Antibiotics Flashcards
Narrow spectrum, beta-lactamase sensitive (natural) penicilins? Give spectrum, place in therapy, side effects, and PEARLS as warranted for this and all other cards.
Penicillin V (PO), Penicillin G (PO, IV) Spectrum Effective against non- β- lactamase producing bacteria • Streptococci • Anaerobes Place in Therapy Oral strep infection Non-purulent cellulitis Syphilis Side Effects • Hypersensitivity reactions
Very narrow spectrum, beta-lactamase resistant (anti-staphylococcal) penicillins?
Oxacillin (IV), Nafcillin (IV), Methicillin. Spectrum • MSSA • Streptococci Place in Therapy MSSA infection Side Effects(Rare) • Nafcillin-thrombophlebitis, neutropenia • Oxacillin-hepatotoxicity, neutropenia PEARLS • Bulky side chain shields β-lactam ring from penicillinase (DEVELOPED TO TREAT PENICILLINASE-PRODUCING MSSA)
Broad spectrum, aminopenicllins?
Ampicillin (IV), Amoxicillin (PO).
Spectrum
• Streptococci, enterococci
• Listeria
• Some gram negatives (Proteus mirabilis, E. coli)
(NOT INDICATED FOR EMPIRIC THERAPY)
Place in Therapy
Amoxicillin: Community-acquired upper respiratory tract infections
IV ampicillin: DOC for enterococcal infections (amp sensitive)
IV ampicillin: Listeria meningitis
IV ampicillin with aminoglycoside: Enterococcal endocarditis
Side Effects
• Hypersensitivity reactions
o Non-IgE rash (delayed hypersensitivity)
o IgE reaction (Type I)
PEARLS
• Still susceptible to effects of β-lactamase produced by Staph and other gram-negative
organisms
• Increased risk of cross-reactivity with cefadroxil & cefprozil due to identical side chain
Extended spectrum (antipseudomonal) penicllins + B-lactamase inhibitor?
Ampicillin/sulbactam (IV), Amoxicillin/clavulanate (PO), Piperacillin/tazobactam (IV), Ticarcillin/clavulanate (IV). Antipseudomonal: Ticarcillin & Piperacillin.
Spectrum
• Enhanced gram-negative activity (Enterobacteriaceae)
• Enhanced gram-positive activity (MSSA)
• Anaerobes including B. fragilis
Place in Therapy
• Pip/taz, Ticar/clav
o Nosocomial infections including pneumonia, intra-abdominal infections, wounds
• Amox/clav, Amp/Sulb
o Animal & Human bites
o Upper respiratory infections (step up from amoxicillin)
o Diabetic foot infection
Side Effects
• Non-IgE rash
• Hypersensitivity reactions
• Amox/clav (Augmentin)-diarrhea
• Piperacillin-tazobactam-thrombocytopenia (rare), interstitial nephritis
First generation cephalosporins?
Cefazolin (IV), Cephalexin (PO). Spectrum • Streptococci, MSSA • Some gram-negatives (β-lactamase limits gram-negative spectrum) • NO Anaerobes, NO Enterococcus Place in Therapy • Definitive therapy based on cultures o E. coli, Klebsiella UTI o MSSA • Surgical prophylaxis Side Effects • Less antigenic than penicillins; higher cross reactivity with PCN than other cephalosporins PEARLS • Not for CSF infections
Second generation cephalosporins?
True cephalosporins: Cefuroxime (IV/PO), Cefaclor (PO), Cefprozil (PO), Loracarbef (PO); Cephamycins: Cefoxitin (IV), Cefotetan (IV).
Spectrum
• True Cephalopsporins and Cephamycins differ
• True Cephalosporins
o Better activity against S. pneumoniae than 1st gen
o Better gram negative activity than 1st gen, but still NO pseudomonas!
• Cephamycins
o Better activity against E. coli and Klebsiella
o ACTIVITY AGAINST ANAEROBES (UNIQUE AMONG
CEPHS)
Place in Therapy
• True Cephs: CA respiratory tract infections
• Cephamycins: Mostly surgical prophylaxis colon surgery
PEARLS
• You may be tempted to use cephamycins for ESBLs based on susceptibility results…don’t do it!
Third generation cephalosporins?
Ceftriaxone (IV), Cefotaxime (IV), Cefdinir (PO), Cefixime (PO), Cefpodoxime (PO), Ceftibutin (PO), Ceftazidime (IV)
.Spectrum
• Activity against Enterobacteriaceae increased
• Ceftriaxone, cefotaxime: S. pneumoniae, H. influenzae, M. catarrhalis
o Probably less active against MSSA than 1st generation cephs
• Ceftazidime: P. aeruginosa
o Poor activity against gram-positive organisms (S. pneumoniae, MSSA)
• STILL NO ACTIVITY AGAINST ENTEROCOCCUS, ANAEROBES
Place in Therapy
• Ceftriaxone (adults) & Cefotaxime (infants)
o Disease states where S. pneumoniae, H. influenzae likely; CAP, meningitis
o Disease states where enteric gram-negatives are likely: intra-abdominal infections (w/flagyl),
UTIs
o Ceftriaxone:lyme
• Ceftazidime & Cefepime
o Nosocomial infections where Pseudomonas is a concern
o Ceftaz has poor gram-positive activity
PEARLS
• No renal dosing required for ceftriaxone; can cause biliary sludging & calcium crystals w/infants
Fourth generation cephalosporin?
Cefepime (IV).
Spectrum
• Excellent gram-negative activity including Pseudomonas
• Better activity against gram positive organisms than ceftazidime
• Think of cefepime as piperacillin/tazobactam without the anaerobic activity
• STILL NO ACTIVITY AGAINST ENTEROCOCCUS, ANAEROBES
Place in Therapy
• Nosocomial infections
• Monotherapy for febrile neutropenia
• Post-neurosurgical meningitis
• Nosocomial pneumonia
Side Effects
• Similar to other beta-lactams
Fifth generation cephalosporins?
Ceftaroline, Ceftobiprole.
Spectrum
• Similar gram-negative activity to ceftriaxone (NO Pseudomonas)
• S. aureus INCLUDING MRSA
• Some enterococcus activity (E. faecalis) {Unlike other
cephalosporins}
• STILL NO ACTIVITY AGAINST ANAEROBES
Place in Therapy
• Monotherapy for complicated skin & soft tissue infections
• Jury’s still out on off-label indications
PEARLS
• Ceftaroline-resistant MRSA reported already
Monobactam?
Aztreonam. Spectrum • GRAM-NEGATIVES including P. aeruginosa • NO ACTIVITY AGAINST GRAM-POSITIVES • NO ACTIVITY AGAINST ANAEROBES • Very similar to aminoglycosides Place in Therapy • Usually used in combination with other agents for nosocomial infections especially in patients with: o Penicillin allergy o Renal dysfunction PEARLS • Shares the same side chain as ceftazidime o Potential for allergic cross-reactivity in patients specifically allergic to ceftazidime
Carbapenems?
Imipenem (w/ cilastatin), Meropenem, Ertapenem, Doripenem.
Spectrum
• Broad-spectrum activity including anaerobes
• ERTAPENEM less broad (NO P. aeruginosa)
• NO MRSA
• Enterococcal coverage relatively poor
Place in Therapy
• Nosocomial infections, especially polymicrobial ones!
• Ertapenem
o Community-acquired intra-abdominal infection
o Polymicrobial infections that do not involve Pseudomonas
o Convenient dosing regimen for outpatient use (once-daily)
Side effects
• Similar to other beta-lactams
• Imipenem: seizures (most often in renal dysfunction)
Vancomycin?
Mechanism of Action
• Binds to D-Ala-D-Ala end of pentapeptide which prevents elongation of peptidoglycan and crosslinking
Mechanism of Resistance
• VISA-rare (thickened cell wall)
• VRE-synthesis of abnormal peptidoglycan precursors (D-Ala-D-Lac)reduces vanco affinity 1,000
fold
Spectrum
• GRAM POSITIVES INCLUDING MRSA, coagulase-negative staph, streptococci, enterococcus
Place in Therapy
• Serious MRSA infection
• DOC for coagulase-negative staph infections
• Enterococcal infections
Side effects
• Renal dysfunction (especially in patients with troughs>20 mg/L)
• Redman syndrome: not a hypersensitivity reaction (histamine release due to high osmolarily of
vanco solution
• True hypersensitivity reactions can occur
Lipoglycopeptides (analogues of vancomycin)?
Dalbavancin, Telavancin, Oritavancin (all IV).
Spectrum
• GRAM POSITIVES INCLUDING MRSA, coagulase-negative staph, streptococci, enterococcus
(Oritavancin, Telavancin active against VRE)
Place in Therapy
• Skin & Soft tissue infection
Dosing
• Telavancin: daily
• Dalbavancin: 2 doses a week apart
• Oritavancin: 1 time dose
Side effects
• Telavancin: nephrotoxicity, metallic taste, nausea
PEARLS
• More rapidly bactericidal than vancomycin
• Resistance a concern with dalbavancin and oritavancin due to LONG half-life
Daptomycin?
Spectrum
• GRAM POSITIVES INCLUDING MRSA, coagulase-negative staph, streptococci,
enterococcus including VRE
Place in Therapy
• Alternative to vancomycin (not effective for pneumonia)
Side effects
• Myalgia that can result in rhabdomyolysis
• Rare: eosinophilic pneumonia
Aminoglycosides?
Gentamicin (IV), Tobramycin (IV/INH), Amikacin (IV), Streptomycin (IM).
Mechanism of Action
• Bind to 30S subunit of bacterial ribosomes
Spectrum
• GRAM NEGATIVES including PSEUDOMONAS
• NO GRAM POSITIVES (unless used as synergy with cell-wall active agent)
• NO ANAEROBES
Place in Therapy
• No better agent empirically when gram-negative sepsis suspected especially
if from urinary source
• MDR infections especially Pseudomonas may still have susceptibility to
aminoglycosides
Side effects
• Renal dysfunction (reduced with extended-interval dosing)
• Ototoxicity-incidence likely underreported
PEARLS
• Rapidly bactericidal with post anti-biotic effect
• Cmax:MIC ratio 8-10 x MIC is associated with improved outcomes
• Extended-interval dosing (sometimes called once-daily dosing) is less
nephrotoxic than when given q8h or q12h
