43 Betalactams Flashcards
(142 cards)
1
Q
Structure of penicillin
A
Thiazolidine ring is attached to a B-lactam ring that carries a secondary amino group (RNH-)
2
Q
What enzymes hydrolyses the B-lactam ring
A
Bacterial B-lactamases
3
Q
Hydrolysis of the B-lactam ring by bacterial B-lactamases yiels??
A
Penicilloic acid , which lacks antibaterial activity
4
Q
3 groups of penicillin
A
Penicillins
Antistaphylococcal penicillins
Extended-spectrum penicillin
5
Q
These penicillin are resistant to staphylococcal B-lactamases
A
Antistaphylococcal penicilins
6
Q
These type of penicillin retain the antibacterial spectrum of penicillin and have improved activity against gram-negative rods
A
Extended-spectrum penicillins
7
Q
Penicillins that can be taken orally and they are stable to gastric acid which makes them suitable for oral administration
A
Penicillin V
Dicloxacillin
Amoxicillin
Amoxicillin/potassium clavulanate
Cloxacillin
8
Q
Penicillins have greatest activity against?
A
Gram-positive organism
Gram negative cocci
Non B-lactamase producing anaerobes
9
Q
Penicillins have little activity against?
A
Gram negative rods
10
Q
Anti-staphylococcal Penicillins are active against?
A
Staphylococci and streptococci
11
Q
Anti-staphylococcal Penicillins are not active against?
A
Enterococci
Anaerobic bacteria
Gram-negative cocci and rods
12
Q
Extended-spectrum penicillins have improved activity against?
A
Gram-negative rods
13
Q
All groups of penicillins are susceptible to hydrolysis by?
A
B-lactamases
14
Q
MOA of penicillins , all B-lactam antibiotics
A
Covalently binds to the active site of PBP which inhibits transpeptidation reaction and halts peptidoglycan synthesis, and the cell dies
15
Q
Cell wall if bacteria is composed of?
A
A complex, cross-inked polymer of polysaccharides and peptides known as PEPTIDOGLYCAN
16
Q
The polysaccharides contains what alternating amino sugars?
A
N-acetylglucosamine and N-acetylmuramic acid.
17
Q
Where does the five amino acid peptide is linked to?
A
To the N-acetylmuramic acid sugar
18
Q
Where does the peptide of peptidoglycan terminates in?
A
In D-alanyl-D-alanine
19
Q
Purpose of cross-links
A
Gives the cell wall its rigidity
20
Q
An enzyme that removes the terminal alanine in the process of forming a cross-link with a nearby peptide
A
Penicillin-binding protein
21
Q
Purpose of bacterial cell wall
A
Maintains cell integrity and prevents cell lysis from high osmotic pressure
22
Q
When does beta-lactam antibiotics kills the bacteria?
A
When they are ONLY actively growing and synthesizing sell wall
23
Q
4 general mechanism of bacterial resistance
A
- Inactivation of antibiotic by B-lactamase
- Modification of target PBP
- Impaired penetration
- Antibiotic efflux
24
Q
The most common mechanism of resistance
A
Beta-lactamase production
25
What bacterial produces AmpC B-lactamases
Pseudomonas aeruginosa and enterobacter sp and extended-spectrum B-lactamases
26
AmpC B-lactamases hydrolyze what kinds of drug?
Cephalosporins and penicillins
27
Carbapenems are highly resistant to hydrlysis to what enzyme?
Penicillinases and cephalosporinases
28
Carbapenems are hydrolyzed by what enzyme?
Metallo-B-lactamases and carbapenemases
29
In what type of bacteria causes impaired penetration?
Only in gram-negative species because of the impermeable outer membrane of their cell wall
30
In what membrane protein channel does beta-lactam antibiotics cross from the outer membrane into the inner membrane of gram-negative organism
Porins
31
Absence of porins or down regulation causes?
Causes impaired penetration which can greatly impair drug entry into the cell
32
Among all oral penicillins, what drug is not impaired by food
Amoxicillin
33
What is the most preferred route of administration in penicillin G?
Intravenous administration
34
At least how many hours should you take oral penicillin before or after a meal
1-2 hours before of after a meal
35
Other areas of the body where penicillin is excreted
Excreted into sputum and breast milk
36
Penicillin is rapidly excreted by?
Kidneys
Tubular secretion - 90% of renal excretion
Glomerular filtration - 10%
37
HL of penicillin G
30 mins
In renal failure = 10hrs
38
HL of ampicllin and extended-spectrum penicillin
1hr. (Slower than penicillin G)
39
Primarily excretion of nafcillin
Biliary excretion
40
Where does oxacillin, dicloxacillin and cloxacillin are secreted or eliminated?
The kidneys and biliary excretion
41
An oral drug of penicillin that can be given without meals
Amoxicillin
42
A drug of choice for infections such as:
streptococci
gram-positive organisms
non-B-lactamase producing anaerobes
gram-negative anaerobic organisms
Penicillin G
43
Route of administration of penicillin G
IV
44
oral form of penicilin
Penicillin V
45
. A drug that is effective in treating B-hemolytic streptococcal pharyngitis
Benzathine penicillin
46
Intramuscularly, this is Effective in th treatment of syphilis
Benzathine penicillin G
47
Dicloxacillin, given orally is suitable for treatment of mild to moderate ____ infections
Localized staphyloccal
48
The first antstaphylococcal penicillin that is no longer used due to high rates of adverse effects
Methicillin
49
What drugs should you give in serious staphylococcal infections such as endocarditis
Oxacillin and nafcillin
50
Why is extended spectrum penicillins have greater activity against penicillin against gram0negative bacteria
Because of their enhanced ability to penetrate the gram-negative outer membrane
They are also inactivated by B-lactamases
51
An extended spectrum penicillin that is given orally to treat and lower respiratory tract infections
Amoxicillin
52
Extended spectrum penicilllins that are the most active oral B-lactam antibiotic against pneumococci
Ampicillin and amoxicillin
53
Extended-spectrum penicillin that is effective for shigellosis
Ampicilin
54
An extended-spectrum penicillin that is no longer used for empirical therapy of UTI and typhoid fever
Ampicillin
55
Two class of aminopenicilins
Amoxicillin and ampicillin
56
Classes of carboxypenicillins
Carbenicillin and ticarcilin
57
A drug that is only availale as a co-formulation with the B-lactamase inhibitor tazobactam
Piperacillin
58
B-lactamase inhibitors that can be combined with amoxicillin, ampicillin, piperacillin and ticarcillin
Clavulanic acid, sulbactam or tazobactam
59
Serious advse effects of penicillins
Hypersensitivity
60
How to evaluate patients if they have type 1 hypersnsitivity
By Skin testing
61
An antibiotic drug that is similar to penicillin but are more stable to many B-lactamases and have a broader spectrum of activity
Cephalosporins
62
What can hydrolyse most cephalosporins
Strains of E coli and klabsiella sp expressing extended-spectrum B-lactamases
63
Cephalosporin Drugs that are very active against gram positive cocci such as streptococci and staphylococci
First-generation cehalosporins
Cefazolin, cefadroxil, cephalexin
64
Widely used first gen cephalosporins in the USA
Cephalexin
65
Excretion of cephalexin is mainly by?
Glomerular filtration and tubular secretion into the urine.
66
Drugs that block tubular secretion
Probenecid
67
The only first-generation parenteral cephalosporin still in generaluse
Cefazolin
68
Route of administration of cefazolin
IV or intramuscularly
69
Excretion of cefazolin
Kidney (dose adjustment req for renal impaired function)
70
A drug of choice for surgical prophylaxis
Cefazolin
71
Cephalosporins that are relatively active against organisms inhibited by first-generation drugs
Second-generation cephalosporins
72
Examples of 2nd generation cephalosporins
Cefoxitin
Cefotetan
Cefuroxime
73
The three 2nd generation cephalosporins that are available in the USA
Cefactor
Cefuroxime
Cefprozil
74
Second generation cephalosporins should not be used in treating what infection?
Enterobacter infection (due to resistant mutants expressive a chromosomal B-lactamase that hydrolyze these compounds)
75
The most commonly used oral cephalosporin in the USA
Cefuroxime axetil
76
What is the preferred parental route of second generation cephalosporin? Is it IV or IM?
IV because IM is painful and should be avoided
77
Second generation drug that has an improved activity against pneumococcus and H influenzae
Cefuroxime
78
Oral, first generation drug used for treating skin and soft tssue infections and UTI
Cephalexin
79
A third generation cephalosporin that is the only agent with useful activity against psuedomonas aeruginosa
Ceftazidime
80
What hydrolyzes 2nd and 3rd gen cephalosporins
AmpC B-lactamases
81
HL of ceftriaxone
7-8 hours
Can be injected once every 24 hrs in dosage of 15-50 mg/kg/d
82
Two dosage recommendation for ceftriaxone
IF:
2g every 12hours - treatment of meningitis
2g every 24hours - treatment for endocarditis
83
HL of third gen cephalosporins
1 - 1.7 (except for ceftriaxone)
84
Regimen of choice for treating most gonococcal infections
IM ceftriaxone with azithromycin
85
Excretion of ceftriaxone
Biliary tract (no dose adjustment)
86
Where do the third gen cephalosporins are secreted?
Kidney(dose adj) except for ceftriaxone which is excreted in the biliary tract
87
Approved treatment for meningitis
Ceftriaxone and cefoxamine
88
The only available fourth generation cephalosporin
Cefepime
89
4th gen cehalosporins are resistant to hydrolysis by?
Chromosonal B-lactamases
90
4th gen cephalosporins are hydrolyzed by?
Extended-spectrum B-lactamases
91
Cefepime is cleared by the?
HL of cefepime?
Kidneys
2hours
92
Useful in the treatment of enterobacter infections
Cefepime (4th gen)
93
Cefepime is commonly used empirically in patients presenting with?
Febrile neutropenia
94
Prodrug of the active metabolite ceftaroline, first drug to be approved for clinical use in the USA
Ceftaroline fosamil
95
Reason why ceftaroline is effective against methicillin resistant staphylococci
Has increased binding to PBP2a, which mediates methicillin resistance in staphylococci
96
Ceftaroline is not active against
AmpC or extended spectrum B-lactamase producing organism
97
A cephalosporin that is active against methicillin resistant staphylococci
Ceftaroline
98
HL and excretion of ceftaroline
2.7 HL - excreted renally (dose adj)
99
A cephalosporin combined with B-lactamase inhibitors that is FDA-approved for the treatment of complicated intra-abdominal infections and UTI
Ceftolozane-tazobactam
And
Ceftazidime-avibactam
100
HL of ceftolozane-tazobactam and ceftazidime-avibactam and excretion
2-3hrs - excreted renally (does adj)
101
Adverse effect of cephalosporins
Hypersensitivity reactions:
Allergy, anaphylaxis
102
Patients with a history of anaphylaxis to penicillins should not receive what kind of cephalosporin
First or second
While
Third and fourth - administered with caution
103
Adverse effect of cephalosporin in
IM
IV
IM - local irritation
IV - thrombophlebitis
104
Cephalosporins that contain a methylthiotetrazole group may cause???
Hypoprothrombinemia and bleeding disorder
105
the only methylthiotetrazole-containing agent used in the USA
Cefotatan
106
What medicine to take in order to prevent hypoprothrombinemia and bleeding disorders in patients taking cephalosporins that contain a methylthiotetrazole group?
PO of vitamin K. 10mg twice weekly
107
Drugs with a monocylclic B-lactam ring
Monobactams
108
The only monobactam available in the USA
Aztreonam
109
Monobactams spectrum of activity is limited only to?
Aerobic gram-negative organisms ( P aeruginosa )
Wala slay activity sa gram + or anaerobes
110
Monobactams are stable to what B-lactamases
AmpC B-lactamases and extended spectrum B-lactamases
111
Does aztreonam crosses the BBB?
Yes
112
Route of administration of aztreonam
IV every 8hrs, 1-2g dose
113
Patient with history of penicillin anaphylaxis should be treated with ?
Aztreonam and not with 1,2,3,4th gen cephalosporins
114
Traditional B-lactamase inhibitors, resembles B-lactam molecule
Clavulanic acid, sulbactam, tazobactam
115
B-lactamase inhibitors are available only in fixed combinations with specific what drug?
Penicillins and cephalosporins
116
The first drug of class in carbapenems
Imipenem
117
Has a wide spectrim with good activity against most gram-negative rods, gram0positive organisms and anaerobes
Imipenem ( carbapenems )
118
What inactivates imipenem and where is it inactivated
Dehydropeptidases in renal tuules
119
Inhibitor or renal dehydropeptidase
Cilastatin
120
Route of administration, g given nd HL of imipenem
IV
0.25g - 0.5g every 6-8hrs
1hr HL
121
A carbapenem that is not degraded by renal dehydropeptidase
Ertapenem
122
The longest HL of a carbapenem
Ertapenem ( 4 hrs )
123
Carbapenems are highly active against
Treatment of enterobacter infections (they are resistant o destruction by the B-lactamase produced by these organims)
124
Most common adverse effect og carbapenem
Imipenem - nausea, vomiting, diarrhea, skin rashes
125
An antibiotic isolated from the bacterium now known as amycolatopsis orientalis
Vancomycin
126
Antibioticc isolated bacterium
Amycolatopsis orientalis
127
Antiobiotic that is active primarily against gram positive bacteria due to its large molecular weight and lack of penetration through gram-negative cell membranes
Vancomycin
128
MOA of vancomycin
Inhibits cell wall synthesis by binding to the D-Ala-D-Ala terminus which inhibits the transglycosylase, preventing elongation of peptidoglycan and cross linking.
129
Resistance to vancomycin in enterococci is due to?
Modification of D-Ala-D-Ala binding site in which the terminal D-Ala is replace with D-lactate.
130
Vancomycin is bactericidal for gram-positive bacteria in concentrations of?
0.5-10 mcg/ml
131
Vancomycin is active against manny gram-positive anaerobes including?
C difficile
132
PO vancomycin is a treatment against?
Colitis caused by C difficile
133
This drug is widely distributed in the body including adipose tissue.
Vancomycin
134
90% of vancomycin is exrcreted by?
Glomerular filtration
135
Parenteral vancomycin treats?
Infections and endocarditis caused by methicillin-resistant staphylococci
136
Vancomycin in combination with gentamicin treats
Enterococcal endocarditis
137
Vancomycin in combinations with cefotaxime, ceftriaxone or rifampin treats?
Meningitis
138
Used as a first line treatment for C difficile colitis
Oral vancomycin
139
Common adverse effects of vancomycin
“Red man” syndrome
140
A glycopeptide antibiotic that is very similar to vancomycin but its difference is that, this drug can be given intramuscularly
Teicoplanin
141
How to prevent red man syndrome
Treat with antihistamine such as diphenhydramine
Bc this syndrome released histamine
142
A semisynthetic lipoglycopeptide derived from vancomycin
Telavancin
