Antibacterials PDF

Antibacterials Huma Murtaza Mphil optometry Senior lecture Ripha International University Introduction  Antibacterials are the substances of drugs that act against invading microorganisms known as bacteria.  Previousl...

Antibacterials Huma Murtaza Mphil optometry Senior lecture Ripha International University Introduction  Antibacterials are the substances of drugs that act against invading microorganisms known as bacteria.  Previously antibacterials synthesized from other microorganism named antibiotics.  Now most of antibacterials are produced synthetically from chemicals. Mechanism of action  By increasing cell membrane permeability causing leakage of cell material, e.g polymyxin, bacitracin etc.  By causing lysis of cell wall, e,g penicillins, vancomycin etc.  By suppressing protein synthesis of bacteriae.g tetracycline, chloramphenicol, erythromycin, clindamycin, etc.  By interfering with DNA function of bacteria, e.g rifampicin, metronidazole.  By inhibiting DNA gyrase activity e.g flouroquinolones.  By causing confusion of mRNA code and changing the permeability of bacteria, e.g aminoglycosides.  By interfering in bacterial metabolism e.g sulphonamides, pyrimethamine, ethambutol. Common toxicities  Chloramphenicol – bone marrow depression  Aminoglycosides- renal and 8th cranial nerve damage  Vancomycin- renal and ototoxicity  Polymyxin B- renal and neurological toxicity  Tetracyclines- hepatic and renal damage  Amphotericin B- bone marrow depression, neurological complications and renal damage. Mechanism of development of drug resistance  There are two important processes by which a microbe may acquire resistance to a particular drug.  Mutation which may be single step or multi step.  Transfer of gene, which involves processes like conjugation, transformation and transduction.  By these mechanism microorganism get resistance by :  Generation of new metabolic pathway that does not involve the antimicrobial concerned.  Development of new enzymes which breakup the antimicrobial molecule.  Alteration in membrane permeability so that effective concentration of the drug does not reach inside the microbial cell. Cross resistance  When an organism become resistant to a particular drug it also exhibits resistance towards some other drugs which are usually structurally(chemically) related to that drug.  Example: resistance developed to a particular sulphonamides means resistance to whole group.this is called cross resistance.  It is of two types :  Two way cross resistance: resistance to erythromycin means resistance to clindamycin and vice versa.  One way cross resistance: resistance to neomycin means resistance to streptomycin also but those resistant to streptomycin may respond to neomycin. Therapeutic guidelines to avoid resistance problems  When prolonged drug therapy (e.g tubercular infection) multiple drugs should be started at a time.  To treat microbe of high pathogenicity e.g E COLI , drug therapy should be continued till the microbes are totally eradicated.  To treat microbe of low pathogenicity unnecessary lengthy period of treatment should be avoided. Antibiotics to avoid during pregnancy  Aminoglycosides  Chloramphenicol  tetracycline,  flouroquinolones,  sulphonamides and nitrofurantoin etc.  Should be avoided because they either have teratogenic effect or may deteriorate fetomaternal well being. Superinfection  Means development of new infection while using antimicrobial agent that occurs due to destruction of normal bacterial flora.  Normal flora serves two defensive functions :  Liberates a chemical called bacitracin which inhibit pathogens  Deprives pathogens from nutrients i.e pathogens have to compete with normal flora for nutrition.  Super infection usually occurs in patients suffering from  AIDS  Diabetes mellitus  Bone marrow depression  Prolonges use of immunosuppresives  Corticosteroids  Pateints undergoing chemotherapy.  The causative organism usually responsible for super infections are  Staphylococci  Candida albicans  Proteus group  Pseudomonas group  Clostridium deficile etc Classes of antibiotics  Sulfonamides  Cephalosporins  Aminoglycosides  Tetracyclines  Chloraomphenicol  Floroquinolones Sulfonamides  Sulfonamides are synthetic bacteriostatic antibiotics that competitively inhibit conversion of p-aminobenzoic acid to dihydrfolate, which bacteria need for folate synthesis. Uses of sulfonamides  Chlamydial infections like trachoma.  Inclusion conjunctivitis(sodium sulfacetamide)  Toxoplasmosis (sulfadiazine+pyrimethamine) Cephalosporins  Cephalosporins are bactericidal and, like other β-lactam antibiotics, disrupt the synthesis of the peptidoglycan layer forming the bacterial cell wall. The peptidoglycan layer is important for cell wall structural integrity.  They are derived from fungus called acremonium.  Adverse effects : Common adverse drug reactions (ADRs) (≥ 1% of patients) associated with the cephalosporin therapy include: diarrhea, nausea, rash, electrolyte disturbances, and pain and inflammation at injection site. Infrequent ADRs (0.1–1% of patients) include vomiting, headache, dizziness, oral and vaginal candidiasis, pseudomembranous colitis, superinfection, eosinophilia, nephrotoxicity, neutropenia, thrombocyt openia, and fever.  Generations of cephalosporins ?  Drug name: ceporex, cefalor, cefaclor, neucef. Aminoglycosides  They are bacterial proteins synthesis inhibitors.  Mainly active against gm negative bacilli  E.g  Gentamycin- 0.3% eye drops  Tobramycin-1%eye drop  Neomycin-0.3-0.5% eye drops Flouroquinolones  quinolone antibiotics in use are fluoroquinolones, which contain a fluorine atom in their chemical structure and are effective against both Gram- negative and Gram-positive bacteria.  One example is ciprofloxacin , one of the most widely used antibiotics worldwide.  Fluoroquinolones act by inhibiting bacterial DNA synthesis.  They bind to and interfere with DNA gyrase and topoisomerase IV enzymes, which are essential for DNA replication, transcription, and repair in bacteria.  Inhibition of these enzymes leads to the accumulation of DNA damage, breakage, and cell death in susceptible bacteria. Uses in eyes  Ciprofloxacin eyedrops are licensed for the treatment of "corneal ulcers and superficial infections of the eye",  ofloxacin eyedrops for "external ocular infections (such as conjunctivitis and keratoconjunctivitis) Tetracyclines & Chloromphenicol  Tetracyclines  Inhibit protein synthesis  Active against both gm + and gm-, some fungi and chylamadia  Used in bacterial blephritis  Bacterial conjunctivitis, keratitis and trachoma  Drug name :tetracycline hydrochloride, histazoline (combo)  Chloromphenicol  Inhibit protein synthesis  Broad spectrum  Bacteriostatic  Used in bacterial conjuctivitis  0.5%eye drop, ointment.  Drug name: optachlor, mexchlor, chloroptic Eye conditions and antibiotic uses  Trachoma: can be treated by topical and systemic tetracyclines, or erythromycin or systemic azithromycine.  Bacterial keratitis (bacterial corneal ulcers): can be treated by topical fortified penicillins, cephalosporins, vancomycins, flouroquinolones, or aminoglycosides.  Bacterial conjunctivitis: is less severe and self limited. Can be treated by topical erythromycin, aminoglycosides, flouroquinolones or chloramphenicol etc can be used. Endophthalmitis  Broad spectrum antibiotics ( vancomycin, aminoglycosides or cephalosporins)  Clindamycin in drug users until bacillus infection can be ruled out  Intravitreal antiobiotics are also indicated.  Vitrectomy may be needed on basis of no response or severity