Antiinfectives Flashcards

1
Q

Selective Toxicity

A

Ability of a drug to injure invading microbes without injuing the cells of the host

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2
Q

Narrow-spectrum Vs. Broad Spectrum

A

Narrow-spectrum are active against only a few microorganisms.
Broad-spectrum antibiotics are active against a wide array of microbes.

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3
Q

Bactericidal vs Bacteriostatic

A

Bactericidal drugs kill bacteria

Bacteriostatic drugs only suppress growth

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4
Q

Mechanisms of Resistance

A

Drug efflux
Altered drug targets
Enzymatic inactivation of drugs

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5
Q

NDM-1 gene

A

Bacteria with NDM-1 gene are resistant to nearly all available antibiotics

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6
Q

Conjugation

A

A process in which DNA coding for drug resistance is transferred from one bacterium to another. An important method by which bacteria acquire resistance.

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7
Q

Relationship between antibiotic use and the emergence of drug-resistant microbes

A

Antibiotics do not cause the genetic changes that underlie resistance. Antibiotics PROMOTE the emergence of drug-resistant organisms by creating selection pressures that favor them.

Broad-spectrum antibiotics promote the emergence of resistance more often than do narrow-spectrum antibiotics.

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8
Q

4 ways to delay the emergence of resistance

A

1) preventing infections
2) diagnosing and treating infection effectively
3) using antimicrobial drugs wisely
4) preventing patient-to-patient transmission

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9
Q

Major force promoting the emergence of resistance

A

The food we eat.

Use of antibiotics in livestock.

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10
Q

Minimum inhibitory concentration

Minimum bactericidal concentraion

A

MIC- The lowest concentration needed to completely suppress bacterial growth. (Less than or equal to 4, lower is better).

MBC0 concentration that reduces the number of bacterial colonies by 99.9%.

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11
Q

Host defenses

A

Essential to the success of antimicrobial therapy.

Ex) immune system, phagocytic cells

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12
Q

Why do patients need to complete the entire prescribed course of antibiotics?

A

Symptoms may abate, but reoccurrence can occur.

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13
Q

When do we combine antibiotics?

A

1) Initial treatment of severe infection
2) Infection with more than one organism
3) treatment of TB
4) Treatment of an infection in which combination therapy can greatly enhance antibacterial effects.

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14
Q

Appropriate use of prophylactic antibiotics

A

1) Certain surgeries
2) Neutropenia
3) Recurrent UTIs
4) Pts at risk of bacterial endocarditis

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15
Q

Monitoring Antimicrobial Therapy

A

Clinical response- Frequency of monitoring is directly proportional to the severity of infection.
Reduction of fever, resolution of symptoms.

Lab Results- Drug levels to ensure levels are sufficient but not toxic. Peak and trough.

Success of therapy indicated by the disappearance of infectious organisms from posttreatment cultures. Cultures can become sterile within hours of treatment (UTI) or may take weeks (TB).

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16
Q

Penicillins

A

Weaken bacterial cell wall, causing cell lysis and death.

Gram-negative bacteria are resistant to penicillins that cannot penetrate the gram-negative cell envelope.

Safest antibiotic available.

Do not combine with aminoglycosides (gentamicin) in the same IV solution.

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17
Q

Beta-lactamases

A

Enzymes that inactivate penicillins.

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18
Q

Principal Adverse Effect of Penicillins

A

Allergic reaction- rash to anapylaxis
If patient is allergic to one penicillin they should be considered cross-allergic to all other penicillins. 1% chance of cross-allergy to cephalosporins.

Vancomycin, erythromycin, and clindamycin are safe and effective alternatives to penicillins.

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19
Q

Penicillin metabolism

A

Eliminated rapidly by the kidneys but can accumulate to harmful levels if renal function is severely impaired.

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20
Q

Penicillin G

A

Narrow antibacterial spectrum

Unstable in the stomach

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21
Q

Benzathine Penicillin G

A

Released very slowly after IM injection and thus produces prolonged antibacterial effects.

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22
Q

Penicillinase-resistant Penicillins

A

Nafcillin

Used primarily against penicillinase-producing strains of Staphylococcus aureaus.

23
Q

Broad-Spectrum Penicillins

A

Amoxicillin and Ampicillin have useful activity against gram-negative bacilli.

24
Q

Extended spectrum Penicillins

A

Ticarcilin

Useful against Pseudomonas aerguinosa

25
Q

Beta-lactase inhibitors

A

Clavulanic acid combined with certain penicillins to increase their activity against beta-lactamase-producing bacteria.

26
Q

Cephalosporins

A

Beta-lactam antibiotics that weaken the bacterial cell wall, causing lysis and death.
Major cause of resistance is production of beta-lactamases.

Four generations. Progressing these drugs show (1) increasing activity against gram-negative bacteria (2) increasing resistance to destruction by beta-lactamases (3) increasing ability to reach the CSF.

27
Q

Cephalosporin Metabolism/Excretion

A

Except for cefoperazone and ceftriaxone all cephalosporins are eliminated by the kidneys and must be given in reduced dosage to patients with renal impairment.

28
Q

Cephalosporin Adverse Effects

A

Allergic reaction. 1% cross-reactivity if allergic to PCNs.

Cefmetazole, cefoperazone, cefotetan, ceftriaxone- bleeding tendendices.

Cefazolin, cefmetazole, cefoperazone, cefotetan can cause disulfiram-like reaction.

29
Q

Carbapenems

A

Imipenem

Beta-lactam antibiotic, broader than those of practically all other antimicrobial drugs.

30
Q

Inhibitors of Cell Wall Synthesis

A

Vancyomycin, Telavancin, Aztreonam, Fosfomycin

Vanco- important but potentially toxic
Used for C. diff, MRSA, Serious infections caused by susceptible organisms in aptients allergic to PCNs.
Principal toxicity is renal failure. CHECK CR CLEARANCE.

31
Q

Tetracyclines

A

Broad-spectrum, bacteriostatic (inhibits protein synthesis)
Tetracyclines are first choice for a few infections: chlamydia, rickettsia (Rocky Mtn spotted fever), Helicobacter pylori (peptic ulcer disease), anthrax, Lyme disease, and mycoplasma pneumoniae.

Insoluble chelates with calcium, iron, mg, aluminum, zinc.

Do not administer with calcium, milk, iron, laxatives containing magnesium and most antacids.

Do not give with renal failure patients.

32
Q

Tetracycline SE/AR

A

Can stain developing teeth, do not give to pregnant women or children younger than 8 years old.

Because they are broad-spectrum can cause suprainfections- CDAD or candida albicans (overgrowth mouth, pharynx, vagina, bowel).

High dose can cause severe liver damage, especially in pregnant and postpartum women with renal impairment.

33
Q

Macrolides

A

Erythromycin, Clarithromycin, Azithromycin

Erythromycin- bacteriostatic inhibits bacterial protein synthesis. Spectrum similar to PCN G and can be used if pt has pcn allergy.
Generally very safe, if used with CYP3A4 increases risk of QT prolongation and sudden cardiac death.

34
Q

Bacteriostatic Inhibitors of Protein Synthesis

A

Clindamycin, Linezolid, Telithromycin, Dalfopristin/Quinupristin, Chloramphenicol, Tigecycline, Retapamulin and Mupirocin

Clindamycin is used primarily as an alternative to PCN for serious gram-positive anaerobic infections.

High incidence of CDAD with clinda.

Linezolid can suppress multidrug-resistant gram-positive pathogens, including VRE and MRSA.

35
Q

Aminoglycosides

A

Gentamycin, Tobramycin, Amikacin

Narrow-spectrum used primarily against aerobic gram-negative bacilli.
Disrupt protein synthesis cause rapid bacterial death.
Highly polar polycations- not absorbed from the GI tract, do not cross BBB, excreted rapidly by the kidneys.

Can cause irreversible injury to sensory cells of the inner ear resulting in hearing loss and disturbed balance. Risk of ototoxicity r/t persistantly elevated trough levels not peak levels.

Nephrotoxicity r/t total cumulative dose not trough levels.

Same dose can cause different plasma levels in differen patients; monitoring serum levels is common. Peak levels must be high enough to kill bacterial; trough levels must be low enough to minimize toxicity.

36
Q

Sulfonamides

A

Inhibit bacterial synthesis of folic acid. Used primarily for UTIs.

AE: Hypersensitivity from rash to Steven’s Johnson syndrome; hemolytic anemia; kernicterus; renal damage.

Bactrum preferred drug for UTIs and PCP for patients with AIDS and other immunodeficiency states.

37
Q

Urinary Tract Infections

A

Escherichia coli most common cause of uncomplicated, community acquired UTIs.

Except for pyelonephritis, most UTIs can be treated at home with oral therapy.

PCN, cephalosporins, and fluoroquinolones may be used for parenteral therapy of UTIs.

Prophylaxis can be acheieved with daily low doses of oral antibiotics (Bactrum).

Nitrofurantoin, Methenamine, Nalidixic acid, and cinoxacin 2nd choice drug.

38
Q

Tuberculosis

A

Most people remain asymptomatic, if left untreated, harbor dormant bacteria for life.
Symptomatic can result from reactiveation or person-to-person transmission.
Inadequate drug therapy caues drug resistance.

39
Q

Drug Therapy for TB

A

TB must always be treated with two (preferrably four) drugs.
6 months to 2 years.
Adherence with directly observed therapy combined with intermittent, rather than daily, dosing.
Methods to evaluate: sputum evaluation, clinical evaluation, chest radiographs.

First line drugs-
isoniazid- peripheral neuropathy by depleting Vit B6. Pyridoxin supplements.
rifamipin- increase metabolism of other drugs; oral contraceptives, warfarin, protease inhibitors, NNRTI. Hepatotoxic.
pyrazinamide- also hepatotoxic, liver injury.
ethambutol- optic neurotis.

40
Q

PPD

A

Purified protein derivative identifies people with latent TB
Zone of induration at the site 48-72 hours later.

Isoniazid taken for daily 9 months for latent TB.

41
Q

Fluoroquinolones

A

Ciprofloxacin

Broad-spectrum, wide variety of clinical applications.
Inhibit DNA gyrase and topoisomerase IV.

42
Q

Fluoroquinolone SE

A

Tendon rupture- discontinue

Phototoxicity- avoid sunlight, sunlamps, protective clothing, sunscreen.

Absorption can be reduced by cationic substances (milk, calcium, antacids).

43
Q

Metronidazole

A

Used to treat infections caused by obligate anaerobic bacteria (C. diff, Bacteroides fragilis).

44
Q

Systemic Fungal Drugs

A

Amphotericin B- binds to ergosterol in the fungal cell membrane, making it more permeable.
Oral is poorly absorbed, so IV is required.
Pretreatment with Benadryl plus analgesic can reduce mild symptoms.
Glucocorticoid for severe reactions.
Meperidine or dantrolene for rigors.

Causes renal injury- minimize kidney damage by infusing 1L of saline prior to infusing.

Do not combine with other nephrotoxic drugs (NSAIDS).

Itraconazole- cardiosuppression liver damage.

45
Q

Superficial Fungal Drugs

A

Can take up to 1 year to treat.

Topical clotrimazole.
Onychomycosis (fungal infection fingernails/toenails).

Oral therapy with terbinafine or itraconazole preferred treatment; vulvovaginal candidiasis can be treated with a single oral dose of fluconazole or short-term topical therapy (one 1200mg miconazole vaginal suppository).

46
Q

Drugs for Herpes Simplex Viruses and Varicella-Zoster Virus

A

Acyclovir- drug of choice. It suppresses viral reproduction by inhibiting viral DNA polymerase and by causing premature termination of viral DNA strand growth.

Acycolvir is eliminated unchanged by the kidneys. Renal damage can be minimized by infusing acyclovir slowly and by ensuring adequate hydration during and after the infusion.

47
Q

Drugs for Cytomegalovirus

A

Ganciclovir, Valganciclovir, Cidofovir, Foscarnet

CMV is a member of the herpesvirus group. Infection with CMV is very common, 50-85% of Americans 40 years and older harbor the virus.

Immunocompromised are at high risk for serious morbidity and even death.

48
Q

Drugs for Hepatitis C

A

Interferon Alfa, Ribavirin, Protease inhibitors, NS5A and NS5B Inhibitors.

HCV protease inhibitors prevent replicating HCV from progressing to its mature, infectious form.
Ribavarin is not effective against HCV infection when used alone, combined with interferon alfa.

HCV protease inhibitors greatly enhance the effects of interferon alfa plus ribacirin and thus are always combined with both of those drugs.

Triple therapy with peginterferon alfa plus ribavirin much more effective than dual therapy.

AE Interferon alfa- flu-like symptoms and severe depression

AE Ribavirin- hemolytic anemia and fetal death/malformation. Contraindicated during pregnancy.

No available vaccine.

49
Q

Drugs for Hepatitis B

A

Hep B can be treated with interferon A or a nucleoside analog, lamivudine. In rare cases can cause lactic acidosis and severe hepatomegaly.

Can be prevented by vaccine.

50
Q

Influenza

A

Vaccination is the best way to prevent influenza

Inactivated influenza vaccine administered IM or intradermal

Live attenuated administered by nasal spray

51
Q

Drugs for Influenza

A

Antiviral drugs: neuraminidase inhibitors and adamantanes.

Start within 48 hours.

Neuraminidase (oseltamivir and zanamivir) highly active against all current strains of influenza A & B. Current drug of choice for treatment and prophylaxis of influenza.

Adamantanes (amantadine and rimantadine) are not.

52
Q

Drugs for RSV

A

Ribavirin- broad spectrum antiviral aerosol and oral.

53
Q

Drugs of choice for Helminthiasis (Parasitic Worms)

A

Pyrantel Pamoate for pin worms.

54
Q

Drugs of choice for Protozoal Infections

A

Netronidazole for trichomoniasis, giardiasis, amebiasis.

Iodoquinol for asymptomatic amebiasis.

Warn against consuming alcohol r/o disulfiram-like reaction.