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1

Beta-Lactamase Inhibitors
clavulanic acid, sulbactam, tazobactam
MOA
Use

MOA: inhibitors of many bacterial beta-lactamases
-inactivates ahminoglycosides
-protects the antibiotic from beta lactamase (penicillinase)
Uses: only in combo with PCN, activity spectrum determined by that of PCN

2

Ceftriaxone (rocephin)
Class
Spectrum
Misc
dose
used to treat? example(s)

--cephalosporin, beta-lactam 3rd generation
--expanded gram negative coverage against: meningococcus, h. flu, neisseira
--crosses BBB
-IV
--meningitis, lymes disease, gonorrhea

3

Ceftazidime
class
spectrum
misc
dose

-cephalosporin, beta lactam, 3rd generation
--expanded gram - coverage: meningococcus, h. flu, neisseria AND PSEUDOMONAS
-IV

4

Cefotaxime
class
spectrum
misc
dose
use to treat? example

--cephalosporin
-expanded gram - coverage: meningococcus, h. flu, neisseria
--crosses BBB
-IV
--treats meningitis

5

Cefepime (maxipime)
class
spectrum
dose form
used to treat

-cephalosporin, beta-lactam, 4th generation
-gram + & -, including: staph aureus, strep pneumo, h. flu, neisseria AND pseudomonas
-IV
-treats: meningitis, sepsis, other serious infections
**crosses BBB, very broad spectrum
**sometimes paired with aminoglycoside when treating pseudomonas

6

What is ceftriaxone (rocephin) the DOC for because of resistance?

gonorrhea
drug is a 3rd generation cephalosporin and is also good at treating lyme disease, and meningitis

7

What is ceftazidime effective in treating and used for?

pseudomonas meningitis
drug is a 3rd generation cephalosporin: ONLY ONE in third generation that can treat pseudomonas

8

What are the third and fourth generations of cephalosporins the DOC for treating?
(cefotaxime, ceftazidime, ceftriazone, cefepime)

gram negative meningitis

9

What drug class is a good alternative for ahminoglycosides?

cephalosporins: 3rd and 4th generation

10

What are the two drugs in the first generation cephalosporins (beta-lactams, cell wall inhibitors) and what are they good against?

cephalexin (keflex) and cefazoin (ansef)

good against gram + strep and staph
some gram negative also some anaerobic cocci

11

What are the most frequently prescribed aminoglycosides?

-Gentamicin
-Tobramycin
-Amikacin

12

In general, what are first generation cephalosporins used for?

-gram positive skin infections
-pneumococcal pneumonia (strep pneumo)
-utis
-prophylaxis for surgery

13

What is streptomycin used for? (think major)

2nd line for TB in combo with other agents
also used in combo with penicillin or ampicillin for endocarditis from: enterococcus facecalis or viridian's strep

14

What is neomycin used for?

prophylaxis for bowel prep for surgery

15

What is different about Tobramycin?

-covers pseudomonas better
-comes in INHALED solution for cystic fibrosis infections (pts that get pseudomonas pneumonia)

16

When are the aminoglycosides used clinically?

-seriously life-threatening GRAM-NEGATIVE infections
-complicated skin, bone or UTIs
-sepsis
-osteomyelitis
-peritonitis and other severe intra-abdominal infections
-severe PID
-endocarditis
-Mycobacterium infection
-neonatal sepsis
-ocular infections (topical)
-otitis externa (topical)

17

What is the spectrum of activity for ahminoglycosides?

-SYNERGISTIC with beta-lactams against GRAM POSITIVE COCCI
-NEGLIGIBLE ANAEROBIC coverage
-broad spectrum for gram-negative coverage
-[ ] dependent killing dose (dose-dependent killing)

18

Aminoglycosides
MOA

-enter cell through porin channels
-bind to 30S subunit of bacterial ribosome thus inhibiting protein synthesis

19

Aminoglycosides
Preggos
Lactation

Preggo: category D (evidence that benefit may outweigh risk)
Lactation : probable safe-safety unknown, does enter breast milk, but not well absorbed orally, thus consider comparable with use during breast feeding

20

Aminoglycosides
CI

-previous allergy or hypersensitive rxn
-Myasthenia gravis (neuromuscular blockade risk too high)

21

Aminoglycosides
Adverse effects

nephrotoxicity
ototoxicity
neurotoxicity
neuromuscular blockade
**why we monitor serum levels

22

What are the risk factors of nephrotoxicity with aminoglycosides?

elderly
renal dysfunction
dehydration
hypotension
liver disease
concomitant use of other nephrotoxins

23

Aminoglycoside nephroxoicity
general concerns on monitoring, outcome

**reversible, non-oliguric renal failure
(acute tubular necrosis)
--Monitor for renal casts, urine output and serum creatine levels
**ONCE DAILY dosing = less toxic because tubular cells have time between dosing intervals to decrease intracellular levels

24

Aminoglycoside ototoxicity
general concerns on monitoring, outcome

-vestibular and cochlear
-most of ototoxicity VESTIBULAR = vertigo, ataxia, loss of balance, tinnitus
-cochlear ototoxicity = high frequency hearing loss
**often IRREVERSIBLE
-related to peak levels

25

What are the most toxic aminoglycosides that cause ototoxicity?

AMIKACIN
neomycin
kanamycin

26

What are the major take home points with Aminoglycosides?

-remain important as SECOND line agent in tx of serious infections from AEROBIC GRAM-NEGATIVE Bacilli (certain gram-positive organisms)
-imporant tx for multi-drug regimen for mycobacterial infections
-monotherapy limited to: tularemia, plague, uncomplicated utis caused by gram-negs

27

What are major take home points for CIs and AEs with aminoglycosides?

Primary toxicities: nephrotoxicity = usually reversible, ototoxicity = vestibular and cochlear (usually irreversible)
-NM blockade is rare but serious
-DO NOT USE with myasthenia gravis

28

What is the best treatment choice for CA-pneumonia (caused by strep pneumo), as well as mycoplasma pneumoniae?

protein synthesis inhibitors
**CA-pneumoina = strep pneumo has a cell wall while mycoplasma pneumonia is atypical and doesn't have a cell wall so need to cover both of them

29

Why is mycoplasma pneumoniae resistant to penicillins and cephalosporins?

because it lacks a peptidoglycan cell wall
**remember that if a organism doesn't have a cell wall, cell wall inhibitors will have no effect--drugs will be useless

30

where do protein synthesis inhibitors exert their antimicrobial effects?

by targeting the bacterial ribosome WITHIN THE CELL
NOT THE CELL WALL

31

What is the spectrum of the tetracylines ?

gram +, gram -, anaerobes

32

How do organisms become resistant to tetracyclines?

-cell develops efflux pumps (pumps drug out of cell)
-forms ribosomal protection proteins (interfere with binding of drug to ribosome)

33

Tetracyclines
Absorption

-adequately but incompletely absorbed after oral ingestion
-taking with dairy, antacids, calcium, iron DECREASES absorption

34

Tetracylines
Distribution

-concentrates in liver, kidney, speen, skin and bind to tissue undergoing calcification (teeth and bones)
-levels insufficient in CSF for therapeutic efficacy
--ALL CROSS PLACENTA and concentrate in fetal bones and dentition

35

Tetracyclines
Elimination for doxycycline

-concentrates in liver
-METABOLIZED and CONJUGATED
-released in bile
-metabolite preferentially excreted via bile into feces

36

Tetracyclines
Elimination for everything but doxycycline

-concentration in liver
-metabolized and conjugated
-released in bile
-reabsorbed in intestine and enter urine via glomerular filtration

37

Tetracyclines
AE

*******effects on calcified tissues--discoloration of teeth and stunting of bones for growth
**gastric discomfort = only can take doxycycline with food
**phototoxicity = sunburn after taking
**vestibular problems = dizzy, nausea, vomiting

38

Tetracyclines
CI

-preggos
-breast feeding = cat D
-children under 8 years (lawsuit)
--caution if renal function (except doxy)
-caution if impaired liver function
-caution in SLE (exacerbation)

39

Like tetracyclines, macrolides don't tend to be used when suspecting what organism?

Staph aureus

40

Macrolides
What are the resistance mechanisms organisms use?

-alteration in binding site of ribosome
-manifestation of efflux pump to get drug out of cell
-enzymatic inactivation

41

Macrolide's
Absorption

-erythromycin base destroyed by gastric acid and enteric coated tablet is required; adequately absorbed on oral administration
-clarithromycin and azithromycin STABLE to stomach acid and readily absorbed

42

Macrolide's
Distribution

-widely distributed in tissues EXCEPT for CSF

43

Macrolides
metabolism

-erythromycin = cytochrome P450 drug
-clarithromycin metabolized by liver and may interfere with other drugs
-azithromycin NOT a P450 drug and tends to have few interactions with other meds

44

Macrolide's
AE

-GI distress including diarrhea especially a problem with erythromycin (azithromycin and clarithromycin better tolerated)
-ototoxicity (erythromycin)
-prolonged QT with erythromycin and clairthromycin (rare)

45

Of the three below, which one(s) are better tolerated and cause less adverse effects?
Azithromycin, erythromycin, clarithromycin

azithromycin and clarithromycin are better tolerated
erythromycin = gi distress and diarrhea

46

Like doxycycline, what drug class isn't good for staphylococcal disease?

macrolides

47

What works better for chlamydial species?

Macrolides

48

What class of antibiotics is excellent for broad spectrum coverage of both typical and atypical pneumonias?

macrolides

49

What is a good alternative FIRST LINE treatment for strep throat (streptococcal pharyngitis) after penicillin?

Macrolides

50

Chloramphenicol
AE

--hemolytic aneima
-APLASTIC ANEMIAs
-GRAY BABY SYNDROME
(can also cause optic neuritis, loss of vision, interferes with other drugs like phenytoin and warfarin)

51

Clindamycin
SE

diarrhea
nausea
skin rash
c.diff

52

What are two common meds that treat infections from anaerobes (SERIOUS INFECTIONS)?

Clindamycin
Metronidazole (Flagyl)
**make sure serious infection, gut infection or penetrating wound of abdomen
also, when think of anaerobes, think gut and vagina

53

When you think of clindamycin what treatments should you think?

anaerobes, and c. diff

54

What fluoroquinolone would you want to use for strep pneumo?

levofloxin because it has gram + activity
cipro only has gram - activity and strep pneumo is gram +

55

What are clinical uses for fluoroquinolone?

UTI (DOC)
pneumonia
stis
skin and soft tissue (not first line)
gi infections
travelers diarrhea
osteomyelitis

56

Fluoroquinolone
MOA

-inhibits ability of bacterial DNA to replicate

57

Fluoroquinolone
spectrum

cipro: gram neg aerobes and pseudomonas
levo: gram -, pseudomonas, gram+ strep pneumo
moxifloxacin: gram -, gram + (strep pneumo), ANAEROBIC

58

Fluoroquinolone
which ones are resp?

fq's that have activity against GM+ organisms including streptococcus = levofloxacin, moxifloxacin

59

FQs
Black box warning?

-increased risk of tendinitis and tendon rupture in all ages
-risk increases in pts over 60, pts taking corticosteroids and pts with liver, kidney or heart transplants

60

FQs
SE

-nausea
-diarrhea
-confusion
-tendon rupture
-tendonitis
-QT prolongation
-peripheral neuropathy with long term use

61

FQs
Major drug interactions?

Ciprofloxacin = POTENT inhibitor of CYO4501A2
warfarin
anti diabetic agens
[DO NOT TAKE: calcium, iron, antacids with b/c decreases absorption]

62

FQs
what pts should not get?

preggo
lactation
pediatrics: arthropathy and osteochondrosis = irreversible!!!!
*caution use in pts with hepatic dysfunction

63

What drug class contains the only oral agent against Pseudomonas?

FQs

64

What is one of the few oral drugs that covers MRSA ?

Bactrim DS

65

What are the most COMMON side affects of Bactrim?

MOST COMMON =Rash, fever, GI sx
ALSO: (rash, fever, NVD, Stevens-Johnsons syndrome, hemolytic anemia if underlying G6PD, Thrombocytopenia, vasculitis

66

What are the SERIOUS SIDE AFFECTS of Bactrim?

Stevens-johnsons syndrome
-if underlying G6PD then causes HEMOLYTIC ANEMIA
-thrombocytopenia
-vasculitis

67

Sulfamethoxazole/ Trimethoprim (SMXTMP) aka Bactrim DS, Septra
--MOA

folic acid synthesis inhibitor

68

Sulfamethoxazole/ Trimethoprim (SMXTMP) aka Bactrim DS, Septra
--spectrum

Wide gram +, wide gram -
NOT anaerobes
toxoplasmosis
MRSA
PCP with HIV

69

If a patient presents with a rash after taking SMX-TMP, what do you do?

pt is allergic to SMX-TMP
cannot have bactrum again

70

What is stevens johnson syndrome?

-cell death causes dermis and epidermis to separate
-hypersensitivity reaction os skin and mucous membranes
-brought on by sulfa drug (Bactrim)

71

SMX-TMP
drug interactions

-70% protein bound
-POTENTIATES EFFECTS OF:
-warfarin, phenytoin, hypoglycemic agents, beta blockers, methotrexate(methotrexate is also inhibiting folic acid so pts on both can get folic acid deficiency)

72

What would you be concerned about a patient on warfarin and SMX-TMP?

bleeding

73

What would you be concerned about a patient on beta blockers and SMX-TMP?

depressed heart rate

74

What would you be concerned about a patient on hypoglycemic agents and SMX-TMP?

low sugars

75

What would you be concerned about a patient on methotrexate and SMX-TMP?

folic acid deficiency

76

SMX-TMP
metabolized?
excreted?

liver
kidney

77

SMX-TMP
most commonly used for?

UTIs

78

SMX-TMP
why isn't it used at term in pregnancy even though its a category C???

-can cause hemolytic anemia and increase in bilirubin that can cause increased cognitive deficiency (Kernicterus)

79

What drug provides the only PO treatment AND prevention of UNCOMPLICATED urinary tract infection?

Nitrofurantion (Macrobid)

80

What drug is CI in pts with CrCl of less tan 60mL/min?

nitrofurantion (macrobid) BECAUSE if pts have decreased renal clearance, not enough of the drug will concentrate there to take care of the infection

81

Nitrofuantion (Macrobid)
SE

-MOST COMMON = nausea, vomiting
-Pulmonary rss = infiltrates, pneumonitis, pulmonary fibrosis
-hepatic effects (rare but include hepatitis, hepatic necrosis)
-Peripheral neuropathy in long term use in pts with renal failure

82

Nitrofuantion (macrobid)
pulmonary rxs

-acute pulm rxs usually manifested by sudden, severe dyspnea, chills, chest pain, fever and cough
-pulm infiltration with consolidation or pleural effusion on radiographs and eosinophilia may also occur
-USUALLY EVIDENT WITHIN THE FIRST WEEK OF TREATMENT AND REVERSIBLE WHEN DRUG IS DC'd

83

Pt presents to you b/c of sudden onset of dyspnea, chest pain, chills and a fever. Upon CXR, you notice infiltration with consolidation and pleural effusion. CBC shows eosinophilia. In pt hx pts states he saw the doctor sometime last week for pain when he pees. He is on a lot of pills and doesn't remember when the doctor gave him for the urinary tract infection. Based on what you know, what med could be causing these symptoms?

Nitrofuantion (Macrobid)

84

Nitrofurantion (Macrobid)
Drug interactions

none that are significant b/c drug concentrates in bladder and urinary tract approx 30 min after taking

85

Nitrofurantion
Preggos?
lactation?
kids?

preggos: not at term b/c of possibility of hemolytic anemia in newborn = not from bilirubin like in sulfas, but from immature erythrocytes
lactation: don't use
kids: safety in kids not established, and drug is CI if pt is less than 1 month old

86

What drug do you avoid using in older adults and also avoid using for long term suppression of infection? Why?

nitrofurantoin (Macrobid)
because of the possibility and risk of pulmonary toxicity leading to pulmonary fibrosis and/or acute pulmonary reactions

87

What is the DOC for treating the following:
anaerobic infections
bacterial vaginosis
trichomoniasis
c. difficile diarrhea

Metronidazole (Flagyl)

88

Metronidazole (Flagyl)
MOA

inhibits bacterial protein synthesis by:
CAUSING DNA STRAND BREAKAGE THEREFORE INHIBITING BACTERIAL PROTEIN SYNTHESIS (different than the FQs who inhibit DNA gyrase thereby inhibiting the ability of the bacterial DNA to replicate)

89

Metronidazole (Flagyl)
Metabolism

-absorbed po and good tissue penetration
-metabolized by liver

90

Metronidazole (Flagyl)
Spectrum of activity

-gram +, gram - ANAEROBES

91

Metronidazole (Flagyl)
side effects: MOST COMMON

N/V, abdominal pain, metallic taste

92

Metronidazole (Flagyl)
SE (other than most common)

seizures (high doses)
peripheral neuropathy (prolonged courses)
pancreatitis

93

Metronidazole (Flagyl)
Drug interactions

-ENHANCES anticoagulant effect of warfarin
-ETOH (flushing, palpitations, N/V)
-Inhibitor of CYP34A so potential for many drug interactions

94

What drug do Phenobarbital, phenytoin, rifampin interact with and what is the interaction?

metronidazole (flagyl)
these drugs increase the metabolism of metronidazole which will decrease the serum concentration thus leading to treatment failure

95

What are viruses?

obligate intracellular parasites

96

What do anti-viral drugs do?

inhibit active replication --so viral growth resumes after drug removal

97

What is essential for the recovery from the viral infection?

effective host immune response

98

Acyclovir
AE

-REVERSIBLE renal toxicity
-neuro sx: encephaopathic changes including somnolence, hallucinations, confusion, coma
-TTP, HUS: immunocompromised
-GI upset
-HA
-rash
-photosensitivity
-Anemia

99

Famciclovir
AE

neutropenia
thrombocytopenia
neuro sx: encephalopathic changes, somnolence, hallucinations, delirium,
-gi
-HA
-fatigue
-abnormal LFTs

100

Valacyclovir
AE

-neuro sx: encephaopathic changes including somnolence, hallucinations, confusion, coma
-TTP, HUS: immunocompromised
-GI upset
-HA
-rash
-photosensitivity
-Anemia

101

Oseltamivir, Zanamavir
MOA

neuraminidase inhibitors= prevent the release of new visions and their spread from cell to cell

102

Oseltamivir, Zanamavir
Spectrum

Influenza A and B
both prophylaxis and acute tx

103

Ribavirin
MOA

inhibition of RNA polymerase

104

Ribavirin
DOC for ?

RSV bronchiolitis and pneumonia in hospital children
-Lassa fever

105

Ribavirin
Alternative DOC for?

influenza, parainfluenza, measles, used in combo with HCV

106

Ribavirin
AE

-BBW hemolytic anemia
-respiratory deterioration
-depression
-suicidal ideation
-bacterial infections
-psychiatric effects
-anxiety
-fatigue
-dizzy

107

Clotrimazole, Keoconazole, Miconazole (topical)
MOA

inhibit synthesis of ergosterol (cell membrane)

108

Cotrimazole
AE

ABNORMAL LIVER FUNCTION with oral
pruritus
N/V
MUST monitor liver tests

109

Mycostatin (Nystatin)
AE

Contact dermatitis
stevens-johnsons syndrome
n/v/d