lyme disease

1

Strategies for the Treatment of Strategies for the Treatment of Lyme DiseaseLyme Disease

2nd International Lyme & Associated Diseases Society2nd International Lyme & Associated Diseases Society(ILADS) Educational Meeting Europe(ILADS) Educational Meeting Europe

May 28, May 28, 201120118:40am 8:40am –– 9:25am9:25am

Augsburg, Germany Augsburg, Germany at the at the AugustanaAugustana SaalSaal, , AnnahofAnnahof AugsburgAugsburg

Steven Harris, MDSteven Harris, MD

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AffiliationsAffiliations

IGeneX, Inc. IGeneX, Inc. -- clinical consultantclinical consultant

QMedRx QMedRx -- medical advisory boardmedical advisory board

Pacific Frontier Medical, Inc Pacific Frontier Medical, Inc -- CEOCEO

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Lyme DiseaseLyme Disease

The discipline of Lyme disease including investigations The discipline of Lyme disease including investigations into the extent of this disease and its optimal treatment is into the extent of this disease and its optimal treatment is still in its infancy. There have been scarcely two fractional still in its infancy. There have been scarcely two fractional generations of clinicians who are confronting the full generations of clinicians who are confronting the full nature of this affliction.nature of this affliction.

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InteractionsInteractions

LYME

BABESIA BARTONELLA

PARASITES

MYCOPLASMA

MORGELLONS

HEAVY METALS

ALLERGY

HORMONAL DYSREGULATION

ADRENAL FATIGUE

PESTICIDES /ENVIRONMENTAL

POLLUTANTS

GEOPATHIC STRESSWORMSPRIONS

ELECTROMAGNETIC STRESS

GENETIC MUTATIONS

DEPRESSION / ANXIETY

DYSBIOSIS / SIBO

VIRUSES

BIOTOXINS

YEAST

MOLD

LEAKY GUT

BACTERIOPHAGES

ANAPLASMA / EHRLICHIA

5


LYME

BABESIA BARTONELLA

PARASITES

MYCOPLASMA

MORGELLONS

HEAVY METALS

ALLERGY


ADRENAL FATIGUE


POLLUTANTS



GENETIC MUTATIONS


DYSBIOSIS / SIBO

VIRUSES

BIOTOXINS

YEAST

MOLD

LEAKY GUT

BACTERIOPHAGES


headaches, night sweats,neuronal death, cardiomyopathy,

breathlessness

6


LYME

BABESIA BARTONELLA

PARASITES

MYCOPLASMA

MORGELLONS

HEAVY METALS

ALLERGY


ADRENAL FATIGUE


POLLUTANTS



GENETIC MUTATIONS


DYSBIOSIS / SIBO

VIRUSES

BIOTOXINS

YEAST

MOLD

LEAKY GUT

BACTERIOPHAGES


bipolar disorder, autism,GI distress, neuropathy,

encephalopathy

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LYME

BABESIA BARTONELLA

PARASITES

MYCOPLASMA

MORGELLONS

HEAVY METALS

ALLERGY


ADRENAL FATIGUE


POLLUTANTS



GENETIC MUTATIONS


DYSBIOSIS / SIBO

VIRUSES

BIOTOXINS

YEAST

MOLD

LEAKY GUT

BACTERIOPHAGES


fever, myalgia,fatigue

8


LYME

BABESIA BARTONELLA

PARASITES

MYCOPLASMA

MORGELLONS

HEAVY METALS

ALLERGY


ADRENAL FATIGUE


POLLUTANTS



GENETIC MUTATIONS


DYSBIOSIS / SIBO

VIRUSES

BIOTOXINS

YEAST

MOLD

LEAKY GUT

BACTERIOPHAGES


constipation, depression,headache, myalgia, brain fog,

fatigue, pain

9


LYME

BABESIA BARTONELLA

PARASITES

MYCOPLASMA

MORGELLONS

HEAVY METALS

ALLERGY


ADRENAL FATIGUE


POLLUTANTS



GENETIC MUTATIONS


DYSBIOSIS / SIBO

VIRUSES

BIOTOXINS

YEAST

MOLD

LEAKY GUT

BACTERIOPHAGES


psych disturbances,arthritis

10


LYME

BABESIA BARTONELLA

PARASITES

MYCOPLASMA

MORGELLONS

HEAVY METALS

ALLERGY


ADRENAL FATIGUE


POLLUTANTS



GENETIC MUTATIONS


DYSBIOSIS / SIBO

VIRUSES

BIOTOXINS

YEAST

MOLD

LEAKY GUT

BACTERIOPHAGES


skin sores

11


LYME

BABESIA BARTONELLA

PARASITES

MYCOPLASMA

MORGELLONS

HEAVY METALS

ALLERGY


ADRENAL FATIGUE


POLLUTANTS



GENETIC MUTATIONS


DYSBIOSIS / SIBO

VIRUSES

BIOTOXINS

YEAST

MOLD

LEAKY GUT

BACTERIOPHAGES


neuropathy, autism, fatigue, prolonged response to abx

12


LYME

BABESIA BARTONELLA

PARASITES

MYCOPLASMA

MORGELLONS

HEAVY METALS

ALLERGY


ADRENAL FATIGUE


POLLUTANTS



GENETIC MUTATIONS


DYSBIOSIS / SIBO

VIRUSES

BIOTOXINS

YEAST

MOLD

LEAKY GUT

BACTERIOPHAGES


hypersensitivity

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LYME

BABESIA BARTONELLA

PARASITES

MYCOPLASMA

MORGELLONS

HEAVY METALS

ALLERGY


ADRENAL FATIGUE


POLLUTANTS



GENETIC MUTATIONS


DYSBIOSIS / SIBO

VIRUSES

BIOTOXINS

YEAST

MOLD

LEAKY GUT

BACTERIOPHAGES


limitless

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LYME

BABESIA BARTONELLA

PARASITES

MYCOPLASMA

MORGELLONS

HEAVY METALS

ALLERGY


ADRENAL FATIGUE


POLLUTANTS



GENETIC MUTATIONS


DYSBIOSIS / SIBO

VIRUSES

BIOTOXINS

YEAST

MOLD

LEAKY GUT

BACTERIOPHAGES


fatigue, dizziness,bad die-off sxs

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LYME

BABESIA BARTONELLA

PARASITES

MYCOPLASMA

MORGELLONS

HEAVY METALS

ALLERGY


ADRENAL FATIGUE


POLLUTANTS



GENETIC MUTATIONS


DYSBIOSIS / SIBO

VIRUSES

BIOTOXINS

YEAST

MOLD

LEAKY GUT

BACTERIOPHAGES


fatigue, chemical sensitivities

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LYME

BABESIA BARTONELLA

PARASITES

MYCOPLASMA

MORGELLONS

HEAVY METALS

ALLERGY


ADRENAL FATIGUE


POLLUTANTS



GENETIC MUTATIONS


DYSBIOSIS / SIBO

VIRUSES

BIOTOXINS

YEAST

MOLD

LEAKY GUT

BACTERIOPHAGES


nervous system dysfunction, poor sleep

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LYME

BABESIA BARTONELLA

PARASITES

MYCOPLASMA

MORGELLONS

HEAVY METALS

ALLERGY


ADRENAL FATIGUE


POLLUTANTS



GENETIC MUTATIONS


DYSBIOSIS / SIBO

VIRUSES

BIOTOXINS

YEAST

MOLD

LEAKY GUT

BACTERIOPHAGES


headache, breathing difficulties,abdominal pain, irritability

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LYME

BABESIA BARTONELLA

PARASITES

MYCOPLASMA

MORGELLONS

HEAVY METALS

ALLERGY


ADRENAL FATIGUE


POLLUTANTS



GENETIC MUTATIONS


DYSBIOSIS / SIBO

VIRUSES

BIOTOXINS

YEAST

MOLD

LEAKY GUT

BACTERIOPHAGES


death

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LYME

BABESIA BARTONELLA

PARASITES

MYCOPLASMA

MORGELLONS

HEAVY METALS

ALLERGY


ADRENAL FATIGUE


POLLUTANTS



GENETIC MUTATIONS


DYSBIOSIS / SIBO

VIRUSES

BIOTOXINS

YEAST

MOLD

LEAKY GUT

BACTERIOPHAGES


bad response to treatment, fatigue, weakness

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LYME

BABESIA BARTONELLA

PARASITES

MYCOPLASMA

MORGELLONS

HEAVY METALS

ALLERGY


ADRENAL FATIGUE


POLLUTANTS



GENETIC MUTATIONS


DYSBIOSIS / SIBO

VIRUSES

BIOTOXINS

YEAST

MOLD

LEAKY GUT

BACTERIOPHAGES


inability to detoxify

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LYME

BABESIA BARTONELLA

PARASITES

MYCOPLASMA

MORGELLONS

HEAVY METALS

ALLERGY


ADRENAL FATIGUE


POLLUTANTS



GENETIC MUTATIONS


DYSBIOSIS / SIBO

VIRUSES

BIOTOXINS

YEAST

MOLD

LEAKY GUT

BACTERIOPHAGES


suicide risk

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LYME

BABESIA BARTONELLA

PARASITES

MYCOPLASMA

MORGELLONS

HEAVY METALS

ALLERGY


ADRENAL FATIGUE


POLLUTANTS



GENETIC MUTATIONS


DYSBIOSIS / SIBO

VIRUSES

BIOTOXINS

YEAST

MOLD

LEAKY GUT

BACTERIOPHAGES


abdominal issues

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LYME

BABESIA BARTONELLA

PARASITES

MYCOPLASMA

MORGELLONS

HEAVY METALS

ALLERGY


ADRENAL FATIGUE


POLLUTANTS



GENETIC MUTATIONS


DYSBIOSIS / SIBO

VIRUSES

BIOTOXINS

YEAST

MOLD

LEAKY GUT

BACTERIOPHAGES


headaches, dizziness,

heightened sxs, fatigue,neuropathy,

pain

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LYME

BABESIA BARTONELLA

PARASITES

MYCOPLASMA

MORGELLONS

HEAVY METALS

ALLERGY


ADRENAL FATIGUE


POLLUTANTS



GENETIC MUTATIONS


DYSBIOSIS / SIBO

VIRUSES

BIOTOXINS

YEAST

MOLD

LEAKY GUT

BACTERIOPHAGES


worsening of everything

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LYME

BABESIA BARTONELLA

PARASITES

MYCOPLASMA

MORGELLONS

HEAVY METALS

ALLERGY


ADRENAL FATIGUE


POLLUTANTS



GENETIC MUTATIONS


DYSBIOSIS / SIBO

VIRUSES

BIOTOXINS

YEAST

MOLD

LEAKY GUT

BACTERIOPHAGES


Varies from insignificant

to inability to treat

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LYME

BABESIA BARTONELLA

PARASITES

MYCOPLASMA

MORGELLONS

HEAVY METALS

ALLERGY


ADRENAL FATIGUE


POLLUTANTS



GENETIC MUTATIONS


DYSBIOSIS / SIBO

VIRUSES

BIOTOXINS

YEAST

MOLD

LEAKY GUT

BACTERIOPHAGES


varies

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LYME

BABESIA BARTONELLA

PARASITES

MYCOPLASMA

MORGELLONS

HEAVY METALS

ALLERGY


ADRENAL FATIGUE


POLLUTANTS



GENETIC MUTATIONS


DYSBIOSIS / SIBO

VIRUSES

BIOTOXINS

YEAST

MOLD

LEAKY GUT

BACTERIOPHAGES


bad die-off sxs,all sxs worse

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LYME

BABESIA BARTONELLA

PARASITES

MYCOPLASMA

MORGELLONS

HEAVY METALS

ALLERGY


ADRENAL FATIGUE


POLLUTANTS



GENETIC MUTATIONS


DYSBIOSIS / SIBO

VIRUSES

BIOTOXINS

YEAST

MOLD

LEAKY GUT

BACTERIOPHAGES


unknown

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What can the clinical state What can the clinical state of the infection mimic?of the infection mimic?

Lupus Lupus Rheumatoid arthritisRheumatoid arthritisPolymyalgia Polymyalgia rheumaticarheumaticaPolymyositis/dermatoPolymyositis/dermatomyositismyositisCFIDSCFIDSFibromyalgiaFibromyalgiaMultiple Chemical Multiple Chemical SensitivitySensitivityBipolar d/oBipolar d/oADHDADHDAutismAutismChronic EBVChronic EBVSchizoaffective d/oSchizoaffective d/o

•• Multiple sclerosisMultiple sclerosis•• CIDPCIDP•• Amyotrophic lateral Amyotrophic lateral

sclerosissclerosis•• Alzheimer's diseaseAlzheimer's disease•• Parkinson's DiseaseParkinson's Disease•• Thyroid diseaseThyroid disease•• Addison's diseaseAddison's disease•• HyperparathyroidismHyperparathyroidism•• Reflex sympathetic Reflex sympathetic

dystrophydystrophy•• MenopauseMenopause

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If Lyme can mimic so many diseases, If Lyme can mimic so many diseases, how can it be diagnosed?how can it be diagnosed?

MyoclonusMyoclonusFasciculationsFasciculationsSevere depression Severe depression (depressive episode)(depressive episode)Body electricBody electricWordWord--finding problemsfinding problemsDysuriaDysuria

A Lyme patient will usually experience 6A Lyme patient will usually experience 6--40+ symptoms at a time.40+ symptoms at a time.

Some wax and wane. Some wax and wane.

Joint painJoint painJoint stiffnessJoint stiffnessJoint swellingJoint swellingLightheadednessLightheadednessFevers / ChillsFevers / ChillsGI upsetGI upsetPelvic painPelvic painBlurry visionBlurry vision

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FatigueFatigueSleep disturbanceSleep disturbanceHeadacheHeadacheTinnitusTinnitusMuscle painMuscle painWorsening symptoms 4 Worsening symptoms 4 days before mensesdays before mensesNeck pain (buffalo hump Neck pain (buffalo hump pain)pain)

Joint crepitusJoint crepitusLow frustration toleranceLow frustration tolerancePoor executive functioning Poor executive functioning Low libidoLow libidoHypoesthesia (regions of Hypoesthesia (regions of numbness)numbness)HyperacusisHyperacusis

Some symptoms tend to remain constantSome symptoms tend to remain constant..

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DysthymiaDysthymiaNeuropathic painNeuropathic painRestless legRestless legTremorTremorAnxietyAnxietyEncephalopathyEncephalopathy

Subdermal fibrous cystsSubdermal fibrous cystsOsteophytesOsteophytesBlood pressure instabilityBlood pressure instabilityAutonomic dysreflexiaAutonomic dysreflexiaMuscle weaknessMuscle weaknessAbdominal painAbdominal pain

Some symptoms are variable.Some symptoms are variable.

Many patients will constantly experience these symptoms.Many patients will constantly experience these symptoms.Other patients will sporadically experience them.Other patients will sporadically experience them.

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If Lyme can mimic so many diseases,If Lyme can mimic so many diseases,how can it be diagnosed?how can it be diagnosed?

1. Establish likely exposure1. Establish likely exposureLeisure activitiesLeisure activitiesResidence vacationsResidence vacationsPets (are they sick?)Pets (are they sick?)OccupationOccupation

2. Ascertain prior experience with antibiotics2. Ascertain prior experience with antibioticsImprovementImprovementWorsening symptomsWorsening symptomsNo changeNo change

3. Focus on life events surrounding transition from wellness to3. Focus on life events surrounding transition from wellness to illnessillnessSurgeriesSurgeriesAccidentsAccidentsHiking tripsHiking tripsSteroidsSteroidsRoot canalsRoot canals

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What To Look For During An ExamWhat To Look For During An ExamLymeLyme

Diffuse myofascial Diffuse myofascial tendernesstendernessIncreased fluid pressure Increased fluid pressure on ballottement of fundion ballottement of fundiAdies pupilAdies pupilOscillating pupilsOscillating pupilsHyperreflexiaHyperreflexiaVertical ridging in nailsVertical ridging in nailsClammy hands and feetClammy hands and feet

Hypothermia 96.0Hypothermia 96.0--97.997.9Joint fluctuance Joint fluctuance –– fingers, fingers, elbows, kneeselbows, kneesJoint crepitusJoint crepitusArrhythmiaArrhythmiaNerve palsy CN 3,4,6,7,8Nerve palsy CN 3,4,6,7,8Paraspinal spasms Paraspinal spasms ––especially C7especially C7

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What To Look For During An ExamWhat To Look For During An ExamLymeLyme

Skin mottlingSkin mottlingHypermelanosisHypermelanosisPsoriasisPsoriasisDermographiaDermographiaHorizontal nystagmusHorizontal nystagmusThrush (coThrush (co--habitation by habitation by yeast is common)yeast is common)Oiling of skinOiling of skinAbdominal distensionAbdominal distensionNonNon--pitting edemapitting edemaBrown exudate on teethBrown exudate on teeth

Plantar tendernessPlantar tendernessSI joint SI joint Myofascial bundlesMyofascial bundlesHoffman reflexHoffman reflexCold acral extremitiesCold acral extremitiesBlack flecks within skin Black flecks within skin ulcers (Morgellons)ulcers (Morgellons)Subdermal fibromasSubdermal fibromasVagus nerve instability: Vagus nerve instability: vasovagal, hypomotilityvasovagal, hypomotility

37

Laboratory support in diagnosisLaboratory support in diagnosis

Lyme borreliosis appears identical to some conditions. The typiLyme borreliosis appears identical to some conditions. The typical cal symptom patterns do not fit except for some pronounced symptoms.symptom patterns do not fit except for some pronounced symptoms.

Some examples includeSome examples include::Multiple sclerosisALSParkinson's diseaseRheumatoid arthritisDementiaChronic fatigue without painBipolar disorderRecurrent acute aseptic meningitisCharcot Marie-ToothGuillian BarreScleroderma

38

In these situations lab support is crucial. One may find higherIn these situations lab support is crucial. One may find higher than 30% than 30% of these patients test positive for Lyme by antibodies, usually of these patients test positive for Lyme by antibodies, usually IgM Western IgM Western blot, bands 31 kDa, 34 kDa, 23blot, bands 31 kDa, 34 kDa, 23--25 kDa, 39 kDa, 58 kDa, 8325 kDa, 39 kDa, 58 kDa, 83--93 kDa in 93 kDa in some combination some combination ANDAND Bb PCR in either serum, whole blood, urine or Bb PCR in either serum, whole blood, urine or tissue. CSF positivity is rare.tissue. CSF positivity is rare.

Tissue biopsies for PCR are typically more sensitive in most LymTissue biopsies for PCR are typically more sensitive in most Lyme e patientspatients-- cartilage, bladder, gallbladder and cystic duct, small intesticartilage, bladder, gallbladder and cystic duct, small intestine ne and colon, endometriosis lesions, jaw, fascia and tendons as weland colon, endometriosis lesions, jaw, fascia and tendons as well as birth l as birth organs. organs.

Bartonella can also be analyzed by DNA probes for tissue presencBartonella can also be analyzed by DNA probes for tissue presence. e. Placenta, foreskin, cord segments, colon, heart will often test Placenta, foreskin, cord segments, colon, heart will often test positive.positive.


39

Lyme Disease TestingLyme Disease Testing

Indirect TestsIndirect TestsDetection of patientDetection of patient’’s immune response to s immune response to Borrelia Borrelia burgdorferiburgdorferi, the causative agent in Lyme disease., the causative agent in Lyme disease.Types:Types:

Serology (Standard ELISA, C6 peptide)Serology (Standard ELISA, C6 peptide)Western BlotWestern BlotImmunofluorescenceImmunofluorescence

Direct TestsDirect TestsDetection of Detection of Borrelia burgdorferiBorrelia burgdorferi--specific proteins (antigens), specific proteins (antigens), DNA and RNA, in patient clinical specimen (blood, serum, DNA and RNA, in patient clinical specimen (blood, serum, urine, CSF, etc).urine, CSF, etc).Types:Types:

Lyme Urine AntigenLyme Urine AntigenPCRPCR

41

Laboratory support in diagnosisLaboratory support in diagnosisWhy Does IgM Persist?Why Does IgM Persist?

Epitope switching.Epitope switching.

Intracellular organism often avoids immune detection.Intracellular organism often avoids immune detection.

Monthly burst out of lymphocytes probably reactivates antibody Monthly burst out of lymphocytes probably reactivates antibody response.response.

IgM Antibodies have no ‘memory’. As they are large molecules, they are broken down readily in the liver. IgM antibody represents either new infection or persistent infection.

42

The Western BlotThe Western Blot

The Western blot is an entry point to confirmation of diagnosis.The Western blot is an entry point to confirmation of diagnosis.

The IgM Western blot will indicate immune system recognition of The IgM Western blot will indicate immune system recognition of and and response to the organism within 3response to the organism within 3--4 months of exposure. In other words, 4 months of exposure. In other words, the organism was likely in the blood stream at some point over tthe organism was likely in the blood stream at some point over the last he last 33--4 months.4 months.

In contrast to common belief expressed in popular medical literaIn contrast to common belief expressed in popular medical literature, false ture, false positives are quite rare (except for possibly 31 kDa).positives are quite rare (except for possibly 31 kDa).

If two or more bands are present, officially 23If two or more bands are present, officially 23--25 kDa, (31 kDa), (34 kDa), 25 kDa, (31 kDa), (34 kDa), 39 kDa, 41 kDa, then according to Dr. Burrascano39 kDa, 41 kDa, then according to Dr. Burrascano’’s inclusion criteria there s inclusion criteria there is a likely presence of Lyme disease.is a likely presence of Lyme disease.

Unofficially, according to Dr. Charles Ray Jones, if 18 kDa, 23Unofficially, according to Dr. Charles Ray Jones, if 18 kDa, 23--25 kDa, 30 25 kDa, 30 kDa, 31 kDa, 34 kDa, 37 kDa, 39 kDa, 83 kDa, 93 kDa in any combikDa, 31 kDa, 34 kDa, 37 kDa, 39 kDa, 83 kDa, 93 kDa in any combination nation or in isolation, the Lyme spirochete is likely present in the inor in isolation, the Lyme spirochete is likely present in the individual.dividual.


43


Outer surface protein A (Osp A) Outer surface protein A (Osp A) –– 31 kDa31 kDaA positive band 31 kDa on IgG and/or IgM Western Blot may A positive band 31 kDa on IgG and/or IgM Western Blot may be a false positive.be a false positive.There is crossThere is cross--reactivity between reactivity between BorreliaBorrelia and several and several viruses.viruses.To confirm that a positive band 31kDa is due to To confirm that a positive band 31kDa is due to BorreliaBorrelia, , order the following test from IGeneX, Inc.order the following test from IGeneX, Inc.

# 488 # 488 –– 31 kDa epitope IgM31 kDa epitope IgM# 489 # 489 –– 31 kDa epitope IgG31 kDa epitope IgG

I recommend ordering this test only if band 31 kDa is positive I recommend ordering this test only if band 31 kDa is positive in isolation, i.e., no other speciesin isolation, i.e., no other species--specific bands are positive.specific bands are positive.

44

CONTROVERSYCONTROVERSYAntibodies of ImportanceAntibodies of Importance

31 kDa (Osp A)31 kDa (Osp A)

34 kDa (Osp B)34 kDa (Osp B)

45

Comparison of the Frequency of Antibody Reactivity to Various B. burgdorferi Protein Bands Between Lyme

Patients, Syphilis Patients, and Normal Controls

Comparison of the Frequency of Antibody Reactivity to Various B. burgdorferi Protein Bands Between Lyme Patients, Syphilis

and Normal Controls

0%10%20%30%40%50%60%70%80%90%

100%

93 83 73 66 60 58 45 41 39 34 31 28 23-25

18

B. burgdorferi Proteins (kDa)

Freq

uenc

y

Lyme (n=189)

Syphilis (n=56)

Normal (n=320)

M a et al. 1992. JCM 30:376

46

Shah et. alShah et. al

Shah, JS, DuCruz I, Wronska D, Harris S, Harris NS. Comparison oShah, JS, DuCruz I, Wronska D, Harris S, Harris NS. Comparison of f Specificity and Sensitivity of IGeneX Lyme Western Blots Using Specificity and Sensitivity of IGeneX Lyme Western Blots Using IGeneX Criteria and CDC Criteria for a Positive Western Blot., IGeneX Criteria and CDC Criteria for a Positive Western Blot., Townsend letter, April 2007Townsend letter, April 2007

ConclusionConclusionIgG 18, 41, and 58 kDa IgG 18, 41, and 58 kDa

Statistically associated with tickStatistically associated with tick--borne diseasesborne diseasesIgG 28, 30, 45, 66 kDa IgG 28, 30, 45, 66 kDa

Not specific markers for Lyme and other tickNot specific markers for Lyme and other tick--borne diseasesborne diseasesIgG and IgM 23IgG and IgM 23--25, 31, 34, 39, 8325, 31, 34, 39, 83--93 93

Highly specific markers for Lyme diseaseHighly specific markers for Lyme disease

Criteria for positive IgM and IgG WB should include bands 23Criteria for positive IgM and IgG WB should include bands 23--25, 31, 34, 39, 41, and 8325, 31, 34, 39, 41, and 83--9393

47


The patient does not have Lyme disease. The patient does not have Lyme disease. Many asymptomatic, healthy partners or siblings of Lyme patientsMany asymptomatic, healthy partners or siblings of Lyme patientsmay test positive if their immune system is exposed an/or are may test positive if their immune system is exposed an/or are warding off a Borrelia infection.warding off a Borrelia infection.One has had the Lyme vaccine. One has had the Lyme vaccine. Lab workers, veterinarians, dentists, and hunters.Lab workers, veterinarians, dentists, and hunters.

One has a healthy immune system and is fighting Bb well.One has a healthy immune system and is fighting Bb well.It is a positive predictor of length of time likely required forIt is a positive predictor of length of time likely required fortreatment.treatment.

Many patients will not develop a positive IgG response until theMany patients will not develop a positive IgG response until the end of end of disease. If a positive IgG is present it will generally indicatdisease. If a positive IgG is present it will generally indicate one of e one of several things:several things:

48


One has multiple exposures to several infected ticks and is veryOne has multiple exposures to several infected ticks and is very

sick.sick.These people often come from the East Coast or EuropeThese people often come from the East Coast or Europe

The elderly often mount a brisk IgG response. The elderly often mount a brisk IgG response.

Nevertheless, consider the likelihood of Lyme and treat if a cliNevertheless, consider the likelihood of Lyme and treat if a clinical nical diagnosis is made. Dondiagnosis is made. Don’’t treat a test result. Treat a patientt treat a test result. Treat a patient

49

Lyme Disease Case Lyme Disease Case Classification by CDCClassification by CDC

CONFIRMED CASEA Case with EM, orA Case of Late Manifestation that is Laboratory Confirmed

Laboratory ConfirmationIsolation of Borrelia burgdorferi from a clinical sample ordemonstration of IgM or IgG antibodies to B. burgdorferii in serum or CSF. A two-test approach using a sensitive ELISA or IFA, followed by Western Blots.

NOTE: The above is a SURVEILLANCE case definition,developed for national reporting of Lyme Disease by CDC. ITIS NOT INTENDED FOR USE IN CLINICAL DIAGNOSIS.

Ref: MMWR 46:RR10

50

DDirect Detectionirect Detection

BiopsyBiopsy

CultureCulture

Antigen CaptureAntigen Capture

Polymerase Chain Reaction Polymerase Chain Reaction (PCR)(PCR)

51

CultureCulture

Schwan TG. , Burgdorfer W., Schrumpf ME, Karstens RH., 1988. Schwan TG. , Burgdorfer W., Schrumpf ME, Karstens RH., 1988. The urinary bladder, a consistent source of B. burgdorferi in The urinary bladder, a consistent source of B. burgdorferi in experimentally infected whiteexperimentally infected white--footed mice. J.Clin Microbiology 26: footed mice. J.Clin Microbiology 26: 893893--895.895.

Spirochetes more frequently isolated from the bladder (94%) Spirochetes more frequently isolated from the bladder (94%) followed by kidney (75%), spleen (61%), blood (13%) and urine followed by kidney (75%), spleen (61%), blood (13%) and urine (0%).(0%).

55

Some patients may remain seronegative for years.

Diagnosis:Diagnosis: Induction of a High Yield Lyme Urine DNA and ProteinInduction of a High Yield Lyme Urine DNA and Protein

If unchallenged serum Western Blot (WB) is negative and high susIf unchallenged serum Western Blot (WB) is negative and high suspicion of picion of Lyme exists Lyme exists can enhance diagnostic yield of WB without resorting to can enhance diagnostic yield of WB without resorting to multimulti--drug urine challenge and costs associated.drug urine challenge and costs associated.

Give a macrolide x 3 weeks OR doxycycline 100mg bid x 3 weeks.Give a macrolide x 3 weeks OR doxycycline 100mg bid x 3 weeks.

On week 4 (four weeks after starting abx, obtain repeat IgM WB. On week 4 (four weeks after starting abx, obtain repeat IgM WB. Pay Pay particular attention to 31 kDa and 34 kDa.particular attention to 31 kDa and 34 kDa.

If negative, wait 6If negative, wait 6--8 weeks before urine induction for protein and DNA.8 weeks before urine induction for protein and DNA.

56Warn your patients of the risks of using antibiotics in this manner.


If a patient suspected of Lyme disease has had negative WB and nIf a patient suspected of Lyme disease has had negative WB and negative egative whole blood PCR can obtain a higher yield of DNA or protein in twhole blood PCR can obtain a higher yield of DNA or protein in the urine by he urine by strategically using antibiotics diagnostically.strategically using antibiotics diagnostically.

Theory: Theory: Bb has a life cycle (about 4 months in the helical form). When Bb has a life cycle (about 4 months in the helical form). When the bacteria dies, the bacteria dies, many of its proteins will be shed into the urine. However, givemany of its proteins will be shed into the urine. However, given the very low n the very low absolute numbers of Bb in the body, randomly testing the urine fabsolute numbers of Bb in the body, randomly testing the urine for pieces of or pieces of dead bacteria will provide low yield. If one can markedly enhandead bacteria will provide low yield. If one can markedly enhance the amount of ce the amount of dead bacteria being shed, one can maximize likelihood of obtainidead bacteria being shed, one can maximize likelihood of obtaining a more ng a more accurate result. accurate result.

Caution: diarrhea, C. difficile, candidiasis, nausea, vomiting, Caution: diarrhea, C. difficile, candidiasis, nausea, vomiting, allergy, allergy, StevensStevens--Johnson syndrome, individual drug side effects.Johnson syndrome, individual drug side effects.

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Many protocols are being used in the US currently by doctors whoMany protocols are being used in the US currently by doctors who are members of are members of the International Lyme and Associated Diseases Society (ILADS).the International Lyme and Associated Diseases Society (ILADS).

Protocol 1Protocol 1Day 1: Ceftriaxone 2 grams IV or IM Day 1: Ceftriaxone 2 grams IV or IM plusplus Benzathine Penicillin 1.2 million units Benzathine Penicillin 1.2 million units IMIMDays 2Days 2--5: Clarithromycin 500mg bid or azithromycin 5005: Clarithromycin 500mg bid or azithromycin 500--600mg qd or 600mg qd or doxycycline 100mg tid or minocycline 100mg tid doxycycline 100mg tid or minocycline 100mg tid plusplus cefuroxime 500mg bid or cefuroxime 500mg bid or amoxicillin 1000mg tid or cefdinir 300mg bid amoxicillin 1000mg tid or cefdinir 300mg bid plusplus metronidazole 500mg bid or metronidazole 500mg bid or tinidazole 500mg tidtinidazole 500mg tidCollect first morning urine samples on days 2, 4, and 6Collect first morning urine samples on days 2, 4, and 6

Protocol 2Protocol 2Days 1Days 1--3: ceftriaxone 2 grams IV or IM (May also add azithromycin 500mg3: ceftriaxone 2 grams IV or IM (May also add azithromycin 500mg qd )qd )Days 2Days 2--5: metronidazole 500mg bid or tinidazole 500mg tid5: metronidazole 500mg bid or tinidazole 500mg tidCollect first morning urine samples on days 2, 4, and 6Collect first morning urine samples on days 2, 4, and 6

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Protocol 3 (lower yield, but easier to tolerate)Protocol 3 (lower yield, but easier to tolerate)Days 1Days 1--7: amoxicillin or cefuroxime or cefdinir 7: amoxicillin or cefuroxime or cefdinir plusplus doxycycline or minocycline or doxycycline or minocycline or azithromycin or clarithromycinazithromycin or clarithromycinCollect first morning urine samples on days 3, 6, and 8Collect first morning urine samples on days 3, 6, and 8

Children:Children:Days 1Days 1--5: age5: age--weighted dosages for protocol 3 with or without Benzathine or weighted dosages for protocol 3 with or without Benzathine or ceftriaxone on day 1ceftriaxone on day 1Do NOT use doxycycline or minocycline in children < 8 years oldDo NOT use doxycycline or minocycline in children < 8 years oldCollect first morning urine samples on days 2, 4, and 6Collect first morning urine samples on days 2, 4, and 6

If menstruating female, time urine collection with menses.

Please have patients use lactobacillus and bifidus +/- saccharomyces to protect GI tract.

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Candida AbsCandida AbsArabinatol levelsArabinatol levelsEBV (VCA, EA, NA)EBV (VCA, EA, NA)HHVHHV--66HHVHHV--77CoxsackieCoxsackieParvovirusParvovirusCMVCMVHIVHIVMycoplasma pneumoniaeMycoplasma pneumoniaeVitamin D 25, vitamin D 1,25Vitamin D 25, vitamin D 1,25ESR / CRPESR / CRPTotal CKTotal CK

Urine heavy metalsUrine heavy metalsStool pathogensStool pathogensH. pyloriH. pyloriHepatitis panelHepatitis panelCBC with diff, reticulocytesCBC with diff, reticulocytesCMPCMPCDCD--57 (HNK57 (HNK--1 panel)1 panel)Thyroid comprehensive panelThyroid comprehensive panelLipid profileLipid profileInsulin levelsInsulin levelsGlucose tolerance testGlucose tolerance testIgG and IgE food antibodiesIgG and IgE food antibodiesHLA typingHLA typing

Ancillary tests to consider

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Salivary cortisolSalivary cortisolDHEADHEASex hormonesSex hormonesSHBGSHBGFerritinFerritinCEACEARPRRPRPhase 1 and 2 hepatic functionPhase 1 and 2 hepatic functionABO RhABO RhUAUAUrine neurotransmitterUrine neurotransmitterOrganic acidsOrganic acids

Urine amino acidsUrine amino acidsEssential elementsEssential elementsNutrigenomic testing for Nutrigenomic testing for methylation cyclemethylation cycleFibrinogen / TAT / Soluble Fibrinogen / TAT / Soluble fibrin monomerfibrin monomerThyroid loading testsThyroid loading testsMucosal Barrier functionMucosal Barrier functionRNase L activity and protein RNase L activity and protein quantificationquantificationElastaseElastaseVitamin deficienciesVitamin deficienciesPregnenolonePregnenoloneAldosteroneAldosterone


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HLA typingHLA typingILIL--66ILIL--22ILIL--11ILIL--1010TNFTNF--alpha and 1 betaalpha and 1 betaααCoccidioidesCoccidioidesHistoplasmaHistoplasmaToxoplasmaToxoplasmaPlasma porphyrinsPlasma porphyrinsAmmoniaAmmoniaLeptin, MSH, VEGFLeptin, MSH, VEGF

ANA with titer, SSANA with titer, SS--A, SSA, SS--B, B, anti DS DNA, Sm/Rnp AB, anti DS DNA, Sm/Rnp AB, complement studies, anticomplement studies, anti--gliadin, TTG, RFgliadin, TTG, RFTotal Immunoglobulin and Total Immunoglobulin and subclassessubclassesIgFIgF--11Arginine stimulation for HGHArginine stimulation for HGHPlasma amino acidsPlasma amino acidsWhole blood elementsWhole blood elementsRed blood cell elementsRed blood cell elementsHair elementsHair elementsKPUKPUSerum mineralsSerum mineralsZinc, copper, magnesiumZinc, copper, magnesium


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Treating Lyme diseaseTreating Lyme disease

The basics of treating Lyme can be found in The basics of treating Lyme can be found in ““Diagnostic Hints and Diagnostic Hints and Treatment Guidelines for Lyme and Other Tick Borne IllnessesTreatment Guidelines for Lyme and Other Tick Borne Illnesses”” by Joseph by Joseph Burrascano Jr, MD.Burrascano Jr, MD.

Generally you can start fast and furious or slow and steady. SoGenerally you can start fast and furious or slow and steady. Some patients me patients do well with a quick aggressive treatment. Many doctors have trdo well with a quick aggressive treatment. Many doctors have tremendous emendous success in the more hearty patients. Other patients may unexpecsuccess in the more hearty patients. Other patients may unexpectedly tedly become quite sick 2become quite sick 2--4 days after starting or even at 214 days after starting or even at 21--28 days after 28 days after treatment begins.treatment begins.

This is usually due to a JarischThis is usually due to a Jarisch--Herxheimer reaction, in which a torrent of Herxheimer reaction, in which a torrent of cytokines and toxins spill into the body humors.cytokines and toxins spill into the body humors.

Symptoms can range from worsening fatigue, joint pain or swellinSymptoms can range from worsening fatigue, joint pain or swelling and g and dysuria to shock, coma and death.dysuria to shock, coma and death.

You may have to You may have to ““play catchplay catch--upup”” for months. for months.

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Some conditions that I recommend not be treated too aggressivelySome conditions that I recommend not be treated too aggressively at first:at first:

Severe neurological conditionsSevere neurological conditionsBaseline abdominal distressBaseline abdominal distressChemically sensitive individualsChemically sensitive individualsChildrenChildrenThe elderlyThe elderlyIf one suspects but does not know coIf one suspects but does not know co--infection statusinfection statusWomen with pelvic pain or frequent headachesWomen with pelvic pain or frequent headachesIn severe early Lyme, aggressive therapy is generally well tolerIn severe early Lyme, aggressive therapy is generally well tolerated.ated.

Aggressive therapy defined:Aggressive therapy defined:

IV medicationsIV medicationsHigh dose antibiotic combinationsHigh dose antibiotic combinationsFlagyl or tinidazole and a high dose antiFlagyl or tinidazole and a high dose anti--spiral medicine.spiral medicine.

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Two very different standards of careTwo very different standards of care

New England Journal of Medicine article states New England Journal of Medicine article states ““Chronic Lyme disease, which is Chronic Lyme disease, which is equated with chronic B. burgdorferi infection, is a misnomer, anequated with chronic B. burgdorferi infection, is a misnomer, and the use of d the use of prolonged, dangerous and expensive antibiotic treatments for it prolonged, dangerous and expensive antibiotic treatments for it is not warrantedis not warranted””(Feder et. Al)(Feder et. Al)IDSA 2006 guidelines for the diagnosis and treatment of Lyme disIDSA 2006 guidelines for the diagnosis and treatment of Lyme diseaseeaseAAN guidelines; independent corroboration?AAN guidelines; independent corroboration?““Prolonged Lyme disease treatmentProlonged Lyme disease treatment”” (Halperin, Journal Neurology)(Halperin, Journal Neurology)

VSVS

A randomized, placeboA randomized, placebo--controlled trial of repeated IV antibiotic therapy for Lyme controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy (Fallon et al, Journal Neurology) encephalopathy (Fallon et al, Journal Neurology) ILADS guidelines for the diagnosis and treatment of Lyme diseaseILADS guidelines for the diagnosis and treatment of Lyme diseaseLyme disease: a turning point (Stricker and Johnson, Future drugLyme disease: a turning point (Stricker and Johnson, Future drugs)s)Treatment of Lyme disease: a medicolegal assessment (Johnson aTreatment of Lyme disease: a medicolegal assessment (Johnson and Stricker, nd Stricker, Future drugs)Future drugs)

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EvidenceEvidence--Based Guidelines for the Based Guidelines for the Management of Lyme DiseaseManagement of Lyme Disease

Since there is currently no definitive test for Lyme disease, laSince there is currently no definitive test for Lyme disease, laboratory boratory results should not be used to exclude an individual from treatmeresults should not be used to exclude an individual from treatment.nt.

Lyme disease is a clinical diagnosis and tests should be used toLyme disease is a clinical diagnosis and tests should be used to support support rather than supersede the physicianrather than supersede the physician’’s judgment.s judgment.

The early use of antibiotics can prevent persistent, recurrent aThe early use of antibiotics can prevent persistent, recurrent and refractory nd refractory Lyme disease.Lyme disease.

The duration of therapy should be guided by clinical response, rThe duration of therapy should be guided by clinical response, rather than ather than by an arbitrary (i.e., 30 day) treatment course.by an arbitrary (i.e., 30 day) treatment course.

The practice of stopping antibiotics to allow for delayed recoveThe practice of stopping antibiotics to allow for delayed recovery is not ry is not recommended for persistent Lyme disease. In these cases, it is recommended for persistent Lyme disease. In these cases, it is reasonable reasonable to continue treatment for several months after clinical and laboto continue treatment for several months after clinical and laboratory ratory abnormalities have begun to resolve and symptoms have disappeareabnormalities have begun to resolve and symptoms have disappeared.d.

Expert Rev Antiinfect Ther 2004;2(1 Suppl):S1Expert Rev Antiinfect Ther 2004;2(1 Suppl):S1--1313

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Evidence for the use of longEvidence for the use of long--term treatmentterm treatment

Bayer ME, Zhang L, Bayer MH. Borrelia burgdorferi DNA in the uriBayer ME, Zhang L, Bayer MH. Borrelia burgdorferi DNA in the urine of treated ne of treated patients with chronic Lyme disease symptoms. A PCR study of 97 cpatients with chronic Lyme disease symptoms. A PCR study of 97 cases. Infection ases. Infection 1996; 24 No.5.1996; 24 No.5.

Cameron, DJ. Lyme Disease Clinical Trial Cameron, DJ. Lyme Disease Clinical Trial -- Effectiveness of Retreatment on HealthEffectiveness of Retreatment on Health--Related Quality of Life. Abstract, Lyme & Other TBDs: Emerging TRelated Quality of Life. Abstract, Lyme & Other TBDs: Emerging Tick Borne ick Borne Diseases, Fri Oct 28th, 2005, Philadelphia, PA.Diseases, Fri Oct 28th, 2005, Philadelphia, PA.

Cimmino MA, Accardo S. Long term treatment of chronic Lyme arthrCimmino MA, Accardo S. Long term treatment of chronic Lyme arthritis with itis with Benzathine penicillin. Ann Rheum Dis 1992 Aug; 51(8):1007Benzathine penicillin. Ann Rheum Dis 1992 Aug; 51(8):1007--8.8.

Cimmino MA, Moggiana GI, Parisi M, Accardo S. Treatment of Lyme Cimmino MA, Moggiana GI, Parisi M, Accardo S. Treatment of Lyme arthritis. arthritis. Infection 1996 JanInfection 1996 Jan--Feb; 24(1):91Feb; 24(1):91--3.3.

Cimperman J, Maraspin V, LotricCimperman J, Maraspin V, Lotric--Furlan S, RuzicFurlan S, Ruzic--Sabljic E, Strle F. Lyme meningitis: Sabljic E, Strle F. Lyme meningitis: a onea one--year follow up controlled study. Wien Klin Wochenschr 1999; 111(year follow up controlled study. Wien Klin Wochenschr 1999; 111(2222--23):96123):961--3.3.

Cimmino MA, Moggiana GI, Parisi M, Accardo S. Treatment of Lyme Cimmino MA, Moggiana GI, Parisi M, Accardo S. Treatment of Lyme arthritis. arthritis. Infection 1996 JanInfection 1996 Jan--Feb; 24(1):91Feb; 24(1):91--3.3.

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Dattwyler RJ, Volkman DJ, Luft BJ, Halperin JJ, Thomas J, GolighDattwyler RJ, Volkman DJ, Luft BJ, Halperin JJ, Thomas J, Golightly MG. tly MG. Seronegative Lyme disease. Dissociation of specific TSeronegative Lyme disease. Dissociation of specific T-- and Band B--lymphocyte responses lymphocyte responses to Borrelia burgdorferi. N Engl J Med 1988 Dec 1; 319(22):1441to Borrelia burgdorferi. N Engl J Med 1988 Dec 1; 319(22):1441--6.6.

Donta ST. Tetracycline therapy for chronic Lyme disease. Clin InDonta ST. Tetracycline therapy for chronic Lyme disease. Clin Infect Dis 1997; 25 fect Dis 1997; 25 Suppl 1:pS52Suppl 1:pS52--6.6.

Fallon BA et al. Repeated antibiotic treatment in chronic Lyme dFallon BA et al. Repeated antibiotic treatment in chronic Lyme disease. J Spirochet isease. J Spirochet Tick Borne Dis, 1999 Fall/Winter:p94Tick Borne Dis, 1999 Fall/Winter:p94--101.101.

Fallon BA et al. A randomized, placeboFallon BA et al. A randomized, placebo--controlled trial of repeated IV antibiotic controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy. Neurology, 2007.therapy for Lyme encephalopathy. Neurology, 2007.

Gasser R, Reisinger E, Eber B, Pokan R, Seinost G, Bergloff J, HGasser R, Reisinger E, Eber B, Pokan R, Seinost G, Bergloff J, Horwarth R, Sedaj B, orwarth R, Sedaj B, Klein W. Cases of Lyme borreliosis resistant to conventional treKlein W. Cases of Lyme borreliosis resistant to conventional treatment: improved atment: improved symptoms with cephalosporin plus specific betasymptoms with cephalosporin plus specific beta--lactamase inhibition. Microb Drug lactamase inhibition. Microb Drug Resist 1995 Winter; 1(4):341Resist 1995 Winter; 1(4):341--4.4.

Georgilis K, Peacocke M, Klempner MS. Fibroblasts protect the LyGeorgilis K, Peacocke M, Klempner MS. Fibroblasts protect the Lyme disease me disease spirochete, Borrelia burgdorferi, from ceftriaxone in vitro. J Ispirochete, Borrelia burgdorferi, from ceftriaxone in vitro. J Infect Dis 1992 Aug; nfect Dis 1992 Aug; 166(2):440166(2):440--4.4.

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Goldings AS, Taylor JP, Rawlings J. Lyme borreliosis in Texas. TGoldings AS, Taylor JP, Rawlings J. Lyme borreliosis in Texas. Tex Med 1991 Sep; ex Med 1991 Sep; 87(9):6287(9):62--6.6.

Hold DA, Pattani NJ, Sinnott JT 4th, Bradley E. Lyme borreliosisHold DA, Pattani NJ, Sinnott JT 4th, Bradley E. Lyme borreliosis. Infect Control Hosp . Infect Control Hosp Epidemiol. 1991 Aug; 12(8):493Epidemiol. 1991 Aug; 12(8):493--6.6.

Hoffmann H. Lyme borreliosis Hoffmann H. Lyme borreliosis -- problems of serological diagnosis. Infection 1996. problems of serological diagnosis. Infection 1996. NovNov--Dec; 24(6):470Dec; 24(6):470--2.2.

Hudson BJ, Steward M, Lennox VA, Fukunaga M, Yabuki M, et al. CuHudson BJ, Steward M, Lennox VA, Fukunaga M, Yabuki M, et al. Culturelture--positive positive Lyme borreliosis. Med J Aust 1998 May 18; 168(10):500Lyme borreliosis. Med J Aust 1998 May 18; 168(10):500--2.2.

Klempner MS, Hu LT, Evans J, Schmid CH, Johnson GM, Trevino RP, Klempner MS, Hu LT, Evans J, Schmid CH, Johnson GM, Trevino RP, Norton D, Norton D, Levy L, Wall D, McCall J, Kosinski M, Weinstein A. Two controlleLevy L, Wall D, McCall J, Kosinski M, Weinstein A. Two controlled trials of antibiotic d trials of antibiotic treatment in patients with persistent symptoms and a history of treatment in patients with persistent symptoms and a history of Lyme disease. N Engl Lyme disease. N Engl J Med 2001. Jul 12; 345(2):85J Med 2001. Jul 12; 345(2):85--92.92.

Krupp, LB et al. Study and treatment of post Lyme disease (STOPKrupp, LB et al. Study and treatment of post Lyme disease (STOP--LD): a randomized LD): a randomized double masked clinical trial. Neurology, 2003. 60(12):p.1923double masked clinical trial. Neurology, 2003. 60(12):p.1923--30.30.

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Kufko IT, MelKufko IT, Mel’’nikov VG, Andreeva EA, Sokolova ZI, Lesniak OM, Beikin laB. nikov VG, Andreeva EA, Sokolova ZI, Lesniak OM, Beikin laB. Comparative study of results of serological diagnosis of Lyme boComparative study of results of serological diagnosis of Lyme borreliosis by indirect rreliosis by indirect immunofluorescence and immunoenzyme analysis. Klin Lab Diagn 199immunofluorescence and immunoenzyme analysis. Klin Lab Diagn 1999; 3:349; 3:34--7.7.

Lawrence C, Lipton RB, Lowy FD, Coyle PK. Seronegative chronic rLawrence C, Lipton RB, Lowy FD, Coyle PK. Seronegative chronic relapsing elapsing neuroborreliosis. Eur Neurol 1995; 35(2):113neuroborreliosis. Eur Neurol 1995; 35(2):113--7.7.

Luft BJ, Dattwyler RJ, Johnson RC, Luger SW, Bosler EM, Rahn DW,Luft BJ, Dattwyler RJ, Johnson RC, Luger SW, Bosler EM, Rahn DW, Masters EJ, Masters EJ, Grunwaldt E, Gadgil SD. Azithromycin compared with amoxicillin iGrunwaldt E, Gadgil SD. Azithromycin compared with amoxicillin in the treatment of n the treatment of erythema migrans. A doubleerythema migrans. A double--blind, randomized, controlled trial. Ann Intern Med 1996 blind, randomized, controlled trial. Ann Intern Med 1996 May 1; 124(9):785May 1; 124(9):785--91.91.

Luft BJ, Volkman DJ, Halperin JJ, Dattwyler RJ. New chemotherapeLuft BJ, Volkman DJ, Halperin JJ, Dattwyler RJ. New chemotherapeutic approaches utic approaches in the treatment of Lyme borreliosis. Ann N Y Acad Sci 1988; 539in the treatment of Lyme borreliosis. Ann N Y Acad Sci 1988; 539:352:352--61.61.

MacDonald AB, Berger BW, Schwan TG. Clinical implications of delMacDonald AB, Berger BW, Schwan TG. Clinical implications of delayed growth of ayed growth of the Lyme borreliosis spirochete, Borrelia burgdorferi. Acta Tropthe Lyme borreliosis spirochete, Borrelia burgdorferi. Acta Trop 1990. Dec; 48(2):891990. Dec; 48(2):89--94.94.

Mursic VP, Wanner G, reinhardt S, Wilske B, Busch U, Marget W. FMursic VP, Wanner G, reinhardt S, Wilske B, Busch U, Marget W. Formation and ormation and cultivation of Borrelia burgdorferi spheroplast Lcultivation of Borrelia burgdorferi spheroplast L--form variants. Infection 1996; form variants. Infection 1996; 24(3):21824(3):218--26.26.

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Oksi, J et al. Borrelia burgdorferi detected by culture and PCR Oksi, J et al. Borrelia burgdorferi detected by culture and PCR in clinical relapse of in clinical relapse of disseminated Lyme borreliosis. Ann med, 1999. 31)3):p225disseminated Lyme borreliosis. Ann med, 1999. 31)3):p225--32.32.

Oksi J, Kalimo H, Marttila RJ, Marjamaki M, Sonninen P, NikoskelOksi J, Kalimo H, Marttila RJ, Marjamaki M, Sonninen P, Nikoskelainen J, Vilijanen ainen J, Vilijanen MK. Inflammatory brain changes in Lyme borreliosis. A report on MK. Inflammatory brain changes in Lyme borreliosis. A report on three patients and three patients and review of literature. Brain 1996. Dec; 119 (Pt6):2143review of literature. Brain 1996. Dec; 119 (Pt6):2143--54.54.

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Petrovic M, Vogelaers D, Van Renterghem, Carton D, De Reuck J, APetrovic M, Vogelaers D, Van Renterghem, Carton D, De Reuck J, Afschrift M. Lyme fschrift M. Lyme borreliosis borreliosis -- a review of the late stages and treatment of four cases. Acta Ca review of the late stages and treatment of four cases. Acta Clin Belg lin Belg 1998. Jun 53(3):1781998. Jun 53(3):178--83.83.

PreacPreac--Mursic V, Weber K, Pfister HW, Wilske B, Gross B, Baumann A, ProMursic V, Weber K, Pfister HW, Wilske B, Gross B, Baumann A, Prokop J. kop J. Survival of Borrelia burgdorferi in antibiotically treated patieSurvival of Borrelia burgdorferi in antibiotically treated patients with Lyme borreliosis. nts with Lyme borreliosis. Infection 1989 NovInfection 1989 Nov--Dec; 17(6):355Dec; 17(6):355--9.9.

Schoen RT. Treatment of Lyme disease. Conn Med 1989. Jun; 53(6):Schoen RT. Treatment of Lyme disease. Conn Med 1989. Jun; 53(6):335335--7.7.

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Steere AC. Lyme disease. N Engl J Med 1989. Aug 31; 321(9):586Steere AC. Lyme disease. N Engl J Med 1989. Aug 31; 321(9):586--96.96.

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Treib J, Fernandez A, Haass A, Grauer MT, Holzer G, Woessner R. Treib J, Fernandez A, Haass A, Grauer MT, Holzer G, Woessner R. Clinical and Clinical and serologic followserologic follow--up in patients with neuroborreliosis. Neurology 1998 Nov; up in patients with neuroborreliosis. Neurology 1998 Nov; 51(5):148951(5):1489--91. 91.

Valesova H, Mailer J, Havlik J, Hulinska D, Hercogova J. LongValesova H, Mailer J, Havlik J, Hulinska D, Hercogova J. Long--term results in term results in patients with Lyme arthritis following treatment with ceftriaxonpatients with Lyme arthritis following treatment with ceftriaxone. Infection 1996; e. Infection 1996; 24(1)9824(1)98--102.102.

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Weber K. Treatment failure in erythema migrans: a review. InfectWeber K. Treatment failure in erythema migrans: a review. Infection 1996; 24:73ion 1996; 24:73--5.5.

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Zamponi N, Cardinali C, Tavoni, MA, Porfiri L, Rossi R, Manca A.Zamponi N, Cardinali C, Tavoni, MA, Porfiri L, Rossi R, Manca A. Chronic Chronic neuroborreliosis in infancy. Ital J Neurol Sci 1999 Oct; 20(5):3neuroborreliosis in infancy. Ital J Neurol Sci 1999 Oct; 20(5):30303--7.7.

Ziska MH, Donta ST, Demarest FC. Physician preferences in the diZiska MH, Donta ST, Demarest FC. Physician preferences in the diagnosis and agnosis and treatment of Lyme disease in the United States. Infection 1996. treatment of Lyme disease in the United States. Infection 1996. MarMar--Apr; 24(2):182Apr; 24(2):182--6.6.

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Treatment of Chronic LymeTreatment of Chronic Lyme

What should one start with?What should one start with?

Doxycycline 100mg tid or minocycline 100mg bid is a good first Doxycycline 100mg tid or minocycline 100mg bid is a good first choice. Use for 6 weeks before considering adding a second agenchoice. Use for 6 weeks before considering adding a second agent t or starting parenteral therapyor starting parenteral therapy

Alternatively, may start with cefdinir 300mg bidAlternatively, may start with cefdinir 300mg bid--tid or cefuroxime tid or cefuroxime 500mg bid500mg bid--tid or amoxicillin 875mg tidtid or amoxicillin 875mg tid

After 3After 3--8 weeks, may increase dose or add a second agent8 weeks, may increase dose or add a second agent

Become comfortable with a few antibiotics. Know their side effect profiles. Consider increasing the dose before adding a second agent.

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What should one start with?

The second agent should be of a different class and work by a different mechanism.

Azithromycin 500 - 600mg qd or clarithromycin 500mg bid is often a good choice if first medicine is a beta-lactam antibiotic.

While the tetracyclines and the macrolides are both ribosomal inhibitors and often not used in combination, in actual practice, this combination has proven quite effective for Lyme.

When choosing an antibiotic think about intracellular activity, central nervous system penetration, bactericidal vs bacteriostatic activity and likelihood of patient compliance. Know how much each medicine costs.

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Recommend against using macrolides as monotherapy for more than 4 weeks due to possible resistance.

Benzathine PCN 1.2 million units 2-3x/week is a good adjunctive treatment as it has good CNS penetration.

Metronidazole/Tinidazole is useful as pulse therapy 2-3 months at a time. Do not use without a cell wall-active drug.

Many ILADS doctors recommend treating two months past the resolution of active symptoms. This can take more than a year.

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Most patients with severe chronic persistent neuroborreliosis will require parenteral therapy. Recommend oral meds for 3-4 months prior to starting IV or IM.

Parenteral drug of choice is Ceftriaxone 2 grams qd-bid 4-7 days a week.

Cefotaxime 2 grams tid or Ampicillin 2-4grams tid-qid is also effective.

Ceftriaxone is not a miracle drug. Very ill patients may be on this for more than one year. It should be used with an intracellular oral drug for at least part of the treatment. Also one should use ursodiol with Ceftriaxone to protect gallbladder.

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Prescribe one or more intracellular acting drugs (doxy, mino, maPrescribe one or more intracellular acting drugs (doxy, mino, macrolides, ketolide, crolides, ketolide, rifampin, quinolones, sulfa.rifampin, quinolones, sulfa.

A cell wall (BA cell wall (B--lactam) antibiotic (PCN, cephalosporin, carbapenem, vancomycin).lactam) antibiotic (PCN, cephalosporin, carbapenem, vancomycin).

A cyst buster (metronidazole, tinidazole, nitrosoxamide, hydroxyA cyst buster (metronidazole, tinidazole, nitrosoxamide, hydroxychloroquine).chloroquine).

The problem is tolerance. One has to tread a fine line. A greaThe problem is tolerance. One has to tread a fine line. A great regimen could be t regimen could be Ketek, doxycycline, Omnicef and metronidazole were it not so toxKetek, doxycycline, Omnicef and metronidazole were it not so toxic and the poor ic and the poor interaction between doxycycline and metronidazole.interaction between doxycycline and metronidazole.

A more realistic approach would be to change combinations regulaA more realistic approach would be to change combinations regularly (q 6rly (q 6--12 12 weeks) to affect different properties of the organism.weeks) to affect different properties of the organism.

I ramp up most patients slowly, maintaining them on two or more I ramp up most patients slowly, maintaining them on two or more medications.medications.

78

Advanced antibiotic strategiesAdvanced antibiotic strategies

After a patient has had 6After a patient has had 6--8 months of ceftriaxone or similar drug, the options 8 months of ceftriaxone or similar drug, the options for care become more complex. for care become more complex.

If a patient has had an IV cell wall drug with or without an intIf a patient has had an IV cell wall drug with or without an intracellular and a racellular and a cyst buster, I would often add IV azithromycin (500mg over 2cyst buster, I would often add IV azithromycin (500mg over 2--3 hours) or 3 hours) or doxycycline (400 mg bolus over 3 hours). In addition I might usdoxycycline (400 mg bolus over 3 hours). In addition I might use Imipenem, e Imipenem, meropenem, or ertapenem (Invanz) instead of the cephalosporin. meropenem, or ertapenem (Invanz) instead of the cephalosporin. After 3After 3--6 6 weeks one could switch one of the drugs for IV Flagyl. Later onweeks one could switch one of the drugs for IV Flagyl. Later one might e might consider Zosyn or Tygacil, pulsed for 3consider Zosyn or Tygacil, pulsed for 3--4 weeks.4 weeks.

If coIf co--infections have already been treated with standard orals, can roinfections have already been treated with standard orals, can rotate IV tate IV levofloxacin, moxifloxacin, clindamycin or IV rifampin.levofloxacin, moxifloxacin, clindamycin or IV rifampin.

Many herbal protocols can be used in addition.Many herbal protocols can be used in addition.

79

Intravenous AntibioticsIntravenous Antibiotics

80

Ceftriaxone (Rocephin)Ceftriaxone (Rocephin)

Pharmacologic CategoryPharmacologic CategoryCephalosporin (3Cephalosporin (3rdrd generation)generation)

Empirical FormulaEmpirical FormulaCC1818HH1818NN88OO77SS33

Structural FormulaStructural Formula

81


Mechanism of ActionMechanism of ActionBactericidalBactericidalInhibits bacterial cell wall synthesisInhibits bacterial cell wall synthesis

Binds to one or more of the penicillinBinds to one or more of the penicillin--binding proteins (PBPs) binding proteins (PBPs) Inhibits final transpeptidation step of peptidoglycan synthesis Inhibits final transpeptidation step of peptidoglycan synthesis in in bacterial cell walls bacterial cell walls Inhibits cell wall biosynthesis Inhibits cell wall biosynthesis Bacteria eventually lyse due to ongoing activity of cell wall auBacteria eventually lyse due to ongoing activity of cell wall autolytic tolytic enzymes while cell wall assembly is arrestedenzymes while cell wall assembly is arrested

DosageDosage2 grams IM qd, 42 grams IM qd, 4--5 days a week5 days a week2 grams IV qd, 7 days a week2 grams IV qd, 7 days a week2 grams IV bid, 4 days a week2 grams IV bid, 4 days a week

82


Warnings/PrecautionsWarnings/PrecautionsGallbladder diseaseGallbladder diseasePrecipitation caused by calciumPrecipitation caused by calcium--containing containing productsproducts

Prescribing InformationPrescribing Informationhttp://www.gene.com/gene/products/informatihttp://www.gene.com/gene/products/information/rocephin/pdf/pi.pdfon/rocephin/pdf/pi.pdf

83

Cefotaxime (Claforan)Cefotaxime (Claforan)

Pharmacologic CategoryPharmacologic CategoryCephalosporinsCephalosporins

Empirical FormulaEmpirical FormulaCC1616HH1616NN55NaONaO77SS22


84


Mechanism of ActionMechanism of ActionBactericidalBactericidalInhibits cell well synthesisInhibits cell well synthesis

DosageDosage2 grams IV q8h2 grams IV q8h

85


Warnings/PrecautionsWarnings/PrecautionsMost frequent adverse reactions include CNS Most frequent adverse reactions include CNS (0.2%),(0.2%), GI GI (1.7%),(1.7%), GU GU (<1%),(<1%), Hematologic Hematologic (<1%)(<1%)

Prescribing InformationPrescribing Informationhttp://products.sanofihttp://products.sanofi--aventis.us/claforan/claforan.pdfaventis.us/claforan/claforan.pdf

86

Imipenem/Cilastatin (Primaxin)Imipenem/Cilastatin (Primaxin)

Pharmacologic CategoryPharmacologic CategoryCarbapenemsCarbapenems

Empirical FormulaEmpirical FormulaCC1212HH1717NN33OO44SS••HH22O / CO / C1616HH2525NN22OO55SNaSNa


87


Mechanism of ActionMechanism of ActionBactericidalBactericidalInhibits cell wall synthesisInhibits cell wall synthesis

DosageDosage1 gram IV q12h1 gram IV q12h

88


Warnings/PrecautionsWarnings/PrecautionsMost frequently reported systemic adverse reactions Most frequently reported systemic adverse reactions were nausea were nausea (2%),(2%), diarrhea diarrhea (1.8%),(1.8%), vomiting vomiting (1.5%),(1.5%), rash rash (0.9%),(0.9%), fever fever (0.5%),(0.5%), hypotension hypotension (0.4%),(0.4%), seizures seizures (0.4%),(0.4%),dizziness dizziness (0.3%),(0.3%), pruritis pruritis (0.3%),(0.3%), urticaria urticaria (0.2%),(0.2%),somnolence somnolence (0.2%)(0.2%)

Prescribing InformationPrescribing Informationhttp://www.merck.com/product/usa/pi_circulars/p/primhttp://www.merck.com/product/usa/pi_circulars/p/primaxin/primaxin_iv_pi.pdfaxin/primaxin_iv_pi.pdf

89

Ertapenem (Invanz)Ertapenem (Invanz)


Empirical FormulaEmpirical FormulaCC2222HH2424NN33OO77SNaSNa


90



DosageDosage1 gram IM qd1 gram IM qd1 gram IV qd1 gram IV qd

91


Warnings/PrecautionsWarnings/PrecautionsMost common adverse reactions were Most common adverse reactions were diarrhea diarrhea (5.5%),(5.5%), infused vein complication infused vein complication (3.7%),(3.7%),nausea nausea (3.1%),(3.1%), headache headache (2.2%),(2.2%), vaginitis in vaginitis in females females (2.1%),(2.1%), phlebitis/thrombophlebitis phlebitis/thrombophlebitis (1.3%)(1.3%)

and vomiting and vomiting (1.1%)(1.1%)

Prescribing InformationPrescribing Informationhttp://www.merck.com/product/usa/pi_circularhttp://www.merck.com/product/usa/pi_circulars/i/invanz/invanz_pi.pdfs/i/invanz/invanz_pi.pdf

92

Meropenem (Merrem)Meropenem (Merrem)


Empirical FormulaEmpirical FormulaCC1717HH2525NN33OO55SS••3H3H22O O


93



Penetrates bacterial cells readily and interferes Penetrates bacterial cells readily and interferes with the synthesis of vital cell wall components, with the synthesis of vital cell wall components, leading to cell deathleading to cell death

DosageDosage2 grams IV q8h2 grams IV q8h

94


Warnings/PrecautionsWarnings/PrecautionsMost common systemic adverse reactions Most common systemic adverse reactions include diarrhea include diarrhea (4.8%),(4.8%), nausea/vomiting nausea/vomiting (3.6%),(3.6%),

headache headache (2.3%),(2.3%), rash rash (1.9%),(1.9%), sepsis sepsis (1.6%),(1.6%),

constipation constipation (1.4%),(1.4%), apnea apnea (1.3%),(1.3%), shock shock (1.2%),(1.2%), and and pruritis pruritis (1.2%)(1.2%)

Prescribing InformationPrescribing Informationhttp://www1.astrazenecahttp://www1.astrazeneca--us.com/pi/MerremIV.pdfus.com/pi/MerremIV.pdf

95

Azithromycin (Zithromax)Azithromycin (Zithromax)

Pharmacologic CategoryPharmacologic CategoryMacrolidesMacrolides

Empirical FormulaEmpirical FormulaCC3838HH7272NN22OO1212


96


Mechanism of ActionMechanism of ActionBacteriostaticBacteriostaticInhibits protein synthesisInhibits protein synthesis

Binds to the 50S ribosomal subunit and inhibits Binds to the 50S ribosomal subunit and inhibits translocation of the peptidyl tRNA from the A to the translocation of the peptidyl tRNA from the A to the P siteP site

Nucleic acid synthesis is not affectedNucleic acid synthesis is not affected

DosageDosage500 mg IV qd, 5500 mg IV qd, 5--7 days a week7 days a week

97


Warnings/PrecautionsWarnings/PrecautionsMost common adverse reactions include Most common adverse reactions include diarrhea, nausea, abdominal pain, vomiting, diarrhea, nausea, abdominal pain, vomiting, anorexia, rash, pruritisanorexia, rash, pruritis

Prescribing InformationPrescribing Informationhttp://www.pfizer.com/files/products/uspi_zithrhttp://www.pfizer.com/files/products/uspi_zithromaxIV.pdfomaxIV.pdf

98

Doxycycline (Vibramycin)Doxycycline (Vibramycin)

Pharmacologic CategoryPharmacologic CategoryTetracyclineTetracycline

Empirical FormulaEmpirical Formula(C(C2222HH2424NN22OO88••HCl)HCl)22••CC22HH55OO••HH22O O


99


Mechanism of ActionMechanism of ActionBacteriostaticBacteriostaticInhibits protein synthesisInhibits protein synthesis

Reversibly binds to the 30S ribosomal subunit and Reversibly binds to the 30S ribosomal subunit and inhibits binding of aminoacyl tRNA to the acceptor inhibits binding of aminoacyl tRNA to the acceptor site on the 70S ribosomesite on the 70S ribosome

DosageDosage300300--400mg IV qd400mg IV qd

100


Warnings/PrecautionsWarnings/PrecautionsCaution against dental discoloration and sun Caution against dental discoloration and sun sensitivitysensitivitySide effects include diarrhea, loss of appetite, Side effects include diarrhea, loss of appetite, nausea, vomiting, headache, rectal discomfortnausea, vomiting, headache, rectal discomfort

Prescribing InformationPrescribing Informationhttp://www.bedfordlabs.com/products/inserts/http://www.bedfordlabs.com/products/inserts/DivDiv--DCYDCY--P03.pdfP03.pdf

101

Tigecycline (Tygacil)Tigecycline (Tygacil)

Pharmacologic CategoryPharmacologic CategoryGlycylcyclinesGlycylcyclines

semisemi--synthetic derivatives of tetracycline with a glycylamido synthetic derivatives of tetracycline with a glycylamido moiety attached at the 9 position of the Dmoiety attached at the 9 position of the D--ring of the base ring of the base moleculemolecule



102


Mechanism of ActionMechanism of ActionInhibits protein translation Inhibits protein translation

Binds to the 30S ribosomal subunit and blocks Binds to the 30S ribosomal subunit and blocks entry of aminoentry of amino--acyl tRNA molecules into the A site acyl tRNA molecules into the A site of the ribosomeof the ribosomeThis prevents incorporation of amino acid residues This prevents incorporation of amino acid residues into elongating peptide chainsinto elongating peptide chains

DosageDosage50mg IV q12h50mg IV q12h

103


Warnings/PrecautionsWarnings/PrecautionsMost common adverse reactions include Most common adverse reactions include nausea, vomiting, diarrhea, abdominal pain, nausea, vomiting, diarrhea, abdominal pain, headache, and increased SGPTheadache, and increased SGPT

Prescribing InformationPrescribing Informationhttp://www.pfizerpro.com/content/showlabelinhttp://www.pfizerpro.com/content/showlabeling.asp?id=491g.asp?id=491

104

Clindamycin (Cleocin)Clindamycin (Cleocin)

Pharmacologic CategoryPharmacologic CategoryLincosamidesLincosamides

Empirical FormulaEmpirical FormulaCC1818HH3434CINCIN220088PS PS


105


Mechanism of ActionMechanism of ActionBacteriostaticBacteriostaticInhibits bacterial protein synthesisInhibits bacterial protein synthesis

Inhibits ribosomal translocation by binding Inhibits ribosomal translocation by binding preferentially to the 23S rRNA of the large bacterial preferentially to the 23S rRNA of the large bacterial ribosome subunitribosome subunit


106


Warnings/PrecautionsWarnings/PrecautionsClostridium difficileClostridium difficile associated diarrhea!associated diarrhea!

Prescribing InformationPrescribing Informationhttp://www.pfizer.com/files/products/uspi_cleohttp://www.pfizer.com/files/products/uspi_cleocin_phosphate.pdfcin_phosphate.pdf

107

Metronidazole (Flagyl)Metronidazole (Flagyl)

Pharmacologic CategoryPharmacologic CategoryNitroimidazoleNitroimidazole



108


Mechanism of ActionMechanism of ActionInhibits nucleic acid synthesisInhibits nucleic acid synthesis

Disrupts the DNADisrupts the DNA’’s helical structure resulting in s helical structure resulting in bacterial cell deathbacterial cell death


109


Warnings/PrecautionsWarnings/PrecautionsAvoid alcoholic beveragesAvoid alcoholic beveragesMost common adverse reactions include nausea, Most common adverse reactions include nausea, sometimes accompanied by headache, anorexia, and sometimes accompanied by headache, anorexia, and occasionally vomiting; diarrhea; epigastric distress; occasionally vomiting; diarrhea; epigastric distress; and abdominal crampingand abdominal cramping

Prescribing InformationPrescribing Informationhttp://www.pfizer.com/files/products/uspi_flagyl.pdfhttp://www.pfizer.com/files/products/uspi_flagyl.pdf

110

AmpicillinAmpicillin

Pharmacologic CategoryPharmacologic CategoryPenicillinPenicillin

Empirical FormulaEmpirical FormulaCC1616HH1919NN33OO44SS


111



DosageDosage

112


Warnings/PrecautionsWarnings/PrecautionsDo not administer in patients with Do not administer in patients with mononucleosismononucleosis

Prescribing InformationPrescribing Informationhttp://www.sagentpharma.com/Products/Ampihttp://www.sagentpharma.com/Products/Ampicillin/Catalog/Ampicillin_PI1.pdfcillin/Catalog/Ampicillin_PI1.pdf

113

Ampicillin/Sulbactam (Unasyn)Ampicillin/Sulbactam (Unasyn)

Pharmacologic CategoryPharmacologic CategoryPenicillin + Penicillin + ββ--lactamase inhibitorlactamase inhibitor

Empirical FormulaEmpirical FormulaCC1616HH1818NN33NaONaO44S / CS / C88HH1010NNaONNaO55SS


114


Mechanism of ActionMechanism of ActionBactericidalBactericidalAmpicillin inhibits cell wall mucopeptide Ampicillin inhibits cell wall mucopeptide biosynthesisbiosynthesisSulbactam inhibits betaSulbactam inhibits beta--lactamases, allowing lactamases, allowing ampicillin to attack and kill the bacteriaampicillin to attack and kill the bacteria

DosageDosage

115


Warnings/PrecautionsWarnings/PrecautionsDo not administer in patients with Do not administer in patients with mononucleosismononucleosisMost common systemic reactions are diarrhea Most common systemic reactions are diarrhea (3%)(3%) and rash and rash (<2%).(<2%).

Prescribing InformationPrescribing Informationhttp://www.pfizer.com/files/products/uspi_unahttp://www.pfizer.com/files/products/uspi_unasyn.pdfsyn.pdf

116

Piperacillin/Tazobactam (Zosyn)Piperacillin/Tazobactam (Zosyn)

Pharmacologic CategoryPharmacologic CategoryPenicillin + Penicillin + ββ--lactamase inhibitorlactamase inhibitor

Empirical FormulaEmpirical FormulaCC2323HH2626NN55NaONaO77S / CS / C1010HH1111NN44NaONaO55S S


117


Mechanism of ActionMechanism of ActionBactericidalBactericidalPiperacillin inhibits septum formation and cell Piperacillin inhibits septum formation and cell wall synthesiswall synthesisTazobactam inhibits betaTazobactam inhibits beta--lactamases lactamases

DosageDosage

118


Warnings/PrecautionsWarnings/PrecautionsMost common adverse reactions include diarrhea, Most common adverse reactions include diarrhea, headache, constipation, nausea, insomnia, rash, headache, constipation, nausea, insomnia, rash, vomiting, dyspepsia, pruritis, stool changes, fever, vomiting, dyspepsia, pruritis, stool changes, fever, agitation, pain, moniliasis, hypertension, dizziness, agitation, pain, moniliasis, hypertension, dizziness, abdominal pain, chest pain, edema, anxiety, rhinitis, abdominal pain, chest pain, edema, anxiety, rhinitis, and dyspnea.and dyspnea.

Prescribing InformationPrescribing Informationhttp://www.pfizerpro.com/content/showlabeling.asp?idhttp://www.pfizerpro.com/content/showlabeling.asp?id=477=477

119

Linezolid (Zyvox)Linezolid (Zyvox)

Pharmacologic CategoryPharmacologic CategoryOxazolidinone Oxazolidinone

Empirical FormulaEmpirical FormulaCC1616HH2020FNFN33OO44


120


Mechanism of ActionMechanism of ActionBinds to a site on the bacterial 23S ribosomal Binds to a site on the bacterial 23S ribosomal RNA of the 50S subunit and prevents the RNA of the 50S subunit and prevents the formation of a functional 70S initiation formation of a functional 70S initiation complex, which is an essential component of complex, which is an essential component of the bacterial translation processthe bacterial translation process

DosageDosage

121


Warnings/PrecautionsWarnings/PrecautionsMyelosuppression (including anemia, leukopenia, Myelosuppression (including anemia, leukopenia, pancytopenia, and thrombocytopenia) and lactic pancytopenia, and thrombocytopenia) and lactic acidosis have been reportedacidosis have been reportedMonitor weekly CBCsMonitor weekly CBCsMost common adverse reactions include diarrhea Most common adverse reactions include diarrhea (2.8%(2.8%--11%),11%), headache headache (0.5%(0.5%--11.3%)11.3%) and nausea and nausea (3.4%(3.4%--9.6%)9.6%)

Prescribing InformationPrescribing Informationhttp://media.pfizer.com/files/products/uspi_zyvox.pdfhttp://media.pfizer.com/files/products/uspi_zyvox.pdf

122

Rifampin (Rifadin)Rifampin (Rifadin)

Pharmacologic CategoryPharmacologic CategoryDerivative of rifamycinDerivative of rifamycin



123


Mechanism of ActionMechanism of ActionInhibits RNA synthesisInhibits RNA synthesis

Blocks RNA transcriptionBlocks RNA transcription

DosageDosage600mg IV qd600mg IV qd

124


Warnings/PrecautionsWarnings/PrecautionsCan enhance metabolism of endogenous substrates, Can enhance metabolism of endogenous substrates, including adrenal hormone, thyroid hormones, and including adrenal hormone, thyroid hormones, and vitamin Dvitamin DCan elevate sex hormone binding globulinCan elevate sex hormone binding globulinCan produce a reddish coloration of bodily fluidsCan produce a reddish coloration of bodily fluidsMany drugMany drug--drug interactionsdrug interactions

Prescribing InformationPrescribing Informationhttp://products.sanofihttp://products.sanofi--aventis.us/rifadin/Rifadin.pdfaventis.us/rifadin/Rifadin.pdf

125

Moxifloxacin (Avelox)Moxifloxacin (Avelox)

Pharmacologic CategoryPharmacologic CategoryQuinolonesQuinolones



126


Mechanism of ActionMechanism of ActionBactericidalBactericidalInhibits topoisomerase II (DNA gyrase) and Inhibits topoisomerase II (DNA gyrase) and topoisomerase IV required for bacterial DNA topoisomerase IV required for bacterial DNA replication, transcription, repair, and recombination. replication, transcription, repair, and recombination. MOA is different from that of macrolides, betaMOA is different from that of macrolides, beta--lactams, aminoglycosides, or tetracyclineslactams, aminoglycosides, or tetracyclines


127


Warnings/PrecautionsWarnings/PrecautionsIncreased risk of tendinitis and tendon ruptureIncreased risk of tendinitis and tendon ruptureMay produce changes in an electrocardiogram (QTc May produce changes in an electrocardiogram (QTc interval prolongation)interval prolongation)Most common adverse reactions include nausea Most common adverse reactions include nausea (6%),(6%),

diarrhea diarrhea (5%),(5%), and dizziness and dizziness (2%)(2%)

Prescribing InformationPrescribing Informationhttp://www.avelox.com/html/pdf/avelox_prescribing.pdhttp://www.avelox.com/html/pdf/avelox_prescribing.pdff

128

Levofloxacin (Levaquin)Levofloxacin (Levaquin)

Pharmacologic CategoryPharmacologic CategoryQuinolonesQuinolones



129


Mechanism of ActionMechanism of ActionInhibits bacterial topoisomerase IV and DNA gyrase Inhibits bacterial topoisomerase IV and DNA gyrase (both of which are type II topoisomerases), enzymes (both of which are type II topoisomerases), enzymes required for DNA replication, transcription, repair and required for DNA replication, transcription, repair and recombinationrecombinationMOA is different from that of aminoglycosides, MOA is different from that of aminoglycosides, macrolides, and betamacrolides, and beta--lactamslactams


130


Warnings/PrecautionsWarnings/PrecautionsIncreased risk of tendinitis and tendon ruptureIncreased risk of tendinitis and tendon ruptureMost common adverse reactions include Most common adverse reactions include nausea, headache, diarrhea, insomnia, nausea, headache, diarrhea, insomnia, constipation, and dizzinessconstipation, and dizziness

Prescribing InformationPrescribing Informationhttp://www.levaquin.com/sites/default/files/pdf/http://www.levaquin.com/sites/default/files/pdf/levaquin.pdf#zoom=100levaquin.pdf#zoom=100

131

Case # 1 (JR)Case # 1 (JR)

132

Case # 2 (JS)Case # 2 (JS)

133

Case # 3 (LH)Case # 3 (LH)

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