Kuliah PPDS S-2 Final Rev3, 19 Sept 2013

8/13/2019 Kuliah PPDS S-2 Final Rev3, 19 Sept 2013

1/91

AntimicrobialChemotherapy

Divisi Penyakit Tropik & Infeksi


2/91

Antimicrobials

Antibacterials Antivirals Antifungals Antiprotozoals

Antihelminths


3/91

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


4/91

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.


5/91

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


6/91

HOST

ANTIBIOTIC MICROORGANISM

PHARMACOKINETICS

HOSTDEFENCE

PHARMACODYNAMICS


7/91

Clinical Used of Antimicrobial

ProphylaxisPre-emptiveEmpiricDefinite


8/91

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


9/91

Antimicrobial Treatment based on MicrobiologicalCulture Results

Microbiological culture results

Colonization Pathogen

No treat Sensitive Resistant

Treat with Antibiotics Optimized

Recommended Combination PKPD Antibiotics


10/91

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 )


11/91

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


12/91

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


13/91

I. Cell wall synthesis1. Cycloserine

2. Glycopeptides (vancomycin, teicoplanin)3. Bacitracin4. Beta-lactams (penicillins, cephalosporins,

carbapenems, monobactams)


14/91

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


15/91

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


16/91

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


17/91

Antibiotik b-Laktam

Terdiri dari:Penisilin & derivatSefalosporinGol. b-Laktamlainnya


18/91

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


19/91

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


20/91

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 + + + + +


21/91

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)


22/91

Monobactam :- Aztreonam

Carbapenems :- Imipenem- Meropenem

- Doripenem

Beta-lactamase inhibitors


23/91

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


24/91

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


25/91

Inhibitors of protein synthesis

1. Aminoglycosides2. Macrolides3. Tetracyclines4. Chloramphenicol

5. Fusidic acid


26/91

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


27/91

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


28/91


1. Aminoglycosides2. Macrolides3. Tetracyclines4. Chloramphenicol5. Fusidic acid

M lid


29/91

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


30/91

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


31/91


1. Aminoglycosides2. Macrolides3. Tetracyclines 4. Chloramphenicol5. Fusidic acid


32/91

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


33/91

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


34/91


1. Aminoglycosides2. Macrolides

3. Tetracyclines4. Chloramphenicol5. Fusidic acid


35/91

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


36/91


1. Aminoglycosides2. Macrolides

3. Tetracyclines4. Chloramphenicol5. Fusidic acid

Drugs acting on bacterial ribosomes


37/91

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


38/91

III. Nucleic acid synthesis:

Inhibition of synthesis of precursorsSulphonamides

TrimethoprimInhibitors of DNA replicationQuinolonesInhibitors of RNA polymerase

Rifampicin


39/91

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


40/91

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:


41/91

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


42/91

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


43/91


44/91

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


45/91

New Resistant Bacteria

Emergence of Antimicrobial Resistance

Susceptible Bacteria

Resistant Bacteria

Resistance Gene Transfer


46/91

Resistant StrainsRare

AntimicrobialExposure

Resistant StrainsDominant

Selection for antimicrobial-resistant Strains

K P ti St t i


47/91

Key Prevention Strategies

Prevent infection

Diagnose and treat

infection effectivelyUse antimicrobial wisely

Prevent transmission


48/91

Fact: Appropriate antimicrobial therapy (correctregimen, timing, dosage, route, and duration)saves lives.

Diagnose & TreatInfection Effectively

Action: Target the pathogen

Concentration independent vs dependent


49/91

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


50/91

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


51/91

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


52/91

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


53/91

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:


54/91

Key Prevention Strategies

OptimizeUse

PreventTransmission

PreventInfection

EffectiveDiagnosis& Treatment

PathogenAntimicrobial-Resistant Pathogen

AntimicrobialResistance

Antimicrobial Use

Infection

Susceptible Pathogen

Antibiotic Policy


55/91

Antibiotic Policy

Classification of antibioticsClass A : Not restrictedClass B : Not restricted but under supervision

Class C : RestrictedImplementationEvaluation and surveillance

Auditing

Classification of antibiotics


56/91

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


57/91

Evaluation and Surveillance


58/91

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


59/91

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


60/91

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


61/91

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


62/91


63/91

ANTIVIRAL

Why do We Use Antivirals ?


64/91

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


65/91

Rational Antiviral Molecule :B h B d id


66/91

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


67/91

Jhavari R, Medscape 2011

The Weapon of Choice:A i i l D


68/91

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


69/91

Emerging Antiviral Treatment

ANTIVIRAL TREATMENT

The Goals of Antiretroviral Therapy


70/91

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


71/91

ANTIFUNGAL TREATMENT

Dilemmas in


72/91

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


73/91

Rational Antifungal Treatment and Option: When to start the antifungal therapy?

ANTIFUNGAL TREATMENT

When to Start Antifungal Therapy ?


74/91

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


75/91

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


76/91

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


77/91

ETIOLOGY

Candida sp Aspergillus spCryptococcus spHistoplasma sp


78/91


79/91

Host factors modifying antibiotic choiceReaches the site of infection -1


80/91

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


81/91

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


82/91

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


83/91

MIC

Time

Cmax

Area Underthe Curve

Time above-MIC

Cmax/MIC ratio AUC/MIC ratio (=AUIC) Time above MIC

Pharmacokinetic/Pharmaco-dynamic(PK/PD)


84/91

(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)


85/91


86/91

Antibiotics in Patients with liver dysfunction (1)


87/91

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)


88/91

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


89/91

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


90/91

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


91/91

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

Kuliah PPDS S-2 Final Rev3, 19 Sept 2013

Documents

Transcript of Kuliah PPDS S-2 Final Rev3, 19 Sept 2013