PDA antibacterials Flashcards
What are infections where -cidal drugs have an advantage?
pts with compromised immune system following in immune-competent pts: -meningitis -endocarditis -deep bone infections -artificial device implants
What type of antibacterials are preferred for patients with competent immune systems with meningitis, endocarditis, deep bone infections, and artificial device implants?
-cidal drugs
What is time dependent killing?
amount of time about the MIC
What is concentration-dependent kkilling?
peak concentration matters most
What does it mean when drugs are concentration and time dependent?
area under curve of concentration over time vs MIC
When do time-dependent killing drugs work on epople?
drugs work best when conc. exceeds 4 times the MIC for greater than 50% of total time
What are beta-lactams dependent on for killing with respect to MIC?
Time-dependent
What type of depedency do amingolycosides have for killing?
concentration dependent and have persistent effect when levels fall below MIC
What type of dependenccy do quinolones have for killiing?
concentration x time (area under curve)
Why do beta-lactams requrie more frequent dosing?
time dependent killers and they have a shorter half life
Where do penicillins have low penetration?
into the csf; although increases during meningitis
How are penicillins eliminated?
renally; by anion transport
What are the half lives of penicillins?
short 30 minutes to 3 hours
How is penicillin V taken?
orally
How is penicllin G taken?
IV/IM
What are the spectrum of peniclin V and penicillin G?
anaerobes (mainly gram positivie) gram positive that are non-beta-lactamase producing 1st line for strep throat very limited gram negative -neisseria meningitidis spirochetes -syphillis
What penicillins are used for beta-lactamase positive staphylococci?
methicillin type drugs; ie oxacillin
MSSA(methicillin sensitive Staph aureus)
What is the spectrum for ampicillin and amoxicillin?
maitain gram postiive (Beta lactamase negative)
-enterococcus
expanded gram negative spectrum
What is the drug of choice for otitis media in otherwise healthy children?
high dose amoxicillin
What is amoxiciiln an althernate choice for in young children and pregnat/breat-feeding women?
Lyme disease
What are 2 important uses for ampicillin that amoxicillin doesnt?
meningitis (neisseria, listeria) bc available by IV GI infections; esp Shigella bc less abosrbed in orally more avaiable in GI tract
What two penicilins have an extended gram-negative spectrum?
ticarcillin and piperacillin
What is the spectrumf or ticarcillin?
retain some gram-pos activity
good for some anaerobes
gram neg spectrum extended to include psuedomonas aeruginosa
What is the spectrum for piperacillin?
gram negative spectrum like ticarcillin but also some pseudomonas and klebsiella
include those that are ticarcillin-resistant
How can one predict severe allergic reaction to penicillin?
pt history
PRE-PEN
-skin test; 90-95% reliable at identifying those at risk for severe allergic reaction
What are the side effects of penicillins?
fever diarrhea(most common side effect) enterocolitis (all anti-biotics can causet his due to C diff infection) elevated liver enzymes hemolytic anemia seizures
What are some common properties of cephalosporins?
well distributed; although only 3rd gen reach CSF
majority require injection
same mechanism as penicillin
What is teh spectrum for 1st generation cephalosporins??
mostly gram positive spectrum
uncomplicated outpatient skin infections
surgical prophylaxis esp for skin flora
What are two cephalosporin 1st generation drugs?
cefazolin and cephalexin
What are two examples of second generation cephalosporins?
cefuroxime and cefoxitin
What is teh only second gen cephalosporin to penetrate CSF?
cefuroxime
What is cefuroxime used to treat?
best second for haemophilus but poor against enterics
good tolerance to many gram negative beta lactamases
What is cefotoxin used to treat?
similar to many second gen but also good for anaerobes including B. fragilis
good tolerance to many gram-neg beta lactamases
What are two 3rd generation cephalosporins?
ceftriaxone and ceftazidime
What cephalosporin is a very good choice for common types of menigitis?
ceftriaxone
What is the therapy of choice for gonorrhea?
ceftriaxone
What is ceftriaxone used to treat?
common types of meningitis gonorrhea sever lyme disease typhoid fever surgical prophylaxis GI tract surgery
What is the half life comparison between 3rd generation cephalosporins?
ceftriaxone long half life 6-9 hours and ceftazidime shorter half life 90 minutes
What is ceftazimide used to treat?
meningitis, brain abcess
pseudomonas aueruginosa esp those resistant ot aminoglycosides
poorest for gram positive
What is the most active 3rd gen cephalosoporin for psuedomonas aeruginosa?
ceftazidime
What is teh poorest 3rd gen cephalosoporin for gram positive?
ceftazidime
What is a fourth generation cephalosporin?
cefepime
What is teh half life of cefepime?
2 hours
What is the spectrum of cefepime?
similar to ceftazidime except more resistant to inducible chromsomally endoced type 1 beta lactamases so covers mroe gram negative strain
What is cefepime used to treat
empirical treatment of serious inpatient infections where both gram positive and gram negative etiologies are possible
What are cephalosporins asa whole bad at treating?
camplobacter legionella C. Diff listeria Acinetobacter enterococcus penicillin resistant strep pneumoniae MRSA
How are cephalosporins excreted?
Renally: GFR and anion secretion
What are teh allergic reactions of cephalosporins?
2-10% ( 1-20% pts cross react with penicilin)
What are teh side effects for sephalosporins?
allergic rxns
GI issues-generational differences
hepatocellular damage
What do extended spectrum Beta-lactamases inactivate?
penicillins as well as drugs considered beta lactamase resistant such as 3rd gen cephalosporins and monobactams
What are the treatment of choice for ESBL (extended spectrum beta lactamase) organisms?
carbapenems
What is the spectrum of imipenem?
broad spepctrum
gram pos and gram negative
resistant to most beta lactamases including ESBLs
What is imipenem not for?
C. diff, MRSA, Enterococcoccus faecium, some psuedomonas, stenophomonas
What class is imipenem?
carbapenem
What is imipenem used for therapeutically?
ill-defined infections
mixed infections
non-responsive or resistant to other drugs (ESBLs)
Why is imipenem given with cilastatin?
to prevent hydrolysis by renal dipeptidases
What are teh side effects of imipenem?
allergic rxns
seizures, dizziness, confusion
nausea, vomitin, diarrhea, pseudomembranous colitis, superinfection
thrombophlebitis
What is aztrenoam used to treat?
gram negative aerobic rods resistant to many beta lactamases
Does aztreonam have allergic cross-reactions with beta-lactams?
no
What are the side effects of aztreonam?
seizures, anaphylaxis, transient EKG changes
- GI issues
- hepatiits, jaudice, confusion
What is hte mechanism of action of vancomycin?
binds to free carboxl end of D-ala-Dala of the pentapetptide interferes with cross–linking of petidoglycan chain
What is vancomycin used to treat?
gram positives only staph, incl MRSA strep pneuomniae; hemolytic strep enterococcus (20-30% resistant VRE) C. dif enterocolitis
How is vancomycin administered?
IV for systemic infection
limited pen into CSF
oral for C. diff eneteroclitis
How is vanocmycin used to treat meningitis?
poor pen without inflamed meninges so used as a second line for cephalosporin resistant by combining 3rd gen cephalosporin and vancomycin together
What are the side effects of vancomycin?
nephrotoxicity red man syndrome ototoxicity phlebitis hypersensitivity, skin rashes, neutropenia
What is the use of fosfomycin?
uncomplicated UTIs caused by E. coli and enterococcus
What are the side effects of fosfomycin?
headache, diarrhea, nausea, vaginitis
dizziness, rash
What is the mechanism of bacitracin?
interferes with cell wall syntehsis by interfereing with carrier that moves early wall components through membrane
What is bacitracin used for?
topical only and used only against the gram positive spectrum
What is the side effect of bacitracin?
allergic dermatitis
What are drugs that target cell membrane?
polmyxin B and E
daptomycin
What is the mechanism of polymyxin B?
branched chain decapeptides; act as cationic detergents taht binds LPS in outer membrane of gram negatives
What are the side effects of polymyxin B?
topical use-few probelms, allergies
systemic use-potential for serious nephrotoxicity and neurotoxicity
What is the mechanism of daptomycin?
binds to bacterial cytoplasmic membrane causing rapid membrane depolarization
stops essential metabolic and catabolic steps
rapidly bactericidal
What is the spectrum of daptomycin?
gram positive spectrum
no cross resistance
What is the use of daptomycin?
for complicated skin and skin structure infections
MRSA
Streptococcus
Enterococcus (vancomycin-susceptile only)
bacteremia
not for pneumonia
What are the side effects of daptomycin?
nausea, diarrhea, GI flora alterations
including C. Diff enterocolitis
muscle pain and weakness
fever, headache, rash, dizziness, injection site rxn
What is the mechanism of action of quinolones?
inhibits alpha and possibly beta subunit of DNA gyrase, thereby interfering with control of DNA winding
bactericidal
How is killing by quinolones best predicted?
AUC24/MIC
more frequent doses
more drug per dose
longer half life
What is the norfloxacin used for?
prototype quinolone for urinary infections
limited use at other sites
What is ciprofloxacin used for?
useful for infections at many sites UTI infectious diarrhea bone and joint infections skin infections not best choice for gram positive infections chlamydia haemophilus anthrax
What is better against gram positive than cirpofloxacin used for?
moxifloxacin and levofloxacin
Quinolones administered how?
oral some also IV
How is quinolones distributed?
many fluorinated drugs are well-distributed
some and the nonfluorinated agents achieve therapeutic concentration onsly in urinary tract
What are the quinolones side effects?
nausea, vomitting, abdominal paiin rare seizure dizziness, headache, restlesness, depression rashes, some serious potentially fatal EKG iregullariteies, arrythmias peripheral neuropathy; rapid onset children cartilage damage cautioned precautions those with seizure disorder and pregnancy arthropathy-tendon rupture
What is the mechanism of nitrofurantoin?
itroreductase enzyme converts tehse drugs to reactive compounts whch ccan damage DNA
What does nitrofurantoi treat?
UTI lower only not renal
What are teh side effects of nitrofurantoin?
nausea, vomiting, diarrhea hypersensitivity, fever, chills peripheral neuropathy acute and chronic pulmonary reaction acute and chronic liver damage granulocytopenia, leukopenia, megaloblatic anemia acute hemolytic anemai
What is the mechanism of rifampin?
binds to and inhibits RNA pollymerase Beta
inhibits RNA synteshis
bacteriacidal
What is rifampin used for?
tuberculosis
meningitis prophylaxis
difficult infections
Wha are the side effects of rifampin?
serious hepatotoxicity
strongly induces many other enzymes including CYP3A
orange color to excrement
may others
What is the mechanism of fidaxomicin?
non competitive inhibitor of RNA polymerase
What is fidaxomicin used for?
clostridium dif infxn; 3rd line
bacteria cidal
What is the spectrum of fidaxomicin?
narrow gram pos mainly clostridium
oral admin, poorly absorbed
limited impact on normal GI flora
What are fidaxomicin side effects?
GI upset, GI bleed, neutropenia
What is the mechanism of action of metronidazole?
anaerobes reduce the nitro group resuting produc damages and disrrupts DNA
bacteriacidal
What are the uses of metronidazole?
anaerobes
C. diff enterocolitis
H. pylori combo therapy
bacterial vaginosis
What are the side effects of metronidazole?
nausea, vomiting, anorexia, diarrhea
transient leukopenia, neutropenia
thrombophlebitis after IV infusion
bacteria and fungal superinfection
Aminoglycosides are unique how?
only protein synthesis inhibitors that are bactericidal
What is teh mechanism of aminoglycosides?
transported into bacteria by energy-requirng aerobic procesc
bind to several ribosomal sites; stop initiation, cause mRNA misreading
What is the primary use of aminoglycosides?
primarily for gram negative aerobic bacilli
poor activity against anaerobes
How do you use aminoglycosides with gram positive bacteria?
cell wall inhibitors plus aminoglycosides lead to increased permeability and death of aminoglycosides
Aminoglycosides have post-antibiotic effect?
sustained activity for several hours after aminoglycoside concentraion ahd dropped below effective levels
concentration dependent killing
Aminoglycosides are restricted to what type of infections?
serious infections
What are teh three aminoglycosides?
gentamicin, tobramycin, amikacin
What ist he choice agent for gentamicin and tobramycin resistant straing?
amikacin
What are the two classic side effects of aminoglycoides?
nephrotoxicity-mostly reversible
ototoxicity-mostly irreversible
neuromuscular blockade-less common; associated with intraabdominal infection
Tetracyclines are what type of mechanism?
transported into cells by protein carrier binds aminoacyl-tRNA to 30S ribosomal subunit
What is teh most common for of resistance to tetracyclines?
drug efflux pumps, resistance to one tetracycline implies resistance to all
Use of tetracycline is the preffered agent for what?
unusual bugs rickettsia lyme disease chlamdia, mycoplasma, ureaplasma(atypical) chancroid (haemophilus ducreyi)
What are the two tetracyline examples?
doxycycline and minocycline
What is doxycycline used for?
alternative for penG-sens syphilis
uncomplicated N. gonorrheae
What is unique about doxycycline among tetracyclines?
has the least affinity for calcium
Binding calcium does what to tetracycline?
inhibits it’s absorption
What are the side efffects of tetracycline?
GI disturbance photosensitization cadida infection teeth discoloration- avoid use in you children contraindicated in pregnancy
Tigecycline is used when?
increased risk of death makes it a last line drug when nothing else is working
Chloramphenicol has what mechanism of action?
binds 50S subunits to prevent protein use
Chloramphenicol has what major side effect and used for what?
very serious can result in bone marrow suppression
alternative in those with serious cephalosporin meningitis
brain abcesses (often anaerobes)
What are the major side effects of chloramphenicol?
Gray baby
bone marrow suppression
-fatal aplastic anemia (1 in 30000)
optic neuritis and blindness
What are the macrolides?
erythromycin, clarithromycin, azithromycin
What is the mechanism of macrolides?
bind 50S subunit and blocks translocation
What is erythromycin used for?
primarily against gram positive
2nd line against strep in allergic
also effective against atypical bugs
-mycoplasma, chlamydia, brdetella, legionella
What is erythromycin side effects?
rapid vomitting and nausea from enhacned GI motility
inhibits CyP3A metabolism
increased risk of arrythmias and cardiac arrest
-doubles risk on its own
5 fold on other CYP3A inhibitors
What is Clarithromycin role?
most expensive macrolide; similar mechanism
also some CV risk
prolongs QT interval
but less GI motility, wider antibacterial spectrum
What is the use of clarithromycin?
same as erythromycin plus: haemophilus influenzae, moraaxella pneicillin resistant strep pneuoniae atypical mycobacteria liscened for heliobacter pylori 3 drug combos are becoming standard
Heliobacter approved eradication include what?
combination with 2 antibiotcs + acid blocker most efective combination
What is the role of azithromycin
very common for outpatient respiratory tract infections
also genita infections-chlamydia and 2nd line for N. gonorrhea
Azithromycin has what adverse reactions?
fewer
still QT prolongation
fewer effects on CYP3A4
What is clindamycin mechanism of action?
binds to 50S ribosomal subunit
What is clindamycin famous for?
causing C. diff infections
What is the use for clindamycin?
Strep and MSSA (gram pos cocci)
suppresses bacterial toxin production
many anaerobes including bacteroides flragiles
What are the side effects of clindamycin?
liver damage
colitis
GI problems
What is the mechanism of linezolid?
binds to 50S ribosomal subunit and interferes with formation of 70S initiation complex
Linezolid is used for what?
gram positive spectrum Vancomycin resistant Enterococcus Staph Aureus including MRSA Strep Nosocomial pneuomniae
What are the side effects of linezolid?
non-selective inhibitor of MAO
diarrhea, eneterocolitis
headache, nausea/vomiting
bone marrow suppresion
What are the anti-folates?
inhibit folate synthesis
sulfamethoxazole
sulfadiazine
trimethoprim
What is mechanism of action of sulfonamides?
competitive analogs of p-aminobenzoic acid, a precursor in folate synthesis
Sulfonamides are used how?
wide spectrum but high resistance
used in combination with others
What is silver sulfadiazine used for?
used topically for infection prevention in burn pts
large amount of its effect is silver
What are the side effects of sulfonamides?
hypersensitivity sunlight makes rashes worse renal damage (crystalluria) potentiate actions of other drugs inhibit CYP2C9 therefore ave an effect on warfarin
Sulfonamides plus trimethorpim has waht sort of effect
-cidal effect; unusual bc its two statics
what is trimethorprim used for?
in combo wit sulfamethoxazole used for uncomplicated UTIs -E.coli and coagulase negative staph upper respiratory tract, ear infections GI infections 1st line in pneumocytis jiroveci
What are the side effects of the TMP/SMX side effects?
all of the sulfa side effects
bone marrow suppression
GI effects
What is one common use of empiric therapy?
uncomplicated cstitis in nonpregnant women
