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90 Cards in this Set
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what are the four b-lactam antimicrobials
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1) penicillins
2) cephalosporins 3) carbapenems 4) monobactams |
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which is the glycopeptide antimicrobial
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glycopeptide antimicrobials
1) Vancomycin |
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interfere w/transpeptidation rxns that seal peptide crosslinks between peptidoglycan chains by interfering w/action of transpeptidase enzymes AKA penicillin-binding proteins PBPs
classified by chemical structure: (can have differences in side chains) |
b-lactam antimicrobials
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are usually highly bactericidal (by causing bacteria to go "poof"), but only to growing bacteria synthesizing new cell walls. Non-multiplying organisms, organisms whose cell wall does not have peptidoglycan (e.g. -- Chlyamidia trachomatis), and cell wall-deficient organisms (e.g. - Mycoplasma) are NOT susceptible
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b-lactam antimicrobials
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enzymes that cleave the b-lactam ring and thereby render penicillin and b- lactam antibiotics inactive
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penicillinases
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To be effective, these must:
• penetrate the cell layers • keep its ring intact • bind to the transpeptidase (PBPs) |
b-lactam antimicrobials
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most active against many gram+ organisms and are susceptible to hydrolysis by b-lactamases. Many organisms (most notably Staphylococcus aureus) have now developed resistance
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natural penicillins
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commonly used to treat infections caused by:
• Streptococci • Staphylococci • Meningococci (Neisseria meningitidis) • Pneumococci (Streptococcus pneumoniae) • Syphillis (Treponema pallidum, a spirochete) |
natural penicillins
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Specific Examples:
Pharyngitis ("strep throat") Group A Streptococcus (Streptococcus pyogenes) Otitis Media Streptococcus pneumoniae Acute Sinusitis Streptococcus pneumoniae Pneumonia Streptococcus pneumoniae Bacterial Meningitis Streptococcus pneumoniae,Neisseria meningitidis Syphillis Treponema pallidum |
natural penicillins
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Added spectra of ____________:
• some gram-negative bacilli (Haemophilus influenza) • some gram-negative enteric bacilli (E. Coli, Salmonella, Shigella, Proteus mirabilis) • Listeria organisms |
aminopenicillins
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extends the activity of the aminopenicillins to include many strains of Pseudomonas aeruginosa, but it has poor activity against most strains of Klebsiella.
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ticarcillin
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an extended (broad) spectrum penicillin that is more active than ticarcillin against Pseudomonas aeruginosa and Klebisella.
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piperacillin
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All of the ___________ can be susceptible to destruction by b-lactamases, which means they lack activity to Staphylococcus aureus.
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extended-spectrum antibiotics (penicillins)
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While this group of penicillins is more active against certain gram-negative rods, they have approx. the same activity as natural penicillins against gram+ bacteria.
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extended-spectrum antibiotics
(penicillins) |
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These drugs provide broad coverage against b-lactamase gram+ bacteria (Staphylococcus aureus) & certain gram-negatives (Haemophilus influenzae)
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Penicillin + b-lactamase Inhibitor
b-lactamase Inhibitors include clavulanic acid, sulbactam & tazobactam Augmentin/XR amoxicillin + clavulanic acid Timentin ticarcillin + clavulanic acid Unasyn ampicillin + sulbactam Zosyn piperacillin + tazobactam |
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Currently available examples include oxacillin, nafcillin, cloxacillin & dicloxacillin
Methicillin is no longer marketed in the US This group is useful not only for group A streptococcus, but also for b-lactamase producing Staphylococcus aureus |
Penicillinase-Resistant Penicillins (Anti-staphylococcal Penicillins)
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Allergic / Hypersensitivity Reactions
• Rash • Fever • Anaphylaxis The most common cause of drug allergy (1-10% of patients will experience an allergic response); There is no direct relationship between the size of the dose and the intensity of allergic response Cross sensitivity -- |
penicillins
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For penicillin-allergic patients, do not treat with a penicillin or
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cephalospirin
5-10% of patients allergic to penicillins are also allergic to cephalosporins |
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Adverse effects
• Pain at site of IM injection • CNS effects (mainly seizures) with large doses • Diarrhea (by destroying the natural GI flora and allowing pathogenic bacteria, such as Clostridium dificile, to grow in their place) |
penicillins
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2 main advantages over the penicillins:
• more resistant to penicillinases (but now susceptible to cephalosporinases) • modification of side chains leads to different spectrums of activity There are 4 major generations |
cephalosporins
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With each new generation, the drugs:
• are able to kill an increasing spectrum of gram-negative bacteria • have increasing resistance to destruction by b-lactamases • have increasing ability to reach the CSF At the same time, the newer tend to be less effective against gram+ organisms. |
cephalosporins
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The Streptococci and Staphylococci are most susceptible to
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first generation cephalosporins
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are inactive against enterococci and MSRA. (not used if person is allergic to penicillin)
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cephalosporins
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• Used as alternatives to penicillin for staphylococcal and streptococcal infections when penicillin cannot be tolerated
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1st generation cephalosporins
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drugs of choice for prophylaxis before surgery to prevent infections from the skin; 2nd & 3rd generation offer no advantage over 1st generation agents, EXCEPT where anaerobes (like B fragilis !!) play an important role, such as for colorectal surgery.
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1st generation cephalosporins
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do not adequately penetrate into CSF and cannot be used to treat meningitis
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1st generation cephalosporins
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These have extended gram-negative coverage beyond 1st generation drugs to include M catarrhalis and Neisseria species; some 2nd generation drugs (e.g. -- Cefuroxime) are also active against H. influenzae --- hence, they can be used occasionally to treat sinusitis and otitis media in patients unresponsive to more established agents
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2nd generation cephalosporins
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• There is NO activity against Pseudomonas aeruginosa
• Are less active against gram-positive organisms • Cefoxitin (in particular) is useful as prophylaxis in colorectal surgery, vaginal or abdominal hysterectomy and appendectomy because of its activity against B. fragilis |
2nd generation cephalosporins
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• A major advantage is expanded gram-negative coverage
• These are used for the multi-drug resistant aerobic gram-negative organisms that cause nosocomial (hospital-acquired) pneumonia, meningitis, sepsis and UTIs. Cephtriaxone has excellent CSF penetration and covers the bacteria causing meningitis (EXCEPT Listeria monocytogenes). It is one of the first-line drugs for meningitis in neonates, children, and adults. • Ceftriaxone is also indicated for gonorrhea (but not Chlamydia!) and Lyme disease |
3rd genation cephalosporin
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• The 4th generation _________ (Cefepime) has greater activity against Pseudomonas aeruginosa compared to 3rd generation drugs
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cephalosporin
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Adverse Effects
• Drug allergy • Pseudomembranous colitis bleeding disorders (hypoprothrominemia) disulfiram-like reaction |
cephalosporins
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Adverse effects:
bleeding disorders disulfiram-like reaction (alcohol must be avoided) |
cephalosporins
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• ____________ has been associated with a dose-dependent biliary sludging syndrome and cholethiasis due to precipitation of drug when its solubility in bile is exceeded
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Ceftriaxone
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This class of drugs is structurally related to b-lactam antibiotics.
Should not be routinely used as first-line therapy unless the pathogen is multi-drug resistant and is known to be sensitive to these drugs |
Carbapenems
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Imipenem, the first drug of this type, has a wide spectrum of activity that includes most gram-negative rods (including P. aeruginosa) and gram-positive organisms and anaerobes (not MRSA).
Meropenem (Merrem) is a newer agent that is similar in spectrum of activity and pharmacology to imipenem |
Carbapenems
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The most common adverse effects are nausea, vomiting, diarrhea, reactions at infusion site and skin rashes. Seizures are more commonly observed with imipenem. Patients allergic to penicillins may be allergic these as well.
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Carbapenems
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These are also structurally related to the b-lactam antibiotics. They are resistant to many b-lactamases and active against gram-negative organisms (including P. aeruginosa), but have no activity against gram-positive organisms or anaerobes.
Clinical use is limited because of the availability of 3rd generation cephalosporins with a broader spectrum of activity and less toxicity. |
MONOBACTAMS
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Aztreonam (Azactam) is the best example, but its clinical use is limited because of the availability of 3rd generation cephalosporins with a broader spectrum of activity and less toxicity.
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MONOBACTAMS
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This antibiotic has a critical role in the treatment of infectious diseases. It inhibits cell wall synthesis, but has a different MOA compared to penicillins, as it does not bind to PBPs. Instead, it acts at a step earlier by preventing the biosynthesis of peptidoglycans.
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GLYCOPEPTIDE ANTIMICROBIALS
VANCOMYCIN (Vancocin) |
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covers virtually all gram-positive organisms, including:
• MRSA • Enterococcus • Multi-resistant staphylococcus epidermidis (in infections of indwelling IV catheters) • Many serious infections (e.g. -- Sreptococcus pneumoniae) in patients allergic to penicillins |
GLYCOPEPTIDE ANTIMICROBIALS
VANCOMYCIN (Vancocin) |
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is given orally but not absorbed orally. It is possible to take advantage of this fact in the treatment of Clostridium difficile pseudomembranous colitis.
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GLYCOPEPTIDE ANTIMICROBIALS
VANCOMYCIN (Vancocin) |
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Adverse Effects
• Is irritating to tissues; thrombophelbitis sometimes follows IV injection • Potentially nephrotoxic when administered in high doses or with aminoglycosides |
GLYCOPEPTIDE ANTIMICROBIALS
VANCOMYCIN (Vancocin) |
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• Rapid infusion or high doses may induce diffuse hyperemia ("RED MAN SYNDROME") in the face, neck and upper body, and can be avoided by extending infusions over 1-2 hours, by reducing the dose, or by pre-treating with a histamine antagonist such as hydroxyzine.
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GLYCOPEPTIDE ANTIMICROBIALS
VANCOMYCIN (Vancocin) |
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what are 6 drug classes that inhibit protein synthesis?
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A. Aminoglycosides
B. Tetracycylines C. Macrolides D. Chloramphenicol E. Clindamycin F. Oxazolidinones |
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All of these agents inhibit protein synthesis in bacteria by inhibiting the function of the 30S subunit of the bacterial ribosome; all are bactericidal
The transport of these antibiotics across the bacterial membrane is oxygen-dependent; thus, these cannot kill anaerobes. Are often used with penicillin, which breaks down the cell wall and can facilitate diffusion into the bacteria. |
aminoglycosides
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Resistance is based on:
• deficiency of the ribosomal receptor (the part of the 30S subunit binds to) • enzymatic destruction of the • lack of permeability to the ______________ (this is why it is used with penicillin) |
aminoglycoside
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At one time, these had been the mainstays of treatment of serious infections due to aerobic gram- negative bacilli (e.g. – the ENTERICS). However, since their use was limited by serious toxicities, they have been replaced to some extent by safer antibiotics such as the 3rd generation cephalosporins and fluoroquinolones.
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aminoglycoside
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are most commonly used to kill:
Resistant gram-negative organisms that are sensitive only to __________ In combination with b-lactam drugs or vancomycin for their synergistic effect on • Enterococci (especially those causing endocarditis) • S aureus & S epidermidis prosthetic valve infection |
aminoglycosides
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Adverse Effects
Ototoxicity • directly related to dose and duration of treatment • it may irreversible • patients simultaneously receiving another ototoxic drug are at greater risk (lasix) • vertigo & loss of balance may also occur because aminoglycosides affect the vestibular apparatus (in addition to the cochlea) |
aminoglycosides
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adverse effects:
Nephrotoxicity • more common than ototoxicity • also dose-dependent and cumulative • kidney damage ranges from mild renal impairment to severe acute tubular necrosis which can be irreversible Neurotoxicity • a curare-like effect with neuromuscular blockade that can result in respiratory paralysis (rare) |
aminoglycosides
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a large group of drugs with common basic chemical structures, antimicrobial activity and pharmacologic properties. Like aminoglycosides, they bind to the 30S ribosomal subunit to inhibit protein synthesis. However, unlike aminoglycosides, they are bacteriostatic.
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TETRACYCLINES
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They are strongly inhibitory for the growth of:
• Mycoplasmas (Mycoplasma pneumoniae – walking pneumonia) • Rickettsiae (Rocky Mountain spotted fever) • Borrelia burgdorferi (Lyme Disease) • Chlamydiae (Chlamydia trachomatis) • Spirochetes (Treponema pallidum) • Vibrio (Vibrio cholera) • H. influenzae |
TETRACYCLINES
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have moderate activity against some vancomycin-resistant entrococci
Are also potential options for therapy of staphylococcal infections, including infections with many methicillin-resistant strains. |
TETRACYCLINES
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Other uses include treatment of acne, animal bites, H. pylori-infected ulcers, and malaria prophylaxis. Plus, it is used with a 3rd generation cephalosporin for the treatment of PID.
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TETRACYCLINES
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Adverse Effects
• Hypersensitivity reactions with fever or skin rashes are uncommon • GI side effects – diarrhea, nausea and anorexia are common • Bones & teeth -- bind to calcium deposited in growing bones & teeth, causing fluorescence, discoloration, enamel dysplasia, deformity and/or growth inhibition; therefore, they should not be given to pregnant women or children under 6 years of age. • Liver – can impair hepatic function or even cause liver necrosis, particularly during pregnancy or in the presence of pre-existing liver disease |
TETRACYCLINES
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a group of closely related compounds characterized by a lactone ring to which various sugars are attached.
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MACROLIDES
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inhibit protein synthesis by binding to the 50S subunit of bacterial ribosomes, thereby blocking addition of amino acids to a growing peptide chain. They generally are bacteriostatic and sometimes bactericidal for gram-positive, including most streptococci and corynebacteria.
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MACROLIDES
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drugs of choice for infection caused by:
• Legionella species (IV erythromycin or azithromycin preferred) • Mycoplasma • Corynebacterium (erythromycin only) • Chlamydia trachomatis (azithromycin only) • Bordetella pertussis (erythromycin only) |
MACROLIDES
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They are also effective in streptococcal (especially for strep throat) and pneumococcal disease in penicillin- allergic patients, although resistance is increasing.
When administered early, erythromycin may shorten the course of Campylobacter enteritis. You may also recall from Fall Qt. that there are topical solutions for mild to moderate acne that contain erythromycin. |
MACROLIDES
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considered one of the safest antibiotics around……but there are some side effects:
• GI irritation -- nausea, vomiting, diarrhea • Rare cholestatic hepatitis • Tinnitus |
MACROLIDES
erythromycin |
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can increase the effects of oral anticoagulants, digoxin, theophylline, and cyclosporine by inhibiting CP450.
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MACROLIDES
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binds to the 50S subunit of ribosomes and inhibits protein synthesis. This drug has a very BROAD spectrum of activity. It is one of the few drugs (like Imipenem) that kills most clinically important bacteria. Gram+, gram-negative, and even anaerobic bacteria are susceptible. It is one of the handful of drugs that can kill the anaerobic Bacteroides fragilis.
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CHLORAMPHENICOL
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Because of its rare but severe side effects, this otherwise excellent drug is used only when there is no alternative antibiotic, and thus the benefits far outweigh the risks:
• It is used to treat bacterial meningitis, when the organism is not yet known and the patient has severe allergies to the penicillins & cephalosporins. The wide spectrum of activity of and excellent penetration into the CSF will protect the patient from the devastating consequences of meningitis. |
CHLORAMPHENICOL
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• Young children and pregnant women who have Rocky Mountain spotted fever cannot be treated with tetracycline…………. then becomes the drug of choice.
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CHLORAMPHENICOL
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Adverse Effects
Bone marrow toxicity • Dose-related, reversible anemia (due to decreased RBC maturation) • Aplastic anemia -- irreversible obliteration of the bone marrow (likely genetic predisposition) |
CHLORAMPHENICOL
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adverse effects:
Gray Baby Syndrome • Neonates, especially preemies, are unable to fully conjugate this in the liver or excrete it through the kidney, resulting in very high blood levels; toxicity occurs with vasomotor collapse, abdominal distention and cyanosis, which appears as an ashen gray color |
CHLORAMPHENICOL
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Can be used topically for mild to moderate acne.
Its MOA is somewhat similar to erythromycin. This is employed primarily in the treatment of infections caused by anaerobic bacteria (e.g. -- Clostridium & Bacteroides fragilis). In cases of penetrating wound infections of the abdomen (e.g. -- knife, bullet), can cover the anaerobes. |
CLINDAMYCIN
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Adverse Effects
• Common side effects include diarrhea, nausea, and skin rashes • Pseudomembranous (antibiotic-associated) colitis |
CLINDAMYCIN
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represent a class of antibacterials of which linezolid (Zyvox) is the one available agent. It blocks the 50S ribosomal subunit and has activity against gram+ organisms including those resistant to other antimicrobials --- MRSA, penicillin-resistant pneumococci and enterococci. Of particular concern are the increasing reports of linezolid-resistant enterococcus, which reinforce that this agent should be used judiciously.
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OXAZOLIDINONES
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what are the two drugs that inhibit nucleic acid synthesis?
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Fluoroquinolones
Metronidazole (Flagyl) |
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This “relatively” new group of antibiotics is expanding, and has become as large and important a group as the penicillins and cephalosporins. The main action is to inhibit an enzyme required for DNA synthesis (bacterial DNA gyrase or bacterial topoisomerase II) causing DNA double strand breaks. Secondarily, they also inhibit a second enzyme (topoisomerase IV) which then interferes with the separation of replicated chromosomal DNA into the respective daughter cells during cell division.
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FLUOROQUINOLONES
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After oral administration, these are well absorbed and distributed widely in body fluids and tissues.
Resistance has started to emerge as a problem with increased use of (particularly among strains of Steptococcus pneumoniae). Resistance is due to one or more point mutations in the binding region of the target enzyme or to a change in the permeability of the organism. Resistance to generally confers cross-resistance to all other members of this class. |
FLUOROQUINOLONES
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1st & 2nd generation generally have poor gram+ coverage. However, exceptions for ciprofloxacin include:
-- Staphylococcus aureus -- Staphylococcus epidermidis -- Bacillus anthracis 3rd & 4th generation drugs have increasing Staphylococcus and Streptococcus coverage (including Streptococcus pneumoniae) |
FLUOROQUINOLONES
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Most do not cover anaerobes. Moxifloxacin (3rd generation) does have activity against B. fragilis, but is not considered a first-line agent
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FLUOROQUINOLONES
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are MOST EFFECTIVE against gram-negatives, including:
• the enterics (except anaerobes); they are used for diarrhea caused by E.Coli, Salmonella, Shigella and Campylobacter • complicated UTIs caused by multi-drug resistant bacteria (e.g.– Pseudomonas aeruginosa); prostatitis and epididymitis • gonococcal urethritis (Neisseria gonorrhoeae) [Note: are not effective for the therapy for Chlamydial infections or nongonococcal urethiritis] • Legionella species • infections of soft tissues, bones (osteomyelitis) and joint, including those caused by gram-negative organisms, Pseudomonas aeruginosa and Staphylococcus aureus (3rd/4th generation drugs) |
FLUOROQUINOLONES
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extremely well tolerated. Common adverse effects include:
• Nausea, vomiting, diarrhea • CNS: headache, dizziness, insomnia Less common adverse effects include: • Skin rash • Elevated LFTs |
FLUOROQUINOLONES
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Rare adverse effects include:
• QT interval prolongation (increases risk of torsades de pointes) • Tendonitis (increases risk of tendon rupture; patients experiencing musculoskeletal symptoms while receiving these should discontinue therapy) - (use caution in adolescents) |
FLUOROQUINOLONES
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actually an anti-protozoal drug used for amebiasis, Giardia lamblia and Trichomonas vaginalis. However, it also has striking antibacterial effects against most anaerobic bugs (e.g. – Clostridium, Bacteroides).
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METRONIDAZOLE (Flagyl)
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It is well absorbed after oral administration and is widely distributed in tissues. Similar to the fluoroquinolones, these also cause DNA strand breaks (but via an entirely different mechanism) and resistance has been emerging.
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METRONIDAZOLE (Flagyl)
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Clinical Uses
• anaerobic bacterial infections • C. difficile colitis • in combination with tetracycline or amoxicillin for therapy of H. pylori infections |
METRONIDAZOLE (Flagyl)
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Adverse Effects / DDIs
• GI: nausea, vomiting, diarrhea, metallic taste • CNS: vertigo, headache • ingestion occasionally results in a disulfiram-like reaction • decreases the metabolism of warfarin |
METRONIDAZOLE (Flagyl)
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Nucleotide and DNA formation require tetrahydrofolate (or tetrahydrofolic acid; TH4). Bacteria make their own TH4 and use PABA to make part of the TH4. Humans don’t make TH4…………we ingest plenty of it in our diet. TMP & SMX act synergistically to shut the down the production of TH4, and, in turn, shut down nucleotide & DNA synthesis. Examples of TMP-SMX include:
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Trimethoprim-Sulfamethoxazole (TMP-SMX) or SMZ
Bactrim and Septra. |
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Sulfonamides (“sulfa drugs”) are rarely used in the treatment of bacterial infections. The combination of _________ can kill many gram-positive and gram-negative bacteria (NOT anaerobes), compared to either one alone.
Well absorbed from the GI tract and widely distributed in tissues and fluids, including the CSF. |
TMP & SMX
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Clinical Uses
covers: • H. influenzae, S. pneumoniae and M. catarrhalis and hence can be used for otitis media, sinusitis, bronchitis, and pneumonia which are frequently caused by these bacteria • many enterics in the GI tract that cause diarrhea such as Shigella, Salmonella and E. Coli • UTIs, prostatitis caused by E. Coli and other enterics |
TMP & SMX
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usually well tolerated. Common side effects:
include rash, nausea & vomiting. should be avoided in those with G6PD deficiency, as significant hemolysis may result. can decrease the metabolism of: • warfarin • oral hypoglycemics (sulfonylureas) • phenytoin by inhibiting hepatic CYP450 enzymes. |
TMP & SMX
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• all cause hepatotoxicity
• all are absorbed orally • all penetrate into most tissues; they must reach caseous granulomas |
isoniazid
rifampin pyrazinamide Another drug used frequently is ethambutol. |
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interferes with biosynthesis of the myocolic acid component of the cell wall of the Mycobacteria.
increases the urinary excretion and depletion of pyridoxine (vitamin B6), which is needed for proper nerve function. will thus lead to decreased B6 levels, characterized by peripheral neuropathy, rash and anemia. It is routine to give B6 with this to potentially avoid these effects. |
Isoniazid (INH)
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inhibits the DNA-dependent RNA polymerase of Mycobacteria
Body fluids such as urine, feces, saliva, sweat, and tears are colored a bright red-orange color. This is not harmful to the patient, but patients must be made aware of this or they will discontinue the medicine in a panic. induces CYP450 enzymes associated with the metabolism of: • warfarin • oral contraceptives • oral hypoglycemics • phenytoin |
Rifampin
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MOA is unknown
In addition to being hepatotoxic, uric acid retention may also occur……….which can precipitate gout (TB drug) |
Pyrazinamide
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MOA is unknown
Most important adverse effect is a dose-dependent, reversible, ocular toxicity that is manifested by: • decreased visual acuity with loss of central vision • color vision loss Visual acuity should be periodically examined while on therapy. (TB drug) |
Ethambutol
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