Antimicrobials - First Aid Flashcards
Antimicrobial Therapy
Antimicrobials:
IV Penicillin
Penicillin G
Antimicrobials:
IM Penicillin
Penicillin G
Antimicrobials:
Oral Penicillin
Penicillin V
Antimicrobials:
prototype β-lactam antibiotics
- Penicillin G (IV and IM form)
- Penicillin V (oral form)
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
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
Antimicrobials:
Adverse Effects
- hypersensitivity reactions
- direct Coombs ⊕ hemolytic anemia
- drug-induced interstitial nephritis
- Penicillin G
- Penicillin V
Antimicrobials:
Resistance
- β-lactamase cleaves the β-lactam ring
- mutations in _____-binding proteins
- Penicillin G
- Penicillin V
Penicillinase-Sensitive Penicillins
- Amoxicillin
- Ampicillin
- Aminopenicillins
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.
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
Penicillinase-Resistant Penicillins
- Dicloxacillin
- Nafcillin
- Oxacillin
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
Antipseudomonal Penicillins
- Piperacillin
- Ticarcillin
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:
Adverse Effects
- hypersensitivity reactions
Antipseudomonal Penicillins
- Piperacillin
- Ticarcillin
_____ are often added to penicillin antibiotics to protect the antibiotic from destruction by β-lactamase (penicillinase).
β-Lactamase Inhibitors
β-Lactamase Inhibitors
CAST
- Clavulanic Acid
- Avibactam
- Sulbactam
- Tazobactam
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:
- Listeria
- Atypicals (Chlamydia, Mycoplasma)
- MRSA
- Enterococci
1st Generation Cephalosporins
- Cefazolin
- Cephalexin
2nd Generation Cephalosporins
- Cefaclor
- Cefoxitin
- Cefuroxime
- Cefotetan
2nd graders wear fake fox fur to tea parties.
3rd Generation Cephalosporins
- Ceftazidime
- Cefpodoxime
- Cefotaxime
- Ceftriaxone
Taz’s tornado blows taxis and trees (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:
- Proteus mirabilis
- E. coli
- Klebsiella 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
- Enterobacter aerogenes
- Neisseria spp.
- Serratia marcescens
- Proteus mirabilis
- E. coli
- Klebsiella 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:
- Doripenem
- Imipenem
- Meropenem
- Ertapenem
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 Lack 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
- Aminoglycosides
- Tetracyclines
50S inhibitors
- Chloramphenicol
- Clindamycin
- Erythromycin (Macrolides)
- Linezolid
“Buy AT 30, CCEL (sell) at 50.”
Aminoglycosides
GNATS:
- Gentamicin
- Neomycin
- Amikacin
- Tobramycin
- Streptomycin
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
- Gentamicin
- Neomycin
- Amikacin
- Tobramycin
- Streptomycin
“Mean” (aminoglycoside) GNATS caNNOT kill anaerobes.
- Nephrotoxicity
- Neuromuscular blockade
- Ototoxicity
- Teratogen
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 Motility
- Arrhythmia
- acute Cholestatic hepatitis
- Rash
- eOsinophilia
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 Treats Marrow Poorly.