarily lend itself to this. I hope that helps put it into better context and perspective.

John

What setting are you practicing in? Vanc at my medical center is usually started empirically in the ER or when patient is first admitted. Most typically for a celluitits or pneumonia. If the patient came in really early in the day then maybe prelim gram stain at the end of the day if lucky, but usually takes about 24 hours. Culture and sensitivity data comes in at 48-72 hours.

Before the new protocol, the ER would dose everybody vanc 1 gram q12h. With the new protocol we developed, all dosing is by pharmacy. Our MIC90 here is indeed <1 and is reviewed annually. Right now, the 5 (now 6) infections emprically dosed to 15-20, everything is empirically dosed to target trough of 10-15. If the MIC comes back ugly for these non-complicated infection, we go up on the trough. But that hasn't been an issue with local sensitivity.

Let's think for a second. First, we don't the infection is even due to staph, we are just covering empirically. Even if it turns out to be staph, ~70-80% are s.aureus and the rest are usually coag negative staph. Of the 70-80%, ~40% MRSA, ~60% MSSA here. Even if it turns out to be MRSA you got MIC90 <1. The 6 specified infections are already dosed to 15-20 per protocol, leaving only the uncomplicated infections. So dosing everyone else to 15-20 would only gain <1% coverage in non-critical infections, while causing more ADEs.

 

[pharmboycu]

What setting are you practicing in? Vanc at my medical center is usually started empirically in the ER or when patient is first admitted. Most typically for a celluitits or pneumonia. If the patient came in really early in the day then maybe prelim gram stain at the end of the day if lucky, but usually takes about 24 hours.

Before the new protocol, the ER would dose everybody vanc 1 gram q12h. With the new protocol we developed, all dosing is by pharmacy. Our MIC90 here is indeed <1 and is reviewed annually. Right now, the 5 (now 6) infections emprically dosed to 15-20, everything is empirically dosed to target trough of 10-15.

Let's think for a second. First, we don't the infection is even due to staph, we are just covering empirically. Even if it turns out to be staph, ~70-80% are s.aureus and the rest are usually coag negative staph. Of the 70-80%, ~40% MRSA, ~60% MSSA here. Even if it turns out to be MRSA you got MIC90 <1. The 6 specified infections are already dosed to 15-20 per protocol, leaving only the uncomplicated infections. So dosing everyone else to 15-20 would only gain <1% coverage in non-critical infections, while causing more ADEs. That just doesn't make sense.

I think we're talking about 2 different animals in 2 different farms... I'm talking about patients already on the floor, not specifically ER patients. The vast majority of patients I run across (probably 95% or so as a guesstimate) have health-care aquired S. aureus, not community acquired. I think this is boiling down to what you see where you practice is distinctly different than what I see where I practice. I'd have to check the antibiogram, but I'd venture to guess our MRSA : MSSA is approximately the inverse of yours.

John

 

[xiphoid2010]

I think we're talking about 2 different animals in 2 different farms... I'm talking about patients already on the floor, not specifically ER patients. The vast majority of patients I run across (probably 95% or so as a guesstimate) have health-care aquired S. aureus, not community acquired. I think this is boiling down to what you see where you practice is distinctly different than what I see where I practice. I'd have to check the antibiogram, but I'd venture to guess our MRSA : MSSA is approximately the inverse of yours.

John

Where are your patients coming from? Don't you have an ER?

 

[pharmboycu]

Where are your patients coming from? Don't you have an ER?

Yes, we do. My floor is not the acute floor-- it's a general medicine floor. Most of my patients are step-down patiens who have been in the hospital for a couple of days or so before getting to my floor.

Here vancomycin is usually started in the ER empirically for suspected sepsis, suspected MRSA pneumonia, and suspected MRSA cellulitis. If we suspect MRSA, there's usually good reason for that suspicion and also usually good reason to believe it's got an MIC that needs 15-20 troughs. When proven wrong, I'm happy to de-escalate or decrease the dose. Unhappily, and not to boast about this because it's not something to be boastful of, but when MRSA results here I'm usually not wrong about needing 15-20 when the MIC's are back.

 

[xiphoid2010]

Yes, we do. My floor is not the acute floor-- it's a general medicine floor. Most of my patients are step-down patiens who have been in the hospital for a couple of days or so before getting to my floor.

Here vancomycin is usually started in the ER empirically for suspected sepsis, suspected MRSA pneumonia, and suspected MRSA cellulitis. If we suspect MRSA, there's usually good reason for that suspicion and also usually good reason to believe it's got an MIC that needs 15-20 troughs. When proven wrong, I'm happy to de-escalate or decrease the dose. Unhappily, and not to boast about this because it's not something to be boastful of, but when MRSA results here I'm usually not wrong about needing 15-20 when the MIC's are back.

Ah, I see where you are coming from. But if they are coming down form ICU, it means they've been there a while, and shouldn't they have C&S by that point? Of course, if it's a new infection that's developed during the hospital stay, then yeah, I can see why you would be much more likely to suspect MRSA. But that would also suggest poor infection control is the main issue here.