Antimicrobials Flashcards

Question

Cephalosporins - Adverse

Answer 1

* Allergic reactions (cross-sensitivity with penicillins can occur) * However, minor penicillin allergic patients often treated successfully with a cephalosporin * Pain at infection site (IM), thrombophlebitis (IV) * Superinfections (eg, C.difficile) * **Cefamandole, cefoperazone & cefotetan** contain methyl-thiotetrazole group, all can cause: * hypoprothrombinemia (Vit. K1 admin can prevent) & * disulfiram-like reactions (avoid alcohol)

Answer 2

* Carbapenem * Synthetic Beta-lactam antibiotics * Resist hydrolysis by most beta-lactamases * Very broad spectrum of activity * Active against penicillinase-producing Gram-positive & negative organisms; aerobes & anaerobes; P.aeruginosa * Not active against carbapenemase producing organisms eg, carbapenem-resistant enterobacteriaceae, carbapenem-resistant klebsiella * Not active against MRSA Indications: use typically restricted to avoid resistance * DOC for: * enterobacter infections * extended-spectrum beta-lactamase producing Gram -ve

Answer 3

* IV * Imipenem forms potentially nephrotoxic metabolite when activated by renal dehydropeptidase I. Combining with enzyme inhibitor Cilastatin prevents metabolism thus prevents toxicity & increases availability. * Meropenem is not metabolized by same enzyme (no need for Cilastatin)

Answer 4

* GI distress (but all antibiotics can cause diarrhea) * High levels of imipenem can provoke seizures * Allergic reactions (partial cross-reactivity with penicillin’s)

Answer 5

* Monobactams * **Aerobic Gram-negative rods ONLY (including pseudomonas)** * No activity against Gram-positive bacteria or anaerobes * Resistant to action of beta-lactamases Indications UTI’s, lower respiratory tract infections, septicemia, skin/structure infections, intraabdominal infections, gynecological infections caused by susceptible Gram- negative bacteria

Answer 6

* Mainly IV or IM * Can be given by inhalation in CF patients * Penetrates CSF when inflamed * Excreted primarily via urine

Answer 7

* Relatively nontoxic * Little cross-hypersensitivity with other beta-lactam antibiotics * Occasional skin rashes / elevation of serum aminotransferases * GI upset, vertigo, headache * Phlebitis or thrombophlebitis reported with IV use

Answer 8

* Bacterial glycoprotein * Bactericidal * Active against Gram-positive bacteria only * Virtually all Gram-negative organisms are intrinsically resistant * Effective against multi-drug resistant organisms (eg, MRSA, enterococci, PRSP) MOA * Binds to the D-Ala-D-Ala terminus of nascent peptidoglycan pentapeptide * Inhibits bacterial cell wall synthesis & peptidoglycan polymerization Resistance * Plasmid-mediated changes in drug permeability * Modification of the D-Ala-D-Ala binding site (D-Ala replaced by D-lactate) Indications: reserved for drug resistant bacteria * Treatment of serious infections caused by Beta-lactam resistant Gram +ve organisms eg, MRSA * Treatment of Gram +ve infections in patients severely **allergic to Beta-lactams** * In combination with an aminoglycoside for empirical treatment of **infective endocarditis; 1st line: vancomycin + gentamycin** * In combination with an aminoglycoside for treatment of enterococcal endocarditis or PRSP * Given orally for the treatment of staphylococcal enterocolitis or antibiotic-associated pseudomembranous colitis (C.difficile)

Answer 9

* Poor oral absorption * Requires slow IV infusion (60-90 min) * Penetrates CSF when inflamed * 90-100% excreted via kidneys

Answer 10

* Mostly minor eg, fever, chills, phlebitis at infusion site * ‘Red man’ or ‘red neck’ syndrome (infusion-related flushing over face and upper torso) * Ototoxicity (drug accumulation) * Nephrotoxicity (drug accumulation)

Answer 11

* Bactericidal * Effective against multiple drugresistance organisms * Inactive against Gram-negative bacteria * Not effective in treatment of pneumonia MOA * Novel mechanism of action -\> useful against multi-drug resistant bacteria * Binds to cell membrane via calcium-dependent insertion of lipid tail * Results in depolarization of cell membrane with K+ efflux -\> cell death Indications * **Recommended for treatment of severe infections caused by MRSA or VRE** * Treatment of complicated skin/structure infections caused by susceptible S.aureus

Answer 12

* IV only * Can accumulate in renal insufficiency

Answer 13

* Constipation, nausea, headache, insomnia * Elevated creatine phosphokinases (recommended to discontinue coadmin. of statins)

Answer 14

* Unique mechanisms -\> no cross resistance * Interferes in late stage cell wall synthesis * Effective against Gram-positive organisms * Marked nephrotoxicity -\> mainly topical use

Answer 15

* Inhibits cytoplasmic enzyme enolpyruvate transferase in early stage of cell wall synthesis * Active against Gram-positive and negative organisms * Oral * Used for treatment of uncomplicated lower UTI’s

Answer 16

* Tetracyclines * Glycylcyclines * Aminoglycosides * Macrolides * Chloramphenicol * Clindamycin * Streptogramins * Linezolid * Mupirocin

Answer 17

* Bind to and interfere with ribosomes * Bacterial ribosome (70S) differs from mammalian (80S) but closely resembles mammalian mitochondrial ribosome * Mostly bacteriostatic

Answer 18

* Doxycycline, Minocycline, Tetracycline * Broad-spectrum: aerobe, anaerobe, parasites, etc… * Bacteriostatic * Activity against many aerobic and anaerobic Gram- positive & Gram-negative organisms MOA * Entry via passive diffusion & energy-dependent transport unique to bacterial inner cytoplasmic membrane * Susceptible cells concentrate drug intracellularly * Bind reversibly to 30S subunit of ribosome, preventing binding of aminoacyl tRNA Resistance * Widespread resistance (usually plasmid mediated) * 3 main mechanisms: * Impaired influx or increased efflux by active protein pump * Production of proteins that interfere with binding to ribosome * Enzymatic inactivation Indications * Most common use = **severe acne & rosacea** * Used in empiric therapy of community-acquired pneumonia (outpatients) * Can be used for infections of respiratory tract, sinuses, middle ear, urinary tract, & intestines * Syphilis (patients allergic to penicillin) * DOC * Chlamydia * Mycoplasma pneumoniae * Lyme disease * Cholera * Anthrax prophylaxis * Rickettsia (Rocky Mountain Spotted Fever, typhus) * Used in combination for * H. pylori eradication * Malaria prophylaxis and treatment * Treatment of plague, tularemia, brucellosis

Answer 19

* Variable oral absorption (decreased by divalent & trivalent cations) * Doxycycline (lipid soluble) = preferred for parenteral admin. and good choice for STD’s and prostatitis * Minocycline = reaches high concentrations in all secretions (useful for eradication of meningococcal carrier state) * Concentrate in liver, kidney, spleen & skin * Excreted primarily in urine except doxycycline (primarily via bile) * TERATOGENIC – all cross placenta & are excreted into breast milk (FDA category D)

Answer 20

* Gastric effects / superinfections (nausea, vomiting, diarrhea) * Discoloration & hypoplasia of teeth, stunting of growth (generally avoided in pregnancy & not given in children under 8y) * Fatal hepatotoxicity (in pregnancy, with high doses, patients with hepatic insufficiency) * Exacerbation of existing renal dysfunction * Photosensitization * Dizziness, vertigo (esp. doxycycline & minocycline)

Answer 21

* Glycycyclines * Structurally similar to tetracyclines * Antibacterial spectrum * Broad-spectrum against multidrug-resistant Gram- positive, some Gram-negative & anaerobic organisms Resistance * Little resistance * Not subject to same resistant mechanisms as tetracyclines (exceptions = efflux pumps of Proteus & Pseudomonas species) Indications * Treatment of complicated skin, soft tissue and intra- abdominal infections * Increased risk of mortality has been observed with tigecycline compared with other antibiotics when used to treat serious infections * FDA recommends considering the use of alternative antimicrobials when treating patients with serious infections

Answer 22

* IV only * Excellent tissue & intracellular penetration * Primarily biliary/fecal elimination Adverse effects * Well tolerated * AE similar to tetracyclines Contraindications: Pregnancy & children \<8y

Answer 23

* Aminoglycosides * Bactericidal * Associated with serious toxicities * Largely replaced by safer antibiotics; reserved for serious infections and only used for short period of time MOA * Passively diffuse across membranes of Gram-negative organisms * Actively transported (O2-dependent) across cytoplasmic membrane * Bind to 30S ribosomal subunit prior to ribosome formation leading to: 1. misreading of mRNA, & 2. inhibition of translocation Resistance: 3 mechanisms * Plasmid-associated synthesis of enzymes that modify and inactivate drug * Decreased accumulation of drug * Receptor protein on 30S ribosomal subunit may be deleted or altered due to mutation

Answer 24

* Concentration-dependent (aminoglycosides) * Time-dependent (penicillins, cephalosporins)

Answer 25

* Most active against aerobic Gram-negative bacteria * Anaerobes lack O2-dependent transport Indications * Used mostly in combination * Empiric therapy of serious infections eg, septicemia, nocosomial respiratory tract infections, complicated UTI’s, endocarditis etc * Once organism is identified aminoglycosides are normally discontinued in favor of less toxic drugs * DOC for * Empiric therapy of infective endocarditis in combination with either a penicillin or (more commonly) vancomycin * Streptomycin is the drug of choice for Plague (Y.Pestis)

Answer 26

* Used as adjunct in treatment for hepatic encephalopathy * Alternative treatment options for hepatic encephalopathy: * Lactulose * Oral vancomycin * Oral metronidazole * Rifaximin

Answer 27

Nonabsorbable disaccharide MOA * Degraded by intestinal bacteria

Answer 28

* Parenteral admin. only (except neomycin - topical) * Once-daily admin. * Well distributed (excluding CSF, bronchial secretions) * High levels in renal cortex & inner ear * 99% excreted in urine (reduce dose in renal insufficiency)

Answer 29

Both time- and concentration-dependent * Ototoxicity * Nephrotoxicity * Neuromuscular blockade (myasthenia gravis = contraindicated) * Pregnancy (contraindicated unless benefits outweigh risks – FDA Category D)

Answer 30

* Macrolides * Mainly used to treat Gram-positive infections * Bacteriostatic (bactericidal at high conc.) MOA * Reversibly bind to 50S subunit inhibiting translocation; bacteriostatic * Binding site is identical or close to that for clindamycin & chloramphenicol Resistance: 3 mechanisms * Reduced membrane permeability or active efflux * Production of esterase that hydrolyze drugs (by enterobacteriaceae) * Modification of ribosomal binding site (by chromosomal mutation or by a methylase) * Complete cross-resistance between erythromycin, azithromycin, & clarithromycin * Partial cross-resistance with clindamycin & streptogramins Antibacterial spectrum * Most active against Gram-positive bacteria (some activity against Gram-negatives) * Spectrum is slightly wider than that of penicillins * Azithromycin, clarithromycin & telithromycin have broader spectrum than erythromycin Indications * Used in empiric therapy of community-acquired pneumonia (outpatient & in combination with beta-lactam for inpatients) * DOC for **Mycoplasma pneumoniae** * Treatment of **upper respiratory tract & soft-tissue infections** (eg, Staph, H.influenzae, S.pneumoniae, enterococci) * Erythromycin = DOC for whooping cough (**B.pertussis**) * **Common substitute for patients with penicillin allergy **

Answer 31

* Clarithromycin, azithromycin, telithromycin = improved oral absorption, longer t1/2, increased bioavailability compared to erythromycin * Azithromycin & telithromycin = greater tissue penetration compared to other macrolides * Erythromycin, clarithromycin & telithromycin = CYP P450 inhibition (NOT azithromycin) * Ex. HIV Pt on multiple meds and fighting pneumonia -\> Azithromycin indicated

Answer 32

Adverse * GI irritation * Hepatic abnormalities (erythromycin & azithromycin) * QT prolongation * Severe reactions are rare (anaphylaxis, colitis) Contraindications * Statins (due to macrolides inhibiting CYP P450) * Telithromycin – fatal hepatotoxicity, exacerbations of myasthenia gravis, & visual disturbances

Answer 33

* Potent inhibitor of protein synthesis * Broad-spectrum (aerobic & anaerobic Gram-positive & - negative organisms) * Bacteriostatic (usually) * Toxicity limits use to life-threatening infections with no alternatives **MOA** * Enters cells via active transport process * Binds reversibly to 50S ribosomal subunit (site adjacent to site of action of macrolides & clindamycin) * Can inhibit protein synthesis in mitochondrial ribosomes -\> bone marrow toxicity * Very broad spectrum * Activity against Gram-positive and negative bacteria, including Rickettisae & anaerobes * N.meningitidis, H.influenzae, Salmonella & bacteroides = highly susceptible * Never given systemically for minor infections (due to adverse effects) **Resistance** * Presence of factor that codes for chloramphenicol acetyltransferase (inactivates drug) * Changes in membrane permeability **Clinical applications** * Serious infections resistant to less toxic drugs * When chloramphenicols penetrability to site of infection is clinically superior to other drugs * Active against many VRE * Topical treatment of eye infections (mainly outside US) **PK** * Oral, IV or topical * Wide distribution (readily enters CSF) * Inhibits hepatic oxidases (3A4 & 2C9) **Adverse** * GI distress * Bone marrow depression * dose-related reversible depression * severe irreversible aplastic anemia * Gray baby syndrome (cyanosis), due to drug accumulation

Answer 34

* MOA = same as macrolides (binds to 50S subunit) * Mainly bacteriostatic * Primarily used against Gram-positive anaerobic bacteria (including bacteroides) * not many drugs effective against anaerobes (only clindamycin and metronidzaole) **Resistance ** * mutation of ribosomal receptor site * modification of the receptor * enzymatic inactivation of drug * Most Gram-negative aerobes & enterococci are intrinsically resistant * Cross-resistant with macrolides **Clinical applications** * Anaerobic infections (eg, bacteroides infections, abscesses, abdominal infections) * Skin and soft tissue infections (streptococci and staphylococci, and some MRSA) * In combination with primaquine as an alternative in PCP * In combination with pyrimethamine as an alternative treatment for toxoplasmosis of brain * Prophylaxis of endocarditis in valvular patients allergic to penicillin **PK** * Oral or IV * Good penetration (including abscesses and bones)

Answer 35

* Potentially fatal pseudomembranous colitis (superinfection of C.difficile) * GI irritation (~ 20% people experience diarrhea) * Skin rashes (~10 %) * Neutropenia & impaired liver function

Answer 36

* Streptogramins * Given as a combination (act synergistically to have bactericidal action) * Long postantibiotic effect MOA * Bind to separate sites on 50S bacterial ribosome * Resistance is uncommon * Gram-positive cocci * Multi-drug resistant bacteria (streptococci, PRSP, MRSA, E.faecium) Clinical applications: Restricted to treatment of infections caused by drug- resistant Staphylococci or VRE PK * IV only * Penetrates macrophages & polymorphonucleocytes * Inhibitors of CYP 3A4

Answer 37

* Infusion related (venous irritation, arthralgia & myalgia) * GI effects * CNS effects (headache, pain)

Answer 38

* Bacteriostatic (cidal against streptococci & Clostridium perfringens) * recommended in the treatment of vancomycin-resistant strains of MRSA **MOA** * Inhibits formation of 70S initiation complex * Binds to unique site on 23S ribosomal RNA of 50S subunit * Most Gram-positive organisms (staphylococci, streptococci, enterococci, Corynebacterium, Listeria monocytogenes) * Moderate activity against mycobacterium tuberculosis **Resistance** * Decreased binding to target site * No cross-resistance with other drug classes **Clinical applications: **Treatment of multi-drug resistant infections **PK** * Oral (100% bioavailable) & IV * Widely distributed (including CSF) * Weak reversible inhibitor of MAO

Answer 39

Well tolerated for short admin. (GI, nausea, diarrhea, headaches, rash) Long-term admin. can cause: * Reversible myelosuppression * Optic & peripheral neuropathy, & lactic acidosis **Contraindications: **Reversible, nonselective inhibitor of MAO** -\> potential interaction w NE and 5HT drugs**

Answer 40

* Narrow spectrum macrocyclic antibiotic * Activity against Gram-positive aerobes and anaerobes especially Clostridia (C. difficile) * No activity against Gram-negative bacteria **MOA: ** Inhibits bacterial protein synthesis by binding to RNA polymerase **Clinical applications** * Treatment of C.difficile colitis (in adults) * Metro, vanco, and Fida all equally effective * Fidaxomicin is DOC for C. difficile in UK **PK**: When administered orally, systemic absorption is negligible but fecal concentrations are high

Answer 41

* Antibiotic belonging to monoxycarbolic acid class * Activity against most Gram-positive cocci, including MRSA and most streptococci (but not enterococci) * Only topical/intranasal agent with activity against MRSA **MOA: **Binds to bacterial isoleucyl transfer-RNA synthetase resulting in the inhibition of protein synthesis **Clinical applications** * Intranasal: Eradication of nasal colonization with MRSA in adult patients and healthcare workers * Topically: Treatment of impetigo or secondary infected traumatic skin lesions due to S.aureus or S.pyogenes

Answer 42

* Resistance develops if used for long periods of time * Mainly local and dermatologic effects (eg, burning, edema, tenderness, dry skin, pruritus)

Answer 43

* Fluoroquinolones * Sulfonamides * Trimethoprim

Answer 44

* First generation: Nalidixic Acid (quinolone) * Second generation: Ciprofloxacin * Third generation: Levofloxacin * Fourth generation: Gemifloxacin, Moxifloxacin Lower generations have excellent Gram-negative activity Higher generations have improved activity against Gram- positives

Answer 45

**MOA** * Broad spectrum, bactericidal drugs * Enter bacterium via porins * Inhibit bacterial DNA replication via interference with topoisomerase II (DNA gyrase) & IV **Resistance** * Emerged rapidly in 2nd generation (esp. C.jejuni, gonococci, Gram-positive cocci, P.aeruginosa & serratia). * Due to chromosomal mutations that: * encode subunits of DNA gyrase (eg, gonococci resistance) and topo IV * regulate expression of efflux pumps (eg, S.aureus, S.pneumonia, M.tuberculosis) * Cross-resistance between drugs occurs **PK** * Good oral bioavailability * Well distributed into all tissues and fluids (including bones) * Iron, zinc, calcium (divalent cations) interfere with absorption * Dosage adjustments required in renal dysfunction (except moxifloxacin)

Answer 46

Uncomplicated UTI’s

Answer 47

* Travelers diarrhea (E.coli) * P.aeruginosa (CF patients) * Prophylaxis against meningitis (alternative to ceftriaxone & rifampin)

Answer 48

* Prostatitis (E.coli) * STD’s (not syphilis) * Skin infections * Acute sinusitis, bronchitis, TB Community acquired pneumonia

Answer 49

Community acquired pneumonia

Answer 50

Levofloxacin, moxifloxacin & gemifloxacin (excellent activity against S.pneumoniae, H.influenzae & M.catarrhalis) Used in treatment of pneumonia when: * First-line agents have failed * In the presence of comorbidities * Patient is an inpatient

Answer 51

* GI distress * CNS, rash , photosensitivity * Connective tissue problems (avoid in pregnancy, nursing mother, under 18’s) – Black Box Warning! * **QT prolongation/Torsade** (moxifloxaci n, gemifloxacin, levofloxacin) -\> use Cotrimoxazole instead * High risk of causing superinfections (C.difficile, C albicans, streptococci Interactions * Theophylline, NSAIDs & corticosteroids = enhance toxicity of fluoroquinolones * 3rd & 4th generation = raise serum levels of warfarin, caffeine & cyclosporine Contraindications * Pregnancy & nursing mothers * Children \< 18y (unless benefits outweigh risks)

Answer 52

* Sulfamethoxazole, Sulfadiazine, Sulfasalazine * Structural analogs of p-aminobenzoic acid (PABA) * Bacteriostatic against Gram-positive & Gram-negative organisms **MOA** * Inhibit bacterial folic acid synthesis * Synthetic analogs of PABA (p-amino-benzoic acid) * Competitive inhibitors (& substrate) of dihydropteroate synthase **Resistance** * Altered dihydropteroate synthase * Decreased cellular permeability * Enhanced PABA production * Decreased intracellular drug accumulation **Clinical applications** * Topical agents (ocular, burn infections) * Oral agents (simple UTI’s) * Sulfasalazine (oral) = ulcerative colitis, enteritis, IBD **PK** * Oral or topical * Can accumulate in renal failure * Acetylated in liver. Can precipitate at neutral or acidic pH -\> kidney damage

Answer 53

* GI distress, fever, rashes (Stevens-Johnson syndrome), photosensitivity are common * Crystalluria (nephrotoxicity) * Hypersensitivity reactions * Hematopoietic disturbances (esp. patients with G6PD deficiency) * Kernicterus (in newborns and infants \<2 months); sulfonamides displace bilirubin -\> kernicterus **Drug interactions: **Warfarin, phenytoin and methotrexate can lead to increased plasma levels **Contraindications: **Newborns & infants \< 2 months (kernicterus) – drugs compete with bilirubin for binding sites on albumin

Answer 54

* Structurally similar to folic acid * Bacteriostatic against Gram-positive & Gram-negative organisms **MOA** * Potent inhibitor of bacterial dihydrofolate reductase * Inhibits purine, pyrimidine & amino acid synthesis **Clinical applications** * UTI’s * Bacterial prostatitis * Bacterial vaginitis **PK** * Mostly (80-90%) excreted unchanged through kidney * Reaches high concentrations in prostatic & vaginal fluids

Answer 55

* Antifolate effects (contraindicated in pregnancy) * Skin rash, pruritus

Answer 56

* Combination of trimethoprim & sulfamethoxazole * Bactericidal **MOA: ** * Synergistic: inhibition of sequential steps in tetrahydrofolic acid synthesis **Clinical applications** * **Uncomplicated UTI’s (drug of choice)** * PCP (drug of choice) * Nocardiosis (drug of choice) * Toxoplasmosis (alternative drug) * Respiratory, ear, sinus infections (H.influenzae, M.catarrhalis) **PK** * Oral admin. generally (can be given IV) * Well distributed (including CSF)

Answer 57

* Dermatologic (common) * GI * Hematologic (hemolytic anemia) * AIDS patients = higher incidence * Contraindicated in pregnancy (esp. 1st trimester)

Answer 58

* Antimicrobial, amebicide & antiprotozoal * Activity against anaerobic bacteria (including bacteroides & Clostridium) * Bactericidal **Clinical applications** * Typically indicated for diseases below diaphragm except brain abscess * C.difficile infections (drug of choice) * Anaerobic or mixed intra-abdominal infections * Vaginitis (trichomonas & bacterial vaginosis, G.vaginalis) * Brain abscesses * H.pylori eradication (in combination) **PK** * Oral, IV, rectal or topical * Wide distribution (including CSF) * Elimination = hepatic metabolism

Answer 59

* GI irritation, stomatitis, peripheral neuropathy (prolonged use) * Headache, dark coloration of urine * Leukopenia, dizziness, ataxia (rarer) * Opportunistic fungal infections * Disulfiram-like effect (avoid alcohol) * Use generally not advised in 1st trimester

Answer 60

* Bacteriostatic & bactericidal * Active against many Gram-positive and Gram-negative bacteria **MOA** * Reduction of nitrofurantoin by bacteria in the urine leads to formation of reactive intermediates that subsequently damage bacterial DNA * Slow emergence of resistance and no cross-resistance **PK: **Rapid elimination (only achieves adequate concentrations in urine)

Answer 61

**Adverse Effects** * Anorexia, nausea & vomiting. * Neuropathies, hemolytic anemia (G6PD deficient patients) **Contraindications** * Significant renal insufficiency * **Pregnancy at term (38-42 weeks) but safe prior to 38 w** * Infants \<1 month (risk of hemolytic anemia)

Antimicrobials Flashcards

(85 cards)