Flashcards in Antibiotics 2 Deck (86):
imipenem-cilastatin, meropenem, ertapenem, doripenem
broad spectrum against gram-positive, gram-negative, and anaerobic organisms. stable against most beta lactamases including ESBLs and AmpCs. hits pseudomonas except ertapenem
what bug developed high level resistance against carbapenems?
carbapenem clinical uses
complicated UTIs, complicated intraabdominal infections, healthcare acquired pneumonia, bone and SSTI, bacterial meningitis. These are usually caused by gram negative things.
carbapenem side effects
generally well tolerated. lower association with c. diff colitis, coag abnormalities, nephrotox or hepatotox. CNS: low incidence of seizures, but higher than other antibiotics.
what drug do carbapenems interact with?
substantially decrease valproic acid concentrations
what is great about the ertapenem halflife?
very long, allows q24h dosing. good for outpatient settings. has poor activity against pseudomonas / acinetobacter though
what is the most active carbapenem against pseudomonas?
gram negative: enterobacteriaceae and pseudomonas. NO ACTIVITY AGAINST GRAM POSITIVE OR ANAEROBIC BACTERIA!
rarely used alone empirically. alternative to penicillin to provide gram-negative coverage in combo with another agent. best used as definitive therapy for gram-neg infections. give if someone has a severe penicillin allergy
vancomycin mechanism of action
inhibits late stages of cell wall synth by binding to the D-Ala D-ala terminus of the nascent peptidoglycan pentapeptide. prevents elongation by inhibiting transglycosylase.
mechanisms of resistance to vancomycin
enterococcus (VRE) can do target modication. VISA can get a thickened cell wall. VRSA gets a plasmid-mediated transfer of the vanA gene cluster from VRE.
gram pos: staphylococci (MRSA, MSSA), streptococci, enterococci, bacillus, corynebacterium.
Anaerobes: peptostrepto, actinomyces, propionibacterium, clostridium.
NO GRAM NEGATIVE ACTIVITY
vancomycin clinical uses
SSTI especially when MRSA is suspected (purulent cellulitis). Bacteremia and endocarditis. Meningitis and ventriculitis. Pneumonia. Bone and joint infection. Neutropenic fever. Surgical prophylaxis. C. diff colitis (only the oral form)
vancomycin side effects
nephrotox at high concentrations, infusion reactions (redman syndrome), maculopapular rash, drug fever, phlebitis, neutropenia, thrombocytopenia
daptomycin mechanism of action
insertion into the gram-positive cell membrane causing depolarization and ulimate cell death. Not a cell-wall active agent. resistance arises due to alteration of the cell membrane.
gram pos: s. aureus, strepto/entero cocci.
Anaerobe: has invitro activity against gram-pos anaerobes
NO GRAM NEGATIVE ACTIVITY
daptomycin clinical uses
SSTI, s. aureus bacteremia and endocarditis, osteoarticular infection, enterococcal infections. Not effective for pneumonia.
why is daptomycin not effective for pneumonia?
it is inactivated by the surfactant!
daptomycin side effects
CPK elevation and possible skeletal muscle damage. paresthesia, peripheral neuropathy. eosinophilic pneumonia-rare. causes myalgias.
telavancin, dalbavancin, oritavancin.
telavancin mechanism of action
binds to cell wall precursors like vancomycin. depolarizes cell membrane. `
vancomycin's spectrum PLUS VISA, VRSA, some VRE isolates
telavancin clinical uses
SSTI, hospital acquired pneumonia. infrequently used.
telavancin side effects
nephrotox, more so than vancomycin. GI: n/v, metallic taste. potentially teratogenic.
dalbavancin mechanism of action
inhibition of cell wall precursors
gram positive: MRSA, MSSA, strep, coag negative staph. NO GRAM NEGATIVE ACTIVITY. Anaerobes: c. perf, c. diff, prop. acnes, peptostrepto
oritavancin mechanism of action
inhibition of cell wall precursors, binds to pentaglycl bridging segment in peptidoglycan and inhibits transpeptidation. interaction and disruption of the cell membrane
similar to dalbavancin, but active against VRE.
dalbavancin and oritavancin clinical uses
SSTI, can be given in infusion centers (good for outpatient setting). very expensive though!!!
gentamicin, tobramycin, amikacin, streptomycin
aminoglycoside mechanism of action
oxygen-dependent, active transport across the bacterial cell membrane. binds to the 30S subunit of ribosomes and interferes with an initiation complex, inhibiting protein synth.
aminoglycoside mechanism of resistance
enzymatic modification, reduced uptake or decreased cell permeability, altered ribosome binding sites.
gram neg: enterobacteriaceae and Pseudomonas
gram pos: synergy with cell wall active agent against enterococcus (cant give as monotherapy)
Amikacin: some types of mycobacteria and nocardia
aminoglycoside clinical uses
infections caused by gram-negative bacilli. UTI. hospital acquired pneumonia when combined with a beta lactam. Enterococcal infection combined with cell wall active agent. Cystic fibrosis. Orthopedic surgery (used in antibiotic cement)
aminoglycosides side effects
nephrotoxicity. ototoxicity. neuromusular damage (rare)
distributed extensively into urine. distribution into tissues
concentration dependent. High peak is important!!! biphasic killing. higher the peak, the faster the killing.
doxycycline, minocycline, tetracycline
tetracycline mechanisms of action
passive diffusion through porins in gram-negative organisms. binds to 30S ribosomal subunit preventing protein synthesis
tetracycline mechanisms of resistance
efflux pump. ribosomal protection (through dissociation of tet from ribosomal binding sites)
atypical: chlamydia and mycoplasma pneumoniae
spirochetes: borrelia, leptospira, treponema pallidum
Gram pos: s. pneumoniae, CA-MRSA
gram neg: h. influenzae, neiserria
rapidly growing mycobacteria
tetracycline clinical uses
tick borne illness Drug of Choice! lyme disease, ehrlichiosis, anaplasmosis. CAP. SSTI caused by CA-MRSA. conbo therapy for h. pylori. prophylaxis for exposure to anthrax, tularemia, plague, Q fever, brucellosis
tetracycline side effects
GI: n/v, diarrhea.
Photosensitivity and hyperpigmentation! MAINLY IN THE HANDS
teeth and bone: tooth discoloration in kids. inhibition of bone growth in infants
Nephrotox and neurotox
glycylcycline chemistry/mechanism of action
9-glycl substitution enables tigecycline to overcome two major types of resistance: efflux pumps and ribosomal protection
organisms covered by tetracycline plus some tetracycline-resistant organisms. Broad spectrum: gram negative, gram positives, anaerobes. activity against stenotrophomonas. Doesn't hit pseudomonas, proteus, providencia, morganella
tigecycline clinical uses
FDA approved for complicated skin and soft tissue infections, intra-abdominal infection, CAP. also used for carbapenem resistant enterobacteriaceae. Not advised for treating bacteremia due to low serum concentrations
tigecycline side effects
GI: significant N/V and diarrhea.
Transaminitis. increased mortality.
azithromycin, clarithromycin, erythromycin.
macrolide mechanism of action
reversible binding to 50S subunit of ribosome.
macrolide mechanisms of resistance
decreased permeability in enterobacteriaceae. Alteration in the 50S receptor site. Alteration in the 23S ribosomal RNA of the 50S ribosomal subunit. Enzymatic inactivation
gram pos: s. pneumoniae, signif resistance in beta hemolytic strep. Gram neg: h. influenzae and m. catarrhalis.
Atypicals: legionella, chlamydia, mycoplasma
macrolides clinical uses
uncomplicated upper and lower respiratory tract infections. Mycobacterial infection. H. pylori in combo with other agents.
macrolides side effects
GI: abdominal cramps, N/V, diarrhea. Thrombophlebitis with erythromycin. Cardiac: QT prolongation -> torsades de pointes
what is the safest macrolide to use?
azithromycin! only has one interaction. much safer than the other macrolides
clindamycin mechanism of action
binding to 50S ribosomal subunit preventing protein synth.
clindamycin mechanisms of resistance
alteration in 23S ribosomal RNA of 50S ribosomal subunit. Alteration in 50S ribosomal proteins of the receptor site. Enzymatic inactivation
gram pos: streptococci including group B strep. Staph aureus.
NO GRAM NEGATIVE ACTIVITY
Anaerobes: B. fragilis, clostridium, peptostreptococcus, fusobacterium, prevotella.
Toxoplasmosis, plasmodium falciparum
clindamycin clinical uses
tends to be an alternative treatment, mainly for surgical prophylaxis and SSTIs caused by staph aureus.
Combo with penicillin for toxic shock. combo with quinine for falciparum malaria
clindamycin side effects
diarrhea, pseudomembranous colitis
oxazolidinone mechanism of action
binds to 23 S ribosomal RNA of the 50S subunit inhibiting protein synthesis
linezolid and tedizolid spectrum
activity against gram-positives: staphylococci, enterococci, streptococci. NO GRAM NEGATIVE ACTIVITY. poor activity against anaerobes.
linezolid and tedizolid clinical uses
tedi is approved for SSTI. linezolid is used for enterococcal infection, nosocomial pneumonia caused by s. aureus, CAP caused by s aureus, SSTI. not recommended for s. aureus bacteremia
linezolid and tedizolid side effects
hematologic toxicity, reversible myelosuppression, mitochondrial toxicity, serotonin syndrome
fluoroquinoline agents and mechanism of action
end in -floxacin. Inhibit DNA gyrase and inhibit topoisomerase IV
gram pos: s. aureus, s. pneumoniae, enterococcus (poor).
gram neg: enterobacteriaceae, h flu, p aeruginosa, atypicals.
moxifloxicin has moderate activity against anaerobes
fluoroquinolone clinical uses
resistance in enterobacteriaceae problematic. UTI. GI and abdominal infections: traveler's diarrhea. STDs: gonoccoal urethritis, chlamydial infection. Respiratory tract infections. Bone and joint infection. cutaneous anthrax. adjunctive therapy in MDR TB
fluoroquinolone side effects
CNS: headache, dizziness, confusion
Tendinitis and tendon rupture rare.
metronidazole mechanisms of action
interacts with DNA to cause a loss of helical DNA structure and strand breakage resulting in inhibition of protein synthesis
metronidazole antimicrobial spectrum
anaerobes: b. fragilis, clostridial species.
metronidazole clinical uses
C. diff diarrhea. intra-abdominal infections. surgical prophylaxis in colon surgery. trichomoniasis.
rifampin, rifabutin, rifaximin
rifamycin mechanism of action
bind to DNA dependent RNA polymerase inhibiting RNA synthesis
gram pos: staphylococci, streptococci, c. diff, listeria
gram neg: h flu, n meningitidis, h. pylori
clinical uses for rifamycins
rifampin: m. tuberculosis infection. adjunct in endocarditis. prophylaxis for n. meningitidis
rifabutin: alternative to rifampin for MAC or tuberculosis
rifaximin: hepactic encephalopathy, recurrent C. diff, traveler's diarrhea
inhibition of synthetic pathways of mycolic acid
pyrazinamide and ethambutol mechanisms of action
ethambutol: inhibits arabinosyl transferase enzymes involved in biosynth of cell walls
bacterial anti-metabolite agents
trimeth-sulfameth mechanism of action
sulfa: interferes with bacterial folic acid synth
trimeth: inhibits dihydrofolic acid reduction to tetrahydrofolate
gram pos: CA-MRSA, MSSA. not ideal for beta hemolytic strep. listeria
Gram neg: enterobacteriaceae. toxoplasmosis, nocardia, pneumocystis. NO ANAEROBES