General Rules On Use of General Rules On Use of Antimicrobial AgentsAntimicrobial Agents

Consultant Microbiologist & Head of the Bacteriology

By: Prof. A.M.Kambal By: Prof. A.M.Kambal

ANTIMICROBIAL AGENTS

ANTIBIOTICS:ANTIBIOTICS:

NATURAL COMPOUNDS PRODUCED BY NATURAL COMPOUNDS PRODUCED BY MICROORGANISM WHICH INHIBIT THE GROWTH MICROORGANISM WHICH INHIBIT THE GROWTH OF OTHER .OF OTHER .

CHEMOTHERAPY:CHEMOTHERAPY:

SYNTHETIC COMPOUNDS.SYNTHETIC COMPOUNDS.

SELECTIVE TOXICITY:SELECTIVE TOXICITY: THE ABILITY TO KILL OR INHIBIT THE THE ABILITY TO KILL OR INHIBIT THE

GROWTH OF MICROORGANISM WITHOUT GROWTH OF MICROORGANISM WITHOUT HARMING THE HOST CELLS.HARMING THE HOST CELLS.

BACTERICIDALBACTERICIDAL: : KILLS BACTERIAKILLS BACTERIA

BACTERIOSTATICBACTERIOSTATIC:: PREVENTS MULTIPLICATIONPREVENTS MULTIPLICATION..

SPECTRIM OF ACTIVITYSPECTRIM OF ACTIVITY::

BROAD SPECTRUM: G+VE& G-VEBROAD SPECTRUM: G+VE& G-VE NARROW SPECTRUM: SELECTIVE ORGANISM.NARROW SPECTRUM: SELECTIVE ORGANISM.

THERAPEUTIC INDEX:THERAPEUTIC INDEX:

THE RATIO OF THE DOSE TOXIC TO THE HOST TO THE RATIO OF THE DOSE TOXIC TO THE HOST TO THE EFFECTIVE THERAPEUTIC DOSE.THE EFFECTIVE THERAPEUTIC DOSE.

EXAMPLES:EXAMPLES:

PENICILLIN: HIGH PENICILLIN: HIGH AMINOGLYCOSIDES: LOW AMINOGLYCOSIDES: LOW POLYMYXIN B: THE LOWEST POLYMYXIN B: THE LOWEST

MECHANISMS OF ACTION OF MECHANISMS OF ACTION OF ANTIMICROBIALSANTIMICROBIALS

1) INHIBITION OF CELL WALL SYNTHESIS.1) INHIBITION OF CELL WALL SYNTHESIS.

2) ALTERATION OF CELL MEMBRANES2) ALTERATION OF CELL MEMBRANES

3) INHIBITION OF PROTEIN SYNTHSIS3) INHIBITION OF PROTEIN SYNTHSIS

4) INHIBITION OF NUCLEIC ACID4) INHIBITION OF NUCLEIC ACID

5) ANTIMETABOLIC OR COMPETITEVE ANTAGONISM.5) ANTIMETABOLIC OR COMPETITEVE ANTAGONISM.

MECHANISMS OF ACTIONMECHANISMS OF ACTION

ANTIMICROBIALS THAT INHIBIT ANTIMICROBIALS THAT INHIBIT CELL WALL SYNTHESISCELL WALL SYNTHESIS

BETA LACTAMSBETA LACTAMS

PENICILLINSPENICILLINS CEPHALOSPORINSCEPHALOSPORINS CARBAPENEMSCARBAPENEMS MONOBACTAMMONOBACTAM

VANCOMYCINVANCOMYCIN BACITRACINBACITRACIN

- LACTAM ANTIBIOTICS:- LACTAM ANTIBIOTICS:

BETA LACTAM RING &ORGANIC ACID.BETA LACTAM RING &ORGANIC ACID. NATURAL &SEMISYNTHETICNATURAL &SEMISYNTHETIC CIDAL ACTIONCIDAL ACTION BIND TO PBP, INTERFERES WITH BIND TO PBP, INTERFERES WITH

TRANSPEPTIDATION REACTIONTRANSPEPTIDATION REACTION

TOXICITYTOXICITY:: HYPERSENS. HYPERSENS. ANAPHYLAXIS, ANAPHYLAXIS, DIARRHOEA, ..ETC.DIARRHOEA, ..ETC.

ANTIBIOTICS THAT INHIBIT PROTIEN ANTIBIOTICS THAT INHIBIT PROTIEN SYNTHESISSYNTHESIS

AMINOGLYCOSIDESAMINOGLYCOSIDES

TETRACYCLINESTETRACYCLINES

CHLORAMPHENICOLCHLORAMPHENICOL

MACROLIDESMACROLIDES

ANTIMICROBIALS THAT ACT ON NUCLEIC ACIDANTIMICROBIALS THAT ACT ON NUCLEIC ACID

RIFAMOICINRIFAMOICIN

QUINOLONESQUINOLONES

METRONIDAZOLEMETRONIDAZOLE

ANTIMETABOLITES:ANTIMETABOLITES:

SULFONAMIDESSULFONAMIDES

TRIMETHOPRIMTRIMETHOPRIM

COMBINATION: BACTRIM/ SEPTRINCOMBINATION: BACTRIM/ SEPTRIN

BLOCK SEQUENTIAL STEPS IN FOLIC ACID SYNTHESISBLOCK SEQUENTIAL STEPS IN FOLIC ACID SYNTHESIS

NOCARDIA,CHLAMYDIA,PROTOZOA,P.CRANIINOCARDIA,CHLAMYDIA,PROTOZOA,P.CRANII

UTI LRTI, OM..UTI LRTI, OM..

GIT.HEPATITIS, BM DEPRESSIN, HYPERSENSITIVITYGIT.HEPATITIS, BM DEPRESSIN, HYPERSENSITIVITY

ANTITUBERCULOUS AGENTS

FIRST LINEFIRST LINE: INH: INH RIFAMPICINRIFAMPICIN ETHAMBUTOLETHAMBUTOL PYRAZINAMIDEPYRAZINAMIDE

SECOND LINE:STREPTOMYCIN PASA CYCLOSERINE,CAPREOMYCIN

ANTIBIOTIC RESISTANCE IN BACTERIAANTIBIOTIC RESISTANCE IN BACTERIA

INDISCRIMINATE USE OF ANTIMICROBIALSINDISCRIMINATE USE OF ANTIMICROBIALS SELECTIVE ADVANTAGE OF ANTIBIOTICSSELECTIVE ADVANTAGE OF ANTIBIOTICS

TYPES OF RESISTANCE:TYPES OF RESISTANCE:

PRIMARYPRIMARY::

INNATE eg. STREPT. &ANAEROBES RESISTANT TO INNATE eg. STREPT. &ANAEROBES RESISTANT TO GENTAMICINGENTAMICIN

ANTIBIOTIC RESISTANCE IN BACTERIA (Continue)ANTIBIOTIC RESISTANCE IN BACTERIA (Continue)

AQUIRED:AQUIRED: 1-MUTATION: MTB R TO SRTEPTOMYCIN1-MUTATION: MTB R TO SRTEPTOMYCIN

2- GENE TRANSFER: PLASMID MEDIATED OR 2- GENE TRANSFER: PLASMID MEDIATED OR TRANSPOSONESTRANSPOSONES

CROSS RESISTANCECROSS RESISTANCE: : R TO ONE GROUP CONFER R TO OTHER OF THE R TO ONE GROUP CONFER R TO OTHER OF THE

SAME GROUPSAME GROUP EG ERYTHROMYCIN & CLINDAMYCINEG ERYTHROMYCIN & CLINDAMYCIN

DISSOCIATE RDISSOCIATE R:: R TO GENTA. DOES NOT CONFER R .TO R TO GENTA. DOES NOT CONFER R .TO

TOBRAMYCINTOBRAMYCIN

MECHANISMS OR RESISTANCEMECHANISMS OR RESISTANCE

1-PERMIABILITY CANGED1-PERMIABILITY CANGED

2-MODIFICATION OF SITE OF ACTION, EG. 2-MODIFICATION OF SITE OF ACTION, EG. MUTATIONMUTATION

3-INACTIVATION BY ENZYMES.EG. BETA 3-INACTIVATION BY ENZYMES.EG. BETA LACTAMASE, AMINOGLYCOSIDES INACTIVATING LACTAMASE, AMINOGLYCOSIDES INACTIVATING ENZYMESENZYMES

BYPASSING BLOCKED METABOLIC REACTION EG. BYPASSING BLOCKED METABOLIC REACTION EG. PABAPABA FOILC ACID BY PLASMID MEDIATED FOILC ACID BY PLASMID MEDIATED

DFR.DFR.

PRINCIPLES OF ANTIMICROBIAL THERAPY:PRINCIPLES OF ANTIMICROBIAL THERAPY:

INDICATIONINDICATION CHOICE OF DRUGCHOICE OF DRUG ROUTEROUTE DOSAGEDOSAGE DURATIONDURATION DISTRIBUTIONDISTRIBUTION EXCRETIONEXCRETION TOXICITYTOXICITY COMBINATIONCOMBINATION PROPHYLAXIS:PROPHYLAXIS:

SHORT TERM:SHORT TERM: MENINGITISMENINGITISLONG TERM:LONG TERM: TB, UTI , RHEUMATIC TB, UTI , RHEUMATIC

FEVERFEVER

All anaerobes are susceptible to flagyl All Streptococci are resistant to aminoglyclosides All anaerobes are resistant to aminoglycosides

e.g. Gentamicin. All anaerobes EXCEPT Bacteriodes fragilis are susceptible to

penicillin. All gram negative organisms are resistant to vancomycin. All gram positive organisms are susceptible to vancomycin

EXCEPT Vancomycin Resistant Enterococci (VRE).

Pseudomonas are resistant to all antibiotic EXCEPT:

a) Aminoglycosides

b) Third generation cephalosporins

e.g. ceftazidime

c) Quinolones e.g. ciprofloxacin

d) Ureidopenicillin. E.g. pipericillin

e) Carbapenems e.g. imipenem and meropenem

Flucloxacillin/cloxacillin is the best therapy for methicillin sensitive Staphylococcus aureus, first generation cephalosporins e.g. cephalex, cephidine can be used for the same purpose.

Patients allergic to penicillin can be treated with microlides. e.g. Erythromycin

Staphylococcus aureus resistance to methicillin are also resistant to flucloxacillin, other penicillins, some macrolides. These are better treated with vancomycin.

β-haemolytic Streptococci – e.g. Group A,B,C etc are always susceptible to penicillin, first, second and third generation cephalosporins and of course Vancomycin.

Patients allergic to penicillin can be treated with macrolides. e.g. Erythromycin.

Enterococci e.g. Enterococcus faecalis are generally Resistant to penicillin, but susceptible to ampicillin.

Enterococci resistant to ampicillin can be treated by vancomycin or teichoplanin.

Enterococci resistant to vancomycin (VRE) are treated by Linozolid, dalphopristin or quinopristin.

Ceftriaxone a (3rd generation cephalosporin) is active against.

a) Streptococcus pneumoniaeb) Neisseria meningitidisc) H. influenzae

This makes it the best empirical therapy of meningitis before knowing the causative agents.

Typhoid fever is treated by:a) Amoxycillinb) Cotrimoxazole (Septrin)c) Chloramphenicol

If resistant to these, then use Ciprofloxacin or Ceftriaxone.

Antimicrobial prophylaxis should be

a) Directed to a known organism as far as possible.

b) It should not be given for more then 3 doses.

Few exceptions are known

e.g. urinary tract infection. In site where immune system does not work well, use bactericidal

antibiotic e.g. Endocarditis Meningitis

Choice of Antibacterial Agents According to Clinical Syndromes:

1. Infections of Skin, Soft tissue and Bone:

a) Cellulitis Uncomplicated:

Causative agents: Staph. aureus Strepto. pyogenes Strepto. agalactiae

Drugs = Cloxacillin, 1st generation cephalosporin

For MRSA = Vancomycin Complicated: e.g. in burns

Causative agents = E.coli, Pseudomonas etc.

Drugs = Piperacillin / Tazobactam, Imipenem etc.

Choice of Antibacterial Agents According to Clinical Syndromes:

b) Bone and Joints:

Oesteomyelitis: Causative agents Staph. aureus Strepto. pyogenes

Drugs as in cellulitis

Septic arthritis Staph. aureus Haemophilus influenzae – Ampicillin, Ceftriaxone Salmonella in sickle cell disease – Ampicillin, Ceftriaxone

Choice of Antibacterial Agents According to Clinical Syndromes:

2. Meningitis: a) Primary causatives agents in children and adults

Strept. pneumoniae N. meningitidis H. influenzae

Drugs = Ceftriaxone Or amoxycillin b) Neonatal meningitis

1. Group B β-haemolytic streptococci2. Gram negative faecal organisms

e.g. E.coli, Klebsiella etc. 3. Listeria monocytogenes

Emperic Drugs Therapy: Ampicillin + gentamicin Ampicillin + Cefotaxime sometimes (Gentamicin)

Choice of Antibacterial Agents According to Clinical Syndromes:

Pneumonia a) Causative agents:

Community acquired Typical Strep. pneumoniae Haemophilus influenzae

Drugs = Ceftriaxone Or Cefuroxime

Atypical: Mycoplasma pneumoniae Chlamydia pneumoniae Legionella pneumophilic

Empiric Drugs Therapy: Ceftriaxone and Erythromycin Or Azithromycin

Choice of Antibacterial Agents According to Clinical Syndrome:

Hospital Acquired Pneumonia Causative agents:

Gram negative rods (Enterobactericae) MRSA Pseudomonas

Drugs = Piperacillin / Tasobactam Or Ceftazidime + Aminoglycoside + Vancomycin for (MRSA)

Urinary Tract Infection:

Causative agents: E.coli (85% of cases) Klebsiella Proteus Enterococcus faecales

Drugs (Emperic) Ampicillin / Amoxycillin Cephalex Trimotheprim / Sulphamethaxole Others according to susceptibility testing

Septicemia / Bacterionema: (Blood Stream Infection)

Any Organism:

Drugs Ampicillin + Aminoglycoside Ceftazidime + Aminoglycoside and (Vancomycin for gram

+ve)

Organisms Causing Dental Infection:

There are usually members of the mouth flora:A. Streptococci

e.g. Other Viridans streptococciB. Anaerobes

Bacteroides Prevotella Viellonella

C. SpirochaetesD. Others spiral organismsE. Other organisms in immunocompromised patients

e.g. Gram negative rods

Treatment of Dental Infection:

Generally penicillin, but now replaced by amoxycillin as it is better absorbed.

In patient allergic to penicillin useA. Clindamycin OrB. Macrolides e.g. erythromycin

In severely ill patient with severe infection vancomycin may be used plus flagyl

In severe infections in immunocompromised patients take specimens for culture and give therapy according to susceptibility testing.