Antibiotics Flashcards
1
Q
Abscesses: what type of environment? Which class not effective?
A
acidic
aminoglycosides
2
Q
Which antibiotics have such good
bioavailability that po = IV availability? (5)
A
– Clindamycin po = IV – Fluoroquinolones po = IV – Septra po = IV – Tetracyclines po = IV – Metronidazole po = IV
3
Q
Time-dependent
antibiotics
(Concentration-INDEPENDENT - dep on amount of time above MIC) (7)
A
B-lactams (Penicillins, Cephalosporins, carbapenems) Vancomycin Macrolides Clindamycin Tetracyclines Linezolid Quinipristin/dalfopristin
4
Q
Concentration-dependent
antibiotics (hit hard, fast, high) (3)
A
Aminoglycosides
Fluoroquinolones
Metronidazole
5
Q
Bacteriostatic vs. bactericidal
A
– Inhibition of cell wall synthesis or protein
synthesis = cidal
– Changes in bacterial physiology = static
– Depends on drug concentration
6
Q
Mech of action: inhibit cell wall synth (4)
A
Vancomycin
Bacitracin
Penicillins
Cephalosporins
7
Q
Mech of action: decrease cell wall integrity (1)
A
b-lactamases
8
Q
Mech of action: inh DNA synth (1)
A
metronidazole
9
Q
Mech of action: inh DNA gyrase
A
Quinolones
10
Q
Mech of action: inh RNA polymerase
A
Rifampicin
11
Q
Mech of action: inh protein synth (50S) (3)
A
erythromycin
chloramphenicol
clindamycin
12
Q
Mech of action: inh protein synth (30S) (2)
A
tetracyclines
streptomycin
13
Q
Mech of action: inh folic acid metabolism
A
sulfonamides
14
Q
B-lactam group: 4 members & mech
A
- Penicillins
- Cephalosporins
- Carbapenems
- Monobactam
Inhibition of cell wall synthesis by binding to penicillin-binding
proteins
15
Q
B-lactam resistance mechs (3)
A
– Inactivation of antibiotic (penicillinase, or
16
Q
Penicillin: 2 types
A
– G procaine (IV)
– G benzathine (IM)
• Penicillin G benzathine : long half life and
elimination
– use is limited to treatment of syphilis, and sometimes
rheumatic heart disease
– V (oral/po)
(Used to be good against Gram+ including anaerobes, but S. aureus is now largely resistant)
17
Q
Penicillin for Tx S. aureus
A
Penicillinase-resistant:
Cloxacillin (gain in S. aureus activity = loss of anaerobic activity)
18
Q
Penicillin with expanded Gram- coverage (E. coli) (2)
A
Aminopenicillins:
– Ampicillin IV
– Amoxicillin (Amoxil) po
19
Q
Penicillin with Pseudomonas aeruginosa coverage (2)
A
– Ticarcillin
– Piperacillin
20
Q
Penicillin / B-lactamase inh combinations (3)
A
• Amoxicillin-clavulanic acid
– Clavulin po, Augmentin (IV/po)
• Ticarcillin-clavulanic acid
– Timentin IV
• Piperacillin-tazobactam
– Zosyn IV, Tazocin IV, Pip/tazo IV
Common side effect: diarrhea due to B-lac inh
21
Q
Penicillin / B-lactamase inh: coverage
A
BROAD SPECTRUM
– All combinations are active against:
• S. aureus
• Most gram-positive organisms including Enterococcus and Listeria
spp
• Most gram-negative respiratory pathogens (Haemophilus and
Moraxella spp)
• Most gram-negative enteric bacteria
• Most anaerobes (gram-positive and gram-negative)
– Timentin and Pip/tazo
• Active against ALL above BUT ALSO Pseudomonas spp
22
Q
Coverage: Penicillin G
or V
A
Gram-positive (GAS, S.pneumoniae)
Anaerobes and some Gram-negative
(N.meningitidis)
23
Q
Coverage: Cloxacillin
A
Gram-positive (GAS, S.aureus)
24
Q
Coverage: Amoxicillin & Ampicillin
A
Gram-positive (GAS S pneumoniae), Better Gram-negative coverage
25
Coverage: Ticarcillin & Piperacillin
Gram-positive but much better Gram-negative coverage – including
P.aeruginosa
26
Coverage: Amoxicillin-clavulanic acid & Piperacillin-tazobactam
Good Gram-positive coverage –
| including S.aureus, increased Gram-negative coverage and anaerobes
27
Important property of cephalosporins
Increased stability against beta-lactamases
28
1st gen cephalosporins (3)
IV: Cefazolin (Ancef)
PO: Cephalexin (Keflex), Cefadroxil (Duricef)
29
2nd gen cephalosporins (3)
IV: Cefuroxime (Zinacef)
PO: Cefuroxime axetil (Ceftin), Cefprozil (Cefzil)
30
3rd gen cephalosporins (4)
IV: Ceftriaxone (Rocephin), Cefotaxime (Claforan), Ceftazidime (Fortaz, Tazicef)
PO: Cefixime (Suprax)
31
4th gen cephalosporin (1)
Cefipime (Maxipime)
32
1st gen cephalosporins: activity
Excellent against Gram-positive – including S.aureus and GAS
Limited against Gram-negative mainly due to emergence of resistance
No anaerobic activity
33
2nd gen cephalosporins: activity
Excellent against Gram-positive
Increased coverage of Gram-negative, mainly respiratory flora
Coverage of Enterobacteriaceae
No anaerobic coverage
Note: 2nd gen cephamycins (Cefoxitin, Cefotetan): Less Gram positive coverage, Good Gram-negative coverage (not P.aeruginosa), * Anaerobic coverage (Bacteroides)
34
3rd gen cephalosporins: activity
```
Less optimal Gram-positive coverage
Excellent Gram-negative coverage
No P.aeruginosa coverage (EXCEPT FOR CEFTAZIDIME)
BBB penetration (IV formulation)
No real anaerobic coverage
Cefixime: poor bioavailability
```
35
4th gen cephalosporins: activity
Good Gram-positive coverage
Good Gram-negative coverage including P.aeruginosa
No anaerobic coverage
36
Cephalosporins: trends in Gram + and - coverage from 1st to 4th gen
Gram+ decreasing from 1st to 3rd, increasing from 3rd to 4th
| Gram- increasing from 1st to 4th
37
Cephalosporins with coverage against Pseudomonas, Campylobacter
Pseudomonas: ceftazidime (the only 3rd gen) and 4th gen
Campylobacter: no coverage
(both are Gram-)
38
Cephalosporins with coverage against Enterococcus and Listeria
None!
| both are Gram+
39
Carbapenems (4)
Meropenem
Imipenem
Ertapenem
Doripenem
40
Monobactams (1)
Aztreonam
41
Carbapenems: coverage
```
BROAD SPECTRUM
– Like BROAD SPECTRUM beta-lactams/beta-
lactamase inhibitor combinations
• Gram-positives (MSSA), gram-negative,
anaerobes
• Usually resistant to beta-lactamases
```
(Recent emergence of carbapenemases in
gram-negative enteric rods
– Emerging problem)
42
Imipenem, meropenem coverage
Excellent activity against Gram-positive (less
against Enterococcus faecium)
Excellent activity against Gram-negative –
including P.aeruginosa
Excellent anaerobic activity
Intrinsic resistance: Stenotrophomonas
maltophilia, C.jeikeium, C.difficile, atypical
bacteria (Mycoplasma, Chlamydia, Legionella),
B.pertussis
Good BBB penetration
43
Ertapenem coverage
Good activity against Enterobacteriaceae and
anaerobes
No activity against P.aeruginosa,
Acinetobacter, PRSP and enterococci
44
Aztreonam coverage
Same as aminoglycosides i.e. aerobic Gram-negative
45
Monobactams: coverage
NARROW SPECTRUM
– Gram-negative aerobic bacteria
• IV formulation
• Rarely used
46
Adverse reactions
| All beta-lactams) (3 mild, 2 serious
Mild side effects
– GI upset
– Diarrhea (beta-lactamase inhibitors; cefixime/Suprax)
– Drug induced neutropenia
Serious side effects
– Seizures
• All beta-lactams lower seizure threshold, some more than others (e.g. imipenem)
– Anaphylaxis
• If anaphylaxis with one penicillin, high risk of reacting to another
penicillin – less risk with cephalosporins
• 10% cross-reactivity between penicillins and carbapenems
47
Which beta-lactams cross the BBB
| appreciably? (5)
```
– Penicillin IV (high dose)
– Ampicillin IV (high dose)
– Third generation cephalosporins IV (high dose)
– Cefepime
– Carbapenems
```
48
Which beta-lactams have activity against MSSA? (5)
– Cloxacillin po/IV (and methicillin)
– b-lactam/b-lactamase combinations (po/IV)
– 1st and 2nd generation cephalosporins po/IV
• 3rd generation IV NOT that good – just OK
– Cefepime
– Carbapenems
49
Which beta-lactams have activity against
| Pseudomonas spp? (5)
```
– Ticarcillin and Piperacillin (IV)
– Timentin and Pip/tazo (IV)
– Ceftazidime (IV)
– Cefepime (IV)
– Carbapenems (IV)
```
50
Which beta-lactams have activity against
| anaerobes? (3)
– Penicillin (po/IV)
– All b-lactam/b-lactamase combinations (po/IV)
– Carbapenems (IV)
51
Glycopeptides (2)
Vancomycin
| Teicoplanin
52
Glycopeptides mech
```
• Inhibition of cell wall synthesis
• Inhibit the CROSS-LINKING of peptidoglycan
• Resistance:
– Enterococcus spp (VRE): Van gene
• Decreased affinity for vancomycin
– S.aureus (VISA; VRSA):
• Increased thickness of cell wall
– Increased D-ala-D-ala: traps glycopeptides
• Emerging problem
– Time-dependent killing
• some Post Antibiotic Effect
```
53
Vancomycin coverage
Possesses only Gram-positive activity –
including anaerobic Gram-positive
Very good activity against C. diff (oral treatment)
54
Vancomycin: administration
• No oral absorption
• Available as oral, IV, intraperitoneal,
intrathecal or intraventricular administration
• No IM: pain and local necrosis
• Renal excretion
• BBB penetration, mainly with inflammation
• Need higher levels to penetrate BBB, bone and cartilage, heart tissue
• Need higher levels when dealing with MRSA
55
Vancomycin: adverse rxs (2)
• Nephrotoxicity
– Usually with accumulation (high trough levels)
– when co-administered with other nephrotoxic
drugs
– Therapeutic drug monitoring to prevent this
```
• When administered over short period (<1hr)
– Histamine release (Red-man syndrome)
• Flushing
• Hives
• Even hypotension
```
56
Macrolides (3)
```
– Erythromycin (IV/po)
• Erythromycin estolate (po)
– Clarithromycin (po)
• Biaxin
– Azithromycin (IV/po)
• Zithromax
```
```
(Newer macrolides have better PK
parameters, e.g. Azithromycin has a long half life;
• Time-dependent killing
• Azithromycin possesses some Post
Antibiotic Effect)
```
57
Ketolides (1)
– Telithromycin (po)
| • Ketek
58
Macrolides/ketolides: Mechanisms of action and resistance
• Inhibition of protein synthesis
• Ketolides: increased affinity for target sites
– less resistance when compared to macrolides
• Resistance:
– Modification of target site (erm)
– Efflux pump (mef)
• Most gram-negatives: intrinsic resistance to
macrolides
– no penetration into gram negative bacteria
– Exceptions: Campylobacter spp, Bordetella pertussis, some
Haemophilus spp
59
Antibacterial spectrum: Macrolides/Ketolides
```
• Essentially:
– Gram-positives
• S. pneumoniae (if S)
• Group A Streptococcus (if S)
– Gram-negatives
• Campylobacter spp
• Bordetella pertussis
– Atypical bacteria
• Mycoplasma spp, Chlamydia spp, Clamydophila spp
– Non-tuberculous mycobacteria
• Clarithromycin, azithromycin
```
60
Erythromycin & clarithromycin coverage
OK activity against S.aureus sensitive to
macrolides, GAS, S.pneumoniae when
sensitive
Alternative for penicillin for allergic patients
Atypical bacteria and B.pertussis
61
Azithromycin coverage
Same as other macrolides except (1) more potent, (2) coverage of H.influenzae
Azithromycin also has some Gram-negative coverage
62
Telithromycin coverage
```
Same as erythromycin but better coverage
against Gram-positive
Not active against S.aureus resistant to
erythromycin
Not active against Enterobacteriaceae
```
63
Do macrolides cross the BBB?
No
64
Adverse reactions: erythromycin
– GI upset with erythromycin (cramps/nausea)
• Because it causes the GI tract to contract it can be used to treat GI reflux in children
– QT prolongation with erythromycin
– Pyloric stenosis if erythromycin is given to
neonates
65
Adverse reactions: telithromycin
- severe liver toxicity
- exacerbations of myasthenia gravis
Since 2007: only licensed for community acquired
pneumonia
• Only as an alternative drug
• BLACK BOX warning from the FDA
• Avoid use in myasthenia gravis patients
66
Aminoglycosides (5)
```
Gentamicin
Tobramycin
Amikacin
Streptomycin
Paromomycin
```
67
Mechanisms of action and resistance: Aminoglycosides
```
• Inhibit protein synthesis
– Act at the level of the ribosomes
• Resistance:
– Efflux pump
– Modification of target (mutated ribosome)
– Enzymatic inactivation of antibiotic
• Bactericidal and concentration-dependent
with Post Antibiotic Effect
```
68
Antibacterial spectrum: Aminoglycosides
• GRAM-NEGATIVE!
• Including Pseudomonas spp
• Except Salmonella spp, Neisseria spp
– Some have activity against TB and non-TB
mycobacteria
– Paromomycin has anti-parasitic activity (Giardia lamblia)
69
Coverage: Gentamicin, Tobramycin, Amikacin
Aerobic or facultative Gram-negative bacteria
– including P aeruginosa
Synergy with cell-wall agents against Grampositive
NO anaerobic coverage
NO Gram-positive coverage
Amikacin best against MAI and other atypical
mycobacteria
70
Paramomycin coverage
Only PO administration – good against
| G.lamblia, E.histolytica
71
Streptomycin coverage
Best against M.tuberculosis, Y.pestis,
| F.tularensis
72
Spectinomycin coverage
Some use against N.gonorrheae
73
Aminoglycosides: oral aborption? Conc- or time-dep killing? BBB penetration? Activity in acidic environ?
```
• NO oral absorption
• Concentration-dependent killing
• No BBB penetration
• Poor activity in acidic environment
– Not good when an abscess is present
```
74
Adverse reactions: Aminoglycosides (3)
• Renal toxicity:
– Associated with high accumulated levels (High trough levels)
– Increased if co-administered with other nephrotoxic drugs
– Reversible
• Vestibular and cochlear toxicity:
– Associated usually with prolonged use
– Tinnitus is the first problem sign
– Irreversible hearing loss
• Muscular blockade:
– Should be avoided in people with neuromuscular diseases (Botulism, Duschenne muscular dystrophy, myasthenia gravis etc)
75
Fluoroquinolones: 3 to remember
* Ciprofloxacin po/IV (Cipro) = 2nd gen
* Levofloxacin po/IV (Levaquin) = “The respiratory quinolone” = 3rd gen
* Moxifloxacin po (Avelox) = 4th gen
76
Mechanisms of action and resistance: Fluoroquinolones
• Inhibition of bacterial DNA synthesis
– DNA gyrase & topoisomerase II/IV
• Resistance:
– Modification of target enzymes
– Decreased bacterial permeability (porins)
– Efflux pump
• Concentration-dependent killing with short Post Antibiotic Effect
77
Antibacterial spectrum: Fluoroquinolones: trends from 1st to 4th generation for coverage against (1) S. pneumoniae, (2) MSSA, (3) enteric Gram- rods, (4) Pseudomonas spp, (5) Atypicals
1st gen: Very limited Gram-negative activity
Not suitable to treat systemic infections
Not used in clinical practice
2nd to 4th gen: increasing coverage against (1) and (2), same coverage against (3) and (5), decreasing coverage against (4)
4th gen only has coverage against Enterococcus faecalis and anaerobes
78
2nd gen fluoroquinolones Ciprofloxacin, Ofloxacin coverage
Best against P.aeruginosa. Good coverage of Gram-negative
Poor Gram-positive coverage
Improved PK parameters, enables treatment of systemic infections
79
2nd gen fluoroquinolone Norfloxacin coverage
Better coverage of Gram-negative – including P.aeruginosa
| No anaerobic activity, poor Gram-positive activity
80
3rd gen fluoroquinolones Levofloxacin
Grepafloxacin
Sparfloxacin
Gemifloxacin coverage
Increased coverage of Gram-positive – mainly S.pneumoniae
Good coverage of atypical bacteria (Moraxella, Legionella, Chlamydia)
Some activity against S.aureus
Gemifloxacin: best of the group against S.pneumoniae
81
4th gen fluoroquinolone Moxifloxacin coverage
Excellent Gram-positive (including S.pneumoniae) and Gram-negative
coverage (+/- against P.aeruginosa)
Anaerobic activity
Active against Enterococcus faecalis
82
4th gen fluoroquinolone Trovafloxacin coverage
Excellent P.aeruginosa activity
Best anaerobic coverage
Fatal liver toxicity
83
Fluoroquinolones: oral absorption? What causes decreased bioavailability? BBB penetration?
* Rapid and good oral absorption (Oral = IV availability)
* Decreased bioavailability with milk and calcium
* Poor BBB penetration
84
Adverse reactions: Fluoroquinolones (main adverse rxs (2), main contraindications (2))
```
• Not approved for use in paediatrics
– growth cartilage damage (e.g. beagles)
– This has not been seen in humans
– Is used in children when NEEDED
• Well tolerated, mainly GI upset
• Prolonged QT interval
• Pregnancy: Contraindicated
```
85
Sulfonamides (3)
Trimethoprim-sulfamethoxazole (Septra)
Sulfadiazine
Dapsone
86
Sulfonamides: mech and resistance
• Bacteriostatic, interfere with folic acid
pathway
• Inhibits bacterial dihydrofolic acid
• Resistance:
– Modification of target
– Decreased permeability
87
Trimethoprim-
| Sulfametoxazole: coverage
Broad spectrum – all bacteria requiring
endogenous folic acid synthesis
Gram-positive and Gram-negative including
Enterobacteriaceae, Shigella, S.maltophilia,
B.cepacia
(No activity against Group A Streptococcus, and Enterococcus spp)
Chlamydia, Nocardia
Pneumocystis jeroveci, Toxoplasma (anti-parasitic activity) - But most have developed resistance
Enterococcus intrinsically resistant
88
Sulfonamides: usual route of administration? Oral bioavailability? BBB penetration? Drugs of choice for which specific infections? (2)
• Usually administered PO (Oral = IV availability)
– IV formulation for Septra exists
• BBB penetration
– But there are better drugs for meningitis
– Worry is increasing resistance of many bacteria
• Drugs of choice for:
– Toxoplasma gondii infections
– Pneumocystis jiroveci
89
Adverse reactions: Sulfonamides (5) and 1 contraindication
```
• GI reactions
• Skin rashes: including Stevens-Johnson
• Kernicterus in children < 1 month of age
– Sulfa drugs are highly protein bound
– Bilirubin displacement from albumin
• Hemolysis in G6PD deficient people
• Allergy and Anaphylaxis
• Pregnancy: Contraindicated
```
90
Tetracyclines (3) and Glycylcycline (1)
• Tetracyclines
– Tetracycline (po/IV)
– Doxycycline (po)
– Minocycline (Topical only; acne treatment)
• Glycylcycline
– Tigecycline (IV)
91
Tetracyclines and Glycylcycline: mech and resistance
* Inhibition of protein synthesis in ribosome and mitochondria
* Time-dependent killing
* Post Antibiotic Effect
• Resistance:
– Efflux pump
– Ribosomal protection through inactivation by specific enzymes
– Tigecycline: increased affinity able to overcome resistance
92
Tetracycline coverage
```
Broad spectrum
Anaerobic Gram-positive and Gram-negative
bacteria
Atypical bacteria and intracellular pathogens,
Vibrio sp., spirochetes
Activity also against parasites
BUT S.pneumoniae, N.gonorrheae now
resistant
```
93
Doxycycline coverage
Same spectrum as tetracycline
Better PK parameters
Doxycycline ONLY (no other tetracyclines): Anti-malarial prophylaxis
94
Tigecycline coverage
Same as tetracyclines but remains active against
organisms resistant to tetracyclines
Active against MRSA, VRE, PRSP
95
Tetracyclines: spectrum
– Gram negative enteric rods
– Anaerobes
– Atypical bacteria
96
Tigecycline: spectrum
```
– Gram negative enteric rods
• Even those resistant to tetracyclines
• Multiresistant Enterobacteriaceae
– Gram positive
• MRSA, VRE, Penicillin-resistant S. pneumoniae
– Anaerobes
– Atypical bacteria
```
97
Tetracyclines and tigecycline: adverse rxs (2)? Contraindications (2)? Oral bioavail?
```
• Rare anaphylaxis
• Photosensitivity
– Rash (doxycycline)
• Not recommended in children under 8 years of age: discoloration of permanent teeth
– Mostly seen with tetracycline
• Tigecycline: not approved for < 18 years of age (No good studies in adolescents)
• Pregnancy: Contraindicated
• Oral = IV availability
```
98
Lincosamides (1)
Clindamycin
99
Mechanisms of action and resistance: Clindamycin
• Inhibition of protein synthesis
• Resistance:
– Similar to macrolides
• Bacteriostatic time-dependent activity
100
Coverage: Clindamycin
```
Good Gram-positive coverage, including
S.pneumoniae and S.aureus (ONLY if erythromycin S - resistance is similar to macrolides)
Good anaerobic activity
No Gram-negative coverage
No activity against Enterococcus sp.
```
101
Clindamycin: oral bioavail? BBB penetration? How is it cleared? Where does it concentrate well?
* Can be administered IM - Oral = IV/IM availability
* No BBB penetration
* Excellent concentration in bone
* Hepatobiliary clearance
102
Adverse reactions: Clindamycin
• Usually well tolerated
• May cause moderate diarrhea
• Associated with C.difficile colitis
– like most other antimicrobials
103
Metronidazole: used since 1950s for what? "Non-bacterial" application?
• Used since the 1950’s for bacterial vaginosis
• Activity against protozoa and parasites
discovered much more recently
• Anti-inflammatory effects at the level of the
colon
– Irrelevant to antimicrobial activity
– Used to “cool off” IBD exacerbations
104
Mechanisms of action and resistance: Metronidazole (Flagyl)
• Toxic to bacteria
– via production of free-radicals
• Very rapidly bactericidal, concentration-dependent
• Resistance:
– Very rare
– Decreased permeability
– Mutated targets in bacteria?
105
Metronidazole coverage
THINK: Anaerobes (gram positive and gram negative)
Clostridium difficile
ALSO THINK: Antiparasitic activity (Giardia lamblia, Entamoeba histolytica)
```
Very good anaerobic activity
Propionebacterium and Actinomyces most
often resistant
Good activity against C.difficile, G.vaginalis,
H.pylori
```
106
Metronidazole: route of admin? Metabolism/excretion? Oral bioavail?
```
• Available forms
– Oral (po)
– IV
– Topical
– Rectal (pr)
```
• Hepatic metabolism
– Avoid alcohol: disulfiram reaction
– Renal excretion
• Oral = IV availability
107
Adverse reactions: Metronidazole (Flagyl) (3)
```
• Well tolerated except GI upset
– Metallic taste in mouth
• CNS adverse effects after prolonged or
high-dose administration
– Headache, confusion
• Disulfiram effect
–With alcohol
```
108
Rifamycins (2)
Rifampin
| Rifabutin
109
Rifamycins: mech and resistance
```
• Inhibition of bacterial
RNA synthesis
– RNA polymerase
• Resistance:
– Multiple mutations in
gene coding beta-subunit of RNA polymerase
– Decreased permeability
```
110
Antibacterial activity: Rifamycins
```
• On their own, rifamycins induce RAPID
resistance
– Never used alone to treat infections
• Always with other antibiotics to buffer
resistance
```
– Can be used alone as prophylaxis
• Against developing meningitis from
N.meningitides, and H. influenzae
111
Antibacterial spectrum: Rifamycins
• THINK:
– Treatment:
• TB
• non-TB mycobacteria
– Post-exposure prophylaxis:
• N. meningitides (meningitis and/or meningococcemia)
• H. influenzae (meningitis)
112
Rifampicin coverage
Better against M.tuberculosis than rifabutin
Active against M.leprae
Bactericidal against S.aureus
Should not be used as monotherapy because
of rapid development of resistance
Post-exposure prophylaxis: N.meningitidis and
H.influenzae (invasive disease)
113
Rifabutin coverage
More lipophilic: better activity against M.avium
intracellulare
Otherwise same as rifampin
114
Rifamycins: route of admin? Metabolism and resulting interactions?
• Rifampin: available only as oral form
– Activity is affected by food
• Rifabutin: less affected by food
• MAJOR drug interactions
– Both are metabolized in the liver and
induce CYP-450 enzymes
115
Rifamycins: Adverse rxs (4)
• Mainly GI
– Nausea
– Increase in liver enzymes
• Skin rashes
• Rifampin:
– Orange-red colouration of body fluids (urine, tears)
• May permanent contact lenses
• Rifabutin:
– Bronze discolouration of skin
– Violet-red colouration of urine
116
Nitrofurantoin: use, mech, resistance
• Only used for UTI treatment and
prophylaxis
– Therapeutic concentrations achieved
ONLY in urine
* Bacteriostatic (low dose) and bactericidal (high dose)
* Unclear mode of action
• Resistance:
– Decreased activity of nitrofurane reductase
117
Nitrofurantoin: coverage
THINK: treatment of uncomplicated UTI
Active against Enterobacteriaceae
Active against some Enterococcus sp,
S.aureus and coagulase-negative
staphylococci (S.saprophyticus)
118
Adverse reactions: Nitrofurantoin (4)
```
• Mainly minor GI disturbances
• 1/5000 pulmonary syndrome with:
– Fever
– Chills
– Difficulty breathing
– Cough
– May be fatal
• Stevens-Johnson Syndrome
• Hemolytic anemia
```
119
Antibiotics specifically produced for
multiresistant gram-positive bacteria
(AGAINST MRSA AND/OR VRE)
• Oxazolidinones
– Linezolid
• Streptogramins
– Quinipristin/Dalfopristin
• Daptomycin
