Antimicrobial Chemotherapy

Divisi Penyakit Tropik & Infeksi

Antimicrobials
Antibacterials Antivirals Antifungals Antiprotozoals Antihelminths

Introduction of New Classes of Antibiotics

1940
Sulfonamides 1936 b-lactams 1940 Cephalosporins 1945 Chloramphenicol 1949 Tetracyclines Aminoglycosides 1950 Macrolides 1952 Glycopeptides 1958 Quinolones Streprogramins 1962 Trimethoprim 1968

1960

1980

2000

Oxazolidinones 2000 Lipopeptides 2003 Ketolides 2004

Wenzel RP. NEJM. 2004;351:523526.

Antibiotic Resistance

A worldwide problem1

Associated with increased morbidity, mortality, and hospital costs1 Occurs in both hospitals and the community2
Results from factors such as antibiotic misuse1

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.

Current Problems of Bacterial Resistance

Policy & Advocacy of IDSA; July 2004 BAD BUGS, NO DRUGS
As Antibiotic Discovery Stagnates A Public Health Crisis Brews

HOST

PHARMACO KINETICS

HOST DEFENCE

ANTIBIOTIC
PHARMACO DYNAMICS

MICROORGANISM

Clinical Used of Antimicrobial

Prophylaxis Pre-emptive Empiric Definite

Strategy for empirical treatment

Patient Outpatient Hospitalized

Stable condition Escalation

Severe or high risk Deescalation

Antibiotic selection based on Susceptibility and resistance pattern Immunity status, co morbidity and organ dysfunction

Antibiotic monotherapy or combination Pohan HT, 2005

Antimicrobial Treatment based on Microbiological Culture Results

Microbiological culture results

Colonization No treat Sensitive Treat with Recommended Antibiotics

Pathogen Resistant Antibiotics Combination Optimized PKPD

Consideration When Choosing an Antibacterial Agent

Outcome
Microbiology
Mechanism of action
Antibacterial spectrum

Concentration at infection site

Drug
PK
Absorption
Distribution Metabolism Excretion Optimal dosing regimen

Pathogen MIC PD

Clinical efficacy Bacterial eradication Compliance with dosing regimen Tolerability Rate of resolution Prevention of resistance

Time vs. concentration dependent killing Bactericidal vs. bacteriostatic activity Tissue penetration Persistence of antibacterial effect

(Scaglione, 2002)

Three basic principles of antimicrobial therapy:

1. Selective toxicity - kill organisms not a man! 2. Reach the site of infection at adequate concentrations 3. Penetrate and bind to target microbe

Klasifikasi & Mekanisme Kerja AM

Dinding kuman
Penisilin, Sefalosporin, Monobaktam, Karbapenem, Glikopeptida, Fosfomisin, Oxasolidine

Membran sitoplasma
Aminoglikosida, Polimiksin B, Kolistin, Amfoterisin B

Sintesis As nukleat Inhibisi biosintesis protein

Aminoglikosida, Linkosamida, Makrolid, Tetrasiklin/Tygecyclin Kloramfenikol, As. Fusidik Rifampisin, As. Fusidik, Quinolon.

Inhibisi b-laktam
As.klavulanat, Sulbaktam, Tasobaktam

As.folat antagonis
Sulfa-Trimethoprim, Kotrimoksasol

I. Cell wall synthesis

1.

2.
3.

4.

Cycloserine Glycopeptides (vancomycin, teicoplanin) Bacitracin Beta-lactams (penicillins, cephalosporins, carbapenems, monobactams)

Inhibitors of bacterial cell wall synthesis

Cytoplasmic membrane NAG synthesis of new cell wall subunit attached to lipid carrier Glycopeptides bind to terminal D-ala-D-ala residues; prevent incorporation of subunit into growing peptidoglycan
NAM P P C55 lipid

L- lysine

Bacitracin Prevents dephosphorylation of phospholipid carrier, which prevents regeneration of carrier necessary for synthesis to continue

Inhibitors of bacterial cell wall synthesis

Cell wall Attachment of new wall unit to growing peptidoglycan
NAG NAM NAG NAM

L- lysine
D- ala

Beta-lactams Bind to and inhibit enzymes which catalyse this link

Beta-lactam antibiotics

Penicillins Cephalosporins Carbapenems Monobactams Cephamycins

All act by binding to penicillinbinding proteins (PBPs) PBPs are enzymes involved in cross-linking bacterial cell wall components Different bacteria may have different PBPs Spectrum of activity depends on whether antibiotic binds to PBPs found in the organism

Antibiotik b-Laktam
Terdiri dari: Penisilin & derivat Sefalosporin Gol. b-Laktam lainnya

Classifications Penicillins

Penicillin G & Penicillin V Penicillinase-resistant penicillins:

Methicillin, Nafcillin, Oxacillin, Cloxacillin & Dicloxacillin (against Stap.aureus) Extended Gr-negative: H.influenzae, E.coli, P.mirabilis

Ampicillin, Amoxicillin, Bacampicillin

Antipseudomonal Penicillins Carboxypenicillins: Carbenicillin &Ticarcillin Ureidopenicillins: Mezlocillin & Piperacillin

The Cephalosporins

First generation

Cephalothin, Cefazolin, Cefadroxil, Cephradine, Cephalexin,

Second generation

Cefuroxime axetil, Cefamandole, Cefoxitin, Cefuroxime Na, Cefonicid, Cefotetan, Ceforanide, Cefaclor, Cefprozil, Loracarbef
Ceftazidime Cefotaxime, Ceftriaxone, Cefoperaxone, Cefdinir, Cefixime, Cefatamet, Ceftibuten Cefepime, Cefpirome Ceftobiprole

Third generation

Fourth generation

Fifth generation

Activity of -lactams against common organisms

Gram (+)ve Staphylo Strepto Entero Penicillins cocci cocci cocci Benzylpenicillin + + R Flucloxacillin + + R Amoxycillin + + + Piperacillin + + + Gram (-)ve Pseudo E.coli monas R R R R + R + + Urine only + + + + R R R + +

Cephalosporins Cephalexin Cefuroxime Ceftriaxone Ceftazidime Carbapenems Imipenem

+ + R R +

+ + + + +

R R R R +

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)

Beta-lactamase inhibitors
Monobactam : - Aztreonam Carbapenems : - Imipenem - Meropenem - Doripenem

Uses for -lactams

Major clinical indication Penicillins Benzylpenicillin Fluclox/Cloxacillin Amp/Amoxycillin Azlo/Piperacillin Cephalosporins Cephalexin Cefuroxime Ceftriaxone Ceftazidime Cefotaxime Carbapenems Imipenem Route Pharyngitis, Pneum, Men, Endocarditis IV IM Skin, Soft tissue, Joint, Bone [G (-)ve] IV IM PO UTI, Enteric fever, Bone, Men, Epi, LRTIs IV IM PO P. aeruginosa & other G (-)ve rods IV

UTIs, UTIs, LRTIs Men, Joint, Bone P. aeruginosa & other G (-)ve rods Men, LRTIs, UTIs, abdominal sepsis
P. aeruginosa & other G (-)ve rods

PO IV IM IV IM IV IM IV IM
IV

II. Inhibitors of protein synthesis

Ribosomal subunits involved in mRNA translation in bacterial systems are smaller (30S & 50S) than in eukaryotic (mammalian) translation (40S & 60S) Most antibiotics acting upon the ribosome are bacteriostatic, but aminoglycosides are

bactericidal

Inhibitors of protein synthesis

1.

2.
3.

4.
5.

Aminoglycosides Macrolides Tetracyclines Chloramphenicol Fusidic acid

Aminoglycosides

Gentamicin Tobramycin Amikacin

First broad spectrum aminoglycoside Similar spectrum to gentamicin Semi-synthetic derivative of kanamycin, active against Gentamicin-resistant G(-)ve rods Toxic- used topically Oldest aminoglycoside now used to treat TB

Neomycin Streptomycin

Drugs acting on bacterial ribosomes Aminoglycosides - general properties

Major weapon in treatment of severe sepsis Fat insoluble and not absorbed orally Entry into cells depends upon oxygen-dependent transport (lacked by streptococci & enterococci) Toxic to the kidney and inner ear - imperative to measure levels

Inhibitors of protein synthesis

1. 2. 3. 4. 5.

Aminoglycosides Macrolides Tetracyclines Chloramphenicol Fusidic acid

Erythromycin Azithromycin Clarithromycin

Macrolides
CH3 O

H3C
HO

Large structures: 14- (Erythromycin & Clarithromycin), 15- (Azithromycin), or 16-membered rings.
HO H3 C H5C2
O O

OH CH3 O

OH O

N(CH3) CH3

CH3 CH3 O

OCH3 O
OH CH3

Macrolides - general properties

Newer macrolides inhibit Mycobacteria, protozoa (T. gondii, E. histolytica, P. falciparum), Campylobacter, Helicobacter, Borrelia, Neisseria & other genital pathogens GI complications, mostly with erythromycin Given orally, but absorbtion & bioavailability variable from one macrolide to another

Inhibitors of protein synthesis

1. 2. 3. 4. 5.

Aminoglycosides Macrolides Tetracyclines Chloramphenicol Fusidic acid

Drugs acting on bacterial ribosomes Tetracyclines

R1 R2 R3 R4 OH

OH

OH OH O

CONH2

Inhibit protein synthesis by preventing amino-acyl transfer RNA from entering the acceptor sites on the ribosome
Semi-synthetic e.g., doxycycline, minocycline, tigecycline

Natural e.g., chlortetracycline, oxytetracycline, tetracycline,

Tigecycline : broad spectrum except Pseudomonas

Drugs acting on bacterial ribosomes Tetracyclines - general properties

Active against many common Gram (+)ve & (-)ve bacteria, chlamydiae, rickettsiae, coxiellae, spirochaetes, some mycobacteria, E histolytica, & plasmodia Given orally, absorbtion affected by food Effect on dentition (chelates Ca) GI intolerance common

Inhibitors of protein synthesis

1.

2.
3.

4.
5.

Aminoglycosides Macrolides Tetracyclines Chloramphenicol Fusidic acid

Chloramphenicol - general properties

H O2 N C OH

NHCOCHCl2 C H CH2OH

Nitrobenzene nucleus - Blocks peptidyl transferase, thereby blocking peptide bond synthesis Bacteriostatic against G(+)ves, many Gram (-)ves (not P. aeruginosa), leptospires, T. pallidum, chlamydiae, mycoplasmas, rickettsiae, & many anaerobes, (B. fragilis less so) Second line agent due to marrow effects Thiamfenicol : minimal side effect

Inhibitors of protein synthesis

1.

2.
3.

4.
5.

Aminoglycosides Macrolides Tetracyclines Chloramphenicol Fusidic acid

Drugs acting on bacterial ribosomes Fusidic acid - general properties

COOH HO

OAc

H HO
H

Active against most Gram (+)ves and Gram (-)ve cocci, including MRSA Some activity against G. lamblia, P. falciparum Some activity against Mycobacteria Mostly used for staphylococcal infections (osteomyelitis) and topically Use for topical

III. Nucleic acid synthesis:

Inhibition of synthesis of precursors Sulphonamides Trimethoprim Inhibitors of DNA replication Quinolones Inhibitors of RNA polymerase Rifampicin

Nucleic acid synthesis: Drugs acting on microbial folate synthesis

Trimethoprim - inhibits folate required for the synthesis of purines and pyrimidines by enzyme inhibition Sulphonamides - also inhibit folate synthesis by enzyme inhibition

Sulphonamides - general properties

Broad spectrum activity Restricted in use by resistance Many interactions with other drugs due to plasma protein binding Principal use has been for treatment of UTIs Useful in treatment of PCP, Nocardia, & Toxoplasma gondii

Nucleic acid synthesis: Inhibitors of DNA replication

Quinolones (eg. ciprofloxacin - a fluoroquinolone) large family of synthetic agents that affect DNA gyrase 5 gen gyrase inhibitors :
Gen

1 : Nalidixic acid Gen 2 : Ciprofloxacine, Ofloxacine Gen 3 : Levofloxacine, Pefloxacine Gen 4 : Gatifloxacine, Moxifloxacine Gen 5 : Gatifloxacine, Gemifloxacine

IV. Antimicrobial agents that affect bacterial DNA and RNA

Rifamycins (eg rifampacin) specific inhibitors of bacterial DNA-dependent RNA polymerase blocks mRNA Metronidazole (a nitroimidazole) When reduced it can react with DNA, oxidizing it and causing strand breaks

Rational antimicrobial therapy

Patient
Clinician Microorganism Microbiologist

Drug

How can we prevent the spread of resistance?

Use of drug that a plasmid codes resistance for can encourages growth of bacteria carrying multiple antibiotic plasmid. Cause of resistance is

Resistance to antibiotics A, B, & C

inappropriate use of Treat with A antibiotics and use of antibiotics as growth promoters in farm animals.

Country-to-country variation.

Emergence of Antimicrobial Resistance

Susceptible Bacteria
Resistant Bacteria

Resistance Gene Transfer New Resistant Bacteria

Selection for antimicrobialresistant Strains

Resistant Strains Rare

Antimicrobial Exposure
Resistant Strains Dominant

Key Prevention Strategies

Prevent infection
Diagnose and treat

infection effectively

Use antimicrobial wisely Prevent transmission

Diagnose & Treat Infection Effectively

Action: Target the pathogen

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

Concentration independent vs dependent killing antibiotics

Concentration-time profile of Ceftazidime

Concentration vs time profile for once daily & conventional aminoglycoside

Ambrose PG. Med Clin North Am 2000; 84(6): 1431-46

Target site concentration after bolus 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 concentration piperacillin in plasma after injection in patients septic shock & healthy volunteers

Time vs concentration piperacillin in the interstitial space & subcutaneus adipose patients septic shock & healthy volunteers

Jaukhadar C. Critical Care Medicine 2001;29:385-391

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 hub use proper methods to obtain & process all cultures

Use Antimicrobials Wisely

Action: Treat infection, not colonization
Fact:
A major cause of antimicrobial overuse is treatment of colonization.

Actions:

treat pneumonia, not the tracheal aspirate treat bacteremia, not the catheter tip or hub treat urinary tract infection, not the indwelling catheter

Antimicrobial Resistance:

Key Prevention Strategies

Susceptible Pathogen Pathogen Antimicrobial-Resistant Pathogen
Prevent Transmission Prevent Infection

Antimicrobial Resistance
Optimize Use

Infection
Effective Diagnosis & Treatment

Antimicrobial Use

Antibiotic Policy

Classification of antibiotics Class A : Not restricted Class B : Not restricted but under supervision Class C : Restricted Implementation Evaluation and surveillance Auditing

Classification of antibiotics
Class A
Aminoglicoside Penicillin Cephalosporin gen.I,II Chloramphenicol Fucidic acid Lincosamide Macrolide Nitroimidazol Fluoroquinolone gen.I,II Tetracyline TMP-SMX Fosfomicin Polypeptide

Class B
Cephalosporine gen III Fluoroquinolone gen III-IV Ertapenem Vancomycin

Class C
Teicoplanin Linezolide Cefepime Cefpirome Ceftazidime Pip-Tazo Carbapenem Tygecicline

Implementation

Antimicrobial Policy in Hospital

Community
Outpatient Class A

Hospital
Class A

Inpatient WARD ICU

Mild Moderate Severe

Class B Class B/C

Class C Class C

Evaluation and Surveillance

1.

Evaluate the quantity of antibiotic usage

Retrospectively from the medical record From medical prescription Copy of prescription

2.

Evaluate the quality of antibiotic usage

Using classification by Gyssens

Evaluation category of Antibiotics Usage by Gyssens

I.

II.

Correct Usage 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 is

a) more effective b) less toxic c) cheaper d) more specific

V.
VI.

No Indication Medical record is insufficient to be evaluated

Surveillance of every inpatient ward, intensive care ward, and surgery room periodically, e.g. monthly surveillance in internal medicine ward Report of surveillance periodically, e.g. report of surveillance in internal medicine ward every 6 months

Auditing

Periodically done by antibiotic team (multi department), commissioned by management of hospital Audit of medical records, copy of prescriptions Percentage of compliance to antibiotic guideline Reward and punishment

Conclusion
Complete knowledge of Antibiotics use is important in successful management of infection The implementation of antibiotic policy is essential in every hospital and health care to promote : rational use of antibiotics, cost-effective therapy and prevent collateral damage

ANTIVIRAL

Why do We Use Antivirals ?

Vaccines are effective at prevention but what about the patient that is already infected ? Viruses can be very swift and deadly and a quick method of curing a patient is needed The market is huge and a remedy would bring about solutions to viral infections such as: Influenza, HIV, Herpes, Hepatitis B, Smallpox, Ebola, Rabies, etc.
Chris Brooks, Antiviral Drugs: An Overview,2007

When to Use Antivirals?

Recommendations for prophylaxis and use of antivirals
1. 2. 3. 4. 5. Treatment of person hospitalized for influenza Treatment of ill health care and emergency services workers Treatment of ill high-risk persons in the community Prophylaxis of health care workers Control outbreaks in high-risk residents of institution (nursing homes and other long-term care facilities) 6. Prophylaxis of essential service workers 7. Prophylaxis of high-risk person hospitalized for illnesses other than influenza 8. Prophylaxis of high-risk persons in the community
Attachment M, Priority Antiviral Distribution

Rational Antiviral Molecule : Bench to Bedside

Mild secondary effects
Broad spectrum Good distribution

Oral administration

Antiviral Molecule

Intracellular activity

Good solubility
Guillaume Castel, et al

Economical

Low molecular weight

Molecules 2011, 16, 3499-3518; doi: 10.3390/molecules16053499

Antiviral Drugs Action

Jhavari R, Medscape 2011

The Weapon of Choice: Antiviral Drugs

v.d.e
Anti-herpesvirus Anti-Influenza agents Antiretrovirals: NRTIs Antiretrovirals: NtRTIs Antiretrovirals: NNRTIs

Antivirals (primarity J05A, also S01AD and D06BB

Aciclovir, Cidofovir, Docosanol, Famciclovir, Fomivirsen, Foscarnet, Ganciclovir, Idoxuridine, Penciclovir, Trifluridine, Tromantadine, Valaciclovir, Valganciclovir, Vidarabine Amantadine, Arbidol, Oseltamivir, Peramivir, Rimantadine, Zanamivir Abacavir, Didanosine, Emtricitabine, Lamivudine, Stavudine, Zalcitabine, Zidovudine Tenofovir Efavirenz, Delavirdine, Nevirapine, Loviride Amprenavir, Atazanavir, Darunavir, Fosamprenavir, Indinavir, Lopinavir, Nelfinavir, Ritonavir, Saquinavir, Tipranavir Enfuvirtide Adefovir, Fomivirsen, Imiquimod, Inosine, Interferon, Podophyllotoxin, Ribavirin, Viramidine

Antiretrovirals: Pls
Antiretrovirals; Fusion inhibitors Other antiviral agents

Chris Brooks, Antiviral Drugs: An Overview, 2007

ANTIVIRAL TREATMENT
Emerging Antiviral Treatment

The Goals of Antiretroviral Therapy

Improve quality of life Reduce HIV related mortality and morbidity Provide maximal and durable suppression of viral load Restore and / or immune function

Guidelines of Antiretroviral Therapy in Adults, Southern African HIV Clinicians Society,2012

ANTIFUNGAL TREATMENT

Dilemmas in Diagnosis Invasive Fungal Infections

Clinical symptoms are not characteristic Fungi can be both colonizers and pathogens, and even laboratory contamination Biopsy is often precluded by co-morbidity Objective evidence usually occurs late in the course of infection

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

When to Start Antifungal Therapy ?

Colonization At risk
Time course No treatment

Invasiveness

Dissemination

Disease probability
Treatment

Overtreatment

Undertreatment

Successful response
Ben E. dePauw. CID 2005;41:1251-3

Selection of Appropriate Antifungal Agents

The appropriate antifungal injection must have the following factors, such as:

Spectrum of activity Good tolerability Reliable efficacy Limited drug interaction Simple drug administration Cost effectiveness

Therapeutic Options
Polyenes Ampho B Deoxycholate Liposomal Ampho B (Ambisome) Ampho B Colloidal Dispersion (ABCD) Ampho B Lipid Complex (ABLC) Itraconazole, Fluconazole, Voriconazole Posaconazole, Ravuconazole Caspofungin, Micafungin, Anidulafungin Flucytosine

Azoles

Echinocandins Antimetabolite

4 MAJOR FUNGAL INFECTION ETIOLOGY

Candida sp Aspergillus sp Cryptococcus sp Histoplasma sp

Host factors modifying antibiotic choice Reaches the site of infection -1

The antibiotic may inhibit the microbe in the laboratory, but will it reach the site of infection? ? requirement to cross blood-brain barrier :
Aminoglycosides (except neonates) Penicillin G, 1st generation cephalosporins Ceftriaxone, chloramphenicol

Cross Poorly Cross with difficulty Cross well

Host factors modifying antibiotic choice 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 significant haematoma

Other factors to consider

Frequency of dosing Correct dose and route Duration IS THE TREATMENT WORKING Is a drug combination necessary Is the combination synergistic, additive, or antagonistic

Pharmacokinetics and pharmacodynamics (PK/PD) of antimicrobial agents

Cmax/MIC ratio
Cmax

AUC/MIC ratio (=AUIC) Time above MIC

Area Under the Curve

MIC
Time Time above-MIC

Pharmacokinetic/Pharmaco-dynamic (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 prevent emergence of resistance (Lister, 2002)
For time-dependent killing pattern: Time above MIC (required: 40% of dosing interval)

Antibiotics in Patients with liver dysfunction(1)

Safe
Aminoglycosides Ampicillin Cephalexin

Possible (with just adjustment)

Azlocilin Aztreonam Cefotaxime

Contraindicated
Cefoperazone Chloramphenicol Clindamycin

Cefoxitin
Cefuroxime Ofloxacin Penicillin G Imipenem

Ceftriaxone
Ceftazidime Ciprofloxacin Erythromycin (except the estolate) Flucloxacillin Fusidic Acid

Co-trimoxazole
Erythromycin estolate Latamoxef Metronidazole Nitrofurantoin Rifampicin

Mezlocillin

Roxithromycin

Antibiotics in Patients with liver dysfunction(2)

Safe Possible (with just adjustment)
Piperacilin Vancomycin Fluconazole

Contraindicated
Sulfonamides Tetracyclines INH

Prothionamide
Pyrazinamide Amphotericin B Grisefulvin Itraconazole Ketoconazole Miconazole

Diffusion of antibiotics into cerebrospinal fluid

Diffusion into CSF
High
Chloramphenicol Co-trimoxazole Fosfomycin

Moderate
Tetracyclines Ofloxacin

Only in meningitis
Penicillin G Isoxazolylpenicillins Ampicillin Cefalotin

Low
Cefazolin Cefazedone

Metronidazole
Flucytosine Fluconazole Prothionamide Pyrazinamide Aciclovir

Acylureidopenicillins
Cefuroxime Cefotaxime Ceftriaxone Ceftazidime Imipenem

Cefotiam
Oral cephalosporins Aztreonam Aminoglycosides Erythromycin Norfloxacin

Zidovudine
Foscarnet

Sulbactam
Ciprofloxacine Vancomycin Miconazole Rifampicin

Clindamycin
Fusidic Acid Ketoconazole Itraconazole Amphotericin B

Antibiotics during pregnancy and lactation period(1)

Agent Penicillin Cephalosporins Aminoglycosides Erythromycin Clincamycin

Embryionic period*
+ + (+) (+)

Post Embryonic period** + + + (+)

Peripartal period***
+ + + (+)

Lactation + + + (+)

Possible foetal impairment None known None known Inner ear damage None known, dont use erythromycin estolate None known, pseudomembranous enterocolitis im mother Disturbance of bone and tooth growth

Tetracyclines

Chloramphenicol
Co-trimoxazole

(+)

(+)
- Contraindicated or
not recommended

+ safe for use

when indicated

Gray syndrome, myelosuppresion

Teratogenic in animal experiments, kernicterus
A
to be prescribed only in exceptional cases indicated

(+) only if clearly

* Embryonic period (1st to 12th wk. of pregnancy) ** Postembryonic period (13th to 39th wk. of pregnancy) *** Peripartal period (40th wk. of pregnancy till delivery )

Antibiotics during pregnancy and lactation period(2)

Agent Post Embryionic Embryonic period * period ** Peripartal period *** Lactation Possible foetal impairment

Fusicid Acid
Rifampicin Vancomycin Quinolones Nitrofurantoin

(+)
(+) -

+
(+) (+)

+
(+) (+)

+
(+) +

None known
Coagulation disorder, liver damage in mother and fetus None known Disturbance of chodral growth Teratogenic in animal experiments

Metronidazole
Amphotericin B * Embryonic period

A
-

A
A(+)

A
A(+) - Contraindicated or
not recommended

A
+

Teratogenic in animal experiments

Abortion and foetal retardation reported + safe for use
when indicated

(1st to 12th wk. of pregnancy)

** Postembryonic period
(13th to 39th wk. of pregnancy)

(+) only if clearly

indicated

to be prescribed only in exceptional cases

*** Peripartal period

(40th wk. of pregnancy till delivery )