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27 ANTIMICROBIAL DRUGS
General Considerations
Keys to successful antimicrobial therapy
1. Selective toxicity
Antimicrobial therapy is an exercise in selective toxicity.
Destroy pathogenic microorganisms with minimal adverse effects to host
2. Adequate blood levels
Sufficient levels to destroy microorganisms in order to prevent development of microbial resistance
Inadequate blood levels of antimicrobials leads to drug resistance.
Mechanism of action
1. Sites of action antimicrobial drugs (Fig. 27-1)
2. Molecular targets of antimicrobial drugs (see Fig. 27-1)
Know molecular target of individual drugs.
a.
b.
c.
d.
e.
f.
Functions
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Kill microorganisms
(1) Concentration-dependent killing
(a) Aminoglycosides
(b) Fluoroquinolones
(2) Time-dependent killing
(a) -Lactam antibiotics
(b) Vancomycin
b. Bacteriostatic agents (see Table 27-3)
Know which drugs are bacteriostatic versus bactericidal.
Suppress bacterial growth and multiplication
2. Prophylactic use of anti-infective agents (Table 27-4)
Figure 27-1 Sites of action of antimicrobial drugs and enzymes that inactivate these drugs. DHFA, dihydrofolic acid; PABA, p-aminobenzoic acid; THFA,
tetrahydrofolic acid.
-Lactams
Vancomycin
Aminoglycosides
Chloramphenicol
Clindamycin
Macrolides
Tetracyclines
Rifampin
Sulfonamides
Trimethoprim
Fluoroquinolones
Decreased
permeability
-Lactams
Tetracyclines
Fluoroquinolones
Increased efflux
Macrolides
Tetracyclines
Fluoroquinolones
-Lactams
Aminoglycosides
Macrolides
Tetracyclines
Chloramphenicol
Table 27-2. Microbial Organisms with Sites of Infection and Drugs of Choice for Treatment
MICROORGANISM
Gram-positive
Staphylococcus
aureus
Streptococcus
pyogenes (group A)
Streptococcus (group
B)
INFECTION
Methicillin susceptible
Nafcillin
Oxacillin
Methicillin resistant
Vancomycin
Linezolid
Quinupristin/dalfopristin
TMP/SMX
Teicoplanin
Pharyngitis
Cellulitis
Penicillin G
Penicillin V
Other -lactams
Macrolides
Meningitis
Cellulitis
Sepsis
Penicillin G (+/aminoglycoside)
Clindamycin
Other -lactams
Macrolides
Bacteremia
Enterococcus
Endocarditis
Enterococcus
Urinary tract
Streptococcus
(viridans group)
Endocarditis
Streptococcus
pneumoniae
Pneumonia
Streptococcus
Streptococcus
pneumoniae
Listeria
monocytogenes
ALTERNATIVES*
Abscess
Cellulitis
Bacteremia
Pneumonia
Endocarditis
Enterococcus
pneumoniae
DRUGS OF CHOICE
Penicillin G (+/aminoglycoside)
Ampicillin
Penicillin G (+/aminoglycoside)
Ampicillin
Ampicillin
Penicillin G (+/aminoglycoside)
Ceftriaxone
Penicillin G
Vancomycin (+/- rifampin)
Vancomycin/gentamicin
Vancomycin
Dalfopristin/quinupristin
Linezolid
Fluoroquinolone
Nitrofurantoin
Cephalosporin
Vancomycin
Levofloxacin
Meningitis
Bacteremia
Meningitis
Endocarditis
Azithromycin
TMP/SMX
Oral cephalosporin
Ceftriaxone
Cefotaxime
Ampicillin
Penicillin G
TMP/SMX
Endocarditis
Gram-negative
Escherichia coli
Urinary tract
Escherichia coli
Bacteremia
TMP/SMX
Ciprofloxacin
Third-generation cephalosporin
Ciprofloxacin
Klebsiella pneumoniae
Proteus mirabilis
Haemophilus
influenzae
Moraxella catarrhalis
Pneumonia
Bacteremia
Urinary tract
Otitis
Sinusitis
Bronchitis
Otitis
Sinusitis
Neisseria
gonorrhoeae
Genital
Pseudomonas
aeruginosa
Urinary tract
Ampicillin
Cefotaxime
Ceftriaxone
Amoxicillin/Clavulanic acid
Ceftriaxone
Cefixime
Ciprofloxacin
Nitrofurantoin
Fosfomycin
TMP/SMX
Ciprofloxacin
TMP/SMX
Oral cephalosporin
Fluoroquinolone
TMP/SMX
Imipenem
Aztreonam
TMP/SMX
Fluoroquinolone
TMP/SMX
TMP/SMX
Macrolide
Sulfonamide
Chloramphenicol
TMP/SMX
Imipenem
Aztreonam
Third generation
cephalosporin
Pseudomonas
aeruginosa
Vibrio cholerae
Helicobacter pylori
Pneumonia
Bacteremia
Cholera
Antipseudomonal penicillin +
aminoglycoside
Ceftazidime
Doxycycline
Fluoroquinolone
Amoxicillin
Clarithromycin
Tinidazole (Rabeprazole,
proton pump inhibitor)
Aztreonam
Carbapenems
Cefepime
TMP/SMX
Tetracycline
Bismuth
Metronidazole
Anaerobes
Bacteroides spp.
Clostridium
perfringens
Clostridium difficile
Abdominal infections
Abscesses
Abscesses
Gangrene
Pseudomembranous colitis
Metronidazole
Clindamycin
Carbapenems
Cefoxitin
Ticarcillin/clavulanic
acid
Penicillin G + clindamycin
Doxycycline
Metronidazole
Vancomycin (oral)
Clostridium difficile
Pseudomembranous colitis
Metronidazole
Vancomycin (oral)
Other
Legionella spp.
Pulmonary
Mycoplasma
pneumoniae
Pulmonary
Chlamydia
pneumoniae
Pulmonary
Chlamydia
trachomatis
Genital
Rickettsia
Doxycycline
Chloramphenicol
Ehrlichia spp.
Ehrlichiosis
Doxycycline
Chloramphenicol
Borrelia burgdorferi
Lyme disease
Azithromycin
Levofloxacin
Azithromycin
Clarithromycin
Erythromycin
Levofloxacin
Clarithromycin
Doxycycline
Doxycycline
Erythromycin
Fluoroquinolone
Doxycycline
Azithromycin
Mycobacterium
tuberculosis
Tuberculosis (Always
use multiple drugs)
Treponema
pallidum
Syphilis
Erythromycin
Ceftriaxone
Cefuroxime axetil
Doxycycline
Amoxicillin
Isoniazid
Rifampin
Ethambutol
Pyrazinamide
Streptomycin
Rifabutin
Benzathine penicillin G
Doxycycline
BACTERIOSTATIC AGENTS
Tetracyclines
Chloramphenicol
Macrolides
Clindamycin
Ethambutol
Linezolid
Sulfonamides
Trimethoprim
Nitrofurantoin
1. Organ-directed toxicity
a. Ototoxicity
b. Hematopoietic toxicity
Drugs that cause hepatotoxicity: tetracyclines, isoniazid, erythromycin, clindamycin, sulfonamides,
amphotericin B
c. Hepatotoxicity
c. Hepatotoxicity
d. Renal toxicity
Drugs that cause renal toxicity: cephalosporins, vancomycin, aminoglycosides, sulfonamides, amphotericin B
2. Idiosyncrasies (unexpected individual reactions)
a. Hemolytic anemias (e.g., in glucose-6-phosphate dehydrogenase [G6PD]-deficient people)
b. Photosensitivity reactions (e.g., tetracycline)
3. Hypersensitivity reactions
These reactions are most notable with penicillins and sulfonamides but can occur with most antimicrobial drugs.
4. Superinfections
a. Candidiasis
Candidiasis is most common superinfection caused by antimicrobial therapy.
Treatment with oral nystatin (local effects), miconazole (local vaginal effects), fluconazole (oral medication for vaginal
candidiasis)
b. Pseudomembranous colitis caused by Clostridium difficile
Treatment with oral metronidazole or vancomycin
Treat pseudomembranous colitis with metronidazole.
c. Staphylococcal enterocolitis
Treatment with oral vancomycin
5. Synergism
a. Aminoglycosides plus penicillins
b. Sulfamethoxazole plus trimethoprim
c. Amphotericin B plus flucytosine
d. Fosfomycin plus -lactams
e. Fosfomycin plus aminoglycosides
f. Fosfomycin plus fluoroquinolones
Be able to distinguish drug combinations that lead to synergism, potentiation, or antagonism.
6. Potentiation
a. Imipenem plus cilastatin
b. Ampicillin plus sulbactam
c. Amoxicillin plus clavulanic acid
d. Piperacillin plus tazobactam
e. Ticarcillin plus clavulanic acid
7. Antagonism
a. Penicillin G plus chloramphenicol
b. Penicillin G plus tetracycline
USE
Cefazolin
Surgical procedures
Cefoxitin, cefotetan
Ampicillin or penicillin
Trimethoprim-sulfamethoxazole
Rifampin
Chloroquine, mefloquine
Malaria
Isoniazid, rifampin
Tuberculosis
Azithromycin
Ciprofloxacin
Ampicillin or azithromycin
IDIOSYNCRATIC
RESPONSES
HYPERSENSITIVITY
REACTIONS
SUPERINFECTIONS
TOXICITY
RESPONSES
REACTIONS
SUPERINFECTIONS
Ototoxicity
Aminoglycosides
Vancomycin
Minocycline
-Lactams
Penicillins
Cephalosporins
Carbapenems
Candidiasis
Broad spectrum
antibiotics
Treatment
Nystatin
Fluconazole
Miconazole
Hematopoietic toxicity
Chloramphenicol
Sulfonamides
Photosensitivity
Tetracyclines
Sulfonamides
Fluoroquinolones
Sulfonamides
Stevens-Johnson
syndrome most
serious
Staphylococcal
enterocolitis
Treatment
Vancomycin
Hepatotoxicity
Tetracyclines
Macrolides
Isoniazid
Sulfonamides
Amphotericin B
Renal toxicity
Aminoglycosides
Vancomycin
Amphotericin B
Cephalosporins
Sulfonamides
Pseudomembranous
colitis (Clostridium
difficile)
Clindamycin
Treatment
Metronidazole
Vancomycin