General Microbiology 6 Antimicrobial Therapy – Flashcards
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What are the 3 categories of empiric therapy?
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Empiric, Prophylactic, and Therapeutic
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What is empiric therapy?
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Empiric therapy is treatment based on clinical signs, symptoms, and laboratory information. Empiric therapy treats for the suspected cause of the disease.
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What determines what drugs are used in microbial therapy?
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Suspected site of infection likely etiology of infection anticipated antimicrobial susceptibility
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If a patient presents to the ER with difficulty breathing, fever, productive infiltrate, chest ray reveals a new infiltrate, and peripheral WBC count is elevated with left shift, what should you treat?
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Treat for the common causes of community acquired pneumonia
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If a patient presents with pain on urination, and increased frequency of urination along with flank pain and fever as well as increased peripheral WBC count with a left shift, what should you treat?
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Treat for the common causes of UTI
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Of the 3 categories of therapy, which is most common for antimicrobial treatment?
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Empiric therapy
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What types of patients are treated with prophylactic therapy?
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At risk patients such as patients who are about to have dental procedures are treated with penicillin because they are at risk of developing endocarditis. Also patients who are about to have a surgical procedure are treated with a first generation cephalosporin to prevent post-surgical infections of S. aureus
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How should prophylactic therapy be administered?
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prophylactic therapy should be in short duration of 1-2 doses and should be active at the time of the procedure
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What is therapeutic therapy?
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A therapy directed at a known etiologic agent with a known antimicrobial susceptibility
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What are the 2 scenarios in which this can occur?
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The patient can either have been on empiric therapy previously or therapeutic therapy can be started without previous empiric therapy
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When is therapeutic therapy started after empiric therapy?
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When a diagnostic test reveals the etiology and susceptibility of an infection and requires/may be treated with another drug. e.g. when a patient has community acquired pneumonia and is started on levofloxacin, but cultures reveal the cause is penicillin susceptible S. pneumoniae
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When is therapeutic therapy started initially?
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When an infection is identified by diagnostic test on an untreated (sometimes asymptomatic) patient. e.g. positive syphilis serology in an asymptomatic patient e.g. positive chlamydia test in an asymptomatic patient e.g. positive rapid strep test in a patient with pharyngitis
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What are examples of peptidoglycan synthesis inhibitors and what bacteria are not affected?
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β-lactam antibiotics and Glycopeptide antibiotics. Mycoplasma, Rickettsia, and Chlamydia are not affected by these drugs because petpidoglycan is not essential to their survival
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What are the types of β-lactam antibiotics?
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Penicillins, Penicllin/Penicillinase inhibitors, Cephalosporins, Carbapenems, and Monobactams
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What is the most important glycopeptide antibiotic?
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Vancomycin
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What are the types of penicillins?
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Penicillin, Ampicillin, Amoxicillin, Naficillin, Methicillin, Pipericillin, Ticarcillin, and Carbenicillin?
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Which penicillins have an extended spectrum?
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Ticarcillin, Pipericillin, and Carbenicillin
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What are the first generation penicillins? What are their characteristics?
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Penicillin, Ampicillin, Amoxicillin They have a narrow spectrum of activity and are susceptible to β-lactamase enzymes produced by many bacteria
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By what mechanism do penicillins work?
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penicillins work by binding to and inhibiting penicillin binding proteins which catalyze the last step of cross-linking parallel chains of GlcNac-MurNac-pentapetide, which is a transpeptidation reaction
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What is susceptible to Penicillin?
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Syphilis, β-hemolytic Streptococcus and other streptococcal species, and Neisseria meningitidis and β-lactamase negative strains of Neisseria gonorrhoeae
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What is susceptible to Ampicillin and Amoxicillin?
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All Penicillin susceptible bacteria with a slightly expanded gram- spectrum such as some wimpy members of Enterobacteriaceae
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What are anti-staphylococcal penicillins? Why are they important?
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β-lactamase stable penicillins such as Naficillin and Methicillin. 95-98% of staphylococci produce β-lactamase. Thus β-lactamase stable penicillins were developed.
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What is susceptible to β-lactamase stable penicillins?
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Staphylococcus aureus without methicillin resistance and most streptococci, but not gram- bacteria
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How has Staphylococcus aureus developed resistance to β-lactamase stable penicillins?
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An altered penicillin binding protein(PBP-2) confers resistance to S. aureus (MRSA)
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What is MRSA resistant to?
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all β-lactam antibiotics
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What proportion of Staphylococcus aureus isolates are methicillin resistant?
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40-60%
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How is MRSA treated?
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Vancomycin
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How is Vancomycin resistant Staphylococcus aureus treated?
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Synercid(quinupristin/dalfopristin) or Linezolid
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What are extended spectrum/anti-pseudomonal penicillins?
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Ticarcillin, Pipericillin, and Carbenicillin
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What is susceptible to extended spectrum/anti-pseudomonal penicillins?
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extended spectrum/anti-pseudomonal penicillins have a broad spectrum against Gram- bacilli. Gram- bacilli have developed their own β- lactamase enzymes
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What is the purpose of penicillin/penicillinase inhibitor combinations?
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Can nullify a bacteria's resistance to an organism
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What are examples of penicillinase?
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Clavulanate, Sulbactam, and Tazobactam
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What is susceptible to Ampicillin/Sulbactam and Amoxicillin/Clavulanate?
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All microbes inhibited by specific penicillins plus organisms producing β-lactamase such as Haemophilus influenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, Staphylococcus aureus, and many anaerobic organisms
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What is susceptible to Ticarcillin/Clavulanate and Pipericillin/Tazobactam?
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All organisms susceptible to extended spectrum penicillins including those that produce β-lactamase. Has a broad gram- spectrum and anaerobe spectrum.
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How are carbapenems different from penicillins and cephalosporins?
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Carbapenems have a methylene replacement for sulfur as well as a double bond in the 5 membered α ring
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What is unique about Imipenem?
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It is one of the smallest β-lactam antibiotics and it is a zwitterion which enables it to pass through the porin channels of the outer membrane of gram- bacteria as
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Why does Imipenem have such a broad spectrum?
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It can pass through the outer membrane of Gram- bacteria, it has an affinity for PBP of many bacteria, and it is resistant to many β-lactamases
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Why were cephalosporins developed?
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After Staphylococcus aureus developed resistance to penicillin by production of β-lactamase.
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What are 1st generation cephalosporins?
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Cephalexin and Cefazolin
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What is susceptible to 1st generation cephalosporins?
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β-lactamase-positive Staphylococcus, Streptococcus pyogenes, but importantly have NO activity against Enterococcus. This has been an important factor in the emergence of Enterococcus as a nosocomial pathogen
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When were first generation cephalosporins used?
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prophylaxis for surgical procedures against Staphylococcus aureus or Streptococcus pyogenes
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What do different generations of cephalosporins do?
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Increasing generation # means increased activity agains gram-
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What are 2nd generation cephalosporins?
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Cefoxitin, Cefuroxime, and Cefotetan
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What is susceptible to 2nd generation cephalosporins?
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more susceptible Enterobacteriaceae, but not more resistant gram- bacilli such as Enterobacter, or Pseudomonas aeruginosa
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What are 3rd generation cephalosporins?
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Ceftazidime, Cefoperazone, Cefotaxime, and Ceftriaxone
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What is susceptible to 3rd generation cephalosporins?
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Broad spectrum of gram- bacilli
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Which 3rd generation cephalosporins are more effective against Pseudomonas aeruginosa?
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Ceftazidime and Cefoperazone
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What is a 4th generation cephalosporin and why are they important?
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Cefepime; good activity against Pseudomonas aeruginosa
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What is unique about Aztreonam?
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It is the only commercially available monobactam.
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What is a monobactam?
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a monocyclic β-lactam antibiotic. There isn't another ring.
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What is the spectrum of Aztreonam?
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PBP of facultatively anaerobic gram- bacteria. It has a similar spectrum to amino glycosides, but has a lower toxicity.
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What is the structure of Vancomycin?
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7 membered peptide chain with a tricyclic structure. It is a disaccharide of vancosamine and glucose. It is very large.
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How does Vancomycin work?
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it blocks both transpeptidation and addition of GlcNac-MurNac-peptide to growing PG chain. Inhibits addition of GlcNac to MurNac as well as transpeptidation.
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What is the spectrum of Vancomycin?
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Vancomycin has a very broad spectrum, but only against gram+ bacteria. Resistance is frequently found in E. faecium and rarely in Staphylococci, but Vancomycin Intermediate Staphylococcus aureus is being recovered more frequently. Can have trouble crossing the blood brain barrier, which can make treating gram+ meningitis tricky
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Which Protein Synthesis Inhibitors act on the 50S subunit?
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Macrolides, Clindamycin, Linezolid, and Streptogramins
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Which Protein Synthesis Inhibitors act on the 30S subunit?
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Tetracyclines and Aminoglycosides(though Aminoglycosides bind to both subunits)
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What drugs are macrolides?
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Erythromycin and Azithromycin
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What is the mechanism of action of macrolides?
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they bind to 50S ribosome and inhibit chain elongation
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Which has a broader spectrum?
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Azithromycin
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What can Erythromycin treat?
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Same spectrum as Penicillin(Syphilis, β-hemolytic Streptococcus and other streptococcal species, and Neisseria meningitidis and β-lactamase negative strains of Neisseria gonorrhoeae), but also treats Mycoplasma, Legionella and Chlamydia
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What can Azithromycin treat?
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Spectrum of Erythromycin and β-lactamase- positive Haemophilus influenzae, Moraxella catarrhalis, and Neisseria gonorrhoeae.
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What is treated with Azithromycin empirically?
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sinusitis, otitis media, and pneumonia
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What is the mechanism of action of Clindamycin?
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Binds to 50S ribosome and inhibits chain elongation.
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What is susceptible to Clindamycin?
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Active against MSSA and many Streptococcus. Also active against most anaerobes both gram- and gram+.
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What is resistant to Clindamycin?
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Enterococcus and gram- aerobes
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What are Linezolid or Streptogramins used against?
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Enterococcus faecium and Staphylococcus aureus that are intermediate or resistant to Vancomycin
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What is the spectrum of Tetracyclines?
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Chlamydia, Mycoplasma, Rickettsia, and Legionella. Similar spectrum to Erythromycin except for inclusion of Rickettsia
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What drugs are aminglycosides?
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Gentamicin, Amikacin, and Tobramycin
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What are aminoglycosides used against?
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Aerobic, gram- bacteria. NOT effective against gram+ bacteria or anaerobes. Can be used synergistically with penicllins to treat Enterococcus.
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What are the dangers of using amino glycosides?
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Renal toxicity and to a lesser extent ototoxicity. Has been replaced by less toxic drugs.
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What is the mechanism of action of quinolones?
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Bacterial DNA is supercoiled in the nucleoid region around basic proteins. Quinolones prevent Toposiomerases II(DNA Gyrase) and IV from functioning normally. which usually unwind or relax supercoiled DNA. Topoisomerase II does this by temporarily breaking the DNA strand and allowing the DNA to unwind and then reconnecting the strands. Turned from + to - supercoil. Quinolones stabilize cut DNA which allows for DNA to start to degrade.
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What is the mechanism of fluoroquinolones?
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Fluoroquinolones act on topisomerase IV which is responsible for separating daughter DNA after replication is complete.
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What is the spectrum of DNA Gyrase Inhibitors
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Broad spectrum against aerobes and facultative anaerobes. Poor action against MRSA and anaerobes.
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What drugs are quinolones?
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Levofloxacin and Ciprofloxacin
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What is Levofloxacin effective against?
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Effective against most aerobes except for MRSA and Enterococcus faecium. Effective against Streptococcus pneumonia, Moraxella catarrhalis, Haemophilus influenza, Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella. Consequently it has become a favorite to treat pneumonia empirically.
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What is Ciprofloxacin effective against?
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Effective against gram- aerobes and MSSA. It is one of the few oral agents effective against Pseudomonas aeruginosa.
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What is the mechanism of action of Metronidazole?
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Enters the cell by passive diffusion and is activated by a reductive process. Produces short lived metabolites that damage bacterial DNA which result in cell death. This process requires low oxygen levels hence the inactivity against aerobes.
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What is the spectrum of Metronidazole?
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Initially used against protozoa such as Trichomonas, Giardia, and Entamoeba. Later found to be active against obligate anaerobes such as Clostridium. Variably effective against gram+ anaerobes such as Actinomyces and Propionibacterium acnes
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When is Metronidazole used?
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In anaerobic infections except for those caused my Actinomyces and Propionibacterium acnes. Penetrates well into all tissue including CNS. Useful in treating brain abscesses, Clostridium difficile colitis, and abdominal abscesses. Since many anaerobic infections are polymicrobial and include facultative anaerobes a combination of treatments may be necessary.
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What is the mechanism of action of Bactrim(Trimethoprim-Sulfamethoxazole)?
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Sulfamethoxazole(SMX) is a structural analogue of p-aminobenzoic acid, which is needed to synthesize dihydrofolic acid and eventually folic acid. Trimethoprim(TMP) inhibits the conversion of dihydrofolate to tetrahydrofolate, which is a cofactor necessary for the synthesis of purines and pyrimidines. TMP-SMX is 50,000-60,000 more active on bacteria.
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What is the spectrum of activity of Bactrim(TMP-SMX)?
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Bactrim is broad spectrum agent that is effective against many aerobic bacteria and some protozoans. Active against both gram+ and gram- bacteria.
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What organisms are resistant to Bactrim(TMP-SMX)?
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Pseudomonas aeruginosa, Bacteroides fragilis, and other anaerobes Campylobacter, Treponema pallidum, Mycobacterium tuberculosis, and Rickettsia. Penicllin resistant Streptococcus pneumoniae MRSA is variably resistant
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What is Bactrim(TMP-SMX) used to treat?
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UTI, Otitis Media, Pneumocystis pnumonia(fungal), Traveler's diarrhea, acute exacerbations of chronic Bronchitis
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What is Daptomycin and how does it work?
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It is a part of anew class of antibiotics called lipopeptides. It binds to the cytoplasmic membrane of gram+ bacteria and disrupts the membrane potential.
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What is Daptomycin effective against?
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It is effective against both aerobic and anaerobic gram+ bacteria including MRSA, VISA, and VRE.
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What is Nitrofurantoin used to treat? Why?
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It is only used to treat uncomplicated cystitis because serum and tissue levels never rise to an effective concentration because it is rapidly excreted by the kidneys.
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How does Nitrofurantion work?
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It damages bacterial DNA.
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What is the spectrum of activity of Nitrofurantoin?
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It is effective against E. coli, Staphylococcus saprophyticus, Group B Streptococcus and Enterococcus including some VRE. However, it is inactive against many Gram- bacilli
