Antimicrobial Part 2 Flashcards

Question

Examples of Aminoglycosides

Answer 1

``` ▪Amikacin ▪Gentamicin—prototype drug ▪Neomycin ▪Streptomycin ▪Tobramycin ```

Answer 2

• Diffuse through porin channels in outer membrane of susceptible pathogens • Also have an O2-dependent system that transports the drug across the cytoplasmic membrane • In the cell, they bind the 30S ribosomal subunit where they interfere with assembly of the functioning ribosome and/or cause the 30S subunit of the complete ribosome to misread genetic code • They are concentration-dependent bactericidal agents—their efficacy is dependent on the Maximum Concentration [Cmax] of the drug above the MIC of the pathogen • For this family, the target Cmax is 8 to 10 times the MIC • They have a postantibiotic effect [PAE]—continued bacterial suppression after the drug concentrations fall below the MIC [the larger the dose, the longer the PAE] • Because of this PAE, high-dose extended interval dosing is often used—and this prescribing strategy reduces renal damage

Answer 3

▪Majority of aerobic gram negative bugs, including [many drug-resistance species]: - Pseudomonas aeruginosa -Klebsiella pneumonia ▪-Enterobacter species ▪Often given with a ß-lactam antibiotic to get a synergistic effect, when treating: - Enterococcus faecalis - Enterococcus faecium infective endocarditis

Answer 4

▪Occurs from: - Efflux pumps - Decreased uptake - Modification and inactivation by plasmid-associated synthesis of enzymes [each of these enzymes is specific to one aminoglycoside]—so cross-resistance is NOT the rule

Answer 5

``` • Polar, polycation structure prevents adequate oral absorption • All [except Neomycin] must be given IM or IV [neomycin causes renal damage if given parenterally—it is given topically for skin infections** or orally as a prep to decontaminate the bowel before GI surgery] ```

Answer 6

``` • Tissue concentration may be subtherapeutic and penetration is variable due to hydrophilicity • Levels in CSF no adequate, even when meninges are inflamed • To treat CNS infections, intrathecal or intraventricular routes needed • All of these agents cross the placental barrier and can accumulate in fetal plasma and in amniotic fluid ```

Answer 7

``` • Neomycin excreted unchanged in feces • Other drugs in the family— 90% of the agent is excreted unchanged in the urine after parenteral dosing—accumulation occurs in those with kidney disease—so these drugs must be renal dosed ```

Answer 8

*** Drug monitoring of Gentamicin, Tobramycin and Amikacin is a MUST to get appropriate dose and to avoid toxicity - Older adults most susceptible to nephrotoxicity and ototoxicity ▪ Ototoxicity—vestibular and auditory—related to high peak levels and duration of therapy - The drugs accumulate in the endolymph and perilymph of inner ear - Deafness is usually irreversible and can affect a fetus - Those getting other ototoxic drugs, such as Cisplatin or loop diuretics are especially at risk

Answer 9

``` Neuromuscular Paralysis Allergic Reactions • Retention of the agent by the proximal renal tubular cells disrupts Ca++ mediated transport processes • This retention causes kidney damage ranging from mild, reversible renal impairment to severe, potentially irreversible ATN ```

Answer 10

``` • Associated with a rapid increase in concentration OR concurrent administration with neuromuscular blockers • Those with MG are especially at risk • Prompt administration of Ca++ gluconate or Neostigmine can reverse the block that causes neuromuscular paralysis ```

Answer 11

``` • Contact dermatitis is a common reaction to topically applied Neomycin—so avoid triple antibiotic ointments [TAO] ```

Answer 12

▪Antimicrobials with a macrocyclic lactone structure to which one or more deoxy sugars are attached

Answer 13

Erythromycin—prototype drug Clarithromycin Azithromycin Telithromycin

Answer 14

▪Bind irreversibly to a site on the 50S ribosome subunit of the bacterial ribosome and inhibiting translocation steps of protein synthesis ▪These agents are bacteriostatic, and may be bacteriocidal at higher doses ▪Their binding site is either identical to or near to that for Clindamycin and Chloramphenicol

Answer 15

``` • Same coverage as PCN G • Considered alternative for those with PCN allergy ```

Answer 16

``` • Coverage is similar to Erythromycin, and also covers: • H. influenzae • Has greater activity against intracellular pathogens, such as: • Chlamydia • Legionella • Moraxella • Ureaplasma species • H. pylori ```

Answer 17

``` • Less active than Erythromycin against Streptococci and Staphylococci, YET • Much more active against respiratory bugs: - H. influenzae - Moraxella catarrhalis • Excess use of this agent has caused growing Streptococcus pneumoniae resistance ```

Answer 18

• Spectrum is much like that of Azithromycin • Structural change with ketolides neutralizes the most common resistance mechanisms that cause macrolide resistance • Ketolides are suspected to become important antimicrobials in the future, as new drugs are in development

Answer 19

▪ Inability of the organism to take up the antibiotic ▪ Presence of efflux pumps ▪ Decreased affinity of the 50S ribosomal subunit for the due to methylation of an adenine in the 23S bacterial ribosomal RNA in Gram + pathogens ▪ Presence of plasmid-associated Erythromycin esterases in Gram – pathogens ▪ Ketolides thought to be effective against macrolide-resistant organisms

Answer 20

• Erythromycin base is destroyed by HCl- acid, so EC or esterified pills are given • All forms are stable in stomach acid and are easily absorbed PO • Food interferes with absorption of Erythromycin and Azithromycin, but increases absorption of Clarithromycin • Erythromycin/Azithromycin are available IV

Answer 21

• Erythromycin well distributed in all tissues except CSF—one of few antimicrobials that gets into prostate and it accumulates in macrophages • All drugs concentrate in the liver • Clarithromycin, Azithromycin and Telithromycin widely distributed in tissues • Azithromycin concentrates in neutrophils, macrophages and fibroblasts, but serum levels are LOW—it has the highest volume of distribution of all macrolides

Answer 22

• Erythromycin and Telithromycin are metabolized in liver—they inhibit oxidation of many drugs through their interaction with CYP 450 • Clarithromycin interferes with metabolism of theophylline, statins and many AEDs

Answer 23

• Azithromycin concentrated and excreted in bile as active drug • Erythromycin and metabolites are excreted in bile • Clarithromycin metabolized in liver as an active drug and metabolites excreted in urine—dose adjust this drug in renal disease

Answer 24

``` • GI upset is most common SE [especially Erythromycin] • High doses of Erythromycin can cause smooth muscle contractions that cause gastric contents to move into the duodenum—and the ADE used to treat gastroparesis and post- operative ileus ```

Answer 25

``` • Occurs most commonly with estolate form of Erythromycin [no longer available in the US] • Has been reported with other formulations in this family ```

Answer 26

``` • Transient deafness has been seen with high dose Erythromycin • Azithromycin has been associated with irreversible sensorineural hearing loss ```

Answer 27

``` • May prolong QTc interval and should be used with caution in patients with proarrhythmic conditions or taking proarrhythmic drugs ```

Answer 28

``` • Patients with liver disease should be treated cautiously if prescribing Erythromycin, Telithromycin and Azithromycin as these agents accumulate in the liver • Severe liver toxicity has occurred with Telithromycin and is the reason it is not currently used in the US ```

Answer 29

``` • Erythromycin, Telithromycin and Clarithromycin can interfere with liver metabolism of many drugs which can result in toxic levels of these agents—Alfuzosin [Uroxatrol], Atorvastatin [Lipitor]; Carbamazepine [Tegretol], PIs, Sildenafil [Viagra], Simvastatin [Zocor], Valproate [Depakote], Warfarin • Change in gut flora from these antibiotics can lead to digoxin toxicity ```

Answer 30

▪Macrocyclic drug similar to a macrolide, with a unique MOA ▪Acts on sigma subunit of the RNA polymerase, disrupting bacterial transcription, terminating protein synthesis and causing cell death ▪Very narrow spectrum of coverage—Gram + aerobes and anaerobes ▪ Is covers Staphylococcus and Streptococcus, mainly used for bactericidal activity against Clostridium difficile ▪Because of unique target site, cross-resistance has NOT been seen ▪ Given orally—minimal systemic absorption and remains in GI tract ▪ Making it ideal to treat Clostridium difficile ▪ ADEs—nausea, vomiting and abdominal pain ▪ Anemia and neutropenia have been seen, but not common ▪ Hypersensitivity, angioedema, SOB and itching have occurred ▪ Use with caution in those allergy to a macrolide ▪ Seems ideal—BUT... AWP for 10 day course is $3100 [cost to patient or insurance is 100 to 200% of AWP—so $6200-9300 for a course of therapy], in spite of this, in 2019, this is the first line agent in severe C. diff infections

Answer 31

▪Broad spectrum antibiotic restricted to life-threatening infections for which no alternatives exist ▪Considered salvage therapy here in the US ▪Used more often in other parts of the world, than it is used here

Answer 32

• Binds reversibly to the bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction • Some of the host mitochondrial ribosomes closely resemble those of the pathogen, protein and ATP production in the host’s organelles may be impaired at high circulating Chloramphenicol levels—causing bone marrow toxicity • The oral form of Chloramphenicol was removed from the market in the US [1992] because of this toxicity

Answer 33

``` • Active against many many pathogens, including: • Chlamydia • Rickettsia • Spirochetes • Anaerobes • Bacteriostatic, but can be bactericidal—depending on dose and organism ```

Answer 34

• Takes place by the presence of enzymes that inactivate Chloramphenicol

Answer 35

``` • After IV dose, it is widely distributed throughout the body and in the CSF • Primarily undergoes hepatic metabolism to an inactive glucuronide, which is then secreted via renal tubules and excreted in the urine • Reduce dose in liver disease and cirrhosis • Secreted in breast milk, so avoid in breastfeeding mums ```

Answer 36

``` • Dose related anemia • Hemolytic anemia in those with G6PD deficiency • Aplastic anemia [not related to dose and can occur after drug is stopped] ```

Answer 37

``` • Infants have decreased ability to glucuronidate this drug and their renal system is not fully developed—so they have decreased ability to excrete the drug—this results in drug build up and this then interferes with function of mitochondrial ribosomes—causing poor feeding, respiratory depression, CV collapse, cyanosis and death • Adults who have received high doses of this drug have experienced this syndrome ```

Answer 38

• This drug interferes with the | metabolism of Warfarin and Phenytoin—which potentiates their effects

Answer 39

▪ MOA is similar to macrolides ▪ Mainly used to treat Gram + bugs, including MRSA, Streptococcus and anaerobes ▪ Resistance mechanisms are the same as they are for Erythromycin and cross-resistance has been described ▪ C. difficile is resistant to Clindamycin, and using it for Gram – anaerobes [Bacteroides species] is decreasing due to resistance ▪ Available orally and IV—oral use is limited by GI side effects ▪ Distributes well into all body fluids, but has poor entry into the CSF ▪This agent undergoes extensive oxidative metabolism to active and inactive forms—and is excreted into the bile and urine ▪Low urinary excretion of the active drug limits its use for UTIs ▪Accumulation has been seen in those with severe renal and/or liver disease ▪ADEs—rash; diarrhea [which may be an overgrowth of C. difficile] ▪ Oral Vancomycin or Metronidazole is usually effective to treat C. difficile from Clindamycin

Answer 40

▪Mixture of [2] streptogramins in a ratio of 30:70, respectively ▪Because there are many ADEs—this agent is reserved for the treatment of severe infections caused by Vancomycin- resistant Enterococcus faecium [VRE], where there are not other options [salvage therapy]

Answer 41

• Each part of this drug binds to a separate sit on the 50S bacterial ribosome • Dalfopristin disrupts elongation by interfering with the addition of new amino acids • Quinupristin prevents elongation similar to the macrolides and causes release of incomplete peptide chains • Synergistically interrupt protein synthesis • Bactericidal against most susceptible organisms and this drug has a long PAE

Answer 42

* Gram + cocci—including those resistant to other antibiotics * Primary use is for E. faecium, including VRE strains [it is bacteriostatic against this strain] * NOT effective against E. faecalis

Answer 43

• Enzymatic processes cause resistance • In some cases, enzyme changes can change the drug from bactericidal to bacteriostatic • Plasmid-associated acetyltransferase inactivates Daslfopristin

Answer 44

• Given IV • Does not achieve therapeutic levels in CSF • Both drugs are metabolized in the liver and excreted in the feces

Answer 45

``` • Venous irritation if given through a peripheral IV • Hyperbilirubinemia in 25%-- from competition with antibiotic for excretion • Arthralgias and myalgias with high doses • Inhibits CYP 450 3A4 isoenzyme; concomitant use of drugs that are metabolized by this route may cause toxicity ```

Answer 46

``` ▪Synthetic oxazolidinones developed to treat Gram + organisms, including resistant pathogens: ▪MRSA ▪VRE ▪Penicillin-resistant Streptococci Linezolid [Zyvox]—prototype drug ```

Answer 47

Linezolid [Zyvox]—prototype drug | Tedizolid [Sivextro]

Answer 48

• Binds to bacterial 23S ribosomal RNA of the 50S subunit—inhibits the forming of 70S initiation complex and translation of bacterial proteins

Answer 49

• Main action is against Gram + pathogens -Streptococci - Staphylococci - Enterococci - Corynebacterium species - Listeria monocytogenes • Moderately active against Mycobacterium TB • Main use is for drug resistant Gram + infections • Bacteriostatic, yet Linezolid is bactericidal against Streptococcus • Linezolid is an alternative to Daptomycin for infections from VRE • Because these agents are bacteriostatic—not recommended as 1st line for MRSA bacteremia

Answer 50

• Occurs from reduced binding at target sites • Reduced susceptibility and resistance has been seen to S. aureus and Enterococci species • Cross-sensitivity to other protein synthesis inhibitors does not occur

Answer 51

• Well absorbed orally and IV • Distribute widely throughout the body • Metabolic pathway of Linezolid not fully known, is metabolized to 2 inactive metabolites, excreted by renal and nonrenal routes • Tedizolid is metabolized by sulfidation and majority of elimination is via the liver and excreted in the feces • No dose reduction is needed for either drug in the presence of renal compromise

Answer 52

• GI [nausea/diarrhea]* • Headache* • Rash* • Thrombocytopenia has been seen when drugs used >10 days • These agents possess nonselective MAO activity and may cause a Serotonin syndrome with large quantities of tyramine-containing foods, SSRIs or MAOIs [reversible when the antimicrobial is stopped] • Irreversible peripheral neuropathy [seen when used >28 days] • Optic neuritis [seen when used >28 days]

Answer 53

``` ▪Ciprofloxacin—prototype drug ▪Delafloxacin [Baxdela] ▪Gemifloxacin [Factive ▪Levofloxacin [Levaquin] ▪Moxifloxacin [Avelox] ▪Ofloxacin ``` ▪ Overuse has caused resistance in Gram + and Gram – pathogens, and it has increased the amount of C. difficile infections, and unmasked many of the untoward ADEs ▪ Currently, these drugs are now considered 2nd line agents for many infections

Answer 54

▪ Following cell wall entry through porin channels, the quinolones bind to DNA gyrase and topoisomerase IV, and then interfere with DNA ligation ▪ This interference increases chromosomal breaks—causing cell lysis ▪ Quinolones have different targets; ▪ Gram – pathogens—DNA gyrase ▪ Gram + pathogens—topoisomerase IV ▪ These agents are bactericidal and exhibit AUC/MIC dependent killing ▪ Modifying the quinolone nucleus has enhanced its coverage with each new generation of drugs in this family

Answer 55

• Naladixic acid • Narrow spectrum • Covers Gram – bacilli, mainly Enterobacteriaceae

Answer 56

``` • Ciprofloxacin • Improved intracellular penetration and broader coverage, including: -Enterobacteriaceae - Pseudomonas aeruginosa - Haemophilus influenzae - Neisseria species - Chlamydia species - Legionella species ```

Answer 57

``` • Levofloxacin • Cover the same pathogens as the 2nd generation drugs, but with expand coverage of Streptococcus subspecies: -Streptococcus pneumoniae - MSSA - Strenotrophomonas maltophilia - Mycobacterium species ```

Answer 58

• Moxifloxacin • Gemifloxacin • Delafloxacin • Enhanced Gram + and more Staphylococcus and Streptococcus coverage - Delafloxacin active against MRSA and Enterococcus faecalis - Delafloxacin and Moxifloxacin cover Bacteroides fragilis and Prevotella species, while still covering Enterobacteriaceae and Haemophilus influenzae - In the 4th generation drugs—only Delafloxacin covers Pseudomonas aeruginosa - These drugs cover atypical bacteria—Moxifloxacin and Delafloxacin cover Mycobacteria species well

Answer 59

``` • Mutations in bacterial genes reduce binding of the quinolone • Reduced intracellular levels is from: - Decrease in membrane permeability OR - Efflux pumps • Alterations in membrane permeability are mediated through a reduction in outer membrane porin proteins, so drug cannot access topoisomerases • Efflux pumps remove the quinolone from the cell • Aminoglycoside acetyltransferase variant acetylates the quinolone ```

Answer 60

``` • Well absorbed after oral dosing • Levofloxacin and Moxifloxacin have bioavailability of >90% • Sucralfate, Aluminum or Magnesium containing antacids, dietary supplements with Zinc or Iron reduce absorption • Ca++ and dairy products interfere with absorption ```

Answer 61

``` • Plasma binding is variable 20 – 80% • These agents distribute well into all tissues and body fluids • Concentration are high in bone, urine [except Moxifloxacin], kidney, prostate tissue and lungs [as compared to serum] • Penetration into the CNS is good • Accumulation in macrophages and PMN leukocytes allows good coverage against intracellular pathogens— Listeria, Chlamydia, Mycobacterium ```

Answer 62

▪Elimination—excreted renally ▪Dosage adjustment needed in renal disease ▪Moxifloxacin is metabolized primarily by the liver— so no dose adjustment is needed for renal disease

Answer 63

▪ Nausea/Vomitig/HA/Dizziness ▪ Photosensitivity—patients need to use sunscreen and avoid excess UV light exposure ▪ Arthropathy is uncommon—but arthralgia and arthritis is often reported in the pediatric patient ▪ All of these agents carry a BB warning for tendinitis, tendon rupture, peripheral neuropathy and CNS effects—hallucinations, anxiety, insomnia, confusion, seizures ▪ Use in pediatrics should be limited to specific scenarios—CF exacerbations ▪ Hepatotoxicity or BS disturbances [usually low BS] has been seen in diabetics ▪ Severe ADEs require immediate cessation of these agents ▪ Fluoroquinolones may prolong the QTc interval—and should be avoided in those predisposed to arrythmias or those already on drug associated with QT prolongation ▪ Cipro inhibits CYP 450 1A2 and 3A4 metabolism—so drug levels of Theophylline, Tizanidine, Warfarin, Ropinirole, Duloxetine, Caffeine, Sildenafil and Zolpidem levels can be increased

Answer 64

▪ Coverage against Gram – bacilli, including Pseudomonas aeruginosa ▪ Used in traveler’s diarrhea, typhoid fever, anthrax ▪ 2nd line for intra-abdominal, lung, skin or urine sourced infection ▪ High dose therapy should be used to treat Pseudomonas

Answer 65

▪ Similar activity to Ciprofloxacin ▪ Enhanced coverage for Streptococcus pneumoniae, and can be used 1st line for CAP ▪ 2nd line therapy for Stenotrophomonas maltophilia

Answer 66

• Enhanced activity against Gram + organisms—Streptococcus pneumoniae, Gram – anaerobes, Mycobacterium subspecies • Can be used for CAP, but not for hospital- acquired pneumoniae [poor coverage of Pseudomonas] • Can be used for mild to moderate intra- abdominal infections—but avoid in patient’s have had a fluoroquinolone in previous 90 days, due to emerging B fragilis resistance • 2nd line for drug susceptible TB

Answer 67

• Indicated for community acquired respiratory infections • Only available orally

Answer 68

``` • Improved activity against Gram + cocci, including MRSA and Enterococcus • An option for acute bacterial skin and skin structure infections • Available IV and PO ```

Answer 69

▪ Folic acid is a coenzyme essential in synthesis of RNA, DNA and certain amino acids ▪ In the absence of folate, cells cannot grow and divide ▪ Humans use dietary folate to synthesize tetrahydrofolic acid ▪ Many bacteria are impermeable to folate derivatives, and rely on their ability to synthesize folate de novo ▪ Sulfonamides inhibit de novo synthesis of folate; Trimethoprim prevents pathogens from converting dihydrofolic acid to tetrahydrofolic acid ▪Sulfonamides and Trimethoprim interfere with the ability of the pathogen to perform DNA creation and allow essential cellular functions ▪Combining Sulfamethoxazole withTrimethoprim [Cotrimoxazole/Bactrim/Septra] provides a synergistic effect

Answer 70

``` • Bacteria use dihydropteroate synthetase to create dihydrofolic acid from its precursor p- aminobenzoic acid [PABA] • Sulfonamides are synthetic analogs of PABA • They compete with PABA to inhibit dihydropteroate synthetase and creation of bacterial dihydrofolic acid • Cotrimoxazole is the prototype drug and is bacteriostatic ```

Answer 71

``` • In vitro action against Gram – and Gram + pathogens: • Enterobacteriaceae • Haemophilus influenzae • Streptococcus spp. • Nocardia • Sulfadiazine [combined with Pyrimethamine] is DOC for Toxoplasmosis ```

Answer 72

``` • Pathogens that get folate from the environment are naturally resistant to Sulfa drugs • Acquired resistance can arise from: • Plasmid transfers • Random mutations • Resistance can be from: • Altered dihydropteroate synthetase • Decreased cellular permeability to Sulfa drugs • Enhance production of natural substrate, PABA • Resistance to one member of the drug family means resistance to ALL ```

Answer 73

• Well absorbed after oral dose • Exception is Sulfasalazine—not absorbed when given PO or per rectum, reserved for treatment of chronic inflammatory diseases [especially those affecting the bowel] • IV use is reserved for those who cannot take oral dosages or who have severe infection • Because of risk of sensitization, Sulfa drugs are usually not given topically • Exception is Silver Sulfadiazine or Mafenide acetate—creams have been used in reducing burn-associated sepsis because they prevent colonization of bacteria • Silver Sulfadiazine is preferred because Mafenide produces pain with application and can contribute to acid-base disturbances

Answer 74

• Bound to serum albumin in circulation and widely distributed throughout body tissues • Penetrate well into CSF [even without inflammation] and cross placental barrier to enter fetal tissues

Answer 75

• Acetylated and conjugated in the liver • Acetylated product does not have any antimicrobial activity, but retains toxic potential to precipitate at neutral or acidic pH—this can cause crystalluria [“stone formation”] and potential damage to the kidney

Answer 76

• Unchanged Sulfa drug and metabolites eliminated via glomerular filtration and secretion • Dose adjustments are needed in renal disease • Are eliminated in breast milk

Answer 77

• Adequate hydration and alkalization of the urine prevent this by reducing concentration of drug and promoting ionization

Answer 78

• Rash • Angioedema • Stevens-Johnson syndrome

Answer 79

• Hemolysis can occur in those with G6PD deficiency • Granulocytopenia and thrombocytopenia can also occur • Fatal reactions from agranulocytosis, aplastic anemia and other blood dyscrasias have been seen

Answer 80

``` • Bilirubin associated brain damage can occur in newborns, because Sulfa drugs displace bilirubin from binding sites on serum albumin; bilirubin is then free to pass into the CNS—because the blood- brain barrier is not fully developed ```

Answer 81

* Sulfamethoxazole potentiates the anticoagulant effect of Warfarin by inhibiting CYP 450 2C9—causing reduced clearance of Warfarin * Sulfonamides also displace Warfarin from binding sites on serum albumin * DO NOT PRESCRIBE SULFONAMIDES to patients on Warfarin—unless there are NO OTHER ALTERNATIVES, and in that case, the Warfarin dose must be reduced by 50 PERCENT * Methotrexate levels can rise through protein binding displacement * Phenytoin levels can increase when sulfonamides are given

Answer 82

• Do not give to newborns and infants less than 2 months of age • Do not give to pregnant women at term • Do not give to patients taking Methenamine, sincethey can crystallize in the presence of formaldehyde produced by Methenamine

Answer 83

▪ Potent inhibitor of bacterial dihydrofolate reductase—initially available in combination with Sulfamethoxazole, and later approved for use as a single antimicrobial ▪ Most commonly used in combination with Sulfamethoxazole • Inhibits bacterial dihydrofolate reductase • Inhibiting this enzyme prevents formation of the metabolically active form of folic acid, tetrahydrofolic acid an interferes with normal functioning of the bacteria

Answer 84

* Coverage similar to that of Sulfamethoxazole * Trimethoprim is 20 – 50 fold more potent than the Sulfonamides * May be used alone to treat UTI, bacterial prostatitis [although quinolones and Cotrimoxazole are preferred]

Answer 85

• Resistance in Gram – bacteria is from the presence of an altered dihydrofolate reductase that has a lower affinity for Trimethoprim • Efflux pumps and decreased permeability to the drug may be part of resistance

Answer 86

• Rapidly absorbed after an oral dose • Weak base—high levels are achieved in acidic prostate and vaginal fluids • Widely distributed in the body tissues and fluids—including CSF • Undergoes some O-demethylation, but 60-80% is renally excreted

Answer 87

• Can produce folic acid deficiency • Megaloblastic anemia • Leukopenia • Granulocytopenia • Pregnant and those with poor diets are especially at risk • These effects can be reversed by giving Folinic acid [Leucovorin] which does not enter bacteria • Has a K+ sparing effect and may cause elevated K+, especially in high doses and when given with other drugs that can elevate K+ [ACE inhibitors]

Answer 88

▪ Trimethoprim + Sulfamethoxazole ▪ Shows greater coverage than either drug used alone ▪ Synergistic activity and similar ½ lives to each of its components

Answer 89

• Synergistic activity of Cotrimoxazole is from the inhibition of 2 steps in the synthesis of tetrahydrofolic acid

Answer 90

Broader coverage than the sulfa drugs • Used to treat UTIs, respiratory infections, as well as: • Pneumocystis jirovecii • Toxoplasmosis • Listeria monocytogenes • Salmonella • Active against MRSA—and can be used in skin and soft tissue infections • DOC for Nocardia and Stenotrophomonas maltophilia

Answer 91

``` • Encountered less often than resistance to either of the components— because the bug would have to have simultaneous resistance to both drugs • Resistance has been seen to E.coli ```

Answer 92

``` • Usually given orally • Can be given IV for severe pneumonia from Pneumocystis • Both components distribute throughout the body • Trimethoprim concentrates in acidic fluids—prostate; and explains the effectiveness in prostatitis • The combined agent crosses the blood-brain barrier • Both drugs and their metabolites are excreted in the urine ```

Answer 93

``` • Similar to those seen with the individual components • Nausea • Vomiting • Skin rash • Hematological toxicity • Elevated K+ ```

Answer 94

▪ Methenamine—Hiprex, Urex ▪ Nitrofurantoin—Macrodantin, MacroBid— prototype drug ▪ In the past, quinolones and Trimethoprim Sulfa have been 1st line for UTIs ▪ Resistance has increased among these pathogens [E. coli and others] in the last decade—and as a result, these older antimicrobials must be considered in our therapies and suppression of UTIs

Answer 95

``` • Absorbed orally • 30% is broken down by gastric juices, unless protected by enteric coating • Reaches the urine through tubular secretion and glomerular filtration • Concentrations are sufficient to treat susceptible organisms • Because of ammonia formation, avoid in liver disease ```

Answer 96

``` • GI distress • At high doses—albuminuria, hematuria and rash • Methenamine mandelate contraindicated in those with renal disease as the mandelate can precipitate—use Methenamine Hippurate • Sulfa drugs react with formaldehyde and cannot be used concomitantly with Methenamine—they can crystalize and mutually antagonize each other ```

Answer 97

▪Been around since 1950s for cystitis—re-emerged with all of the resistance to Enterobacteriaceae ▪Now considered 1st line for uncomplicated cystitis ▪This drug works by inhibiting DNA and RNA synthesis ▪Covers E. coli, Klebsiella spp., Enterococcus spp., and Staphylococcus spp. ▪Following oral dose, it is absorbed; near 40% is excreted unchanged in the urine

Answer 98

▪ADEs—nausea, vomiting, diarrhea ▪Use of microcrystalline formula reduces the GI toxicity ▪Rare complications—pulmonary fibrosis [do not use in patients with pre-existing lung disease], neuropathy, autoimmune hepatitis—these complications are seen with prolonged use [greater than 1 month] ▪Those with impaired renal function—should not take this drug—as it increases the chance of ADEs ▪ Not effective in pyelonephritis ▪ Do not prescribe in those with calculated GFR <35 cc/minute

Antimicrobial Part 2 Flashcards

(124 cards)