Dr Khulood Alsaraf

Antimicrobial drugs

infections because of their selective toxicity (the ability to kill an invading M.O without harming the cells of the host ).

: are effective in the treatment of

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.

Selection of antimicrobial agents

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 bacteria Bacteriocidal drugs

inhibit the growth of kill bacteria

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

Chemotherapeutic spectra

1-Naturally(inherent): pseudomonas aeruginosa resistant to penicillin G 2-Acquired : staph. aureus resistant to penicillin G after previous exposure

Resistance to antibacterial

Combination of antimicrobial drugs

Advantages

1-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 occur 2-In treatment of enterococcal endocarditis 3-when there is a risk of developing resistant organisms 2-Infection of unknown origin

Disadvantages

A 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 [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 -lactam antibiotics

Fungi of genous cephalosporium cephalosporin's Fungi of genous penicillium penicillin's And the others which are synthetic -lactam antibiotics Carbapenems, & monobactams

Mechanism of action
The B-lactam antibiotics structurally resemble the terminal Dalanyl-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 -lactam ring 2-Alteration of penicillin-binding proteins [PBPs] 3-Reduction of antibiotic access to PBPs 4-Elaboration of antibiotic efflex mechanism

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

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

1-Natural penicillins
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 -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.

orally administered phenoxy methyl derivative of Penicillin G

Used to treat streptococcal Infections

B-Penicillin V

2-Antistaphylococcal {PenicillinaseResistant} Penicillins

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

Nafcillin & Oxacillin

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

Cloxacillin & Dicloxacillin

Orally effective used for : mild staphylococcal infection like Impetigo

3-Aminopenicillins
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 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 penicillins
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- -lactamase inhibitor combinations

Ampicillin-sulbactum [parenteral formulation] Ticarcillin-clavulanic acid [parenteral formulation] Piperacillin-tazobactam [parenteral formulation] Amoxicillin-clavulanic acid [oral bioavailability]
The addition of -lactamase inhibitor significantly broadens the spectrum of antibacterial activity against -lactamase-producing organism.

Clinical uses
Known or suspected mixed bacterial flora such as Biliary infection Diabetic foot ulcer peritonitis