Antibiotics Flashcards
1
Q
Which drugs inhibit bacterial cell-wall synthesis
A
- penicillin
- cephalosporins
- monobactams
- carbapenems
- bacitracin
- fosfomycin
- vancomycin
2
Q
B-Lactams (4)
A
penicillin
cephalosporins
monobactams
carbapenems
3
Q
Antitubercular agents
A
isoniazid
rifampin
pyrazinamide
ethambutol
4
Q
inhibit bacterial cell membrane synthesis
A
daptomycin
colistin
5
Q
inhibit bacterial protein synthesis
A
macrolides tetracycline aminoglycosides clindamycin lenezolid mupirocin
6
Q
inhibit nucleic acid synthesis
A
fluoriquinolines
trimethoprim
sulfamethoxazole
metronidazole
7
Q
30S Subunit protein synthesis blocker
A
tetracyclines
aminoglycosides
8
Q
50S subunit protein synthesis
A
macrolides clindamycin linezolid chloramphenicol stretogramins
9
Q
Penicillins (MOA)
A
bind to penicillin-binding proteins on cell wall to inhibit further synthesis
10
Q
Penicillin Bacterial Resistance
A
- Production of B lactamase enzymes that destroy B lactam ring of penicillin molecule
- OR mutation of PBP to prevent binding by penicillin
11
Q
Penicillins (PK)
A
relatively short half-lives
most eliminated by kidney unchanged
12
Q
Penicillin adverse reactions
A
Hypersensitivity Reactions
immediate: anaphylaxis, articaria, edema
accelerated: 1-72 hrs, urticaria
Delayed: days to weeks, rash, fever, serum sickness
Cross sensitivity exists between all penicillins - avoid if history of immediate or accelerated reaction with any of penicillin group
13
Q
Penicillin G
A
- natural penicillin the first penicillin
- very acid labile and only given IV with 30 min half life
- dosed in units (1 million units = 0.6 gm)
14
Q
Procaine penicillin G
A
-suspension given IM that lasts from 1-4 days depending on dose
15
Q
Benzathine penicillin G
A
suspension given IM that can last up to several weeks
16
Q
Penicillin V
A
oral form of penicillin that is more acid stable
17
Q
Natural Penicillins - What is it used for?
A
-Narrow spectrum antibiotic active against Streptococci, Neisseria miningitidis, Clostridium sp and treponema pallidum (syphillis)
18
Q
aminopenicillins
A
first of semisynthetic penicillins which are all produced from 6-aminopenicillinamic acid
19
Q
Ampicillin
A
- an aminopenicillin
- IV
- 80 min half life must be given 4 times a day
20
Q
amoxicillin
A
- an aminopenicillin
- most common antibiotic prescribed
- oral equivalent of ampicillin
- can be given 2-3 times a day and higher doses used in suspicion of penicillin-resistant pneumococcus
21
Q
Aminopenicillins - Reactions
A
- ampicillin rash with both amoxicillin and ampicillin in up to 10 % of individuals
- 60% incidence of rash in mononucleosis present or taking allopurinol for gout
22
Q
aminopenicillins - Uses
A
- active against common upper respiratory tract pathogens
- S. pyogenes
- S. pneumoniae
- hemophilus influenza
- some activity against enterococcus and common community gram-negative bacteria such as E. coli, and proteus sp
- NO STAPH AFFECTS
23
Q
Extended-Spectrum Penicillins
A
Anti-pseudomonal penicillins
24
Q
Piperacillin
A
- extended spectrum penicillins
- most common agents in class
- given IV
- usually used in combination with tazobactam (zosyn)
- excreted via the biliary tract
25
Carbenicillin, ticarcillin, mezlocillin
-extended-spectrum penicillin
| E-older agents rarely used now
26
Extended-Spectrum Penicillins (Adverse Effects)
- sodium overload with high doses
| - thrombocytopenia with high doses
27
Extended-Spectrum Penicillins - What is it used for?
- extended activity against gram-negative bacteria
- pseudomonas aeruginosa activity (combine with aminoglycoside antibiotic for serious P. aeruginosa infections)
- Bacteremia, pneumonia, neutropenic fever
- retains activity against enterococcus
- NO STAPH ACTIVITY
28
Clavulanic acid
- B-lactamase inhibitor+penicillin combo
- with amoxicillin = augmentin
- for diabetic foot wounds, bites, Staphylococcal infections
29
Sulbactam
- B-lactamase inhibitor+penicillin combinations
| - with ampicillin=UNASYN
30
Tazobactam
- B-lactamase inhibitor+penicillin combo
- with piperacillin = ZOSYN
- most widely used IV antibiotic in hospitals
- active against more gram + and gram - and anaerobic bacteria
31
B-lactamase Inhibitor/Penicillin Combinations (MOA)
- B-lactamase inhibitors preferentially combine with B-lactamase enzymes produced by bacteria and inactivate them
- make penicillins more active against previously resistant bacteria - increase activity against Staph, gram - and anaerobic
- does not increase activity against bacteria that are resistant because of altered PBPs (MRSA)
- same kinetics, adverse effects, etc as penicillins used alone
32
Penicillinase-Resistant Penicillins
-semisynthetic penicillins specifically developed to treat Staph resistant to penicillins
33
Methicillin
very first penicillinase-resistant penicillins
| -MRSA appears in 1961
34
Nafcillin
-penicillinase-resistant penicillin
-IV
-used 4-6 times a day
can cause phlebitis at IV site as well as serum sickness
35
Dicloxacillin
- penicillinase-resistant penicillin
| - oral equivalent of nafcillin
36
Cephalosporins
- similar to penicillins (sehre B-lactam ring) but more stable to B lactamases
- similar MOA to penicillin
37
Cephalosporins - Bacterial Resistance
- bacteria producing variety of B-lactamase enzymes that destroy lactam ring of molecule
- no activity against MRSA except for new drug ceftaroline
- no activity against Enterococcus sp or Listeria
38
Cephalosporins - PK
- half-lives vary from short to very long
| - most eliminated by kidney unchanged
39
Cephalosporins - Adverse Reactions
- hypersensitivity reactions less common than penicillins
- cross sensitivity with penicillins is minimal unless history of anaphylactic reaction with penicillins
- bacterial resistance tends to develop quickly with use
40
Cefazolin
- 1st generation cephalosporin
- IV
- given every 8 hours
41
Cephalexin
- 1st generation cephalosporin
- oral
- short half life
42
Cephradine
- 1st generation cephalosporin
| - oral
43
Cefadroxil
- 1st generation cephalosporin
- long half life
- PO
44
1st Generation Cephalosporins (USES)
- active against steptococcus sp and methicillin-sensitive staphylococcus (MSSA)
- also active against strains of E. coli and klebsiella sp
- cefzolin widely used in hospitals for wound infections and surgical prophylaxis
- cephalexin widely used in community for staphylococcal and streptococcal infections
45
cefuroxime
- 2nd generation cephalosporins
- IV
- for upper respiratory infections
46
cefaclor
- 2nd generation cephalosporin
| - oral
47
cefprozil
- 2nd generation cephalosporin
| - oral
48
2nd generation cephalosporin - What is it used for?
- increased activity against gram negative bacteria including klebsiella pneumoniae, menophilus influenzae, and moraxella catarrhalis
- for community-acquired penumonia and more resistant upper respiratory infections such as otitis media
49
Cefotaxime
- 3rd generation cephalosporins
- IV
- short half life
50
Ceftriaxone
-3rd generation cephalosporin
-long half line
give once daily IM/IV
51
Ceftazidime
- 3rd generation cephalosporins
- only 3rd generation with activity against pseudomonas
- useful alternative to piperacillin
52
Cefixime
- 3rd generation cephalosporin
| - PO
53
Cefpodoxime
- 3rd generation cephalosporin
| - PO
54
3rd Generation Cephalosporins - What are they used for?
- IV forms with wide range of activity against gram (-) bacteria as well as gram (+) bacteria
- used for nosocomial infections, pneumonia, meningitis, advanced lyme disease
55
Cefepime
- 4th generation cephalosporin
- only given IV
- more resistant to chromosomal B-lactamase enzymes
- good activity against Enterobacteriaceae and Pseudomonas aeruginosa
- unlike ceftazidime, also good activity against penicillin-resistant Streptococcus pneumoniae
56
Ceftaroline
- 5th generation cephalosporin
- IV only
- first beta-lactam approved for treatment of MRSA infections
- otherwise antibacterial spectrum most similar to 3rd generation cephalosporin, ceftriaxone
- no activity against pseudomonas or enterococcus species
57
Azteronam
- monobactam
- only given IV
- has monocyclic B-lactam ring
- no cross sensitivity in patients with history of severe penicillin of cephalosporin hypersensitivity reactions
- activity similar to ceftazidime with activity against many gram-negative bacteria as well as pseudomonas
- NO ACTIVITY against GRAM POSITIVE
- used for patients with B-lactam allergies
58
Carbapenems
- broadest spectrum of antibacterial drugs available - reserved for life threatening or multi-resistant infections
- structurally related to other B-lactam antibiotics
- all given intravenously
59
Imipenem-cilistatin
- carbapenem
- cilistatin inhibits the enzyme that hydrolyzes imipenem in kidney - helps increase half life but still give every 8 hours
60
meropenem
a carbapenem
61
erapenem
carbapenem
| longest half life give once daily
62
doripenem
carbapenem - preferred agent
| -more active against pseudomonas than others
63
carbapenem - uses
- serious polymicrobial and nosocomial infections due to highly resistant bacteria
- imipenem, doripenem and meropenem (but not ertapenem) also have activity against pseudomonas
64
carbapenems - Adverse
- can be neurotoxic
- greater chance of superinfections
- high cost
- some cross sensitivity in penicillin-allergic patients
- seizures!
65
Bacitracin
- inhibitors of bacteria cell wall synthesis
- topical, active against gram positive bacteria only
- highly nephrotocix if given systemically
- poor oral absorption
- used to treat skin infections due to streptococcus and staphylococcus
66
fosfomysin
- inhibitor of bacteria cell wall synthesis
- oral agent now starting to be recommended for gram-negative urinary infections - if suspected or known resistance to sulfa and fluoroquinolone antibiotics
67
Nitrofurantoin
- bacteria cell wall synthesis inhibitor
- only used for UTI
- bactericial against E. coli, enterococcus, and other common UTI organisms
- commonly causes GI irritation, nausea and vomiting
- should avoid in elderly due to increased risk of pneumonitis and neuropathy
- contraindicate in renal failure
68
Vancomycin (MOA)
- glycopeptide molecule with high molecular weight
| - inhibits cell wall synthesis by blocking elongation of peptoglycan molecule
69
Vancomycin Bacterial Susceptibility
- bactericidal against most gram-positive bacteria including those resistant to B-lactam antibiotics
- no activity against gram-negative bacteria
- some eterococci have become resistant and are known as vancomycin-resistant eterococci or VRE
70
Vancomycin - Route
- usually given IV
- not absorbed orally
- oral vancomycin remains in GI tract and only used to treat clostridium difficle colitis
71
Vancomycin - PK
- eliminated by kidney in direct proportion to creatinine clearance
- narrow therapeutic index - must monitor peak and through levels
72
Vancomycin -Adverse reactions
- Red Man Syndrome - infusion reaction due to massive histamine release if given too fast or in too high a dose -> treat with antihistamine
- ototoxicity at higher doses
73
Vancomycin - What do you use it for?
- reserved for known or suspected infections due to MRSA
- also used in combination with aminoglycoside for serious Enterococcus infections
- oral vancomycin only used to treat pseudomembranous colitis secondary to Clostridium difficile infection
74
Daptomycin
- bacterial cell membrane synthesis
- unique cyclic lippeptide active against gram-positive bacteria-only available in IV form
- old drug
- concentration-dependent activity
75
Colistin
- bacterial cell membrane synthesis inhibitors
- starting to be used for MDR resistant bacteria such as CRE
- nephrotoxic like aminoglycosides
- intravenous
76
Macrolide MOA
reversibly bind to 50S ribosomal subunit
77
Macrolide - Bacterial susceptibility
- usually bacteriostatic effect
- Streptococcus sp and Staphylococcus
- some activity against hemophilus influenzae and bordetella
- activity against atypical bacteria (mycoplasma, leionella, chlamydophyla) that cause pneumonia
78
Macrolide - What is it used for?
- for upper and lower respiratory infections potentially due to atyipcal bacteria
- IV azithromycin used extensively in hospitals for pneumonia
- for penicillin-allergic patients
- for chlamydia STD infections
- clarithromycin for mycobacterium avian complex (MAC)
79
Erythromycin
- macrolide
- IV form rarely used, orally available as base, stearate, estolate, and ethylsuccinate salts
- given 3-4 times a day
80
Erythromycin - Adverse Effects
- agonist for motillin receptors leads to abdominal pain and diarhea
- high IV doses can cause ototocity
81
Erythromycin - drug interactions
- inhibits CYP 450 3A4 enzyme responsible for metabolizing 50% of drugs
- will increase serum levels of statins, benzodiazepenes, calcium channel blockers, cyclosporine and many more
82
Clartihromycin
- macrolide
- very similar to erythromycin but better absorbed - higher serum levels and lower GI levels
- not available as IV, can give twice daily
- has less GI adverse effects
- same drug interactions as erythromycin but stronger
83
Azithromycin
- most popular and safest macrolide
- IV and oral
- half life of 60 hours requires loading dose and once daily Z Pack ( give 3-5 days)
- minimal adverse reactions, no drug interactions
84
Tetracyclines
MOA: reversibly bind to 30S ribosomal subunit of bacteria
Bacterial susceptibility: bacteriostatic, activity against gram-positive and gram-negative bacteria. Activity against ricketsiae, chlamydiae, mycoplasma and some protozoa
85
Tetracycline - Adverse reactions
- GI irritation
- photosensitivity
- discoloration of tooth enamel in children and fetus
- hepatotoxicity possible with extended use
86
tetracycline - drug interactions
- cations such as calcium will bind to tetracyclines and prevent absorption
- avoid giving with dairy products or antacids
87
tetracycline - what is it used for?
-lyme disease, erlichiosis, rocky mountain spotted fever, atypical pneumonia, pelvic inflammatory disease, tetracycline and minocycline for acne
88
Tetracycline
-rarely used now because of lower bioavailability and short half life - have to give 4x daily
89
doxycycline
- most popular tetracycline
- given both IV and oral (good bioequivalence)
- has long half life and can be given once or twice a day depending on infection
90
minocycline
- tetracycline
- popular for acne due to high distribution in skin
- very expensive
91
Tigecycline
- new tetracycline, IV drug for complicated skin and intra-abdominal infections
- bacteriostatic
- active against gram-positive (including MRSA), gram-negative, and anaerobic bacteria
- not active against pseudomonas or proteus species
- reserve for antibiotic-resistant infections
- Adverse: frequent naseau and vomiting
92
aminoglycoside MOA
IRREVERSIBLY binds to 30S ribosomal subunit of bacteria
93
aminoglycoside - bacterial susceptibility
- bactericidal activity against most gram-negative bacteria, including pseudomonas
- streptococci are resistant to agents when used alone
- synergystic activity when combined with B-lactam antibiotics
94
aminoglycoside - what is it used for?
bacteremia, pneumonia, intra-abdominal infections, and other serious infections due to gram-negative bacteria
95
aminoglycoside - PK
- only available for IV or IM use - unable to be absorbed orally
- short half life of 2-3 hours
- give high dose once daily due to concentration-dependent effect on bacterial killing
- eliminated renally and accumulate in renal failure
- monitor peak and through levels due to narrow therapeutic window
96
aminoglycoside - adverse reactions
- very nephrotoxic - can accumulate in renal tubules and cause acute renal failure
- also ototoxic at high doses for extended periods of use
97
Tobramycin
-aminoglycoside - inhaled form for cystic fibrosis patients with pseudomonas pneumomniae
98
neomycin
- aminoglycoside
- most toxic and never used as IV
- used in topical formulas in combination with other antibiotics
- oral form sometimes used for prophylaxis before elective bowel surgery
99
streptomycin
- aminoglycoside (1st one)
| - used IV or IM as second-line therapy for active tuberculosis
100
clindamycin MOA
- aminoglycoside
| - binds to same 50S ribosomal subunit as macrolide antibiotics
101
clindamycin - bacterial susceptibility
- bacteriostatic activity
- inhibits Streptococci, staphylococci, and pneumococci
- inhibits anaerobic bacteria such as bacteroides fragilis and clostridium perfinges
102
Clindamycin - what is it used for?
- anaerobic infections such as intra-abdominal wounds, gynecologic infections, abscesses, and aspiration penumonia
- for gram-positive infections in penicillin-allergic patients
- for newly discovered community-acquired MRSA
103
clindamycin - PK
- can be given IV or orally
| - metabolized by liver
104
Clindamycin - adverse reactions
- GI upset such as nausea and diarrhea
| - primary antibiotic to cause antibiotic -associated pseudomembranous colitis
105
Linezolid (MOA)
oxazolidinedione with unique activity against bacterial 50S subunit of bacteria
106
Linezolid - Bacterial susceptibility
- bacteriostatic activity
- active against most gram-positive bacteria, including most strains resistant to other antibiotics
- resistance may occur with overuse
107
Linezolid - USES
should be reserved for infections caused by mutli-drug resistant bacteria such as VRE and MRSA
108
Linezolid - PK
- oral or IV with 100% F
| - metabolized by the liver with half life of 4-6 hours
109
Linezolid - Adverse reactions
hematologic toxicity - can cause thrombocytopenia and neutropenia with extended use
110
Mupirocin
- bactroban
- unrelated to other antibiotics only used in topical preparations for treating staphylococcal infections
- should be reserved for suspected for definite MRSA to avoid development of resistance
- also used for impetigo caused by streptococci or staphylococci
- special nasal formulation available to eliminate carriage of MRSA
111
fluoroquinolone (MOA)
inhibit DNA gyrase and topoisomerase that are essential for maintaining bacterial DNA structure and function
112
fluoroquinolone (Bacterial Susceptability)
- bactericidal activity against most gram-negative bacteria
- active against atypical bacteria
- 3rd generation agents also have good activity against gram-positive bacteria (except staphylococci)
113
fluoroquinolone - what is it used for?
- complicated urinary tract infections and prostatitis
- serious infections secondary to gram0negative bacteria such as bacteremia and intra-abdominal infections
- 3rd generation agents used for severe pneumonia
- infectious diarrhea secondary to salmonella and shigella
- for penicillin-resistant anthrax
114
fluoroquinolone - PK
- most available as both IV and oral forms
- distribute very well into most tissues
- renal excretion
115
Fluoroquinolone - Adverse Reactions
- causes arthropathy in developing animals - avoid in children less than 18 years old and during pregnancy
- neurotoxic in high doses (irritability, seizures)
116
Fluoroquinolone - drug interactions
- absorption of oral dosage forms inhibited by cations such as calcium, magnesium, iron and zinc (multivitamins and antacids)
- inhibit metabolism of caffein and theophylline
117
ciprofloxacin
- 2nd generation fluoroquinolone (most commonly used)
- only quionolone with activity against pseudomonas aeruginosa
- poor activity against gram-positive bacteria, shorter half life requires 2x a day - IV or oral
118
Norfloxacin
still used for urinary tract infections - doesnt achieve high enough serum levels for systemic infections
119
3rd Generation Fluoroquinolones
- known as respiratory fluoroquinolones
- active against most bacteria responsible for respiratory infections including atypical bacteria and multidrug-resistant streptococcus pneumoniae
120
Levofloxacin
-3rd generation fluoroquinolone
-most common; used for serious infections
-renal elimination with normal half life = 7 hrs
given once daily IV or oral
121
moxifloxacin
- 3rd generation fluoroquinolone
- has better activity against anaerobic bacteria than levofloxacin
- metabolized by liver so should not be used for urinary tract infections
- given once daily IV or oral
122
gemifloxacin
- 3rd generation fluoroquinolone
- oral only
- hepatic metabolism
- greater incidence of rash
- twice as expensive as other 2nd generation agents
123
Bactrim - Bacterial Susceptibility
- bactericidal activity against most gram-positive and gram-negative bacteria including CA-MRSA
- active against nocardia, penumocystic, jiroveci
- no activity against enetrococci, atypical bacteria, anaerobic bacteria or pseudomonas aeruginosa
124
Bactrim - Uses
- primary drug for urinary tract infections
- secondary drug for upper and lower respiratory tract infections, sepsis, meningitis, travelers-diarrhea, typhoid, cholera
125
bactrim - PK
- can be given both oral and IV
- well distributed in tissues including CSF
- 50% excreted by kidneys
- half life 12 hours can be dosed 2x a day
126
Bactrim - adverse reactions
- hypersensitivity
- exfoliative dermatitis adn stevens johnson syndrome
- high doses for P. jiroveci infections in AIDS: can cause thrombocytopenia and neutropenia, high incidence of allergic reactions and hyperkalemia
127
Bactrim - imp. drug interactions
-can increase serum levels ad toxicity of warfarin, phytoin and oral sulfonylureas
128
Metronidazole
- both antibacterial and antiprotozoal
- nitromidazole that is readily taken up only by anaerobic bacteria and then reduced to a toxic metabolite
- disrupts DNA helical structure only in anaerobic bacteria
- best single agent to treat anaserobic infections, including abdominal infections and C. difficile colitis
- available oral or IV - Avoid alcohol
