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Anti-biotics 1. B-lactams A. Ampicillin, amoxicillin : extends the spectrum of penicillin G to some gram-negative rods i. High rates of resistance have lessened the value of ampicillin and amoxicillin as empirical therapy in some situations. For example, >80% of isolates of E. coli and P. mirabilis are resistant in many hospitals, as are B. 30% of isolates of H. influenzae; penicillinase-resistant penicillins(methicillin, oxacillin) : drugs of choice for systemic or deep staphylococcal infections i. on average, 40% of S. aureus isolates and >70% of coagulase-negative staphylococcal isolates acquired in U.S. hospitals are resistant to these agents C. antipseudomonal penicillins(Tazocin-4.5g tid mix c 5dw 100cc, NS에 mix해도 됨. Lactatedringer’s와는 섞이면 안됨. ) i. AG should generally be added to tazocin for Tx. Of serius infections caused by pseudomonas aeruginosa or for nosocomial pneumonia st D. 1 cepha : cefazolin E. 2nd cepha : cefoxitin, cefotetan F. 3rd cepha : i. Ceftriaxone : 1. has a long serum half-life(2g#1), 2. high serum and CSF levels (with inflammation). -> drugs of choice for empirical therapy for bacterial meningitis (except that caused by Listeria and by highly penicillin-resistant pneumococcal strains) 3. drugs of choice for nonpseudomonal hospital-acquired pneumonia. ii. cefotaxime iii. ceftazidime : anti-pseudomonal activity G. 4th cepha : cefepime(maxipime 2g#2) - anti-pseudomonal activity H. Carbapenems : excellent activity in vitro against virtually all bacterial pathogens except Stenotrophomonas, methicillin-resistant staphylococci, and E. faecium i. Prepenem(0.5g qid) 1. imipenem + cilastatin(renal dipeptidase inhibitor) 2. Imipenem has dose-related central nervous system side effects that are less frequent with meropenem ii. Meropen(0.5~1g tid) 1. activity vs aerobic gram(-) slightly higher than imipenem. 2. activity vs staphylo & strepto slightly lower 3. vs anaerobe : equal to imipenem 4. I. biliary excretion : 3-300% (imipenem:minimal) aztreonam(azactam) i. spectrum limited to gram-negative enteric bacilli. It has no activity against any grampositive or anaerobic bacterium. Its gram-negative spectrum is similar to that of ceftazidime, with equally good activity against Pseudomonas. Aztreonam's primary advantages are its theoretical ability to preserve the normal gram-positive and anaerobic flora and the lack of cross-reactive immediate hypersensitivity in patients who have had this type of reaction to other 2. -lactam antibiotics. glycopeptide A. vancomycin i. Vancomycin serves as second-line therapy for most gram-positive bacterial infections but is the drug of choice for infections caused by methicillin-resistant staphylococci or Corynebacterium jeikeium and for serious infections in penicillin-allergic patients. ii. Given orally (a route by which it is not absorbed), vancomycin can be used to treat antibiotic-associated pseudomembranous colitis caused by C. difficile in patients who have failed to respond to metronidazole 3. Aminoglycosides A. activity limited to gram-negative bacteria and staphylococci, no activity against anaerobic bacteria and are not effective in environments that are acidic or have a low oxygen tension B. synergistically bactericidal in combination with a cell wall-active agent C. renal and otic toxicity, D. their diminished activity at certain sites of infection (e.g., abscesses and the central nervous system), 4. Macrolides and Ketolides A. drug of choice for infections due to Legionella, Campylobacter, and Mycoplasma B. Clarithromycin and azithromycin have an antibacterial spectrum similar to that of erythromycin in vitro. However, azithromycin has greater activity against Chlamydia. 5. lincosamide A. 6. 7. clindamycin(fullgram 600mg tid) i. activity against most gram-positive and gram-negative strict anaerobes ii. pseudomembranous colitis, the major serious side effect of this drug. SULFONAMIDES AND TRIMETHOPRIM A. For nosocomial infections due to Stenotrophomonas, TMP-SMX is the drug of choice. B. IV = PO C. PCP FLUOROQUINOLONES A. ciprofloxacin - the oral agents with greatest activity against P. aeruginosa; (citopcin 400mg#2 IVF, 1000mg#2 PO) B. C. the newer quinolones have an expanded spectrum of activity against gram-positive cocci i. levofloxacine(cravit 250mg-750mg qd) ii. gatifloxacine(gatiflo 400mg IV, PO qd) iii. moxifloxacine(avelox 400mg #1 IVF) almagel, MgO, ulcermin, bismuth, oral iron, oral calcium can markedly impair absorption of oral Quinolones 8. metronidazole (1500mg#3 IVF) A. spectrum limited to anaerobic bacteria, especially gram-negative species (e.g., Bacteroides spp.). B. Because of its spectrum and its ability to penetrate into the area of infection, metronidazole is one of the drugs of choice for the treatment of any abscess in which the involvement of obligate anaerobes is suspected (e.g., lung, brain, or intraabdominal abscesses). Other antibacterial agents should be used in combination with metronidazole if facultative and aerobic pathogens are also thought to be involved. Metronidazole is the drug of choice for the treatment of bacterial vaginosis and antibiotic-associated pseudomembranous colitis 9. linezolid A. spectrum limited to gram-positive bacteria B. active against vancomycin-resistant enterococci (both E. faecium and E. faecalis) and is one of the drugs of choice for treating infections due to these organisms. However, since this drug has only bacteriostatic activity, it has limited utility in treating complicated S. aureus infections MECHANISMS OF ACTION INHIBITION OF CELL-WALL SYNTHESIS : GLYCOPEPTIDES, -LACTAM INHIBITION OF PROTEIN SYNTHESIS : AMINOGLYCOSIDES, MACROLIDE , LINEZOLID INHIBITION OF BACTERIAL METABOLISM : TRIMETHOPRIM/SULFAMETHOXAZOLE INHIBITION OF NUCLEIC ACID METRONIDAZOLE 1. CAP(ATS-guideline) Pseudomonas를 cover? ICU? SYNTHESIS OR ACTIVITY : QUINOLONE, RIFAMPIN. the need for ICU admission could be defined by using a rule that required the presence of either - two of three minor criteria (systolic BP < 90 mm Hg, multilobar disease, PaO2/FIO2 ratio < 250) or - one of two major criteria (need for mechanical ventilation or septic shock). - With this rule the sensitivity was 78%, the specificity was 94%, the positive predictive value was 75%, and the negative predictive value was 95% (48). *anti pseudomonal agent : cefobactam, maxipime, tazocin, meropen, prepenem, cefazime, azactam 2. HAP Onset? MDR risk? 3. PCP -steroid indication(D>35, PaO2<70) -U-prin 4T tid – total 21days -solondo 40mg bid x 5 days, then 40mg qd x 5 days, then 20mg qd x 11 days -Pts with PCP or CD4<200 -> prophylaxis for life 4. liver abscess - metro + cefpiran + AG 5. biliary sepsis - tazocin or ubacillin + AG + metro, if life threatening->prepenem 6. UTI - acute uncomplicated cystitis in women : citopcin PO x 3days - UTIs in men : citopcin PO x 7 days, urologic study:treatment fails, recurrent infection, APN - APN : mild – outpatient Severe(N/V, pregnant) – IV 3rd cepha, citopcin Do not respond to Tx. Withing 48h -> search for renal abscess or calculi 7. PD peritonitis - Cefazolin + ceftazidime Cefazolin(loading dose:500mg/L, maintenance:125mg/L) Ceftazidime(loading dose:250mg/L, maintenance:125mg/L) 8. neutropenic fever Inclusion of vancomycin in initial empirical therapy may be prudent for selected patients with the following clinical findings: (1) clinically suspected serious catheter-related infections (e.g., bacteremia,cellulitis) (2) known colonization with penicillin- and cephalosporin-resistant pneumococci or methicillin-resistant S.aureus (3) positive results of blood culture for gram-positive bacteria before final identification and susceptibility testing, (4) hypotension or other evidence of cardiovascular impairment