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
Tetracyclines?
Doycycline (IV/PO), Minocycline (PO), Tetracycline.
Mechanism of Action
• Bind to 30S ribosomal subunit of bacterial ribosomes
Spectrum
• ATYPICALS
• Some gram positives including CA-MRSA
• Limited gram negatives, incl. NO pseudomonas!
Place in Therapy
• Tick-borne illnesses
• Uncomplicated upper respiratory tract infections
• Option for CA-MRSA uncomplicated infections
Side effects
• GI
• Phototoxicity, discoloration of teeth (children)
Drug Interactions
• Divalent cations (calcium, magnesium, iron)
Glycylcycline?
Tigecycline. Mechanism of Action • Binds to 30 S subunit of bacterial ribosome • glycyl side chain presents efflux that causes resistance with other tetracyclines Spectrum • ATYPICALS • Broad spectrum • Some gram-negative “holes” including Pseudomonas Place in Therapy • “Back-pocket” drug for MDR infections or polymicrobial infections where a single agent is desired • Intra-abdominal infections Side effects • GI-N/V, diarrhea (significant) PEARLS • Not for bacteremia due to large Vd
Macrolides?
Azithromycin, Clarithromycin, Erythromycin.
Mechanism of Actions
• Reversible binding to 50S subunit of ribosome
Spectrum
• ATYPICALS
• Strep (resistance problematic) ~30% of S. pneumoniae is resistant to
azithromycin in our community
• Some gram-negatives (respiratory pathogens)
Place in Therapy
• Uncomplicated respiratory tract infections (use now limited by resistance)
Side effects
• GI, Hepatitis
PEARLS
• Erythromycin & clarithromycin are strong inhibitors of CYP 3A4: Increase concentrations of 3A substrates (ex. most statins!! – myopathy!!).
Clindamycin?
Mechanism of Action
• Bind to 50S ribosomal subunit
Spectrum
• Gram-positives including MRSA, however, resistance increasing; no effec against Gram-negative rods
o ~30% of MRSA/MSSA are resistant in our area
• Mouth anaerobes
Place in Therapy
• Community-acquired skin and soft tissue infection if uncertain about
pathogen (S. aureus vs. strep)
• Adjunctive therapy for severe group A strep (GAS) infections
• Alternative surgical prophylaxis in PCN-allergic patients
Side effects
• Higher incidence of C. difficile infection than other antibiotics.
Oxazolidinones?
Linezolid & Tedizolid.
Mechanism of Action
• Bind to 23S ribosomal RNA of the 50S subunit
Spectrum
• Gram-positives including MRSA, VRE, coag (-) staph, strep
o Resistance rare
Place in Therapy
• VRE infections
• Alternative to vancomycin
• Avoid for MRSA bacteremia/endocarditis
Side effects
• Bone marrow suppression (usually after 2 weeks of use)
• Peripheral neuropathy with long-term use
Drug Interactions
• Weakly inhibit MAOI: possibility of serotonin syndrome with serotonergic
agents
o No reports with tedizolid, although recently released drug
o In most cases, especially with inpatients, monitoring for signs of
serotonin syndrome permits the patient to receive the drug safely.
Quinolones?
Ciprofloxacin (IV/PO), Levofloxacin (IV/PO), Moxifloxacin (IV/PO).
Mechanism of Action
• Inhibit DNA gyrase
• Inhibit topoisomerase IV
Spectrum
• Moxifloxacin & Levofloxacin are termed “respiratory quinolones”. That is based on their activity
against S. PNEUMONIAE (NOT CIPRO!)
• ATYPICALS
• Gram-negatives including Pseudomonas (minus moxifloxacin)
• Moxifloxacin, unlike others, has anaerobic activity
Place in Therapy
• Upper & lower respiratory tract infections – covers atypicals so useful empirically!
• Intra-abdominal & GI infections
• UTI
• Bone & Joint
Side effects
• GI, CNS, QT prolongation, tendon rupture
• Higher association with C. difficile than other agents (NAP-1 strains)
Drug Interactions
• Oral: chelates with divalent cations, Don’t take with antacids :)
PEARLS
• Resistance problematic
• May exacerbate myasthenia gravis
Folic acid synthesis inhibitor?
Trimethroprim/Sulfamethoxazole (TMP-SMX).
Mechanism of Action
• Interference with folic acid synthesis
Spectrum
• Some gram-positive activity (CA-MRSA/MSSA)
• β-hemolytic strep activity is poor
• Some gram-negatives (resistance is an issue)
• Stenotrophomonas (nosocomial pathogen)
• Listeria
• Nocardia, toxoplasmosis, Pneumocystis jiroveccii
Place in Therapy
• Uncomplicated cystitis
• Pathogenic-specific therapy against organisms listed above
• PCP propylaxis
Side effects
• Dermatologic, renal, hematologic
Drug Interactions
• Warfarin-increases INR
