Pharmacology - Antimicrobial Therapy II & III - Jeffrey Steele Flashcards
1
Q
What cephalosporins cover Pseudomonas?
A
Cefepime
Ceftazidine
2
Q
Use: Ceftaroline (5th gen)
A
MSSA, MRSA
E. faecalis
S. pneumoniae
Complicated SSTI
Approved for CAP
3
Q
Class: Avibactam
A
Novel beta-lactamase inhibitor
4
Q
Use: Ceftolazone/Tazobactam
A
Pseudomonas and non-beta-lactamase producing enterobacteriaceae;
Complicated UTI;
Complicated intra-abdominal infection
5
Q
Class: Imipenem-cilastatin; Meropenem; Ertapenem; Doripenem
A
Carbapenems
6
Q
What carbapenem is not recommended for use against Pseudomonas?
A
Ertapenem
7
Q
What carbapenem is recommended for use against E. faecalis?
A
Imipenem
8
Q
Use: Carbapenems
A
cUTI; cIAI; CAP; Bone and SSTI; Bacterial meningitis, post-surgical (Miripenem) meningitis
9
Q
What class of antibiotics is most likely to cause seizures (1%)?
A
Carbapenems
Often in patients with renal dysfunction, when drug is used in high doses
10
Q
What Carbapenem is most effective against Pseudomonas?
A
Doripenem
11
Q
Class: Aztreonam
A
Monobactam
12
Q
Spectrum: Aztreonam
A
Gram negs only - Enterobacteriaceae and Pseudomonas
13
Q
Class: Vancomycin
A
Glycopeptide
14
Q
MOA: Vancomycin
A
Inhibits late stages of cell wall synthesis
– Binds to the D-Ala-D-Ala terminus of the nascent peptidoglycan pentapeptide
– Inhibits transglycosylase preventing elongation of peptidoglycan and cross-linking
15
Q
Spectrum: Vancomycin
A
MRSA MSSA (less effective than beta-lactam) Coag-neg staph ie Staph epidermidis; Strep; Enterococci; Bacillus spp; Corynebacterium spp; – Peptostreptococcus – Actinomyces – Propionibacterium – Clostridium
16
Q
Does Vancomycin have gram neg activity?
A
No
17
Q
If MRSA is suspected, such as in a purulent cellulitis, what drug is recommended?
A
Vancomycin
18
Q
Uses: Vancomycin
A
– SSTI, Especially when MRSA is suspected (purulent cellulitis)
• Bacteremia & Endocarditis
– Caused by Enterococcus, MRSA, coagulase-negative Staph
• Meningitis & Ventriculitis
– Community-acquired (for cephalosporin-resistant S. pneumoniae) – Hospital-acquired (for skin flora, MRSA)
• Pneumonia
– HAP, HCAP
• Bone & Joint Infection
• Neutropenic Fever
• Surgical prophylaxis
• C. difficile colitis (ORAL FORM ONLY)
19
Q
Side effects: Vancomycin
A
• Nephrotoxicity – Concomitant nephrotoxins, e.g aminoglycosides, amphotericin • Infusion reactions – Redman syndrome • Secondary to histamine release • Maculopapular rash – SJS, TEN • Drug fever • Phlebitis • Neutropenia • Thrombocytopenia
20
Q
Only use PO Vancomycin for:
A
C. Diff colitis, because it’s a big molecule –> poorly absorbed
21
Q
MOA: Daptomycin
A
Insertion into the gram-positive cell membrane causing depolarization and ultimate cell death
• Disclaimer: unique MOA. Not a cell-wall active agent
22
Q
Spectrum: Daptomycin
A
MSSA, MRSA, VISA
Strep
Enterococci including VRE
Has activity against gram pos anaerobes
23
Q
Does Daptomycin have gram neg activity?
A
NO
24
Q
Why is Daptomycin not effective for use in pneumonia?
A
Pulmonary surfactant inactivates the drug
25
Use: Daptomycin
SSTI
Staph aureus bacteremia and endocarditis;
Osteoarticular infection;
Enterococcal infections
26
Side effects: Daptomycin
Paresthesia
Peripheral neuropathy;
Eosinophilic pneumonia;
CPK elevation and possible skeletal muscle damage
27
Class: Gentamicin (IV)
Aminoglycosides
28
Class: Tobamycin (IV/inh)
Aminoglycosides
29
Class: Amikacin (IV/inh)
Aminoglycosides
30
Class: Streptomycin (IM)
Aminoglycosides
31
MOA: Aminoglycosides
Bind to the 30S subunit of bacterial ribosomes and interfere with an initiation complex between mRNA (messenger RNA) and the 30S subunit, inhibiting protein synthesis
32
Spectrum: Aminoglycosides
Gram-negative
– Enterobacteriaceae & Pseudomonas
• Gram-positive
– Synergy with cell wall active agent against Enterococcus. CANNOTGIVEAS MONOTHERAPY
33
What aminoglycoside is recommended for use against mycobacteria and Nocardia?
Amikacin
34
Do aminoglycosides have activity against anaerobes?
No
35
Side effects: Gentamicin, Amikacin
Nephrotixicity;
Ototoxicity - risk increased with loop diuretics;
Neuromuscular damage
36
Class: Minocycline (IV/PO)
Tetracycline
37
MOA: Tetracyclines
Passive diffusion through porins in gram- negative organism;
| Bind to 30S ribosomal subunit preventing protein synthesis
38
What drug class is recommended for atypical organisms such as Chlamydia pneumoniae and Mycoplasma pneumoniae?
Tetracyclines
39
What drug class is recommended for spirochetes such as Borrelia burgdorferi, Leptospira, and Treponema pallidum?
Tetracyclines
40
What drug class is recommended for the rickettsiae?
Tetracyclines
41
Spectrum: Tetracyclines
```
Atypical Organisms
– Chlamydia pneumoniae – Mycoplasma pneumoniae
• Spirochetes
– Borrelia burgdorferi – Leptospira
– Treponema pallidum
• Rickettsiae
• Gram positive
– S. pneumoniae (although resistance may be an issue) – CA-MRSA
• Gram negative – H. influenzae
– Neiserria spp.
• Rapidly growing Mycobacteria
```
42
Uses: Tetracyclines
```
Tick-borne illness (DOC)
– Lyme disease
– Ehrlichiosis
– Anaplasmosis
• CAP
– Patients with low risk of S. pneumoniae resistance
• SSTI caused by CA-MRSA
• Combination therapy for H. pylori
• Prophylaxis
– Exposure to anthrax, tularemia, plague, Q fever, brucellosis
```
43
Side Effects: Tetracyclines
```
Photosensitivity;
Hyperpigmentation
Blue discoloration of skin;
Nephrotoxocity;
Neurotoxicity with Minocycline;
Erosive esophagitis
```
44
Why should tetracyclines not be given to children?
Discoloration of teeth AND inhibition of bone growth in infants (reversible)
45
What kind of neurotoxicity occurs with tetracyclines?
Vertigo, Tinnitus;
| Pseudotumor cerebri with prolonged use
46
What kind of nephrotoxicity can occur with tetracycline use?
Expired tetracycline resulting in reversible Fanconi-like syndrome (doesn’t happen with current formulation)
47
What drugs should be avoided when tetracyclines are administered?
Antacids
Sucralfate
Multivitamins
Iron
48
Class: Tigecycline
Glycylcycline
49
MOA: Tigecycline
9-glycl substitution enables tigecycline to overcome two major types of resistance
– Efflux pumps
– Ribosomal protection
50
Spectrum: Tigecycline
Broad-spectrum;
| gram-negative, gram-positives, anaerobes (includes MRSA, VRE & Acinetobacter)
51
What 4 gram negative bugs canNOT be treated with Tigecycline?
– Pseudomonas
– Proteus
– Providencia
– Morganella
52
Side effects: Tigecycline
• GI
– Significant nausea (~25%), vomiting (18%), diarrhea
• Transaminitis
• Increased mortality
– Black Box warning regarding
– Use in situations when alternative agents are not suitable
53
Class: Azithromycin (IV/PO)
Macrolide
54
Class: Clarithromycin (PO)
Macrolide
55
Class: Erythromycin (IV/PO)
Macrolide
Not used much anymore
56
Class: Macrolides
Reversible binding to 50S subunit of ribosome
57
Spectrum: Macrolides
```
• Gram-positive
– S. pneumoniae (significant resistance)
– Significant resistance in β-hemolytic strep
• Gram-negative
– H. influenzae, M. catarrhalis
• Atypicals
– Legionella, Chlamydia, Mycoplasma
• Anaerobes
– Actinomyces
```
58
Uses: Macrolides
• Uncomplicated upper & lower respiratory tract infections
– Usually in patients without prior antibiotics due to risk of resistant S. pneumoniae
• Mycobacterial infection – M. avium (seen in HIV crowd)
• H. pylori (clarithromycin>azithromycin) in combination with other agents
59
Side effects: Macrolides
```
• GI
– Erythromycin>azithromycin,clarithromycin – Abdominal cramps, N/V, diarrhea
• Thrombophlebitis (IV) – Erythromycin
• Cardiac
– QT-prolongation
• Torsades de pointes
```
60
Class: Clindamycin
Lincosamide
61
MOA: Clindamycin
Binding to 50S ribosomal subunit preventing protein synthesis
62
Are Clindamycin effective against gram neg bugs?
NO, Gram pos only
63
Why is Clindamycin indicated for use in TSS Strep?
Mitigates toxin production
64
Side effects: Clindamycin
* Diarrhea (up to 20% of patients)
| * Pseudomembranous colitis
65
Class: Linezolid (IV/PO)
Oxazolidinones
66
Class: Tedizolid (PO)
Oxazolidinones
67
MOA: Oxazolidinones (Linezolid, Tedizolid)
Binds to 23 S ribosomal RNA of the 50S subunit inhibiting protein synthesis
68
Why should Linezolid be avoided in the treatment of Staph aureus bacteremia?
• Vancomycin or daptomycin are recommended as 1st- line therapy
69
Use: Linezolid
– Enterococcal infection including bacteremia
– Nosocomial pneumonia caused by S. aureus
– CAP caused by S. aureus
– SSTI
70
Use: Tedizolid
SSTI
71
T/F: Linezolid has gram negative activity.
```
FALSE
Linezolid use is:
– Staphylococci
• S. aureus (MRSA, MSSA)
• Coagulase-negative
– Enterococci including VRE
– Streptococci
```
72
Side effects: Linezolid
```
• Hematologic toxicity
• Reversible myelosuppression
– Thrombocytopenia (most common)
– Anemia
• MitochondrialToxicity
– Peripheral neuropathy, optic neuropathy – Lactic acidosis
• Serotonin Syndrome (SS)
– Inhibition of MAO can result in SS when given with serotonergic agents
```
73
Name the three nucleic acid synthesis inhibitors.
Fluoroquinolones;
Metronidazole;
Rifamycins
74
Class:
– Rifampin
– Rifabutin
– Rifaximin
Rifamycin - Nucleic acid synthesis inhibitors
75
Class:
– Ciprofloxacin
– Levofloxacin
– Moxifloxacin
Fluoroquinolones - Nucleic acid synthesis inhibitors
76
Class: Metronidazole
No technical class - Nucleic acid synthesis inhibitor
77
MOA: Fluoroquinolones
* Inhibit DNA gyrase
| * Inhibit topoisomerase IV
78
What are the ONLY oral antipseudomonal agents?
Fluoroquinolones
– Ciprofloxacin
– Levofloxacin
– Moxifloxacin
79
Spectrum: Fluoroquinolones
– S. pneumoniae
• levofloxacin & moxifloxacin;
– Enterobacteriaceae
– H. influenzae
– P. aeruginosa: Ciprofloxacin & levofloxacin
– Atypicals (Legionella, Chlamydia, Mycoplasma);
• Mycobacterium
80
Resistance in what bugs is an issue for Fluoroquinolone use?
Resistance in Enterobacteriaceae problematic
81
What is the antibiotic of choice for anthrax?
Fluoroquinolones
– Ciprofloxacin
– Levofloxacin
– Moxifloxacin
82
What is the recommended adjunctive therapy in MDR pulmonary TB?
Fluoroquinolones
– Ciprofloxacin
– Levofloxacin
– Moxifloxacin
83
T/F: Fluoroquinolones are just as effective PO as IV.
True
| Good drug for transitioning out of the hospital
84
Avoid Ciprofloxacin in conjunction with what drugs?
Theophylline --> Seizure
| Tizanidine --> Hypotension
85
MOA: Metronidazole
Interacts with DNA to cause a loss of helical DNA structure and strand breakage resulting in inhibition of protein synthesis
86
Spectrum: Metronidazole
```
• Anaerobes
– B. fragilis
– Clostridial species including difficile
• Protozoa
– Trichomonas
– Giardia
– Entamoeba histolytica
```
87
Side effects: Metronidazole
* Metallic taste
* Minor GI disturbances
* Peripheral neuropathy (with long-term use or very high doses)
* Disulfiram reaction with alcohol
88
Use: Metronidazole
* C. difficile diarrhea
* Intra-abdominal infections in combination with other agents
* Surgical prophylaxis in colon surgery (with other agents)
* Trichomoniasis
89
MOA: Rifamycins
Bind to DNA-dependent RNA polymerase inhibiting RNA synthesis
90
T/F: Rifamycins such as Rifampin inhibit biofilms.
True
91
Spectrum: Rifamycin
```
• Gram-positive
– Staphylococci
– Streptococci
– C. difficile
– Listeria
• Gram-negative
– H. influenzae
– N. meningitidis
– H. pylori
• Mycobacterium
```
92
Use: Rifampin
– M. tuberculosis infection
– Other Mycobacterium infections
– Adjunctive treatment in prosthetic valve endocarditis (S. aureus) and for prosthetic joint infection
– Prophylaxis N. meningitidis
93
Use: Rifaximin
– Hepatic encephalopathy
– Recurrent C. difficile
– Traveler’s diarrhea
94
Side effects: Rifampin
– Rifampin-associated flulike syndrome • Onset is latent
– Thrombocytopenia, hemolysis
– Renal failure
– Transaminitis
• Increased incidence of hepatotoxicity when combined with INH
or pyrazinamide
95
Rifampin interacts with what liver enzymes, lowering the concentration of other drugs?
3A4*
1A2
2C
2D6
96
What are the main anti-TB drugs?
* Isoniazid (INH)
* Pyrazinamide
* Ethambutol
97
Side effects: Isoniazid
```
• Hepatitis
– 10-20% of patients have asymptomatic minor transaminitis
• Neurotoxicity
– Peripheral neuropathy
• Pyridoxine can alleviate
– Memory loss, psychosis
• Hypersensitivity reactions
```
98
Class: Trimethoprim-Sulfamethoxazole (Bactrim)
Bacterial anti-metabolites
99
MOA: Trimethoprim-Sulfamethoxazole
Sulfamethoxazole: Interferes with bacterial folic acid synthesis and growth via inhibition of dihydrofolic acid formation from paraaminobenzoic acid (PABA)
Trimethoprim: inhibits dihydrofolic acid reduction to tetrahydrofolate resulting in sequential inhibition of enzymes of the folic acid pathway
100
What are the two drugs of choice for listeria?
Ampicillin;
| Trimethoprim-Sulfamethoxazole
101
What is the drug of choice for Stenotrophomonas (hosp)?
Trimethoprim-Sulfamethoxazole
102
Is Trimethoprim-Sulfamethoxazole effective against anaerobes?
NO
103
Spectrum: Trimethoprim-Sulfamethoxazole
```
• Gram-Positive
– CA-MRSA/MSSA
– S. pneumoniae
• Not ideal for β-hemolytic strep
– Listeria
• Gram-Negative
– Enterobacteriaceae (E. coli, Klebsiella, Enterobacter, etc.)-resistance varies
– DOC-Stenotrophomonas
• Toxoplasmosis, Nocardia, Pneumocystis
```
104
Uses: Trimethoprim-Sulfamethoxazole
* Prophylaxis & treatment Pneumocystis jiroveccii pneumonia
* Toxoplasmosis encephalitis
* Urinary tract infection
* Listeria meningitis
* CA-MRSA
105
Side effects: Trimethoprim-Sulfamethoxazole
RASH - SJS, TEN possible also
more common in HIV patients;
• Hematologic
– Bone marrow suppression (usually at higher doses)
• Renal
– Pseudo-renal failure: TMP can inhibit creatinine secretion
– AIN from sulfamethoxazole
– Hyperkalemia-TMP essentially acts as a K+ sparing diuretic
106
Avoid warfarin when administering what antibiotic?
Trimethoprim-Sulfamethoxazole
Warfarin (inhibition of CYP 2C9 by TMP/SMX) leading to increase in INR
