Anti-Microbials Flashcards
What does selective toxicity mean in respects to anti-microbial?
anti-microbials’ MoA do not harm the host (us), only do damage to bacteria, ex.:
- disrupt cell wall of BacT
- inhibit an enzyme unique to BacT
- disrupt bacterial protein synthesis
Antimicrobial Classes (5)
Narrow-spectrum (active against few bugs)
Broad spectrum (active against a variety of bugs)
Virus (antiviral)
Fungus (antifungal)
Protozoa (antiprotozoal)
Beta-Lactam Anti-microbials MoA/classes
MoA: inhibit bacterial growth by interfering with a specific step in bacterial cell wall synthesis
BACTERICIDAL
classes: penicillins, cephalosporins, monobactams, carbapenems
Narrow spectrum penicillins & route
- penicillin G - IV
- penicillin VK- PO
Narrow spectrum penicillins (anti-staphylococcal)
- nafcillin
- oxacillin
- cloxacillin (PO)
- dicloxacillin
Broad spectrum penicillins & route
(aminopenicillins)
- ampicillin- IV, PO
- amoxicillin- PO
*improved activity against gram -, but destroyed by B-lactamases
Extended-spectrum penicillins & route
(anti-pseudomonal)
- Piperacillin (IV)
- Ticarcillin (IV)
bacterial mechanisms of resistance to B-lactams
- Inactivation of antibiotic by B- lactamase
- Modification of target PBP’s
- Presence of efflux pump
- Impaired penetration of drug to target PBP’s
Penicillin AEs
very safe, least toxic; AEs due to hypersensitivity
- rash most common
Penicillin anaphylaxis
- Immediate: urticartia, anaphylaxis, laryngeal edema
- accelerated: urticartia, less severe
- Late: maculopapular rash, drug fever, hemolytic anemia, thrombocytopenia, interstitial nephritis
**avoid all other B-Lactams
Cephalosporin changes with generation
The higher up in generation
- increasing ability to reach CSF
- increasing resistance to destruction by B-lactamases
- increasing activity against gram - bacteria and anaerobes
1st generation Cephalosporins/spectrum/use
Cefadroxil - PO
Cefazolin - IV
Cephalexin - PO
- active against gram + cocci
- for UTI, minor staph lesions, cellulitis
2nd Generation Cephalosporins/spectrum/use
Cefoxitin - IV
Cefotetan - IV
Cefuroxime - PO and IV
Cefaclor
- less active against gram -; more against gram +
- for sinusitis, otitis, and lower respiratory infections
Cephamycins drugs (sub group of 2nd gen)
Cefocitin
Cefotetan
- active against anaerobes
- for diverticulitis, peritonitis, abdominal/colorectal surgical prophylaxis
3rd Generation Cephalosporins/spectrum/use
Cefotaxime- IV
Ceftrazidime - IV
Ceftriaxone - IV/IM
- more active against gram -; crosses BBB, used in HAIs
- for complicated CAIs of resp. tract, blood, intra-abdominal, skin/soft tissue, and UTI
4th Generation Cephalosporins/spectrum
Cefepime - IV/IM
- good gram - & + coverage, with activity against Pseudomonas
5th Generation Cephalosporins/spectrum
Ceftaroline - IV
- broad gram-positive and gram-negative organism coverage, including MRSA; does not cover Pseudomonas
“6th” Generation Cephalosporin/use
Cefiderocol - IV
Clinical Uses: hospital acquired pneumonia, complicated UTI
AE of Cephalosporins
patients with anaphylaxis, hives, angioedema, to penicillins should not get cephalosporins
- opportunistic infections with broader spectrum
- hypoprothrombinemia if on warfarin
Carbapenems drug/class
*drugs in this class end in -penem
- Imipenem
BACTERICIDAL
AE of Carbapenems
HA
Seizures
Nausea
Lowers valproic acid concentrations
Monobactam drug
Aztreonam (Azactam)
Other B-lactam drugs/use
- Clavulanic acid
- Sulbactam
- Tazobactam
- inhibit B-lactamases protecting penicillins from inactivation; used only in combo with PCNs
Glycopeptides drug, moa, use
- Vancomycin - IV (targets gram + bacteria)
- moa: inhibit cell wall
- use: sepsis or endocarditis caused by MRSA, meningitis with highly penicillin resistant pneumococcus
Lipoglycopeptides drug/moa/use
- Telavancin
- moa: inhibits cell wall synthesis and disrupts BacT cell membrane
- complicated skin and skin structure infections, covers VRE, MRSA
Tetracyclines drugs/acting time
- tetracycline –> short
- demeclocycline –> intermediate
- doxycycline, minocycline –> long acting
Tetracyclines spectrum/use
- BACTERIOSTATIC inhibits protein synthesis
- broad spectrum for gram + & -
- DOC for mycoplasma pneumoniae, chlamydiae, rickettsiae
also H pylori, acne, AECB, CAP
Tetracylines AE
- GI (N/V, diarrhea) most common reasons for D/C
- teeth and bones: tetracyclines bind Ca+ in new bones leading to tooth discoloration or bone deformation/growth inhibition
- Photosensitivity
Tetracycline Resistance
- Efflux by active transport protein pump encoded on plasmid
- Ribosome protection by proteins that interfere with
tetracycline binding - Enzymatic inactivation
Macrolides drugs/use
- mainly BACTERIOSTATIC; -cidal in high concentrations
- Erythromycin
- Azithromycin
- Clarithromycin
- DOC in diphtheria, all Chlamydial infections, CAP; mainly against gram +
Macrolides AE
- GI: anorexia, nausea, vomiting and diarrhea most common reason for D/C
- acute hepatitis as hypersensitivity
- drug interactions: inhibitor of CYP3A4 (Erythromycin and Clarithromycin ONLY); can prolong QT interval & increase risk for sudden cardiac death
Clindamycin moa/AEs/use
penicillin alternative, anaerobes; BACTERIOSTATIC
MOA: Penetrates saliva, sputum, pleural fluid and bone but not CSF
AE: psedomembranous colitis (suprainfection)
Clinical Use: head and neck infections
Linezolid moa/use
MOA: also inhibits protein synthesis by preventing formation of the ribosome complex; BACTERIOSTATIC
Clinical Use: Vancomycin resist. enterobacteria; multiple-drug resistant organisms
Aminoglycosides drugs/moa/use
- gentamicin, streptomycin, tobramycin
- MOA: BACTERICIDAL inhibitors of protein synthesis, against gram - enteric bacteria
- Clinical Use: bacteriemia and sepsis
Aminoglycosides AE
- ototoxicity and nephrotoxicity
aminoglycosides dosing
- concentration dependent killing; greater conc. kill more bacteria at faster rate (once daily dosing)
- killing also occurs for several hours after med cleared from body
Antimetabolites MOA/spectrum
MOA: analogs of PABA that compete for a synthetic enzyme and block folic acid synthesis needed for DNA; BACTERIOSTATIC
- targets both gram + & -, chlamydia, inhibits some enterics
Trimethropim- sulfamethoxazole (Bactrim) use/AEs
- anti-metabolite
- P carinii pneumonia, shigellosis, salmonella (traveler’s diarrhea), UTI’s, prostatitis, otitis and upper resp tract infections, CAP
- AE: frequent hypersensitivity reactions
and rashes, photosensitivity, GI (N&V), hemolytic anemia, bone marrow depression
Fluoroquinolones drugs/moa
- Fluoroquinolones (anything ending in -floxacin, ex. ciprofloxacin)
- MoA: block bacterial DNA synthesis by inhibiting DNA gyrase (required for DNA replication) Also inhibits topoisomerase. BACTERICIDAL
Fluoroquinolones use/ AEs
- resp., UTI’s, soft tissue bone and joint infections, gonococcal infections; newer versions better for gram +’s
- N/V, diarrhea, may prolong QT interval, tendonitis, cipro inhibits CYP1A2- increase levels, increase toxicity, hypoglycemia (most likely to occur in pts with DM)
Metronidalzole (Flagyl) moa/use/AEs
MOA: BACTERICIDAL, antiprotozoal with potent activity against anaerobes
Clinical Use: intra-abdominal infections, antibiotic associated enterocolitis, trichomonas vaginitis, giardiasis, triple therapy for H.pylori ulcer disease
AE: GI (N/V, metallic taste), CNS rxns -> seizures, peripheral neuropathy
-Azole Antifungals moa/use/drugs
MOA: reduce ergosterol synthesis by inhibiting fungal CYP enzymes
Clinical Use: antifungal
drugs are anything ending in -azole, ex. fuconazole, ketoconazole
Antimicrobials in Pregnancy
Avoid if possible: chloramphenicol
metronidazole
trimethoprim
sulfonamides (last trimester)
Contraindicated:
fluoroqinolones
tetracyclines
