Pharm 1 Lecture 12: Antibiotics PPT 2

What is the mechanism of action of beta lactams and Vancomycin?

inhibit bacterial wall synthesis

What is the mechanism of action of sulfonamides and trimethoprim?

inhibit folate synthesis

What is the mechanism of action of macrolides and tetracyclines?

inhibit bacterial protein synthesis

What is the mechanism of action of aminoglycosides, chloramphenicol, and clindamycin?

inhibit bacterial protein synthesis

What is the mechanism of action of Isoniazid?

inhibit bacterial cell membrane structure and function

What is the mechanism of action of Fluoroquinolones and Rifampin?

inhibit bacterial nucleic acid function or synthesis

TMP-SMX (Bactrim) (oral, IV) MOA

 both antifolates

 Sulfamethoxazole competes with PABA, inhibiting bacterial synthesis
of dihydrofolic acid
 Trimethoprim binds and reversibly inhibits dihydrofolate reductase,
blocking production of tetrahydrofolic acid from dihydrofolic acid
 Synergistic

first line for pneumocystitis jirovecii pneumonia (PJP) and prostatis

TMP-SMX

pneumocystitis jirovecii pneumonia (PCP or PJP PJP)

• atypical fungus that synthesizes its own folic acid to survive

• opportunistic infection in patients with HIV or AIDs (immunocomp)

• Tx and prophylaxis: TMP-SMX (oral, IV) (21 days)

What determines pediatric dosing for TMP-SMX?

trimethoprim

Renal adjustment for TMP-SMX

Renally dosed if CrCL < 30

What are the most common adverse effects of Trimethoprim-Sulfamethoxazole? (oral, IV)

skin rash

bone marrow suppression

↑ serum creatinine

hyperkalemia

Do you give TMP-SMX for purulent or nonpurulent cellulitis (caused by MRSA)?

purulent cellulitis

Trimethoprim-Sulfamethoxazole (oral, IV) indications

uncomplicated UTI: 1st line

skin: PURULENT cellulitis (MRSA), abscess

bacterial prostatitis

pneumocystitis jirovecii pneumonia (PJP)

In which patients should you AVOID using trimethoprim-sulfamethoxazole? (oral, IV)

CI: folic acid deficiency, G6PD deficiency

relative CI: pregnancy

TMP-SMX adult dosing (oral, IV)

Trimethoprim 160mg - Sulfamethoxazole 800mg

Which antibiotics inhibit nucleic acid function or synthesis?

Fluoroquinolones

Rifampin

fluoroquinolones MOA

Bactericidal: blocks bacterial DNA synthesis causing bacterial cell death

Ciprofloxacin (oral, IV, opthalamic drops) mainly covers WHAT pathogens?

gram-negative, Pseudonomas, enteric GNRs (from the gut)

no S. pneumoniae (not a respiratory fluoroquinolone)

Levofloxacin (oral, IV, opthalamic drops) mainly covers WHAT pathogens?

Pseudonomas, typicals, atypicals, enteric GNRs

Which 2 fluoroquinolones are respiratory (cover CAP: typicals and atypicals)?

Levofloxacin and Moxifloxacin

Which 2 fluoroquinolones cover Pseudonomas

Ciprofloxacin (stronger) and Levofloxacin

Moxifloxacin (oral, IV, opthalamic drops) mainly covers WHAT pathogens?

gram positive

and anaerobes

and atypicals

no Pseudonomas

do not treat UTIs

Moxifloxacin should NOT be used to treat what?

UTIs

Ciprofloxacin should NOT be used to treat what?

respiratory

Which fluoroquinolone is preferred for GI infections?

Ciprofloxacin

What are the common adverse effects of Fluoroquinolones?

C. diff

CNS effects / peripheral neuropathy

QTc prolongation

Aortic aneurysm

tendinopathy

photosensitivity

MG exacerbation

do not combine w/ steroids

Which fluoroquinolone covers Pseudonomas best? (e.g., swimmers ear or stepping on a nail)

Ciprofloxacin

Fluoroquinolones has drug interactions with what?

metal cations!!!!

calcium

iron

magnesium

aluminum

In what populations should Fluoroquinolones be avoided?

athletes

children

elderly

homeless

pregnancy/breastfeeding

MG

using steroids

what covers typical organisms for CAP?

 Streptococcus Pneumoniae
 Haemophilus influenzae
 Moraxella catarrhalis

beta-lactams:

Amoxicillin
Augmentin
Cefdinir (3rd generation ceph)

what covers atypical organisms for CAP?

 Mycoplasma pneumoniae
 Chlamydophila pneumoniae
 Legionella

Azithromycin
Clarithromycin

Doxycycline

Ofloxacin is indicated in what infections?

pneumonia

prostatitis

STIs

uncomplicated skin

UTIs

What infections can Metronidazole (Flagyl) (PO, IV, topical) be used to treat?

MOA: DNA-damaging

Anaerobes
• C. difficile
• Bacteroides fragilis
• Gardnerella vaginalis
• Peptostreptococcus

Protozoans
• Trichomonas vaginalis
• Giardia lamblia

• Bacterial Vaginosis
• Trichomoniasis (STI)
• C. difficile diarrhea (alternate agent)
• Rosacea (topical)

• H. pylori infections (in combo with other drugs)
  • Amebiasis, intestinal (dysentery)
  • Intra-abdominal infections

Can you prescribe Doxy in pregnancy for Chlamydia?

no, use Azithromycin instead

What are the most common adverse effects of Metronidazole (Flagyl) (PO / IV / topical)?

metallic taste

Disulfiram-like reaction (when combined with alcohol)

CNS effects

What should you AVOID while taking Metronidazole (Flagyl)? (PO / IV / topical)

ALCOHOL USE

within 3 days of discontinuation

Metronidazole (Flagyl) (PO / IV / topical) inhibits the metabolism of what drug?

Warfarin is inhibited by what antibiotic?

Nitrofurantoin (Macrobid)

one indication: uncomplicated UTI

BID dosing

avoid in CKD

What are the causative organisms and pharmacologic treatments for purulent vs. nonpurulent cellulitis?

Nonpurulent cellulitis:
- Organisms: Streptococcus pyogenes (Group A Strep) and MSSA
- Treatment: Cephalexin, Dicloxacillin

Purulent cellulitis:
- Organisms: Staphylococcus aureus (MSSA, MRSA)
- Treatment: TMP-SMX, Doxycycline, or Clindamycin (I&D if abscess is present)

Erysipelas

• Superficial form of cellulitis with dermal lymphatic involvement

• usually GAS / strep pyogenes

• Tx: Amoxicillin, Cephalexin

most likely bacteria causing abscess

MRSA

Group B strep Prevention of Neonatal Sepsis treatment?

IV Penicillin G (narrower spectrum)

impetigo Tx

• cover S. aureus and S. pyogenes

• Topical: Mupirocin (Bactroban)

• oral (for widespread infection): Cephalexin or Dicloxacillin (unless MRSA suspected)

What is the most common adverse effects of Rifampin?

Hepatitis

What is Isoniazid used to treat?

SPECIFICALLY tuberculosis

Bacitracin

• prophylaxis in superficial burn wounds

• can cause allergic contact dermatitis

Neomycin (an ingredient in Neosporin) can cause

allergic contact dermatitis can be caused by ___

first line for AOE

Ciprofloxacin or Ofloxacin (topical)
± steroid

first line for AOM (with or without perforation of TM)

Amoxicillin (high-dose) or Amoxicillin-clavulanate (Augmentin)
(if AOM refractory to trx, or recurrent AOM)

first line for bacterial conjunctivitis

Ciprofloxacin or Ofloxacin

first line for CAP w/o comorbidities

Amoxicillin
or
Amoxicillin + macrolide

first line for CAP w/ comorbidities (Empiric coverage for
“Typical” and “Atypical” organisms)

Amoxicillin-clavulanate (Augmentin)
or
Cephalosporin
PLUS
Doxycycline
or
Azithromycin

first line for atypical pneumonia

Doxycycline or Azithromycin

first line for animal bites

Amoxicillin-clavulanate (Augmentin)

first line for uncomplicated UTI

Nitrofurantoin (Macrobid)
or
TMP-SMX (Bactrim)
or
Fosfomycin single dose
or
Pivmecillinam
(indicated for women only)

first line for Acute Pyelonephritis (subtype of complicated UTI: flank pain/CVA tenderness + febrile)

Ciprofloxacin or Levofloxacin
or
TMP-SMX (if susceptible)
or
2nd vs 3rd gen cephalosporins

first line for C. difficile diarrhea

Fidaxomicin (Dificid) BID x 10 days
or
Oral vancomycin QID x 10 days

abx coverage

Antibiotics with anaerobe coverage

What are the adverse effects associated with Isoniazid?

hepatitis!!!

peripheral neuropathy

CNS effects

Isoniazid inhibits the metabolism of what drugs?

seizure drugs

What 4 drugs are used to treat Tuberculosis and AE of each?

RIPE:

Rifampin or Rifapentine

• Red-orange urine/tears
• Hepatitis
• GI upset
• Drug-drug interactions

Isoniazide

• Hepatitis
• Peripheral neuropathy (Co-administer with vitamin B6)

Pyrazinamide

• Hepatitis
• Hyperuricemia

Ethambutol

• Red-green colorblindness
• Optic neuritis with blurred vision

What 3 medications are used to treat Leprosy?

Dapsone

Clofazimine

Rifampin

Dapsone can also be used to treat WHAT?

PJP!!!!

What adverse effects are associated with Dapsone?

Hemolysis!!!

methemoglobinemia

peripheral neuropathy

What patients should NOT take Dapsone?

ppl w G6PD deficiencies

Dapsone is absorbed WHERE?

GI tract!!!

↓

Reaches high doses in the skin

↓

eliminated in urine

Clofazimine can protect against WHAT?

erythema nodosum leprosum

Clofazimine can also be used to treat WHAT?

tb

non-tb mycobacteria

What should patients be advised of before taking Clofazimine?

it'll turn their skin pink and then scary black

What adverse effect frequently occurs with the use of topical bacitracin?

allergic contact dermatitis

Polysporin is a combination of what?

Bacitracin and Polymyxin B

Neosporin is a combination of what?

Bacitracin, Polymyxin B, and Neomycin

What does Bacitracin do in the nose holes?

decrease colonization of staph

Mupirocin is effective at treating what?

impetigo!!!!!!

caused by staph or strep

What does Mupirocin do to the nose holes?

irritate the mucous membranes

Bacitracin is effective against what organisms?

gram-positive!!!!

and anaerobic thangs

Mupirocin is effective against what organisms?

gram-positive aerobes!!!

Polymyxin B sulfate is effective against what organisms?

gram-negative!!!!

Polymyxin B Sulfate can cause WHAT when applied to open wounds?

neurotoxicity and nephrotoxicity

Neomycin and Gentamicin

AE: allergic contact dermatitis

treat gram negative