Pharmacology - Antimicrobial Therapy II & III - Jeffrey Steele Flashcards Preview

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Flashcards in Pharmacology - Antimicrobial Therapy II & III - Jeffrey Steele Deck (106):
1

What cephalosporins cover Pseudomonas?

Cefepime
Ceftazidine

2

Use: Ceftaroline (5th gen)

MSSA, MRSA
E. faecalis
S. pneumoniae

Complicated SSTI
Approved for CAP

3

Class: Avibactam

Novel beta-lactamase inhibitor

4

Use: Ceftolazone/Tazobactam

Pseudomonas and non-beta-lactamase producing enterobacteriaceae;
Complicated UTI;
Complicated intra-abdominal infection

5

Class:
Imipenem-cilastatin;
Meropenem;
Ertapenem;
Doripenem

Carbapenems

6

What carbapenem is not recommended for use against Pseudomonas?

Ertapenem

7

What carbapenem is recommended for use against E. faecalis?

Imipenem

8

Use: Carbapenems

cUTI;
cIAI;
CAP;
Bone and SSTI;
Bacterial meningitis, post-surgical (Miripenem) meningitis

9

What class of antibiotics is most likely to cause seizures (1%)?

Carbapenems
Often in patients with renal dysfunction, when drug is used in high doses

10

What Carbapenem is most effective against Pseudomonas?

Doripenem

11

Class: Aztreonam

Monobactam

12

Spectrum: Aztreonam

Gram negs only - Enterobacteriaceae and Pseudomonas

13

Class: Vancomycin

Glycopeptide

14

MOA: Vancomycin

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

Spectrum: Vancomycin

MRSA
MSSA (less effective than beta-lactam)
Coag-neg staph ie Staph epidermidis;
Strep;
Enterococci;
Bacillus spp; Corynebacterium spp;
– Peptostreptococcus
– Actinomyces
– Propionibacterium
– Clostridium

16

Does Vancomycin have gram neg activity?

No

17

If MRSA is suspected, such as in a purulent cellulitis, what drug is recommended?

Vancomycin

18

Uses: Vancomycin

– SSTI, Especially when MRSA is suspected (purulent cellulitis)
β€’ Bacteremia & Endocarditis
– Caused by Enterococcus, MRSA, coagulase-negative Staph
β€’ Meningitis & Ventriculitis
– Community-acquired (for cephalosporin-resistant S. pneumoniae) – Hospital-acquired (for skin flora, MRSA)
β€’ Pneumonia
– HAP, HCAP
β€’ Bone & Joint Infection
β€’ Neutropenic Fever
β€’ Surgical prophylaxis
β€’ C. difficile colitis (ORAL FORM ONLY)

19

Side effects: Vancomycin

β€’ Nephrotoxicity
– Concomitant nephrotoxins, e.g aminoglycosides, amphotericin
β€’ Infusion reactions
– Redman syndrome
β€’ Secondary to histamine release
β€’ Maculopapular rash – SJS, TEN
β€’ Drug fever
β€’ Phlebitis
β€’ Neutropenia
β€’ Thrombocytopenia

20

Only use PO Vancomycin for:

C. Diff colitis, because it's a big molecule --> poorly absorbed

21

MOA: Daptomycin

Insertion into the gram-positive cell membrane causing depolarization and ultimate cell death

β€’ Disclaimer: unique MOA. Not a cell-wall active agent

22

Spectrum: Daptomycin

MSSA, MRSA, VISA
Strep
Enterococci including VRE
Has activity against gram pos anaerobes

23

Does Daptomycin have gram neg activity?

NO

24

Why is Daptomycin not effective for use in pneumonia?

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
β€’ 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
β€’ Spirochetes
– Borrelia burgdorferi – Leptospira
– Treponema pallidum
β€’ Rickettsiae
β€’ Gram positive
– S. pneumoniae (although resistance may be an issue) – CA-MRSA
β€’ Gram negative – H. influenzae
– Neiserria spp.
β€’ Rapidly growing Mycobacteria

42

Uses: Tetracyclines

Tick-borne illness (DOC)
– Lyme disease
– Ehrlichiosis
– Anaplasmosis
β€’ CAP
– Patients with low risk of S. pneumoniae resistance
β€’ SSTI caused by CA-MRSA
β€’ Combination therapy for H. pylori
β€’ 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

β€’ GI
– Significant nausea (~25%), vomiting (18%), diarrhea
β€’ Transaminitis
β€’ 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

β€’ Gram-positive
– S. pneumoniae (significant resistance)
– Significant resistance in Ξ²-hemolytic strep
β€’ Gram-negative
– H. influenzae, M. catarrhalis
β€’ Atypicals
– Legionella, Chlamydia, Mycoplasma
β€’ Anaerobes
– Actinomyces

58

Uses: Macrolides

β€’ Uncomplicated upper & lower respiratory tract infections
– Usually in patients without prior antibiotics due to risk of resistant S. pneumoniae
β€’ Mycobacterial infection – M. avium (seen in HIV crowd)
β€’ H. pylori (clarithromycin>azithromycin) in combination with other agents

59

Side effects: Macrolides

β€’ GI
– Erythromycin>azithromycin,clarithromycin – Abdominal cramps, N/V, diarrhea
β€’ Thrombophlebitis (IV) – Erythromycin
β€’ Cardiac
– QT-prolongation
β€’ 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

β€’ Diarrhea (up to 20% of patients)
β€’ 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?

β€’ 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
β€’ S. aureus (MRSA, MSSA)
β€’ Coagulase-negative
– Enterococci including VRE
– Streptococci

72

Side effects: Linezolid

β€’ Hematologic toxicity
β€’ Reversible myelosuppression
– Thrombocytopenia (most common)
– Anemia
β€’ MitochondrialToxicity
– Peripheral neuropathy, optic neuropathy – Lactic acidosis
β€’ 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

β€’ Inhibit DNA gyrase
β€’ Inhibit topoisomerase IV

78

What are the ONLY oral antipseudomonal agents?

Fluoroquinolones
– Ciprofloxacin
– Levofloxacin
– Moxifloxacin

79

Spectrum: Fluoroquinolones

– S. pneumoniae
β€’ levofloxacin & moxifloxacin;
– Enterobacteriaceae
– H. influenzae
– P. aeruginosa: Ciprofloxacin & levofloxacin
– Atypicals (Legionella, Chlamydia, Mycoplasma);
β€’ 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

β€’ Anaerobes
– B. fragilis
– Clostridial species including difficile
β€’ Protozoa
– Trichomonas
– Giardia
– Entamoeba histolytica

87

Side effects: Metronidazole

β€’ Metallic taste
β€’ Minor GI disturbances
β€’ Peripheral neuropathy (with long-term use or very high doses)
β€’ Disulfiram reaction with alcohol

88

Use: Metronidazole

β€’ C. difficile diarrhea
β€’ Intra-abdominal infections in combination with other agents
β€’ Surgical prophylaxis in colon surgery (with other agents)
β€’ 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

β€’ Gram-positive
– Staphylococci
– Streptococci
– C. difficile
– Listeria
β€’ Gram-negative
– H. influenzae
– N. meningitidis
– H. pylori
β€’ 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 β€’ Onset is latent
– Thrombocytopenia, hemolysis
– Renal failure
– Transaminitis
β€’ 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?

β€’ Isoniazid (INH)
β€’ Pyrazinamide
β€’ Ethambutol

97

Side effects: Isoniazid

β€’ Hepatitis
– 10-20% of patients have asymptomatic minor transaminitis
β€’ Neurotoxicity
– Peripheral neuropathy
β€’ Pyridoxine can alleviate
– Memory loss, psychosis
β€’ 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

β€’ Gram-Positive
– CA-MRSA/MSSA
– S. pneumoniae
β€’ Not ideal for Ξ²-hemolytic strep
– Listeria
β€’ Gram-Negative
– Enterobacteriaceae (E. coli, Klebsiella, Enterobacter, etc.)-resistance varies
– DOC-Stenotrophomonas
β€’ Toxoplasmosis, Nocardia, Pneumocystis

104

Uses: Trimethoprim-Sulfamethoxazole

β€’ Prophylaxis & treatment Pneumocystis jiroveccii pneumonia
β€’ Toxoplasmosis encephalitis
β€’ Urinary tract infection
β€’ Listeria meningitis
β€’ CA-MRSA

105

Side effects: Trimethoprim-Sulfamethoxazole

RASH - SJS, TEN possible also
more common in HIV patients;

β€’ Hematologic
– Bone marrow suppression (usually at higher doses)
β€’ 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