Overview of Antimicrobial Agents Flashcards
Natural Penicillins
Penicillin G(IV, IM)
Penicillin V (PO)
Anti-staphylococcal Penicillins
Oxacillin(IV, IM)
Dicloxacillin(PO)
Nafcillin (IV, IM)
Aminopenicillins*
Ampicillin(PO, IV, IM)
Amoxicillin(PO)
Anti-pseudomonalPenicillins
Piperacillin (IV)
First Generation Cephalosporins
Cefazolin(IV, IM)
Cephalexin [Keflex] (PO)
Second Generation Cephalosporins
Cefoxitin(IV)
Cefuroxime (PO, IV, IM)
Third Generation Cephalosporins*
Ceftriaxone[Rocephin] (IV, IM)
Ceftazidime(IV, IM)
Fourth Generation Cephalosporins*
Cefepime(IV, IM)
Carbapenems
Imipenem/cilastatin (IV)
Meropenem(IV)*
Ertapenem(IV, IM)*
Monobactams
Aztreonam (IV, IM, INH)
B-lactamase Inhibitors*
Ampicillin-sulbactam(IV)
Amoxicillin-clavulanic acid [Augmentin] (PO)
Piperacillin-tazobactam(IV)
Glycopeptides*
Vancomycin(PO, IV)
Lipopeptides
Daptomycin(IV)
Fluoroquinolones
Ciprofloxacin [Cipro] (PO, IV, topical)
Levofloxacin(PO, IV, topical)*
Moxifloxacin (PO, IV, topical)
Aminoglycosides
Tobramycin (IV, IM, INH, topical)
Gentamicin(IV, IM, topical)*
Tetracyclines/Glycylcyclines
Minocycline (PO, IV)
Doxycycline(PO, IV)*
Macrolides/Ketolides
Clarithromycin (PO)
Azithromycin[Zithromax, Z-pak] (PO, IV, topical)*
Lincosamides*
Clindamycin[Cleocin] (PO, IV, IM, topical)
Sulfonamides/Trimethoprim
Sulfamethoxazole/trimethoprim (PO, IV)
Most common categories
penicillins and macrolides
Top 5 drugs:
Azithromycin Amoxicillin Amoxicillin-clavulanate Ciprofloxacin Cephalexin
Ask yourself whether an antimicrobial agent is warranted:
Is an antimicrobial indicated based on clinical findings?
Have appropriate cultures been obtained?
What is the most likely causative organism?
What must be done to prevent secondary exposure?
Is there clinical evidence or established guidelinesthat have determined antimicrobial therapy provides a clinical benefit?
prophylaxis
no infection
pre-emptive
infection
empiric
symptoms
definitive
pathogen isolated
suppression
resolution
A 37 yofemale with a history of end-stage renal disease, on dialysis, is admitted to the hospital with healthcare-associated pneumonia. Antibiotics are initiated to cover the most likely pathogen(s).
empiric
A 68 yomale presents for a total hip replacement. Prior to surgery, he is given one dose of cefazolin to prevent development of a surgical wound infection
prophylaxis
A 37 yofemale with a history of end-stage renal disease, on dialysis, is admitted to the hospital with healthcare-associated pneumonia. Cultures result with sensitive Pseudomonas, vancomycin is discontinued
definitive
An 8 yomale presents to the ED with a perforated appendix. Antibiotics are initiated pre-operatively to reduce risk of intra-abdominal abscess & wound infection
pre-emptive
A 75 yomale presents to his PCP for follow-up of prosthetic hip joint infection. He receives continued low dose antimicrobial therapy. Hip prosthesis was unable to be removed and replaced during hospitalization.
suppressive
Gram Positive cocci anaerobic
peptococcus
peptostreptococcus
Gram Positive cocci aerobic clusters coagulase positie
staph aureas
Gram Positive coccie aerobic clusters coagulase negative
staph epi staph saprophyticus staph hominis staph hemolyticus staph warneri
Gram Positive cocci aerobic diplococci
streptococcus pneumonia
entrococcus
Gram Positive cocci aerobic chains b hemolytic
strep pyogenes group a
strep agalectiae group b
strep groups cfg
Gram Positive cocci aerobic chains a hemolytic
viridans strep
strep pneumonia
Gram Positive bacilli anaerobic
c diff clostridium perfringens actinomyces lactobacillus
Gram Positive bacilli aerobic
bacillus anthracis
nocardia
listeria
acynebacterium jelkelium
Gram Negative bacilli anaerobic
prevotella
fusobacterium
bacteroides
Gram Negative bacilli aerobic lactose fermenting oxidase positive
aeromonas
pasteurella
vibrio
Gram Negative bacilli aerobic lactose fermenting oxidase negative
ecoli
klebsiella
enterobacter
citrobacter
Gram Negative bacilli aerobic non lactose fermenting oxidase postiive
pseudomonas flavobacterium aitaligenes achromobacter moraxella
Gram Negative bacilli aerobic non lactose fermenting oxidase negative
proteus proficendia serrates morganella slamonella shigella strenotrophomonas acinetobacter
Gram Negative bacilli aerobic misc
brucella bordetella campylobacter pasteurella vibrio
Gram Negative cocci
Neisseria meningitides
neisseriia gonohorrhoaea
vellionella
Gram Negative coccbacilli
h influenza
Moraxella catarrhalis
Susceptible:
Likely to inhibit pathogenic microorganism
Intermediate:
May be effective at higher dosage, more frequent administration, or in specific body site
Resistant:
Not effective at inhibiting growth of microorganism
Minimum inhibitory concentration (MIC):
lowest concentration of drug required to inhibit growth
Breakpoints established by Clinical and Laboratory Standards Institute (CLSI)
Clinical and Laboratory Standards Institute (CLSI) Breakpoints
MIC (μg/mL
Susceptible ≤ 4
Intermediate 8-16
Resistant ≥ 32
Clinical and Laboratory Standards Institute (CLSI) Breakpoints
Zone Diameter (mm)
Susceptible ≥ 20
Intermediate 15-19
Resistant ≤ 14
Zone Diameter (mm)
Act on a single or a limited group of microorganisms
Extended-spectrum
Active against gram-positive bacteria but also against significant number of gram-negative bacteria
Broad-spectrum
Act on a wide variety of bacterial species, including both gram-positive and gram-negative
Bacteriostatic:
arrests growth and replication of bacteria (limits spread of infection)
Bactericidal:
kills bacterial
Concentration-dependent killing: rate and extent of killing increase with increasing drug concentrations
Time-dependent killing: activity continues as long as serum concentration above minimum bactericidal concentration
Bacteriostatic vs. Bactericidal
This concept is relative
Certain drugs are –cidalagainst specific bacteria while –static against others
Drug-drug enhancement or synergism
Gentamicin –ineffective against enterococci in the absence of a cell-wall inhibitor
Combining penicillin with gentamicin leads to bactericidal activity
Antimicrobials classified based on
Class and spectrum of microorganisms it kills
Biochemical pathway it interferes with
Chemical structure
Site of Antibacterial Action
cell wall synthesis
cycloserine vancomycin bacitracin fosfomycin penicillins cephalosporins monbactams carbapenems
Site of Antibacterial Action folic aid metabolism
Bactrim both
paba
Site of Antibacterial Action
cell membrane
polymyxins
Site of Antibacterial Action
dna replication (dna gyrase)
nalidixic acid
quinolones
Site of Antibacterial Action
dna dependent rna polymerase
rifampin
Site of Antibacterial Action
protein synthesis (50 S)
erythromycin
chloramphenicol
clindamycin
Site of Antibacterial Action
protein synthesis (30S)
tetracyclin spectinomycin streptomycin gentamicin tobramycin amikacin
Site of Antibacterial Action
Cell wall synthesis Cell membrane synthesis Protein synthesis Nucleic acid metabolism Function of topoisomerases Folate synthesis
cell wall inihbitors
blactams
penicillins
cephalosporins
1-4th gnereations
carbapenems
monobactams
cell wall inihbitors
other antibiotics
bacitracin
vancomycin
daptomycin
cell wall inihbitors
blactamase inhibitors
clavulanic acid
sulbactam
tazobactam
β-Lactam Mechanism of Action
Time-dependent; structural analogs of D-Ala-D-Ala; covalently bind penicillin-binding proteins (PBPs), inhibit the last transpeptidation step in cell wall synthesis
β-Lactamase Inhibitors
Amoxicillin + clavulanic acid, ticarcillin + clavulanic acid, ampicillin + sulbactam, piperacillin + tazobactam
MOA: prevent destruction of B-lactam antibiotics
Fluoroquinolone Mechanism of Action
Concentration-dependent, targets bacterial DNA gyrase& topoisomerase IV. Prevents relaxation of positive supercoils
Inhibitors of Protein Synthesis
Formation of initiation complex
Amino-acid incorporation
Formation of peptide bond
Translocation
Aminoglycosides moa
blocks initiation of protein synthesis
blocks further translation and elicits premature termination
incorporation of incorrect amino acid
Tetracyclines moa
binds 30 s and block the a site
Macrolides moa
bind 50s they inhibit translocation
Sulfonamides and Trimethoprim moa
Inhibit folic acid synthesis; block sequential steps in pathway.
pcp pneumonia
block sequential steps in folic acid production
Β-Lactams
MOA
structural analogs of D-Ala-D-Ala; covalently bind penicillin-binding proteins (PBPs), inhibit transpeptidation
Β-Lactams
resistance
Structural difference in PBPs
Decreased PBP affinity
Inability for drug to reach site of action (i.e. gram-negative organisms)
Active efflux pumps
Drug destruction/inactivation by B-lactamases
Natural Penicillins
drugs
Penicillin G (IV, IM), penicillin V (PO)
Natural Penicillins spectrum
highly effective against gram-positive cocci (GPC) but easily hydrolyzed by penicillinase
Natural Penicillins
therapeutic use
narrow-spectrum, Streptococcus pneumoniaepneumonia and meningitis. Penicillin V for Streptococcus pyogenespharyngitis, toxic shock, viridians streptococci endocarditis if susceptible, syphilis
Anti-Staphylococcal Penicillins
drugs
Oxacillin (IV, IM), dicloxacillin (PO), nafcillin (IV, IM)
Anti-Staphylococcal Penicillins
spectrum
penicillinase resistant; agents of first choice for Staphylococcus aureus(MSSA) and Staphylococcus epidermidis(MSSE) that are not methicillin resistant
Anti-Staphylococcal Penicillins
therapeutic use
estricted to infections with known Staphylococcussensitivity
Aminopenicillins
drugs*
Ampicillin(PO, IV, IM), amoxicillin(PO)
Aminopenicillins
spectrum*
extended-spectrum; extends beyond gram-positive to gram-negative (Haemophilus influenzae, Escherichia coli, Proteus mirabilis), Listeria monocytogenes, susceptible meningococci, enterococci
Aminopenicillins
therapeutic use*
upper respiratory tract infections (S. pyogenes, S. pneumoniae, H. influenzae), sinusitis, otitis media, enterococcalinfections
Anti-PseudomonalPenicillins
drugs
Ticarcillin(IV), piperacillin(IV)*
Anti-PseudomonalPenicillins
spectrum*
Spectrum: extends spectrum to Pseudomonas aeruginosa, Enterobacter, and Proteusspp.
Anti-PseudomonalPenicillins
therapeutic use*
serious gram-negative infections, hospital acquired pneumonia (HAP), immunocompromised patients, bacteremia, burn infections, UTI
Penicillins
Adverse effects:
Allergic reactions (0.7-10%)
Anaphylaxis (0.004-0.04%)
Nausea, vomiting, mild to severe diarrhea
Pseudomembranous colitis
1st-Generation Cephalosporins
drugs
Cefazolin(IV, IM), cephalexin (PO)
1st-Generation Cephalosporins
spectum
good gram-positive coverage, modest gram-negative (covers Moraxella, E. coli, Klebsiellapneumoniae, P. mirabilis), orally active anaerobes
1st-Generation Cephalosporins
therapeutic use
skin and soft tissue infections (SSTIs), surgical prophylaxis
2nd-Generation Cephalosporins
drugs
Cefoxitin (IV), cefuroxime (PO, IV, IM)
2nd-Generation Cephalosporins
spectrum
somewhat increased activity against gram-negative, but less active than 3rd-generation. Subset active against Bacteroidesfragilis
2nd-Generation Cephalosporins
therapeutic use
used in gram-negative mixed anaerobic (intra-abdominal infections, pelvic inflammatory disease, diabetic foot infections)
3rd-Generation Cephalosporins
drugs*
Ceftriaxone(IV, IM), ceftazidime(IV, IM)
3rd-Generation Cephalosporins
spectrum*
less active against gram-positive, more active against Enterobacteriaceae(although resistance increasing due to B-lactamase producing strains)
3rd-Generation Cephalosporins
therapeutic use*
serious gram-negative infections (Klebsiella, Proteus, Providencia, Serratia, Haemophilus), ceftriaxone DOC for all forms of gonorrhea & severe Lyme’s disease; meningitis. Ceftazidimecovers Pseudomonas
4th-Generation Cephalosporin
drugs*
Cefepime(IV, IM)
4th-Generation Cephalosporin
spectrum*
extends beyond 3rd-generation, useful in serious infections in hospitalized patients. Effective against Pseudomonas
4th-Generation Cephalosporin
therapeutic use*
empirical treatment of nosocomial infections
Cephalosporins
Adverse effects:
1% risk of cross-reactivity to penicillins
Diarrhea
Carbapenems
drugs*
Imipenem/cilastatin (IV), meropenem(IV), ertapenem(IV, IM)
Carbapenems
spectrum*
aerobes & anaerobes; gram-positive, Enterobacteriaceae, Pseudomonas, Acinetobacter.Stenotrophomonasmaltophiliais resistant.
Carbapenems
therapeutic use
UTI, lower respiratory tract infection (LRTI), intra-abdominal, gynecological, SSTI, bone and joint infections
Carbapenems
adverse effects*
Nausea/vomiting (1-20%), seizures (1.5%), hypersensitivity
Monobactam
drugs
Aztreonam (IV, IM, INH)
Monobactam
spectrum
activity against gram-negative (Enterobacteriaceae, Pseudomonas, H. influenzae, gonococci), no activity against GPC or anaerobes
Monobactam
therapeutic use
patients who are allergic to B-lactams appear not to react to aztreonam > effective for gram-negative infections which would usually be treated with B-lactam
Glycopeptides
drugs
Vancomycin (PO, IV)
Glycopeptides
moa
inhibits cell wall synthesis binding with high affinity to D-Ala-D-Ala terminal of cell wall precursor units.
Glycopeptides
resistance
alteration of D-Ala-D-Ala target to D-alanyl-D-lactate or D-alanyl-D-serine which binds glycopeptides poorly. Intermediate resistance may also occur
Glycopeptides
spectrum
broad gram-positive coverage –S. aureus(including MRSA), S. epidermidis(including MRSE), Streptococci, Bacillus, Corynebacterium spp., Actinomyces, Clostridium
Glycopeptides
therapeutic use
osteomyelitis, endocarditis, MRSA, Streptococcus, enterococci, CNS infections, bacteremia, orallyfor C. difficile
Glycopeptides
adverse effects
Macular skin rash, chills, fever, rash
Red-man syndrome (histamine release): extreme flushing, tachycardia, hypotension
Ototoxicity, nephrotoxicity (33% with initial trough > 20 mcg/mL)
Fluoroquinolones
moa
concentration-dependent; targets bacterial DNA gyrase & topoisomerase IV.
Fluoroquinolones
spectrum
E. coli, Salmonella, Shigella, Enterobacter, Campylobacter, Neisseria, Pseudomonas aeruginosa, S. aureus(not MRSA), limited coverage of Streptococcusspp.
*Levofloxacin, moxifloxacin, “respiratory fluoroquinolones” cover Streptococcusspp.
Fluoroquinolones
therapeutic use
UTI, prostatitis, STI (chlamydia, Neisseria gonorrhoeae), traveler’s diarrhea, shigellosis, bone, joint, SSTI infections, diabetic foot infections
Fluoroquinolones
Adverse effects:
GI 3-17% (mild nausea, vomiting, abdominal discomfort)
CNS 0.9-11% (mild headache, dizziness, delirium, rare hallucinations)
Rash, photosensitivity, Achilles tendon rupture (CI in children)
Aminoglycosides
drugs*
Tobramycin (IV, IM, INH, topical), gentamicin(IV, IM, topical)*
Aminoglycosides
moa*
concentration-dependent; binds 30S ribosomal subunit, disrupts normal cycle of ribosomal function
Aminoglycosides
spectrum*
aerobic gram-negative bacteria, limited action against gram-positive, synergistic bactericidal effects in gram-positive with cell wall active agent
Aminoglycosides
therapeutic use*
UTI (not uncomplicated), used if resistance to other agents, seriously ill patients, pneumonia (infective against S. pneumoniaeand anaerobes), HAP, peritonitis, synergy in bacterial endocarditis, tobramycin inhalation in CF
Aminoglycosides
adverse effects*
Ototoxicity (may be as high as 25%)
Nephrotoxicity (8-26%)
Neuromuscular block and apnea
Tetracyclines/Glycylcyclines
drugs*
Minocycline (PO, IV), doxycycline(PO, IV)*, tigecycline(IV)
Tetracyclines/Glycylcyclines
moa*
bacteriostatic; binds 30S bacterial ribosome. Prevents access of aminoacyl tRNAto acceptor (A) site on mRNA ribosome complex
Tetracyclines/Glycylcyclines
spectrum*
wide range of aerobic/anaerobic gram-positive and -negative activity; effective for: Rickettsia, Coxiellaburnetii, Mycoplasma pneumoniae, Chlamydiaspp, Legionella, atypical mycobacterium, Plasmodium, Borreliaburgdorferi(Lyme’s disease), Treponema pallidum(syphilis)
Tetracyclines/Glycylcyclines
therapeutic use*
CAP, atypical CAP coverage, community acquired SSTIs, community acquired MRSA, acne, Rickettsialinfections (Rocky Mountain Spotted Fever), Q fever, anthrax
Tetracyclines/Glycylcyclines
adverse effects*
GI (epigastric burning, nausea, vomiting, diarrhea) Superinfections of C. difficile Photosensitivity Teeth discoloration Thrombophlebitis
Macrolides/Ketolides
drugs*
Clarithromycin (PO), azithromycin(PO, IV, topical)*
Macrolides/Ketolides
moa*
bacteriostatic; binds reversibly to 50S ribosomal subunit, inhibits translocation
Macrolides/Ketolides therapeutic use*
respiratory tract infections (spectrum S. pneumoniae, H. influenzae, and atypicals: Mycoplasma, Chalmydophilia, Legionella), alternative for otitis media, sinusitis, bronchitis, and SSTIs. Pertussis, gastroenteritis, H. pylori, Mycobacterial infections
Macrolides/Ketolides
adverse effects*
GI (epigastric distress)
Hepatotoxicity
Arrhythmia
QT prolongation
Macrolides/Ketolides
drug interaction*
CYP3A4 inhibition –prolongs effects of digoxin, warfarin….
Lincosamides
drugs*
Clindamycin(PO, IV, IM, topical)
Lincosamides
moa*
binds 50S subunit of bacterial ribosome, suppresses protein synthesis
Lincosamides
spectrum*
pneumococci, S. pyogenes, viridansStreptococci, MSSA, anaerobes (B. fragilis)
Lincosamides
therapeutic use*
SSTIs, necrotizing SSTIs, lung abscesses, anaerobic lung and pleural space infections, topically for acne vulgaris
Lincosamides
adverse effects*
GI diarrhea (2-20%) Pseudomembranous colitis (0.01-10%) Due to C. difficile Skin rashes (10%) Reversible increase in aminotransferase activity May potentiate neuromuscular blockade
Oxazolidinones
drug*
Linezolid(PO, IV)
Oxazolidinones
moa*
inhibits protein synthesis binding P site of 50S ribosomal subunit, prevents formation of initiation complexes
Oxazolidinones
spectum
gram-positive Staphylococcus(MSSA, MRSA, VRSA), Streptococcus(penicillin resistant S. pneumoniae), enterococci (VRE), gram-positive anaerobic cocci, gram-positive rods (Corynebacterium, L. monocytogenes)
Oxazolidinones
therapeutic use*
VRE faecium(SSTI, UTI, bacteremia), nosocomial pneumonia caused by MSSA and MRSA, CAP, complicated/uncomplicated SSTI infections
Oxazolidinones
adverse effects*
Myelosuppression [thrombocytopenia (2.4%),anemia, leukopenia]
Headache
Rash
Oxazolidinones
drug interactions*
weak, nonspecific inhibitor of monoamine oxidase
no novel antimocrobial moa since
1987
azithromycin used mostly for
cap
amoxicillin used mostly for
upper resp tract
otitis media
teichoic acid
stabilized peptidoglycin
lps
it is hydrophobic and is toxic called endotoxin when released can cause shock
concentration dependant killing drugs
aminoglycosides and fluoroquinolones
time dependent killing drugs
b lactams and vancomycins
cell wall inhibitors
bacteriostatic are usually
protein synthesis inhibitors
cd dependant dosing
qd
time dependant dosing
require frequent dosing to make sure we have enough over a certain amount of time
enterococci are
gram pos
fq extra
normal gyrase prevents this so they inhibit this and it is not allowed to reform the dna strands that have been cleaved already and it is released and damaged
Aminoglycosides
bacterialcidial bind 30s
Tetracyclines
binds 30 s and block the a site
Macrolides
bind 50s they inhibit translocation
bind 50s they inhibit translocation extra
pcp pneumonia
block sequential steps in folic acid production
2nd-Generation Cephalosporins used for
aspiration related mbc of mixed anaerobic
Ceftriaxone has no
pseudomonal coverage
ceftazidimehas good
psuedomonal coverage
Carbapenems save for
save for last line more serious infections if there is another drug that would work
serious resistant infecction
carbapenams must be stopped with
renal problems
use linezolid if resistant to
vancomycin
Red-man syndrome (histamine release): extreme flushing, tachycardia, hypotension
direct toxic effect on mass cells, not an allergy
fq spectrum
broad gram neg
Fluoroquinolones ci
chondorocyte damage
pregnancy breast feeding and children it is ci
ag don’t target
anaerobes bc they require o2 to get into the cell
tetracyclines cover
atypicals
lincosamide coverage
good gram positive and anaerobes
aspiration pneumonia
Oxazolidinones di
serotonin syndrome
cant give with ssri