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Review of Antimicrobial Therapy
Overview
79
Astronomy
6th Grade
03/21/2014

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Term
Natural Penicillins
Definition
Pen VK (oral); pen G (IV), pen G procaine or benzathine (IV/IM)
Term
Natural PCNs Activity
Definition
gram-positive (except Staph), non-bacteroides anaerobes, +/- gram-negatives
Term
Natural PCNs Indications
Definition
strep. infections (otitis media, pharyngitis, meningitis and skin infections); STDs (syphilis +/- gonorrhea)- pen G procaine and pen G benzathine increase compliance- big syringes IM ceftriaxone and 1 g Azithro; increasing incidence of pen-resistant S. pneumoniae (PRSP)- pen-producing N. gonorrhea (PPNG)- 50% of gonorrhea
Term
Probenicid plus PCN
Definition
will enhance PCN blood levels (20 min half life)
Term
Penicillinase resistsant PCNs (or anti-staphylococcal PCNs)
Definition
dicloxacillin (oral); nafcillin = oxcillin (IV)
Term
anti-staphylococcal PCNs Indications
Definition
primary is Staph infections (cellulitis, sepsis, pneumonia +/- UTIs), empiric therapy for bacterial endocarditis
Term
anti-staph PCNs Acitivity
Definition
enhanced to cover Staph (PCNase producing)- especially in drug users
Term
amino-penicillins
Definition
amoxicillin (PO), ampicillin (IV)
Term
amino-penicillins activity
Definition
broader coverage against gram - bugs (e. coli, klebsiella and haemophilus) but like the natural they are inactivated by PCNases (no good against Staph)- wimpy gram -
Term
amino-penicillins indications
Definition
upper resp. tract infections like otitis media and sinusitis, pharyngitis; amoxicillin extensively used for pediatric infections, especially respiratory
Term
has an increased tendency to cause diarrhea
Definition
ampicillin
Term
hepatically eliminated and doesn't require renal adjustment
Definition
nafcillin
Term
preferred over ampicillin for oral therapy (40% H. flu (+) beta lactamase)
Definition
amoxicillin
Term
help stabilize b-lactamase enzymes (Augmentin and Unasyn)
Definition
beta-lactamase inhibitor combos
Term
can overcome some strains of PRSP
Definition
higher b-lactam doses
Term
anti-pseudomonal PCNs
Definition
Hospital acquired gram -; Piperacillin > mezlocillin> ticarcillin > carbenicillin; single agents mostly obsolete- replaced by piperacillin/tazobactam (Zosyn)
Term
antispeudomonal PCNs indications
Definition
serious gram negative infections (sepsis, pneumonia, abdominal infections, osteomyelitis); hospital acquired infections, especially Pseudomonas
Term
Anti-Pseudomonal Reactions
Definition
sodium content of Ticar/Carbenicillin may cause a problem in CHF patients
Term
Penicillins
Definition
inhibition of cell wall synthesis which results in membrane lysis
Term
Cephalosporins
Definition
inhibition of cell wall synthesis which results in membrane lysis
Term
Cephalosporin Spectrum
Definition
in general, as you move from 1st to 3rd generation you gain greater gram negative coverage at the expensve of gram positive coverage; exception: 4th generation- cefipine
Term
cephalosporins adverse reactions
Definition
generally well tolerated; about 10% of pts allergic to PC are cross-reactive to cephs; the ones with 3 methyl thiotetrazole componenet may predispose pts to bleeding abnormalities or cause a disulfiram reaction
Term
cephalosporins: except for cefoperazone
Definition
are renally eliminated: may need to adjust in renal dysfunction
Term
only parenteral agent used for the 1st gen cephs
Definition
cefazoline
Term
stand alone 2nd gen: no anaerobic activity like other 2nd gen cephs, available an oral form (Ceftin) for step down therapy after IV
Definition
cefuroxime
Term
3rd gen ceph with the longest half life of all cephs (dosed once daily)
Definition
ceftriaxone
Term
efficient at crossing the blood brain barrier into the CSF (meningitis)
Definition
cefotaxime
Term
tend to be the primary workhorses of the 3rd gen cephs
Definition
ceftriaxone and cefotaxime
Term
preferred cephalosporin for Pseudomonas infections
Definition
ceftazidime
Term
1st generation cephalosporins
Definition
Anti-staph PCN- Cefazoline only real 1st gen
Term
1st gen ceph: activity
Definition
primarily gram positive (including Staph) but not enterococci. also active against wimpy gram - bugs (e. coli, klebsiella, proteus)
Term
1st gen cephs indications:
Definition
widely used for surgical prophylaxis; cellulitis and other skin infections, susceptible gram + infections, strep infections (OM, pharyngitis, meningitis, skin infections)
Term
2nd gen cephs (kind of forgotten)Activity
Definition
increased against gram negative bugs (Haemophilus, enterocbacter, Neisseria and anaerobes)
Term
2nd gen cephs indications
Definition
2 primary types: those with anaerobic activity (most of the agents)- replaced by Zosyn; those without anaerobic activity (cefuroxime), but good activity for respiratory infections - few that are available IV and oral, replaced by levofloxacin; Outside of surgical prophylaxis these agents are not used very often
Term
3rd generation cephs- Anti PS PCN
Definition
most active against stubborn gram negative organisms such as Pseudomonas, Serratia, Providencia, Citrobacter, Acinetobacter
Term
3rd gen cephs indications
Definition
1. cefotaxime or cceftriaxone and 2. ceftrazidime. double therapy; primarily used in hospital-acquired infections involving gram - bugs; serious gram - infections such a sepsis, pneumonia, meningitis; infections caused by organisms resistant to 1st and 2nd gen; empiric therapy until cultures are known; ceftriaxone IM as a single dose for treating STDs
Term
4th generation cephalosporins- cefepime- similar to Zosyn
Definition
touted as having the same activity of 3rd gen cephs without losing the gram + activity typically seen with the 1st gen cephs
Term
anti- MRSA ceph
Definition
ceftaroline (Teflaro)
Term
patients who are allergic to beta lactams shouldn't be with these
Definition
carbapenems
Term
Carbapenems
Definition
inhibition of cell wall synthesis
Term
Carbapenem Agents
Definition
Imipenem/Cilastatin (Primaxin); Meropenem (Merrem); Ertapenem (invanze)- all are IV
Term
Carbapenem Activity
Definition
the BROADEST SPECTRUM abx currently available. Active against anerobes, gram + cocci (including enterococcus) and gram - organisms (including pseudomonas) --- covers a lot of things but not very deep
Term
Carbapenem indications
Definition
excellent for empiric coverage pending culture results- then need to fine tune therapy; used in situations where several bacteria are involved in the infection; used in severe infections resistant to other agents
Term
carbapenems adverse reactions
Definition
pseudomembraneous colitis and superinfection are common problems because it can kill good bacteria also; seizures (beta lactam like abx) may also occur with large doses and prolonged treatment
Term
carbapenem 1:1 combination to avoid inactivation by renal dipeptidases
Definition
with cilastatin (enzyme inhibitor)
Term
Quinolones
Definition
bactericidal agents that inhibit DNA gyrase. New MOA
Term
quinolone agents
Definition
ciprofloxacin, levofloxacin, moxifloxacin (most IV and oral)
Term
quinolone activity
Definition
older agents have good activity against gram negative bugs and are fairly active against gram positive bugs (exception: cipro has poor coverage against strep pneumoniae); newer agents have enhanced gram + activity but cover gram - to a lesser extent
Term
referred to as the pneumococcal quinolones
Definition
gatifloxacin, moxifloxacin, gemifloxacin
Term
referred to as the respiratory quinolones
Definition
levofloxacin, moxifloxicin
Term
Quinolones Indications
Definition
treating pneumonia, bone and joint infections, prostatitis, cellulitis, UTI's and infectious diarrhea; newer agents target CAP; follow up oral therapy for infections requiring prolonged antimicrobial therapy; become popular agents for empiric therapy
Term
one of the few studied drugs used for the treatment of anthrax
Definition
Ciprofloxacin
Term
Quinolones Adverse Reactions
Definition
generally well tolerated; mild SE include GI complaints, CNS problems, glucose control; some have been limited due to phototoxicity, hepatotoxicity, cardiovascular side effects
Term
not approved for use in pediatric patients- used for cystic fibrosis
Definition
Quinolones
Term
Macrolides: Old- Erythromycin
Definition
Inhibition of protein synthesis
Term
Macrolides Agents
Definition
Erythromycin (PO and IV), Clarithromycin (Biaxin oral), Azithromycin (Zithromax oral and IV)
Term
Macrolides Activity
Definition
used primarily for gram + cocci and bacilli, particularly in community acquired infections that may involve "atypical" bacteria. Little activity against hospital acquired gram -
Term
Macrolides Indications
Definition
community acquired respiratory infections (atypical organizms: Mycoplasma, Chlamydia, Legionella)
Term
azithromycin:
Definition
1000 mg dose x 1 for STDs
Term
clarithromycin:
Definition
for MAC infections in HIV
Term
Macrolides Adverse Reactions
Definition
biggest problem with erythromycin is GI disturbances (nausea, vomiting, diarrhea); IV erythromycin can cause severe pain-- thrombophlebitis; clarith (1 g doses) can cause metallic taste
Term
can interfere with metabolism of many drugs; common alternative of penicillin allergy
Definition
erythromycin
Term
Rx interactions
Definition
erythro >> clari/azith
Term
QT interval
Definition
astemizole/terfenadine/cisapride
Term
newer macrlolides
Definition
longer half-life and better GI profile
Term
Aminoglycosides: Gram - IV
Definition
Bactericidal agents that inhibit protein synthesis
Term
Aminoglycoside Agents
Definition
gentamicin, tobramycin, amikacin, streptomycin (IV agents); neomycin (oral)
Term
Aminoglycoside Activity
Definition
excellent activity against gram - organisms, including pseudomonas (tobra > gent). Limited usefulness for gram + but gent is frequently used for synergistic activity vs. Enterococcus
Term
Aminoglycoside Indication
Definition
frequently used for hospital-acquired gram - infections involving the more stubborn gram - rods; pneumonias, sepsis, UTI/pyelonephritis, meningitis, osteomyelitis; neomycin (oral) is used to prep the bowels for surgical procedures (Selective decontamination)
Term
Aminoglycosides Adverse Reactions
Definition
most feared ADR is nephrotoxicity and oto/vestibular toxicity
Term
primary agents; amikacin is usually reserved for refractory/resistant infections
Definition
gentamicin and tobramycin
Term
need for pharmacokinetic monitoring for optimal effect and reduced toxicity; nephrotoxicity is reversible upon discontinuing therapy, oto/vestibular is irreversible; once daily dosing approach- short txt courses/still need to monitor
Definition
Aminoglycosides
Term
Vancomycin Gram + IV
Definition
inhibition of cell wall synthesis (at a step prior to beta-lactams), also believed to have additional mechanisms (direct effect on membrane and inhibition of RNA synthesis)
Term
Vancomycin Activity
Definition
limited to ONLY gram + organisms, including MRSA; reserved for serious resistant gram + infections; infections in pts with life-threatening penicillin allergies (anaphylaxis); second line agent for C diff.
Term
Vancomycin Adverse Reactions
Definition
potential for nephro and ototoxicity exists (espc if used w/ aminoglycosides); phlebitis and Red Mans Syndrome- purity and rate-related ADR
Term
pharmacokinetically monitored agent- 10-15 mg/kg w/ trough of 5-10 mg/L; daily dosing due to long half life- NOT the pharmacodynamic principles used for gent
Definition
Vancomycin
Term
Pharmacodynamics
Definition
incorporates both PK data and microbiology data (MIC)
Term
Concentration-dependent killing: Peak looks at y axis
Definition
more is better. Bacterial kill is related to dose. Higher the cmax (peak) = better kill. Aminoglycosides- once daily (extended dosing)
Term
Concentration independent (Time-dependent) killing: looks at x axis
Definition
key issue is time that the concentration is above the MIC (T>MIC) - beta lactams
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