Penicillins/Cephalosporins/Quinolones/Sulfonamides Flashcards
Penicillins/Cephalosporins MOA
- Bind/inhibit PBP’s (penicillin-binding-proteins)
*bacterial transpeptidase enzymes required for new bacterial cell wall synthesis (i.e. peptidoglycan cross-linking)
- Bacterialcidal
*defective cell walls cause osmotic swelling/release of autolytic enzymes and bacterial lysis
Penicillins/Cephalosporins Resistance
- Beta-lactamase (most common)
*bacterial enzymes that break open/inactivate B-lactam ring (penicillinases, cephalosporinases)
- Modification of target penicillin binding proteins (PBPs)
- Impaired penetration of drug to target PBPs
- Presence of bacterial efflux pump
Probenecid
- Use of Probenecid increases bioavailability (i.e., blood levels) of all penicillins; inhibits tubular secretion of B-lactam antibiotics
Pencillins- antimicrobial spectrum- narrow spectrum
- Penicillin G
*sodium or potassium salt, IM, IV
- Penicillin V
*potassium, PO
Penicillin V
- 1st gen penicillin
- Only one of first gen that is orally available
- Only used for minor infections
Penicillin G Spectrum
- Considered narrow spectrum drug
- Stapn (non-R); Strep species (ear/throat/sinus pneumonia), Spirochetes (i.e., Treponema pallidum (syphilis), Borrelia burgdoferi (Lyme disease)
- Serious enterococcal infections w/aminoglycosides
- Pen G not resistant to B-lactamases
- Difficulty penetrating gram (-) rods
- Cross-reactivity to other pens regarding the allergic reactions
Antistaphylococcal penicillins
- Nafcillin
*IM, IV
Nafcillin use
- Indicated only for resistant staphylococcal (i.e., gram (+) cocci) infections; i.e. B-lactamase-producers
- MRSA is resistant
- Serious staph infections combined w/aminoglycosides
Aminopenicillins
- Ampicillin (PO, IM, IV)
- Amoxicillin (PO)
Aminopenicillins use
- 2nd generation penicillins
- Advantage of reliable oral bioavailability vs pen G
- Gram (+) spectrum similar to PEN G plus activity against Streptococcus faecalis (enterococcus)
- Not effective against gram (-) Proteus vulgaris, Pseudomonas aeurginosa, Serratia, Gonococci
- Common gram (-) rods: E. coli, P. mirabilis, H. influenzae, Salmonella/Shigella, anaerobes
- Not resistant to B-lactamases
Antipseudomonal 3rd Gen
- Ticarcillin (IM,IV)
Ticarcillin use
- Antipseudomonal (3rd gen. penicillin)
- Main indication: Gram (-) P. vulgaris, P. aeruginosa (often in combo w/ an aminoglycoside)
- Not resistant to B-lactamase
- Poor oral bioavailability
Antipseudomonal 4th Gen.
- Piperacillin (IM, IV)
Piperacillin use
- Antipseudomonal (4th gen penicllin)
- Broad spectrum antibacterial activity
- Spectrum similar to 3rd gen w/greater ptoency/effectiveness against more gm (-)
- Reserved for super-serious infections
*often used w/an aminoglycoside (e.g. Streptomycin) for serious infections w/enterococci (e.g. endocarditis)
Beta-Lactamase inhibitors
- Suicide molecules: bind/inhibit lactamase enzymes (e.g., clavulanic acid, sulbactam, tazobactum)
- Diff inhibitors combined w/extended spectrum penicillins (e.g., piperacillin-tazobactum)
- Basic antibacterial spectrum usually the same or slightly increased, hopefull the inhibitor ties up the lactamase so that the antibiotic is not inactivated
Imipenem-cilastatin
- Carbapenems; MOA similar to Pens
- IV
- Broad spectrum: gm (+), gm (-), and anaerobes
- Cross-reactivity w/Pen allergic rxn
- Demonstrates good resistance to beta-lactamases
- Used only parenterally
Aztreonam (Azactam)
- Monobactam
- MOA similar to pens
- IV
- High affinity for PBP of gm (-); poor affinity for PBPs of gm (+) or anaerobes
- No cross-reactivity w/Pen allergic rxn.
- Demonstrates good resistance to beta lactamases
- Used only parenterally
Vancomycin use
- Glycopeptide that inhibits transglycosylase (cell wall synthesis)
- Bactericidal for gm (+) bacteria (e.g. MRSA)
- Renal elimination
- No cross-reactivity w/Pen allergic rxn.
- Demonstrates good resistance to beta-lactamases
- Used only parenterally
Penicillin Clinical Indications
- Otitis media (ear infection)
- Sinusitis (sinus infection)
- Pharyngitis (throat infection)
- Lower respiratory infections
- UTI’s
- Systemic infections
Cephalosporins Characteristics
- Beta-lactam antibiotics w/larger B-lactam ring structure; more resistant to B-lactamases; often effective in penicilin-R infections
- Cross-allergenicity w/Pens; about 5-10%
- Effective against staphylococcal infections and typhoid fever
Cephalosporin Gen characteristics
- From 1st (cefazolin) to 4th (Cefepime)
- Gradual decrease in gm (+) coverage
- Increase in gm (-) coverage
- Increse in CNS penetration (3/4th)
- Increase in resistance to inactivation by B-lactamases
Cephalosporin Pharmacokinetics
- Excretion: mostly unchanged in urine; exception cefoperazone and ceftriaxone w/ increased amounts via liver/biliary/GI
- Probenacid slows/blocks tubular secretion
1st Gen Cephalosporin Spectrum
- Cefazolin
*Preferred use for surgical prophylaxis; has long t1/2 than other
- Gm (-) similar to 2nd gen pens- not effective against gm (-) Proteus vulgaris, Pseudomonas aeruginosa, Serratia, Gonococci
2nd Gen Cephalosporin Spectrum
- Cefoxitin
*effective against Bacteriodes fragilis and most anaerobs
- Main feature: increase gm (-) activity including against beta-lactamase-producing H. influenzae or K. pneumoniae and penicillin-resistant pneumococci
- Not active against P. aeruginosa
3rd Gen Cephalosporin Spectrum
- Usually less gm (+) activity than 1 and 2 gen., however, used in gm (+) meningitis (e.g. pneumonococci) due to good lipid solubility to penetrate CNS
- Ceftriaxone
*drug of choice for resistant gonorrhea (N. gonorrhoeae)
*sing IM dose for uncomplicated cases and meningits
- Cefixime can be used orally in place of Ceftriaxone
4th Gen Cephalosporin
- Cefepime
Cephalosporin Clinical Indications
- Alternative to Pens in beta-lactamse-producing bacteri
- Otitis, sinusitis, lower respiratory tract infections
- Surgical prophylaxis (e.g., Cefazolin)
- Meningitis, resistant gonorrhea 3rd gen (e.g., Ceftriaxone)
*common gram (-) infections
Quinolones/Fluoroquinolones MOA
- Bactericidal- inhibits bacterial DNA gyrase
Quinolones/1st Gen.
- Nalidixic acid and Cinoxacin
- Limited usage
- Resistance develops rapidly to these drugs within a few days (usually mutation of DNA gyrase binding)
Fluoroquinolones/ 2nd Gen.
- Addition of fluoride and side rings significantly extends gm (-) spectrum adds some gm (+) acivity but unreliable
- Ciprofloxacin
*PO, IV
- Ofloxacin
*PO, IV
Fluoroquinolones 2nd Gen. Pharmakokinetics
- Low CNS levels
- Good PO, but interference by antacid formulations w/ Al, Mg, Zn, Ca may result in 50% decrease. This is also true of most fluoroquinolones
- Mixed excretion: urine/GI, unchanged and metabolized; all reach effective conc. in urine/GI and accumulate in renal failure except moxifloxacin (biliary excretion)
- Ciprofloxacin inhibits CYP-450 drug metabolizing enzymes, may increase t1/2 of other drugs
Fluoroquinolones 2nd Gen. Spectrum
- Broad gram (-): most Klebsiella, Enterobacteriaceae, Psuedomonas (Cipro most active/potent)
Fluoroquinolones Clinical Uses
- Wide use: skin/soft tissue, bone/joint, UTI/GI (Travelers diarrhea), respiratory, otitis media; advantage of PO in serious gm (-) infections, e.g., Pseudomonas; use for prophylaxis in neutropenic patients (e.g. Ofloxacin)
- Not indicated for CNS/meningitis due to low penetration
Fluoroquinolones 3rd Gen.
- Increase PO absorptin, inc Vd, tissue conc > serum conc.
- Longer t1/2, may allow once/day dosing
- Levofloxacin, t1/2 - 7hr
- Moxifloxacin, t1/2 - 10hr
- Better gm (+) coverage- can be used as an alternative for ear infections (otitis media) and upper respiratory infections- NOT as effective as Cipro for gm (-)
Fluoroquinolones 3rd. Gen Spectrum
- Increased gm (+), esp. for streptococci; gm (-) similiar to Cipro; however Cipro generally considered most active against gm (-)
Fluoroquinolone Adverse Effects
- Skin: rash, allergy, photosensitivity (2 types): photoallergic (uncommon) and phototoxicity, highest incidence w/lomefloxacin, other less
- Nephrotoxicity- crystaluria may occur in alkaline urine
- Joint swelling, tendonitis, tendon rupture
*contraindicated: pregnancy/nursing/children
Sulfonamides MOA
- Inhibit dihydropteroate synthase, enzyme catalyzing conversion PABA to folic acid required for DNA synthesis
*inhibiting the generation of Dihydrofolic acid
- No cross-reactivity w/Pen allergic rxns.
Sulfonamide Spectrum
- Gm (-): E. coli, P. mirababilis for uncomplicated UTI’s; this is main indication for systemic use of sulfonamides adm. alone
Sulfonamide Pharmacokinetics
- Good PO bioavailability
- Excretion: mainly urinary, both metabolites and unchanged (acidic urine decreased solubility and cause crystalline drug deposits; alkaline urine favors solubility and excretion
Sulfonamides Clinical Indications
- Systemic use: sulfisoxazole and sulfamethoxazole, primarily for UTIs
- Local use: sulfasalazine, bowel lumen (ulcerative colitis)
- Topical use: sulfacetamide (opthalmic infections)
Sulfonamides Adverse Effects
- Alergy; rash
- Hemolytic anemia
- CNS; newborn at risk to dev. Kernicterus (yellow pigment in basal ganglia due to bilirubin)
- Renal; nephrotoxicity/crystalluria in acidic urine
Trimethoprim/Sulfamethoxazole Characteristics
- Resistance develops quickly when either drug is used alone
Trimethoprim/Sulfamethoxazole Spectrum
- Gm (-) activity is main indication and includes most gm (-) bacteria and Enterobacteriaceae, not Pseudomonas
- Indications: UTIs, GI, respiratory infections (doc for Pneumocystis jiroveci), prostatitis/vaginitis, otitis media
Trimethoprim Adverse Effects
- Increased incidence of adverse effects in AIDS patients w/TMP/SMX: fever, rash, decreased blood cells; folate deficiency may cause macrocytic anemia; supplement w/folinic acid
Sulfonamides Precaution for UTIs
- No FQ, no sulonamides near term
Prostatitis Treatment
- Give a Fluoroquinolone
- Male <35 w/infection often due to C. trachomatis- Ofloxacin BID 7 days, 6 weeks if chronic infection; Cipro not used anymore
