Flashcards in miscellaneous abx Deck (42):
Vancomycin (Vancocin) administration/metabolism
IV (poor oral absorption)
-widely distributed and does penetrate the CSF when the meninges are inflamed
-90% of vancomycin is eliminated by renal excretion, adjust dose with renal failure
Vancomycin (Vancocin) MOA
inhibits bacterial cell wall synthesis by binding to the D- alanyl-D-alanine portion of the peptidoglycan pentapeptide, bactericidal
how does resistance to Vancomycin develop?
bacterial enzymes that can induce alterations in the cell wall precursors so that vancomycin can’t bind as well
i.e. Vancomycin resistant enterococci replace D-alanyl-D- alanine with D-alanyl-D lactate or D-alanyl-D-serine
MRSA, MSSA, S. epidermidis, Streptococci, Corynebacterium diptheria, Clostridium spp. (the only anaerobe effective against)
NOT against G-s
serious staph infections
G+ infections in pts allergic to PCNs/cephs (tx w. aminoglycoside for synergism)
C. diff colitis (oral vanco)
staph meningitis in a PCN-allergic pt, if caused by S. pneumo include with a 3rd gen ceph
-Ototoxicity and Nephrotoxicity: (rare)m ore common when given in combo with another ototoxic abx (i.e. amino glycoside)
-“Red man” or “Red Neck” syndrome – If vancomycin is infused too rapidly
is can cause flushing of the face, neck and torso due to histamine release.
minor: Injection site irritation, and chills and fever
-oral and parental, distributed widely EXCEPT does not penetrate well into the CNS even with inflammation of the meninges
-does have good abscess penetration
clindamycin MOA: similar to ??
imilar to erythromycin and chloramphenicol – binds to *50 S* ribosomal subunit and inhibits bacterial protein synthesis; bacteriostatic
resistance to clindamycin develops how?
-Mutations in the 50 S bacterial ribosomal subunit which prevents Clindamycin binding
-Modification of the binding site by the enzyme methylase that prevent clindamycin binding
-Enzymatic inactivation of clindamycin
-Bac resistant to clindamycin are usually resistant to
erythromycin. (similar mech)
most Staph aureus strains (has activity against some community acquired MRSA), Strept. Pneumoniae, but enterococci are resistant.
-NOT useful against G- AEROBES
-is active against G- and G+ anaerobes (B. fragilis and C. perfringens)
-anaerobic infections (abscesses)- NOT brain abscesses
-used in combo w. amino glycoside/ceph to tx deep wounds
-*ppx against endocarditis in valvular heart dis. pts who are having dental procedures
-alternative to PCN/ceph in allergic pts
-PCP and toxoplasma gondii (+pyrimethamine) in AIDS pt
*C. diff-induced Pseudomembranous colitis* (tx w. oral Vancomycin, Metronidazole, and Cholestyramine (not orally w. vanco: antagonistic effect)
Nitrofurantoin (Furadantin, Macrobid, Macrodantin)
-Rapidly absorbed after oral admin, metabolized/excreted by glomerular filtration and tubular secretion (40% of free drug is found in the urine), often so quickly drug effects not seen!
-don't use in renal failure
-reduced forms can damage DNA, both bactericidal and static
-admin w. acidifying agent (more active @ pH
-G+ and G- bac
-NOT effective against Pseudomonas and many Proteus strains (resistant)
-Bac resistance takes a long time to develop and there is no cross resistance with other abx
-tx UTIS and for ppx for recurrent UTIs (used of UTIs caused by E. coli resistant to TMP-SMX and FQs)
*GI: anorexia, N/V
*hemolytic anemia (rare, seen in pts w. G6PD deficiency)
-neurological, pulmonary fibrosis, chronic active hepatitis, allergic reactions
-contraindicated in renal failure, caution w. preggos
Polymyxin B sulfate (generic) MOA
what does resistance involve?
interacts with cell membrane phospholipids, and disrupts cell membrane perm., and causing leakage of intracellular components, bactericidal
-Resistance may involve inability of the polymyxins to pass through the cell wall.
polymyxin B spectrum
only susceptible G- bac (e.g. Enterobacter aerogenes, E. coli, Klebsiella pneumonia, H. influenzae, Acinetobacter baumannii, Pseudomonas aeuriginosa)
polymyxin B uses
topical treatment of Infections of the eye, skin, mucous membranes, ear, wounds, burns (G-s)
-used IV as alternative for drug-resistant resp. tract infections (HAP, HCAP, VAP) caused by DR-G-
-septicemia, UTIs (IV, IM)
-meningitis (typ. in combo)
-irrigate the bladder to prevent bacteriuria/bacteremia assoc. w. indwelling catheters (used w. neomycin)
polymyxin B SEs (both dose-dependent) (why polymyxins are reserved as alternate tx)
*Neurotoxicity*: (facial flushing; dizziness that may progress to ataxia; mental confusion; nystagmus; muscle weakness; drowsiness; giddiness; peripheral paresthesia, visual disturbances, slurred speech, coma and seizures)
*Nephrotoxicity*: (albuminuria, proteinuria, cylindruria, azotemia, inc. in serum creatinine (dec. in creatinine clearance), acute tubular necrosis, oliguria, hematuria, leukocyturia, and excessive excretion of e-lytes)
-oral, IV, rectal, topical (vag)
-widely distributed, including the CNS and brain abscesses
-crosses the placenta and appears in breast milk
-metabolized in the liver and exreted by the kidneys
reduction of the drug to compounds that bind to intracellular macromolecules, bactericidal
-*active against clindamycin-resistant B. fragilis (*drug of choice in adults*)
-bactericidal activity against Anaerobes (including bacteriodes fragilis)
-NOT v. effective against Not very effective against G+ and G- AEROBES
-Anaerobic infections (soft tissue infection, intra-abdominal infections, pelvic infections, brain abscesses).
-C. diff Pseudomembranous colitis
-PUD caused by H. pylori (Triple therapy)
-Carcinogenic potential, don’t use in pregnancy or in women during breast
-Disulfiram-like interaction with alcohol.
-opthalmic and dermatologic ointments
-not used much parenterally because of nephrotoxicity
-inhibits cell wall formation, interferes with the lipid that carries peptidoglycan subunits to the site of cell wall formation.
-No cross resistance with other antimicrobials.
-similar spec. to PCN: G+ cocci and bacilli
-G-s such as Neisseria, H. influenzae; and the spirochete Treponema palladium
-topically for open wounds to eradicate mixed microorgs
-eye infections (e.g. conjunctivitis)
(may be used in combo, i.e.: bacitracin + polymyxin + neomycin)
Serious nephrotoxicity from parenteral use; renal failure due to tubular and glomerular necrosis.
-Hypersensitivity reactions from topical use are rare.
Quinupristin/Dalfopristin (Synercid) used for ??
IV tx of bacteremia and other life threatening infections caused by vancomycin-resistant Enterococcus faecium, and complicated skin infections caused by S. aureus and Strep pyogenes (when resistant to other abx, or contraindicated due to allergy)
-Enterococcus faecium, MRSA/MSSA, S. epidermidis, PCN-susc. and resistant S. pneumo
Quinupristin/Dalfopristin (Synercid) MOA
(similar to the macrolide)
-inhibits bac protein synthesis by binding to the *50 S* ribosomal subunit.
-The two drugs bind to different sites on the 50 S ribosome and prevent the extrusion of new proteins which results in bacterial cell death.
Quinupristin/Dalfopristin (Synercid) resistance occurs via ??
Modification of the quinupristin binding site on the 50S ribosomal subunit, enzymatic destruction of dalfopristin or efflux
-Erythema, pain, itching and burning at the site of infusion
Oral admin, Parenteral
Bacterial protein synthesis inhibitor by binding to the 50S bacterial ribosomal
subunit and prevents formation of the 70S translational initiation complex; Bactericidal for Streptococci with bacteriostatic activity against many other bac
Linezolid Resistance in ?? and ?? is caused by ??
enterococci and staphylococci
point mutations in the 23S rRNA of the 50S subunit.
-Vanco-resistant Enterococcus facacium
-Nosocomial pneumonia or CAP due to S. aureus
or PCN-susc. Strep pneumo
-Skin/skin structure infections: MRSA and Strep Pyogenes
*reversible inhibitor of monoamine oxidase* (co-
admin with tyramine rich foods can result in HTN)
-oral formulation contains phenylalanine, avoid in PKUs
-C. diff-assoc. colitis
-poor oral absorption, admin IV
-avoid IM due to musc. tox
-80% excreted in the urine, adjust dose if creatinine clearance is below 30 mL/min
Daptomycin (Cubicin) MOA
concentration-dependent killing effect by binding to and depolarizing bacterial cell membranes which leads to loss of membrane potential, postassium efflux, and cell death.
-no known resistance mechs
-Bactericidal for aerobic, facultative and anaerobic G+ bac
-Complicated skin/skin structure infections caused by MRSA/MSSA, hemolytic streptococci, and vanco-susc. E. faecalis