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In The Name of Allah In The Name of Allah

Miscellaneous Antimicrobial Agents By: Dr. M. Minaiyan Isfahan University of Medical Science Miscellaneous Antimicrobial Agents By: Dr. M. Minaiyan Isfahan University of Medical Science

Linezolid n n n It is active against staphylococci, streptococci, enterococci, and gram-positive rods Linezolid n n n It is active against staphylococci, streptococci, enterococci, and gram-positive rods such as corynebacteria and Listeria monocytogenes It is primarily a bacteriostatic agent (Protein Synthesis Inhibitor) except for streptococci, for which it is bactericidal The recommended dosage for most indications is 600 mg twice daily, either orally or intravenously

Linezolid (ADR and Toxicity) n n Thrombocytopenia is the most common manifestation (seen in Linezolid (ADR and Toxicity) n n Thrombocytopenia is the most common manifestation (seen in approximately 3% of treatment courses) Anemia and neutropenia Optic and peripheral neuropathy and lactic acidosis have been reported with prolonged courses of linezolid Interactions with MAOI and SSRIs

Linezolid (Clinical Uses) n n n Vancomycin-resistant enterococcal infections Nosocomial pneumonia Community-acquired pneumonia Skin Linezolid (Clinical Uses) n n n Vancomycin-resistant enterococcal infections Nosocomial pneumonia Community-acquired pneumonia Skin infections, complicated or uncomplicated. It should be reserved for treatment of infections caused by multidrug-resistant gram-positive bacteria.

Teicoplanin n A glycopeptide similar to vancomycin Its mechanism of action is also similar Teicoplanin n A glycopeptide similar to vancomycin Its mechanism of action is also similar to vancomycin but it can be used in MRSA strains are sometimes resistant to vancomycin It is used IV and IM with a long half life (4070 h)

Mupirocin n It is isolated from P. fluoresence (Psudomonic acid) Topical use is only Mupirocin n It is isolated from P. fluoresence (Psudomonic acid) Topical use is only justified because of rapid inactivation within the circulation Inhibits Isoleucyl-t. RNA synthase specially in Staphylococcus aurous

Mupirocin n n It is effective to treat Staphyloccocal infections both methicillin-susceptible and methicillin-resistant Mupirocin n n It is effective to treat Staphyloccocal infections both methicillin-susceptible and methicillin-resistant species More than 95% of S. aurous isolates are still susceptible Impetigo and minor skin lesions are main clinical indications It might be used for nasal staphylococcal carriage eradication

Polymyxins n n n They are basic peptides which act as cationic detergents and Polymyxins n n n They are basic peptides which act as cationic detergents and damage cell membrane Two common type are: polymyxin B and polymyxin E (Colistin) Gram negative aerobes are usually susceptible Gram positive aerobes, Proteus and Neisseria species are usually resistant. Because of significant toxicity, their clinical uses are limited to topical uses.

Nalidixic Acid n n It is a quinolone but not fluorinated congener Gram negative Nalidixic Acid n n It is a quinolone but not fluorinated congener Gram negative bacteria is the main spectrum of action P. aeroginosae and Proteus strains are resistant Only in urinary tract, it reaches to bactericidal levels

Nitrofurantoin n n A urinary antiseptic with specific action on E. coli in lower Nitrofurantoin n n A urinary antiseptic with specific action on E. coli in lower urinary infections Cross resistance and acquired resistance are usually uncommon but P. aeroginosa and Proteous sp are resisatnt It is contraindicated in patients with renal insufficiency Undergone redox reactions to produce active metabolite and exert toxic reactions with DNA

Nitrofurantoin n n The best antibacterial efficiency is attained in urine p. H of Nitrofurantoin n n The best antibacterial efficiency is attained in urine p. H of 5. 5 and lower It should not be used for upper UTIs It is very suitable for prevention of recurrent UTIs in women. Nitrofurantoin antagonise the action of Nalidixic acid and might causes neurophathy and hemolytic anemia in patients with G 6 PD deficiency.

Methenamine Mandelate n n Produces formaldehyde as well as mandelic acid in acidic medium Methenamine Mandelate n n Produces formaldehyde as well as mandelic acid in acidic medium of urine (p. H 5. 5) It should not be used concurrently with Sulfonamides because of insoluble metabolite production and resultant antagonism Proteus species are usually resistant Patients taking this drug may have false positive results for urine catecholamine tests.

Disinfectants and Antiseptics Disinfectants and Antiseptics

Definition n n Disinfectants are strong chemical agents that inhibit or kill micro-organisms Antiseptics Definition n n Disinfectants are strong chemical agents that inhibit or kill micro-organisms Antiseptics are disinfectants with sufficiently lower toxicity that they can be used directly on skin and mucus membranes. Sterillants kill both the vegetative and spores of microorganisms. Products are devoid of any vital or vegetative microorganism and their residues are named sterile and pyrogen free.

Alcohols (60 -90%) (Ethanol-Isopropyl Alcohol) n n n Advantages Rapid action Effective on vegetative Alcohols (60 -90%) (Ethanol-Isopropyl Alcohol) n n n Advantages Rapid action Effective on vegetative bacteria specially gram +, Tuberclosis, Fungi, Lipophylic viruses Low cost n n Disadvantages Inactive on spores, hydrophilic viruses Without residual effect Skin drying properties Flammable and must be allowed to evaporate before cautery, electrosurgery and laser surgery.

Chlorhexidine gluconate (2 -%) n n n Advantages Most activity against gram+ bacteria With Chlorhexidine gluconate (2 -%) n n n Advantages Most activity against gram+ bacteria With residual effect Moderate activity against fungi and viruses Spore generation might be inhibited by the presence of detergent Safe as mouth wash n n n Disadvantages Intercats with non-ionic and anionic detergents e. g. soaps, surfactants It should not be used during the surgery of middle ear and neurosurgery Slower action rather than alcohols

Halogens (Iodine, Iodophores, Chlorine) Iodine n n Tincture of iodine contains 2% iodine & Halogens (Iodine, Iodophores, Chlorine) Iodine n n Tincture of iodine contains 2% iodine & 2. 4% Na. I dissolved in alcohol The most rapid acting detergent on intact skin (1 min for bacteria and 15 min for spores) It is effective on all forms of microorganisms Hypersensitivity reactions and coloring properties are most common limitations

Ionophores (Betadin, PVP) n n n Complex of iodine and surface active agent (Ionophore) Ionophores (Betadin, PVP) n n n Complex of iodine and surface active agent (Ionophore) with disinfectant and antiseptic properties It is used as antiseptic, disinfectant and scrub solution Better activity of iodine with less hypersensitivity reactions The amount of available free iodine depends on degree of dilution More concentrated solutions are suitable for disinfection.

Chlorine (Hypochlorite Na, 5. 25%) n n House hold bleach and the most common Chlorine (Hypochlorite Na, 5. 25%) n n House hold bleach and the most common disinfectant and oxidizing agent A 1/10 dilution produces 5000 ppm chlorine which is enough for killing spores Dilution with tap water causes a p. H of 7. 5 -8 which retains its activity for several months Surface proteins, blood, serum and feces interact with it and causes inactivation

Chlorine (Hypochlorite Na, 5. 25%) n n n Chlorine interacts with formaldehyde and produces Chlorine (Hypochlorite Na, 5. 25%) n n n Chlorine interacts with formaldehyde and produces bis-chloromethyl molecules which are carcinogenic and must be avoided Hypochlorite sodium is corrosive for metal surfaces Its mixing with acids and urine should be avoided because of chlorine gas production

Benzalkanium Chloride (Cetrimide, Savlon, Cetavlon, Detol, . . n n n Quaternary ammonium compound Benzalkanium Chloride (Cetrimide, Savlon, Cetavlon, Detol, . . n n n Quaternary ammonium compound which acts as cationic detergent Precipitates proteins, inactivates enzymes and disrupts cell membranes They are bacteriostatic, fungistatic virustatic and sporostatic agents. Gram positives are more susceptible than gram negatives (Tubercle and P. aeroginosa are exceptions) Inactivated in the presence of anionic detergents and surfactants as well as Ca, Mg, Fe, & Al ions

Aldehydes (Formaldehyde-Glutaraldehyde) n n n Are suitable disinfectants and sterillants for instruments (dialysis, spirometery, Aldehydes (Formaldehyde-Glutaraldehyde) n n n Are suitable disinfectants and sterillants for instruments (dialysis, spirometery, endoscopy, dentistry apparatus, …) They are not corrosive for metal, plastic and rubber materials They alkylate chemical groups in proteins and nucleic acids Formaldehyde 40%= Formalin 100% Formaldehyde 4%= Formalin 10% Formaldehyde 8%= Formalin 20%

Aldehydes (Formaldehyde-Glutaraldehyde) n n n n Formalin 10% is quite suitable for tissue fixation Aldehydes (Formaldehyde-Glutaraldehyde) n n n n Formalin 10% is quite suitable for tissue fixation Formalin 20% is preferable as germicide & sporocidal Glutaraldehyde Solutions of 2% W/V are most common. It should be alkalinized to p. H 7. 7 -8. 5 for maximum efficacy Once activated, solutions are stable for 14 days after which polymerization reduces its activity Formaldehyde has pungent odor and is irritant. They are allergic and carcinogenic so exposure limitations should be critically considered

Hydrogen Peroxide n n Strong oxidizing agent with bactericidal, fungicidal, virucidal and sporocial effects Hydrogen Peroxide n n Strong oxidizing agent with bactericidal, fungicidal, virucidal and sporocial effects The decomposed by-products are not toxic and pollutant for environment In concentrations of 10 -25% are sporocial In concentrations of 3 -6% are disinfectants for medical devices, soft lenses, prosthetic devices and cartons containing milk or juices

Heavy Metals (Mercury and Sliver) n n Disadvantages: Biological toxicity, Environmental pollution, Acquired resistance, Heavy Metals (Mercury and Sliver) n n Disadvantages: Biological toxicity, Environmental pollution, Acquired resistance, Hypersensitivity reactions, Surface absorption (rubber-plastic) Thiomersal (0. 001 -0. 004%) is used as preservative in vaccines, antitoxins and immune sera Silver nitrate (0. 1%) in ophthalmic drops for preventing ophthalmic gonococcal infections. Silver sulfadiazine slowly releases silver for suppressing bacterial growth in burn wounds

Notes n n Hand washing with soap and warm water is the most important Notes n n Hand washing with soap and warm water is the most important means of preventing infection transmission Usage of skin disinfectants and detergents as surgical scrabs are recommended only before the surgical operations

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