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AntimicrobialChemotherapy
Divisi Penyakit Tropik & Infeksi
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Antimicrobials
Antibacterials Antivirals Antifungals Antiprotozoals
Antihelminths
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Sulfonamides 1936
b-lactams 1940Cephalosporins 1945Chloramphenicol 1949
Tetracyclines Aminoglycosides 1950
Macrolides 1952
Glycopeptides 1958
QuinolonesStreprogramins 1962
Trimethoprim 1968
1940 1960 1980 2000
Oxazolidinones 2000
Lipopeptides 2003
Introduction of New Classes of Antibiotics
Ketolides 2004
Wenzel RP. NEJM. 2004;351:523
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A worldwide problem 1
Associated with increasedmorbidity, mortality, andhospital costs 1
Occurs in both hospitals and the community 2
Results from factors such as
antibiotic misuse1
Antibiotic Resistance
Source:1: R. A. Kulkarni et al. Indian J Surg. 2005: Volume 67(6): 308-315.2 Ben-David D, Rubenstein E. Curr Opin Infect Dis 2002;15:151-156.
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Policy Advocacy of IDSA; July 2004 BAD B UGS N O D RUGS
As Antibiotic Discovery Stagnates A Public Health Crisis Brews
Current Problems of Bacterial Resistance
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HOST
ANTIBIOTIC MICROORGANISM
PHARMACOKINETICS
HOSTDEFENCE
PHARMACODYNAMICS
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Clinical Used of Antimicrobial
ProphylaxisPre-emptiveEmpiricDefinite
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Strategy for empirical treatmentPatient
Outpatient Hospitalized
Stable condition Severe or high risk
Escalation Deescalation
Antibiotic selection based onSusceptibility and resistance patternImmunity status, co morbidity and organ dysfunction
Antibiotic monotherapy or combination
Pohan HT, 2005
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Antimicrobial Treatment based on MicrobiologicalCulture Results
Microbiological culture results
Colonization Pathogen
No treat Sensitive Resistant
Treat with Antibiotics Optimized
Recommended Combination PKPD Antibiotics
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Consideration When Choosingan Antibacterial Agent
Microbiology Mechanism of action Antibacterial spectrum
DrugPK
Absorption Distribution Metabolism
Excretion Optimal dosingregimen
Concentrationat infection site
Pathogen MIC
PD Time vs. concentrationdependent killing
Bactericidal vs. bacteriostatic activity Tissue penetration Persistence of antibacterial effect
Outcome
Clinical efficacy Bacterial eradication Compliance with
dosing regimen Tolerability Rate of resolution Prevention of resistance
( Scaglione, 2002 )
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Three basic principles ofantimicrobial therapy:
1. Selective toxicity - kill organisms not a man!2. Reach the site of infection at adequate concentrations3. Penetrate and bind to target microbe
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Klasifikasi & Mekanisme Kerja AM
Dinding kumanPenisilin,
Sefalosporin,Monobaktam,Karbapenem,Glikopeptida,Fosfomisin,Oxasolidine
Inhibisi biosintesisprotein
Aminoglikosida,Linkosamida,Makrolid,Tetrasiklin/TygecyclinKloramfenikol,
As. Fusidik
As.folat antagonisSulfa-Trimethoprim,Kotrimoksasol
Inhibisi b-laktam As.klavulanat,Sulbaktam,
Tasobaktam
Sintesis As nukleatRifampisin,
As. Fusidik,Quinolon.
Membran sitoplasma Aminoglikosida, Polimiksin B,Kolistin, Amfoterisin B
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I. Cell wall synthesis1. Cycloserine
2. Glycopeptides (vancomycin, teicoplanin)3. Bacitracin4. Beta-lactams (penicillins, cephalosporins,
carbapenems, monobactams)
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Inhibitors of bacterial cell wall synthesisCytoplasmicmembrane
synthesis of newcell
wall subunitattached
to lipid carrier
Glycopeptides bind to terminal
D-ala-D-ala residues;
prevent incorporation ofsubunit into growing
peptidoglycan
NAG NAM P P C55 lipid
BacitracinPreventsdephosphorylation
of phospholipidcarrier, which
preventsregeneration ofcarrier necessaryfor synthesis tocontinue
L- lysine
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Inhibitors of bacterial cell wall synthesisCell wall Attachment of new wall unit to growing peptidoglycan
Beta-lactamsBind to and inhibit enzymes which catalyse this link
NAG NAM NAG NAM
L- lysine
D- ala
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Beta-lactam antibiotics
Penicillins
CephalosporinsCarbapenemsMonobactamsCephamycins
All act by binding to penicillin- binding proteins ( PBP s)PBPs are enzymes involved incross-linking bacterial cell wallcomponentsDifferent bacteria may havedifferent PBPsSpectrum of activity depends onwhether antibiotic binds to PBPsfound in the organism
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Antibiotik b-Laktam
Terdiri dari:Penisilin & derivatSefalosporinGol. b-Laktamlainnya
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Classifications PenicillinsPenicillin G & Penicillin VPenicillinase-resistant penicillins:
Methicillin, Nafcillin, Oxacillin, Cloxacillin & Dicloxacillin(against Stap.aureus )
Ampicillin, Amoxicillin, Bacampicillin Extended Gr-negative: H.influenzae, E.coli, P.mirabilis
Antipseudomonal Penicillins
Carboxypenicillins: Carbenicillin &Ticarcillin Ureidopenicillins: Mezlocillin & Piperacillin
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First generation Cephalothin, Cefazolin, Cefadroxil, Cephradine, Cephalexin,
Second generation Cefuroxime axetil, Cefamandole, Cefoxitin, Cefuroxime Na,
Cefonicid, Cefotetan, Ceforanide, Cefaclor, Cefprozil, Loracarbef
Third generation Ceftazidime Cefotaxime, Ceftriaxone, Cefoperaxone, Cefdinir,
Cefixime, Cefatamet, Ceftibuten
Fourth generation
Cefepime, CefpiromeFifth generation
Ceftobiprole
The Cephalosporins
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Activity of -lactams against common organisms
PenicillinsBenzylpenicillinFlucloxacillinAmoxycillinPiperacillinCephalosporinsCephalexinCefuroximeCeftriaxoneCeftazidime
Staphylococci
++++
E.coli RR++
Streptococci
++++
Enterococci
RR++
Pseudomonas
RRR+
++RR
++++
RRRR
RRR+
Urine only+++
Gram (+)ve Gram (-)ve
CarbapenemsImipenem + + + + +
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Beta-lactamase inhibitors
Clavulanic acid:- used with amoxycillin (Augmentin)- used with ticarcillin (Timentin)Sulbactam:- used with ampicillin (unavailable in UK)
Tazobactam - used with piperacillin (Tazocin)
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Monobactam :- Aztreonam
Carbapenems :- Imipenem- Meropenem
- Doripenem
Beta-lactamase inhibitors
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Uses for -lactams
PenicillinsBenzylpenicillinFluclox/CloxacillinAmp/AmoxycillinAzlo/Piperacillin
CephalosporinsCephalexinCefuroximeCeftriaxoneCeftazidimeCefotaxime
Pharyngitis, Pneum, Men, EndocarditisSkin, Soft tissue, Joint, Bone [G (-)ve]UTI, Enteric fever, Bone, Men, Epi, LRTIsP. aeruginosa & other G (-)ve rods
IV IMIV IM POIV IM PO
IV
UTIs,UTIs, LRTIsMen, Joint, BoneP. aeruginosa & other G (-)ve rodsMen, LRTIs, UTIs, abdominal sepsis
POIV IMIV IMIV IMIV IM
Major clinical indication Route
CarbapenemsImipenem P. aeruginosa & other G (-)ve rods IV
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II. Inhibitors of protein synthesis
Ribosomal subunits involved in mRNA translationin bacterial systems are smaller (30S & 50S) thanin eukaryotic (mammalian) translation (40S & 60S)Most antibiotics acting upon the ribosome arebacteriostatic , but aminoglycosides arebactericidal
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Inhibitors of protein synthesis
1. Aminoglycosides2. Macrolides3. Tetracyclines4. Chloramphenicol
5. Fusidic acid
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Aminoglycosides
Gentamicin Tobramycin Amikacin
Neomycin
Streptomycin
First broad spectrum aminoglycosideSimilar spectrum to gentamicinSemi-synthetic derivative ofkanamycin, active against
Gentamicin-resistant G(-)ve rods
Toxic- used topically
Oldest aminoglycoside now usedto treat TB
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Drugs acting on bacterial ribosomes Aminoglycosides - general properties
Major weapon in treatment of severe sepsisFat insoluble and not absorbed orallyEntry into cells depends upon oxygen-dependent transport (lacked by streptococci & enterococci)
Toxic to the kidney and inner ear - imperative to
measure levels
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Inhibitors of protein synthesis
1. Aminoglycosides2. Macrolides3. Tetracyclines4. Chloramphenicol5. Fusidic acid
M lid
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MacrolidesErythromycin
AzithromycinClarithromycin
Large structures:
14- (Erythromycin &Clarithromycin),
15- (Azithromycin), or16-membered rings.
CH 3
CH 3
OH CH 3
O
CH 3
O
O
H 5C 2
H 3C HO
HO
H 3C
O
O
OH N(CH 3
CH 3
O
O CH 3
OCHOH
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Macrolides - general properties
Newer macrolides inhibit Mycobacteria, protozoa ( T. gondii, E. histolytica,P. falciparum ), Campylobacter, Helicobacter,Borrelia, Neisseria & other genital pathogensGI complications , mostly with erythromycinGiven orally , but absorbtion & bioavailability
variable from one macrolide to another
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Inhibitors of protein synthesis
1. Aminoglycosides2. Macrolides3. Tetracyclines 4. Chloramphenicol5. Fusidic acid
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Drugs acting on bacterial ribosomes Tetracyclines
Natural e.g.,chlortetracycline,oxytetracycline, tetracycline,
Semi-synthetic e.g.,doxycycline, minocycline,tigecycline
OH O OH O
OHR 1 R 2 R 3 R 4
CONH 2OH
Inhibit protein synthesisby preventing amino-acyltransfer RNA fromentering the acceptorsites on the ribosome
Tigecycline : broad spectrum except Pseudomonas
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Drugs acting on bacterial ribosomes Tetracyclines - general properties
Active against many common Gram (+)ve &(-)ve bacteria, chlamydiae, rickettsiae,coxiellae, spirochaetes, some mycobacteria,E histolytica , & plasmodiaGiven orally , absorbtion affected by foodEffect on dentition (chelates Ca)
GI intolerance common
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Inhibitors of protein synthesis
1. Aminoglycosides2. Macrolides
3. Tetracyclines4. Chloramphenicol5. Fusidic acid
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Chloramphenicol - general properties
Nitrobenzene nucleus - Blocks peptidyl transferase,thereby blocking peptide bond synthesisBacteriostatic against G(+)ves, many Gram (-)ves(not P. aeruginosa ), leptospires, T. pallidum ,chlamydiae, mycoplasmas, rickettsiae, & manyanaerobes, ( B. fragilis less so)Second line agent due to marrow effects
Thiamfenicol : minimal side effect
C
OH
H
CH 2OHCO2 N
H
NHCOCHCl 2
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Inhibitors of protein synthesis
1. Aminoglycosides2. Macrolides
3. Tetracyclines4. Chloramphenicol5. Fusidic acid
Drugs acting on bacterial ribosomes
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Drugs acting on bacterial ribosomesFusidic acid - general properties
Active against most Gram (+)vesand Gram (-)ve cocci, includingMRSASome activity againstG. lamblia , P. falciparumSome activity against MycobacteriaMostly used for staphylococcalinfections (osteomyelitis) andtopicallyUse for topical
COOH
HHO
H
HHO
OAc
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III. Nucleic acid synthesis:
Inhibition of synthesis of precursorsSulphonamides
TrimethoprimInhibitors of DNA replicationQuinolonesInhibitors of RNA polymerase
Rifampicin
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Nucleic acid synthesis:Drugs acting on microbial folate synthesis
Trimethoprim - inhibits folate requiredfor the synthesis of purines and
pyrimidines by enzyme inhibition
Sulphonamides - also inhibit folate
synthesis by enzyme inhibition
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Sulphonamides - general properties
Broad spectrum activityRestricted in use by resistance
Many interactions with other drugs due to plasma protein bindingPrincipal use has been for treatment of UTIsUseful in treatment of PCP, Nocardia, &
Toxoplasma gondii
Nucleic acid synthesis:
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Nucleic acid synthesis:Inhibitors of DNA replication
Quinolones (eg. ciprofloxacin - a fluoroquinolone)large family of synthetic agents that affect DNAgyrase5 gen gyrase inhibitors :
Gen 1 : Nalidixic acidGen 2 : Ciprofloxacine, OfloxacineGen 3 : Levofloxacine, PefloxacineGen 4 : Gatifloxacine, MoxifloxacineGen 5 : Gatifloxacine, Gemifloxacine
IV A i i bi l h ff
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IV. Antimicrobial agents that affectbacterial DNA and RNA
Rifamycins (eg rifampacin) specific inhibitorsof bacterial DNA-dependent RNA polymerase
blocks mRNAMetronidazole (a nitroimidazole) Whenreduced it can react with DNA, oxidizing itand causing strand breaks
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How can we prevent the spread ofresistance?
Use of drug that a plasmidcodes resistance for canencourages growth of bacteriacarrying multiple antibiotic
plasmid.Cause of resistance isinappropriate use ofantibiotics and use ofantibiotics as growth
promoters in farm animals.Country-to-country variation.
Resistance to antibiotics A, B, & C
Treat with A
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New Resistant Bacteria
Emergence of Antimicrobial Resistance
Susceptible Bacteria
Resistant Bacteria
Resistance Gene Transfer
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Resistant StrainsRare
AntimicrobialExposure
Resistant StrainsDominant
Selection for antimicrobial-resistant Strains
K P ti St t i
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Key Prevention Strategies
Prevent infection
Diagnose and treat
infection effectivelyUse antimicrobial wisely
Prevent transmission
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Fact: Appropriate antimicrobial therapy (correctregimen, timing, dosage, route, and duration)saves lives.
Diagnose & TreatInfection Effectively
Action: Target the pathogen
Concentration independent vs dependent
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p pkilling antibiotics
Ambrose PG. Med Clin North Am 2000; 84(6): 1431-46
Concentration-time profile of Ceftazidime Concentration vs time profile for once daily& conventional aminoglycoside
Target site concentration after
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gbolus injection vs continuous infusion of Cefpirome
Concentration in the interstitial space fluid skletal muscle & subcutaneus adipose
tissue after bolus injection (red symbols) & continuous infusion (yellow symbols)
Hollenstein. Clin Pharmacol Ther 2000;67:229-36
Time vs unbound concentrationi illi i l ft i j ti i
Time vs concentration piperacillin in theinterstitial space & subcutaneus adipose
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piperacillin in plasma after injection in patients septic shock & healthy volunteers
Jaukhadar C. Critical Care Medicine 2001;29:385-391
interstitial space & subcutaneus adipose patients septic shock & healthy volunteers
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Use Antimicrobials Wisely
Action : Treat infection,not contamination
Fact: A major cause of antimicrobial overuse is treatment of
contaminated cultures.
Actions:use proper antisepsis for blood & other cultures
culture the blood, not the skin or catheter hubuse proper methods to obtain & process all cultures
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Use Antimicrobials Wisely
Action: Treat infection,not colonization
Fact: A major cause of antimicrobial overuse is treatment ofcolonization.
Actions:treat pneumonia, not the tracheal aspiratetreat bacteremia, not the catheter tip or hub
treat urinary tract infection, not the indwellingcatheter
Antimicrobial Resistance:
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Key Prevention Strategies
OptimizeUse
PreventTransmission
PreventInfection
EffectiveDiagnosis& Treatment
PathogenAntimicrobial-Resistant Pathogen
AntimicrobialResistance
Antimicrobial Use
Infection
Susceptible Pathogen
Antibiotic Policy
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Antibiotic Policy
Classification of antibioticsClass A : Not restrictedClass B : Not restricted but under supervision
Class C : RestrictedImplementationEvaluation and surveillance
Auditing
Classification of antibiotics
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Class A Class B Class C Aminoglicoside
PenicillinCephalosporin gen.I,IIChloramphenicolFucidic acidLincosamide
MacrolideNitroimidazolFluoroquinolone
gen.I,II Tetracyline
TMP-SMXFosfomicinPolypeptide
Cephalosporine gen III
Fluoroquinolonegen III-IV
Ertapenem Vancomycin
Teicoplanin
LinezolideCefepimeCefpiromeCeftazidimePip-Tazo
Carbapenem Tygecicline
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Evaluation and Surveillance
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1. Evaluate the quantity of antibiotic usageRetrospectively from the medical recordFrom medical prescription
Copy of prescription2. Evaluate the quality of antibiotic usage
Using classification by Gyssens
Evaluation and Surveillance
Evaluation category of Antibiotics Usage
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by GyssensI. Correct UsageII. Incorrect due to:
a) Incorrect dose b) Incorrect interval c) Incorrect route
III. Incorrect due to:a) duration too long b) duration too short
IV. Incorrect due to: Alternative drug that isa) more effective b) less toxic c) cheaper d) more specific
V. No Indication VI. Medical record is insufficient to be evaluated
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Surveillance of every inpatient ward, intensive care ward, and surgery room periodically, e.g. monthlysurveillance in internal medicine ward
Report of surveillance periodically, e.g. report ofsurveillance in internal medicine ward every 6 months
Auditing
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Auditing
Periodically done by antibiotic team (multidepartment), commissioned by management ofhospital
Audit of medical records, copy of prescriptionsPercentage of compliance to antibiotic guidelineReward and punishment
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ANTIVIRAL
Why do We Use Antivirals ?
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Vaccines are effective at prevention but whatabout the patient that is already infected ?
Viruses can be very swift and deadly and a quickmethod of curing a patient is needed
The market is huge and a remedy would bringabout solutions to viral infections such as:Influenza, HIV, Herpes, Hepatitis B, Smallpox,Ebola, Rabies, etc.
Chris Brooks, Antiviral Drugs: An Overview,2007
y
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Rational Antiviral Molecule :B h B d id
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Molecules 2011, 16, 3499-3518; doi:10.3390/molecules16053499
Guillaume Castel, et al
Bench to Bedside
Broadspectrum
Gooddistribution
Intracellularactivity
Low molecular
weightEconomicalGood solubility
Oraladministration
Mild secondaryeffects
AntiviralMolecule
Antiviral Drugs Action
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Jhavari R, Medscape 2011
The Weapon of Choice:A i i l D
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Chris Brooks, Antiviral Drugs: An Overview, 2007
Antiviral Drugs v.d.e Antivirals (primarity J05A, also S01AD and D06BB
Anti-herpesvirus Aciclovir, Cidofovir, Docosanol, Famciclovir, Fomivirsen, Foscarnet, Ganciclovir, Idoxuridine,Penciclovir, Trifluridine, Tromantadine, Valaciclovir, Valganciclovir, Vidarabine
Anti-Influenza agents Amantadine, Arbidol, Oseltamivir, Peramivir, Rimantadine, Zanamivir
Antiretrovirals: NRTIs Abacavir, Didanosine, Emtricitabine, Lamivudine, Stavudine, Zalcitabine, Zidovudine
Antiretrovirals: NtRTIs Tenofovir
Antiretrovirals: NNRTIs Efavirenz, Delavirdine, Nevirapine, Loviride
Antiretrovirals: Pls Amprenavir, Atazanavir, Darunavir, Fosamprenavir, Indinavir, Lopinavir, Nelfinavir, Ritonavir,Saquinavir, Tipranavir
Antiretrovirals; Fusioninhibitors Enfuvirtide
Other antiviral agents Adefovir, Fomivirsen, Imiquimod, Inosine, Interferon, Podophyllotoxin, Ribavirin, Viramidine
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Emerging Antiviral Treatment
ANTIVIRAL TREATMENT
The Goals of Antiretroviral Therapy
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Improve quality of lifeReduce HIV related mortality and morbidityProvide maximal and durable suppression of
viral loadRestore and / or immune function
Guidelines of Antiretroviral Therapy in Adults, Southern African HIV Clinicians Society,2012
py
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ANTIFUNGAL TREATMENT
Dilemmas in
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Clinical symptoms are not characteristic
Fungi can be both colonizers and pathogens, and even
laboratory contaminationBiopsy is often precluded by co-morbidity
Objective evidence usually occurs late in the course of
infection
Diagnosis Invasive Fungal Infections
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Rational Antifungal Treatment and Option: When to start the antifungal therapy?
ANTIFUNGAL TREATMENT
When to Start Antifungal Therapy ?
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Time course Disease probability
No treatment Treatment
Colonization Invasiveness Dissemination At risk
Successful response
Overtreatment Undertreatment
Ben E. dePauw. CID 2005;41:1251-3
Selection of Appropriate Antifungal Agents
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The appropriate antifungal injection must have thefollowing factors, such as:
Spectrum of activity
Good tolerabilityReliable efficacyLimited drug interactionSimple drug administration
Cost effectiveness
Selection of Appropriate Antifungal Agents
Therapeutic Options
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Ampho B Deoxycholate
Liposomal Ampho B (Ambisome) Ampho B Colloidal Dispersion (ABCD) Ampho B Lipid Complex (ABLC)
Itraconazole, Fluconazole, VoriconazolePosaconazole, Ravuconazole
Caspofungin , Micafungin , Anidulafungin
Flucytosine
Polyenes
Azoles
Echinocandins
Antimetabolite
4 MAJOR FUNGAL INFECTION
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ETIOLOGY
Candida sp Aspergillus spCryptococcus spHistoplasma sp
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Host factors modifying antibiotic choiceReaches the site of infection -1
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The antibiotic may inhibit the microbe inthe laboratory, but will it reach the site ofinfection?? requirement to cross blood-brain barrier :
Cross Poorly Aminoglycosides (except neonates)Cross with difficulty Penicillin G, 1st generation
cephalosporins
Cross well Ceftriaxone, chloramphenicol
Host factors modifying antibiotic choiceReaches the site of infection -2
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Reaches the site of infection 2
Penetration is generally poor in endocarditis,bones & devitalised tissue High-dose prolonged therapy is required Route of excretion:- Drugs concentrated in bile
are more effective in treating cholangitis, e.g.ampicillin (or cephalexin for E.coli UTI) Pus: can bind and inactivate aminoglycosides Haematoma: penicillins & tetracycline bind to
Hb - may be less effective with significanthaematoma
Other factors to consider
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Frequency of dosingCorrect dose and routeDurationIS THE TREATMENT WORKINGIs a drug combination necessaryIs the combination synergistic, additive, orantagonistic
Pharmacokinetics and pharmacodynamics(PK/PD) of antimicrobial agents
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MIC
Time
Cmax
Area Underthe Curve
Time above-MIC
Cmax/MIC ratio AUC/MIC ratio (=AUIC) Time above MIC
Pharmacokinetic/Pharmaco-dynamic(PK/PD)
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(PK/PD) parameters
For concentration-dependent killing pattern: AUC/MIC (required: 125 for Gram negative and
30 for Gram positive pathogens, respectively )
Cmax/MIC (required: 10) required to preventemergence of resistance (Lister, 2002)
For time-dependent killing pattern: Time above MIC (required: 40% of dosing interval)
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Antibiotics in Patients with liver dysfunction (1)
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Safe Possible (with justadjustment) Contraindicated
Aminoglycosides Azlocilin Cefoperazone
Ampicillin Aztreonam Chloramphenicol
Cephalexin Cefotaxime Clindamycin
Cefoxitin Ceftriaxone Co-trimoxazole
Cefuroxime Ceftazidime Erythromycin estolate
Ofloxacin Ciprofloxacin Latamoxef
Penicillin G Erythromycin (except the estolate) Metronidazole
Imipenem Flucloxacillin Nitrofurantoin
Fusidic Acid RifampicinMezlocillin Roxithromycin
Antibiotics in Patients with liver dysfunction (2)
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Safe Possible (with justadjustment) Contraindicated
Piperacilin Sulfonamides
Vancomycin Tetracyclines
Fluconazole INH
Prothionamide
Pyrazinamide
Amphotericin B
Grisefulvin
Itraconazole
Ketoconazole
Miconazole
Diffusion of antibiotics into cerebrospinal fluidDiffusion into CSF
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High Moderate Only in meningitis LowChloramphenicol Tetracyclines Penicillin G Cefalotin
Co-trimoxazole Ofloxacin Isoxazolylpenicillins Cefazolin
Fosfomycin Ampicillin Cefazedone
Metronidazole Acylureidopenicillins Cefotiam
Flucytosine Cefuroxime Oral cephalosporins
Fluconazole Cefotaxime Aztreonam
Prothionamide Ceftriaxone AminoglycosidesPyrazinamide Ceftazidime Erythromycin
Aciclovir Imipenem Norfloxacin
Zidovudine Sulbactam Clindamycin
Foscarnet Ciprofloxacine Fusidic Acid
Vancomycin KetoconazoleMiconazole Itraconazole
Rifampicin Amphotericin B
Antibiotics during pregnancy and lactation period (1)Agent
Embryionicperiod*
PostEmbryonicperiod**
Peripartalperiod*** Lactation Possible foetal impairment
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Penicillin + + + + None known
Cephalosporins + + + + None known
Aminoglycosides - - - - Inner ear damage
Erythromycin (+) + + + None known, dont useerythromycin estolate
Clincamycin (+) (+) (+) (+) None known,pseudomembranousenterocolitis im mother
Tetracyclines - - - - Disturbance of bone and toothgrowth
Chloramphenicol - - - - Gray syndrome,myelosuppresion
Co-trimoxazole (+) (+) - - Teratogenic in animalexperiments, kernicterus
- Contraindicated ornot recommended
(+) only if clearlyindicated
+ safe for usewhen indicated
A to be prescribedonly in exceptional cases
* Embryonic period (1 st to 12 th wk. of pregnancy) ** Postembryonic period (13 th to 39 th wk. of pregnancy)*** Peripartal period (40 th wk. of pregnancy till delivery )
Antibiotics during pregnancy and lactation period (2)
Agent Embryionicperiod *
PostEmbryonic Peripartal
period ***Lactation Possible foetal impairment
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period period ** period
Fusicid Acid (+) + + + None known
Rifampicin - - - - Coagulation disorder, liverdamage in mother and fetus
Vancomycin (+) (+) (+) (+) None known
Quinolones - - - - Disturbance of chodral growth
Nitrofurantoin - (+) (+) + Teratogenic in animalexperiments
Metronidazole A A A A Teratogenic in animalexperiments
Amphotericin B - A(+) A(+) + Abortion and foetal retardationreported
* Embryonic period(1 st to 12 th wk. of pregnancy)
** Postembryonic period(13 th to 39 th wk. of pregnancy)
*** Peripartal period(40 th wk. of pregnancy till delivery )
- Contraindicated ornot recommended
(+) only if clearlyindicated
+ safe for usewhen indicated
A to be prescribedonly in exceptional cases