感染的治疗（英文ppt）treatmentof

Treatment of Infection Professor Mark Pallen Treatment of Infection How Do Antimicrobials Work? Key concept: selective toxicity the antimicrobial agent blocks or inhibits a metabolic pathway in a micro- organism which is either absent or is radically different in the mammalian cells of the human host Principle of antibiotic spectrum Different antibiotics target different kinds of bacteria i.e., different spectrum of activity Examples: Penicillin G (= original pen.) mainly streptococci (narrow spectrum) Vancomycin only Gram-positive bacteria (intermediate spectrum) Carbapenems many different bacteria (very broad spectrum) Treatment of Infection Anti-Microbial Drug Targets Antimicrobials acting on the bacterial cell wall Interfere with synthesis of peptidoglycan layer in cell wall eventually cause cell lysis bind to and inhibit activity of enzymes responsible for peptidoglycan synthesis aka “penicillin-binding proteins” Antimicrobials acting on the bacterial cell wall Beta-lactams: Penicillins benzylpenicillin flucloxacillin ampicillin piperacillin Antimicrobials acting on the bacterial cell wall Beta-lactams: Cephalosporins Orally active cephradine cephalexin Broad spectrum cefuroxime cefotaxme ceftriaxone ceftazidime Antimicrobials acting on the bacterial cell wall Unusual beta-lactams Carbapenems Imipenem, meropenem very wide spectrum Monobactams Aztreonam only Gram-negatives Glycopeptides only Gram-positives, but broad spectrum vancomycin teicoplanin Antimicrobials acting on nucleic acid synthesis Inhibitors Of Precursor Synthesis sulphonamides / Questions to ask before starting antibiotics Does this patient actually need antibiotics? What is best treatment? What are the likely organisms? Where is the infection? How much, how often, what route, for how long? How much does it cost? Are there any problems in using antibiotics in this patient? Have you taken bacteriology specimens first?! Clinical use of antibiotics Gillespie SH & Bamford KB. 2003. Medical microbiology & infection at a glance. Does this patient need antibiotics? Is the patient even infected? e.g. urethral syndrome vs UTI Is it a viral infection? e.g. the common cold Is the infection trivial or self-limiting? most diarrhoea Are there more appropriate treatments? physiotherapy for bronchitis treatment of pus is drainage treatment of foreign body infection is removing the foreign body Best antibiotic(s) for these organisms ? For some organisms sensitivities are entirely predictable e.g. Streptococcus pyogenes always penicillin-sensitive For most organisms, sensitivity tests contribute to rational therapy e.g. coliforms in UTI Knowledge of local resistance problems contributes to choice of empirical therapy Best antibiotic(s) for this site of infection ? Depends on penetration of antibiotic into tissues e.g. gentamicin given iv does not enter CSF or gut E.g. azithromycin accumulates in cells even though levels low in serum Depends on mode of excretion e.g. amoxycillin excreted in massive amounts in urine Are there any problems with this regimen in this patient? Allergy usually only a problem with penicillins, and, less often, with cephalosporins (10% cross sensitivity) Ampicillin Rash develops if patient has glandular fever or lymphoma Not related to general penicillin allergy Are there any problems with this regimen in this patient? Side Effects some occur with almost any antibiotic Gastric upset Antibiotic-associated diarrhoea C. difficile infection pseudo-membranous colitis an be fatal Overgrowth of resistant organisms “Thrush” in the community VREs, MRSAs, Candida in ITU Are there any problems with this regimen in this patient? Organ-specific side effects damage to kidneys, ears, liver, bone marrow chloramphenicol produces rare aplastic anaemia vancomycin can cause “red man syndrome“ rifampicin discolours tears, urine contact lenses, can cause “flu-likesyndrome“ erythromycin causes gastric irritation ethambutol can cause ocular damage Aminoglycosides and vancomycin can cause ear and kidney damage Are there any problems with this regimen in this patient? Care needed in patients with metabolic problems renal failure liver failure genetic diseases Drug interactions e.g. gentamicin and frusamide Use in pregnancy, breast feeding, children Check in the BNF! Other Questions to Ask How much? How long for? How frequently?