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75 Cards in this Set
- Front
- Back
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MIC stands for..
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Minimum inhibitory concentration.
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MBC stands for...
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Minimum bacteriocidal concentration.
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Resistance to an antibiotic means that...
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A bug will not be killed by a given antibiotic at a clinically achievable concentration.
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What is a break point?
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A committee assigned number that determines resistance vs. susceptibility.
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Effectiveness of a beta lactam is determined by...
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Time (duration) over MIC
Total time the concetration is higher than the MIC MUST be at least 50% of the dosing curve for clinical success. |
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Effectiveness of a fluoroquinolone is determined by...
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Area under the curve/MIC
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Effectiveness of an aminoglycoside is determined by...
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Cmax/MIC
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The relationship between pharmacokinetics and MIC is called...
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Pharmacodynamics
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Is the MIC sufficient to determine the susceptibility of an organism to an antibiotic IN A PATIENT?
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No.
The MIC must be lower than the break point for an organism to be susceptible. |
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The three possible relationships between two different antibiotics in working on a particular bug are....
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Synergy
Indifference Antagonism |
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Beta lactams include...
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Penicillins
Cephalosporins Carbapenems Monobactam |
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The MLS group of antibiotics includes...
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Macrolides
Lincosamides (Lincomycin) Streptogramins |
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What are the properties of beta lactam antibiotics?
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Drugs that contain a beta lactam ring.
(a ring with an amide bond that is often drawn as a square). They bind PBP in the cell wall. They are bacteriocidal. Spectrum is dependent on subclasses within classes (The R group). Pharmacodynamics is time dependant. They generally achieve good serum, urine and tissue levels but CSF levels vary considerably amongst the drugs. |
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What is a PBP?
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Penicillin binding protein in the cell wall of a bacterium which normally functions as a transpeptidase enzyme.
It is responsible for crosslinking petidoglycan in the normal bacterial cell wall. No crosslinking as in when we treat with beta-lactams means a weak cell wall and osmotic dysregulation. |
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In what three ways can bacteria develop resistance to beta lactams?
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They can develop beta lactamases.
They can alter their PBP's so they don't bind beta lactams as strongly. They can decrease their permeability so that the beta lactam does not get to the PBP. |
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beta lactamases can be made by either G- or G+ organisms. They can be on a plasmid or on the chromosome. They are more important for G- though because...
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In G- organisms the beta lactamase can hang out in significant concentrations between the two membranes.
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What are beta lactamase inhibitors and what are three examples of them?
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"Suicide" molecules that resemble beta lactams and irreversibly bind beta lactamase.
Clavulanic acid Sulbactam Tazobactam |
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What is a beta lactamase?
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A disposable enzyme made by some bugs that can dismantle beta lactam antibiotics.
It can be inducible in some cases. |
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What is included in the penicillin class antibiotics?
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-Penicillin
(IV and PO) -Amino penicillins Ampicillin IV (Ampicillin/sulbactam) Amoxicillin-PO -Antistaphylococcal penicillins Methicillin Oxacillin Nafcillin Dicloxacillin—PO -Extended spectrum penicillin (Antipseudomonal penicillin) Ticarcillin (Ticarcillin/clavulanate) Piperacillin (Piperacillin/tazobactam) |
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What is penicillin G useful for?
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Streptococci, (A, B strep).
Enterococci Spirochetes: syphilis, Lyme, leptospirosis Sometimes used as empiric therapy for periodontal disease. Resistance is a concern with: Pneumococcus Enterococcus Strep viridans (NOT A&B) |
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What is the primary drug used to treat syphillis?
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Benzathine penicillin.
Depot prep. with LONG half life. Very painful shot. |
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What are the properties of the antistaphylococcal penicillins; methicillin, nafcillin, oxacillin, and dicloxacillin...
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Have a short half life.
Resistance to them occurs through PBP alteration as in MRSA. If this happens no beta lactams will work. |
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The aminopenicillins; ampicillin and amoxicillin extend the spectrum of penicillin to include...
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More G- rods like H. influenza and H. pylori.
They are often paired with beta lactamase inhibitors as in Augmentin and Unasyn. |
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Ticarcillin and Piperacillin are unique penicillins in that they are...
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Antipseudomonals
There is no useful oral preparation though. Can be coupled with beta lactamase inhibitor as follows: ticarcillin + clavulanic acid (Timentin ®) piperacillin + tazobactam (Zosyn ®) |
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What are cephalosporins?
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Beta lactams
They are more stable to beta lactamases than penicillin. Resistance is acquired through altered PBP's or very high levels of inducible beta lactamases in G-'s High therapeutic to toxicity ratio (i.e. safe) 3rd generation cephalosporins (ceftriaxone, ceftazidime) have good CNS penetration. |
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What are the first generation cephalosporins?
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Cefazolin—IV
Cephalothin –IV & PO |
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What are the second generation cephalosporins?
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Cefoxitin--IV
Cefuroxime—IV and PO |
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What are the third generation cephalosporins?
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Broad spectrum
Ceftriaxone Anti-pseudomonal Ceftazidime |
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what is a fourth generation cephalosporin?
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Cefepime.
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What are 1st generation cephalosporins (Cefazolin, Cephalothin) good for?
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They are generally better against gram-positives (i.e. staph and strep)
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2nd generation cephalosporin (Cefoxitine, Cefuroxime) are an improvement over 1st generation cephalosporins because they also pick up...
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Haemophilus influenzae and Enterobacteriaceae
Some also cover anaerobes. |
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3rd and 4th generation Cephalosporins are best for treating...
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G- infections
They have NO anaerobic activity though. |
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Cephalothin's trade name is...
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Ceflex
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1st generation cephalosporins are commonly prescribed for...
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Skin and soft tissue infections
Bone and joint infections Surgical prophylaxis |
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2nd generation cephalosporins are commonly prescribed for...
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Respiratory tract infections.
Intraabdominal infections Gut surgery prophylaxis (for anaerobes) Still good for skin and soft tissue. |
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3rd generation cephalosporins are commonly prescribed for...
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Meningitis
Gonorrhea Pneumonia Fever in neutropenic patients |
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4th generation cephalosporins are commonly prescribed for...
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Nosocomial infections
Pneumonia |
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The third generation cephalosporin, cefazidime is the only 3rd generation that does well against...
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Pseudomonas
Ceftriaxone does not work but is much better against pneumococcus. |
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The spectrum of cefepine (4th generation) is sort of like giving...
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Ceftriaxone
Cefazidime It covers both pseudomonas and pneumococccus. |
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How many drugs are currently in the antibiotic class monobactams?
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One
Aztreonam |
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What is aztreonam?
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Beta lactams
Subclass Monobactams Activity ONLY against G-aerobes but includes Pseudomonas. Poor cross allergenicity with other beta-lactams so good for G- infections with penicillin or cephalosporin allergy. VERY expensive. |
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What are carbapenems?
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Beta lactams
Binds to PBP Very beta lactamase stable. G+,G-, aerobic and anaerobic activity.Broadest spectrum beta lactam. Hypersensitivity cross reacts with penicillin. Drug of choice for 3rd generation cephalosporin resistant klebsiella and enterobacter. “Achilles heels” include MRSA, enterococci. Listeria, and some esoteric gram negative rods. Most important resistance mechanism is reduced permeabilty of G- outer membrane. Some organisms can make carbapenemases which are beta lactamases with a very bad attitude. |
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What are the three most commonly used carbapenems?
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-Imipenem-
combined with cilastatin, a renal dipeptidase inhibitor, extends half-life and protects against nephrotoxicity. -Meropenem- Does not need cilastatin Less likely to cause seizures Less nausea -Ertapenem- Once a day dosing makes it attractive for home care BUT it has less activity than the other two carbapenems for pseudomonas and acinetobacter. |
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Vancomycin
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NOT an aminoglycoside. It is a GLYCOPEPTIDE.
Bacteriocidal. (cell wall synthesis attack) Crosses GI mucosa very poorly in either direction. Not removed by dialysis. Only good for G+ because it is too big to penetrate G- porons. Interferes with cell wall synthesis by binding to terminal d-alanine-d-alanine of peptidoglycan precursor. Mechanism has NOTHING to do with PBP. 1st generation cephalosporin beta-lactams are better at Staph but Vanco will kill MRSA. Resistance is acquired if terminal D-alanin turns into D-lactate as in VRSA. |
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Macrolides
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Act on the ribosome
Time above MIC important for killing (just like beta lactams) Resistance is acquired by ribosomal methylation or by drug efflux. |
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Erythromycin
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Macrolide
ie. ribosome and time above MIC Good for G+'s and intracellulars. Staph, Strep, Pneumococcus,Mycoplasma, Chlamydia,Legionella, Diptheria etc. |
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Clarithromycin/Azithromycin
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Macrolide
Same spectrum as erythromycin plus coverage of H.flu and moraxella. Also useful for H.pylori and mycobacteria just like erythromycin. They are easier on GI than erythromycin and have better kinetics and dynamics. Cross ressistance with erythromycin by ribosome methylation and efflux. |
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Streptogramin
(Quinupristin/dalfopristin) Synercid ® |
Ribosome action
(The S in MLS) Role currently limited to therapy of resistant gram positive infections including MRSA. NOT active against some enterococcus species. |
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Aminoglycosides
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Bactericidal.
Acts on ribosome. G- drug. No activity against anaerobes. Concentration dependent. NOT time dependent like beta lactams. Dosed in big slugs. Low therapeutic index requires serum level monitoring. Synergy with beta lactams (penicillins) and vancomysin against enterococcus, strep and listeria. Prolonged post antibiotic effect. Gentamycin/tobramycin Streptomycin Amikacin Resistance by inactivation (sulfation, acetylation, phosphorylation) |
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What are aminoglycosides useful for?
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Enterococcus or other severe nosocomial infections.
Endocarditis. Streptomycin for: Plague Tularemia Brucellosis |
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Clindamycin
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Acts on the ribosome
Resistance by ribosomal methylation (like MLS drugs). Shuts down toxin production in group A strep because it takes out the ribosome. Usually used in combination with beta-lactam for serious strep infection. Good oral agent for Staph including some MRSA. Excellent for "above the diaphragm" anaerobes and pulmonary abcesses. Has some nonbacterial action for pneumocystis carinii pneumonia and toxoplasmosis (with pyrimethamine). |
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Tetracyclines
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Ribosomal action.
Bacteriostatic. Resistance through altered ribosome or drug efflux Pretty broad spectrum, no pseudomonas action. Tetracycline—cheap Doxycycline—cheap Minocycline—Not cheap chlamydia borreliosis vibrio rickettsia malaria |
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For H. pylori, the recommended tetracycline class antibiotic is...
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Tetracycline NOT doxycycline
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Glycylcyclines like the drug Tigecycline are similar to tetracyclines. What do we know about them?
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Ribosome attack
Resistance is through drug efflux not ribosomal mutation. Spectrum is broader than tetracycline but excludes pseudomonas and acinetobacter Drug is expensive and only given IV. N/V/D in 20% Usually used for mixed infections. |
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Co-trimoxazoles:
Trimethoprim/sulfamethoxazole(Bactrim) |
Block nucleotide synthesis.
(PABA to folic acid and folic acid to folinic acid) Resistance through increased production of dihydrofolate reductase. Good CNS penetration. Broad spectrum: NOT Pseudomonas aeruginosa, anaerobes, mycoplasmas. Good for CA-MRSA. used for: CA-MRSA UTI’s Respiratory infections (not Group A strep. Pharyngitis) PCP Enteric fevers Traveler’s diarrhea Brucellosis Nocardiosis Listeria and some G- meningitis. |
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Metronidazole (Flagil)
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Cidal agent with unknown mechanism.
Good for "below the diaphragm" anaerobes, protozoa and bacterial vaginosis. |
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For C.diffcile colitis we use...
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Vancomycin and metronidazole.
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Fluoroquinolones
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Inhibit DNA gyrase and topoisomerase.
Bactericidal. Highly bioavailable. all have Good G- coverage(Cipro has more G+) Effectiveness: area under curve/MIC Resistance: DNA gyrase/topoisomerase mutation. Drug efflux. Levofloxacin Moxifloxacin (best against anaerobes) Ciprofloxacin (best against P. aeruginosa) UTI's GI STD RTI GNR osteomyelitis (cipro) NOT for surgical prophylaxis. |
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Rifamycins
(Rifampin) |
Mostly G+
Inhibits DNA dependent RNA polymerase. Resistance: Can rapidly occur due to enzyme mutations. Penetrates biofilms very well. TB Leprosy Difficult G+ infections in combination therapy. |
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Lipopeptides:
(Daptomycin) |
New class of antibiotic
Calcium dependent increase in membrane permeability to potassium. Activity against all G+ including MRSA and vancomycin resistant enterococcus. Resistance rare and not well defined Expensive |
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Oxazolidine
(Linezolid) |
New class of antibiotic
Inhibits protein synthesis at level of ribosomal translation Resistance not well defined—probably ribosomal mutation Activity against gram positives including MRSA and vancomycin resistant enterococcus Can be given orally (one of few oral drugs that can be used against MRSA) Expensive |
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Polymyxins
(Polymyxin B or colistin) |
Old antibiotics brought back to treat multiple drug resistant gram-negatives such as pseudomonas and acinetobacter.
Intercalates with LPS in gram negative membrane. Resistance not well understood. Toxic |
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Which antibiotics treat pseudomonas?
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Antipseudomonal penicillins.
(piperacillin, ticeracillin) 3rd and 4th generation cephalosporins as well as ceftazidime. Carbapenems. Aminoglycosides. Aztreonam. Ciprofloxacin. |
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What are the best choices for Group A strep pharyngitis or skin infection?
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Penicillin VK
or Oral cephalosporin (1st gen. best for G+) or Clindamycin (if beta-lactam allergy is a problem) or Macrolide (erythro, clarithro, azithro) |
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What would be used for very severe Group A strep infections like necrotizing fascitis, pneumonia or bacteremia ?
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High dose penicillin + clindamycin.
Vanco+clindamycin if allergic to penicillin. |
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What are the drugs of choice for Group B Streptococcus & enterococcus infections?
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IV penicillin or ampicillin
often combined with gentamycin. Vancomycin used if PCN allergic or for enterococcus resistant to PCN/AMP |
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What can we do if there is an infection with enterococcus that is resistant to penicillin, ampicillin and vancomycin?
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Use Linezolid, Synercid or daptomycin
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What do we do for serious staph aureus infections?
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Nafcillin, oxacillin, methicillin
IV every 4-6 hours; short half life 1st generation cephalosporin (cefazolin, cephalothin) Vancomycin Potentially could use linezolid, daptomycin or Synercid if cannot use vancomycin. |
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The drug usually used for CA-MRSA is ....
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Trimethoprim/sulfamethoxazole
The big gun is linezolid though. |
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The treatment of choice for syphillis is...
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Penicillin
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The treatment of choice for lyme disease is....
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Amoxicillin
Doxycycline Ceftriaxone (tertiary or chronic) |
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The treatment of choice for anthrax is....
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Ciprofloxacin
Doxycycline |
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Treatment for E.Coli UTI?
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Trimethoprim/sulfamethoxazole
oral 2nd or 3rd generation cephalosporin Ciprofloxacin or levofloxacin |
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Treatment for E.Coli Travelers diarrhea (ETEC)?
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Quinolone: Cipro or levo
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What are the treatments of choice for anaerobes?
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Metronidazole
Clindamycin (particularly oral anaerobes) Extended spectrum penicillins Better with beta-lactamase inhibitior Ampicillin/sulbactam, piperacillin/tazobactam, ticarcillin,clavulanate Carbapenems |
