Good tissue penetration, time dependent, most are renally eliminated

Class adverse effects: hypersensitivity: nausea/vomiting/diarrhea/seizures at high doses

Differences in transpeptidases and hydrophilicity make differences in B-lactams 

Natural Penicillin

IV only

Renal elimination

Very short half life (~30 minutes)

Most bacteria are resistant

Useful spectrum: streptococci, enterococci, Treponema palldium

Main uses: susceptible streptococcal infections, syphillis

phenoxymethylpenicillin

By mouth only

Renal elimination

Very short half life (~30 minutes; frequent dosing required)

Most bacteria are resistant 

Useful spectrum: streptococcus, enterococcus, Treponema pallidum

Main uses: susceptible streptococcal infections, syphillis

Penicillinase resistant penicillins

Methicillin, nafcillin, oxacillin, dicloxacillin, and cloxacillin 

Contain bulky R group that will inhibit many B-lactamases

Dicloxacillin and cloxacillin are oral

Methicillin: acute interstitial nephritis (removed from market), nafcillin is hepatically eliminated and has high incidence of phlebitis

Useful spectrum: MSSA, streptococci

Main use: susceptible staphylococcal infections (endocarditis, cellulitis) 

High incidence of acute interstitial nephritis

Anti-staphlycococcal Penicillin ("penicillinase resistant" penicillins)

Anti-staphylcoccal penicillin

Hepatically eliminated

has a high incidence of phlebitis 

MSSA, streptococci

Main use: susceptible staphylococcal infections (cellulitis, endocarditis)

Staph can still be resistant to them via their PBP 

Anti-staphylococcals kill staph susceptible to them better than vancomycin

Ampicillin, Amoxicillin, Bacampicillin

Ampicillin = IV, PO; Amoxicillin = PO (better bioavailability)

Susceptible to B-lactamases

Amino group confers improved gram negative specificity

Useful spectrum: streptococci, enterococci, non-b-lactamase producing GNR: listeria, H pylori

Main Uses: URIs, UTIs, PUD, enterococcal infections 

Streptococcus, enterococci, some non-B-lactamase producing GNR - Listeria, H pylori

Main Uses: URIs, UTIs, PUD, enterococcal infections 

Ureidopenicillins (piperacillin, mezlocillin, azlocillin) - ureidocillins have saturable renal and biliary excretion

Carboxypenicillins (carbenicillin -- oral; rest are IV, ticarcillin)

AE: thrombocytopenia

Useful spectrum: as aminopenicillins, plus pseudomonas, better coverage againsts GNR 

Susceptible to B lactamases

Penetrate cell wall of pseudomonas, unlike aminopenicillins

Main uses: HAP, nosocomial infections 

As aminopenicillins, pseudomonas, better coverage vs GNR

Main Uses: HAP, nosocomial infections 

Useful spectrum = parent drug + most b-lactamase producing bacteria 

- streptococci, MSSA, enterococci

- better GNR coverage than parent drugs alone

- anaerobes (like to make B lactamase) 

Amp/sublactam + amox/clav are not active against pseudomonas 

Broad spectrum leads to good empiric coverage for nosocominal organisms

Less potential to induce resistance compared to cephalosporins, but does occur

Main uses: GI infections, abcesses, HAP, serious nosocomial infections, diabetic wound infections 

All have 6 membered rings attached to B-lactam ring

All have same MOA as other B lactams

Less B-lactamase susceptible than most penicillins

Classified by generations

Cefazolin (IV), Cephalexin (PO)

Cephalexin and Cefadroxil are PO 

Cephadrine is both IV and PO 

Eliminated renally

No CNS penetration

Useful spectrum: MSSA, streptococci, some GNR

Main uses: Surgical prophylaxis, cellulitis, UTIs

Cefuroxime (PO/IV)

PO: Cefaclor, Loracarbef, cefprozil, cefdinir

Somewhat worse gram positive coverage, but somewhat better gram - coverage including Neisseria

Cefotetan and Cefoxitin have anaerobic activity

Main use: URTIs, surgical prophylaxis (cefotetin, cefoxitin), gonorrhea 

MSSA, streptococci, some GNRs

Surgical prophylaxis, cellulitis URIs

cefazolin, cephalexin (PO)

cefotetan, cefoxitin

Main Uses: URTIs, surgical prophylaxis, gonorrhea 

Ceftriaxone, Cefotaxime, Cetazidime

Cefpodoxime, cefixime, ceftibuten (PO), the rest are all IV 

Decreased antistaph activity but increased antistrep except ceftazidime, cefixime (PO), and ceftibuten (PO) which have little or no useful gram positive activity -- better gram negative activity

Ceftazidime, cefoperazone active vs pseudomonas aeruginosa

Eliminated renally, except ceftriaxone and cefoperazone; ceftriaxone has dual elimination and can cause biliary sludging in neonates 

Main Uses: meningitis, CAP/HAP, lyme disease, SSSIs, UTIs, febrile neutropenia 

Ceftazidime, cefixime (PO), and ceftibuten (PO)

little or no useful gram positive coverage

better gram negative coverage

Cefoperazone and ceftriaxone

-- Ceftriaxone has dual elimination and can cause biliary sludging in neonates 

Cefepime (IV only)

Eliminated renally

useful spectrum: MSSA, streptococci, GNR including pseudomonas

Main uses: HAP, nosocomial infections, febrile neutropenia

Cetraroline (IV only)

Anti MRSA cephalosproin

Useful spectrum: MRSA and MSSA, streptococci, enteric GNR

Not useful against pseudomonas

Susceptible to B lactamases

Indicated Uses: SSSIs, CAP 

Aztreonam (IV only) 

Only active vs gram - rods, including Pseudomonas

Renally eliminated

Not cross reactive with other beta lactam allergies, except ceftazidime

Main use: gram negative infections in patients with allergies to other beta lactams 

Imipenem/Cilastatin, Meropenem, Doripenem, Ertapenem

IV only

Renally eliminated

Additional AEs: higher incidence of seizures (especially imipenem); nausea

Stable to most B lactamases

metabolized by renal dihydropeptidase; cilastatin inhibits this

MSSA, streptococci, E faecalis, anaerobes

Many GNR including P aeruginosa

B lactatmase producing GNR 

- Carbapenemaes now exist and are spreading

Main uses: nosocomial infections, mixed aerobic/anaerobic infections, febrile neutropenia

Vancomycin; Teicoplanin

Bind to terminal D-ala-D-ala chain of peptidoglycan, halting cell wall synthesis

Time dependent, poor availability

Spectrum: gram positive aerobes and anaerobes, including MRSA

Do not kill b lactam susceptible staph as quickly as b lactams

**drugs of choice for MRSA infections**

Pharmacokinetic levels (Vancomycin)

- Overutilized

- Traditional peak (25-40), trough (5-15) (now higher bc resistance)

Levels not well correlated to efficacy or toxicity

Main value: checking for appropriate dosing in patients with renal dysfunction/altered volumes of distribution 

Red-man Syndrome: when infused quickly, not an allergy

Nephrotoxicity, ototoxicity

Largely a problem with older formulations (mississippi mud)

Increased renal damage possible with concurrent nephrotoxins

Main uses: MRSA infections, gram positive infections in patients with severe beta lactam allergy 

Telavancin (Oritivancin, dalbavancin)

Bind to terminal D-ala-D-ala portion of peptidoglycan AND disrupts cell membrane (lipophilic chain helps)

effective against some vancomycin resistant strains

AE: taste disturbances, headache, dizziness, foamy urine, injection site reaction

Indications: cSSSIs; also studied in HAP

taste disturbances, headache, dizziness, foamy urine, injection site reaction, nephrotoxicity worse than vancomycin

Indication: cSSSIs, also studied in HAP

Peptide antibiotic

Interpheres with dephosphorylation of bactoprenol pyrophosphate, disrupting peptidoglycan translocation 

Highly nephrotoxic, virtually always used topically

Useful spectrum: gram positive cocci and bacilli (topical infections)

Main use: minor skin infections 

Spectrum: gram positive cocci and bacilli

main use: minor skin infections

Inhibits peptidoglycan monomer synthesis

Use: UTIs

Available IV in Europe

Used for multi drug resistant infections

Inhibits the enzyme that links D-ala molecules

Use: TB 

cyclic lipopeptide

MOA: inserts into cell membrane of gram positive oranisms, leading to cation leak, depolarization, and cell death

Bactericidal 

Concentration dependent, Poorly absorbed so IV only

Inactive in lungs (inactivated by surfactant)

Exceted renally

Gram positive aerobes and anaerobes, including MRSA and VRE 

Anaerobic activity poorly studied

AE: CK kinase elevation - rhabdomyolysis possibility

Uses: bacteremia, skin and soft tissue infections, endocarditis 

Creatinine Kinase Elevation - possiblity of rhabdomyolysis 

Colistin (polymyxin E)

Polymyxin B

MOA: bind to cell membrane of gram negative organisms, ad disrupts permeability; rapidly bactericidal

AE: nephrotoxicity (common), neurotoxicity (uncommon)

Concentration dependent

Excreted renally (PK not well studied)

Given by inhalation (CF), IV, or topically

Gram - organisms, including MDR strains of Pseudomonas, Acinetobacter, Klebsiella 

Uses: treatment of MDR GNR infections, topical infections, and prophylaxis of pneumonia in CF patients 

Inactive againsts Serratia, Providentia