Beta-lactams

Mechanism of Action:  Irreversibly bind to pencilin binding proteins (PBPs) inhibiting the final stage (transpeptidation) of bacterial cell wall synthesis causing osmotic rupture and death (BACTERICIDAL)

Pharmacodynamics:  TIME-DEPENDENT KILING; maximize duration of exposure; minimal post-antibioic effect (EXCEPTION: carbapenems vs gram negative organisms); Synergy with aminoglycoside against Enterococcus

Mechanism of Resistance: 1. Alteration of PBPs causing decreased affinity to drugs

                                      2. Production of beta-lactamases that break beta-lactam ring

                                                   3. Alteration of outer-membrane permeability

Adverse Effects: diarrhea (cetriaxone, ampicillin, Augmentin), IgE HSNs (rash, hivies, itching, redness, tachycardia, anxiety, abdominal pain, SOB), seizures (carbopenems & high dose PCNs), neutropenia/leukopenia (PCNs>cephs), thrombocytopenia (extended spec PCNs), increased INR & PTT (cephs w. MTT side chain), cholestasis/gallstones (cetriaxone), hyerbilrubinemia (cetriaxone), drug-induce hepatitis (oxacillin>nafcillin), interstitial nephritis

Drug Interactions: Probenacid decreases beta-lactam excretion by inhibitng active tubular secretion

                                    Beta-lactams decreaase OCs' efficacy by killing bacteria that mediate  

                                    enterohepatic recirculation, which delays metabolism of OCs

PCN Cross-Sensitivity: cephalosporins: 3-10%

                                           carbapenems: ≤50%

                                           monobactams: <1%

Natural Penicillins

Dosage Forms: Penicillin Gs are injectables while penicillin V is available as an oral solution and tablet

Spectrum: Streptococcus, Actinomyces, and other gram (+)'s; Treponema pallidum (syphillis pathogen)

Phamacokinetics: Food inhibits absorption of PCN VK

                                  Low protein binding, can enter CNS with inflammed meninges and high doses

                                  Primarily eliminated through active renal tubular secretion; biliary is secondary path

Warnings: PCN G crosses placent and distributes into breast milk

                     Hyperkalemia

Dosing&Adminstration: Renal impairment and dialysis require dose adjustments

                                             Benzathine and procaine formulas are for IM depot administration

Antistaphylococcal Penicillins

(Penicillinase-resistant)

Dosage Forms: Cloxacillin, Nafcillin, and Oxacillin are available as injectables; Dicloxacillin and oxacillin are available as oral solutions and capsules

Spectrum: MSSA, S. epidermidis, and other Staphs, also some Streptococcus and Peptostreptococci

Pharmacokinetics: Food inhibits the absorption of the oral products (dicloxacillin and oxacillin)

                                    Highly protein-bound

                                    Primarily elimated renally by tubular secretion or glomerular filtration and

                                    secondarily by biliary route

Warnings: Cross placenta and distributes into breast milk; can cause neutropenia, hepatitis (oxacillin), and interstitial nephritis (nafcillin)

Dosage&administration: Adjust dose in patients with severe hepatic impairment OR in patients with hepatic AND renal impairment (i.e. DON'T need to adjust in patients who are ONLY renally impaired)

Aminopenicillins

Dosage forms: Amoxicillin is availabe as an oral solution, tablet, and capsule; ampicllin is available as an oral suspension and an injectable

Spectrum: Streptococci, Enterococci, Listeria, Salmonella (amoxicillin), Shigella (ampicillin), a few other gram postives and negatives and the spirochete: Borrelia burgdorferi (Lyme disease pathogen)

Pharmcokinetics: Food inhibits absorption of ampicillin

                                  Low protein binding, ampicilling penetrates CNS with inflamed meninges & high

                                  doses while amoxicillin can penetrate inner ear fluid

                                  Primarily eliminated renally through tubular secretion and glomerular filtration

Warnings: Crosses placenta and distributes into breast milk; causes diarrhea (amp>amox)

Dosage&Administration:  Renal impairment and dialysis require dose adjustment

Antipseudomonal Penicillins

Dosage Forms:  Carbenicillin is an oral tablet; Ticarcillin is an injection that contains clavulanate; pipercillin is an injectable

Spectrum: Streptococci, E2nterocooci, Clostridium, Pseudomonas, some other gram (-) & few gram (+)

Pharmacokinetics: Low oral bioavailability (carbenicillin)

                                    Low protein binding; can penetrate CNS with inflamed meninges

                                    Primarily eliminated by tubular secretion and glomerular filtration

Warnings: Cross placenta and distribute into breast milk

                     Fluid overload (ticarcillin and pipercillin due to salts in formulation)

                     In vitro inactivation of aminoglycosides that can interfere with some lab tests

Dosage&Administration:  Ticarcillin only requires dose adjustment in patients with severe hepatic impairment AND renal impairment while others need to be adjusted in patients with renal impairment or on dialysis

Beta-lactam/Beta-lactamase inhibitor combinations

Dosage forms: Amoxicillin/clavulanic acid (AUGMENTIN) is avaible as an oral suspension and tablet while ampicillin/sulbactam (UNASYN), piperacillin/tazobactam (ZOSYN), and ticarcillin/cavulanic acid (TIMENTIN) are all injectibles

Spectrum: MSSA, Strep, Clostridium, Haemophilus, Bacteroides, Pseudomonas (pip/tazo & ticar/clav), and several other gram (-) and a few other gram (+), plus the spirochete Borrelia burgdorferi (Lyme disease pathogen--only amox/clav & amp/sul)

Pharmacokinetics: Low protein binding and primarily renal elimination

Warnings: Cross placenta and distribute into breast milk; diarrhea (amox/clav); fluid overload

Dosage&Administration: Adjust doses in patients with renal impairment or on dialysis

Cephalosporins

Spectrum: NO ATYPICAL COVERAGE, as you move up in generations you lose gram (+) coverage and gain gram (-)

Pharmacokinetics: Food increases absorption of cefuroxime axetil (CEFTIN), cefditoren(SPECTRACEF)

                                    and cefpodoxime (VANTIN)

                                    CNS penetrators: cefotaxime, ceftriaxone (ROCEPHIN), ceftazidime

                                    Biliary elimination: ceftriaxone (ROCEPHIN) & cefoperazone

                                    Renal & Biliary:  cefpodoxime (VANTIN)

                                    Renal only:  all others

Drug interactions: Cefoperazone & cefotetan have MTT side chains that lead to disulfiram reactions with ethanol and increased bleeding potential with anticoagulants

Warnings: Anemia/neutropenia/leukopenia  and coagulopathy with use >2 weeks; HSN reactions, biliary sludging/cholelithiasis (ceftriaxone esp in neonates particularly if given with calcium b/c incompatible so separate infusions of Ca2+ and ceftriazone by at least 48 hours), interstiatial nephritis 

Dosing&administration: Renal dose adjustments for all except ceftriaxone & cefoperazone, which are NOT renally eliminated; NO dose adjustments needed for hepatic impairment even if severe

1st Generation Cephalosporins

Drugs: Cefadroxil (DURICEF), cefazolin (ANCEF), cephalexin (KEFLEX)

Dosage forms: Cefadroxil comes as an oral solution, tablet, and capsule; cephalexin comes as an oral suspension and a capsule; cefazolin is only injectable

Spectrum: MSSA, Strep, and a few community acquired gram (-)

2nd Generation Cephalosporins

Drugs: Cefaclor (RANICLOR), cefotetan (CEFOTAN), cefoxitin (MEFOXIN), cefprozil (CEFZIL), cefuroxime (ZINACEF), cefuroxime axetil (CEFTIN)

Dosage Forms:  cefotetan, cefoxitin, and cefuroxime (ZINACEF) are injectables while rest are oral

Spectrum: MSSA, Strep and several gram (-); cefotetan & cefoxitin have moderate anerobe coverage