Antibiotic / Class / MOA / Antibacterial Spectrum / Penetration / Clearance / Adverse Effects / Contraindications / Special Considerations /

INHIBITORS OF CELL WALL SYNTHESIS

Penicillin G / Standard Penicillins
(β-lactam) / Interfere with last step of CWS: cross-linkage step; lysis occurs / Gram +, spirochetes, some anaerobes / NOT CSF (unless inflamed meninges), NOT prostate, bone or eye / Renal (unchanged) / Beware of allergies; Renal insufficiency: adjust dose (seizures at high doses) / Must be given IV; Short half-life
Penicillin V / Standard Penicillins
(β-lactam) / Same as above / Same as above / Same as above / Renal / Same as above / Oral use; Only for minor infections (dental);
Methicillin / Anti- Staph Penicillins
(β-lactam) / Same as above / As above, esp. β-lactamase producing Staph. /

Same as above

/ Renal /

Nephrotoxic

/ Given IV for serious systemic infections; Nafcillin preferred; β-lactamase resistant
Nafcillin / Anti-Staph Penicillins
(β-lactam) / Same as above /

Same as above

/ Same as above / Renal /

Same as Pen G (Not nephrotoxic)

/

Same as above

Dicloxacillin / Anti-Staph Penicillins
(β-lactam) / Same as above / Same as above / Same as above / Renal / Same as Pen G / Administered orally (children) for mild local Staph infections.
Ampicillin / Aminopenicillins
(β-lactam) / Same as above / Same as Pen G plus Gram– bacilli / rods / Same as above / Renal / Resistance a problem; Superinfections (C. dificile) common;
↓ effectiveness of birth-control pills / Used to treat serious infections by penicillin susceptible organisms, incl. anaerobes, some Gram-; use w/ β-lactamase inhibitor (sublactam)
Amoxicillin / Aminopenicillins
(β-lactam) / Same as above / Same as Pen G plus Gram– bacilli / rods /

Same as above

/ Renal /

Same as above

/ Used prophylactically by dentists; DOC for URI, sinusitis, otitis, lower resp. infections; use w/ β-lactamase inhibitor (calvulonate)
Ticarcillin / Anti-Pseudomonal Penicillins
(β-lactam) / Same as above / As above, plus Gram- bacilli (Klebsiella, Enterobacter, Pseudomonas) /

Same as above

/ Renal /

Same as Pen G

/ Due to development of resistance, usually given in combination with aminoglycoside
Piperacillin / Anti-Pseudomonal Penicillins
(β-lactam) / Same as above / Same as above / Same as above / Renal / Same as Pen G / Same as above
Cefazolin / 1st gen. Cephalosporins
(β-lactam) / Same as above / Pen G substitute; also for Proteus, E. coli, Klebsiella / Same as above / Renal / Potentially nephrotoxic; 5-15% cross-reactivity with penicillin allergies – only use if delayed type allergy to pen. / Parenteral; surgical prophylaxis when poss. skin microbes involved
Ineffective against MRSA, Listeria, C. dificile, enterococci
Cephalexin / 1st gen. Cephalosporins
(β-lactam) / Same as above /

Same as above

/ Same as above / Renal /

Same as above

/ Oral;
Ineffective against MRSA, Listeria, C. dificile, enterococci
Cefoxitin / 2nd gen. Cephalosporins
(β-lactam) / Same as above / As above, plus Haemophilus, some Enterobacter & Neisseria
(HENPEcK) /

Same as Pen G

/ Renal /

Same as above

/ Parenteral; good against B. fragilis (anaerobe), For interabdom. sepsis, gyn. sepsis; colorectal surgery
Cefuroxime / 2nd gen. Cephalosporins
(β-lactam) / Same as above /

Same as above

/ CSF (Penetrates BBB) / Renal /

Same as above

/ Parenteral; Cefuroxime axetil = oral; For bronchitis, pneumonia in elderly, immunocompromised
Cefixime / 3rd gen. Cephalosporins
(β-lactam) / Same as above / Less effective for Gram+, extended range against Gram- bacilli (HENPEcK + other enterics) /

Same as Pen G

/ Renal /

Same as above

/

Oral, once daily

Ceftriaxone / 3rd gen. Cephalosporins
(β-lactam) / Same as above / Same as above / Good CSF penetration, and bone /

Hepatic

/ Same as above / Parenteral; DOC for Lyme disease and meningitis
Imipenem / Carbapenems
(β-lactam) / Same as above / Broadest spectrum: Gram- and +, anaerobes (incl. B. fragilis), some Pseudomonas / Good distribution in skin, soft tissue, bone, joints, CSF / Renal / GI upset, skin rash, reaction at infusion site, seizures in patients with renal insufficiency / Always administered with Cilastatin (IV), otherwise inactivated in renal tubules: Primaxin = Imipenem + Cilastatin; Resistant to most β-lactamases; use for organisms resistant to other drugs (pen, etc); DOC for Enterobacter
Vancomycin / Inhibits CWS at an earlier step than the β-lactams / Gram+; effective against some MRSA / Inflammation allows penetration into meninges / Renal / Fever, chills, phlebitis at infusion site, tachycardia, hypotension; Shock & flushing due to histamine release if rapid infusion; Ototoxicity, nephrotoxicity; allergies / Synergism with aminoglycosides; Penicillin substitute; Restricted use for serious infections due to β-lactam resistant Gm+ organisms; Slow IV drip, orally only for C. difficile colitis
INHIBITORS OF PROTEIN SYNTHESIS
Gentamicin / Aminoglycosides / Binds 30S (and 50S) subunit, inhibits initiation of protein synthesis / Gram-, (some Gram+) aerobic only / NOT CSF, eye, or respiratory syst.
Good in bone. / Renal / Worst ototoxicity of aminoglycosides; nephrotoxicity, vestibular damage, Neuromuscular paralysis at high conc. / Concentration-dependent killing, significant post-antibiotic effect (once daily dosing); Combine with β-lactams; Used w/Vancomycin for MRSA
Streptomycin / Aminoglycosides / Binds 30S subunit, inhibits initiation of protein synthesis / Gram- aerobic only /

Same as above

/ Renal / Major resistance problem; irreversible vestibular damage, fetal hearing loss (contraindicated w/ pregnancy); Neuromuscular paralysis at high conc. / Concentration-dependent killing, significant post-antibiotic effect; Second-line anti-TB; plague; tularemia (w/ penicillin)
Tobramycin / Aminoglycosides / Binds 30S (and 50S) subunit, inhibits initiation of protein synthesis / Gram- aerobic only /

Same as above

/ Renal / Ototoxicity, nephrotoxicity, vestibular damage; Neuromuscular paralysis at high conc. / Concentration-dependent killing, significant post-antibiotic effect; More expensive than Gentamicin
Tetracycline / Tetracyclines / Binds 30S subunit, inhibits binding of a.a.-tRNA; bacteriostatic / Broad spectrum: Gram- and + and obligate anaerobes, intracellular / CSF; concentrates in liver, kidney, spleen, skin, calcifying tissues / Renal / Phototoxicity ; hepatotoxicity; Contraindicated in pregnant ♀ and children under 8; C.dificile colitis;
↓ effectiveness of bcp’s; ↑ effects of warfarin / Major drug for rickettsial diseases and cholera, Mycoplasma, Chlamydia, Lyme disease
Doxycycline / Tetracyclines / Binds 30S subunit, inhibits binding of a.a.-tRNA; bacteriostatic /

Same as above

/ Same as above /

Hepatic

/ Same as above /

Same as above

Erythromycin / Macrolides / Irreversibly binds to 50S subunit, inhibits translocation step of prot. synthesis / Same as Penicillin G, also H. influenzae, N. meningitis, N. gonorrheae, Chlamydia, Mycoplasma / Prostate; concentrates in liver, macrophages /
Hepatic
/ Inhibits p450 (potentiates other drug fx); contraindicated with hepatic dysfunction; GI distress, temp. ototoxicity; resistance / Alternative to Penicillin G for allergic patients; DOC for Chlamydia during pregnancy
Clarithromycin / Macrolides /

Same as above

/ Same as above / Same as above / Renal / Inhibits p450 (potentiates other drug fx); resistance / Longer half life than erythromycin, less GI upset
Azithromycin / Macrolides /

Same as above

/

Same as above

/

Same as above

/
Hepatic
/ Temporary ototoxicity; resistance a major issue / Rapidly absorbed, well tolerated orally; DOC for Legionnaire’s disease
Clindamycin / Lincosamides / Binds to 50S subunit to prevent protein synthesis – bacteriostatic to bactericidal / Gram+ aerobes, Gram- and + anaerobes, esp. B. fragilis / Concentrates in bone – NOT CSF /
Hepatic
/ Diarrhea; Significant risk of superinfection (C. difficile); Drug interference with chloramphenicol or Macrolides; May inhibit NMJ / DOC for severe anaerobic infections (Bacteroides, etc.); taken orally or IV
Chloramphenicol / Binds to 50S subunit, inhibits peptidyl transferase - bacteriostatic / Broad spectrum: Gram- and +, rickettsiae, Chlamydia, anaerobes / Well distributed, including CSF, intracellular / Hepatic metabolism then renal excretion / BAD! Severe bone marrow aplasia; Gray baby syndrome; superinfections (pseudomemb. colitis); allergies; Inhibits p450, so drug interactions / Few uses due to adverse effects; Good to treat S. typhi; Refractory cases of meningitis or patients with β-lactam allergies, brain abscesses or intraabdominal infect.
Streptogramins / Bind two different sites on 50S subunit – bacteriostatic or bactericidal / Gram+ cocci; Legionella, M. pneumoniae, Chlamydia pneumoniae / Mostly hepatic / Pain/phlebitis at infusion site; arthralgias and myalgias; Inhibits p450, so drug interactions / RESERVED for serious infections with resistant Gram + bugs like E. faecium, MRSA; IV slow drip, NOT with saline/heparin
Linezolid / Prevents formation of 70S ribosome – Unique effect, precedes steps inhibited by other PSI’s / Gram+ cocci, bacilli, anaerobes and aerobes; Listeria monocytogenes / 80% renal – but no dosage adjustment needed for renal insuff. / Seems well-tolerated; thrombocytopenia, GI distress, HA, rash; NO EFFECT on p450 / RESERVED for multi-drug resistant strains of S. aureus, E. faecium, S. pneumoniae
MRSA DOC
INHIBITORS OF NUCLEIC ACID SYNTHESIS
Metronidazole / When activated, attacks, fragments bacterial DNA / Only active in obligate anaerobes: Bacteroides, Clostridium; also protozoa / Most tissues, incl. bone and CSF / Hepatic metabolism, mostly renal excretion / Nausea, HA, dizziness; Alcohol contraindicated; peripheral neuropathy with prolonged use / DOC for Bacteroides; Good for endocarditis, brain abscesses, C. difficile colitis
Ciprofloxacin / Quinolones and Fluoroquinolones / Inhibit DNA gyrase, so DNA replication blocked - bactericidal / Gram – cocci and bacilli / High levels in bone, prostate, kidney / Hepatic and renal (beware renal insuf.) / N/V, HA, diz; nephrotoxicity, phototoxicity; Contraindicated in pregnancy, children - arthropathy; Inhibits p450, so drug interactions; w/ NSAIDS ↑ CNS stim.effects - seizures / DOC for UTI’s, prostatitis; synergism with β-lactams;
CF-associated Pseudomonas infections
Rifampin / Rifamycins / Inhibits RNA polymerase - bactericidal / Many Gram- and +, esp. Mycobacterium / Distributes well, including CSF / Hepatic metabolism and recirculation; renal and hepatic elimination / NOT given as single agent due to resistance; Hepatotoxicity; Induces p450, so ↓ effect of bcp’s, anticoag’s, estrogens, glucocort’s / Mainstay for TB treatment (w/ Isoniazid); MRSA;
INHIBITORS OF METABOLISM
Sulfamethoxazole / Sulfonamides / Inhibits dihydropteroate synthetase (folate synthesis) / Nocardia, Chlamydia, E. coli, Proteus, H. influenzae, S. pyogenes, S. pneumoniae / Well distributed, including CSF / Hepatic metabolism, renal excretion (beware renal insuf.) / Resistance; Nephrotox; allergies; Kernicterus - contraindicated in pregnant ♀ and newborns; Anemia (w/G6PD def.?); Inhibits p450 / For UTI’s, usu. in combination with trimethoprim; otitis, bronchitis, sinusitis, P. carinii pneumonia
Trimethoprim / Inhibits dihydrofolate reductase (folate synthesis) / Similar to sulfonamides, but 20-50X more potent / Concentrates in acidic prostate and vaginal fluids / Similar to above / Same as above; permanent renal damage if poor renal fxn; AIDS patients adverse rxns / Combined with Sulfamethoxazole (=Co-trimoxazole); UTI; prostatitis; also see above

Also remember the β-lactamase inhibitors: Clavulanic acid, Sulbactam and Tazobactam