Aminoglycosides
PHARMACOLOGY REVIEWER
LONG EXAM 2
ANTIMICROBIAL GROUPS AND ANTIMICROBIAL RESISTANCE
Drug
Mechanism
PK
Streptomycin
Binds 30S →
blocks initiation
& causes
misreading
A: IM only (not absorbed
orally). D: Extracellular;
poor CSF. M: None. E:
Renal (GF).
Same
A: IV/IM. D:
Extracellular; poor CSF;
accumulates in
kidney/ear. M: None. E:
Renal (GF).
Tobramycin
Same
A: IV/IM, inhaled for CF.
D: Extracellular, poor
CSF. M: None. E: Renal.
Amikacin
Same; less
enzyme
inactivation
A: IV/IM. D: Wide but
poor CSF. M: None. E:
Renal.
Netilmicin
Same
A: IV/IM. D:
Extracellular. M: None.
E: Renal.
Gentamicin
PD
Indications
Spectrum
Side/Adverse
Toxicity
Contraindications
Dosage
Rapid
(parenteral)
TB (2nd line),
plague, tularemia,
enterococcal
endocarditis (with
penicillin)
Gram− bacilli,
Mycobacterium,
some Gram+
(with β-lactam)
Vestibular
dysfunction,
rash, fever
Ototoxicity,
nephrotoxicity
Pregnancy, renal
failure
15
mg/kg/day
IM
Rapid IV/IM
Severe G−
infections (sepsis,
pneumonia, UTI),
enterococcal
endocarditis (with
βlactam/vancomycin)
Broad Gram−
rods, synergy
vs Gram+ cocci
Nephrotoxicity,
ototoxicity
Vestibular +
renal toxicity
Pregnancy, renal
failure
3–5
mg/kg/day
IV/IM
Rapid
Pseudomonas
infections (esp. CF,
pneumonia)
Strong vs
Pseudomonas
Nephrotoxicity >
gentamicin
Nephro-, ototoxicity
Same
3–5
mg/kg/day
IV/IM;
inhaled 300
mg bid
Same
Rapid
Severe nosocomial
infections, TB
resistant to
streptomycin
Broad G− incl.
Pseudomonas,
Acinetobacter;
some resistant
TB
Oto- +
nephrotoxicity
Auditory
toxicity
(irreversible)
Same
15
mg/kg/day
IV/IM
Same
Rapid
Severe G−
infections
Similar to
gentamicin
Less nephrotoxic
than gentamicin
Ototoxicity
Same
4–6
mg/kg/day
IV/IM
Conc.dependent
bactericidal
Conc.dependent,
PAE
Same
Onset
smsoriano
PHARMACOLOGY REVIEWER
LONG EXAM 2
Drug
Mechanism
PK
Same (too toxic for
systemic use)
A: Oral (not absorbed),
topical. D: GI lumen
(oral use). M: None. E:
Feces.
Local
bactericidal
Kanamycin
Same
A: IM, oral (not
absorbed). D:
Extracellular. M: None.
E: Renal.
Paromomycin
Same
Plazomicin
Newer
aminoglycoside
Aminoglycosides
Neomycin
Spectinomycin
ANTIMICROBIAL GROUPS AND ANTIMICROBIAL RESISTANCE
Drug
Spectinomycin
Mechanism
Binds 30S, inhibits
translocation
(similar to
aminoglycosides
but no misreading)
Indications
Spectrum
Side/Adverse
Toxicity
Local
Topical skin, oral
for bowel
sterilization,
hepatic
encephalopathy
Gram− >
Gram+, limited
systemic
GI upset, contact
dermatitis
Severe oto- &
nephrotoxicity
if systemic
Systemic use
Oral 1 g q6h
(short
course);
topical
Same
Rapid
TB (rarely used),
bowel sterilization
Broad G−,
some
mycobacteria
High
oto/nephrotoxicity
Severe toxicity
Same
15 mg/kg/day
IM
A: Oral (not absorbed).
D: Stays in gut. M:
None. E: Feces.
Local
Local
Intestinal
amebiasis,
cryptosporidiosis
Luminal
parasites,
some G−
GI upset
Rare systemic
None
Oral 25–35
mg/kg/day
A: IV only. D:
Extracellular. M: None.
E: Renal.
Same
Rapid
MDR
Enterobacteriaceae
MDR Gram−
rods incl. CRE
Similar to
aminoglycosides
Nephro/ototoxicity
Renal impairment
15 mg/kg/day
IV
Toxicity
Contraindications
Dosage
PK
A: IM injection. D:
Extracellular, not CNS.
M: Minimal. E: Renal.
PD
PD
Bacteriostatic
Onset
Onset
Rapid IM
Indications
Gonorrhea
(penicillin- or
ciprofloxacinresistant
strains)
Spectrum
N.
gonorrhoeae
only
Side/Adverse
Pain at injection
site, fever, nausea
Rare
nephrotoxicity
Contraindications
Pregnancy
(relative)
Dosage
2 g IM single
dose
smsoriano
PHARMACOLOGY REVIEWER
LONG EXAM 2
Spectrum
Common
side/adverse
Notable
toxicity
Contraindications
Used only as fixed-dose
combo with trimethoprim;
see TMP-SMX below.
Broad activity vs many
gram-positive and
gram-negative bacteria;
some Nocardia,
Chlamydia, several
protozoa; Rickettsiae
not susceptible;
Pseudomonas
intrinsically resistant.
Rash, fever,
photosensitivity;
GU
“crystalluria/urinary
disturbances”
(class).
Kernicterus
risk (class);
see class AEs.
Avoid when
sulfonamide is
contraindicated;
(chapter
emphasizes
neonatal/pregnancy
risk at class level).
Bacteriostatic
With pyrimethamine for
toxoplasmosis
As above
As above
As above
As above
Bacteriostatic
With pyrimethamine for
malaria (historical/where
used); resistance & severe
reactions limit use
As above
Severe cutaneous
reactions cited
historically; see
text.
Severe skin
reactions
(noted);
Use restricted; see
text.
Same (acts in
gut; prodrug split
in colon)
A: poorly absorbed (designed
for local action). D: local in
bowel. M/E: metabolized to
sulfapyridine + 5-ASA in colon;
systemic exposure less
emphasized.
Local effect
Inflammatory bowel
disease
Local GI
pathogens/inflammation
context (not used as
systemic antibacterial).
GI intolerance
possible (class).
—
—
Sodium
sulfacetamide
(topical/ophthalmic)
Same
A: topical ocular. D: local. M/E:
not emphasized.
Local
Bacterial conjunctivitis
(2nd-line)
Ocular surface bacteria
Local irritation
possible
—
—
Silver
sulfadiazine
(topical)
Same; silver
adds broad
topical activity
A/D: topical local. M/E: not
emphasized.
Local
Burns (prevention/treatment
of infection)
Broad topical coverage
Local reactions
—
—
Mafenide acetate
(topical)
Same; also
inhibits
carbonic
anhydrase
A/D: topical; systemic
absorption can occur.
Broad topical
Pain on
application;
metabolic
acidosis (due to
CA inhibition)
Metabolic
acidosis risk
—
Drug
MOA
PK
Sulfamethoxazole
(oral absorbable;
used mainly in
combo)
PABA analog;
competitively
inhibits
dihydropteroate
synthase →
blocks folate
synthesis
A: well absorbed from small
intestine. D: widely distributed
incl. CSF; variable protein
binding. M: hepatic
acetylation/glucuronidation.
E: urinary excretion; t½ ↑ in
renal failure.
Bacteriostatic
alone
Sulfadiazine (oral
absorbable)
Same as above
As above for oral absorbable
sulfonamides.
Same
Long half-life (class note longacting); otherwise as above.
Sulfasalazine (oral
non-absorbable)
Sulfadoxine (oral
absorbable; longacting)
Sulfonamides
ANTIMICROBIAL GROUPS AND ANTIMICROBIAL RESISTANCE
PD
Local
Indications
Burns (alternative)
smsoriano
Trimethoprim (TMP), Pyrimethamine, and TMP–SMX
PHARMACOLOGY REVIEWER
LONG EXAM 2
ANTIMICROBIAL GROUPS AND ANTIMICROBIAL RESISTANCE
Drug / Combo
MOA
PK
Trimethoprim
(TMP)
Selectively inhibits
bacterial dihydrofolate
reductase → blocks
tetrahydrofolate formation
(downstream of
sulfonamides).
A: oral; concentrates in
acidic prostatic &
vaginal fluids. D:
distributes to body
fluids/CSF. M: minimal.
E: renal.
Pyrimethamine
TMP–SMX (cotrimoxazole)
Inhibits protozoal DHFR
Oral
Sequential blockade of
folate synthesis (DHPS +
DHFR) → synergy;
bactericidal vs many
organisms compared with
sulfonamide alone.
A: oral and IV; oral
tablets include singlestrength (80/400 mg) &
double-strength
(160/800 mg); IV
formulations described.
D: wide tissue
distribution. M: limited. E:
renal.
PD
Indications
Bacteriostati
c alone
UTIs, prostatitis, respiratory
pathogens—most often combined
with SMX; TMP alone discussed
mechanistically.
—
With sulfadiazine for
toxoplasmosis; also with
sulfadoxine for malaria
(resistance/toxicity limit use)
Bactericidal
(combo)
UTIs, prostatitis,
Shigella/Salmonella (selected
situations), Nocardia, S. aureus
(many community strains
susceptible), respiratory
pathogens (H. influenzae, M.
catarrhalis), and Pneumocystis
jirovecii (treatment/prophylaxis).
Spectrum
Common side/adverse
Notable toxicity
Nausea, vomiting, rash (when
in combo noted);
megaloblastic
anemia/leukopenia/granulocy
topenia (folate-related).
—
Protozoa
(Toxoplasma;
Plasmodium with
sulfadoxine)
—
Bone-marrow
suppression risk
noted when
combined;
leucovorin often cogiven (described in
text).
Broad across listed
organisms
Nausea, vomiting, rash; folaterelated cytopenias;
hyperkalemia reported.
Severe cutaneous
reactions are
discussed with
sulfonamide
component in class
notes.
Active vs many
UTI/resp pathogens
when combined
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Trimethoprim (TMP), Pyrimethamine, and TMP–SMX
PHARMACOLOGY REVIEWER
LONG EXAM 2
ANTIMICROBIAL GROUPS AND ANTIMICROBIAL RESISTANCE
Drug / Combo
MOA
PK
Trimethoprim
(TMP)
Selectively inhibits
bacterial dihydrofolate
reductase → blocks
tetrahydrofolate formation
(downstream of
sulfonamides).
A: oral; concentrates in
acidic prostatic &
vaginal fluids. D:
distributes to body
fluids/CSF. M: minimal.
E: renal.
Pyrimethamine
TMP–SMX (cotrimoxazole)
Inhibits protozoal DHFR
Oral
Sequential blockade of
folate synthesis (DHPS +
DHFR) → synergy;
bactericidal vs many
organisms compared with
sulfonamide alone.
A: oral and IV; oral
tablets include singlestrength (80/400 mg) &
double-strength
(160/800 mg); IV
formulations described.
D: wide tissue
distribution. M: limited. E:
renal.
PD
Indications
Bacteriostati
c alone
UTIs, prostatitis, respiratory
pathogens—most often combined
with SMX; TMP alone discussed
mechanistically.
—
With sulfadiazine for
toxoplasmosis; also with
sulfadoxine for malaria
(resistance/toxicity limit use)
Bactericidal
(combo)
UTIs, prostatitis,
Shigella/Salmonella (selected
situations), Nocardia, S. aureus
(many community strains
susceptible), respiratory
pathogens (H. influenzae, M.
catarrhalis), and Pneumocystis
jirovecii (treatment/prophylaxis).
Spectrum
Active vs many
UTI/resp pathogens
when combined
Protozoa
(Toxoplasma;
Plasmodium with
sulfadoxine)
Broad across listed
organisms
Common side/adverse
Notable toxicity
Nausea, vomiting, rash (when
in combo noted);
megaloblastic
anemia/leukopenia/granulocy
topenia (folate-related).
—
—
Bone-marrow
suppression risk
noted when
combined;
leucovorin often cogiven (described in
text).
Nausea, vomiting, rash; folaterelated cytopenias;
hyperkalemia reported.
Severe cutaneous
reactions are
discussed with
sulfonamide
component in class
notes.
smsoriano
PHARMACOLOGY REVIEWER
LONG EXAM 2
Drug
MOA
ANTIMICROBIAL GROUPS AND ANTIMICROBIAL RESISTANCE
PK
Common
side/adverse
Notable toxicity
CI
Strong vs gram-neg rods; less
pneumococcal activity (per class
narrative)
QT risk (class), tendons (class)
Avoid in
pregnancy/children
(class cautions)
t½: ~8 h; F: ~58%; Cmax:
~7.5; Oral: 450 mg bid;
Excretion: renal
Bactericidal
Activity vs gram-positive &
gram-negative; newer agent
described
Broad incl. MRSA/gram-neg per class
discussion
—
Class cautions
t½: ~8 h; F: ~70%; Cmax:
~1.6; Oral: 320 mg qd;
Excretion: renal & nonrenal
Bactericidal
“Respiratory” FQ (chapter)
Enhanced pneumococcal activity
QT risk noted among class
Class cautions
Bactericidal
“Respiratory” FQ; community
pathogens
Broad incl. pneumococcus; gram-neg
QT risk (class)
Class cautions
Bactericidal
Respiratory/anaerobic
coverage mentioned in
narrative
Good gram-positive/anaerobe activity;
not renal route
QT prolongation emphasized
among class
Avoid where QT risk
high; not relied upon
for UTIs (non-renal
excretion)
Delafloxacin
Gemifloxacin
Moxifloxacin
Spectrum
Bactericidal
Ciprofloxacin
Levofloxacin
Indications
UTIs; broad gram-negative
infections incl.
Pseudomonas; GI pathogens
mentioned in chapter
narrative
t½: ~3–5 h; F: ~70%; Cmax:
~2.4 mg/L; Oral dose: 500
mg bid; Excretion: renal
Inhibit DNA gyrase
(topoisomerase II) and
topoisomerase IV,
blocking DNA synthesis;
bactericidal.
PD
t½: ~7–10 h; F: ~0.99
(≈100%); Cmax: ~3.1; Oral:
500–750 mg qd; Excretion:
renal
t½: ~10 h; F: ~0.86; Cmax:
~3.1; Oral: 400 mg qd;
Excretion: non-renal
(hepatic)
Norfloxacin
t½: ~3–5 h; F: ~0.35–0.70
(35–70%); Cmax: ~1.1; Oral:
400 mg bid; Excretion: renal
Bactericidal
UTIs (narrower use)
Urinary pathogens
—
Class cautions
Ofloxacin
t½: ~5–7 h; F: ~0.95; Cmax:
~3.0; Oral: 400 mg bid;
Excretion: renal
Bactericidal
UTIs and systemic gram-neg
infections
Broad gram-neg
—
Class cautions
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