benefits of narrow spectrum ABX
o Most effective on susceptible organism
o Less disturbance of host flora
benefits and consequences of broad spectrum ABX
greater scope of activity for initial empiric coverage
more likely to cause superinfections
ABX with activity to MSSA
Dicloxacillin ** Amox/Clav-Augmentin ** PIP-TAZ ** Cephalosporins (all) ** Macrolides Tetracyclines Clindamycin SMX/TMP (Bactrim)
ABX with activity to MRSA
Vancomycin **
Tetracyclines **
Clindamycin **
SMX/TMP (Bactrim)
Note: possibly 5th Gen cephalosporins
ABX that treat Gonorrhea (gram - cocci)
Ceftriaxone (3rd Gen) **
Macrolides
Tetracyclines
ABX that treat pseudomonas (gram - rod with tough outer membrane)
PIP-TAZ ** Ceftazidime (3rd Gen) ** Aminoglycosides ** Cipro (uFQ) ** Levo (u+rFQ) **
ABX that treat C. Diff (+ anaerobe)
Vancomycin ** (severe)
Metronidazole **
ABX that treat B Fragilis (- anaerobe)
Amox/Clav (Augmentin)
PIP-TAZ **
Clindamycin **
Metronidazole **
ABX that treat chlamydia (atypical)
Macrolides **
Tetracyclines **
FQs (all) **
SMX/TMP (Bactrim)
ABX that treat mycoplasma (atypical)
Macrolides **
Tetracyclines **
FQs (all) **
3 determinants of bactericidal vs. bacteriostatic
mechanism of action (target)
concentration in vivo
specific micro-organism
targets for antimicrobials
- Inhibition of synthesis/damage to cell wall
- Inhibition of synthesis/damage to cell membrane
- Inhibition/modification of protein synthesis
- Modification of synthesis/metabolism of nucleic acids
- Modification of intermediary metabolism (folate metabolism)
bactericidal mechanisms (organisms killed)
o Inhibition of cell wall synthesis
o Disruption of cell membrane function
o Interference with DNA function or synthesis
bacteriostatic mechanisms (organisms prevented from growing)
o Inhibition of protein synthesis (exception: aminoglycosides (AGs → -cidal)
o Inhibition of intermediary metabolic pathways (unless combo, TMP/SMX –> -cidal)
advantages of bactericidal agents
- Preferred in severe infections
- Act more quickly and action is often irreversible
- Compensate for pts with impaired host defense
- Required for treatment of infections in locations that are not accessible to host immune system responses (e.g., endocarditic vegetations and cerebrospinal fluid / CNS)
pharmacodynamics of antimicrobial therapy
ensures that the ABX has antimicrobial activity against the specific infectious organisms
pharmacokinetics of antimicrobial therapy
ensures that a sufficient concentration gets to the site of infection and remains active for a sufficient duration
- absorption, distribution, and metabolism / elimination
ABX that readily enter CNS
Cephalosporins (3rd/4th): best for use
TMP/SMX (Bactrim)
Metronidazole (DNA inhibitors)
Rifampin (anti-TB)
ABX to avoid in pregnancy (cross placenta)
Tetracyclines –> bone/tooth development
Aminoglycosides –> 8th nerve/renal tox
Fluoroquinolones: black box for arthralgia / tendon rupture
Nitrofurantoin: no 3rd trimester (hemolytic anemia)
Metronidazole: no 1st trimester
TMP/SMX → kernicterus
selective distribution: beneficial accumulations
Clindamycin into bone (osteomyelitis)
Macrolides into pulmonary cells (URI / pneumonia)
Tetracyclines into gingival crevicular fluid and sebum (periodontitis and acne)
Nitrofurantoin rapid excretion into urine (beneficial in UTIs)
selective distribution: toxic accumulations
Amino glycoside: bind to cells of inner ear (ototoxicity) and renal brush border (nephrotoxicity)
Tetracyclines: bind to Ca++ in developing bone and teeth
inducers of hepatic metabolism (CYP450) = hepatotoxicity
- Rifampin: anti-tubercular agent
* Isoniazid: anti-tubercular agent
inhibitors of hepatic metabolism (CYP450)
Fluoroquinolones (especially Ciprofloxacin)
Erythromycin and Clarithromycin (NOT Azithromycin)
Metronidazole → antabuse rx due to inhibition of liver metabolism of EtOH
Also, anti-fungal agents that inhibit CYP450 drug metabolism (not part of DQ-CRIMES)
• Itraconazole (Triazole)
• Ketaconazole (Imidazole)
• Terbinafine
what anti-microbial agent can stain your contacts orange and make you have orange secretions (urine, sweat, tears)
rifampin (anti-TB)
which ABX exhibit post-ABX effects (ABXs that continue to kill or inhibit growth of bacteria for several hours after the concentration of the drug falls below the MIC)
aminoglycosides
fluoroquinolones
which ABX exhibits concentration-dependent killing
aminoglycosides
why is multi-drug regime essential in treatment of TB
3 subpopulations exist and resistance to any one drug is very high
- no practical way to quantitate % in given patient
• Intracellular in caseating granulomas
• Extracellular and rapidly dividing
• Intracellular in macrophages
candida - anti-fungal treatment
oropharyngeal/esophageal candidiasis and systemic vulvovaginal candidiasis: fluconazole (Diflucan)
oral and vaginal candidiasis: clotrimazole (Lotrimin) and Miconazole (Monistat): topical only
superficial: Nystatin (topical only)
superficial dermatophytosis (athlete’s foot, jock itch, etc.) and onychomycosis (nail infection) - anti-fungal treatment
systemic therapy for either: itraconazole
once daily oral dose (nail infections): PO Terbinafine
topical for dermatophytosis: Terbinafine
life-threatening systemic fungal infections - anti-fungal treatment
amphotericin B (IV or topical only)
- very toxic: nephrotoxicity and anemia
- pre-dose with Benadryl, Ibuprofen, Prednisone
invasive aspergillosis
amphotericin B (1st choice)
itraconazole
caspofungin (if refractory to either of above)
recommended premedication before Amphotericin B treatment (very toxic!)
diphenhydramine (Benadryl)
ibuprofen
prednisone