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123 Cards in this Set

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Staph aureus (MRSA) - Skin Infections
Trimethoprim/Sulfamethoxazole (oral)
Staph aureus (MRSA) - Bacteremia
Vancomycin (IV)
Staph aureus (MSSA) - Skin infections
Cephalexin (oral)
Staph aureus (MSSA) - Bacteremia
Nafcillin (IV)
Streptococcus pyogenes
Penicillin
Mycobacterium tuberculosis (prophylaxis)
Isoniazid
Mycobacterium tuberculosis (Active disease)
Isoniazid + Rifampin + Pyrazinamide + Ethambutol
Acute Otitis Media (Strep pneumo, Haemophilus influenzae)
Amoxicillin
Chronic/recurrent Otitis Media (Strep pneumo, Haemophilus influenzae)
Amoxicillin/Clavulanate
Sinunitis
Amoxicillin/Clavulanate
Community acquired acute cystitis (E. coli)
nitrofurantoin or trimethoprim/sulfamethoxazole
Neisseria gonorrhoeae
ceftriaxone + (azithromycin or doxycycline) [to cover Chlamydia]
Chlamydia trachomatis
(azithromycin or doxycycline) + ceftriaxone [to cover N. gonorrhoeae]
Treponema pallidum
Penicillin
Borrelia burgdorferi
Beta lactam or doxycycline
Rickettsial diseases
Doxycycline
Acquired Abx Resistance (AAR) - Staph aureus
methicilin resistance (MRSA) and vancomycin resistance (VISA, VRSA)
AAR: Strep pneumo
penicillin resistance, multiple resistance
AAR: Enterococcus faecium
Vancomycin resistance (VRE) and multiple resistane
AAR: Mycobacterium tuberculosis
multiple resistance
AAR: Pseudomonas aeruginosa, Acinetobacter baumanii
rapid development of multiple resistance, carbapanemases.
AAR: Enteric bacteria - Klebsiella, Enterobacter
Extended spectrum beta-lactamases, carbpenemases
Selective toxicity
Microorganism is inhibited or killed without harm to the host cells
Therapeutic Index
Measure of the difference in effective dose relative to toxic dose
Antimicrobial spectrum
Range of organisms that are inhibited by a given agent
Most prescribed abx
1) Beta lactam (cell wall synthesis
2) Macrolides (protein synthesis)
3) Fluoroquinolones (DNA synthesis)
*Vancomycin (function)
Binds to peptides, prevent incorporation into chain
Bacitracin (function)
inhibits recycling of lipid carrier
Beta lactam types
Penicillins, Cephalosporins, Carbapenems, Monobactams, B-lactamase inhibitors
Beta-lactam mech of action
Act as structural analog of D-alanyl D-alanine. Prevent peptide-xlinking of peptidogylcan
Beta lactam mech. of resistance
Production of B-lactamase (acquired or inducible), production of altered penicillin binding proteins, impermeability and/or efflux (Pseudomonas)
Beta lactam toxicity
Hypersensitivity: very safe in non sensitive individuals
Penicillin binding proteins (PBPs)
Enzymes (carboxypeptidases, transpeptidases, endopeptidases) which normally function in synthesis and turnover of peptido. Binding to beta-lactam abx disrupts their normal function
B-lactam: Penicillins (types)
Natural penicillins (gram + organisms), Penicillinase Resistant Penicillins (S. aureus - MRSA), Aminopenicillins (gram neg enteric), Penicillins against Pseudomonas, Penicillins combined with B-lactamase inhibitors
B-lactam: Cephalosporins (5th gen)
Effective against MRSA and penicillin resistant Strep pneumo.
B-lactam: Carbapenems (examples)
Imipenem, meropenem, ertapenem, doripenem
B-lactam: Carbapenems
broadest spectrum of all b-lactam abx, greatest resistance to bacterial b-lactamases, abx of last resort for serious gram neg infections such as extended spectrum beta-lactamase producing enteric bacteria
Acquired resistance to B-lactam abx
Production of penicillinase/beta lactamases, altered PBPs, and decreased permeability or active efflux
MRSA (methicillin-resistant S. aureus)
Staph aureus that have acquired resistance to beta-lactam class of abx through acquisition of a gene (mecA) encoding altered penicillin binding protein
HA-MRSA: healthcare associated
1) acquired in hospital or other health care settings
2) bacteremia, sepsis, pneumonia, surgical site infection
3) strains likely to be resistant to other abx as well (tetracycline, macrolides, clindamycin)
CA-MRSA: community acquired (REPLACING HA-MRSA IN HOSPITALS)
1) infections in persons who have not been in a health care facility
2) skin infections most common
3) strains tend to be more virulent
4) strains tend to be more sensitive to other abx but trend is toward acquisition of additional resistance
Glycopeptide abx - Vancomycin, telavancin
used against multiple resistant staph (MRSA), enterococci, abx-associated colitis
Vancomycin/Telavancin Administration
IV, oral for abx-associated colitis
Vancomycin/Telavancin Mech of action
Binds to D-alanyl D-alanine of peptido subunit, prevents incorporation of subunit into glycan chain, prevents peptide x-linking
Vancomycin/Telavancin Mech of Resistance
acquisition of genes encoding incorporation of D-lactate or serine instead of D-alanine at te terminal position of the pentapeptide - clinically imp in Enterococcus faecium

intermediate resistance (eg. staph aureus: VISA): thickening of peptido
Telavancin effective against...
VISA and some VRE
Vancomycin/Telavancin Toxicity
Phlebitis at site of infusion, neurotoxicity (hearing loss)

Telavancin: renal toxicity
Newer abx for MRSA and serious gram positive bacterial infections
Telavancin, Daptomycin, Linezolid
Daptomycin (Cubicin)
New abx class: cyclic lipopeptide

IV administration


Used for skin and subcutaneous infections caused by Gram-positive organisms (Staphylococcus including MRSA, Streptococcus, Entercoccus),
Staphylococcus aureus bacteremia, endocarditis

Poor penetration in lungs, inactivated by surfactant
Daptomycin (Cubicin) Mech of Action
Membrane depolarization, K+ efflux, rapid cell death
Daptomycin (Cubicin) Mech of Resistance
Thickening of peptidoglycan (Daptomycin-resistant strains also less sensitive to vancomycin (VISA))

Altered membrane lipid with increased positive charge

Mutations in transcriptional regulators and enzymes involved in phospholipid metabolism (E. faecium)
Daptomycin (Cubicin) Toxicities (mild & reversible)
Muscle weakness and pain (increased creatinine phosphokinase levels)

Gastrointestinal disturbances
Oxazolidinones – Linezolid (Zyvox)
Broadest spectrum drug available against Gram-positives:
useful against MRSA, penicillin-resistant Streptococcus pneumoniae, and vancomycin-resistant enterococci (VRE)
Oxazolidinones – Linezolid (Zyvox) Mech of action
Inhibits protein synthesis by binding to 50S subunit, preventing formation of translation initiation complex
Oxazolidinones – Linezolid (Zyvox) Mech of resistance
Mutations in 23S rRNA (rare)
Methylation of 23S rRNA (gene encoded on mobile genetic element)
Oxazolidinones – Linezolid (Zyvox) Toxicity
myelosuppression (thrombocytopenia, anemia), gastrointestinal disturbance, neuropathy
Abx targeting protein synthesis (LIST)
Mupirocin
Linezolid
Aminoglycosides
Tetracyclines/Tigecycline
Chloramphenicol/Clindamycin/Retapamulin
Streptogramins
Macrolides
Macrolides (types)
erythromycin, clarithromycin, azithromycin (Zithromax)
Macrolides (function)
Oral and IV administration (clarithromycin oral only)


Useful for pneumonia, sinusitis, Chlamydia, Mycobacterium avium/intracellulare, Toxoplasma (protozoan parasite)
Macrolides Mech of action
Blocks polypeptide exit tunnel in 50S ribosomal subunit, inhibits translocation
Macrolides resistance
methylation of ribosomal RNA
efflux (seen is S. aureus)
Macrolides toxicity
gastrointestinal irritation
Clindamycin
Anaerobic infections, community acquired MRSA

Administration: oral, IV, topical
Clindamycin Mech of Action
Associate with 50S ribosomal subunit. Inhibits formation of peptide bonds.
Clindamycin Resistance
methylation of rRNA (cross resistance with macrolides)
Clindamycin Adverse Effects
allergic reactions, diarrhea, antibiotic-associated colitis (toxin production by Clostridium difficile)
Synercid
Streptogramins - quinoprinstin - dalfopristin


Bactericidal antibiotic for severe Gram-positive infections (MRSA, some Enterococcus)
Synercid Mech of Action
Inhibits protein synthesis (interferes with tRNA translocation)

Synergistic binding of two components to 50S ribosome preventing peptidyl transfer, and blocking exit tunnel
Synercid Mech of Resistance
Enzymatic inactivation
(lyase, acetyltransferase)
Synercid Toxicity
Arthralgia, myalgia (severe, limits use of this antibiotic)

Drug interactions
Aminoglycosides (types)
streptomycin, gentamicin, tobramycin, neomycin
Aminoglycosides (info)
Synergistic with ß-lactam antibiotics and vancomycin for serious Gram-positive infections

Useful against Pseudomonas aeruginosa

Inactive against anaerobes

Administration usually IV, monitoring of serum levels required
Aerosolized tobramycin used for cystic fibrosis patients
Aminoglycosides Mech of action
Bind to 30S and 50S ribosomal subunits, cause misreading of mRNA and premature release of ribosome
Aminoglycosides mech of resistance
Production of aminoglycoside-modifying enzymes
Modification of outer membrane porins, efflux (P. aeruginosa)
Aminoglycosides toxicity
renal, acoustic and vestibular, neuromuscular blockade

As a class, the most toxic of current widely used antibiotics
Tetracyclines (Types)
doxycycline, minocycline
Tetracyclines (Function)
Broad spectrum of activity

Effective for intracellular pathogens (e.g. Chlamydia trachomatis)

Oral administration
Tetracyclines Mech of Action
Bind to 30S ribosomal subunit, inhibit binding of aminoacyl tRNA to ribosome
Tetracyclines Mechanism of resistance
active efflux from the bacterial cell, ribosomal protection
Tetracyclines Toxicity
Hypersensitivity, discoloration of teeth in children, hepatotoxicity in pregnant women
Tigecycline
structurally related to tetra

Broad spectrum of activity
Approved (2005) for skin and soft tissue infections (incl. MRSA), intra-abdominal infections, pneumonia. Use limited by low serum levels.

IV administration
Tigecycline Mech of Action
Binds to 30S ribosomal subunit, inhibit binding of aminoacyl tRNA to ribosome (same as tetracyclines)
Tigecycline Mech of Resistance
Efflux (rare)
Tigencycline Toxicity
Nausea, vomiting
FDA warns of increase in all-cause mortality associated with tigecycline treatment of serious infection (Sept., 2010)
Mupirocin (Bactroban)
Useful for eradication of nasal carriage of MRSA, treatment of skin infections caused by Staphylococcus aureus and Streptococcus pyogenes – topically applied
Mechanism of action
Inhibits protein synthesis by binding isoleucine-tRNA ligase, prevents protein synthesis by blocking incorporation of isoleucine in proteins
Mechanism of resistance
Acquisition of plasmd carrying gene encoding resisant target enzyme (mupA)
Resistance increasing among MRSA
Toxicity
occasional irrritation at site of administration
Abx targeting nucleic acids
Fluoroquinolones
Rifampin
Fidaxomicin (2011)
Fluoroquinolones
Broad spectrum, expanding range of drugs in this class
3rd and 4th generation drugs require once daily dosing

Oral and IV administration
Fluoroquinolones mech of action
bind to DNA gyrase, topoisomerases, preventing DNA replication
Fluoroquinolone mech of resistance
mutations in DNA gyrase, topoisomerases

Efflux, target protection (plasmid mediated)
FluoroquinoloneToxicity
tendon rupture in adults, especially those over 60 years of age

mild gastrointestinal irritation

reversible joint toxicity in children

cardiac arrythmias

neuropathies
Fluoroquinolone 2nd Generation: ciprofloxacin – aerobic Gram negatives
UTI, enteric infections, Pseudomonas aeruginosa
Rifampin
Useful only in prophylaxis or in combination

Important in treatment of tuberculosis

Prophylaxis of meningococcal disease

Oral and IV administration
Rifampin mech of action
Binds to bacterial RNA polymerase preventing the synthesis of RNA
Rifampin mech of resistance
mutation in RNA polymerase, occurs with high frequency
Rifampin Toxicity
discoloration of urine, secretions

affects metabolism of other drugs - Cytochrome P450 induction

Rifaximin - non-absorbable version, intestinal infections
Fidaxomicin (approved 2011)
Effective for Clostridium difficile antibiotic-associated colitis

Oral administration, non-absorbable
Fidaxomicin mech of action
Binds to bacterial RNA polymerase preventing the synthesis of RNA
Fidaxomicin mech of resistance
mutation in RNA polymerase
Fidaxomicin toxicity
mild toxicities
Abx (DNA damage)
Metronidazole (Flagyl)
Nitrofurantoin
Metronidazole
active against anaerobes and Trichomonas vaginalis, Entamoeba histolytica, Giardia lamblia (protozoan parasites).
Nitrofurantoin
use limited to treatment and prophylaxis of urinary tract infections caused by E. coli
Nitrofurantoin Mechanism of action
reactive intermediates damage DNA. Prodrug is reduced to short lived radical nitro anion.
Nitrofurantoin Mechanism of resistance
mutations in reductases necessary for activation of the antibiotic
Abx (antimetabolites)
Sulfonamides, trimethoprim, trimethoprim sulfamethoxazole
Sulfonamides
structural analogs of para-amino benzoic acid, prevents bacterial synthesis of folic acid
Trimethoprim
structural analog of dihydrofolic acid, an intermediate in folate metabolism, and competitively inhibits the bacterial dihydrofolate reductase
Trimethoprim sulfamethoxazole (Bactrim, Septra)
Used for otitis/sinusitus, E. coli urinary tract infections, MRSA skin and soft tissue infections
Broad spectrum of activity, is also active against the fungus Pneumocystis jiroveci
Antimetabolite Mech of Resistance
Used for otitis/sinusitus, E. coli urinary tract infections, MRSA skin and soft tissue infections
Broad spectrum of activity, is also active against the fungus Pneumocystis jiroveci
Antimetabolite toxicity
Used for otitis/sinusitus, E. coli urinary tract infections, MRSA skin and soft tissue infections
Broad spectrum of activity, is also active against the fungus Pneumocystis jiroveci
Bacteriostatic activity
An agent will stop the growth of a microorganism, but does not rapidly kill it.
Bactericidal activity
rapid killing of the microbe
MIC (minimum inhibitory concentration)
lowest concentration which will inhibit the growth of a specific microorganism
MBC
minimum bactericidal concentration
Additive response
the effect is roughly the summation of the effects of each agent
Antagonistic response
the overall effect is less than the response of one of the agents used alone
Synergistic response
the combination has an antimicrobial effect greater than the sum of the effects of each agent
Intrinsic resistance
Resistance to an antibiotic is a characteristic of the microbial species
Acquired resistance
Acquired by mutation, or introduction of a gene encoding resistance from another bacterial cell
Mechanisms of resistance
Inactivation of the antibiotic
Decreased access of antibiotic to target
Alteration of the target