Candyman's Usmle Antimicrobials

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Bacteriostatic antibiotics

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-All protein synthesis inhibitors except aminoglycosides (tetracylines, chloramphenicol, clindamycin, macrolides, linezolid)
-TMP-SMX

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Bacteriocidal antibiotics

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-Aminoglycosides
-Penicillins (G,V)
-Penicillinase-resistant penicillins (methicillin, nafcillin, dicloxacillin)
-Aminopenicillins (ampicillin, amoxacillin)
-Ticarcillin, carbenicillin, piperacillin
-Cephalosporins
-Vancomycin
-Fluoroquinolones
-Metronidazole

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Penicillin G/V toxicity

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-hypersensitivity rxn
-hemolytic anemia

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Penicillin G/V spectrum

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Gram + cocci and rods
Gram - cocci
Spirochetes

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Tx for staph aureus

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If MSSA: methicillin, nafcillin, dicloxacillin (penicillinase resistant)
If MRSA: vancomycin

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Spectrum of aminopenicillins (ampicillin and amoxicillin)

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AMPICILLIN/AMOXICILLIN
-wider spectrum penicillins, but penicillinase susceptible
-thus, combine with clavulanic acid (=penicillinase inhibitor)
-Gram +s and Gram - rods (H. flu, E. coli, Listeria, Proteus, Salmonella, Enterococci)

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Toxicity of aminopenicillins (ampicillin/amoxicillin)

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-hypersensitivty rxns
-pseudomembranous colitis

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Anti-pseudomonal penicillins

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Ticarcillin, carbenicillin, piperacillin
-Susceptible to penicillinase (so co-administer clavulanic acid)

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Ceftriaxone, cefotaxime, ceftazidime

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3rd generation cephalosporins
-used to tx serious Gram - infections resistant to other beta-lactams, meningitis (e.g. pseudomonas and gonorrhea)

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Cefepime

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4th generation cephalosporin
-better coverage against pseudomonas and gram +s

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Cefoxitin, cefaclor, cefuroxime

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2nd generation cephalosporins
-Gram + cocci
-Proteus, E. Coli, Klebsiella (PECK)
-H. flu, Enterobacter, Neisseria spp., Serratia (HENS)

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Cefazolin, cephalexin

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1st generation cephalosporins
-Gram + cocci
-Proteus, E. Coli, Klebsiella

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Toxicity of cephalosporins

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-hypersensitivity rxns
-potentiates nephrotoxicity of aminoglycosides
-disulfiram-like rxn with EtOH

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Monobactam resistant to beta-lactamases

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Aztreonam
-Inhibits cell wall synthesis by binding to PBP3
-Coverage: Gram - rods, no coverage against Gram +s or anaerobes
-For those w/ penicillin allergy who cannot tolerate aminoglycosides

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Drug of choice for enterobacter

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Imipenem/cilastatin
-broad spectrum, beta lactamase resistant carbapenem
-always administered with cilastatin to slow renal inactivation
-Gram + cocci, Gram - rods, ENTEROBACTER
-lots o toxicities

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Used for serious, Gram + MDR organisms (e.g. MRSA and C. diff)

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Vancomycin
-binds D-ALA-D-ALA and inhibits cell wall synthesis, bacteriocidal
-minor side effects, including red man syndrome

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Protein Synthesis Inhibitors

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30S: Aminoglycosides, Tetracyclines
50S: Chloramphenicol, Clindamycin, Erythromycin (macrolides), Lincosamides, Linezolid

"buy AT 30, CCELL at 50"

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Aminoglycosides

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Gentamycin, Neomycin, Amikacin, Tobramycin
-require O2 for uptake so ineffective against anaerobes
-severe gram-negative infections
-neomycin used to wipe out gut flora b/f bowel surgery

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Aminoglycoside toxicity

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Nephrotoxicity (w/ cephalosporin), Ototoxicity (w/ furosemide), Teratogen

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Tetracyclines

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Tetracycline, doxycycline, demeclocycline, minocycline
-Used for acne, chlamydia, Lyme disease, Rickettsia et al.
-Administration with milk, antacids, iron --> malabsorption

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Tetracycline toxicity

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-GI distress
-Discoloration of teeth and poor bone growth in children
-Photosensitivity

CONTRAINDICATED IN PREGNANCY

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Macrolides

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Erythromycin, azithromycin, clarithromycin
-URIs, atypical pneumonias (mycoplasma, legionella), STDs (chlamydia, neisseria)

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Macrolide toxicity

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GI discomfort
Acute cholestatic hepatitis
Eosinophilia
Increased [] of oral anticogulants

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Chloramphenical toxicity

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Aplastic anemia
Gray baby syndrome

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Clindamycin toxicity

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Pseudomembranous colitis (C. diff overgrowth)

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Treats anaerobes above the diaphragm (B. fragilis, Clostridium perfringens)

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Clindamycin

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Sulfa drug allergy

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Pts who cannot tolerate sulfa drugs, should not take:
-Sulfonamides (sulfamethoxazole, sulfisoxazole, sulfadiazine)
-Sulfonylureas
-Sulfasalazine
-Acetazolamide, Furosemide, Thiazides

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Sulfamethoxazole, sulfisoxazole, sulfadiazine

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Sulfonamides
-PABA antimetabolites, inhibit dihydropteroate synthetase
-Spectrum: gram+/-, Nocardia, Chlamydia
-Produce oxidative stress --> hemolysis if G6PD deficient
-Synergistic with trimethoprim, pyrimethamine

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Spectrum of Trimethoprim (TMP)

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Used in combination with sulfonamides (TMP-SMX) causing sequential block of folate synthesis
-Used for recurrent UTIs, shigella, salmonella, PCP

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Ciprofloxacin, norfloxacin, ofloxacin, levofloxacin

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Fluoroquinolones: Ciprofloxacin, norfloxacin, ofloxacin, levofloxacin
-Inhibit DNA gyrase (topoisomerase II)
-Can't co-administer antacids, Ca2+, iron --> malabsorption of drug
-Spectrum: GNRs of urinary and GI tracts (including Pseudomonas), Neisseria, some GPs

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Toxicity causes tendonitis and tendon rupture in adults, leg cramps and myalgias in children

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Fluoroquinolones: Ciprofloxacin, norfloxacin, ofloxacin, levofloxacin
-Inhibit DNA gyrase (topoisomerase II)
-Can't co-administer antacids, Ca2+, iron --> malabsorption of drug
-Spectrum: GNRs of urinary and GI tracts (including Pseudomonas), Neisseria, some GPs

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Spectrum of metronidazole

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Giardia, Entamoeba, Trichomonas
Gardnerella, Anaerobes, H. Pylori

"GET GAP w/ metro"

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Triple therapy for H. pylori

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1) Metronidazole
2) Bismuth (pepto bismol)
3) Amoxicillin (or tetracycline)

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MOA of polymyxins

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Polymyxin B/E
-Bind cell membranes and disrupt osmotic properties

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Tx of MRSA

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Vancomycin

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Tx of VRE

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Linezolid, streptogramins (quinupristin, dalfopristin)

"Streptogramins are PRISTINe"

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Amantadine

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Blocks viral penetration & uncoating (via M2 protein); also causes dopamine release from intact nerve terminals
-Used for prophylaxis and tx of influenza A and Parkinson's
-Rimantidine has fewer CNS effects

Note: 90% infuenza A resistant due to mutated M2 protein

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Zanamivir, oseltamivir

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Inhibits influenza neuraminidase, blocking release of progeny virus
-Used for influenza A & B

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Ribavirin

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Inhibits synthesis of guanine nucleotides [by competitively inhibiting IMP dehydrog]
-RSV, chronic HCV
-Causes hemolytic anemia, severely teratogenic

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Acyclovir

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-Guanosine analog. Must be phosphorylated first by viral kinase and then by cellular enzymes
-Inhibits viral DNA polymerase by chain termination
-HSV1/2, EBV
-VZV (famciclovir)
-No effect on latent infection

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Ganciclovir

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-Guanosine analog. Must be phosphorylated first by viral kinase and then by cellular enzymes
-Preferentially inhibits viral DNA polymerase
-Used for CMV!!!

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Tx of HSV1/2, EBV

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Acyclovir
-Guanosine analog. Must be phosphorylated first by viral kinase and then by cellular enzymes
-Inhibits viral DNA polymerase by chain termination
-HSV1/2, EBV
-VZV (famciclovir)
-No effect on latent infection

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Tx of CMV

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Ganciclovir
-Guanosine analog. Must be phosphorylated first by viral kinase and then by cellular enzymes
-Preferentially inhibits viral DNA polymerase
-Used for CMV!!!

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Tx of VZV

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Famciclovir
-Guanosine analog. Must be phosphorylated first by viral kinase and then by cellular enzymes
-Inhibits viral DNA polymerase by chain termination
-HSV1/2, EBV
-VZV (famciclovir)
-No effect on latent infection

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Foscarnet

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Viral DNA polymerase inhibitor, [binds to pyrophosphate binding site]
-Does not require activation by viral kinase
-Used for CMV when ganciclovir fails
-Used for HSV when acyclovir fails

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Used for CMV when ganciclovir fails
Used for HSV when acyclovir fails

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Foscarnet
-Viral DNA polymerase inhibitor, [binds to pyrophosphate binding site]

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IFN-alpha

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Chronic hep B & C
Kaposi's sarcoma

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IFN-beta

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MS

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IFN-gamma

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NADPH oxidase deficiency

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MOA of interferons

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Induce ribonuclease that degrades viral mRNA

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Ritonavir, indinavir, etc.

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Protease inhibitors (-navir)

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Zidovudine (AZT), didanosine (ddI), zalcitabine (ddC), stavudine (d4T), lamivudine (3TC), abacavir

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Nucleoside RTIs

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Nevirapine, Efavirenz, delavirdine

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Non-nucleoside RTIs

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Enfuvirtide

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Fusion inhibitor
-viral fusion mediated by gp120 binding CD4/CCR5

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Used for general prophylaxis and during pregnancy to reduce risk of fetal transmission of HIV

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Zidovudine (ZDV = AZT)
-nucleoside RTI

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Bind ergosterol in fungal cell membrane and form membrane pores that allow leakage of electrolytes

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Amphotericin B, Nystatin

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Nystatin

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Antifungal
-MOA: Binds ergosterol in fungal cell membrane and form membrane pores that allow leakage of electrolytes
-Too toxic for systemic use, but used topically for diaper rash and vaginal candidiasis and "swish and swallow" for thrush

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Inhibit ergosterol synthesis

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Azoles (fluconazole, ketoconazole, etc.)
-Used for systemic mycoses
-Fluconazole for cryptococcal meningitis in AIDS pts (crosses BBB)
-Ketoconazole for Blasto, Coccidio, Histo, Candida & hypercortisolism

Toxicity: gynecomastia, inhibit cytochrome P-450

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Flucytosine

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Antifungal
-Inhibits DNA synthesis by conversion to 5-FU (humans do not convert 5-FC --> 5-FU)
-Used in systemic fungal infections in combination w/ amphotericin B

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Tx of invasive aspergillosis

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Caspofungin
-inhibits cell wall synthesis by inhibiting synthesis of beta-glucan

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Tx of dermatophytoses (especially onychomycosis)

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Terbinafine
-inhibits fungal enzyme squalene epoxidase --> decreased ergosterol synthesis

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Griseofulvin

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Anti-fungal
-Interferes w/ microtubule fxn and disrupts mitosis

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TB prophylaxis

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Isoniazid (INH)

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TB treatment

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Rifampin, Isoniazid, Pyrazinamide, Ethambutol (causes optic neuropathy and R-G colorblindness)