Antifungal Resistance Among Candida Species from Pharmacotherapy

[Guest guest]

Just come across this post on Resistance caused by low dose Fluconazole ..

From: NickDate: 5/7/2003Time: 9:41:48 PMRemote Name: 66.74.176.15CommentsThis just out - consistent with what (UK) keeps repeating on this forum - institutions are finally recognizing that administering low dose antifungals such as Fluconazole at 200mg/day invariably leads to resistance, and are abandoning the practice.http://www.medscape.com/viewarticle/412677_5Antifungal Resistance Among Candida Species from PharmacotherapyClinical Implications The primary factor driving the emergence of antifungal resistance appears to be selective pressure resulting from increased administration of systemic antifungal agents. Given the seriousness of fungal infections and difficulties linked with their diagnosis, restricting empiric antifungal therapy may not be the best solution for combating resistance. Furthermore, when resistance does occur it is generally after pro-longed exposure to relatively low concentrations of drug. Such is the case when antifungal prophylaxis is given to immunocompromised patients.[3,34,37] Therefore, strategies for combating the emergence and spread of resistance should focus on three primary areas: reducing administration of prophylactic regimens; establishing optimal regimens to prevent suboptimal drug exposure; and ensuring aggressive surveillance to detect changes in patterns of antifungal susceptibility patterns. Perhaps one of the most significant developments that may slow the emergence of resistance is widespread administration of highly active antiretroviral therapy. With these regimens, patients' CD4+ counts often improve dramatically. As a result, patients are at decreased risk for acquiring opportunistic infections, including oropharyngeal candidiasis and other fungal infections. This observation led to recommendations that prophylactic regimens targeted against a variety of opportunistic pathogens may be discontinued. Indeed, improvement in immune status secondary to effective antiretroviral therapy resulted in reduced rates of carriage of C. albicans and oropharyngeal candidiasis.[82] A trend toward a reduction in the frequency of isolation of fluconazole-resistant C. albicans was also noted.A fundamental belief among infectious disease practitioners is that exposure of a microbe to subtherapeutic concentrations of antimicrobial is one of the surest ways to elicit resistance. This premise was validated for fungi in vitro by numerous investigators with a variety of agents.[78,79,83] Unfortunately, because of historical inability to diagnose fungal infections with a high degree of reliability and due to fear of drug-related toxicities, clinicians have not been aggressive with dosing of antifungal drugs. In defense of clinicians, it was not until the recent past that antifungal susceptibility testing and pharmaco-dynamic properties gained acceptance and provided some insight into the appropriateness of dosing strategies. Concentration-dependent fungicidal activity was described for polyene antifungals.[84,85] Data such as these support a trend that has been occurring in clinical practice, which is to prescribe increasing dosages of amphotericin B.[23-25] Similarly, with respect to azole antifungals, pharmacodynamic data and clinical data generated independently support the notion that the likelihood of treatment success is greatest if drug concentrations are maintained above the MIC of the pathogen.[17, 84]Such results should prompt clinicians to become familiar with antifungal surveillance data in their institutions and prescribe empiric azole regimens accordingly. In most institutions this means abandoning the practice of administering low-dosage fluconazole 100-200 mg/day and beginning therapy with at least 400 mg/day.Finally, although routine antifungal susceptibility testing is not yet recommended at the patient level, it can be an extremely important tool at the institution level. Periodic assessment of susceptibility patterns not only assists clinicians in selecting appropriate empiric dosing regimens but can provide early warning regarding shifts in these patterns. The significance of both of these points may be greatly increased as new antifungal drugs are introduced into clinical practice

[Guest guest]

That sounds like what I keep blabbing about.Don't mess around with

bugs they win.The more you leave today the more chances of them

picking up resistance plasmids.Remember this low dose approiach

comes from an arthritis forum wherby the people would get violentl;y

ill on full dose so a lesser dose was initiated.I suppose in those

circumstances a little is better than nothing.

> Just come across this post on Resistance caused by low dose

Fluconazole

> ..

>

>

> From: Nick

> Date: 5/7/2003

> Time: 9:41:48 PM

> Remote Name: 66.74.176.15

>

>

> Comments

> This just out - consistent with what (UK) keeps repeating on

this

> forum - institutions are finally recognizing that administering

low dose

> antifungals such as Fluconazole at 200mg/day invariably leads to

resistance,

> and are abandoning the practice.

>

>

> http://www.medscape.com/viewarticle/412677_5

>

> Antifungal Resistance Among Candida Species from Pharmacotherapy

>

> Clinical Implications The primary factor driving the emergence of

antifungal

> resistance appears to be selective pressure resulting from

increased

> administration of systemic antifungal agents. Given the

seriousness of

> fungal infections and difficulties linked with their diagnosis,

restricting

> empiric antifungal therapy may not be the best solution for

combating

> resistance. Furthermore, when resistance does occur it is

generally after

> pro-longed exposure to relatively low concentrations of drug. Such

is the

> case when antifungal prophylaxis is given to immunocompromised

> patients.[3,34,37] Therefore, strategies for combating the

emergence and

> spread of resistance should focus on three primary areas: reducing

> administration of prophylactic regimens; establishing optimal

regimens to

> prevent suboptimal drug exposure; and ensuring aggressive

surveillance to

> detect changes in patterns of antifungal susceptibility patterns.

Perhaps

> one of the most significant developments that may slow the

emergence of

> resistance is widespread administration of highly active

antiretroviral

> therapy. With these regimens, patients' CD4+ counts often improve

> dramatically. As a result, patients are at decreased risk for

acquiring

> opportunistic infections, including oropharyngeal candidiasis and

other

> fungal infections. This observation led to recommendations that

prophylactic

> regimens targeted against a variety of opportunistic pathogens may

be

> discontinued. Indeed, improvement in immune status secondary to

effective

> antiretroviral therapy resulted in reduced rates of carriage of C.

albicans

> and oropharyngeal candidiasis.[82] A trend toward a reduction in

the

> frequency of isolation of fluconazole-resistant C. albicans was

also noted.

>

> A fundamental belief among infectious disease practitioners is

that exposure

> of a microbe to subtherapeutic concentrations of antimicrobial is

one of the

> surest ways to elicit resistance. This premise was validated for

fungi in

> vitro by numerous investigators with a variety of agents.[78,79,83]

> Unfortunately, because of historical inability to diagnose fungal

infections

> with a high degree of reliability and due to fear of drug-related

> toxicities, clinicians have not been aggressive with dosing of

antifungal

> drugs. In defense of clinicians, it was not until the recent past

that

> antifungal susceptibility testing and pharmaco-dynamic properties

gained

> acceptance and provided some insight into the appropriateness of

dosing

> strategies. Concentration-dependent fungicidal activity was

described for

> polyene antifungals.[84,85] Data such as these support a trend

that has been

> occurring in clinical practice, which is to prescribe increasing

dosages of

> amphotericin B.[23-25] Similarly, with respect to azole

antifungals,

> pharmacodynamic data and clinical data generated independently

support the

> notion that the likelihood of treatment success is greatest if drug

> concentrations are maintained above the MIC of the pathogen.[17,

84]

>

> Such results should prompt clinicians to become familiar with

antifungal

> surveillance data in their institutions and prescribe empiric

azole regimens

> accordingly. In most institutions this means abandoning the

practice of

> administering low-dosage fluconazole 100-200 mg/day and beginning

therapy

> with at least 400 mg/day.

>

> Finally, although routine antifungal susceptibility testing is not

yet

> recommended at the patient level, it can be an extremely important

tool at

> the institution level. Periodic assessment of susceptibility

patterns not

> only assists clinicians in selecting appropriate empiric dosing

regimens but

> can provide early warning regarding shifts in these patterns. The

> significance of both of these points may be greatly increased as

new

> antifungal drugs are introduced into clinical practice

>

> --

> No virus found in this outgoing message.

> Checked by AVG Anti-Virus.

> Version: 7.0.323 / Virus Database: 267.7.3/15 - Release Date:

14/06/2005

[Guest guest]

Thanks for this ,

I'm going to ask my doc for a script with " medically necessary " on

it, to get me up to 400mg per day. So far, Insurance wants to cover

10 per month! GRRRR.

penny

>

>

> > Just come across this post on Resistance caused by low dose

> Fluconazole

> > ..

> >

> >

> > From: Nick

> > Date: 5/7/2003

> > Time: 9:41:48 PM

> > Remote Name: 66.74.176.15

> >

> >

> > Comments

> > This just out - consistent with what (UK) keeps repeating

on

> this

> > forum - institutions are finally recognizing that administering

> low dose

> > antifungals such as Fluconazole at 200mg/day invariably leads to

> resistance,

> > and are abandoning the practice.

> >

> >

> > http://www.medscape.com/viewarticle/412677_5

> >

> > Antifungal Resistance Among Candida Species from Pharmacotherapy

> >

> > Clinical Implications The primary factor driving the emergence

of

> antifungal

> > resistance appears to be selective pressure resulting from

> increased

> > administration of systemic antifungal agents. Given the

> seriousness of

> > fungal infections and difficulties linked with their diagnosis,

> restricting

> > empiric antifungal therapy may not be the best solution for

> combating

> > resistance. Furthermore, when resistance does occur it is

> generally after

> > pro-longed exposure to relatively low concentrations of drug.

Such

> is the

> > case when antifungal prophylaxis is given to immunocompromised

> > patients.[3,34,37] Therefore, strategies for combating the

> emergence and

> > spread of resistance should focus on three primary areas:

reducing

> > administration of prophylactic regimens; establishing optimal

> regimens to

> > prevent suboptimal drug exposure; and ensuring aggressive

> surveillance to

> > detect changes in patterns of antifungal susceptibility

patterns.

> Perhaps

> > one of the most significant developments that may slow the

> emergence of

> > resistance is widespread administration of highly active

> antiretroviral

> > therapy. With these regimens, patients' CD4+ counts often improve

> > dramatically. As a result, patients are at decreased risk for

> acquiring

> > opportunistic infections, including oropharyngeal candidiasis

and

> other

> > fungal infections. This observation led to recommendations that

> prophylactic

> > regimens targeted against a variety of opportunistic pathogens

may

> be

> > discontinued. Indeed, improvement in immune status secondary to

> effective

> > antiretroviral therapy resulted in reduced rates of carriage of

C.

> albicans

> > and oropharyngeal candidiasis.[82] A trend toward a reduction in

> the

> > frequency of isolation of fluconazole-resistant C. albicans was

> also noted.

> >

> > A fundamental belief among infectious disease practitioners is

> that exposure

> > of a microbe to subtherapeutic concentrations of antimicrobial

is

> one of the

> > surest ways to elicit resistance. This premise was validated for

> fungi in

> > vitro by numerous investigators with a variety of agents.

[78,79,83]

> > Unfortunately, because of historical inability to diagnose

fungal

> infections

> > with a high degree of reliability and due to fear of drug-related

> > toxicities, clinicians have not been aggressive with dosing of

> antifungal

> > drugs. In defense of clinicians, it was not until the recent

past

> that

> > antifungal susceptibility testing and pharmaco-dynamic

properties

> gained

> > acceptance and provided some insight into the appropriateness of

> dosing

> > strategies. Concentration-dependent fungicidal activity was

> described for

> > polyene antifungals.[84,85] Data such as these support a trend

> that has been

> > occurring in clinical practice, which is to prescribe increasing

> dosages of

> > amphotericin B.[23-25] Similarly, with respect to azole

> antifungals,

> > pharmacodynamic data and clinical data generated independently

> support the

> > notion that the likelihood of treatment success is greatest if

drug

> > concentrations are maintained above the MIC of the pathogen.[17,

> 84]

> >

> > Such results should prompt clinicians to become familiar with

> antifungal

> > surveillance data in their institutions and prescribe empiric

> azole regimens

> > accordingly. In most institutions this means abandoning the

> practice of

> > administering low-dosage fluconazole 100-200 mg/day and

beginning

> therapy

> > with at least 400 mg/day.

> >

> > Finally, although routine antifungal susceptibility testing is

not

> yet

> > recommended at the patient level, it can be an extremely

important

> tool at

> > the institution level. Periodic assessment of susceptibility

> patterns not

> > only assists clinicians in selecting appropriate empiric dosing

> regimens but

> > can provide early warning regarding shifts in these patterns. The

> > significance of both of these points may be greatly increased as

> new

> > antifungal drugs are introduced into clinical practice

> >

> > --

> > No virus found in this outgoing message.

> > Checked by AVG Anti-Virus.

> > Version: 7.0.323 / Virus Database: 267.7.3/15 - Release Date:

> 14/06/2005