Dr Khulood Alsaraf

Antimicrobial drugs : are effective in the treatment of infections because of their selective toxicity (the ability to kill an invading M.O without harming the cells of the host ).

Antibacterial & antimicrobial: are substances that inhibit the growth or kill bacteria or other M.O like bacteria, viruses, fungi & protozoa

Antibiotics : refers to chemicals that are produced by one kind of M.O that inhibits the growth of or kill another.

A-The site of the infection B-Oganism identity & its sensitivity to a particular agent C-The safety of the agent D-Patient factor E-The cost of therapy

Bacteriostatic drugs inhibit the growth of bacteria Bacteriocidal drugs kill bacteria

Selection of antimicrobial agents

Chemotherapeutic spectra

A-Narrow spectrum B-Extended spectrum C-Broad spectrum

Resistance to antibacterial1-Naturally(inherent): pseudomonas aeruginosa resistant to penicillin G

2-Acquired : staph. aureus resistant to penicillin G after previous exposure

Combination of antimicrobial drugs

Advantages1-Reduced the possibility of superinfection

2-Decreases the emergence of resistant organism 3-Minimizes toxicity

Combination of antimicrobial agents should only be used in special situation such as:1-when mixed infection occur2-In treatment of enterococcal endocarditis 3-when there is a risk of developing resistant organisms2-Infection of unknown origin

DisadvantagesA No. of antibiotic act only when organism are growing.

Prophylactic antibiotics Are used in certain clinical situations such as:1- Pretreatment may prevent streptococcal infection in patients with a history of rheumatic heart disease.2- Pretreatment of patients undergoing dental extractions who have implanted prosthetic devices.3- Pretreatment may prevent T.B or meningitis among individuals who are in close contact with infected patients.4-Ttreatment prior to most surgical procedure can decrease the incidence of infection afterwards.5- Protect the fetus in the case of an HIV – infected, pregnant woman.

Classification of antimicrobial agents

1-According to their chemical structure like [β-lactams, Aminoglycosides]

2-According to the mechanism of action [cell walls synthesis inhibitors]

3-According to the activity against particular type of organisms [bacteria, fungi, ……..]

Cell wall inhibitors β-lactam antibiotics

Fungi of genous cephalosporium cephalosporin'sFungi of genous penicillium penicillin's

And the others which are synthetic β-lactam antibioticsCarbapenems, & monobactams

Mechanism of action

The B-lactam antibiotics structurally resemble the terminal D-alanyl-D-alanine (D-Ala-D-Ala) in the pentapeptides on peptidoglycan (murein)Bacterial transpeptidases covalently bind the B-lactam antibiotics at the enzyme active site and the resultant acyl enzyme mol. is stable and inactive.The intact B-lactam ring is required for antibiotic action. The B-lactam ring modifies the active serine site on transpeptidases and blocks further enzyme function. Thus the bac. die when the cell is lysis (cell breakdown) as a result of cell wall syn. inhibition.

Mechanism of resistance

1-Inactivation of β-lactam ring 2-Alteration of penicillin-binding proteins [PBPs]

3-Reduction of antibiotic access to PBPs4-Elaboration of antibiotic efflex mechanism

Hydrolysis of β-lactam ring by β-lactamases [penicillinases or cephalosporinases]

The penicillin’s are a large group of bacteriostatic comp. that can be subdivided & classified by their chemical str. & spectrum of activity.

1-Natural penicillin’s

A-Penicillin G [Benzyl penicillin]: I.m, I.v therapy

Clinical uses 1-Endocarditis caused by S.viridans [or S. bovis] 2-Pharyngitis [group A β-hemolytic stre.]3-Syphilis [Trepanesoma pallidum]4-I.v Penicillin G is among the antibiotic of first choice for meningitis therapy [S. pneumoniae]5-A depot formulation of benzathine Penicillin G used for rheumatic fever prophylaxis.

B-Penicillin V orally administered phenoxy methyl derivative of Penicillin G Used to treat streptococcal Infections

Nafcillin, Oxacillin, Cloxacillin & Dicloxacillin : more resistant to bacterial β-lactamases than is Penicillin G.

Nafcillin & OxacillinParenterally effective used for : cellulitis, endocarditis, osteomyelitis, pneumonia, septic arthritis & toxic shock syndrome

Cloxacillin & DicloxacillinOrally effective used for : mild staphylococcal infection like Impetigo

2-Antistaphylococcal {Penicillinase -Resistant} Penicillin’s

3-Aminopenicillin’s

Ampicillin & Amoxicillin

Ampicillin 1 -achieve therapeutic conc. in the CSF only during

inflammation, therefore its effective treatment for meningitis caused by Listeria monocytogenens.

2-serious infection like enterococcal endocarditis & pneumonia caused by β-lactamase-negative H. influenzae.

Amoxicillin oral therapy for:Otitis media, Sinusitis, & in multidrug regimens for the eradication of H. pylori in duodenal & gastric ulcer

4 -Antipseudomonal penicillin’s

Mezlocillin, Piperacillin & Ticarcillin

Parenteral antibiotic used clinically in :1-patients with known or suspected P. aeruginosa infection.

2-To treat pneumonias associated with cystic fibrosis or mechanical ventilation

Carbenicillin

Orally antipseudomonal penicillin, used to treat UTI caused by P.aeruginosa, Proteus spp. & E.coli.

5 -β-lactamase inhibitor combinations

Ampicillin-sulbactum [parenteral formulation]

Ticarcillin-clavulanic acid [parenteral formulation]

Piperacillin-tazobactam [parenteral formulation]

Amoxicillin-clavulanic acid [oral bioavailability]

The addition of β-lactamase inhibitor significantly broadens the spectrum of antibacterial activity against β-lactamase-producing organism.

Clinical uses

Known or suspected mixed bacterial flora such as Biliary infectionDiabetic foot ulcerperitonitis