Antibiotics Flashcards
1
Q
What is the mechanism of action of the B-Lactam abx?
A
Bind to penicillin-binding proteins–PBPs
2
Q
What is a significant cause of resistance in gram-negative organisms?
A
B-lactamase
3
Q
Name the natural penicillins
A
Penicillin G and V
4
Q
What are the penicillinase-resistant penicillins or anti staphylococcal penicillins?
A
Oxacillin
Nafcillin
Dicloxacillin
5
Q
What are the aminopenicillins?
A
Ampicillin
Amoxicillin
6
Q
What are the anti-pseudomonad penicillins?
A
Ticarcillin
Piperacillin
7
Q
What is the drug of choice for T. palladium (syphilis) infection?
A
Penicillin
8
Q
What are the strep infections treated with penicillin?
A
S. pneumoniae
B-hemolytic streptococci
Viridian group strep
9
Q
What Gram negative organism is treated with penicillin?
A
N. meningitidis
10
Q
What abx are used for the tx of MSSA?
A
Anti-staphylococcal penicillins–Oxacillin, Nafcillin, Dicloxacillin
11
Q
Why are Oxacillin, Nafcillin, Dicloxacillin great Abx to use against MSSA?
A
Bulky side chain streakily shields the B-lactam ring–Prevents degradation from penicillinase
12
Q
Why do the anti-staphylococcal penicillins Oxacillin, Nafcillin, Dicloxacillin lack activity against gram negative bacteria ?
A
Bulky side chain precepts entry into gram-negative cell
13
Q
What are the side effects of Oxacillin?
A
Hepatotoxicity and neutropenia
14
Q
What are the side effects of Nafcillin?
A
Hepatotoxicity and neutropenia + thrombophlebitis
15
Q
What is the major advantage to using Ampicillin and Amoxicillin?
A
Amino group increases hydrophilicity–improving penetration into gram-negative cell membrane
16
Q
Ampicillin and amoxicillin are the drugs of choice for what?
A
Enterococcus
17
Q
Amoxicillin clinical uses are?
A
Otitis media
Upper and lower-respiratory tract infections
Lyme disease
18
Q
IV ampicillin is used for?
A
Listeria
DOC for Enterococcal infection
19
Q
Which amino penicillin is better absorbed PO?
A
Amoxicillin
20
Q
What is the primary use of Piperacillin and Ticarcillin?
A
Used in combination with a B-lactamase inhibitor to expand spectrum to include B-lactamase-producing organims
21
Q
Name the extended spectrum penicillins/B-lactamase inhibitor combinations
A
Piperacillin/tazobactam–zosyn
Amoxicillin/clavulanate–Augmentin
22
Q
What ate the two extended spectrum penicillins/B-lactamase inhibitor combinations that are active against Pseudomonas aeruginosa?
A
Pip/taz and tic/clav
23
Q
Name the first generation cephalosporins…
A
Cefazolin
Cephalexin
Cephadroxil
24
Q
What is the mechanism of action of the cephalosporins–Gen 1-4?
A
Form a complex with a PBP, prevent extracellular transpeptidase activity
These are broader spectrum than penicillins
25
What cephalosporin is DOC for surgical prophylaxis?
Cefazolin
26
What is the spectrum for the 1st gen cephalosporins?
MSSA and streptococci
```
Some enteric Gram negative rods
-Proteus mirabilis
-E. coli
-Klebsiella pneumonia
PEcK
```
27
Name the 2nd generation cephalosporins...
Cefuroxime
Cefoxitin
Cefotetan
28
What are the 2nd generation cephalosporins used for?
Gram-positive--staph and strep--> less active than 1st gens
Gram-negative--H. flu and N. gonorrheae
29
Name the 3rd generation cephalosporins...
Ceftazadime
Cefpodoxime
Ceftriaxone
30
What are the uses for the 3rd generation cephalosporins?
Extended activity against enterobacteriaceae
| Strep
31
What is Ceftazidime active against?
Third gen--Pseudomonas
32
What are the 3rd generations cephalosporins associated with--in terms of dz?
C. difficile diarrhea
33
Why shouldn't Ceftriaxone be used in neonates?
Biliary sludging and kernicterus--interaction with Ca++ containing solutions causing precipitation
34
What drug should be used in neonates instead of ceftriaxone?
Cefotaxime
35
Name the 4th generation cephalosporins?
Cefepime
36
What are the clinical uses of the 4th generation cephalosporins--cefepime?
Gram-negative--enterobacteriaceae and pseudomonas
Gram-positive--MSSA and S. pneumoniae
Geared toward nosocomial infections--pseudomonas
37
Why are the 4th gen cephalosporins used to tx meningitis?
Can cross BBB
38
Name the 5th generation cephalosporins?
Ceftaroline
39
What is unique about the 5th gen cephalosporins--Ceftaroline?
Possesses a side chain that mimics a portion of the cell wall structure and acts as a "Trojan horse" allowing access to the PBP2a
40
What are the uses of the 5th gen cephalosporins--Ceftaroline?
Gram-positive--S. aueus--MSSA and MRSA, E. faecalis, S. Pneumoniae
41
What is the major use of Ceftazidime/Avibactam?
Complicated UTI and intraabdominal infection
Increases Gram negative spectrum
42
Name the Carbapenems...
Imipenem-cilastatin
Meropenem
Ertapenem
Doripenem
43
What are the uses of the carbapenems?
Broad spectrum--Excludes MRSA
Used for highly-resistant organisms
44
What is the major rare side effect seen with carbapenems?
Seizures
45
What drug interaction is seen with carbapenems?
Decrease valproic acid concentrations
46
What is Ertapenem used for?
Has a long t 1/2 making it ideal for outpatient polymicrobial infections
47
Which carbapenem has the most activity against pseudomonas?
Doripenem
48
Name the Monobactam...
Aztreonam
49
What are the primary uses of aztreonam--monobactam?
Gram-negative--Enterobacteriaceae and Pseudomonas
Rarely used alone--alternative to penicillin to provide gram-negative in combination with another agent
50
What is the mechanism of action of Vancomycin?
Inhibits late stages of cell wall synthesis
- Binds to D-Ala-D-Ala terminus of the nascent peptidoglycan pentapeptide
- Inhibits transglycosylase preventing elongation of peptidoglycan and cross-linking
51
What are the uses of Vancomycin?
Gram-positive
- Staph--MRSA
- Strep
- Enterococci
- Bacillus spp and Corynebacterium spp
Anaerobes
- Peptostreptococcus
- Actinomyces
- Propionibacterium
- Clostridium--C. diff oral form
DOES NOT work for Gram negative
52
What can occur with vancomycin infusion?
Redman syndrome--Secondary to histamine release
53
What is the mechanism of action for Daptomycin a lipopeptide?
Insertion into the gram-positive cell membrane causing depolarization and ultimate cell death
--Penetrates bacterial cell wall--forming a channel for subsequent leakage of intracellular ions
54
What is the mechanism of resistance for daptomycin?
Alteration of cell membrane--increased fluidity, increased net surface charge, reduced daptomycin surface binding
55
What are the uses for daptomycin?
Gram-positive--Staph, strep, enterococci--VRE
NO GRAM-Negative activity
56
Why isn't daptomycin used for pneumonia?
Not effective fro pneumonia due to inactivation by pulmonary surfactant
57
What are the side effects of daptomycin?
Myalgia and rarely rhabdomyolysis
Eosinophilic pneumonia
58
Name the lipoglycopeptides...
Telavancin
Dalbavancin
Oritavancin
59
What are the lipoglycopeptides telavancin, dalbavancin, and oritavancin?
Binds to same target as vancomycin and inhibits transglycosylation
They have similar coverage with compared to vanco BUT are active against VRE and have more anaerobe coverage
60
What are the side effects of the lipoglycopeptides telavancin, dalbavancin, and oritavancin?
```
Metallic taste
Nausea
HA
Nephrotoxicity
Teratogenic--Telavancin
```
61
What drug is reserved for pseudomonas species resistant to all other antibacterials?
Colistin--penetrates bacterial cell wall, forcing a channel for subsequent leakage of intracellular ions
62
All protein synthesis inhibitors are bacteriostatic EXCEPT?
Aminoglycosides
63
What abx target the 30s ribosomal subunit?
Aminoglycosides--gentamicin, tobramycin, amikacin
Tetracyclines--doxycycline, minocycline
Glycylcyclines--tigecycline
64
What abx target the 50s ribosomal subunit?
Macrolides--azithromycin, clarithromycin
Clinamycin
Oxazolidinones--linezolid, tedizolid
65
Name the aminoglycosides...
Gentamicin
Tobramycin
Amikacin
Streptomycin
66
What is the mechanism of aminoglycosides?
Bind to the 30s subunit of bacterial ribosomes and interfere with an initiation complex btw mRNA and the 30s subunit--inhibits protein synthesis
Bacteriacidal
67
Why are aminoglycosides ineffective against anaerobes?
They have an oxygen dependent uptake mechanism
68
What are the uses of the aminoglycosides?
Gram-negative
-Enterobacteriaceae and Pseudomonas
Gram-positive
-Synergy with cell wall active agent against enterococcus--CANNOT give as mono therapy
69
What are the side effects of the aminoglycosides?
Nephrotoxicity
Ototoxicity
Neuromuscular blockage
70
Name the tetracyclines
Doxycycline
Minocycline
Tetracycline
71
What is the mechanism of action of the tetracyclines?
Passive diffusion through porins in gram-negative organism
| -Bind 30s ribosomal subunit preventing protein synthesis
72
What are the uses of the tetracyclines?
```
Atypical organisms
-C. pneumoniae
-M. pneumoniae
Spirochetes
-Borrelia burgodorferi
-Leptospira
-T. pallidum
Rickettsiae
Gram-positive
-S. pneumoniae
-CA-MRSA
Gram-negative
-H. influenzae
-Neiserria spp
```
73
Tetracyclines are the DOC for what?
Tick-borne illnesses
- Lyme
- Ehrlichiosis
- Anaplasmosis
74
What are the drug interactions that occur with tetracyclines?
Di, Tri-valent cations--oral forms only
- Reduced tetracycline absorption
- Avoid coadminstration with antacids, sucralfate, multivitamins, iron, etc
75
What allows tigecycline to overcome two major resistances and what are these?
9-glycl substitution
Efflux pumps and Ribosomal protection
76
What are the uses for tigecycline?
Broad-spectrum--includes MRSA, VRE and acinetobacter
77
Tigecycline is one of the only drugs effective against what?
Carbapenem-resistant enterobacteriaceae--CRE
78
What are the macrolides?
Azithromycin
Clarithromycin
Erythromycin
79
What is the mechanism of action of the macrolides--Azithromycin, Clarithromycin, Erythromycin?
Reversible binding to 50s subunit--blocks translocation by inference with tRNA release following peptide bond formation
80
What are the macrolides effective for?
Intracelular pathogens
- Mycoplasma
- Chlamydia
- Legionella
H. influenzae
S. pneumoniae--high level of resistance
81
What are the side effects seen with marcolides?
Thrombophlebitis
| QT-prolongation--Torsades
82
What is the mechanism of action of Clindamycin?
Binding to 50s ribosomal subunit preventing protein synthesis --at A site--blocking peptide bond formation
83
What is clindamycin used for in combination therapy?
Plasmodium falciparum with quinine
| Toxic-shock syndrome with penicillin
84
What are the side effects of clindamycin?
Diarrhea and pseudomembranous colitis --C. diff
85
What is the mechanism of action of linezolid and tedizolid--oxaxolidinones?
Binds to 23 S ribosomal RNA of the 50S subunit inhibiting protein synthesis
86
What are the uses for linezolid and tedizolid?
Gram-positives
- Staph--MRSA and MSSA
- Enterococci--VRE
- Strep
87
What drugs are recommended fro 1st line therapy of S. aureus bacteremia?
Vancomycin and daptomycin
88
What are the side effects of linezolid and tedizolid?
Bone marrow suppression--thrombocytopenia after 2 wks
Lactic acidosis
Optic neuritis
Peripheral neuropathy
Irreversibly inhibits MOA which poses a risk for serotonin syndrome with serotonergic drugs
89
What are the Nucleic acid synthesis inhibitors?
Fluoroquinolones--Ciprofloxacin, Levofloxacin, Moxifloxacin
Metronidazole
Rifamycins--Rifampin, Rifabutin, Rifaximin
90
Name the Fluoroquinolones...
Ciprofloxacin
Levofloxacin
Moxifloxacin
91
What is the mechanism of action of the fluoroquinolones?
Inhibit DNA gyrase
Inhibit topoisomerase IV--Quinolones trap or stabilize the enzyme DNR complexes after strand breakage and before resealing of DNA
92
What is Ciprofloxacin used for?
Enterobactericeae
Pseudomonas--PO
Atypicals
93
What is Levofloxacin used for?
Pseudomonas-PO
94
What is Moxifloxacin used for?
Anaerobes
95
What are the major side effects of the fluoroquinolone?
Tendinitis--tendon rupture
| QT prlongation--Moxifloxacin
96
What are the drug interactions for the fluoroquinolones?
Di-, tri-valent cations
Ciprofloxacin--inhibits CYP 1A2
- Increase theophylline levels--can lead to seizure
- Increases tizanidine concentrations resulting in hypotension
97
What is the mechanism of action of metronidazole?
Interacts with DNA to cause a loss of helical DNA structure and strand breakage resulting in inhibition of protein synthesis
--Reduced only under anaerobic conditions to an active free radical which damages bacterial and certain protozoal DNA
98
What are the uses of metronidazole?
Anaerobes
- B. fragilis
- Clostridial species--including difficile
Protozoa
- Trichomonas
- Giardia
- Entamoeba histolytica
99
Name the Rifamycins...
Rifampin
Rifabutin
Rifaximin
100
What is the mechanism of action of the Rifamycins?
Bind to DNA-dependent RNA polymerase inhibiting RNA synthesis
101
What are the uses for Rifampin?
Mycobacterium tuberculosis
| Staph aureus
102
What are the side effects of Rifampin?
Flu-like symptoms--> fever, myalgia, interstitial nephritis
Thrombocytopenia, hemolysis
Transaminitis
103
What is Rifampin an inducer of?
CYP 450 system--lower concentration of substrates
104
What is the mechanism of action of Isoniazid?
Inhibition of synthetic pathways of mycolic acid
105
What are the side effects of isoniazid?
Hepatitis
| Neurotoxicity --peripheral neuropathy--pyridoxine can alleviate
106
What is the mechanism of action of Ethambutol?
Inhibits arabinosyl transferase enzymes involved in biosynthesis of cell wall
107
What are the 4 drugs used for TB tx?
Rifampin
Isoniazid
Pyrazinamide
Ethambutol
108
What is the mechanism of action of Sulfamethoxazole?
Interferes with bacterial folic acid synthesis and growth via inhibition of dihydrofolic acid formation from paraaminobenzoic acid (PABA)
109
What is the mechanism of action of Trimethoprim?
Inhibits dihydrofolic acid reduction to tetrahydrofolate resulting in sequential inhibition of enzymes of the folic acid pathway
110
What are the uses for Sulfamethoxazole/Trimethoprim?
Uncomplicated UTIs
Pneumocystis
Pneumonia
Toxoplasmosis infections in immunocompromised pts
111
Trimethoprim-Sulfamethoxazole is prophylaxis and tx for?
Pneumocystis jiroveccii pneumonia
112
What is the major drug interaction that occurs with trimethoprim-sulfamethoxazole?
Warfarin--inhibition of CYP 2C9 leading to increase in INR
