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Factors Affecting the

Kinetics
1. Release from the dosage form
2. Absorption from the site of administration
INTRODUCTION OF into the bloodstream
ANTIBACTERIAL AGENTS 3. Distribution to various parts of the body
4. Rate of elimination from the body via
metabolism or excretion of unchanged drug

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Time dependent
vs.
★ Time-Dependent Killing Concentration dependent

Time Dependent Concentration dependent

★ Concentration-Dependent 1. Beta-lactams 1. Aminoglycoside
Killing 2. Glycopeptide 2. Quinolone
3. Clindamycin 3. Metronidazole
4. Marcolide

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Class of Antibacterial Agents Penicillins (需penicillin test)

 β-Lactams  Fluoroquinolones
 Natural penicillin: penicillin G
1. Penicillins  Marcolide
 Penicillinase-resistent penicillin:
2. Cephalosporins  Trimethoprim-
sulfamethoxazole oxacillin(iv), methicillin(iv)
3. Aztreonam
 Tetracyclines dicloxacillin (po)
4. Carbapenem
 Metronidazole  Broad-spectrum penicillin:
 Aminoglycoside
amoxicillin (po), ampicillin (po,iv)
 Glycopeptide
 Extend-spectrum penicillin
ticarcillin(iv), piperacillin(iv)

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β-Lactam and β-lactamase inhibitor 1st generation Cephalosporins

1. Cefazolin (1–2 g IV/IM q8h)

 Ampicillin + Sulbactam = Unasyn (q6h)
2. Cephalothin, cephapirin, and cephradine (1–2 g IV/IM
 Amoxicillin + Clavulanic acid = Augementin(q8h) q4–6h)
3. Ulex, po, 250mg/tab, 2#q6h
 Ticarcillin + Clavulanic acid = Timentin
Indication: (SSEKP)
 Piperacillin + Tazobactam = Tazocin
staphylococci
streptococci
Escherichia coli,
Klebsiella
Proteus species. Community-acquired

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2nd generation Cephalosporins

Cephamycin
Cefuroxime (Zinacef, zinnat po) (1.5 g IV/IM q8h)
above the diaphragm:  Cefoxitin (Mefoxin) (1–2 g IV q4–8h),
 Staphylococcus, Streptococcus, E.coli, Klebsiella, Proteus  Cefmetazole (CMZ) (2 g IV q6–12h):
 GNB: H. influenzae, M.catarrhis, Nessiera gonorrhoeae, N.  Below-the-diaphragm
menigitidis, Salmonella, Shigella (x) Staphylococcus, Streptococcus
Indication: (o) GNB as cefuroxime
1. Community acquired pneumonia (CAP),
(o) Anaerobic: B. fragilis
2. Tonsillitis, otitis media, bronchitis, sinusitis
3. Soft tissue infection, Indication:
4. Complicated UTI  Intraabdominal, gynecologic surgical prophylaxis
and infections, dirviticulitis, PID
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3rd generation Cephalosporins 3rd generation Cephalosporins

 Ceftriaxone (Rocephine) (1–2 g IV/IM q12–24h),

 Cefotaxime ( Claforan) (1–2 g IV/IM q4–12h),
 Cefoperazone (CPZ) (2–4 g IV q12h)
 Ceftazidime ( Fortum) (1–2 g IV/IM q8h)
 Flomoxef (Flumarin)
 Moxalactam (Shiomarin)
 Oral: cefixime(Cefspan), cefpodoxime (Banan)
Anti- P. aeruginosa– ceftazidime, CPZ
Good CNS penetration
Spectrum:
 GNB: Enterobacteriacae(emergent resistance in E. cloacae), H.
influenze, M catarrhalis, Nessieria spp.
 P. aeruginosa: ceftazidime, cefoperazone
 Anaerobic(x)
Indication:
meningitis, serious infection, multidrug resistance GNB
SE: cholecystits-like syndrome in ceftriaxone

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4th generation Cephalosporins Aztreonam

 Cefepime (Maxipime) (500 mg–2 g IV/IM q8–12h)  Aztreonam (azactam) (1–2 g IV/IM q6–12h)
 Cefpirome (Cefrom) (1-2 g IV)  Aerobic GNB only, including P. aeruginosa
 In vitro activity:  No gram-positive or anaerobic activity.
G(+): S. aureus, Streptococci
 Useful in patients with known PCN or
G(-): * Enterobacteriaceae
cephalosporin allergies, as no apparent cross
* H. influenzae, M.catarrhis
* P.aeruginosa (Cefepime) reactivity is present.

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Carbapenem Aminoglycosides
 Gentamicin
 Imipenem (500 mg–1 g IV/IM q6–8h)
 Meropenem (1 g IV q8h): less seizure activity  Tobramycin
 The widest spectrum ß-lactam antibiotic  Amikacin
 Active against most GP, GN bacteria, anaerobic  Streptomycin
 Carbapenem resistance bacteria:
1. Ampicillin resistant enterococci
2. Oxacillin-resistance S. aureus (ORSA)
3. Stenotrophomonas maltophilia
4. Burkholderia cepacia
5. Corynebacterium Jeikeium

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Spectrum of aminoglycosides Glycopeptide

Gram negative aerobes Vancomycin

 Community acquired G(-) organism  15 mg/kg IV q12h; 30 mg/kg IV q12h for meningitis
 Hospital acquires G(-) organism  Peak level: (25-40), 給藥後0.5-1 hr
 Trough level(8-12,5-10): 給藥前
Gram positive aerobes
 Against GPC in combination with ß-lactam or Teicoplanin
glycopeptide (synergic effect)
 Loading: 400 mg(6mg/kg) q12h x 3
 3~5 days for severe S. aureus infection
Maintain: 400 mg(6mg/kg) qd
 Combination for severe Enterococus infection
 Trend of less renal toxicity
Anaerobe (x)
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Indication of Glycopeptide Fluoroquinolones

 Serious infections caused by ORSA  Ofloxacin

 Serious infections caused by ampicillin-resistant  Lomefloxacin
enterococci
 Cirpofloxacin
 Serious infections caused by gram-positive bacteria in
patient allergic to other therapies  Levofloxacin
 Oral treatment of Clostridium difficile colitis not  Moxifloxacin
responded to oral metronidazole
 Immunocompromised status with high suspicion of G(+)
infections

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Andriole’s classification of Quinolones Ciprofloxacin

G(+) G(-) Anaerobe

1st G × O ×  The most active quinolone against P. aeruginosa

(non-fluo)
 Poor activity against gram-positive cocci and
2nd G IIA Ciprofloxacin, × O × Lack activity against anaerobes
(fluo-) Lomefloxacin, streptococcus,
Ofloxacin, enterococcus,  Second-line agents for TB therapy
Levofloxacin except levofloxacin
 Oral and IV therapy give similar maximum serum
2nd G IIB sparfloxacin O O O esp streptococcus
levels.
(fluo-)
3rd G Travofloxacin O O O esp streptococcus
(fluo-) Gatifloxacin
Moxifloxacin
gemifloxacin
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Adverse effects of Fluoroquinolones Macrolide antibiotics

 Not be used in
 Erythromycin (250–500 mg PO qid or 0.5–1.0 g IV q6h;
* p’ts < 18 y/o
poorly tolerated through peripheral veins)
* pregnant or lactating women.
 Clarithromycin (250–500 mg PO bid)
 Age-related arthropathy
 Azithromycin (500 mg PO × 1 day, then 250 mg PO qd × 4
 Discontinued in pts with joint pain or tendonitis
days (Zpack); 250–500 mg PO qd; 500 mg IV qd)
(Achilles tendon)

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Major Indications for Erythromycin Macrolide

Erythromycin: gram positive cocci except enterococcus.

 Chlamydia pneumoniae  Atypical respiratory tract infection
 Chlamydia trachomatis  Resistance in H. influenzae, M catarrhalis
 Legionella pneumophila
 Mycoplasma pneumoniae Clarithromycin: enhanced activity against upper respiratory
pathogen (H. influenzae, M catarrhalis).
 Bordetella pertussis
 Sinusitis, bronchitis, otitis media, pharyngitis, CAP
 Corynebacterium diphtheriae
 Soft tissue infection
 Campylobacter jejuni gastroenteritis
 MAC infection in HIV
 Bartonella henselae(cat scratch disease), Bartonella
quintana(Bacillary angiomatosis)  H. pylori infection
 Prevention of infection after colorectal surgery
Azithromycin: less drug interaction as erythromycin and
clarithromycin
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Trimethoprim-sulfamethoxazole
Trimethoprim-sulfamethoxazole
 Excellent tissue penetration, including bone, prostate,
 Trimethoprim to sulfamethoxazole: 1: 5 and CNS.
 1amp or 1 tab:  A broad spectrum of activity (not inhibit P. aeruginosa or
80mg trimethoprim/400mg sulfamethoxazole anaerobes).
 Use in
 The IV preparation: * PCP pneumonia and PCP prophylaxis in AIDS p’t
5 mg/kg IV q8h (based on the trimethoprim) * Stenotrophomonas maltophilia
for serious infections * Trophermyma whippleii
* Nocardia infections
 The oral preparations: almost completely bioavailable * Sinusitis, otitis media, bronchitis, prostatis,
UTI (2#bid)
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Adverse effect of TMP-SMA Tetracyclines

 Bone marrow suppression  Tetracycline (250–500 mg PO q6h)

 Interstitial nephritis  Doxycycline (100 PO/IV q12h)
 Cholestatic jaundice  Minocycline (200 mg IV/PO, then 100 mg IV/PO q12h)
 Severe hypersensitivity reactions  In vitro activity:
(Stevens-Johnson / erythema multiforme) -- 1. Chlamydiae
2. Mycoplasma
3. Rickettsiae
4. Vibrio spp and Aeromonas spp

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Metronidazole Anaerobic infections

 Metronidazole (250–750 mg PO/IV q8h)  Empyema

 It has excellent tissue penetration, including abscess  Lung abscess

cavities, bone, and CNS.  Peritonitis
 greater activity against gram-negative than gram-  Intra-abdominal abscess
positive anaerobes but is active against Clostridium  Pelvic, tubular, ovarian abscess, or Caution !
perfringens and difficile.  Endometritis
 Protozoan infections that are routinely treated with
 B.fragilis: 33% resistance
metronidazole include Giardia, Entamoeba histolytica,
and Trichomonas vaginalis

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Synergistic Effect
Indication for Combination Therapy

 Prevention of the emergence of resistant  Enterococci, Streptococci: ß-lactam +

mutants. aminoglycoside
 Synergistic or additive activity
 Pseudomonas: Anti-pseudomonas
 Therapy directed against multiple potential
penicillin/cephasporin + aminoglycoside
pathogens
 Febrile, leukopenic patient  K. pneumoniae: cephasporin + aminoglycoside

 Vibrio spp, Aromonas spp: 3rd generation

cephasporin + doxycyclin/minocyclin:

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High Oral Bioavailability Penetration Of BBB

 Amoxicillin  Cephalexin  Penicillin  Chloramphenicol
 Doxycycline  Minocyclin  Ampicillin  Vancomycin
 TMP-SMX  Metronidazole  Oxacillin  Rifampin
 Chloramphenicol  Clindamycin  3rd generation  Metronidazole
 Fluoroquinolone  Fluconazole cephasporin  TMP-SMX
 Carbapenems

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Avoid commitant drugs with potential to prolong

QTc: torasdes de pointes, Vf
Antiarrythmic antiinfective AntiHTN CNS drug Misc

Amiodarone Clarithro Nicardipine Fluxetine Salmeterol

Resperidone
Disopyramide
Erythro
Foscarnet
Moexipril
Isradipine
Sertraline
Tricyclics
Sumatriptan
Thanks for your attention !
Flecainide Mefloquine Bepridil Venlafaxine
Sotalol Petamidine Haloperidol
QuinidineProca Phenothiazine
namide
Ibutilide
Dofetilide

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Tigecycline

daptomycin

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