Term
| 3rd Gen Cephalosporins: Adverse effects |
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Definition
Few and Low
Hypersensitivity
Superinfection risk
Nearly no nephro tox |
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Term
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Definition
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Term
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Definition
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Term
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Definition
best anti-pseudomonal
3rd gen |
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Term
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Definition
70% eliminated via bile
3rd gen |
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Term
| Spectum of activity and clinical use of Cephalosporins |
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Definition
All active against most G+ cocci (including penicillinase-producing)
many stains of G- bacilli
Relatively ineffective against enterococci |
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Term
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Definition
[Cephalothin, cefazolin, cephalexin)
Strongest action on G+, weakest on G-
Certain nephro tox to a certain degree
Not effective against pseudomonas
Camparitivly stable against B-lactamase
Cheifly used in treating penicillinase-productive aurococcus (S. aureus) and surgical prophylaxis
No CNF penetration |
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Term
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Definition
(cefamandole, cefoxitin, cefaclor, cefonicid, cefuroxime, cefotetan, cefprozil)
Similar or less G+ activity than 1st gen
G- activity increased
Some effective against anaerobes (B.fragilis)
Ineffective against p.aeruginosa
Stable to B-lactimases
Less nephrotoxicity
Cefuroxime only 2nd gen to cross BBB for use in meningitis (H.influenza/sepsis) |
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Term
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Definition
(cefotaxime, ceftizoxime, ceftriaxone, cefoperazone, ceftazidime, cefixime, cefpodoxime)
Broadest spectrum
Highest G- activity
Lowest G+ activity
Highest resistance to B-lactimase
Best CSF penetration
No nephrotoxicity
Ceftizoxime: good activity B.fragilis
Some effective agains P.aeruginosa and enteric bacilli |
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Term
| Nephrotoxicity of Cephalosporins |
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Definition
1st gen: certain nephrotox (Renal damage, interstitial nephritis and tubular necrosis
2nd gen slight
3rd almost none |
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Term
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Definition
IV
— Once daily dosing (95% protein bound long half-‐life)
— Spectrum: Strep. pneumoniae, most Enterbacteriaceae,
— Excretion: 50% urine, 50% Mbile no need to adjust for renal insufficiency
— CSF penetration: 5-‐15% in meningitis, 1.5% with out inflammation
— DoC: bacterial meningitis, CAP, Strep. viridans endocarditis (+gent)
— ADRs
— Cholestasis
— Elevated bilirubin (displacement)
— Diarrhea |
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Term
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Definition
IV
. Spectrum: Strep pneumo, Neisseria spp., most Gram (--‐) enterics, M. catarrhalis and H. flu (including β--‐ Lactamase +)
. DoC: bacterial meningitis (esp. in peds + amp if < 4 weeks), CAP, complicated UTI/pyelonephritis, Bacterial Peritonitis |
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Term
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Definition
IV
. Spectrum: Enteric GNR (including Pseudomonas; some Acinetobacter)
. No anaerobic activity (same for cefotaxime and ceftriaxone)
DoC: Pseudomonas infections (UTIs, pneumonia, meningitis, abdominal). |
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Term
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Definition
(Maxipime)
. Broad spectrum including Pseudomonas
. More resistant to beta--‐lactamase Than 3rd generation
. Enhanced activity against certain Gram negative bacilli, including Enterobacter, Citrobacter and Serratia.
. Uses. Severe Community Acquired Pneumonia requiring Intensive Care.
. Not effective v ESBL producing organisms.
IV
. NON--‐Spectrum MRSA, C. diff, Burkholderia, Stenotrophomonas, gram--‐negative anaerobes
. Stable vs. de--‐repressed chromosomal β--‐lactamases, but not ESBL
. Less β--‐lactamase induction than 3rd Cephs
. DoC: HAP, febrile neutropenia
4th gen Cephalosporins |
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Term
| Pharmacokinetics of Cephalosporins |
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Definition
Cephalosporins are given parenterally and orally.
Extent Of binding to plasma protein vary from one to another. e.g. Cefazolin is 80% protein bound ( hence, long t1/2 ) Cephalexin Is 10--‐15% protein bound
Relatively lipid insoluble ( like penicillins ) Hence,do not penetrate Cells or the CNS, except for third generations.
Mostly excreted unchanged by the kidney (glomerular & tubular secretion ), except, ceftazidime & cefoperazone( glomerular)
Probenecid slows Their elimination and Prolong their half--‐live ( except Ceftazidime & cefoperazone)
Half--‐life 30--‐90 min; ceftriaxone 4--‐7 hr |
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Term
| Therapeutic uses of Cephalosporins |
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Definition
1. Alternatives to penicillin in allergic pts
2. Upper respitory tract infections and otitis media (cefaclor, cefixime, cefuroxime axetil, cefprozil)
3. Septicaemia caused by G- bacteria (P.aeruginosae) A penicillin (eg. piperacillin/ticarcillin) + aminoglycoside OR a cephalosporin (eg. ceftazidime) + AG
4. UTI (cefuroxime, cefixime)
5. Prophlaxis in surgery Appendectomy ( bowel anaerobes ) eg. Cefoxitin Obstetrical &gynecological, urological, orthopedic procedures, Etc ( S. aureus
& S. epidermidis ) eg. Cefazoline
6. Meningitis--‐ N. Meningitidis Ceftriaxone Cefotaxime( pref. in neonate)
7. Gonococcal infections Ceftriaxone |
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Term
| Adverse effects of Cephalosporins |
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Definition
1. Hypersensitivity reactions--‐ most common Anaphylaxis, bronchspasm, urticarial Maculopapular rash--‐ more common
2. Nephrotoxicity ; esp. Cephradine
3. Thrombophlebitis ( i.v admin. )
4. Superinfections
5. Diarrhea--‐oral cephalosporins, cefoperazone, ceftriaxone & moxalactam.
6. cefamandole, moxalactam & cefoperazone may cause:
a) bleeding disorders
b) Flushing, tachycardia, vomiting with alcohol intake |
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Term
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Definition
Monobactam
1. Highly resistant to B-lactamases
2. Highly active vs. aerobic G- (P.aeruginosa & penicillinase H.influenzae and gonococci) but poorly active vs. G+ cocci and anaerobs
3. Spectrum similar to aminoglycosides |
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Term
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Definition
Carbapenems
Hydrolyzed by dehydropeptidase so formulation contains cilastatin (inhibitor)
2.Spectrum is broadest of b-lactams
3. G+ and G- (not methicillin-resistant staph), enterobacteriaceae, P.aeruginosa, anaerobs, B.fragilis
4. Gonococci and H.influenzae risistant tonatral penicillin and ampicillin are susceptible to imipenem
5. Mainly used in UTI, respiratory, skin,soft tissue
6. Also staphylococcal endocarditis, (NOT CNS infections) |
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Term
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Definition
Topical Application
§Against G+ |
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Term
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Definition
Clycopeptide
Important “last line” against antibiotic Resistant S. Aureus |
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Term
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Definition
MOA: Binds to precursor units of bacterial cell walls, inhibiting cell wall synthesis, also inhibits RNA synthesis
Bactericidal antibiotic for G+ in conc of 0.5-10 ug/mL
Pharm effect
1. Very effective against staph including B-lactamaces and G+ cocci like streptococcus viridans, enterococci, and pneumococcus
2. Also clostridium, corynebacterium diphtheria, and bacillus anthracis
Clinical Use
Orrally for antibiotic associated Pseudomembranous colitis by C.difficile
IV for serious G+ coccal infections like enteroclitis, septicemia (especially for those caused by penicillin resistant pneumococcus and staphylococci
AE
1. Phlebitis at injection site
2. Nephro and oto tox (rare with monotherapy[risk factors: renal impairment, prolonged therapy, high doses, high serum conc, other meds])
3. Red-man/red-neck syndrome |
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Term
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Definition
| Member of th Lipopeptide class of antibiotics, similar to daptomycin |
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Term
| Polymixin B Antibacterial activity |
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Definition
Polymyxins are only Active against gram negative bacteria (P. aeruginosa, E. coli, K. pneumoniae), while daptomycin is used to treat gram positive Bacteria .
The polymyxins are highly Nephrotoxic and are thus only used topically |
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Term
| Polymyxins: Mechanism of action |
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Definition
Bind The the Lipopolysaccharide in The outer membrane, thus destroying OM integrity. .
Bind to The cytoplasmic membrane (to the phosphatidylethanolamine) and Make the membrane More permeable. |
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Term
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Definition
• Friulimicin B is A naturally Occurring cyclic lipopeptide, produced by the Actinomycete Actinoplanes Friuliensis •
It consists Of a macrocyclic Decapeptide core and a lipid tail, nterlinked by an exocyclic amino acid •
Excellent activity against gram--‐positive pathogens, including multidrug--‐resistant strains. •
Friulimicin is water and amphiphilic, with an overall negative charge. Amphiphilicity is enhance in presence of Ca2+, which is also indispensable for antimicrobial activity. |
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