24) Cell Wall Inhibitors Flashcards
(225 cards)
1
Q
Beta-lactam antibiotics
A
- Drugs with structures containing a beta-lactam ring
- Includes penicillins, cephalosporins and carbapenems
2
Q
Beta-lactamases
A
- Bacterial enzymes (penicillinases, cephalosporinases) that hydrolyze the beta-lactam ring
3
Q
Minimal inhibitory concentration (MIC)
A
- Lowest concentration of antimicrobial drug capable of inhibiting growth of an organism in a defined growth medium
4
Q
Penicillin-binding protein (PBPs)
A
- Bacterial cytoplasmic membrane proteins that act as the initial receptors for penicillins and other beta-lactam antibiotics
5
Q
Peptidoglycans
A
- Chains of polysaccharides that are cross-linked to form the bacterial cell wall
6
Q
Selective toxicity
A
- More toxic to the invader than to the host
7
Q
Transpeptidases
A
- Bacterial enzymes involved in the cross-linking of linear peptidoglycan chains, the final step in cell wall synthesis
8
Q
Bactericidal
A
- An antimicrobial drug that can eradicate an infection in the absence of host defense mechanisms
- Kills bacteria
9
Q
Bacteriostatic
A
- An antimicrobial drug that inhibits antimicrobial growth but requires host defense mechanisms to eradicate the infection
- Does not kill bacteria
10
Q
Bactericidal agents
A
- Aminoglycosides
- Bacitracin
- Beta-lactam antibiotics
- Daptomycin
- Fosfomycin
- Glycopeptide antibiotics
- Isoniazid
- Fidaxomicin
- Metronidazole
- Polymixins
- Pyrazinamide
- Fluoroquinolones
- Rifampin
- Streptogramins
11
Q
Bacteriostatic agents
A
- Chloramphenicol
- Clindamycin
- Ethambutol
- Macrolides
- Nitrofurantoin
- Oxazolidinones
- Sulfonamides
- Tetracyclines
- Tigecycline
- Trimethoprim
12
Q
Antibiotic classes that are bacterial cell wall/membrane inhibitors
A
- Penicillins
- Beta-lactamase inhibitors
- Cephalosporins
- Carbapenems
- Monobactams
- Polymixins
- Glycopeptides
- Lipopeptides
13
Q
Antibiotic classes that are bcterial protein synthesis inhibitors
A
- Macrolides
- Lincosamides
- Aminoglycosides
- Tetracyclines
- Glycylcycline
- Oxazolidinones
- Streptogramins
14
Q
Antibiotic classes that inhibit bacterial DNA/RNA
A
- Fluoroquinolones
- Folate antagonists
- Rifamycin derivatives
- Anti-clostridium agent
- Nitroimidazole
- Nitrofurans
15
Q
Anti-mycobacterials
A
- Rifamycin derivatives
- Isoniazid
- Pyrazinamide
- Ethambutol
16
Q
Peptidoglycan (murein) layers are critical for bacterial survival
A
- Protect against toxic outside influences
- Provide the strength required to resist high osmotic pressures (otherwise will lead to plasma membrane rupture)
17
Q
Mycobacterium tuberculosis does not retain any common bacteriological stain due to
A
- High lipid content in its wall
- Neither Gram-positive nor Gram-negative
18
Q
Stages of cell wall synthesis
A
- Cytoplasmic stage
- Membrane stage
- Extracellular stage
19
Q
Cytoplasmic stage
A
- Synthesis of precursors (NAG, NAM)
- Targeted by cycloserine and fosfomycin
20
Q
Membrane stage
A
- Transfer of the precursors from the cytosol to membrane
- Incorporation into the growing peptidoglycan
- Targeted by bacitracin, vancomycin
21
Q
Extracellular stage
A
- Cross-linking of linear chains of peptidoglycans by transpeptidases
- Targeted by beta-lactams
22
Q
NAG and NAM
A
- N-acetyl glucosamine
- N-acetyl muramic acid
23
Q
Fosfomycin
A
- Inhibits enol pyruvate transferase specifically MurA (cytoplasmic stage)
24
Q
Cycloserine
A
- Inhibits racemase (cytoplasmic stage)
25
Bacitracin
- Inhibits phosphatase (membrane stage)
26
Vancomycin and teicoplanin
- Does not not inhibit an enzyme
| - Binds to the D-Ala-D-Ala terminal of the growing peptide chain (membrane stage)
27
Extracelular stage steps
- Neighboring peptidoglycan chains are cross-linked through their peptide chain by transpeptidases
- Cross-linking makes the cell wall stronger
- Transpeptidase is one of the penicillin binding protein (PBP)
- When the covalent bond occurs with the D-alanine (in purple) the second D-alanine leaves
- Beta-lactams inhibit transpeptidase
28
Beta-lactams MOA
- Bind to the penicillin binding protein (PBPs) specifically transpeptidase in the cytoplasmic membrane of the bacteria
- Inhibit transpeptidation reaction (cross-linking)
- Activate the autolytic enzyme that cause lesions in the cell wall
29
Molecular mechanism of interaction between beta-lactam and bacterial cell wall
- Formation of a covalent bond between serine and beta-lactam (irreversible)
- Serine in the bacterial cell wall is not a free nucleophile anymore and cannot help in building the bacterial cell wall
30
Mechanism of resistance between beta-lactam and bacterial cell wall interaction
- When beta-lactamase are released from bacteria they target beta-lactam antibiotics
- Hydroxyl group of the serine linked to the beta-lactamase will form a covalent bond with the beta-lactam
- Opens the ring leading to an ineffective antibiotic
31
Properties of PNC
- Rapidly eliminated by kidneys
| - Short half lives of 30-90 min
32
Broad spectrum β-lactams cover
- Gram positive bacteria
| - Gram negative bacteria
33
Narrow spectrum β-lactams cover
- Gram positive bacteria only
34
To penetrate the outer membrane in Gram negative bacteria,
- Hydrophilic antibiotics pass through the porins better than hydrophobic ones
35
Hydrophilic antibiotics tend to have
- Broader spectrum
36
Hydrophobic drugs tend to have
- Narrow spectrum of action
37
Hydrophobic drugs
- Axacillin
- Dicloxacillin
- Nafcillin
- Methicillin
- Penicillin G
38
Hydrophilic drugs
- Ampicillin
- Amoxicillin
- Piperacillin
- Ticarcillin
39
Properties providing resistance to β-lactam
- Bacteria acquiring β-lactamase encoding gene
- Altering transpeptidase or PBP by changing its ability to bind to β-lactam
- Inability to penetrate β-lactam site of action (decreased permeability or porin reduction)
- Activating efflux pump systems that remove β-lactam from its site of action
40
Hypersensitivity to β-lactam may cause
- Anaphylactic reaction (rash, itchiness, nausea, vomiting and shortness of breath)
- Potential cross-sensitivity between β-lactams
41
PNC eliminates the GI microflora leading to
- Potential superinfection
| - Risk of Chlostridium difficile associated diarrhea CDAD
42
Drug-induced hemolytic anemia (red blood cells are destroyed faster than they can be made)
- PNCs modify the protein on the surface of RBCs (β-lactam binds to the RBC)
- Complex is phagocytosed by macrophage
- Antigen presented to CD4
- Leads to stimulation of B cells, and formation of IgG antibodies specific to β-lactam-modified epitope
43
Penicillin G, Benzathine U.S. box warning
- Not for IV use because of cardiopulmonary arrest
44
Penicillin G, Benzathine CI/warnings
- Hypersensitivity to beta-lactam (anaphylactic)
- Superinfection if prolonged use (Clostridium difficile colitis)
- Seizures
45
Penicillin G, Benzathine cardio ADRs
- Hypotension
| - Tachycardia
46
Penicillin G, Benzathine CNS ADRs
- Anxiety
- Headaches
- Fatigue
47
Penicillin G, Benzathine skin ADRs
- Diaphoresis
48
Penicillin G, Benzathine GI ADRs
- Bloody stool
- Nausea, vomiting
- Intestinal necrosis
49
Penicillin G, Benzathine genitourinary ADRs
- Impotence
| - Hematuria
50
Penicillin G, Benzathine hepatic ADRs
- Increase AST
51
Penicillin G, Benzathine immune system ADRs
- Jarish-Herxheimer reaction (shaking, chills, rise in temp, intensification of skin rashed)
52
Penicillin G, Benzathine renal ADRs
- Increase serum creatinine, BUN
53
Penicillin G, Benzathine respiratory ADRs
- Cyanosis
54
Penicillin G, Benzathine pharmacokinetics
- Renal metabolism
| - 60% protein binding
55
Penicillin G, procaine CI/warnings
- Fibrosis and atrophy due to IM route
- Methemoglobinemia after anesthesia or G6PD deficiency
- Not IV because of neurovascular damage
- Mental disturbances
56
Penicillin G, procaine ADRs
- Not defined
57
Penicillin G, procaine pharmacokinetics
- Renal metabolism
| - 60% protein binding
58
Penicillin V, potassium ADRs
- Nausea, vomiting
- Diarrhea
- Mild candidiasis
59
Penicillin V, potassium pharmacokinets
- Renal metabolism
| - 80% protein binding
60
Nafcillin CI/warnings
- Hypersensitivity to beta-lactams (anaphylactic)
- Extravasation when IV
- Hepatic increase in LFT
- Neurotoxicity
- Superinfection if prolonged use (Clostridium difficile colitis)
61
Nafcillin cardio ADRs
- Local thrombophlebitis
62
Nafcillin CNS ADRs
- Neurotoxicity
63
Nafcillin GI ADRs
- Cholestasis
| - C. dificile associated diarrhea
64
Nafcillin hematological ADRs
- Agranulocytosis
- Bone marrow suppression
- Neutropenia
65
Nafcillin hepatic ADRs
- Increased LFT
66
Nafcillin pharmacokinetics
- Hepatic metabolism
- Enterohepatic circulation
- Excretion in feces
- 90% protein binding
67
Oxacillin CI/warnings
- Hepatitis
68
Oxacillin ADRs
- C. dificile associated diarrhea
- Increased LFT (hepatic)
- Actute renal tubular disease
69
Oxacilin pharmacokinetics
- Metabolism not known
| - 90% protein binding
70
Dicloxacillin CI/warnings
- None
71
Dicloxacillin ADRs
- Abdominal pain
| - Nausea, vomiting
72
Dicloxacillin pharmacokinetics
- CYP2C19 inducer
- 90% protein binding
- Excretion in feces and urine unchanged
73
Methicillin CI/warning
- None
74
Methicillin ADRs
- Neutropenia
- Thrombocytopenia
- Agranulogytosis
- Increased LFTs
- Acute renal disease
75
Methicillin pharmacokinetics
- Hepatic metabolism
| - Renal excretion
76
Methicillin family is linked to
- Methicillin resistant staphylococcus aureus (MRSA)
77
Amino-PNC antibiotic names
- Amoxicillin
| - Ampicillin
78
Amoxicillin CI/warnings
- Hypersensitivity to beta-lactams (anaphylactic)
| - Superinfection if prolonged use (Clostridium difficile colitis)
79
Amoxicillin CNS ADRs
- Headaches, agitation, seizures, confusion, mood
80
Amoxicilin GI ADRs
- N,D,V
| - C. difficile-associated diarrhea
81
Amoxicillin genitourinary ADRs
- Vulvovaginal infection
82
Amoxicillin cardio/hematological ADRs
- Hypersensitivity angitis
- Neutropenia
- Thrombocytopenia
- Agranulocytosis
83
Amoxicillin systemic ADRs
- Serum-sickness reaction
| - Fever
84
Amoxicillin hepatic ADRs
- Increase LFTs
85
Amoxicillin pharmacokinetics
- Metabolism not known
- 20% protein binding
- Distributed broadly into tissues, but not CSF unless meningitis
86
Ampicillin CI/warnings
- Non-allergic rash in kids
87
Ampicillin CNS ADRs
- Headaches
- Agitation
- Seizures
- Confusion
- Mood
88
Ampicillin GI ADRs
- Nausea, vomiting
| - Diarrhea
89
Ampicillin hematological ADRs
- Neutropenia
- Thrombocytopenia
- Agranulocytosis
90
Ampicillin hepatic ADRs
- Increase LFTs
91
Ampicillin systemic ADRs
- Serum-sickness reaction
92
Ampicillin pharmacokinetics
- Metabolism not known
| - 15% protein binding
93
Anti-pseudomonal peicillin
- Piperacillin (ureidoPNC)
| - Ticarcillin (carboxyPNC)
94
Piperacillin (ureidoPNC) CI/warnings
- Bleeding in renal impaired patients
| - Leukopenia neutropenia
95
Piperacillin (ureidoPNC) hematological ADRs
- Local thrombophlebitis
- Hemolytic anemia
- Agranulocytosis
96
Piperacillin (ureidoPNC) CNS ADRs
- Confusion
- Seizure
- Drowsiness
97
Piperacillin (ureidoPNC) dermatological ADRs
- Skin rash
| - Urticaria
98
Piperacillin (ureidoPNC) renal ADRs
- Hypokalemia
| - Acute renal failure
99
Piperacillin (ureidoPNC) systemic ADRs
- Fever
| - Jarisch-Herxheimer reaction
100
Piperacillin (ureidoPNC) pharmacokinetics
- Metabolism not known
| - 25% protein binding
101
Ticarcillin (carboxyPNC) CI/warnings
- Bleeding in renal impaired patients
| - Hypokalemia
102
Ticarcillin (carboxyPNC) hematological ADRs
- Local thrombophlebitis
103
Ticarcillin (carboxyPNC) renal ADRs
- Hypernatremia
| - Hypokalemia
104
Ticarcillin (carboxyPNC) CNS ADRs
- Confusion
- Seizure
- Drowsiness
105
Ticarcillin (carboxyPNC) dermatological ADRs
- Skin rash
106
Ticarcillin (carboxyPNC) pharmacokinetics
- Metabolism not known
| - Renally excreted
107
β-lactamase inhibitors combinations generic/brand names
- Amoxicillin/ticarcillin + clavulanic acid (Augmentin, Timentin)
- Piperacillin + Tazobactam (Zosyn)
- Ampicillin + Sulbactam (Unasyn)
- Ceftazidime + Avibactam (Avycaz)
- Meropenem + Varobactam (Vabomere)
108
Amoxicillin/ticarcillin + clavulanic acid (Augmentin, Timentin) CI/warnings
- Hypersensitivity to beta-lactams (anaphylactic)
- Superinfection if prolonged use (Clostridium difficile colitis)
- Diarrhea (higher than amoxicillin alone)
- Hepatic dysfunction
109
Piperacillin + Tazobactam (Zosyn) CI/warnings
- Serious skin reaction (toxic epidermal necrolysis TEN)
- High sodium content
- Abnormal clotting times
- Nephrotoxic
110
Ampicillin + Sulbactam (Unasyn) CI/warnings
- Hepatic dysfunction
| - Rash
111
Ceftazidime + Avibactam (Avycaz) CI/warnings
- Neurotoxicity
112
Meropenem + Varobactam (Vabomere) CI/warnings
- Seizures
| - Brain lesions
113
Amoxicillin/ticarcillin + clavulanic acid (Augmentin, Timentin) ADRs
- Diarrhea
- Rash
- Nausea, vomiting
- Vaginitis
- Candidiasis
114
Amoxicillin/ticarcillin + clavulanic acid (Augmentin, Timentin) pharmacokinetics
- Hepatically metabolized
- 20% protein binding
- Renally excreted
115
Piperacillin + Tazobactam (Zosyn) ADRs
- Vaginitis
- Candidiasis
- Hypotension, hypotension flushing
- Hypoglycemia
116
Piperacillin + Tazobactam (Zosyn) pharmacokinetics
- 30% protein binding
| - Renally excreted unchanged
117
Ampicillin + Sulbactam (Unasyn) ADRs
- Pain at injection site
118
Ampicillin + Sulbactam (Unasyn) pharmacokinetics
- 30% protein binding
| - Renally excreted unchanged
119
Ceftazidime + Avibactam (Avycaz) ADRs
- Positive direct coombs test
| - Pain at injection site
120
Ceftazidime + Avibactam (Avycaz) pharmacokinetics
- Not metabolized
- Excreted in urine
- 10% protein binding
121
Meropenem + Varobactam (Vabomere) ADRs
- Phlebitis
- Headaches
- Hypokalemia
- Increased LFT
- Fever
- Injection pain
122
Meropenem + Varobactam (Vabomere) pharmacokinetics
- Not metabolized
- Renally excreted
- 30% protein binding
123
1st generation cephalosporins
- Cephalexin
- Cefadroxil
- Cefazolin
124
1st generation cephalosporin spectrum
- Gram+ cocci (staphylococci, streptococci)
125
2nd generation cephalosporins
- Cefuroxime
- Cefotetan
- Cefaclor
- Cefoxitin
- Cefprozil
126
2nd generation cephalosporin spectrum
- Less activity against G+
| - More extended against G- (e.g. B. fragilis, H. influenzae; M. catarrhalis)
127
3rd generation cephalosporins
- Cefdinir
- Cefotaxime
- Ceftriaxone
- Ceftazidime
- Cefpodoxime
- Cefixime
128
3rd generation cephalosporin spectrum
- Less activity against G+
- More extended against G- resistant to other β-lactams and able to penetrate the BBB (except for cefixime) e.g. S. marcescens; beta-lactamase producing strains of H. influenzae; Neisseria
129
3rd generation cephalosporins with anti-pseudonomal activity
- Cefoperazone
| - Ceftazidime
130
4th generation cephalosporins
- Cefepine
131
4th generation cephalosporin spectrum
- More resistant to beta-lactamase produced G- including Enterobacter, Haemophilius; Neisseria and anti-pseudomonal
- Combines the G+ of the 1st generation and the G- of the 3rd generation of cephalosporins
132
5th generation cephalosporins
- Ceftaroline
133
5th generation cephalosporin spectrum
- Has G- and G+ coverage, especially against Methicillin-resistant Staphylococci (MRSA) and Vancomycin resistant Staphylococcus aureus (VRSA)
134
Characteristics of cephalosporins
- 2nd gen onward is more resistant to β-lactamases
- Many are orally absorbed
- Primarily excreted in the kidneys (dosage reduced if renal insufficiency)
135
Cephalosporins and the CNS
- Several (like ceftriaxone, cefotaxime, ceftazidime, cefepime) can enter CSF when meningitis is present
136
Cephalosporin-induced disulfiram like reaction
- Facial flushing
- Angioedema
- Hypotension shock
- Death
137
Cephalexin, cefadroxil, cefazolin (1st gen) CI/warnings
- Hypersensitivity to beta-lactams (anaphylactic)
- Superinfection if prolonged use (Clostridium difficile colitis)
- Increase INR: Decrease synthesis of vitamin K leading to bleeding in patients on anticoagulants
- PNC cross- allergy
- Seizure; colitis
138
Cephalexin, cefadroxil, cefazolin (1st gen) ADRs
- CNS: agitation, confusion, fatigue
- Dermatological: rash, Steven Johnson syndrome
- GI: diarrhea, gastritis
- Genital candidiasis, vaginitis
- Renal: increase BUN, renal failure
- Hemolytic anemia, neutropenia thrombocytopenia, eosinophilia
- Increase LFTs
139
Cefalexin (1st gen) pharmacokinetics
- Metabolism unknown
- Renally excreted unchanged
- 10% protein binding
140
Cefadroxil (1st gen) pharmacokinetics
- Metabolism unknown
- Renally excreted unchanged
- 20% protein binding
141
Cefazolin (1st gen) pharmacokinetics
- Metabolism unknown
- Renally excreted unchanged
- 80% protein binding
142
Cefuroxine (2nd gen) ADRs
- Jarisch-Herxheimer reaction
143
Cefuroxine (2nd gen) pharmacokinetics
- 50% protein binding
144
Cefotetan (2nd gen) CI/warnings
- Hemolytic anemia
145
Cefotetan (2nd gen) ADRs
- Increase prothrombin time
146
Cefotetan (2nd gen) pharmacokinetics
- 80% protein binding
147
Cefalcor (2nd gen) pharmacokinetics
- Substrate of OAT1/3
| - 25% protein binding
148
Cefoxitin (2nd gen) pharmacokinetics
- 80% protein binding
149
Cefprozil (2nd gen) pharmacokinetics
- 25% protein binding
150
Cefdinir (3rd gen) CI/warnings
- Hypersensitivity to beta-lactams (anaphylactic)
- Superinfection if prolonged use (Clostridium difficile colitis)
- PNC cross- allergy
- Colitis
151
Cefdinir (3rd gen) ADRs
- Diarrhea
152
Cefdinir (3rd gen) pharmacokinetics
- Metabolism unknown
| - 60-70% protein binding
153
Cefotaxime (3rd gen) CI/warnings
- Arrythmia
| - Granulocytopenia
154
Cefotaxime (3rd gen) pharmacokinetics
- 50% protein binding
155
Ceftriaxone (3rd gen) CI/warnings
- Not in neonates with hyperbilirubinemia (displace bilirubin from albumin binding sites)
- Increase INR; hemolytic anemia
- Pancreatitis (secondary to biliary obstruction)
156
Ceftriaxone (3rd gen) ADRs
- Increase BUN
- Abnormal gallbladder sonograms
- Skin tightness
157
Ceftriaxone (3rd gen) pharmacokinetics
- 85% protein binding
| - Eliminated in the bile
158
Ceftazidime (3rd gen) CI/warnings
- Neurotoxicity
159
Ceftazidime (3rd gen) ADRs
- Positive direct Coombs test (the blood has antibodies that fight against RBC)
160
Ceftazidime (3rd gen) pharmacokinetics
- Less than 10% protein binding
161
Cefpodoxime (3rd gen) pharmacokinetics
- 20% protein binding
162
Cefixime (3rd gen) CI/warnings
- Severe cutaneous reactions
- Hemolytic
- Renal failure
163
Cefixime (3rd gen) pharmacokinetics
65% protein binding
164
Cefepime (4th gen) CI/warnings
- Increase INR
- Neurotoxicity
- Renal failure
165
Cefepime (4th gen) ADRs
- Positive direct Coombs test
166
Cefepime (4th gen) pharamcokinetics
- 20% protein binding
167
Ceftaroline (5th gen) CI/warnings
- Hemolytic anemia
| - Renal failure
168
Ceftaroline (5th gen) ADRs
- Positive direct Coombs test
169
Ceftaroline (5th gen) pharmacokinetics
- 20% protein binding
170
Carbapenems coverage
- G+ cocci
- G- rods
- Anaerobes
171
Carbapenems (names)
- Imipenem
- Meropenem
- Doripenem
- Ertapenem
172
Imipinem CI/warnings
- Hypersensitivity to beta-lactams (anaphylactic)
- CNS disorders: Confusion and seizures
- Superinfection if prolonged use (Clostridium difficile colitis)
- Renal impairment
173
Imipinem ADRs
- Decrease hematocrit
- Eosinophilia, thrombocytopenia, neutropenia
- Increase LFTs
- N;V;D
174
Imipinem pharmacokinets
- Administered with cilastatin because it is inactivated by renal dehydropeptidase 1 enzyme (Cilastatin inhibits dehydropeptidase 1)
- Renally excreted
- 30% protein binding
175
Meropenem, Doripenem, Ertapenem CI/warnings
- Severe cutaneous effects
176
Meropenem ADRs
- Cardiovascular hyper/hypotension
- Bradychardia
- Peripheral edema
- Hypoglycemia
177
Meropenem pharmacokinetics
- 20% protein binding
| - Renally excreted
178
Doripenem pharmacokinetics
- 8% protein binding
| - Renally excreted
179
Ertapenem ADRs
- Edema
| - Neutropenia
180
Ertapenem pharmacokinetics
- 85% protein binding
181
Monobactam: Aztreonam coverage
- Resistant to beta-lactamases produced by G- rods (Klebsiella, Pseudomonas, Serratia)
- No activity against G+ bacteria
182
Monobactam: Aztreonam warning
- It can be used for patients with PNC hypersensitivity (has no cross-sensitivity with other beta-lactams except ceftazidime)
- Superinfection if prolonged use (Clostridium difficile colitis)
183
Monobactam: Aztreonam adverse effects
- Neutropenia (mainly in children)
- IV site phlebitis
- Increase LFTs
- NVD
- Eosinophilia, thrombocytopenia
- Skin rash
- Increase serum creatinine (most in children)
184
Monobactam: Aztreonam pharmacokinetics
- Renally excreted
| - Can distribute in CSF when meningitis
185
Misc. characteristics about beta-lactams
- They all inhibit transpeptidases
- All lack activity against MRSA except ceftaroline (5th generation cephalosporin)
- Because of the beta-lactam they cause hypersensitivity and potential cross-sensitivity
186
Other non-beta-lactam cell wall inhibitors
- Glycopeptides
- Polymixin
- Phosphonic acid derivative
- Bacitracin
- Lipopeptide
187
Glycopeptides (non-beta-lactam cell wall inhibitors)
- Vancomycin
- Telavanin
- Oritavancin
- Dalbavancin
188
Polymixin (non-beta-lactam cell wall inhibitors)
- Polymixin B
| - Colistin (polymixin E)
189
Phosphonic acid derivative (non-beta-lactam cell wall inhibitors)
- Fosfomycin
190
Lipopeptide (non-beta-lactam cell wall inhibitors)
- Daptomycin
191
Glycopeptides MOA
- Bactericidal glycoprotein that binds to the D-Ala D-Ala terminal of the peptidoglycan pentapeptide side chain
- Inhibits transglycosylation (adding glycoside)
- Prevents elongation of the peptidoglycan (cover G+ rod, cocci and MRSA)
192
Fosfomycin MOA
- Antimetabolite inhibitor of the cytosolic enolpyruvate transferase (MurA)
- Prevents the formation of N-acetylmuramic acid (NAM), an essential precursor for the peptidoglycan chain formation
193
Bacitracin MOA
- Peptide that inhibits the phosphatase of bactroprenol
194
Cycloserine MOA
- Inhibits the racemase
195
Polymixin MOA
- Cationic polypeptide that binds to the phospholipid (lipopolysaccharide LPS of G-) of the outer membrane
- Alters permeability and damage bacterial cytoplasmic membrane leading to leakage of intracellular content
196
Daptomycin MOA
- Cyclic lipopeptide
- Inserts into the cytoplasmic membran
- Causes potassium leak and cell death (integration into G+ bacteria)
197
Fosfomycin warnings
- Electrolyte abnormality
- Hepatic injury
- Hypersensitivity
- Superinfection
198
Fosfomycin ADRs
- Headache
- Rash
- NVD
- Vaginitis
199
Fosfomycin pharmacokinetics
- No protein binding metabolism unknown
| - Renal/fecal elimination
200
Polymixin warnings
- US box warning: nephrotoxicity, neurotoxicity (respiratory paralysis)
201
Polymixin ADRs
- Facial flushing
- Neurotoxicity
- Rash
- Hypocalcemia, hypochloremia, hypokalemia, hyponatremia
- Pain on injection
- Neuromuscular blockade
202
Polymixin pharmacokinetics
- Not absorbed in GI
- Tissue distribution is poor
- 60% protein binding
- Renally excreted
203
Colistin warnings
- Bronchoconstriction when inhaled
- CNS toxicity: neurological disturbances
- Renal toxicity
- Respiratory arrest
204
Colistin ADRs
- Neurotoxicity
| - Acute renal failure
205
Colistin pharmacokinetics
- Not absorbed in GI
- Renally excreted
- 50% protein binding
206
Bacitracin warnings
- US box warning: nephrotoxicity
- Anaphylaxis
- Renal failure
207
Bacitracin ADRs
- Skin rash
- Albuminuria
- NV
- Nephrotoxicity from tubular and glomerular necrosis
208
Bacitracin pharmacokinetics
- Renally excreted
| - Well distributed
209
Daptomycin warnings
- Eosinophilia pneumonia
- Hypersensitivity
- Rhabdomyolysis
- Myopathy
- Peripheral neuropathy
210
Daptomycin ADRs
- Hypertension/hypotension
- Headaches
- Rash
- Diarrhea
- UTI
- Abnormal LFTs
211
Daptomycin pharmacokinetic
- 90% protein binding
| - Renally excreted
212
Vancomycin warnings
- US box warning: not during pregnancy
- Extravasation and thrombophlebitis
- Neurotoxicity
- Neutropenia
- Ototoxicity
- Superinfection
213
Vancomycin ADRs
- Hypotension with flushing
- Fever
- Eosinophilia
- Red man syndrome
214
Vancomycin pharmacokinetics
- Renally eliminated
215
Telavancin warnings
- US box warning: not during pregnancy; nephrotoxicity
- Anaphylaxis
- Cardiac conduction alteration
- Infusion reaction rash
216
Telavancin ADRs
- Metallic taste
- NVD
- Increased SCr
217
Telavancin pharmacokinetics
- Renal/fecal excretion
| - 90% protein binding
218
Oritavancin warnings
- Hypersensitivity infusion reaction
| - Osteomyelitis
219
Oritavancin ADRs
- Tachycardia
- Headache
- Hyperuricemia
- Hypoglycemia
- Anemia
- Increase LFT
- Bronchospasm
- Injection site pain
220
Oritavancin pharmacokinetics
- Renal/fecal excretion
| - 85% protein binding
221
Dalbavancin warnings
- Hepatic effects
| - Hypersensitivity infusion reactions
222
Dalbavancin ADRs
- Flushing
- Phlebitis
- Headache
- Hypoglycemia
- NDV
- Hepatotoxicity
- Increase INR
- Leukopenia
- Neutropenia
- Thrombocytopenia
- Red man syndrome
223
Dalbavancin pharmacokinetics
- 93% protein binding
| - Renal/fecal excretion
224
Red Man Syndrome
- Anaphylaxis because of rapid infusion
- Skin thickens
- Rash on the face, neck, and upper torso
225
Resistance mechanisms to glycopeptides
- Overexpression of ligase enzymes (VanA) enzymes that catalyze the formation of D-Ala-D-lactate instead of D-ala-D-Ala
- Vancomycin does not bind to D-Ala-D-lactate
