clinical aspects of antimicrobial therapy

Clinical Aspects Clinical Aspects of Antimicrobial of Antimicrobial Therapy Therapy

CONTENTS OF LECTURE CONTENTS OF LECTURE

Empiric Antibiotic GuidelinesEmpiric Antibiotic Guidelines Antibiotic Policy, Audit, SurveillanceAntibiotic Policy, Audit, Surveillance Summary of commonly used Summary of commonly used

antibioticsantibiotics For this session a copy of the For this session a copy of the

Empiric Antibiotics guidelines for SJH Empiric Antibiotics guidelines for SJH should be used by each student for should be used by each student for clinical scenariosclinical scenarios

ANTIBIOTICSANTIBIOTICS

May be: May be: BacteriostaticBacteriostatic – inhibits growth of – inhibits growth of

Bacteria, so acts by preventing Bacteria, so acts by preventing bacteria from multiplying and then bacteria from multiplying and then hosts defences deal with the small hosts defences deal with the small number of bacteria leftnumber of bacteria left

BactericidialBactericidial – kills Bacteria, so – kills Bacteria, so eliminates bacteriaeliminates bacteria

Available www.ndsc.ie

SARI REPORT APRIL 2001 SARI REPORT APRIL 2001 RECOMMENDED RECOMMENDED STRATEGIESSTRATEGIES

Recommended Recommended InfrastructureInfrastructure

Surveillance Surveillance of of Antimicrobial Antimicrobial ResistanceResistance

National National Reference Reference LaboratoriesLaboratories

Monitoring Monitoring Supply Supply and and UseUse of of AntimicrobialsAntimicrobials

Development of Development of Guidance for Guidance for Appropriate Use of Appropriate Use of AntibioticsAntibiotics

EducationEducation in relation in relation to appropriate use of to appropriate use of AntibioticsAntibiotics

Development ofDevelopment of Principles Principles in relation in relation to to Infection ControlInfection Control

Future Future ResearchResearch in in the Areathe Area

On www.ndsc.ieOn www.ndsc.ie

St.James`s Hospital St.James`s Hospital Empiric Antibiotic Empiric Antibiotic Guidelines-June 2005 Guidelines-June 2005

St.James`s Hospital Empiric St.James`s Hospital Empiric Antibiotic Guidelines-June Antibiotic Guidelines-June 20052005

These guidelines are developed on a These guidelines are developed on a yearly basis by the Antimicrobial yearly basis by the Antimicrobial Sub-Committee of the Pharmacy and Sub-Committee of the Pharmacy and Therapeutics Committee. Printed in Therapeutics Committee. Printed in the Prescriber`s guide, distributed the Prescriber`s guide, distributed throughout the hospital ( all doctors, throughout the hospital ( all doctors, pharmacists, wards etc) and pharmacists, wards etc) and available on the St.James`s intranetavailable on the St.James`s intranet

Objectives- to Objectives- to understand :understand :

Principles of Antibiotic GuidelinesPrinciples of Antibiotic Guidelines Therapeutic Drug Therapeutic Drug

Monitoring( Glycopeptides, Monitoring( Glycopeptides, Aminoglycosides)Aminoglycosides)

Guidelines for Empiric Treatment of Guidelines for Empiric Treatment of common infectionscommon infections

Principles of Surgical ProphylaxisPrinciples of Surgical Prophylaxis Empiric guidelines for Surgical Empiric guidelines for Surgical

ProphylaxisProphylaxis Guidelines for the prevention of Guidelines for the prevention of

EndocarditisEndocarditis

Principles of Antibiotic Principles of Antibiotic GuidelinesGuidelines

Guide to the empiric use of Guide to the empiric use of antibiotics.antibiotics.

Empiric treatment is the choice of Empiric treatment is the choice of antibiotic prior to sensitivity results antibiotic prior to sensitivity results being availablebeing available

Avoid unnecessary use .If clinically Avoid unnecessary use .If clinically feasible await results of feasible await results of microscopy/culture/susceptibility microscopy/culture/susceptibility data for directed therapydata for directed therapy


Specimens for microbiology should be Specimens for microbiology should be taken prior to commencement of empiric taken prior to commencement of empiric treatemnt. In an emergency , at a treatemnt. In an emergency , at a minimum a set of blood cultures should minimum a set of blood cultures should be taken e.g meningitis.be taken e.g meningitis.

Ensure any history of allergy is Ensure any history of allergy is documented on the cover of notes and documented on the cover of notes and drug kardex prior to commencing drug kardex prior to commencing antibioticsantibiotics

Prescribing PracticePrescribing Practice-Document reason for starting agent or any -Document reason for starting agent or any

changechange


Empiric antibiotics should be Empiric antibiotics should be reviewed once Gram satin/ reviewed once Gram satin/ mcroscopy/culture/sensitivity or mcroscopy/culture/sensitivity or PCR available.Empiric therapy PCR available.Empiric therapy should be changed to directed should be changed to directed therapy as soon as possible. therapy as soon as possible. Directed therapyDirected therapy should be the should be the narrowest spectrum antibiotic to narrowest spectrum antibiotic to adequately cover the pathogensadequately cover the pathogens


Pharmacokinetics and Pharmacodynamics Pharmacokinetics and Pharmacodynamics issues may necessitate dose issues may necessitate dose adjustments( e.g renal impairment etc). adjustments( e.g renal impairment etc). Doses of antibiotics should take into Doses of antibiotics should take into account creatinine clearance and review account creatinine clearance and review regularly. Consider co prescribed regularly. Consider co prescribed interacting drugsinteracting drugs

Refer to BNF, hospital pharmacist, Refer to BNF, hospital pharmacist, Microbiologist or Infectious disease Microbiologist or Infectious disease physician if advice about dose is requiredphysician if advice about dose is required

DefinitionsDefinitions

PharmacokineticPharmacokineticss

Mathematical Mathematical study of the rate study of the rate process involved process involved in absorption, in absorption, distribution, distribution, metabolism and metabolism and excretionexcretion

PharmacodynamicsPharmacodynamics Time course of drug Time course of drug

effects and other effects and other interactions interactions between between antimicrobials and antimicrobials and the bacterium(MIC, the bacterium(MIC, Post Antibiotic Post Antibiotic Effect and Effect and interactions interactions between the between the immune system immune system and the agent)and the agent)


All antibiotic prescriptions should be All antibiotic prescriptions should be reviewed after 48 hoursreviewed after 48 hours

Consider i/v to oral switchConsider i/v to oral switch In general avoid topical antibiotic use. In general avoid topical antibiotic use.

When topical antibiotics are used do not When topical antibiotics are used do not use antibiotic used systemicallyuse antibiotic used systemically

Consultations from Clinical Microbiology Consultations from Clinical Microbiology ext.2039 or Infectious Diseases Bleep ext.2039 or Infectious Diseases Bleep 192 or ext. 2507/2402 are encouraged192 or ext. 2507/2402 are encouraged

General Principles of General Principles of TherapyTherapy

Avoid unnecessary useAvoid unnecessary use- e.g clinical well - e.g clinical well patient and CSU colonization, leg ulcers patient and CSU colonization, leg ulcers colonization, post-operative atelectasiscolonization, post-operative atelectasis

Choice of suitable drugChoice of suitable drug Toxicity e;g allergy, enhancement of Toxicity e;g allergy, enhancement of

toxicity, change of flora etctoxicity, change of flora etc Combined therapy Combined therapy Prescribing PracticePrescribing Practice-Document reason for starting agent or any -Document reason for starting agent or any

changechange


- Generic names to be usedGeneric names to be used- Specify dose, number of doses or period of Specify dose, number of doses or period of

time , review at 48 hours with results of time , review at 48 hours with results of investigations and clinical statusinvestigations and clinical status

- If no improvement within 36-48 hours checkIf no improvement within 36-48 hours check- (1) Adequate dose and /or level of drug(1) Adequate dose and /or level of drug- (2) Host defences e.g drain abscess, removal (2) Host defences e.g drain abscess, removal

of foreign material etcof foreign material etc- (3) Is the drug active against fastidious or (3) Is the drug active against fastidious or

difficult organisms to isolate, consult with difficult organisms to isolate, consult with microbiologistmicrobiologist


Do regular antibiotic rounds/review use to Do regular antibiotic rounds/review use to avoid unnecessary prolonged coursesavoid unnecessary prolonged courses

Oral if possible instead of I/V preparations Oral if possible instead of I/V preparations Criteria for I/V to Oral switchCriteria for I/V to Oral switch

-Fever settled-Fever settled

-wcc returning to normal-wcc returning to normal

-Patient clinically stable-Patient clinically stable

-No gastrointestinal upset-No gastrointestinal upset


Reserve AntibioticsReserve Antibiotics- Use to be discussed with consultant Use to be discussed with consultant

or microbiologist or microbiologist - Reasons are to preserve usefulness Reasons are to preserve usefulness

by avoiding emergence of resistanceby avoiding emergence of resistance- Where toxic effects do not justify Where toxic effects do not justify

use in trivial infectionsuse in trivial infections- ExpenseExpense


Antibiotic Tables ( see hospital policies)Antibiotic Tables ( see hospital policies)- for use empirically before results of for use empirically before results of

Culture and Sensitivity availableCulture and Sensitivity available- Change when this information is Change when this information is

available TO DIRECTED THERAPYavailable TO DIRECTED THERAPY- Specimens ( e.g for culture , PCR etc) Specimens ( e.g for culture , PCR etc)

should be taken before commencing should be taken before commencing therapy exception e.g meningitis)therapy exception e.g meningitis)

- In serious sepsis Parental route of In serious sepsis Parental route of Administration to be useAdministration to be use


Pharmacokinetics/ Pharmacodynamic Pharmacokinetics/ Pharmacodynamic may require dose/choice adjustmentmay require dose/choice adjustment

Avoid use of topical antibiotics, use Avoid use of topical antibiotics, use those not used systemicallythose not used systemically

Consultations Microbiologists or ID Consultations Microbiologists or ID physiciansphysicians

Treatment and Prophylaxis clearly Treatment and Prophylaxis clearly defineddefined

CLASSIFICATIONCLASSIFICATION

Concentration dependent bactericidal Concentration dependent bactericidal activityactivity

-Aminoglycosides-Aminoglycosides-Quinolones-Quinolones-Carbapenems-Carbapenems Time dependent bactericidal activityTime dependent bactericidal activity-B-lactams-B-lactams-Glycopeptides-Glycopeptides Bacteriostatic ActivityBacteriostatic Activity-Erythromycin-Erythromycin-Tetracycline-Tetracycline

Therapeutic Drug Therapeutic Drug MonitoringMonitoring

TDM necessary to ensure therapeutic TDM necessary to ensure therapeutic efficacy of a drug while ensuring toxic and efficacy of a drug while ensuring toxic and sub therapeutic doses are avoided.sub therapeutic doses are avoided.

TDM is performed on drugs with narrow TDM is performed on drugs with narrow therapeutic indices such as glycopeptides ( therapeutic indices such as glycopeptides ( e.g vancomycin) and aminoglycosides (e,g e.g vancomycin) and aminoglycosides (e,g gentamicin)gentamicin)

These drugs may be associated with These drugs may be associated with toxicity so levels should be regularly toxicity so levels should be regularly monitoredmonitored

ANTIBIOTIC ASSAYSANTIBIOTIC ASSAYS Assay when an antibiotic has a narrow Assay when an antibiotic has a narrow

therapeutic index e.g Aminoglysocidestherapeutic index e.g Aminoglysocides Assay when normal route of excretion is Assay when normal route of excretion is

impaired e.g. patient with renal impairment impaired e.g. patient with renal impairment on vancomycinon vancomycin

Assay in patients receiving prolonged Assay in patients receiving prolonged therapy for serious infection e.g. endocarditistherapy for serious infection e.g. endocarditis

Assay in Neonates with serious infectionAssay in Neonates with serious infection Assay if failure to respond to therapyAssay if failure to respond to therapy Assay to check complianceAssay to check compliance

Concentration Dependent Concentration Dependent Killing Killing

Trough1

Peak

Time

Conc

Example: Aminoglycosides

Therapeutic Range

Time Dependent KillingTime Dependent Killing

MIC

Time

Conc

Example: Glycopeptides

General advice on taking General advice on taking levelslevels

It is important to ensure the levels are It is important to ensure the levels are taken at the correct time.taken at the correct time.

FrequencyFrequency: first level see tables, repeat : first level see tables, repeat levels twice weekly for those with stable levels twice weekly for those with stable renal function, more frequently if renal renal function, more frequently if renal function rapidly changingfunction rapidly changing

WhenWhen: See tables. In general trough must : See tables. In general trough must be taken immediately before the next due be taken immediately before the next due dose.Peak one hour after administration of dose.Peak one hour after administration of dose.dose.

Levels done twice Saturday and once Levels done twice Saturday and once sundaysunday

General advice on taking General advice on taking levelslevels

Label correctly: if intermittent irregular Label correctly: if intermittent irregular dosing label as troughdosing label as trough

Random levels are not interpretableRandom levels are not interpretable Action to be taken on receipt of Action to be taken on receipt of

levels, levels, - If level is within therapeutic range, If level is within therapeutic range,

continue current dosingcontinue current dosing- Putting an antibiotic on hold is not Putting an antibiotic on hold is not

an appropriate intervention. Modify an appropriate intervention. Modify the dosing interval and / or dose.the dosing interval and / or dose.

- Advice from clinical Microbiology(ext Advice from clinical Microbiology(ext 2985) or ID Pharmacist2985) or ID Pharmacist

In general interpretation of In general interpretation of levelslevels

If trough high, dosing interval needs to If trough high, dosing interval needs to be prolonged where appropriatebe prolonged where appropriate

If trough is low( subtherpeutic) dosing If trough is low( subtherpeutic) dosing interval needs to be shortened and /or interval needs to be shortened and /or dose will need to be increased where dose will need to be increased where appropriateappropriate

If peak high, dose needs to be reduced If peak high, dose needs to be reduced where appropriatewhere appropriate

If peak low the dose may need to be If peak low the dose may need to be increased where appropriateincreased where appropriate

Example: VancomycinExample: Vancomycin Order bloods for renal function and Order bloods for renal function and

calculate CrClcalculate CrCl Vancomycin is the first line glycopeptide Vancomycin is the first line glycopeptide

in SJHin SJH Normal dose normal renal function 1 g Normal dose normal renal function 1 g

B.DB.D Recommended range Recommended range -Trough- 5-12 mg/l-Trough- 5-12 mg/lNormally taken before 3Normally taken before 3rdrd dose doseToxicity and Efficacy best determined by Toxicity and Efficacy best determined by

trough leveltrough level

Page 134

Creatinine ClearanceCreatinine Clearance

CrCl= (x)(140-age)(IBW) CrCl= (x)(140-age)(IBW)

Serum Creatinine

X= 1.23 males, x= 1.04 for females

Male IBW= 50 KG+ ( 2.3 kg) x (inches over 5 feet)Female IBW= 45.5KG + ( 2.3 kg) x (inches over 5 feet)

Using Empiric GuidelinesUsing Empiric Guidelines

Clinical symptoms/SignsClinical symptoms/Signs Table FormatTable Format Follow general principles covered Follow general principles covered

earlyearly

Example page 136Example page 136

75 year gent with cough purulent 75 year gent with cough purulent sputum, pyrexia, confusion, RR sputum, pyrexia, confusion, RR 22/min22/min

BP 110/70mmHg, BP 110/70mmHg,

COMMUNITY ACQUIRED PNEUMONIA: COMMUNITY ACQUIRED PNEUMONIA: WHAT’S CAUSING IT?WHAT’S CAUSING IT?

Page 136

Common pathogens?Common pathogens? Adult empiric therapy?Adult empiric therapy? What tests to be sentWhat tests to be sent Then directed therapyThen directed therapy

Using empiric guidelinesUsing empiric guidelines

Page 137Page 137 20 year presents with celluitis right 20 year presents with celluitis right

arm arm No history of therapyNo history of therapy Empiric therapy?Empiric therapy?

Using Empiric guidelines Using Empiric guidelines page 138page 138

60 year gent admitted with 60 year gent admitted with abdominal pain 12 hours duration , abdominal pain 12 hours duration , generalised guarding, boardlike generalised guarding, boardlike rigidityrigidity

Air under diaphragm on CXRAir under diaphragm on CXR Empiric therapy?Empiric therapy?

Using guidelines page 141Using guidelines page 141

20 year old presenting with severe 20 year old presenting with severe headache, neck stiffness, non-headache, neck stiffness, non-blanching rashblanching rash

Empiric treatment?Empiric treatment?

Using Empiric GuidelinesUsing Empiric Guidelines

Patient 48 age female presents Patient 48 age female presents with malaise, anorexia, fever for 3 with malaise, anorexia, fever for 3 weeksweeks

New heart murmur heardNew heart murmur heard

Osler`s nodesTender, s/c nodules

Janeway lesionsNontender Erythematous,Haemorrhagic,Or pustular Lesions often On palms or soles

Using Empiric guidelines Using Empiric guidelines page 145page 145

Common pathogensCommon pathogens Therapy?Therapy? Tests to be sent?Tests to be sent?

Surgical ProphylaxisSurgical Prophylaxis

Page 149Page 149 For ERCP?For ERCP? For femoral-popliteal bypass?For femoral-popliteal bypass? For Compound fracture?For Compound fracture?

Guidelines for prevention of Guidelines for prevention of Endocarditis PAGE 151Endocarditis PAGE 151

Patient with prosthetic valve Patient with prosthetic valve undergoing dental extractions undergoing dental extractions under general anaesthetic ( history under general anaesthetic ( history of treatment of RTI 3 weeks earlier of treatment of RTI 3 weeks earlier with co-amoxiclav)?with co-amoxiclav)?

Site of Site of InfectionInfection

Likely Likely OrganismsOrganisms

Empirical Tx.Empirical Tx.

MeningitisMeningitis S. pneumoniae, S. pneumoniae, N. meningitidisN. meningitidis, , H. influenzaeH. influenzae

Cefotaxime 2g Cefotaxime 2g 4hourly 4hourly

(+/- Vancomycin) (+/- Vancomycin) + rifampicin + rifampicin 600mg bd po/iv600mg bd po/iv

EndocarditiEndocarditiss

(native (native valve)valve)

Streptococci,Streptococci,

S. aureus,S. aureus,(MSSA)(MSSA)

EnterococciEnterococci

Benzylpenicillin Benzylpenicillin 2.4G 4 hourly 2.4G 4 hourly I/v+ Flucloxacillin I/v+ Flucloxacillin 2g 4 hourly I/v+ 2g 4 hourly I/v+ I/vI/v

Gentamicin1mg/Gentamicin1mg/kg tds I.vkg tds I.v

Abdominal Abdominal SepsisSepsis

GNBs, GNBs, Anaerobes, Anaerobes, enterococcienterococci

Amoxicillin-Amoxicillin-clavulanate + clavulanate + ciprofloxacin ciprofloxacin +metronidazole( +metronidazole( all I/v)all I/v)

Site of Site of InfectionInfection

Likely Likely OrganismsOrganisms

Empirical Tx.Empirical Tx.

Community Community Acquired Acquired InfectionInfection

S. S. pneumoniae, pneumoniae, H. influenzae,H. influenzae,

consider consider atypiatypicalscals

Amoxicillin-Amoxicillin-clavulanate +/-clavulanate +/-Clarithromycin(I/Clarithromycin(I/v or po)v or po)

CellulitisCellulitis Group A Group A StreptococcusStreptococcus

S. AureusS. Aureus

Benzylpenicillin Benzylpenicillin I/vI/v

++

Flucloxacillin I/vFlucloxacillin I/v

OsteomyelitisOsteomyelitis S. S. Aureus(MSSA)Aureus(MSSA)

Flucloxacillin I/v Flucloxacillin I/v ++

Fusidic acid p/oFusidic acid p/o

Simple cystitis Simple cystitis (no catheter)(no catheter)

E. coliE. coli, other , other GNB, coag neg GNB, coag neg staphstaph

Trimethoprim orTrimethoprim or

NitrofurantoinNitrofurantoin

Spectrum of ActivitySpectrum of Activity Benzyl penicillinBenzyl penicillin: mainly active against Gram : mainly active against Gram

Positive organisms e.g. Streptococci and Positive organisms e.g. Streptococci and StaphylococciStaphylococci

UreidopenicillinsUreidopenicillins: active against certain gram : active against certain gram positive and gram negative organismspositive and gram negative organisms

Anti-pseudomonal Penicillins Anti-pseudomonal Penicillins active against active against gram positive organisms(s) and gram negatives gram positive organisms(s) and gram negatives and pseudomonadsand pseudomonads

CephalosporinsCephalosporins: Broad spectrum of activity : Broad spectrum of activity gram negative and positive organisms, different gram negative and positive organisms, different generations have different spectra of activity.generations have different spectra of activity.

CarbapenemsCarbapenems

Imipenem, meropenemImipenem, meropenem: have a very : have a very broad spectrum activity against gram-broad spectrum activity against gram-negative bacteria, anaerobes, strepsnegative bacteria, anaerobes, streps

Now used to treat gram negative Now used to treat gram negative infections due to so called infections due to so called ESBLESBL producing producing organisms eg, organisms eg, E coli, KlebsiellaE coli, Klebsiella

ErtapenemErtapenem is a new member of the group is a new member of the group but its not active against Pseudomonasbut its not active against Pseudomonas

Cephalosporins: main usesCephalosporins: main uses

CefuroximeCefuroxime: surgical prophylaxis: surgical prophylaxis Cefotaxime/ceftriaxoneCefotaxime/ceftriaxone: meningitis : meningitis

nosocomial infections nosocomial infections excludingexcluding Pseudomonal, Pseudomonal,

CeftazidimeCeftazidime: nosocomial infections : nosocomial infections includingincluding Pseudomonal Pseudomonal

Other major antibiotic Other major antibiotic groups: groups: aminoglycosidesaminoglycosides

Gentamicin, amikacinGentamicin, amikacin (tobramycin, (tobramycin, streptomycin)streptomycin)

Mainly active against gram negative Mainly active against gram negative bacteriabacteria

Mainly used to treat nosocomial Mainly used to treat nosocomial infections: pneumonia in ITU, septicaemiainfections: pneumonia in ITU, septicaemia

Limiting factors are nephrotoxicity (and Limiting factors are nephrotoxicity (and ototoxicity) and resistanceototoxicity) and resistance

Also used in combinationAlso used in combination

Current major antibiotic Current major antibiotic resistance problems: resistance problems: community infectionscommunity infections

Respiratory tractRespiratory tract: penicillin resistance in : penicillin resistance in pneumococcus increasingpneumococcus increasing

GastrointestinalGastrointestinal: quinolone resistance in : quinolone resistance in CampylobacterCampylobacter

Sexually transmittedSexually transmitted: penicillin, quinolone : penicillin, quinolone resistance in gonococcusresistance in gonococcus

Urinary tractUrinary tract: beta lactam resistance in : beta lactam resistance in Esch Esch colicoli

MRSA and MDRTBMRSA and MDRTB Tropical: multidrug resistance in Tropical: multidrug resistance in Salmonella Salmonella

typhi, Shigella spp, malariatyphi, Shigella spp, malaria

Current major resistance Current major resistance problems: hospital infectionsproblems: hospital infections

MRSAMRSA: current strains are often multiply-: current strains are often multiply-antibiotic resistantantibiotic resistant

VISA/GISAVISA/GISA: intermediate resistance to : intermediate resistance to glycopeptides (thickened cell wall)glycopeptides (thickened cell wall)

VRSA/GRSAVRSA/GRSA: highly resistant (transferable : highly resistant (transferable on plasmids) from enterococcion plasmids) from enterococci

VREVRE: enterococci (multiply resistant): enterococci (multiply resistant) Broad spectrum beta lactam resistant Broad spectrum beta lactam resistant

((ESBLESBL) ) Esch coli, Klebsiella spp.Esch coli, Klebsiella spp. Multiply antibiotic resistant enterobacteria: Multiply antibiotic resistant enterobacteria:

Acinetobacter, Stenotrophomonas, Serratia Acinetobacter, Stenotrophomonas, Serratia spp.spp.

clinical aspects of antimicrobial therapy

Documents

empiric therapy

empiric use of antibiotics

empiric antibiotics

choice of antibiotic

antibiotic guidelinesguide

narrowest spectrum antibiotic

hospital pharmacist

doses of antibiotics