Clindamycin,

Chloramphenicol, Streptogramin, Oxazolidinones IDK2014

DRUG Clindamycin Chlorine-substituted derivative of Lincomycin (from Streptomyces lincolnensis) PK Oral : serum conc.= 2-3 ug/ml IV: 5-15 ug/ml (600 mg q 8 hrs.) 90% protein-bound Elimination: Liver, bile, urine Good penetration into most tissues except brain & CSF MOA Interferes with formation of initiation complexes & aminoacyl translocation reaction = inhibition of protein synthesis Identical binding site with erythromycin on the 50s bacterial ribosome subunit ACTIVITY RESISTANT: Enterococci G(-) aerobic pathogens poor permeability of outer membrane Clostridium difficile Mutation of ribosomal receptor site Modification of receptor by methylases Enzymatic inactivation SUSCEPTIBLE: Streptococci Staphylococci Pneumococci Bacteroides/other anaerobes CLINICAL USE/S Severe Anaerobic infections: Bacteroides With Aminoglycoside/Cephalosporin: for penetrating wounds of the abdomen & the gut Septic abortion Pelvic abscesses Aspiration pneumonia Prophylactic: for endocarditis in pxs w/ valvular heart disease undergoing dental procedure With Primaquine = for Pneumocystis carinii pneumonia (AIDS) With Pyrimethamine = for Toxoplasmosis of the brain (AIDS) ADVERSE EFFECT/S Diarrhea, nausea Skin rashes Impaired liver function Neutropenia Antibiotic-related colitis (caused by colonization of C. difficile)

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Clindamycin, Chloramphenicol, Streptogramin, Oxazolidinones IDK2014

DRUG Chloramphenicol MOA Inhibition of peptide bond formation at the 50 S subunit Blocks binding of the aminoacyl moiety of the charged tRNA molecule to the acceptor site of Ribosomal mRNA complex ACTIVITY CLINICAL USE/S ADVERSE EFFECTS BACTERICIDAL: 1. Typhoid Fever 1. HEMATOLOGIC 2. CNS infections - Bone Marrow & Red cell production Haemophilus influenzae suppression Meningitis Neisseria meningitides A. Anemia, serum iron, cellular Brain Abscess Bacteroides fragilis marrow 3. Anaerobic infections BACTERIOSTATIC: Dose related > 25mcg/mL 4. Deep ocular infections Treponema Reversible C. diphteriae ALTERNATIVE TX: Prolonged treatment (1 2 Rickettsia 1. Pneumococcal/ weeks) Pneumococci Meningococcal MOA: Extension of pharmacologic Chlamydia Meningitis effect Streptococci DRUG: Benzyl PCN B. Aplastic Anemia Pancytopenia E. coli S. epidermidis 2. Rickettsial Infections DRUG: Non-dose related Shigella Tetracycline Irreversible -> fatal S. aureus MOA: Idiosyncratic reaction Salmonella 2. GRAY SYNDROME in INFANTS: RESISTANT : Inadequate Glucuronyl P. Aeruginosa transferase Providencia > 50 mg/kg/day = accumulate Acitenobacter Flaccidity, vomiting, S. Marcesens hypothermia, gray color, P. Rettgeri shock, collapse 3. NEUROLOGIC Low-level Resistance: Optic neuritis, peripheral Mutants less permeable to the neuritis, headache, drug opthalmoplegia, confusion Chloramphenicol acetyltransferase: 4. OTHERS: RARE plasmid-encoded enzyme = GIT, Allergic reactions, inactivates the drug Superinfections

PK ABSORPTION: 75 90% from the GIT Oral preparation PALMITATE Parenteral preparation SUCCINATE Serum Level : IV = ORAL DISTRIBUTION: 45% protein bound Brain and CSF 65% Aqueous & vitreous humour Synovial, pleural, ascitic fluid Placenta, breast milk METABOLISM: 90% Glucoronide Conjugation 2% Deacetylation - reduce dosage in hepatic failure ELIMINATION: 90% Excretion in urine (small amount) Bile or feces

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Clindamycin, Chloramphenicol, Streptogramin, Oxazolidinones IDK2014

DRUG Streptogramins QUINOPRISTIN- DALFOPRISTIN Dalfopristin streptogramin A Quinupristin streptogramin B Quinopristin- Dalfopristin = 30:70 ratio Bactericidal (most organisms, except Enterococcus faecium) MOA PK Administered IV Rapid metabolism: o Quinopristin (0.85 hrs) o Dlafopristin (0.7 hrs) Not metabolized by CYP450 enzymes BUT significantly inhibits CYP3A4(metabolizes warfarin, diazepam, astemizole, terfenadine, cisapride, cyclosporine, non-nucleoside reverse transcriptase inhibitors) Elimination: o Fecal route: 75 % o Urine: < 20 % Dose adjustments NOT necessary in: Renal failure Peritoneal Hemodialysis Dose adjusted in Hepatic insufficiency ACTIVITY G (+) cocci (inc. resistant strains of Streptococci) Staphyloccoci (Methicillin- resistant & suscebtible strains) PCN-resistant strains of S. pneumoniae E. faecium (not E. faecalis) CLINICAL USE/S Treatment of infections caused by staphylococci or by vancomycin- resistant strains of E. faecium, but not E. faecalis ADVERSE EFFECTS Infusion-related events: o pain at injection site o phlebitis o arthralgia-myalgia syndrome

FDLL

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Clindamycin, Chloramphenicol, Streptogramin, Oxazolidinones IDK2014

DRUG Oxazolidinones MOA Prevents formation of ribosome complex that initiates protein synthesis : Binds to 23S ribosomal RNA of the 50S subunit PK Oral = 100% bioavailability Metabolism: o Oxidation = 2 inactive metabolites Does not induce/inhibit CYP450 enzymes Dose: 600 mg 2x/day Pear serum conc. = 18 ug/ml ACTIVITY Resistance mutation of linezolid binding site on 23S ribosomal RNA BACTERIOSTATIC G (+) pathogens: o Staphyloccoci, o anaerobic cocci G (+) rods: Corynebacteria, o Listeria monocytogenes BACTERICIDAL Streptococci CLINICAL USE/S Nosocomial pneumonias Community-acquired pneumonia Vancomycin-resistant E. faecium infxns. Skin infections Multiple drug-resistant G(+) bacteria ADVERSE EFFECT/S Thrombocytopenia - > 2 weeks admn. Neutropenia (in predisposed pxs. or pxs with bone marrow suppression)

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