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The Sanford Guide to Antimicrobial Therapy Johns Hopkins Abx Guide (not free any more) Palm
iSilo program Epocrates
Gram-positives Anti-staph PCNs (nafcillin, methicillin, oxacillins) Penicillin G/V Clindamycin Linezolid Fluoroquinolines Vancomyci n Rifampin Sulfonamides Aminoglycosides Tetracyclines Imipenem Meropene m Amoxicillin Ampicillin Macrolides
Aztreona m
1st Generation
2nd Generation
Beta-lactam ABX
Penicillins Cephalosporins Aztreonam Carbapenems
Exception
Vancomycin
Beta-lactam structure
Mechanism of Action
1. All beta-lactams bind penicillin-binding proteins (PBPs) 2. All beta-lactams block transpeptidase cross-linking of cell wall 3. Activate autolytic enzymes, causing osmotic damage (bactericidal)
1st Generation
Drugs
Penicillin G and V
Clinical use
Narrow spectrum (mainly gram-positives)
Sensitive to beta-lactamases
Means: on an exam, penicillin G or V is never the answer for treating Staph
Exam questions:
DOC for syphillis (benzathine penicillin), DOC in strep infections, especially to prevent rheumatic fever DOC for susceptible pneumococci
2nd Generation
Drugs
Nafcillin, Methicillin, Oxacillin, Cloxacillin, Diclaxicillin To overcome the beta-lactamase resistance, these drugs were developed but they became so narrow spectrum that they only clinically are used for Staph. These drugs created the superbug MRSA
Beta-lactamase Altered PBPs
3rd Generation
Drugs
Aminopenicillins
Ampicillin Amoxicillin
Clinical use
Broad spectrum (gram positive and gram negatives, but NOT beta-lactamase resistant)
Famous for treating:
H. flu and Listeria (ampicillin) Lyme Disease (amox) DOC in peds and pregnancy Enterococci
Drug companies made body guards, clavulanic acid and sulbactam, to protect the aminopenicillins from beta-lactamases.
4th Generation
Drugs
Anti-pseudomonal penicillins
Ticarcillin Piperacillin Carbenicillin
Clinical use
Pseudomonas Synergistic effect when combined with aminoglycosides. Parenteral penicillins usually combined with beta-lactamase inhibitors
Pharmacokinetics of Penicillins
Rule: All penicillins are water soluble, except nafcillin. Water soluble substances:
Are excreted by the kidneys.
Means adjustments in renal failure and are potentially renal toxic
Toxicity
Rule: Penicillins cause allergies
Come from fungal organisms
Means already immunogenic
Toxicity
Jarisch-Herxheimer reaction in Rx of syphilis Fever, chills, headache, myalgias, and exacerbation of syphilitic cutaneous lesions Ampicillin causes a famous maculopapular rash when given to patients with infectious mono (EBV).
Cephalosporins
Mechanism of action and resistance:
same as penicillins
Clinical use
Gram positives
And a few gram negatives PEcK (Proteus, E. coli, Klebsiella)
Pharmacokinetics
Do not enter CNS
Clinical use
Gram negatives: HEN PEcKS (H. flu, Enterobacter, Neisseria, Proteus, E. coli, Klebsiella, Serratia)
Pharmacokinetics
Do not enter CNS, except cefuroxime
Clinical use
1st generation + 2nd generation = 3rd generation (gram positive and negative) +anaerobes
Pharmacokinetics
Ceftriaxone is lipid soluble
Means good entry into CNS Means metabolized and excreted into bowel
Can cause sludge in gallbladder
Boards:
Ceftazidime for pseudomonaz Ceftriaxone for gonorrhea and meningitis
Clinical use
3rd Generation + more beta-lactamase resistance
Toxicity
Same as penicillins Disuliram-like reaction w/ ethanol
In cephalosporins with a methylthiotetrazole group, i.e. cefamandole, cefoperazone, cefotetan
azole portion gives us the disulfiram-like reaction
Metronidazole
Aztreonam
Mechanism:
Monobactam resistant to beta-lactamases Inhibits cell wall synthesis (same as penicillins) Synergistic with aminoglycosides
Clinical use
Gram negative rods only (pseudomonas)
Toxicity
No cross-allergenicity w/ penicillins
Imipenem/cilastatin, Meropenem
Mechanism
Carbapenems resistant to beta-lactamases Inhibits cell wall synthesis (same as penicillins) Cilastatin inhibits renal dihydropeptidase I which decreased inactivation of imipenem in kidney.
Clinical use
Decerebrate Antibiotics
Dont need to think about coverage, can work on almost anything
Toxicity
Imipenem famous for CNS toxicity (seizures) Meropenem has reduced risk of seizures
Vancomycin
Mechanism
Inhibits cell wall mucopeptide formation by binding D-ala D-ala portion of cell wall precursors (USMLE TQ)
Resistance occurs when changed to D-ala D-lac
Clinical use
Gram positive multidrug-resistant organisms
MRSA (IV) C. difficile (PO)
Toxicity
Nephro and ototoxic Red man syndrome with rapid infusion
Can prevent w/ antihistamine pretreatment
Gram-positives Anti-staph PCNs (nafcillin, methicillin, oxacillins) Penicillin G/V 50s ribosome Vancomyci n Nucleus 30s ribosome Imipenem Meropene m Amoxicillin Ampicillin
Aztreona m
1st Generation
2nd Generation
Rule: All protein synthesis inhibitors are bacteriostatic, except for the aminoglycosides.
Tetracyclines
Drugs
Doxycycline Minocycline Demeclocycline Tetracycline
Mechanism
Reversibly bind to the 30S ribosome and inhibit binding of aminoacyl-t-RNA to the acceptor site.
Tetracyclines
Clinical use
Very broad spectrum Important use for spirochetes and intracellular bugs
Rickettsial Infections Chlamydia
Toxicity
Chelators of divalent ions
Means they deposit in bones and teeth Means contraindicated in pregnancy and in kids who are still growing Means cant take with antacids or iron.
Boards:
Doxycycline is lipid soluble; means good STDs and prostatitis Minocycline is very water soluble and enters all secretions, especially saliva; means useful for meningococcus prophylaxis Demeclocycline inhibits the release of ADH; means can be used for SIADH
Aminoglycosides
Drugs
Gentamycin, neomycin, amikacin, tobramycin, streptomycin
Mechanism
Taken up by an oxygen dependent pump and bind to the 30S ribosomal unit and Induce the binding of the wrong t-RNA-AA complex, resulting in the synthesis of false proteins. (Bactericidal)
Aminoglycosides
Clinical use
Gram negative aerobes only! (pseudomonas) Synergistic w/ beta-lactams Neomycin for bowel surgery Tobramycin for Pseudomonas
Toxicity
Amino (NH3) + glycoside (OH) makes extremely polar
Means membrane penetration in a bacteria is dependent on a special oxygen pump and only covers gram negative aerobes Means renally excreted and renal toxic Means can be trapped in inner ear and is ototoxic
Neuromuscular blockade
Macrolides
Drugs:
Erythromycin Azithromycin Clarithromycin
Mechanism
Inhibit protein synthesis by blocking translocation, bind to 50S ribosomal subunit (resistance is through methylation at binding site)
Macrolides
Clinical use
Same broad coverage as tetracyclines URIs and atypical pneumonias (Mycoplasma, Legionella, Chlamydia) Neisseria Alternative for penicillin allergic patients
Toxicities
Stimulate motilin receptor (erythromycin) causing GI upset Lipid soluble, except azithromycin
Means P450 interactions (erythromycin is a famous inhibitor) and liver problems (acute cholestatic hepatitis)
Clindamycin
Mechanism
Blocks peptide bond formation at 50S ribosomal subunit (bacteriostatic)
Clinical use
Gram-positives and anaerobes
Means can easily cause C. diff colitis
Linezolid
Mechanism
Linezolid binds on the 23S portion of the 50S subunit close to the peptidyl transferase and chloramphenicol binding sites.
Clinical
Famous for treating gram-positive drug resistant bugs (MRSA, and multidrug resistant pneumococcus)
Toxicity
Usually well tolerated Thrombocytopenia MAOI (avoid tyramine containing food)
Quinupristin/Dalfopristin
Mechanism
Protein synthesis inhibitors that bind the 50S ribosomal subunit
Clinical use
VRE
Toxicity
P-450 inhibitor
Fluoroquinolones
Drugs
Ciprofloxacin Gatifloxacin Levofloxacin Moxifloxacin Ofloxacin
Mechanism
Inhibits DNA gyrase (topoisomerase II) (Bactericidal)
Fluoroquinolones
Clinical use
Gram-negative rods of UTI and diarrhea Were 1st oral treatment of gram-negative sepsis
Means were overused, leading to resistance
Toxicity
QT prolongation and arrhythmias Hypo/hyperglycemia Achilles tendon rupture or tendinitis has occurred rarely
Rifampin
Mechanism
Inhibits DNA-dependent RNA polymerase
Clinical use
TB (in combo and in prophylaxis) Famous for prophylaxis of meningococcus and H. flu
Toxicity
Hepatotoxic Revs up P-450 Rs:
RNA polymerase inhibitor Revs up P-450 Red/orange body fluids
Sulfonamides
Mechanism
Inhibits bacterial dihydropteroate synthase by competing for binding sites with paminobenzoic acid (PABA), a precursor required for bacterial synthesis of folic acid. Trimethoprim binds tightly to bacterial dihydrofolate reductase. Synergistic with sulfonamides.
Sulfonamides
Clinical use
Resistance to sulfonamides is common PCP prophylaxis (PO) and treatment (IV)
TrimethoprimSulfamethoxazole, (TMP-SMX) If sulfa allergy use pentamidine (antiprotozoal agent)
Toxicity
Allergies (sulfa allergies, hemolytic anemia, SJS) Carried by albumin
Means can cause kernicterus
Metronidazole
Mechanism
Toxic metabolites
Means causes GI disturbance, glossitis (metallic taste in mouth), urethritis
Clinical use
Anaerobes G.E.T. on the Metro (Giardia, Entamoeba, Trichomonas) C. diff colitis (PO)
Toxicity
Metronidazole
Disulfiram-like reaction w/ ethanol
Mechanisms of Resistance
Rule: Every bacteria is gram negative, except for the gram-positives and oddballs.
Oddballs
Mycoplasma (no cell wall) Ureaplasma (no cell wall) Legionella (silver stain) Chlamydia (obligate intracellular) Rickettsia (obligate intracellular) Mycobacterium (acid-fast) Treponema (spirochete) Borrelia (spirochete)
Gram-positives
Gram-negatives
Cell Wall
Gram-positives
Gram-negatives
Cell Wall
Gram-positives Anti-staph PCNs (nafcillin, methicillin, oxacillins) Penicillin G/V 50s ribosome Vancomyci n Nucleus 30s ribosome
Cell Wall
Aztreona m
Gram-positives Anti-staph PCNs (nafcillin, methicillin, oxacillins) Penicillin G/V 50s ribosome Vancomyci n Nucleus 30s ribosome
Cell Wall
Aztreona m
1st Generation
2nd Generation
Gram-positives Anti-staph PCNs (nafcillin, methicillin, oxacillins) Penicillin G/V 50s ribosome Vancomyci n Nucleus 30s ribosome
Amoxicillin Ampicillin
Aztreona m
1st Generation
2nd Generation
Gram-positives Anti-staph PCNs (nafcillin, methicillin, oxacillins) Penicillin G/V 50s ribosome Vancomyci n Nucleus 30s ribosome Imipenem Meropene m Amoxicillin Ampicillin
Aztreona m
1st Generation
2nd Generation
Gram-positives Anti-staph PCNs (nafcillin, methicillin, oxacillins) Penicillin G/V Clindamycin Linezolid Vancomyci n Nucleus Aminoglycosides Tetracyclines Imipenem Meropene m Amoxicillin Ampicillin Macrolides
Aztreona m
1st Generation
2nd Generation
Gram-positives Anti-staph PCNs (nafcillin, methicillin, oxacillins) Penicillin G/V Clindamycin Linezolid Fluoroquinolines Vancomyci n Rifampin Sulfonamides Aminoglycosides Tetracyclines Imipenem Meropene m Amoxicillin Ampicillin Macrolides
Aztreona m
1st Generation
2nd Generation
Look for contraindications to using your antibiotic. Is the patient too young or too pregnant?
Dont use tetracyclines, aminoglycosides, fluoroquinolones, sulfonamides.
Tetracyclines Vancomycin
Newbor n
Adul t
Practice Question
A 16-year-old high school cheerleader presents with low grade fever, pleuritic pain and a nonproductive cough. A sample tube of her blood was placed in ice, and "grains of sand" appeared in the glass portion of the tube. Therapy should include which of the following? A. Ampicillin B. Erythromycin C. Oxygen and external cooling D. Penicillin G E. Ribavirin
Practice Question
A 58-year-old alcoholic man with multiple dental caries develops a pulmonary abscess and is treated with antibiotics. Several days later, he develops nausea, vomiting, abdominal pain, and voluminous green diarrhea. Which of the following antibiotics is most likely responsible for this patient's symptoms? A. Chloramphenicol B. Clindamycin C. Gentamicin D. Metronidazole E. Vancomycin
Practice Question
Which of the following organisms is most likely to be implicated as a cause of urethritis that persists after antibiotic therapy for gonorrhea? A. Actinomyces B. Chlamydia C. Mycobacteria D. Nocardia E. Rickettsia
Practice Question
A 33-year-old woman presents with fever, vomiting, severe irritative voiding symptoms, and pronounced costovertebral angle tenderness. Laboratory evaluation reveals leukocytosis with a left shift; blood cultures indicate bacteremia. Urinalysis shows pyuria, mild hematuria, and gram-negative bacteria. Which of the following drugs would best treat this patient's infection? A. Ampicillin and gentamicin B. Erythromycin C. Gentamicin and vancomycin D. Tetracycline
Practice Question
A 35-year-old male undergoes an appendectomy. Several days later, an abscess has formed at the surgical site. It does not improve with administration of a cephalosporin, but does respond to nafcillin. The infecting organism most likely produced an enzyme that would hydrolyze which bond in the above molecule? A. A B. B C. C D. D