Antimicrobials: _Clinical Use_ extended-spectrum penicillin H. influenzae H. pylori E. coli Listeria monocytogenes Proteus mirabilis Salmonella Shigella Enterococci

Penicillinase-Sensitive Penicillins Amoxicillin Ampicillin Aminopenicillins Ampicillin/Amoxicillin HHELPSS kill Enterococci. H. influenzae H. pylori E. coli Listeria monocytogenes Proteus mirabilis Salmonella Shigella Enterococci

Antimicrobials: _Adverse Effects_ hypersensitivity reactions rash pseudomembranous colitis

Penicillinase-Sensitive Penicillins Amoxicillin Ampicillin Aminopenicillins

Antimicrobials: _Resistance_ Penicillinase (a type of β-lactamase) cleaves β-lactam ring

Penicillinase-Sensitive Penicillins Amoxicillin Ampicillin Aminopenicillins

Antimicrobials: _Mechanism of Action_ same as penicillin narrow spectrum bulky R group blocks access of β-lactamase to β-lactam ring

Penicillinase-Resistant Penicillins Dicloxacillin Nafcillin Oxacillin

Antimicrobials: _Clinical Use_ S. aureus (except MRSA)

Penicillinase-Resistant Penicillins Dicloxacillin Nafcillin Oxacillin “Use naf (Nafcillin) for staph.”

Antimicrobials: _Adverse Effects_ hypersensitivity reactions interstitial nephritis

Penicillinase-Resistant Penicillins Dicloxacillin Nafcillin Oxacillin

Antimicrobials: _Resistance_ MRSA has altered penicillin-binding protein target site

Penicillinase-Resistant Penicillins Dicloxacillin Nafcillin Oxacillin

Antimicrobials: _Mechanism of Action_ same as penicillin extended spectrum penicillinase sensitive use with β-lactamase inhibitors

Antipseudomonal Penicillins Piperacillin Ticarcillin

Antimicrobials: _Clinical Use_ Pseudomonas spp. Gram ⊝ Rods

Antipseudomonal Penicillins Piperacillin Ticarcillin

Antimicrobials - First Aid Flashcards by Grazielle Verzosa

Antimicrobial Therapy

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Antimicrobials:

IV Penicillin

Penicillin G

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Antimicrobials:

IM Penicillin

Penicillin G

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Antimicrobials:

Oral Penicillin

Penicillin V

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Antimicrobials:

prototype β-lactam antibiotics

Penicillin G (IV and IM form)
Penicillin V (oral form)

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Antimicrobials:

Mechanism of Action

D-Ala-D-Ala structural analog
bind _____-binding proteins (transpeptidases)
block transpeptidase cross-linking of peptidoglycan in cell wall
activate autolytic enzymes

Penicillin G
Penicillin V

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Antimicrobials:

Clinical Use

mostly used for gram ⊕ organisms (S. pneumoniae, S. pyogenes, Actinomyces)
also used for gram ⊝ cocci (N. meningitidis) and spirochetes (T. pallidum)
bactericidal for gram ⊕ cocci, gram ⊕ rods, gram ⊝ cocci, and spirochetes
β-lactamase sensitive

Penicillin G
Penicillin V

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Antimicrobials:

Adverse Effects

hypersensitivity reactions
direct Coombs ⊕ hemolytic anemia
drug-induced interstitial nephritis

Penicillin G
Penicillin V

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Antimicrobials:

Resistance

β-lactamase cleaves the β-lactam ring
mutations in _____-binding proteins

Penicillin G
Penicillin V

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Penicillinase-Sensitive Penicillins

Amoxicillin
Ampicillin
Aminopenicillins

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Antimicrobials:

Mechanism of Action

same as penicillin
wider spectrum
combine with clavulanic acid to protect against destruction by β-lactamas

Penicillinase-Sensitive Penicillins

Amoxicillin
Ampicillin
Aminopenicillins

AMinoPenicillins are AMPed-up penicillin.
AmOxicillin has greater Oral bioavailability than ampicillin.

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Antimicrobials:

Clinical Use

extended-spectrum penicillin
- H. influenzae
- H. pylori
- E. coli
- Listeria monocytogenes
- Proteus mirabilis
- Salmonella
- Shigella
- Enterococci

Penicillinase-Sensitive Penicillins

Amoxicillin
Ampicillin
Aminopenicillins

Ampicillin/Amoxicillin HHELPSS kill Enterococci.

H. influenzae
H. pylori
E. coli
Listeria monocytogenes
Proteus mirabilis
Salmonella
Shigella
Enterococci

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Antimicrobials:

Adverse Effects

hypersensitivity reactions
rash
pseudomembranous colitis

Penicillinase-Sensitive Penicillins

Amoxicillin
Ampicillin
Aminopenicillins

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Antimicrobials:

Resistance

Penicillinase (a type of β-lactamase) cleaves β-lactam ring

Penicillinase-Sensitive Penicillins

Amoxicillin
Ampicillin
Aminopenicillins

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Penicillinase-Resistant Penicillins

Dicloxacillin
Nafcillin
Oxacillin

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Antimicrobials:

Mechanism of Action

same as penicillin
narrow spectrum
bulky R group blocks access of β-lactamase to β-lactam ring

Penicillinase-Resistant Penicillins

Dicloxacillin
Nafcillin
Oxacillin

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Antimicrobials:

Clinical Use

S. aureus (except MRSA)

Penicillinase-Resistant Penicillins

Dicloxacillin
Nafcillin
Oxacillin

“Use naf (Nafcillin) for staph.”

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Antimicrobials:

Adverse Effects

hypersensitivity reactions
interstitial nephritis

Penicillinase-Resistant Penicillins

Dicloxacillin
Nafcillin
Oxacillin

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Antimicrobials:

Resistance

MRSA has altered penicillin-binding protein target site

Penicillinase-Resistant Penicillins

Dicloxacillin
Nafcillin
Oxacillin

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Antipseudomonal Penicillins

Piperacillin
Ticarcillin

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Antimicrobials:

Mechanism of Action

same as penicillin
extended spectrum
penicillinase sensitive
use with β-lactamase inhibitors

Antipseudomonal Penicillins

Piperacillin
Ticarcillin

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Antimicrobials:

Clinical Use

Pseudomonas spp.
Gram ⊝ Rods

Antipseudomonal Penicillins

Piperacillin
Ticarcillin

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Antimicrobials:

Adverse Effects

hypersensitivity reactions

Antipseudomonal Penicillins

Piperacillin
Ticarcillin

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_____ are often added to penicillin antibiotics to protect the antibiotic from destruction by β-lactamase (penicillinase).

β-Lactamase Inhibitors

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β-Lactamase Inhibitors

**CAST** * **C**lavulanic Acid * **A**vibactam * **S**ulbactam * **T**azobactam

Antimicrobials: _Mechanism of Action_ * β-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases * bactericidal

Cephalosporins

Organisms typically not covered by 1st–4th generation cephalosporins are \_\_\_\_\_.

**LAME**: * **L**isteria * **A**typicals (*Chlamydia*, *Mycoplasma*) * **M**RSA * **E**nterococci

1st Generation Cephalosporins

* Cefazolin * Cephalexin

2nd Generation Cephalosporins

* Ce**fac**lor * Ce**fox**itin * Ce**fur**oxime * Cefo**te**tan **2nd** graders wear **fake** **fox** **fur** to t**e**a parties.

3rd Generation Cephalosporins

* Cef**taz**idime * Cefpo**do**xime * Cefo**taxi**me * Cef**tri**axone **Taz**'s torna**do** blows **taxi**s and **tree**s (**3**) away.

4th Generation Cephalosporins

Cefepime

5th Generation Cephalosporins

Ceftaroline

Antimicrobials: _Clinical Use_ * Gram ⊕ Cocci * *Proteus mirabilis* * *E. coli* * *Klebsiella pneumoniae* * used prior to surgery to prevent *S. aureus* wound infections

1st Generation Cephalosporins * Cefazolin—prior to surgery, S. aureus * Cephalexin **PEcK**: * ***P**roteus mirabilis* * ***E**. **c**oli* * ***K**lebsiella pneumoniae*

Antimicrobials: _Clinical Use_ * Gram ⊕ Cocci * *H. influenzae* * *Enterobacter aerogenes* * *Neisseria* spp. * *Serratia marcescens* * *Proteus mirabilis* * *E. coli* * *Klebsiella pneumoniae*

2nd Generation Cephalosporins * Cefaclor * Cefoxitin * Cefuroxime * Cefotetan **HENS PEcK**: * ***H**. influenzae* * ***E**nterobacter aerogenes* * ***N**eisseria* spp. * ***S**erratia marcescens* * ***P**roteus mirabilis* * ***E**. **c**oli* * ***K**lebsiella pneumoniae*

Antimicrobials: _Clinical Use_ * serious gram ⊝ infections resistant to other β-lactams * can cross blood-brain barrier

3rd Generation Cephalosporins * Ceftazidime—*Pseudomonas* * Cefpodoxime * Cefotaxime * Ceftriaxone—meningitis, gonorrhea, disseminated Lyme disease

Antimicrobials: _Clinical Use_ * Gram ⊝ * ↑ activity against *Pseudomonas* and gram ⊕ organisms

4th Generation Cephalosporins * Cefepime

Antimicrobials: _Clinical Use_ * broad gram ⊕ and gram ⊝ organism coverage * *Listeria* * MRSA * *Enterococcus faecalis* * does not cover *Pseudomonas*

5th Generation Cephalosporins * Ceftaroline

Antimicrobials: _Adverse Effects_ * hypersensitivity reactions * autoimmune hemolytic anemia * disulfiram-like reaction * vitamin K deficiency * low rate of cross-reactivity even in penicillin-allergic patients * ↑ nephrotoxicity of aminoglycosides

Cephalosporins

Antimicrobials: _Resistance_ * inactivated by \_\_\_\_\_ases (a type of β-lactamase) * structural change in penicillin-binding proteins (transpeptidases)

Cephalosporins

Carbapenems

**DIME:** * **D**oripenem * **I**mipenem * **M**eropenem * **E**rtapenem **DIME** antibiotics are given when there is a **10**/10 (life-threatening) infection.

Antimicrobials: _Mechanism of Action_ * broad-spectrum * β-lactamase–resistant * always administered with Cilastatin (inhibitor of renal dehydropeptidase I) to ↓ inactivation of drug in renal tubules

Carbapenems * Imipenem With imipenem, “the kill is **lastin’** with **Cilastatin**.” Newer Carbapenems * Ertapenem (limited *Pseudomonas* coverage) * Doripenem

Antimicrobials: _Clinical Use_ * Gram ⊕ Cocci * Gram ⊝ Rods * Anaerobes * wide spectrum and significant side effects limit use to life-threatening infections or after other drugs have failed

Carbapenems * Doripenem * Imipenem * Meropenem—↓ risk of seizures, stable to dehydropeptidase I * Ertapenem

Antimicrobials: _Adverse Effects_ * GI distress * rash * CNS toxicity (seizures) at high plasma levels

Carbapenems * Doripenem * Imipenem * Meropenem * Ertapenem

Monobactams

Aztreonam

Antimicrobials: _Mechanism of Action_ * less susceptible to β-lactamases * prevents peptidoglycan cross-linking by binding to penicillin-binding protein 3 * synergistic with aminoglycosides * no cross-allergenicity with penicillins

Monobactams * Aztreonam

Antimicrobials: _Clinical Use_ * Gram ⊝ Rods * no activity against gram ⊕ rods or anaerobes * for penicillin-allergic patients and those with renal insufficiency who cannot tolerate aminoglycosides

Monobactams * Aztreonam

Antimicrobials: _Adverse Effects_ * usually nontoxic * occasional GI upset

Monobactams * Aztreonam

Antimicrobials: _Mechanism of Action_ * inhibits cell wall peptidoglycan formation by binding D-Ala-D-Ala portion of cell wall precursors * bactericidal against most bacteria (bacteriostatic against *C. difficile*) * not susceptible to β-lactamases

Vancomycin

Antimicrobials: _Clinical Use_ * Gram ⊕ * serious, multidrug-resistant organisms, including MRSA, *S. epidermidis*, sensitive *Enterococcus* species, and *Clostridium difficile* (oral dose for pseudomembranous colitis)

Vancomycin

Antimicrobials: _Adverse Effects_ * well tolerated in general * nephrotoxicity * ototoxicity * thrombophlebitis * Red Man Syndrome * diffuse flushing * largely preventable by pretreatment with antihistamines and slow infusion rate * DRESS Syndrome * drug reaction with eosinophilia and systemic symptoms

Vancomycin

Antimicrobials: _Resistance_ * occurs in bacteria (eg, *Enterococcus)* via amino acid modification of D-Ala-D-Ala to D-Ala-D-Lac

Vancomycin If you **Lac**k a **D-Ala** (dollar), you can’t ride the **van**.

Protein Synthesis Inhibitors

\_\_\_\_\_ specifically target smaller bacterial ribosome (70S, made of 30S and 50S subunits), leaving human ribosome (80S) unaffected.

Protein Synthesis Inhibitors

Protein synthesis inhibitors are all bacteriostatic, except \_\_\_\_\_.

* Aminoglycosides (bactericidal) * Linezolid (variable)

Protein Synthesis Inhibitors

30S inhibitors * **A**minoglycosides * **T**etracyclines 50S inhibitors * **C**hloramphenicol * **C**lindamycin * **E**rythromycin (Macrolides) * **L**inezolid “Buy **AT 30**, **CCEL** (sell) at **50**.”

Aminoglycosides

**GNATS:** * **G**entamicin * **N**eomycin * **A**mikacin * **T**obramycin * **S**treptomycin

Antimicrobials: _Mechanism of Action_ * bactericidal * irreversible inhibition of initiation complex through binding of the 30S subunit * can cause misreading of mRNA * also block translocation * require O₂ for uptake * ineffective against anaerobes

Aminoglycosides * Gentamicin * Neomycin * Amikacin * Tobramycin * Streptomycin

Antimicrobials: _Clinical Use_ * severe gram ⊝ rod infections * synergistic with β-lactam antibiotics * bowel surgery

Aminoglycosides * Gentamicin * Neomycin—bowel surgery * Amikacin * Tobramycin * Streptomycin

Antimicrobials: _Adverse Effects_ * nephrotoxicity * neuromuscular blockade * ototoxicity (especially when used with loop diuretics) * teratogen

Aminoglycosides * **G**entamicin * **N**eomycin * **A**mikacin * **T**obramycin * **S**treptomycin “**Mean**” (a**min**oglycoside) **GNATS** ca**NNOT** kill anaerobes. * **N**ephrotoxicity * **N**euromuscular blockade * **O**totoxicity * **T**eratogen

Antimicrobials: _Resistance_ * bacterial transferase enzymes inactivate the drug by acetylation, phosphorylation, or adenylation

Aminoglycosides * Gentamicin * Neomycin * Amikacin * Tobramycin * Streptomycin

Tetracyclines

* Tetracycline * Doxycycline * Minocycline

Antimicrobials: _Mechanism of Action_ * bacteriostatic * bind to 30S and prevent attachment of aminoacyl-tRNA * limited CNS penetration * not taken with milk (Ca²⁺), antacids (Ca²⁺ or Mg²⁺), or iron-containing preparations because divalent cations inhibit drugs’ absorption in the gut

Tetracyclines * Tetracycline * Doxycycline—fecally eliminated, can be used in patients with renal failure * Minocycline

Antimicrobials: _Clinical Use_ * *Borrelia burgdorferi* * *M. pneumoniae* * drugs’ ability to accumulate intracellularly makes them very effective against *Rickettsia* and *Chlamydia* * also used to treat acne

Tetracyclines * Tetracycline * Doxycycline—MRSA * Minocycline

Antimicrobials: _Adverse Effects_ * GI distress * discoloration of teeth and inhibition of bone growth in children * photosensitivity * contraindicated in pregnancy

Tetracyclines * Tetracycline * Doxycycline * Minocycline

Antimicrobials: _Resistance_ * ↓ uptake or ↑ efflux out of bacterial cells by plasmid-encoded transport pumps

Tetracyclines * Tetracycline * Doxycycline * Minocycline

Glycylcyclines

Tigecycline

Antimicrobials: _Mechanism of Action_ * tetracycline derivative * binds to 30S, inhibiting protein synthesis * generally bacteriostatic

Glycylcyclines * Tigecycline

Antimicrobials: _Clinical Use_ * broad-spectrum anaerobic, gram ⊝, and gram ⊕ coverage * multidrug-resistant organisms (MRSA, VRE) or infections requiring deep tissue penetration

Glycylcyclines * Tigecycline

Antimicrobials: _Adverse Effects_ * GI symptoms: nausea, vomiting

Glycylcyclines * Tigecycline

Antimicrobials: _Mechanism of Action_ * blocks peptidyltransferase at 50S ribosomal subunit * bacteriostatic

Chloramphenicol

Antimicrobials: _Clinical Use_ * meningitis (*Haemophilus influenzae*, *Neisseria meningitidis*, *Streptococcus pneumoniae*) and rickettsial diseases (eg. Rocky Mountain Spotted Fever [*Rickettsia rickettsii*]). * limited use due to toxicity but often still used in developing countries because of low cost

Chloramphenicol

Antimicrobials: _Adverse Effects_ * anemia (dose dependent) * aplastic anemia (dose independent) * gray baby syndrome (in premature infants because they lack liver UDP-glucuronosyltransferase)

Chloramphenicol

Antimicrobials: _Resistance_ * plasmid-encoded acetyltransferase inactivates the drug

Chloramphenicol

Antimicrobials: _Mechanism of Action_ * blocks peptide transfer (translocation) at 50S ribosomal subunit * bacteriostatic

Clindamycin

Antimicrobials: _Clinical Use_ * anaerobic infections (eg. *Bacteroides* spp.,*Clostridium perfringens*) in aspiration pneumonia, lung abscesses, and oral * infections * also effective against invasive group A streptococcal infection * treats anaerobic infections above the diaphragm vs. metronidazole

Clindamycin

Antimicrobials: _Adverse Effects_ * pseudomembranous colitis (*C. difficile* overgrowth) * fever * diarrhea

Clindamycin

Oxazolidinones

Linezolid

Antimicrobials: _Mechanism of Action_ * inhibit protein synthesis by binding to 50S subunit and preventing formation of the initiation complex

Oxazolidinones * Linezolid

Antimicrobials: _Clinical Use_ * Gram ⊕ * MRSA * VRE

Oxazolidinones * Linezolid

Antimicrobials: _Adverse Effects_ * bone marrow suppression (especially thrombocytopenia) * peripheral neuropathy * serotonin syndrome

Oxazolidinones * Linezolid

Antimicrobials: _Resistance_ * point mutation of ribosomal RNA

Oxazolidinones * Linezolid

Macrolides

* Azithromycin * Clarithromycin * Erythromycin

Antimicrobials: _Mechanism of Action_ * inhibit protein synthesis by blocking translocation (“macroslides”) * bind to the 23S rRNA of the 50S ribosomal subunit * bacteriostatic

Macrolides * Azithromycin * Clarithromycin * Erythromycin

Antimicrobials: _Clinical Use_ * atypical pneumonias (*Mycoplasma*, *Chlamydia*, *Legionella*) * STIs (*Chlamydia*) * Gram ⊕ Cocci (streptococcal infections in patients allergic to penicillin) * *B. pertussis*

Macrolides * Azithromycin * Clarithromycin * Erythromycin

Antimicrobials: _Adverse Effects_ * gastrointestinal motility issues * arrhythmia caused by prolonged QT interval * acute cholestatic hepatitis * rash * eosinophilia * increases serum concentration of theophylline and oral anticoagulants

Macrolides * Azithromycin * Clarithromycin—inhibit cytochrome P-450 * Erythromycin—inhibit cytochrome P-450 **MACRO**: * gastrointestinal **M**otility * **A**rrhythmia * acute **C**holestatic hepatitis * **R**ash * e**O**sinophilia

Antimicrobials: _Resistance_ * methylation of 23S rRNA-binding site prevents binding of drug

Macrolides * Azithromycin * Clarithromycin * Erythromycin

Polymyxins

* Colistin (Polymyxin E) * Polymyxin B

Antimicrobials: _Mechanism of Action_ * cation polypeptides that bind to phospholipids on cell membrane of gram ⊝ bacteria * disrupt cell membrane integrity → leakage of cellular components → cell death

Polymyxins * Colistin (Polymyxin E) * Polymyxin B

Antimicrobials: _Clinical Use_ * salvage therapy for multidrug-resistant gram ⊝ bacteria (eg. *P. aeruginosa*, *E. coli*, *K. pneumoniae*)

Polymyxins * Colistin (Polymyxin E) * Polymyxin B—component of a triple antibiotic ointment used for superficial skin infections

Antimicrobials: _Adverse Effects_ * nephrotoxicity * neurotoxicity (eg. slurred speech, weakness, paresthesias) * respiratory failure

Polymyxins * Colistin (Polymyxin E) * Polymyxin B

Sulfonamides

* Sulfamethoxazole (SMX) * Sulfisoxazole * Sulfadiazine

Antimicrobials: _Mechanism of Action_ * inhibit dihydropteroate synthase, thus inhibiting folate synthesis * bacteriostatic (bactericidal when combined with trimethoprim)

Sulfonamides * Sulfamethoxazole (SMX) * Sulfisoxazole * Sulfadiazine

Antimicrobials: _Clinical Use_ * Gram ⊕ * Gram ⊝ * *Nocardia*

Sulfonamides * Sulfamethoxazole (SMX) * Sulfisoxazole * Sulfadiazine \*TMP-SMX for simple UTI

Antimicrobials: _Adverse Effects_ * hypersensitivity reactions * hemolysis if G6PD deficient * nephrotoxicity (tubulointerstitial nephritis) * photosensitivity * Stevens-Johnson Syndrome * kernicterus in infants * displace other drugs from albumin (eg. warfarin)

Sulfonamides * Sulfamethoxazole (SMX) * Sulfisoxazole * Sulfadiazine

Antimicrobials: _Resistance_ * altered enzyme (bacterial dihydropteroate synthase), ↓ uptake, or ↑ PABA synthesis

Sulfonamides * Sulfamethoxazole (SMX) * Sulfisoxazole * Sulfadiazine

Antimicrobials: _Mechanism of Action_ * similar to sulfonamides * structurally distinct agent

Dapsone

Antimicrobials: _Clinical Use_ * Leprosy (lepromatous and tuberculoid) * *Pneumocystis jirovecii* prophylaxis

Dapsone

Antimicrobials: _Adverse Effects_ * hemolysis if G6PD deficient * methemoglobinemia

Dapsone

Antimicrobials: _Mechanism of Action_ * inhibits bacterial dihydrofolate reductase * bacteriostatic

Trimethoprim

Antimicrobials: _Clinical Use_ * used in combination with sulfonamides * causing sequential block of folate synthesis * combination used for UTIs * *Shigella* * *Salmonella* * *Pneumocystis jirovecii* pneumonia treatment and prophylaxis * *Toxoplasmosis* prophylaxis

Trimethoprim

Antimicrobials: _Adverse Effects_ * megaloblastic anemia * leukopenia * granulocytopenia * may be avoided with coadministration of folinic acid

Trimethoprim **TMP** **T**reats **M**arrow **P**oorly.

Fluoroquinolones

* Ciprofloxacin * Enoxacin * Norfloxacin * Ofloxacin * Gemifloxacin * Levofloxacin * Moxifloxacin

Respiratory Fluoroquinolones

* Gemifloxacin * Levofloxacin * Moxifloxacin

Antimicrobials: _Mechanism of Action_ * inhibit prokaryotic enzymes topoisomerase II (DNA gyrase) and topoisomerase IV * bactericidal * must not be taken with antacids

Fluoroquinolones

Antimicrobials: _Clinical Use_ * Gram ⊝ Rods of urinary and GI tracts (including *Pseudomonas*) * some gram ⊕ organisms * otitis externa

Fluoroquinolones

Antimicrobials: _Adverse Effects_ * GI upset * superinfections * skin rashes * headache * dizziness * less commonly, can cause leg cramps and myalgias * contraindicated in pregnant women, nursing mothers, and children \< 18 years old due to possible damage to cartilage * some may prolong QT interval * tendonitis or tendon rupture in people \> 60 years old and in patients taking prednisone

Fluoroquinolones * Ciprofloxacin —inhibits cytochrome P-450 Fluoroquino**lones** hurt attachments to your **bones**.

Antimicrobials: _Resistance_ * chromosome-encoded mutation in DNA gyrase, plasmid-mediated resistance, efflux pumps

Fluoroquinolones

Antimicrobials: _Mechanism of Action_ * lipopeptide that disrupts cell membranes of gram ⊕ cocci by creating transmembrane channels

Daptomycin

Antimicrobials: _Clinical Use_ * *S. aureus skin* infections (especially MRSA) * bacteremia * endocarditis * VRE * not used for pneumonia (avidly binds to and is inactivated by surfactant)

Daptomycin

Antimicrobials: _Adverse Effects_ * myopathy * rhabdomyolysis

Daptomycin

Antimicrobials: _Mechanism of Action_ * forms toxic free radical metabolites in the bacterial cell that damage DNA * bactericidal * antiprotozoal

Metronidazole

Antimicrobials: _Clinical Use_ * treats *Giardia*, *Entamoeba*, *Trichomonas*, *Gardnerella vaginalis*, Anaerobes (*Bacteroides*, *C. difficile*) * can be used in place of amoxicillin in *H. pylori* “triple therapy” in case of penicillin allergy * treats anaerobic infection below the diaphragm vs. clindamycin (anaerobic infections above diaphragm)

Metronidazole **GET GAP** on the **Metro** with metronidazole! * **G**iardia * **E**ntamoeba * **T**richomonas * **G**ardnerella vaginalis * **A**naerobes (Bacteroides, C. difficile) * H. **P**ylori

Antimicrobials: _Adverse Effects_ * Disulfiram-like reaction (severe flushing, tachycardia, hypotension) with alcohol * headache, * metallic taste

Metronidazole

Antimycobacterial Drugs: *M. tuberculosis* Prophylaxis

Isoniazid

Antimycobacterial Drugs: *M. tuberculosis* Treatment

**RIPE** for Treatment: * **R**ifampin * **I**soniazid * **P**yrazinamide * **E**thambutol

Antimycobacterial Drugs: *M. avium–intracellulare* Prophylaxis

* Azithromycin * Rifabutin

Antimycobacterial Drugs: *M. avium–intracellulare* Treatment

* Azithromycin or Clarithromycin + Ethambutol * can add Rifabutin or Ciprofloxacin \*More drug resistant than *M. tuberculosis*

Antimycobacterial Drugs: *M. leprae* Prophylaxis

N/A

Antimycobacterial Drugs: *M. leprae* Treatment

* Tuberculoid * long-term treatment * Dapsone * Rifampin * Lepromatous * add Clofazimine

Mycobacterial Cell

Rifamycins

* Rifampin * Rifabutin

Antimicrobials: _Adverse Effects_ inhibit DNA-dependent RNA polymerase

Rifamycins * Rifampin * Rifabutin Rifampin’s **4 R**’s: * **R**NA polymerase inhibitor * **R**amps up microsomal cytochrome P-450 * **R**ed/orange body fluids * **R**apid resistance if used alone

Antimicrobials: _Clinical Use_ * *Mycobacterium tuberculosis* * delay resistance to Dapsone when used for leprosy * used for meningococcal prophylaxis and chemoprophylaxis in contacts of children with *H. influenzae* type b

Rifamycins * Rifampin * Rifabutin

Antimicrobials: _Adverse Effects_ * minor hepatotoxicity and drug interactions (↑ cytochrome P-450) * orange body fluids (nonhazardous side effect)

Rifamycins * Rifampin * Rifabutin—favored in patients with HIV infection due to less cytochrome P-450 stimulation **Rifampin**’s **4 R**’s: * **R**NA polymerase inhibitor * **R**amps up microsomal cytochrome P-450 * **R**ed/orange body fluids * **R**apid resistance if used alone **R**if**amp**in **ramp**s up cytochrome P-450, **but** rifa**but**in does not.

Antimicrobials: _Resistance_ * mutations reduce drug binding to RNA polymerase * monotherapy rapidly leads to resistance

Rifamycins * Rifampin * Rifabutin **Rifampin**’s **4 R**’s: * **R**NA polymerase inhibitor * **R**amps up microsomal cytochrome P-450 * **R**ed/orange body fluids * **R**apid resistance if used alone

Antimicrobials: _Mechanism of Action_ * ↓ synthesis of mycolic acids * bacterial catalase-peroxidase (encoded by KatG) needed to convert INH to active metabolite

Isoniazid

Antimicrobials: _Clinical Use_ * *Mycobacterium tuberculosis* * the only agent used as solo prophylaxis against TB * also used as monotherapy for latent TB * different half-lives in fast vs. slow acetylators

Isoniazid

Antimicrobials: _Adverse Effects_ * hepatotoxicity * P-450 inhibition * drug-induced SLE * anion gap metabolic acidosis * vitamin B6 deficiency (peripheral neuropathy, sideroblastic anemia) * administer with Pyridoxine (B6)

Isoniazid **INH** **I**njures **N**eurons and **H**epatocytes.

Antimicrobials: _Resistance_ * mutations leading to underexpression of KatG

Isoniazid

Antimicrobials: _Mechanism of Action_ * uncertain * a prodrug that is converted to the active compound Pyrazinoic acid * works best at acidic pH (eg. in host phagolysosomes)

Pyrazinamide

Antimicrobials: _Adverse Effects_ * hyperuricemia * hepatotoxicity

Pyrazinamide

Antimicrobials: _Mechanism of Action_ * ↓ carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltransferase

Ethambutol

Antimicrobials: _Adverse Effects_ * optic neuropathy (red-green color blindness)

Ethambutol **Eye**thambutol

Antimicrobials: _Mechanism of Action_ * interferes with 30S component of ribosome

Streptomycin

Antimicrobials: _Adverse Effects_ * tinnitus * vertigo * ataxia * nephrotoxicity

Streptomycin

Antimicrobials: _Clinical Use_ * *Mycobacterium tuberculosis*

* Pyrazinamide * Ethambutol * Streptomycin (2nd line)

Antimicrobial Prophylaxis: high risk for endocarditis and undergoing surgical or dental procedures

Amoxicillin

Antimicrobial Prophylaxis: exposure to gonorrhea

Ceftriaxone

Antimicrobial Prophylaxis: history of recurrent UTIs

TMP-SMX

Antimicrobial Prophylaxis: exposure to meningococcal infection

* Ceftriaxone * Ciprofloxacin * Rifampin

Antimicrobial Prophylaxis: pregnant woman carrying group B strep

* Penicillin G * Ampicillin

Antimicrobial Prophylaxis: prevention of gonococcal conjunctivitis in newborn

Erythromycin eye ointment

Antimicrobial Prophylaxis: prevention of postsurgical infection due to *S. aureus*

Cefazolin

Antimicrobial Prophylaxis: prophylaxis of strep pharyngitis in child with prior rheumatic fever

* Benzathine Penicillin G * Oral Penicillin V

Antimicrobial Prophylaxis: exposure to syphilis

Benzathine Penicillin G

Prophylaxis in HIV patients: * CD4 \< 200 cells/mm³ * *Pneumocystis* pneumonia

TMP-SMX

Prophylaxis in HIV patients: * CD4 \< 100 cells/mm³ * *Pneumocystis* pneumonia * *Toxoplasmosis*

TMP-SMX

Prophylaxis in HIV patients: * CD4 \< 50 cells/mm³ * *Mycobacterium avium* Complex

* Azithromycin * Clarithromycin

Treatment of Highly Resistant Bacteria: MRSA

* Vancomycin * Daptomycin * Linezolid * Tigecycline * Ceftaroline * Doxycycline

Treatment of Highly Resistant Bacteria: VRE

* Linezolid * Streptogramins (Quinupristin, Dalfopristin)

Treatment of Highly Resistant Bacteria: Multidrug-Resistant *P. aeruginosa*

* Polymyxin B * Polymyxin E (Colistin)

Treatment of Highly Resistant Bacteria: Multidrug-Resistant *Acinetobacter baumannii*

* Polymyxin B * Polymyxin E (Colistin)

Antifungal Therapy

Antimicrobials: _Mechanism of Action_ * binds ergosterol (unique to fungi) * forms membrane pores that allow leakage of electrolytes

Amphotericin B Ampho**ter**icin “**tear**s” holes in the fungal membrane by forming pores.

Antimicrobials: _Clinical Use_ * serious, systemic mycoses * *Cryptococcus* (amphotericin B with/without flucytosine for cryptococcal meningitis) * *Blastomyces* * *Coccidioides* * *Histoplasma* * *Candida* * *Mucor* * intrathecally for fungal meningitis * supplement K⁺ and Mg²⁺ because of altered renal tubule permeability

Amphotericin B

Antimicrobials: _Adverse Effects_ * fever/chills (“shake and bake”) * hypotension * nephrotoxicity * arrhythmias * anemia * IV phlebitis * hydration ↓ nephrotoxicity * liposomal form ↓ toxicity

Amphotericin B

Antimicrobials: _Mechanism of Action_ * same as Amphotericin B * topical use only as too toxic for systemic use

Nystatin

Antimicrobials: _Clinical Use_ * “swish and swallow” for oral candidiasis (thrush) * topical for diaper rash or vaginal candidiasis

Nystatin

Antimicrobials: _Mechanism of Action_ * inhibits DNA and RNA biosynthesis by conversion to 5-fluorouracil by cytosine deaminase

Flucytosine

Antimicrobials: _Clinical Use_ * systemic fungal infections (especially meningitis caused by *Cryptococcus*) in combination with amphotericin B

Flucytosine

Antimicrobials: _Adverse Effects_ * bone marrow suppression

Flucytosine

Azoles

* Clotrimazole * Fluconazole * Isavuconazole * Itraconazole * Ketoconazole * Miconazole * Voriconazole

Antimicrobials: _Mechanism of Action_ * inhibit fungal sterol (ergosterol) synthesis by inhibiting the cytochrome P-450 enzyme that converts lanosterol to ergosterol

Azoles

Antimicrobials: _Clinical Use_ * local and less serious systemic mycoses

Azoles

Antimicrobials: _Clinical Use_ * for chronic suppression of cryptococcal meningitis in AIDS patients and candidal infections of all types

Fluconazole

Antimicrobials: _Clinical Use_ * *Blastomyces* * *Coccidioides* * *Histoplasma*

Itraconazole

Antimicrobials: _Clinical Use_ * topical fungal infections

* Clotrimazole * Miconazole

Antimicrobials: _Clinical Use_ * *Aspergillus* * *Candida*

Voriconazole

Antimicrobials: _Clinical Use_ * *Aspergillus* * *Mucor*

Isavuconazole

Antimicrobials: _Adverse Effects_ * testosterone synthesis inhibition (gynecomastia) * liver dysfunction (inhibits cytochrome P-450)

Azoles Ketoconazole—gynecomastia

Antimicrobials: _Mechanism of Action_ * inhibits the fungal enzyme squalene epoxidase

Terbinafine

Antimicrobials: _Clinical Use_ * dermatophytoses (especially onychomycosis—fungal infection of finger or toe nails)

Terbinafine

Antimicrobials: _Adverse Effects_ * GI upset * headaches * hepatotoxicity * taste disturbance

Terbinafine

Echinocandins

* Anidulafungin * Caspofungin * Micafungin

Antimicrobials: Mechanism of Action * inhibit cell wall synthesis by inhibiting synthesis of β-glucan

Echinocandins * Anidulafungin * Caspofungin * Micafungin

Antimicrobials: _Clinical Use_ * invasive aspergillosis * *Candida*

Echinocandins * Anidulafungin * Caspofungin * Micafungin

Antimicrobials: _Adverse Effects_ * GI upset * flushing (by histamine release)

Echinocandins * Anidulafungin * Caspofungin * Micafungin

Antimicrobials: _Mechanism of Action_ * interferes with microtubule function * disrupts mitosis * deposits in keratin-containing tissues (eg. nails)

Griseofulvin

Antimicrobials: _Clinical Use_ * oral treatment of superficial infections * inhibits growth of dermatophytes (tinea, ringworm)

Griseofulvin

Antimicrobials: _Adverse Effects_ * teratogenic * carcinogenic * confusion * headaches * disulfiram-like reaction * ↑ cytochrome P-450 and warfarin metabolism

Griseofulvin

Antiprotozoal Therapy: Toxoplasmosis

Pyrimethamine

Antiprotozoal Therapy: ## Footnote *Trypanosoma brucei*

* Suramin * Melarsoprol

Antiprotozoal Therapy: Trypanosoma cruzi

Nifurtimox

Antiprotozoal Therapy: Leishmaniasis

Sodium Stibogluconate

Anti-Mite/Louse Therapy

* Permethrin * inhibits Na+ channel deactivation → neuronal membrane depolarization) * Malathion * acetylcholinesterase inhibitor * Lindane * blocks GABA channels → neurotoxicity \*used to treat scabies (*Sarcoptes scabiei*) and lice (*Pediculus* and *Pthirus*) Treat **PML** (**P**esty **M**ites and **L**ice) with **PML** (**P**ermethrin, **M**alathion, **L**indane), because they **NAG** you (**N**a, **A**ChE, **G**ABA blockade).

Antimicrobials: _Mechanism of Action_ * blocks detoxification of heme into hemozoin * heme accumulates and is toxic to plasmodia

Chloroquine

Antimicrobials: _Clinical Use_ * treatment of plasmodial species other than *P. falciparum* (frequency of resistance is too high) * resistance due to membrane pump that ↓ intracellular concentration of drug

Chloroquine

Antimicrobials: _Adverse Effects_ * retinopathy * pruritus (especially in dark-skinned individuals)

Chloroquine

Antimicrobials: _Clinical Use_ * *P. falciparum*

* Artemether/Lumefantrine * Atovaquone/Proguanil

Antimicrobials: _Clinical Use_ * life-threatening malaria

* Quinidine—US * Quinine * Artesunate

Antihelminthic Therapy

Helminths get **PIMP’D**. * **P**yrantel pamoate * **I**vermectin * **M**ebendazole (microtubule inhibitor) * **P**raziquantel * **D**iethylcarbamazine.

Antiviral Therapy

Antimicrobials: _Mechanism of Action_ * inhibit influenza neuraminidase → ↓ release of progeny virus

* Oseltamivir * Zanamivir

Antimicrobials: _Clinical Use_ * treatment and prevention of both influenza A and B * beginning therapy within 48 hours of symptom onset may shorten duration of illness

* Oseltamivir * Zanamivir

Antimicrobials: _Mechanism of Action_ * guanosine analogs * monophosphorylated by HSV/VZV thymidine kinase and not phosphorylated in uninfected cells → few adverse effects * triphosphate formed by cellular enzymes * preferentially inhibit viral DNA polymerase by chain termination

* Acyclovir * Famciclovir * Valacyclovir

Antimicrobials: _Clinical Use_ * HSV and VZV * weak activity against EBV * no activity against CMV * used for HSV-induced mucocutaneous and genital lesions as well as for encephalitis * prophylaxis in immunocompromised patients * no effect on latent forms of HSV and VZV

* Acyclovir * Famciclovir—herpes zoster * Valacyclovir—prodrug of acyclovir, better oral bioavailability

Antimicrobials: _Adverse Effects_ * obstructive crystalline nephropathy and acute renal failure if not adequately hydrated

* Acyclovir * Famciclovir * Valacyclovir

Antimicrobials: _Resistance_ * mutated viral thymidine kinase

* Acyclovir * Famciclovir * Valacyclovir

Antimicrobials: _Mechanism of Action_ * 5′-monophosphate formed by a CMV viral kinase * Guanosine analog * triphosphate formed by cellular kinases * preferentially inhibits viral DNA polymerase

Ganciclovir

Antimicrobials: _Clinical Use_ * CMV * immunocompromised patients

Ganciclovir \*Valganciclovir—prodrug of ganciclovir, better oral bioavailability

Antimicrobials: _Adverse Effects_ * bone marrow suppression (leukopenia, neutropenia, thrombocytopenia) * renal toxicity * more toxic to host enzymes than acyclovir

Ganciclovir

Antimicrobials: _Resistance_ * mutated viral kinase

Ganciclovir

Antimicrobials: _Mechanism of Action_ * Pyrofosphate analog * viral DNA/RNA polymerase inhibitor and HIV reverse transcriptase inhibitor * binds to pyrophosphate-binding site of enzyme * does not require any kinase activation

Foscarnet **Fos**carnet = pyro**fos**phate analog

Antimicrobials: _Clinical Use_ * CMV retinitis in immunocompromised patients when Ganciclovir fails * Acyclovir-resistant HSV

Foscarnet

Antimicrobials: _Adverse Effects_ * nephrotoxicity * electrolyte abnormalities (hypo- or hypercalcemia, hypo- or hyperphosphatemia, hypokalemia, hypomagnesemia) can lead to seizures

Foscarnet

Antimicrobials: _Resistance_ * mutated DNA polymerase

Foscarnet

Antimicrobials: _Mechanism of Action_ * preferentially inhibits viral DNA polymerase * does not require phosphorylation by viral kinase

Cidofovir

Antimicrobials: _Clinical Use_ * CMV retinitis in immunocompromised patients * Acyclovir-resistant HSV * long half-life

Cidofovir

Antimicrobials: _Adverse Effects_ * nephrotoxicity (coadminister with probenecid and IV saline to ↓ toxicity)

Cidofovir

HIV Therapy

Highly Active Antiretroviral Therapy (HAART) \*often initiated at the time of HIV diagnosis

Strongest Indication for HAART

* low CD4+ cell counts (\< 500 cells/mm³) * high viral load

Highly Active Antiretroviral Therapy (HAART) regimen consists of \_\_\_\_\_.

3 drugs to prevent resistance * 2 NRTIs * an integrase inhibitor

Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

* Abacavir (ABC) * Didanosine (ddI) * Emtricitabine (FTC) * Lamivudine (3TC) * Stavudine (d4T) * Tenofovir (TDF) * Zidovudine (ZDV, formerly AZT)

HIV Therapy: * competitively inhibit nucleotide binding to reverse transcriptase and terminate the DNA chain (lack a 3′ OH group) * need to be phosphorylated to be active

Nucleoside Reverse Transcriptase Inhibitors (NRTIs) **T**enofovir is a nucleo**T**ide; the others are nucleosides.

HIV Therapy: can be used for general prophylaxis and during pregnancy to ↓ risk of fetal transmission

Zidovudine (ZDV, formerly AZT)

HIV Therapy: * bone marrow suppression (can be reversed with granulocyte colony-stimulating factor [G-CSF] and erythropoietin) * peripheral neuropathy * lactic acidosis (nucleosides) * anemia (ZDV) * pancreatitis (Didanosine)

Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

HIV Therapy: contraindicated if patient has HLA-B\*5701 mutation due to ↑ risk of hypersensitivit

Abacavir

Non-Nucleoside Reverse-Transcriptase Inhibitors (NNRTIs)

* Delavirdine * Efavirenz * Nevirapine

HIV Therapy: * bind to reverse transcriptase at site different from NRTIs * do not require phosphorylation to be active or compete with nucleotides * rash and hepatotoxicity are common

Non-Nucleoside Reverse-Transcriptase Inhibitors (NNRTIs)

HIV Therapy: vivid dreams and CNS symptoms are commo

Efavirenz

HIV Therapy: NNRTIs contraindicated in pregnancy

* Delavirdine * Efavirenz

Protease Inhibitors

* Atazanavir * Darunavir * Fosamprenavir * Indinavir * Lopinavir * Ritonavir * Saquinavir **Navir** (never) **tease** a pro**tease**.

HIV Therapy: * assembly of virions depends on HIV-1 protease (pol gene), which cleaves the polypeptide products of HIV mRNA into their functional parts * prevent maturation of new viruses * hyperglycemia, GI intolerance (nausea, diarrhea), lipodystrophy (Cushing-like syndrome)

Protease Inhibitors

HIV Therapy: can “boost” other drug concentrations by inhibiting cytochrome P-450

Ritonavir

HIV Therapy: * nephropathy * hematuria * thrombocytopenia

Indinavir

HIV Therapy: * potent CYP/UGT inducer * reduces protease inhibitor concentrations

Rifampin \*use rifabutin instead

Integrase Inhibitors

* Dolutegravir * Elvitegravir * Raltegravir

HIV Therapy: * inhibits HIV genome integration into host cell chromosome by reversibly inhibiting HIV integrase * ↑ creatine kinase

Integrase Inhibitors

Fusion Inhibitors

* Enfuvirtide * Maraviroc

HIV Therapy: * binds gp41, inhibiting viral entry * skin reaction at injection sites

Enfuvirtide En**fu**virtide inhibits **fu**sion.

HIV Therapy: * binds CCR-5 on surface of T cells/monocytes * inhibits interaction with gp120

Maraviroc Maravir**oc** inhibits d**oc**king.

Antimicrobials: _Mechanism of Action_ * glycoproteins normally synthesized by virus-infected cells, exhibiting a wide range of antiviral and antitumoral properties

Interferons

Antimicrobials: _Clinical Use_ * chronic HBV and HVC * Kaposi sarcoma * hairy cell leukemia * condyloma acuminatum * renal cell carcinoma * malignant melanoma * multiple sclerosis * chronic granulomatous disease

Interferons

Antimicrobials: _Adverse Effects_ * flu-like symptoms * depression * neutropenia * myopathy

Interferons

Antimicrobials: * Hepatitis C * viral phosphoprotein (NS5A) inhibitor * NS5A plays important role in replication

Ledipasvir

Antimicrobials: * Hepatitis C * inhibits synthesis of guanine nucleotides by competitively inhibiting inosine monophosphate dehydrogenase * hemolytic anemia * severe teratogen

Ribavirin

Antimicrobials: * Hepatitis C * HCV protease (NS3/4A) * prevents viral replication * photosensitivity reactions * rash

Simeprevir

Antimicrobials: * Hepatitis C * inhibits HCV RNA-dependent RNA polymerase (NS5B) acting as a chain terminator * fatigue * headache * nausea

Sofosbuvir

\_\_\_\_\_ is the reduction of pathogenic organism counts to safe levels.

Disinfection

\_\_\_\_\_ the inactivation of all microbes including spores.

Sterilization

Disinfection and Sterilization: * pressurized steam at \> 120°C * sporicidal * may not reliably inactivate prions

Autoclave

Disinfection and Sterilization: * denature proteins and disrupt cell membranes * not sporicidal

* Alcohols * Chlorhexidine

Disinfection and Sterilization: * oxidizes and denatures proteins * sporicidal

Chlorine

Disinfection and Sterilization: * free radical oxidation * sporicidal

Hydrogen Peroxide

Disinfection and Sterilization: * halogenation of DNA, RNA, and proteins * may be sporicidal

* Iodine * Iodophors

Disinfection and Sterilization: * impair permeability of cell membranes * not sporicidal

Quaternary Amines

Antimicrobials to Avoid in Pregnancy

**T**ake **R**eally **G**ood **C**are to keep **C**hildren **SAF**e. * **T**etracyclines * **R**ibavirin * **G**riseofulvin * **C**hloramphenicol * **C**larithromycin * **S**ulfonamides * **A**minoglycosides * **F**luoroquinolones

Antimicrobials to Avoid in Pregnancy: * discolored teeth * inhibition of bone growth

Tetracyclines

Antimicrobials to Avoid in Pregnancy: teratogenic

* Ribavirin * Griseofulvin

Antimicrobials to Avoid in Pregnancy: Gray Baby Syndrome

Chloramphenicol

Antimicrobials to Avoid in Pregnancy: embryotoxic

Clarithromycin

Antimicrobials to Avoid in Pregnancy: kernicterus

Sulfonamides

Antimicrobials to Avoid in Pregnancy: ototoxicity

Aminoglycosides

Antimicrobials to Avoid in Pregnancy: cartilage damage

Fluoroquinolones

Antimicrobials - First Aid Flashcards

(254 cards)