Maximal damage to the bacteria minimal damage to

理想的抗生素 Maximal damage to the bacteria, minimal damage to the host –selective toxicity Single use High effectiveness Low cost No side-effect

Principles of antibiotic therapy Host factors Allergy history Age, Body weight, Renal/liver function Immune status Site of infection: pathogen, route of antibiotics Disease severity Pregnancy

Empirical therapy must be adjusted after culture become available Definite antimicrobial therapy –change broadspectrum coverage to specific pathogen De-escalating therapy

Pathogens of community-acquired infection Pulmonary: S. pneumoniae, H. influenzae, M. catarrhalis Skin & soft tissue: Streptococci, Staphylococci, Enterobacterioceae Intraabdomen: Enterobacterioceae, Anaerobes, Enterococci CNS: S. pneumoniae, H. influenzae, N. meningitidis

Pathogens of nosocmial infection Pulmonary: Enterobacterioceae, Pseudomonas, Acinetobacter, MRSA Intraabdomen: Enterobacterioceae, Pseudomonas, Anaerobes, Enterococci, Candida CNS: MRSA, Pseudomonas

Allergic reactions to antibiotics Fixed drug eruption Skin rash (maculopapular) Exfoliativedermatitis Stevens-Johnson Syndrome (Toxic epidermal necrolysis) Anaphylactic shock

Fixed rug eruption

Skin rash (maculopapular)

Stevens-Johnson Syndrome (Toxic epidermal necrolysis)

Antibiotics Penicillins Beta-lactmase inhibitors Cephalosporins Carbapenems Monobactams Sulfonamides & trimethoprim Aminoglycosides Quinolones Tetracycline Metronidazole Macrolides Tigecycline Glycopeptide Colistimethate sodium

Penicillins Natural PCNs Penicillin G, Penicillin V, benzathine PCN Penicillinase-resistant PCNs Oxacillin, Prostaphylin Amionopenicillins Amoxicillin, Ampicillin Anti-pseudomonal PCNs Ticarcillin, Piperacillin

Antimicrobial spectrum of Penicillin-G Streptococcus spp. Anaerobes Neisseria spp. (Meningococcus, Gonococcus) Actinomycosis Animal bite (Pasteurella multocida) 螺旋體: Syphilis, Leptospirosis

Penicillinase-resistant Penicillins oxacillin Penicillinase (β-lactamase) inhibitor Anti-staphylococcal penicillins Less active than penicillin-G against all other penicillin-susceptible microorganisms

Adverse effects-PCNs Anaphylaxis, anemia, leukopenia Oxacillin: hepatitis Ticarcillin: coagulation abnormality bleeding

Beta-lactam/beta-lactamatase inhibitor Sulbactam Ampicillin + Sulbactam Clavulanic acid Amoxycillin + Clavulanate Ticarcillin + Clavulanate Tazobactam Piperacillin + Tazobactam

Antipseudomonal Penicillins Pip. /tazo, Ticarcillin + Clavulanate Pseudomonas species Many strains of Enterobacter Anaerobics except β-lactamase producing Bacteroides species Less active against gram positive isolates

Adverse effects of penicillin Anaphylaxis, anemia, leukopenia Oxacillin: hepatitis Ticarcillin: coagulation abnormality bleeding

Sulbactam (Maxtam) Sulbactam is an irreversible inhibitor of betalactamase Combinations of sulbactam with beta-lactam antibiotics Dose: 0. 5 ~ 1. 0 gm 6 ~ 8 with other antibiotics not > 4. 0 gm/day Cefoperazone/sulbactam Ampicillin/sulbactam

Cephalosporins First generation Second generation Third generation Fourth generation

Cephalosporins Against GPC 1 st > 2 nd > cephamycins > 3 rd Against GNB 1 st < 2 nd < cephamycins < 3 rd

First Generation Cefazolin Streptococcus Staphylococcus (methicillin-susceptible) E. coli P. mirabilis K. pneumoniae Cefadroxil Ceflexin Cephradine

Second Generation Cefmetazole Cefuroxime Cefalor Cefuroxime above the diaphragm: cefuroxime. below the diaphragm: cefmetazole (cephamycins, B. fragilis) Cefmatazole : ESBL-producing Enterobacteriaceae

Third generation Cefoperazone Cefotaxime Ceftazidime Ceftriaxone Flumarin Cefixime Cefpodoxime ceftibuten Resistant Gram-negative microorganisms（Nosocomial infections） : Serratia, Citrobacter, Enterobacter, Pseudomonas, β-lactamase producing H. influenzae. Better BBB penetration among cephalosporins (except cefoperazone) Indication: nosocomial infections (mainly GNB), GNB meningitis

Fourth Generation Cefepime Cefpirome Good anti-pseudomonal effect Good CNS penetration Preserve antimicrobial effect to G(+) bacteria

Adverse effects of cephalosporins Cefamandole, cefmetazole, cefoperazone, cefotetan vitamin K-dependent clotting factor metabolism

Monobactam (Aztreonam) Only gram-negative aerobes Alternative in penicillin- and cephalosporinallergic patients

Sulfonamides and trimethoprim Inhibit folic acid metabolism Treatment of PCP, Nocardia, Toxaplasma, Sternotrophomonus Aderverse effect: cholestatic jaudice, bone marrow suppression, severe hypersensitivity (Stevens-Johnson syndrome)

Carbapenem Group Classification Group 1 Broad-spectrum carbapenems, with limited activity against non-fermentative Gram-negative bacilli (NFGNB, e. g. Pseudomonas, Acinetobacter) , that are particularly suitable for community-acquired infections (e. g. ertapenem) Group 2 Broad-spectrum carbapenems, with activity against nonfermentative Gram-negative bacilli (e. g. Pseudomonas, Acinetobacter), that are particularly suitable for nosocomial infections (e. g. imipenem and meropenem) Group 3 Carbapenems with clinical activity against Methicillin. Resistant Staphylococcus (e. g. In development) J Antimicrob Chemotherapy

Side effect of Carbapenems Anaphylaxis Interstitial nephritis Anemia Leukopenia Precipitate seizure activity, especially old patients, CRI, preexisting seizure disorder or CNS pathology

Aminoglycosides Antimicrobial Spectrum: - All Gram negative bacilli - Staphylococcus aureus Dosage: Gentamicin: loading ~ 2 mg/kg maintenance ~ 3 -5 mg/kg/day Amikacin: loading ~ 7. 5 mg/kg maintenance ~ 5 mg/kg Q 8 H or 7. 5 mg/kg q 12 H Exacin : 8 mgs/kg/day Single daily (once-daily) dosing (SDD) Short course (3 -5 days)

Adverse effects of aminoglycosides Nephrotoxicity Ototoxicity Neuromuscular paralysis ~ High dose/infrequent administration DECREASES the rate of tissue uptake — DELAY the onset of toxicity, doesn’t prevent it from happening ~ All patients, if treated for a long enough time, will eventually develop toxicity

Fluoroquinolones Group I: - Nalidixic acid - Enteric or urinary tract infections Group II: - Ciprofloxacin, Ofloxacin, Levofloxacin - GNR (P. aeruginosa), S. pneumoniae, atypicals Group III: - Moxifloxacin, Gemifloxacin - GPB ( S. pneumoniae↑), atypicals, anaerobes, GNR (P. aeruginosa↓) - Respiratory tract infections

Glycopeptides Vancomycin & Teicoplanin Non-β-lactam cell wall synthesis inhibitor Spectrum: GPC & GPB Avoid oral use, except AAC (antibioticassociated colitis)

Tetracyclines STD Rickettsial diseases - Chlamydial diseases Brucellosis - Gonorrhea Tularemia (doxycycline + ceftriaxone) - Syphilis Relapsing fever

Tigecycline (a new class Glycylcyclines) Gram-positive Bacteria Gram-negative Bacteria 。Staphylococcus: MRSA, MRSE 。E. coli (including ESBLs) 。VRE: E. faecium, E. faecalis 。Kl ebsiella pneumoniae 。Streptococcus agalactiae (including ESBLs) 。S treptococcus anginosus group 。K. oxytoca 。Streptococcus pyogenes 。Acinetobacter baumannii (Resistant strains) Anaerobes 。Citrobacter freundii 。B. fragilis group 。Enterobacter cloacae 。Prevotella spp. 。Enterobacter aerogenes 。Peptostreptococcus spp. 。Stenotrophomonas maltophilia 。C. perfringens Atypical 。Chlamydia pneumoniae Does not have good activity 。Mycoplasma pneumoniae against 。Legionella P. aeruginosa Proteus. Providencia

Colistimethate sodium Pseudomonas aeruginosa infections in cystic fibrosis , multidrug-resistant Acinetobacter infection E-coli , Klebsiella sp ( ESBL) , Enterobacter Colomycin 1, 000 units = 80 mg colistimethate 6 to 12 mg/kg colistimethate sodium per day 60 kg man, recommended dose for Colomycin is 240 to 480 mg of colistimethate sodium Nephrotoxicity (damage to the kidneys) and neurotoxicity

抗生素使用常見的五大錯誤 Antibiotic = scanol (antipyretic) S vs R (susceptible vs resistant) 4 > 3 >2 > 1 Treat colonization Vancomycin+ imipenem(atomic bomb)

Colonization Positive culture for sputum, urine, bile, stool and skin swab without symptoms or signs of infection, Not recommend for using antibiotics Except: asymptomatic bacteriuria before urological work up and in pregnancy should be treated

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