抗感染及抗感染药物（英文ppt）

Antibiotics Antiviral Antifungal Antimalarial Antiseptic will eventually lead to bacterial death One of the first groups of antibiotics Sulfadiazine (Coptin) Sulfamethoxazole Sulfisoxazole (Gantrisin) Used to treat otitis media, UTIs, other conditions Often combined with another antibiotic Sulfamethoxazole-trimethoprim (Bactrim) Bacteriostatic action Prevent synthesis of folic acid required for synthesis of purines and nucleic acid Do not affect human cells or certain bacteria they can use preformed folic acid Only affect organisms that synthesize their own folic acid Treatment of UTIs caused by susceptible strains of: Enterobacter spp., Escherichia coli, Klebsiella spp., Proteus mirabilis, Proteus vulgaris, Staphylococcus aureus Nocardiosis (caused by Nocardia - pneumonia) Pneumocystis jiroveci pneumonia (PJP) co-trimoxazole (Bactrim, Septra) Upper respiratory tract infections trimethoprim/sulfamethoxazole (co-trimoxazole, Bactrim, Septra) Used to treat UTIs, PJP, otitis media, other conditions erythromycin/sulfisoxazole (Pediazole) Used to treat otitis media Body System Adverse Effects Blood Hemolytic and aplastic anemia, agranulocytosis, thrombocytopenia Integumentary Photosensitivity, exfoliative dermatitis, Stevens-Johnson syndrome, epidermal necrolysis GI Nausea, vomiting, diarrhea, pancreatitis Other Convulsions, crystalluria, toxic nephrosis, headache, peripheral neuritis, urticaria Sulfonamides Should be taken with at least 2000 mL of fluid per day, unless contraindicated Oral forms should be taken with food or milk to reduce GI upset Natural penicillins Penicillinase-resistant penicillins Aminopenicillins Extended-spectrum penicillins Natural penicillins penicillin G, penicillin V potassium Penicillinase-resistant drugs cloxacillin, dicloxacillin, nafcillin, oxacillin Aminopenicillins amoxicillin, ampicillin, bacampicillin Extended-spectrum drugs piperacillin, ticarcillin, carbenicillin First introduced in the 1940s Bactericidal: inhibit cell wall synthesis Kill a wide variety of bacteria Also called “-lactams” Bacteria produce enzymes capable of destroying penicillins These enzymes are known as -lactamases As a result, the medication is not effect Chemicals used to inhibit these enzymes: Clavulanic acid Tazobactam Sulbactam Bind with -lactamase and prevent the enzyme from breaking down the penicillin - making the drug more effective Penicillin-lactamase inhibitor combination drugs ampicillin + sulbactam = Unasyn amoxicillin + clavulanic acid = Augmentin ticarcillin + clavulanic acid = Timentin piperacillin + tazobactam = Zosyn Penicillins enter the bacteria via the cell wall Inside the cell they bind to penicillin-binding protein Once bound, normal cell wall synthesis is disrupted Result: bacteria cells die from cell lysis Penicillins do not kill other cells in the body Prevention and treatment of infections caused by susceptible bacteria, such as: Gram-positive bacteria Streptococcus, Enterococcus, Staphylococcus Allergic reactions occur in 0.7% to 4% of cases Urticaria, pruritus, angioedema Those allergic to penicillins have a fourfold to sixfold increased risk of allergy to other -lactam antibiotics Cross-reactivity between penicillins and cephalosporins is between 1% and 18% Common adverse effects Nausea, vomiting, diarrhea, abdominal pain Other adverse effects are less common MANY interactions! NSAIDs Oral contraceptives warfarin Others Any patient taking a penicillin should be carefully monitored for an allergic reaction for at least 30 minutes after its administration The effectiveness of oral penicillins is decreased when taken with caffeine, citrus fruit, cola beverages, fruit juices, or tomato juice Administer with at least 6 ounces of water Four Generations: Semisynthetic derivatives from a fungus Structurally and pharmacologically related to penicillins Bactericidal action Broad spectrum Divided into groups according to antimicrobial activity Used for surgical prophylaxis, URIs, otitis media cefazolin (Ancef and Kefzol): IV or IM cephalexin (Keflex): PO Good gram-positive coverage Better gram-negative coverage than first generation Cefmetazole IV Cefprozil (Cefzil) PO Cefoxitin (Mefoxin) IV Cefaclor (Ceclor) PO cefoxitin (Mefoxin): IV and IM Used prophylactically for abdominal or colorectal surgeries Also kills anaerobes cefuroxime (Kefurox and Ceftin): PO Surgical prophylaxis Does not kill anaerobes ceftriaxone (Rocephin) IV and IM, long half-life, once-a-day dosing Elimination is primarily hepatic Easily passes meninges and diffused into CSF to treat CNS infections ceftazidime (Fortaz, Tazidime) IV and IM forms Excellent gram-negative coverage Used for difficult-to-treat organisms such as Pseudomonas Eliminated renally instead of biliary route Excellent spectrum of coverage Newest cephalosporin drugs Broader spectrum of antibacterial activity than third generation, especially against gram- positive bacteria Tx: UTI, Skin infections, pneumonia cefepime (Maxipime) GM +/- cefdinir cefditoren pivoxil (Spectracef) Similar to penicillins Mild diarrhea, abdominal cramps, rash, pruritis, redness, edema Potential cross-sensitivity with penicillins if allergies exist Orally administered forms should be given with food to decrease GI upset, even though this will delay absorption Some of these drugs may cause a disulfiram (Antabuse)-like reaction when taken with alcohol Very broad-spectrum antibacterial action Reserved for complicated body cavity and connective tissue infections May cause drug-induced seizure activity All given parenterally imipenem-cilastatin (Primaxin) Used for treatment of bone, joint, skin, and soft tissue infections Cilastatin inhibits an enzyme that breaks down imipenem meropenem (Merrem) bacterial meningitis ertapenem (Invanz) - newest aztreonam (Azactam) Synthetic -lactam antibiotic Primarily active against aerobic gram-negative bacteria (E. coli, Klebsiella spp., Pseudomonas spp.) Bactericidal Used for moderately severe systemic infections and UTIs Prevent protein synthesis within bacterial cells Considered bacteriostatic - Bacteria will eventually die In high enough concentrations, may also be bactericidal erythromycin (E-mycin azithromycin (Zithromax) clarithromycin (Biaxin) Adverse Effects: GI effects, primarily with erythromycin Nausea, vomiting, diarrhea, hepatotoxicity, flatulence, jaundice, anorexia Newer drugs, azithromycin and clarithromycin: fewer GI adverse effects, longer duration of action, better efficacy, better tissue penetration These drugs are highly protein-bound and will cause severe interactions with other protein-bound drugs The absorption of oral erythromycin is enhanced when taken on an empty stomach, but because of the high incidence of GI upset, many drugs are taken after a meal or snack telithromycin (Ketek) Only drug in this class Better antibacterial coverage than macrolides Active against gram-positive bacteria, including multi-drug resistant strains of S. pneumoniae Active against selected gram-negative bacteria Indications: Community-acquired pneumonia, acute bacterial sinusitis, bacterial exacerbations of chronic bronchitis Adverse reactions include: Headache, dizziness, GI discomfort, altered potassium levels, prolonged QT intervals Natural and semisynthetic Obtained from cultures of Streptomyces Bacteriostaticinhibit bacterial growth Inhibit protein synthesis Stop many essential functions of the bacteria demeclocycline (Declomycin) oxytetracycline tetracycline doxycycline (Doryx, Vibramycin) Minocycline Strong affinity for calcium Discoloration of permanent teeth and tooth enamel in fetuses and children, or nursing infants if taken by the mother May retard fetal skeletal development if taken during pregnancy Alteration in intestinal flora may result in: Superinfection (overgrowth of nonsusceptible organisms such as Candida) Diarrhea Pseudomembranous colitis Milk products, iron preparations, antacids, and other dairy products should be avoided because of the chelation and drug-binding that occurs All medications should be taken with 6 to 8 ounces of fluid, preferably water Due to photosensitivity, avoid sunlight and tanning beds Before beginning therapy, assess drug allergies; renal, liver, and cardiac function; and other lab studies Be sure to obtain patient health history, including immune status Assess for conditions that may be contraindications to antibiotic use or that may indicate cautious use Assess for potential drug interactions It is ESSENTIAL to obtain cultures from appropriate sites BEFORE beginning antibiotic therapy Each class of antibiotics has specific adverse effects and drug interactions that must be carefully assessed and monitored The most common adverse effects of antibiotics are nausea, vomiting, and diarrhea All oral antibiotics are absorbed better if taken with at least 6 to 8 ounces of water Monitor for therapeutic effects Improvement of signs and symptoms of infection Return to normal vital signs Negative culture and sensitivity tests Disappearance of fever, lethargy, drainage, and redness Monitor for adverse reactions Therapeutic drug monitoring Minimum inhibitory concentration (MIC) Concentration-dependent killing Once-daily dosing vs. multi-daily dosing Peak and trough blood levels Synergistic effects Post-antibiotic effect (PAE) Ototoxicity Temporary or permanent hearing loss, balance problems Nephrotoxicity Varying degrees of reduced renal function Rising serum creatinine may indicate reduced creatinine clearance Monitor trough levels every 3 days while on therapy or as ordered gentamicin (Garamycin) kanamycin neomycin (Neo-Fradin) streptomycin tobramycin (Nebcin) amikacin (Amikin) netilmicin paromomycin Natural and semisynthetic Produced from Streptomyces Poor oral absorption; no PO forms Very potent antibiotics with serious toxicities Bactericidal; prevents protein synthesis Kill mostly gram-negative; some gram-positive Used to kill gram-negative bacteria Pseudomonas, E. coli, Proteus, Klebsiella, Serratia Often used in combination with other antibiotics for synergistic effects Certain gram-positive infections that are resistant to other antibiotics Aminoglycosides poorly absorbed through the GI tract - given IV Exception: neomycin Given orally or by enema - decontaminate the GI tract before surgical procedures Ototoxicity and nephrotoxicity are the most significant Headache Paresthesia Fever Superinfections Vertigo Skin rash Dizziness ciprofloxacin (Cipro) norfloxacin (Noroxin) levofloxacin (Levaquin) gatifloxacin (Tequin) moxifloxacin (Avelox) gemifloxacin (Factive) Also called “quinolones” Excellent oral absorption Absorption reduced by antacids Effective against gram-negative organisms and some gram-positive organisms Mechanism of Action: Bactericidal Alter DNA of bacteria, causing death Do not affect human DNA Lower respiratory tract infections Bone and joint infections Infectious diarrhea Urinary tract infections Skin infections Sexually transmitted diseases Anthrax Body System Adverse Effects CNS Headache, dizziness, fatigue, depression, restlessness, insomnia GI Nausea, vomiting, diarrhea, constipation, thrush, increased LFTs Integumentary Rash, pruritus, urticaria, flushing, photosensitivity (with lomefloxacin) Other Fever, chills, blurred vision, tinnitus clindamycin (Cleocin) dapsone linezolid (Zyvox) metronidazole (Flagyl) nitrofurantoin (Macrodantin) quinupristin and dalfopristin (Synercid) daptomycin (Cubicin) clindamycin (Cleocin) Used for chronic bone infections, GU infections, intraabdominal infections, other serious infections May cause pseudomembranous colitis dapsone Used for leprosy (Hansens disease), PJP pneumonia associated with HIV/AIDS, other uses linezolid (Zyvox) New class: oxazolidinones Used to treat vancomycin-resistant Enterococcus faecium (VREF, VRE), hospital-acquired skin and skin structure infections, including those with MRSA May cause hypotension, serotonin syndrome if taken with SSRIs, and reactions if taken with tyramine- containing foods nitrofurantoin (Macrodantin) Primarily used for UTIs (E. coli, S. aureus, Klebsiella spp., Enterobacter spp.) Use carefully if renal function is impaired Drug concentrates in the urine Usually well-tolerated if patient is kept well- hydrated quinupristin and dalfopristin (Synercid) 30:70 combination, work synergistically Used for bacteremia and infections caused by vancomycin-resistant Enterococcus (VRE) and other complicated skin infections May cause arthralgias, myalgias daptomycin (Cubicin) New class: lipopeptide Used to treat complicated skin and soft-tissue infections Natural, bactericidal antibiotic - Destroys cell wall Treatment of choice for MRSA, and other gram-positive infections Must monitor blood levels to ensure therapeutic levels and prevent toxicity May cause ototoxicity and nephrotoxicity Should be infused over 60 minutes - Monitor IV site closely Red man syndrome may occur Flushing/itching of head, neck, face, upper trunk Antihistamine may be ordered to reduce these effects Ensure adequate hydration (2 L fluids/24 hr) if not contraindicated to prevent nephrotoxicity Before beginning