MISC abx Flashcards
Beta lactam- PCN: side chain impacts (4)
Spectrum
Stability to stomach acid
Cross-hypersensitivity
Susceptibility to bacterial degradative enzymes
adverse rxns to PCN (6)
- Allergic rxns
- GI side effects such as nausea, vomiting and diarrhea
- Nephritis – acute interstitial nephritis (nafcillin)
- Neurotoxicity – can cause seizures
- Hematologic – with therapy > 2 weeks -decrease coagulation
- Secondary infections: ex/ C. diff or vaginal candidiasis from suppressing normal flora
3 classes of PCNs
Penicillins AKA natural penicillins
Anti-staphylococcal penicillins
Extended spectrum penicillins
natural PCNs and how you administer
Penicillin G is given parenterally
Penicillin Benzathine is given IM
Penicillin V is a potassium salt, is more acid-stable, and able to be given orally
“Natural Voluptuous Girls = Benza-yonce”
what is used for gangrene and syphilis treatment?
natural PCN
spectrum of natural PCN?
treats: Gram pos. cocci and rods, and anaerobes, Gram neg cocci, and spirochetes
Little activity against gram negative rods because penicillin can’t penetrate their outer membrane
Not effective for S. Aureus
PCN MOA
inactivate transpepsidase, disrupt cross-linking (PBPs) –> cell lysis. effect mostly cells that are growing/dividing
Anti-staph PCN MOA + spectrum
Same MOA as penicillin G, but are beta-lactamase (penicillinase) resistant penicillins
Spectrum
Staphylococcus aureus (MSSA)
Streptococcus Grp A, B
extended spectrum PCN - subgroups and general spectrum
Ampicillin/amox and pipercillin/ticarcillin- greater activity against gram neg. (diff. side chain allows to better penetrate outer wall)
ampicillin/amox spectrum
Spectrum: Same as natural penicillins PLUS: gram pos and gram neg.
Not effective for pseudomonas aeruginosa or MSSA or MRSA
pipercillin/ticarcillin spectrum
natural PCN spectrum + gram negs (including pseudomonas)
Spectrum: same as ampicillin PLUS
Pseudomonas + other gram pos.
Resistance can develop so save them for when you really need them.
Used in very ill patients often in combination with another antibiotic to prevent resistance & increase killing power
Anti-staph PCN subgroups (4)
Naficillin, Oxacillin, Dicloxicillin, Methacillin
drug test for staff? “Nah… Oxy + Meth Dictate (me)”
beta lactamase inhibitor MOA
Beta lactamase is an enzyme made by bacteria that breaks apart the beta lactam ring of the ABX.
Beta lactamases are a source of resistance.
If you give an inhibitor of the enzyme that is produced by the bacteria with the Abx, the bacteria will not be as resistant to the Abx
beta lactimase inhibitor subgroups
Clavulanic acid
Avibactam (combined with ceftazidime)
Sulbactam
Tazobactam
“CAST” -inhibits from being “betta…” or
“Clara, Avi, Sultan, Taz”
beta lactams: subgroups
PCNs, Beta-inhibitors, cephalosporins, carbopenems, monobactams
dosing for combo beta-lactam inhibitors and beta lactam
Available in fixed combinations (don’t use inhibitor on its own- only in combo)
The dose is based on the strength of the primary antibiotic – not the beta lactamase inhibitor.
cephalosporins: general features
- beta lactam ring like penicillins, w/ diff base compound attached
- Generally more stable in face of beta lactamases so overall broader spectrum than PCNs
- Work similar (on bacterial cell wall) as PCN- similar resistance problems
- Potential option for PCN-allergic patient
- Bactericidal
cephalosporin: categorizing for generations
Five generations
- Generations are based on when they are made & what they kill.
- significant modification made to the group that really changed the spectrum = a new generation.
- First generation the oldest
- higher generations for deadlier bacteria species (more coverage of bacteria overall)
PK of cephalosporins: admin. distribution. elimination
Administration
-Many IV, fewer oral due to poor oral absorption
Distribution:
-Good, but CSF penetration limited to Ceftriazone, cefotaxime. All cross placenta
Elimination
-Tubular secretion and or glomerular filtration
Exception: ceftriaxone – eliminated in bile/feces
4 combos of Beta lactamase inhibitor w/ Abx
Amoxicillin + clavulanic acid = Augmentin
Ampicillin + sulbactam = Unasyn
Ticarcillin + clavulanic acid = Timentin
Piperacillin + tazobactam = Zosyn
adverse rxns to cephalosporins: hypersensitivity rxns most significant between what two types of Abx?
PCN and 1st gen cephalorsporins
*Allergy to cephalosporin = 10 % chance of allergy to PCN
Allergy to PCN = 5% change of allergy to cephalosporin
adverse rxns to cephalosporins
Hypersensitivity reactions:
GI
Superinfections: (C. difficile and vaginal candidiasis, thrush
Hypoprothrombinemia (low prothrombin level) with some cephalosporins)
Give vitamin K twice a week to prevent bleeding if giving antibiotic long term
Disulfiram-like reaction with cefotetan- (induced vomitting)
Increase nephrotoxicity of aminoglycosides
1st gen cephalosporins
Cef-azolin, Ceph-alexin
” Cefa’s PEcK” - all 1st gen only use Cefa- (except 2nd gen cefaclor)
gram + cocci: Streptococci, staphylococci
PEcK: Proteus mirabilis, E. coli, Klebsiella
Doesn’t cover: MRSA, Pseudomonas
2nd gen cephalosporins
Ce-foxtin Ce-furoxime Ce-fote-tan Cefacl-or Cef-prozil
“Fox Fur For Tan Or Prozac”
2nd gen cephalosporins Spectrum
First generation spectrum
gram + cocci: Streptococci, staphylococci
HENS PEcK
PEcK Proteus mirabilis E. coli Klebsiella PLUS: H. Influenzae Enterobacter aerogenes Neisseria spp. Serratia marcescens
Don’t get: enterococcus, Pseudomonas, or MRSA
what is cephalexin used for?
UTIs (b/c kills some gm-rods)
Skin infections (abscess and cellulitis b/c kills staph)
Otitis media, pharyngitis (b/c kill strep).
clinical uses for 2nd gen cephalosporins
Sinusitis & otitis if mildly allergic to PCN ( but Extended spectrum PCN preferred) Lower respiratory tract infections Pneumonia H. flu Moraxella catarrhalis
Cefuroxime is special for community acquired pneumonia (CAP)
b/c kills resistant H flu, strep pneumonia well
special characteristics of 3rd gen Cephalosporins
increased gram neg. coverage and only ceph.
that crosses blood brain barrier (BBB)
“Ceftaz as tazmanian devil- potent and only one that gets pseudamonas)
3rd generation cephalosporins
Cef-dinir Ceftri-axone Cef-tazidime ----(Ceftazidime/azobactam) Cefo-taxime Cef-podoxime
cephalosporins in 3rd gen all w/ suffix “-ime”
PLUS “Dine Alone” -CefDinir CeftriAzone “
3rd gen ceph spectrum
Spectrum:Great gram neg. coverage
Ceftriaxone:
Meningitis
Gonorrhea
Lyme disease
Ceftazidime
Pseudomonas coverage
Do NOT use for MRSA
clinical uses for 3rd gen cephalosporin
Clinical Uses:
Multidrug resistant gram negative organisms
HAP – Ceftazidime only
CAP
(hospital and community acquired pneumonias)
Gonorrhea
4th generation cephalosporins
Cefepime “Pi me”
Like 3rd generation more resistant to more beta lactamases
Spectrum:
Combines gram + (Streptococci & staphylococci) activity of 1st generation with wider gram – (Enterobacter, E. coli, Klebsiella) spectrum of 3rd generation
Increased activity against pseudomonas
Use: Similar to 3rd generation
5th generation Cephalosporin
Ceftaroline
Broad Spectrum:Gram positive and negative
PLUS LAME (1st-4th generation don’t cover) Listeria Atypical (Chlamydia, Mycoplasma) MRSA Enterococcus faecalis
NO Pseudomonas
monobactams: name, spectrum, adverse effects
Aztreonam
Less susceptible to beta-lactamases
Spectrum:
No gm + or anaerobe coverage
Great Gram – aerobic rods & Pseudomonas aeruginosa
Hospital drug for serious gm – infections that are resistant to other drugs or if PCN allergic and can’t use other drugs
Renally cleared – prolonged t1/2 in renal failure
Carbapenems: names,
“DIME”
Doripenem, Imipenem, Meropenem, Ertapenem
Bactericidal
“DIME” for life-threatening infections
takeaway: great broad spectrum, one of the agents (imipenem) needs to be given with cilastin to inhibit other enzyme so you can keep imipenem around . others are resistant to that enzyme
Cell Wall Antibiotics- Target PBPs
No beta lactam ring, but work on the cell wall: These work on cell wall but DONT have Beta Lactam Ring - target proteins - polypeptides
Glycopeptides
-Vancomycin- most important one
Cell membrane active agents
- Daptomycin
- Polymyxin B & Polymyxin E (Colistin)
-Fosfomycin
Vancomycin MOA
MOA:
Inhibits cell wall synthesis by binding to D-Ala-D-Ala portion of the growing peptide during cell wall synthesis
–> inhibition of transpeptidase preventing further elongation and cross-linking
Same result as beta-lactams, but targets a different site
Bactericidal
Time-dependent killing
Spectrum:
Great gm + coverage
MRSA, S. epidermidis, sensitive enterococcus, C. diff.
NO gm- anaerobes or gm-
There is now VRE (vancomycin resistant enterococcus), a bad resistant bug
Vancomycin PK: absorbtion, admin, excretion
Not absorbed from GI tract, given IV
If given orally it is not being absorbed and giving it to act topically in the GI tract (C. diff)
Slow administration – 1 hour
Renal excretion - dosage adjust in renal failure
Increased nephrotoxicity when given with other nephrotoxic drugs
Follow hospital protocol for drug dosing
vancomycin Adverse Rxns
“Well tolerated but NOT trouble free”
Nephrotoxicity – especially if given with other nephrotoxic drugs (aminoglycosides)
Ototoxicity - especially if given with other ototoxic drugs (aminoglycosides)
Thrombophlebitis- Irritates tissue at site of injection
And-redman’s syndrome
skin flushing low BP from histamine release when give IV too fast
Clinical Uses for Vancomycin
Serious MRSA infections
if MSSA, methicillin sensitive staph aureus, use antistaph penicillins
Pseudomembranous enterocolitis due to C. diff.
Endocarditis
Patients allergic to beta-lactams
Daptomycin MOA
MOA:
Binds to cell membrane of organism leading to rapid depolarization, potassium efflux and cell death
Inhibits DNA, RNA, & protein synthesis
Bactericidal
Concentration-dependent killing
Daptomycin Spectrum + adverse effect
Spectrum
Staphylococcus (MRSA), Enterococcus (including VRE)
NO gram negative activity
use: sepsis
Toxicity: skeletal muscle myalgia & weakness
Polymixin B and E: MOA
MOA:
Bind to phospholipid of gram neg and act like a detergent
(Disrupts membrane integrity)
Leads to leakage of cellular components and cell death
Bactericidal – time-dependent killing
Polymixcin B and E uses
Used for salvage therapy for multi-drug resistant gram negative
Pseudomonas, E. coli, Klebsiella
Nephrotoxic and Neurotoxic (weakness, slurred speech)
Fosfomycin MOA + excretion
MOA:
Inhibits early cell wall synthesis in gm + and gm- in urine only
Bactericidal
Excreted unchanged by kidneys
Uncomplicated lower UTI only
only for UTIs , if infection has moved further up, this drug wont be effective
