Pharmacology of Antibacterials Flashcards
1
Q
[Cell Wall Structure] How do Gram(+) and Gram(–) bacteria differ structurally?
A
Gram(+): thick peptidoglycan, 1 membrane, external beta-lactamases. Gram(–): thin peptidoglycan, 2 membranes, periplasmic beta-lactamases, porins for drug entry.
2
Q
[Cell Wall Structure] Why do Gram(–) bacteria need less beta-lactamase than Gram(+)?
A
Gram(–) beta-lactamases are in the periplasmic space, so they are localized and efficient, unlike Gram(+) which secrete them externally.
3
Q
[Mechanism of Action] How do beta-lactams kill bacteria?
A
They inhibit transpeptidase (PBP) enzymes, preventing peptidoglycan cross-linking → weak cell wall → osmotic lysis.
4
Q
[Resistance Mechanisms] What are common resistance mechanisms to beta-lactams?
A
1) Beta-lactamase production, 2) Altered PBPs, 3) Decreased uptake (porins), 4) Efflux pumps.
5
Q
[Allergy & Stability] Why can beta-lactams cause allergies?
A
They act as haptens, binding to host proteins and triggering an immune response. Cross-reactivity is common across beta-lactams.
6
Q
[Allergy & Stability] Why is Penicillin V more acid-stable than Penicillin G?
A
Pen V has an ether oxygen that reduces nucleophilicity of the amide carbonyl, slowing ring-opening hydrolysis in acid.
7
Q
[Beta-lactamase Inhibitors] How do beta-lactamase inhibitors work?
A
They acylate the serine in the beta-lactamase active site, preventing the enzyme from hydrolyzing beta-lactam antibiotics.
8
Q
[Beta-lactamase Inhibitors] Give examples of beta-lactamase inhibitor combinations.
A
Amoxicillin/clavulanate (Augmentin), Ampicillin/sulbactam (Unasyn), Piperacillin/tazobactam (Zosyn), Ceftazidime/avibactam (Avycaz).
9
Q
[Cephalosporins] How are cephalosporin generations classified?
A
Based on Gram(–) activity: 1st gen = Gram(+); 2nd = some Gram(–); 3rd = broad Gram(–); 4th = Pseudomonas; 5th = MRSA.
10
Q
[Cephalosporins] What makes ceftaroline unique among cephalosporins?
A
It inhibits PBP2a and is active against MRSA—a rare feature among beta-lactams.
11
Q
[Cephalosporins] What is the general trend in cephalosporin generations?
A
Increasing Gram(–) activity and decreased Gram(+) activity from 1st to 3rd generation. 4th and 5th regain some Gram(+) and target MDR bacteria.
12
Q
[Cephalosporins] What feature of 3rd gen cephalosporins enhances beta-lactamase resistance?
A
Presence of a syn methoximino oxime ether group at the 7-position of the cephalosporin ring.
13
Q
[Cephalosporins] What group on C-3 increases oral bioavailability?
A
A chemically stable, unreactive group like a vinyl or methyl group (e.g., cefixime, cephalexin).
14
Q
[Penicillins] Why is ampicillin effective against Gram(–) bacteria?
A
It has a positively charged amino group that allows transport through hydrophilic porin channels of Gram(–) bacteria.
15
Q
[Penicillins] Why does amoxicillin have better oral absorption than ampicillin?
A
The addition of a phenolic OH group increases hydrophilicity and improves GI absorption.
16
Q
[Mechanism of Action] Why are beta-lactams selective for bacterial cells?
A
They target PBPs involved in cell wall synthesis—structures absent in human cells.
17
Q
[Mechanism of Action] What makes beta-lactams chemically reactive?
A
The four-membered beta-lactam ring is highly strained, making it susceptible to nucleophilic attack.
18
Q
[Penicillins] What is the mechanism of action of penicillins?
A
Inhibit bacterial transpeptidase enzymes (PBPs), preventing peptidoglycan cross-linking in the cell wall.
19
Q
[Penicillins] Name examples of beta-lactamase-sensitive penicillins.
A
Penicillin G, Penicillin V, Ampicillin, Amoxicillin.
20
Q
[Penicillins] Name examples of beta-lactamase-resistant penicillins.
A
Methicillin, Nafcillin, Oxacillin, Dicloxacillin.
21
Q
[Beta-lactamase Inhibitors] Name 4 beta-lactamase inhibitors and their MOA.
A
Clavulanate, Sulbactam, Tazobactam, Avibactam. MOA: irreversibly bind to beta-lactamase active site (Ser), preventing drug hydrolysis.
22
Q
[Cephalosporins] What drugs belong to the 1st generation of cephalosporins?
A
Cefazolin (parenteral), Cephalexin (oral). Mainly Gram(+).
23
Q
[Cephalosporins] What drugs belong to the 2nd generation?
A
Cefuroxime, Cefaclor. Better Gram(–) activity than 1st gen.
24
Q
[Cephalosporins] What drugs belong to the 3rd generation?
A
Ceftriaxone, Cefotaxime, Ceftazidime. Broad Gram(–), less Gram(+).
25
[Cephalosporins] What drug is in the 4th generation and what makes it unique?
Cefepime. Active against Pseudomonas, resistant to many beta-lactamases.
26
[Cephalosporins] What is the unique 5th generation cephalosporin and its use?
Ceftaroline. Inhibits PBP2a and is active against MRSA.
27
[Penicillins] What is the mechanism of action of penicillins?
Inhibit bacterial transpeptidase enzymes (PBPs), preventing peptidoglycan cross-linking in the cell wall.
28
[Penicillins] Name examples of beta-lactamase-sensitive penicillins.
Penicillin G, Penicillin V, Ampicillin, Amoxicillin.
29
[Penicillins] Name examples of beta-lactamase-resistant penicillins.
Methicillin, Nafcillin, Oxacillin, Dicloxacillin.
30
[Beta-lactamase Inhibitors] Name 4 beta-lactamase inhibitors and their MOA.
Clavulanate, Sulbactam, Tazobactam, Avibactam. MOA: irreversibly bind to beta-lactamase active site (Ser), preventing drug hydrolysis.
31
[Cephalosporins] What drugs belong to the 1st generation of cephalosporins?
Cefazolin (parenteral), Cephalexin (oral). Mainly Gram(+).
32
[Cephalosporins] What drugs belong to the 2nd generation?
Cefuroxime, Cefaclor. Better Gram(–) activity than 1st gen.
33
[Cephalosporins] What drugs belong to the 3rd generation?
Ceftriaxone, Cefotaxime, Ceftazidime. Broad Gram(–), less Gram(+).
34
[Cephalosporins] What drug is in the 4th generation and what makes it unique?
Cefepime. Active against Pseudomonas, resistant to many beta-lactamases.
35
[Cephalosporins] What is the unique 5th generation cephalosporin and its use?
Ceftaroline. Inhibits PBP2a and is active against MRSA.
36
[Cephamycins] What is a key structural feature of cephamycins?
7α-methoxyl group, which increases β-lactamase stability.
37
[Cephamycins] What side effect is associated with cefotetan?
Releases N-methylthiotetrazole → can cause hypoprothrombinemia and disulfiram-like reaction with ethanol.
38
[Carbapenems] What is imipenem's mechanism of action?
Inhibits PBPs and β-lactamases. Broad spectrum activity.
39
[Carbapenems] Why is cilastatin co-administered with imipenem?
Prevents degradation by renal dehydropeptidase-1.
40
[Monobactams] What is the spectrum of activity of aztreonam?
Gram(-) bacteria only. Can be used in penicillin-allergic patients.
41
[Monobactams] What structural feature increases reactivity of aztreonam?
Sulfamic acid group and oxime ether.
42
[Glycopeptides] How does vancomycin work?
Binds D-Ala-D-Ala terminus → inhibits transglycosylation and transpeptidation of peptidoglycan.
43
[Glycopeptides] What is the mechanism of vancomycin resistance?
Change D-Ala-D-Ala → D-Ala-D-Lac → reduces binding 1000x.
44
[Lipoglycopeptides] How do oritavancin, telavancin, and dalbavancin work?
Inhibit transpeptidation, transglycosylation, and disrupt membranes.
45
[Lipoglycopeptides] Which lipoglycopeptides can be dosed once due to long half-lives?
Dalbavancin (204 h), Oritavancin (245 h).
46
[Streptogramins] What is Synercid and what are its components?
A mix of quinupristin and dalfopristin (30:70).
47
[Streptogramins] What are the MOAs of quinupristin and dalfopristin?
Quinupristin blocks ribosomal tunnel; dalfopristin inhibits peptidyl transferase.
48
[Oxazolidinones] What is the MOA of linezolid?
Binds 50S ribosomal subunit → blocks formation of 70S initiation complex.
49
[Oxazolidinones] What is linezolid's therapeutic use?
MRSA, VRE, nosocomial pneumonia. Used when other options fail.
50
[Oxazolidinones] What is a notable side effect of long-term linezolid use?
Myelosuppression and peripheral neuropathy.
51
[Oxazolidinones] How does tedizolid differ from linezolid?
More potent against MRSA. Same MOA. Prodrug activated by phosphatases.
52
[Aminoglycosides] What is the core structure of aminoglycosides?
1,3-diaminocyclitol: either streptidine or 2-deoxystreptamine.
53
[Aminoglycosides] What is the mechanism of action?
Bind 30S subunit → interfere with initiation, cause misreading, nonsense proteins → disrupt membrane, cell death.
54
[Aminoglycosides] How do aminoglycosides enter bacteria?
Displace Mg++/Ca++ in outer membrane, then use active transport into the cytoplasm.
55
[Aminoglycosides] What are the main resistance mechanisms?
1) Metabolism (acetylation, adenylation, phosphorylation), 2) Altered ribosome (16S rRNA), 3) Altered uptake.
56
[Aminoglycosides] What are common toxicities?
Ototoxicity (irreversible), nephrotoxicity (reversible), curare-like paralysis at high doses.
57
[Aminoglycosides] Why are aminoglycosides combined with penicillins?
Synergistic bactericidal effect, especially for endocarditis.
58
[Aminoglycosides] Which aminoglycosides are oral and why?
Neomycin and paromomycin – not absorbed orally, used to suppress gut flora pre-surgery.
59
[Amikacin] What is unique about amikacin?
Modified from kanamycin A; resists metabolism; used for nosocomial infections, TB, and resistant Gram(–) strains.
60
[Tobramycin] Why is tobramycin effective for Pseudomonas?
Lacks 3'-OH so not phosphorylated; still adenylated and acetylated. Used in gentamicin-resistant Pseudomonas.
61
[Gentamicin] What are its major uses?
UTIs, burns, bone/joint infections. Topical and ophthalmic forms available.
62
[Streptomycin] What is the primary use of streptomycin?
Tuberculosis, bubonic plague, tularemia.
63
[Plazomicin] What is plazomicin used for?
Complicated UTIs due to resistant Gram(–) organisms (E. coli, Klebsiella, Proteus, Enterobacter).
64
[Macrolides] What is the mechanism of action of macrolides?
Bind 50S subunit, inhibit peptidyl-tRNA translocation from A to P site. Bacteriostatic.
65
[Macrolides] What are the resistance mechanisms?
1) Esterases, 2) 23S rRNA methylation (A2058), 3) A→G mutation, 4) Efflux pumps.
66
[Macrolides] Why is erythromycin acid-labile?
Forms intramolecular ketal under acidic conditions (inactivates drug).
67
[Macrolides] How are clarithromycin and azithromycin more stable than erythromycin?
Clarithromycin has 6-OCH3; azithromycin has no ketone (N-methylamine at C-9).
68
[Macrolides] What are clinical indications for erythromycin?
Mycoplasma, strep pharyngitis (pen-allergic), Legionella, pertussis, Campylobacter.
69
[Macrolides] What are macrolide side effects?
GI cramps, allergic rash, cholestatic hepatitis, QT prolongation, pyloric stenosis (infants).
70
[Macrolides] Which macrolides inhibit CYP3A4?
Erythromycin and clarithromycin (not azithromycin). May increase drug levels/toxicity.
71
[Clindamycin] What is the mechanism of action of clindamycin?
Binds 50S ribosomal subunit → inhibits protein synthesis like macrolides.
72
[Clindamycin] What are major clinical uses?
Anaerobic infections, MRSA, toxoplasmosis, acne, bacterial vaginosis, lung abscess.
73
[Clindamycin] What limits clindamycin's use?
Risk of pseudomembranous colitis due to C. difficile.
74
[Tetracyclines] What is the mechanism of action of tetracyclines?
Bind 30S subunit → block aminoacyl-tRNA binding to A site → inhibit protein synthesis.
75
[Tetracyclines] Why should tetracyclines not be taken with dairy or antacids?
Chelate Ca2+, Mg2+, Fe2+ → ↓ absorption.
76
[Tetracyclines] What causes tetracycline-induced tooth discoloration?
Chelation with Ca2+ in teeth during formation + photooxidation.
77
[Tetracyclines] What are 2 degradation reactions tetracyclines undergo?
1) Epimerization → inactive form. 2) Dehydration → toxic 4-epianhydrotetracycline.
78
[Minocycline] What are key features of minocycline?
No C6-OH → less toxic. Good bioavailability. Vestibular side effects (vertigo).
79
[Doxycycline] Why is doxycycline preferred?
No C6-OH (less GI toxicity), high oral bioavailability, long half-life for once-daily dosing.
80
[Tigecycline] What makes tigecycline unique?
Parenteral glycylcycline, broad spectrum, stable to resistance, but hepatotoxicity risk.
81
[Sarecycline] What is sarecycline used for?
Once-daily oral tetracycline for acne. Avoid in pregnancy; interacts with anticoagulants, iron.
82
[Omadacycline] What is omadacycline used for?
Pneumonia, skin infections. IV/oral. Broad-spectrum. Teratogenic.
83
[Chloramphenicol] What is the mechanism of action?
Binds 50S → inhibits peptidyl transferase → blocks peptide bond formation.
84
[Chloramphenicol] What is the most serious toxicity?
Aplastic anemia (rare, usually fatal). Also causes reversible marrow suppression.
85
[Chloramphenicol] What are key interactions or metabolism points?
Inhibits CYP enzymes. Metabolized by glucuronidation. Avoid in neonates.
86
[Fluoroquinolones] What is the mechanism of action?
Inhibit DNA gyrase and topoisomerase IV → block DNA replication → cell death.
87
[Quinolones] What defines 2nd, 3rd, and 4th gen fluoroquinolones?
2nd: Gram– focus (e.g., ciprofloxacin). 3rd/4th: more Gram+, like levofloxacin, moxifloxacin.
88
[Quinolones] What adverse effects are associated with fluoroquinolones?
Tendon rupture, CNS effects, neuropathy, QT prolongation, GI upset.
89
[Quinolones] How do fluoroquinolones resist degradation?
Mutations in DNA gyrase, efflux pumps, porin mutations. Cross-resistance common.
90
[Penicillins] How do Gram(+) and Gram(–) bacteria differ in structure relevant to penicillin activity?
Gram(+): thick peptidoglycan, 1 membrane, external beta-lactamases. Gram(–): thin wall, 2 membranes, periplasmic beta-lactamases, porins.
91
[Penicillins] What is the mechanism of action of penicillins?
Inhibit transpeptidase → block peptidoglycan crosslinking → weak cell wall → lysis.
92
[Cephalosporins] How are cephalosporins classified by generation?
1st gen: mostly Gram(+); 2nd: more Gram(–); 3rd: broad Gram(–); 4th: Pseudomonas; 5th: MRSA-active.
93
[Cephalosporins] How does the oxime ether at C-7 influence beta-lactamase stability?
Syn-oxime ethers are more stable against hydrolysis by beta-lactamases than anti-oxime ethers.
94
[Vancomycin] What is the mechanism of action of vancomycin?
Binds D-Ala-D-Ala on cell wall precursors → inhibits transglycosylation and crosslinking.
95
[Vancomycin] What is a major resistance mechanism to vancomycin?
D-Ala-D-Ala replaced with D-Ala-D-Lac → reduces binding affinity.
96
[Aminoglycosides] What is the mechanism of action of aminoglycosides?
Bind 30S → interfere with initiation and cause misreading of mRNA → defective proteins.
97
[Aminoglycosides] What are the major toxicities of aminoglycosides?
Nephrotoxicity (reversible), ototoxicity (irreversible), and neuromuscular blockade.
98
[Macrolides] What is the mechanism of action of macrolides?
Bind 50S → inhibit translocation step of protein synthesis → bacteriostatic.
99
[Macrolides] What are common bacterial resistance mechanisms to macrolides?
Methylation of 23S rRNA (A2058), esterase production, efflux pumps.
100
[Tetracyclines] Why should tetracyclines not be given with calcium or iron?
They chelate multivalent metals → ↓ oral absorption.
101
[Tetracyclines] What is the MOA of tetracyclines?
Bind 30S → block aminoacyl-tRNA from entering A site → inhibit protein synthesis.
102
[Quinolones] What is the mechanism of action of quinolones?
Inhibit DNA gyrase and topoisomerase IV → block DNA replication and repair.
103
[Quinolones] What are major side effects of fluoroquinolones?
Tendon rupture, QT prolongation, CNS effects, GI upset, photosensitivity.
104
[Sulfonamides] What is the mechanism of action of sulfonamides?
Inhibit dihydropteroate synthase → block folate synthesis in bacteria.
105
[Sulfonamides] Why are sulfonamides selective for bacteria?
Humans do not synthesize folate de novo (rely on dietary folate).
106
[Penicillins] What is the main chemical feature of penicillins that confers acid stability?
An electron-withdrawing group (e.g., phenoxymethyl in Pen V) near the amide carbonyl reduces ring-opening.
107
[Penicillins] How do beta-lactamase inhibitors like clavulanate work?
Irreversibly bind to beta-lactamase active site → prevent degradation of penicillin.
108
[Cephalosporins] How do acetate vs. carbamate side chains at C-3 affect enzymatic hydrolysis?
Acetate: esterases hydrolyze → inactive. Carbamate: more stable to hydrolysis.
109
[Carbapenems] Why is imipenem co-administered with cilastatin?
Cilastatin inhibits renal dehydropeptidase-1, which degrades imipenem.
110
[Monobactams] What is unique about aztreonam’s spectrum and structure?
Active only against Gram(–); lacks fused ring, has sulfamic acid for reactivity.
111
[Vancomycin] What are major toxicities of vancomycin?
Red man syndrome, nephrotoxicity, ototoxicity.
112
[Lipoglycopeptides] How do dalbavancin and oritavancin differ in half-life from vancomycin?
Dalbavancin: 204 h, Oritavancin: 245 h vs. Vancomycin: ~6 h.
113
[Streptogramins] What is the MOA of dalfopristin?
Inhibits peptidyl transferase on 50S → prevents peptide bond formation.
114
[Oxazolidinones] What is a major side effect of linezolid?
Myelosuppression, neuropathy with long use. Also inhibits MAO → serotonin syndrome risk.
115
[Tetracyclines] Why is doxycycline the tetracycline of choice?
High oral bioavailability, no C-6 OH (↓ GI issues, no nephrotoxicity), long half-life.
116
[Quinolones] Why should fluoroquinolones not be taken with dairy or antacids?
Chelate metal ions (Ca, Mg, Fe) → ↓ oral absorption and efficacy.
117
[Sulfonamides] How is sulfasalazine activated in the body?
Intestinal bacteria cleave it into sulfapyridine and 5-aminosalicylic acid → local anti-inflammatory effects.
118
[Penicillins] How do Gram(+) and Gram(–) bacteria differ in structure relevant to penicillin activity?
Gram(+): thick peptidoglycan, 1 membrane, external beta-lactamases. Gram(–): thin wall, 2 membranes, periplasmic beta-lactamases, porins.
119
[Penicillins] What is the mechanism of action of penicillins?
Inhibit transpeptidase → block peptidoglycan crosslinking → weak cell wall → lysis.
120
[Cephalosporins] How are cephalosporins classified by generation?
1st gen: mostly Gram(+); 2nd: more Gram(–); 3rd: broad Gram(–); 4th: Pseudomonas; 5th: MRSA-active.
121
[Cephalosporins] How does the oxime ether at C-7 influence beta-lactamase stability?
Syn-oxime ethers are more stable against hydrolysis by beta-lactamases than anti-oxime ethers.
122
[Vancomycin] What is the mechanism of action of vancomycin?
Binds D-Ala-D-Ala on cell wall precursors → inhibits transglycosylation and crosslinking.
123
[Vancomycin] What is a major resistance mechanism to vancomycin?
D-Ala-D-Ala replaced with D-Ala-D-Lac → reduces binding affinity.
124
[Aminoglycosides] What is the mechanism of action of aminoglycosides?
Bind 30S → interfere with initiation and cause misreading of mRNA → defective proteins.
125
[Aminoglycosides] What are the major toxicities of aminoglycosides?
Nephrotoxicity (reversible), ototoxicity (irreversible), and neuromuscular blockade.
126
[Macrolides] What is the mechanism of action of macrolides?
Bind 50S → inhibit translocation step of protein synthesis → bacteriostatic.
127
[Macrolides] What are common bacterial resistance mechanisms to macrolides?
Methylation of 23S rRNA (A2058), esterase production, efflux pumps.
128
[Tetracyclines] Why should tetracyclines not be given with calcium or iron?
They chelate multivalent metals → ↓ oral absorption.
129
[Tetracyclines] What is the MOA of tetracyclines?
Bind 30S → block aminoacyl-tRNA from entering A site → inhibit protein synthesis.
130
[Quinolones] What is the mechanism of action of quinolones?
Inhibit DNA gyrase and topoisomerase IV → block DNA replication and repair.
131
[Quinolones] What are major side effects of fluoroquinolones?
Tendon rupture, QT prolongation, CNS effects, GI upset, photosensitivity.
132
[Sulfonamides] What is the mechanism of action of sulfonamides?
Inhibit dihydropteroate synthase → block folate synthesis in bacteria.
133
[Sulfonamides] Why are sulfonamides selective for bacteria?
Humans do not synthesize folate de novo (rely on dietary folate).
134
[Penicillins] What is the main chemical feature of penicillins that confers acid stability?
An electron-withdrawing group (e.g., phenoxymethyl in Pen V) near the amide carbonyl reduces ring-opening.
135
[Penicillins] How do beta-lactamase inhibitors like clavulanate work?
Irreversibly bind to beta-lactamase active site → prevent degradation of penicillin.
136
[Cephalosporins] How do acetate vs. carbamate side chains at C-3 affect enzymatic hydrolysis?
Acetate: esterases hydrolyze → inactive. Carbamate: more stable to hydrolysis.
137
[Carbapenems] Why is imipenem co-administered with cilastatin?
Cilastatin inhibits renal dehydropeptidase-1, which degrades imipenem.
138
[Monobactams] What is unique about aztreonam’s spectrum and structure?
Active only against Gram(–); lacks fused ring, has sulfamic acid for reactivity.
139
[Vancomycin] What are major toxicities of vancomycin?
Red man syndrome, nephrotoxicity, ototoxicity.
140
[Lipoglycopeptides] How do dalbavancin and oritavancin differ in half-life from vancomycin?
Dalbavancin: 204 h, Oritavancin: 245 h vs. Vancomycin: ~6 h.
141
[Streptogramins] What is the MOA of dalfopristin?
Inhibits peptidyl transferase on 50S → prevents peptide bond formation.
142
[Oxazolidinones] What is a major side effect of linezolid?
Myelosuppression, neuropathy with long use. Also inhibits MAO → serotonin syndrome risk.
143
[Tetracyclines] Why is doxycycline the tetracycline of choice?
High oral bioavailability, no C-6 OH (↓ GI issues, no nephrotoxicity), long half-life.
144
[Quinolones] Why should fluoroquinolones not be taken with dairy or antacids?
Chelate metal ions (Ca, Mg, Fe) → ↓ oral absorption and efficacy.
145
[Sulfonamides] How is sulfasalazine activated in the body?
Intestinal bacteria cleave it into sulfapyridine and 5-aminosalicylic acid → local anti-inflammatory effects.
146
[Penicillins] How does probenecid prolong penicillin half-life?
Inhibits tubular secretion in kidneys → increases serum concentration and duration.
147
[Penicillins] How does lipophilicity affect serum protein binding of penicillins?
More lipophilic penicillins bind more to serum proteins → reduced free drug levels.
148
[Penicillins] How are penicillins excreted?
Mostly renal excretion via tubular secretion. Adjust dose in renal impairment.
149
[Cephalosporins] What makes cefepime resistant to beta-lactamases?
Syn-methoximino group + positively charged N-methylpyrrolidine increases reactivity and penetration.
150
[Cephalosporins] What structural feature confers oral bioavailability in cephalosporins?
Acid-stable 3-position substituents (e.g., vinyl or methyl group).
151
[Carbapenems] What makes carbapenems highly reactive?
Replacement of sulfur with methylene increases strain in the beta-lactam ring.
152
[Monobactams] What is the cross-allergenicity of monobactams with penicillins?
Low to none, due to structural dissimilarity.
153
[Vancomycin] What are the primary uses of vancomycin?
MRSA, C. difficile (oral), serious Gram(+) infections in beta-lactam allergic patients.
154
[Streptogramins] How do quinupristin and dalfopristin act synergistically?
Dalfopristin alters ribosome conformation to enhance quinupristin binding.
155
[Streptogramins] What are Synercid's major side effects?
Arthralgia, myalgia, infusion site reactions, hyperbilirubinemia.
156
[Oxazolidinones] How does resistance to linezolid occur?
Mutation in 23S rRNA prevents binding to 50S ribosome.
157
[Oxazolidinones] What is the mechanism of drug interactions with linezolid?
Inhibits MAO → risk of serotonin syndrome with serotonergic agents.
158
[Tetracyclines] Why are minocycline and doxycycline safer for the kidneys?
Lack C6-OH → no dehydration to nephrotoxic epianhydrotetracycline.
159
[Tetracyclines] What causes Fanconi syndrome with old tetracyclines?
Degraded product 4-epianhydrotetracycline is nephrotoxic.
160
[Quinolones] How do quinolones kill bacteria?
Stabilize DNA cleavage complex → block religation → double-strand breaks → cell death.
161
[Quinolones] What is the function of DNA gyrase vs. topoisomerase IV?
Gyrase: supercoils DNA (Gram–). Topo IV: separates daughter DNA (Gram+).
162
[Sulfonamides] What is the mechanism of trimethoprim?
Inhibits dihydrofolate reductase → blocks tetrahydrofolate synthesis.
163
[Sulfonamides] Why are sulfonamides combined with trimethoprim?
Sequential blockade of folate pathway → synergistic bactericidal effect.
164
[Penicillins] Which penicillins cover Streptococcus spp. (Group Strep, Viridans, PSSP)?
Penicillin G, Ampicillin, Amoxicillin (Una, Aug), Piperacillin (Zosyn).
165
[Penicillins] Which penicillins cover MSSA?
Nafcillin, Oxacillin, Dicloxacillin (anti-staphylococcal penicillins).
166
[Penicillins] Which beta-lactam/beta-lactamase inhibitor combinations improve Gram(–) and anaerobe coverage?
Unasyn (ampicillin/sulbactam), Augmentin (amoxicillin/clavulanate), Zosyn (piperacillin/tazobactam).
167
[Cephalosporins] Which generation of cephalosporins is best for Pseudomonas coverage?
4th generation (cefepime) and antipseudomonal 3rd gen (ceftazidime).
168
[Cephalosporins] Which cephalosporins cover MRSA?
5th generation cephalosporin ceftaroline.
169
[Carbapenems] Which carbapenems cover Pseudomonas and ESBL-producing organisms?
Imipenem, meropenem, and doripenem (not ertapenem).
170
[Carbapenems] Which carbapenem lacks activity against Pseudomonas?
Ertapenem.
171
[Monobactam] What is aztreonam’s spectrum of activity?
Gram-negative aerobes, including Pseudomonas. No Gram-positive or anaerobic coverage.
172
[Vancomycin] What does vancomycin cover?
Gram-positive organisms: MRSA, MSSA, Strep, Enterococcus (not VRE), and C. difficile (oral only).
173
[Tetracyclines] Which tetracyclines cover MRSA and atypicals?
Doxycycline, minocycline, tigecycline, and omadacycline.
174
[Macrolides] What are macrolides (e.g., azithromycin) good for?
Atypicals (Legionella, Mycoplasma), H. influenzae, M. catarrhalis, and some Strep spp.
175
[Fluoroquinolones] Which fluoroquinolones cover Pseudomonas?
Levofloxacin and ciprofloxacin.
176
[Fluoroquinolones] Which fluoroquinolone does NOT cover urinary pathogens?
Moxifloxacin (poor urinary concentrations).
177
[TMP-SMX] What is TMP-SMX used for?
MRSA, E. coli, Proteus, Klebsiella, and Pneumocystis jirovecii.
178
[Clindamycin] What does clindamycin cover?
Gram-positive anaerobes (ADA), Streptococcus, MSSA, some CA-MRSA; not good for Gram-negatives.
179
[Metronidazole] What infections is metronidazole used for?
Below the diaphragm anaerobes (Bacteroides), C. difficile, Trichomonas, Giardia.
180
[Gram-Negatives] Which beta-lactams cover ESBL-producing organisms?
Carbapenems (e.g., meropenem), ceftazidime/avibactam, cefiderocol.
181
[Gram-Negatives] Which antibiotics cover Enterobacter, Serratia, and Citrobacter (AmpC producers)?
Carbapenems, cefepime, and sometimes cefiderocol.
182
[Anaerobes] Which antibiotics cover above-diaphragm anaerobes (e.g., Peptostreptococcus)?
Clindamycin, penicillin, Unasyn, Augmentin.
183
[Anaerobes] Which antibiotics are reliable for below-diaphragm anaerobes (e.g., Bacteroides fragilis)?
Metronidazole, Unasyn, Augmentin, Zosyn, carbapenems, cephamycins (cefoxitin, cefotetan).
184
[Atypicals] Which antibiotic classes cover atypical organisms (e.g., Legionella, Mycoplasma)?
Macrolides, tetracyclines, and fluoroquinolones.
185
[MRSA] What oral antibiotics are commonly used for community-acquired MRSA?
TMP-SMX, doxycycline, clindamycin (check D-test), linezolid.
186
[MRSA] What IV antibiotics are used for hospital-acquired or invasive MRSA?
Vancomycin, daptomycin (not for pneumonia), ceftaroline, linezolid.
187
[VRE] What agents are active against vancomycin-resistant Enterococcus?
Linezolid, daptomycin, tigecycline, and Synercid (E. faecium only).
188
[Limitations] Why is clindamycin not used for Gram-negative infections?
Poor Gram-negative coverage; limited to Gram-positive and anaerobes above diaphragm.
189
[Limitations] Why is ertapenem not used for Pseudomonas or Acinetobacter?
It lacks activity against these organisms, unlike other carbapenems.
