clinical aspects of antimicrobial therapy. contents of lecture empiric antibiotic guidelines empiric...
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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
Principles of Antibiotic Principles of Antibiotic GuidelinesGuidelines
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
Principles of Antibiotic Principles of Antibiotic GuidelinesGuidelines
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
Principles of Antibiotic Principles of Antibiotic GuidelinesGuidelines
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)
Principles of Antibiotic Principles of Antibiotic GuidelinesGuidelines
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
General Principles of General Principles of TherapyTherapy
- 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
General Principles of General Principles of TherapyTherapy
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
General Principles of General Principles of TherapyTherapy
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
General Principles of General Principles of TherapyTherapy
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
General Principles of General Principles of TherapyTherapy
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 136Page 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.