Clin Med - Antimicrobials II (complete)

when are beta-lactams not appropriate

serious beta-lactam allergy

resistant organisms

poor tissue penetration for the suspected infection

when is specific coverage needed

atypical pathogens

MRSA

Anaerobes

Resistant gram-negative organisms

mycobacterial infections

patient factors that affect drug selection

pregnancy status

renal or hepatic dysfunction

QT prolongation risk

drug interactions

history of C. difficile

aerobic bacteria

grow in presence of oxygen

common in respiratory, urinary, bloodstream, and may skin infections

anaerobic bacteria

grow best in low-oxygen environments

common in abscesses, aspiration, oral/dental infection, intra-abdominal infections, pelvic infections and diabetic foot infections

clinical cues for anaerobes

foul-smelling drainage

abscess formation

necrotic tissue

infection near mucosal surfaces

aspiration or bowel perforation

common aminoglycoside agents

gentamycin

tobramycin

amikacin

mechanism

inhibit bacterial protein synthesis at the 30s ribsomal subunit

bactericidal activity

concentration-dependent killing

clinical role of aminoglycosides

serious aerobic gram-negative infection

pseudomonas coverage

often used in combination therapy for severe infections

limited routine use because of toxicity

important limitation of aminoglycosides

poor activity against anaerobes

poor oral absorption

requires parenteral dosing for systemic infection

high-yield toxicities for aminoglycosides

nephrotoxicity

ototoxicity

vestibular toxicity

neuromuscular blockade

risk factors for toxicity with aminoglycosides

pre-existing renal impairment

older age

dehydration

prolonged therapy

high trough concentrations

concomitant nephrotoxic drugs

monitoring for aminoglycosides

baseline and ongoing renal function

drug levels when indicated

hearing or balance symptoms

neuromuscular weakness in high-risk patients

patient counseling for amnoglycosides

report decreased hearing, ringing in the ears, dizziness, or balance problems

report decreased urination or new weakness

class/MOA of gentamicin

aminoglycoside; inhibits30S ribosomal subunit; bactericidal; concentration-dependent killing

best clinical uses for gentamicin

serious aerobic gram-negative infections

complicated UTI or pyelonephritis

gram-negative sepsis

selected pseudomonas infections

synergy in select endocarditis regimens

major do not miss risks for gentamicin

nephrotoxicity

ototoxicity: hearing loss, tinnitus, vestibular toxicity

neuromuscular blockade

higher risk with renal impairment or prolonged therapy

key interactions/barriers for gentamicin

IV or IM for systemic infections

poor anaerobic coverage

increased nephrotoxicity with vancomycin, amphotericin B, NSAIDs IV contrast, calcineurin inhibitors

increased ototoxicity risk with loop diuretics

use caution in myasthenia gravis

monitoring/counseling for gentamicin

- monitor renal function, urine output, and drug levels when indicated

- assess for hearing changes tinnitus, dizziness, vertigo, or weakness

- counsel patients to report decreased urination, ringing in the ears, balance problems, or new weakness

fluoroquinolones common agents

ciprofloxacin

levofloxacin

moxifloxacin

mechanism for fluoroquinolones

inhibit bacterial DNA replication

target DNA gyrase and topoisomerase IV

bactericidal

concentration-dependent killing

clinical role of fluoroquinolones

gram-negative infections

complicated UTI and pyelonephritis

some respiratory infections

pseudomonas coverage with selected agents

important limitations of fluoroquinolones

broad use has decrease because of resistance and safety concerns

avoid when safer, narrower options are appropriate

high-yield toxicities for fluoroquinolones

tendinitis and tendon rupture

QT prolongation

CNS effects

Peripheral neuropathy

dysglycemia

increased risk of aortic aneurysm/dissection in high-risk patients

best clinical association for ciprofloxacin

gram-negative infections

complicated UTI or pyelonephritis

GI infections

Pseudomonas

key limitation of ciprofloxacin

weak streptococcus pneumoniae coverage; not preferred for community-acquired pneumonia

best clinical association for levofloxacin

respiratory infections

complicated UTI or pyelonephritis

selected pseudomonas infections

key limitation of levofloxacin

QT risk

tendon risk

resistance concerns

best clinical association for moxifloxacin

respiratory infections

some anaerobic coverage

key limitation of moxifloxacin

poor urinary concerntration; not preferred for UTI

major adverse effects with fluoroquinolones

tendinitis and tendon rupture

peripheral neuropathy

CNS effect: confusion, agitation, insomnia, seizures

QT prolongation

dysglycemia

photosensitivity

GI upset and C. difficile risk

clinical principle of fluoroquinolone tx

use only when benefits outweigh risks

avoid when safer, narrower options are appropriate

high-risk patients for fluoroquinolone therapy

older adults

transplant recipients

patients taking corticosteroids

patients with seizure disorders

patients with prolonged QT or arrhythmia risk

patients with known or high-risk aortic aneurysm/dissection

patients with significant renal impairment

class/MOA for levofloxacin

fluoroquinolone; inhibits DNA. gyrase/topoisomerase IV; bactericidal

best clinical uses for levofloxacin

community-acquired pneumonia when appropriate

complicated UTI or pyelonephritis

selected gram-negative infections

selected pseudomonas infections

major do not miss risks of fluoroquinolones

tendinitis and tendon rupture

peripheral neuropathy

CNS effects: confusion, agitation, seizures

QT prolongation

can worsen myasthenia gravis

caution with aortic aneurysm/dissection risk

key interaction/barriers for levofloxacin

avoid taking with antacids, iron, zinc, calcium, or sucralfate

increased tendon risk with corticosteroids

QT risk with other QT-prolonging drugs

broad-spectrum drug; avoid when safer narrower options work

monitoring/counseling for levofloxacin

monitor renal function and clinical response

watch for tendon pain, neuropathy, mental status changes, palpitations, severe diarrhea

counsel patients to separate from mineral supplements and report tendon or nerve symptoms promptly

macrolides common agents

azithromycin

clarithromycin

erythromycin

mechanism of action for macrolides

inhibit bacterial protein synthesis at the 50S subunit

generally baceriostatic

clinical role of macrolides

atypical respiratory pathogens

community-acquired pneumonia in selected patients

pertussis

chlamydia in pregnancy

some STIs

MAC prophylaxis or treatment in selected immunocompromised patients

important limitations of macrolides

increasing respiratory resistance

QT prolongation risk

GI intolerance, especially erythromycin

drug interactions, especially clarithromycin and erythromycin

clinical pearl for macrolides

azithromycin has fewer CYP drug interactions than clarithromycin or erythromycin

azithromycin best clinical uses

atypical respiratory infections

community-acquired pneuomonia in selected patients

pertussis treatment or post-exposure prophylaxis

chlamydia in pregnancy

major do not miss risk for azithromycin

QT prolongation and rare torsades de pointes

GI upset

hepatotoxicity, rare but serious

can worsen myasthenia gravis

key interactions/barriers to azithromycin tx

fewer CYP interaction than clarithromycin or erythromycin

caution with other QT prolonging drugs

increasing resistance limits use for some respiratory infections

use only when bacterial infection is suspected or confirmed

monitoring/counseling for azithromycin

monitor clinical response and diarrhea

consider QT prolongation risk in high-risk patients

counsel patients to report palpitations, syncope, severe diarrhea, jaundice, dark urine, or worsening muscle weakness

common tetracycline agents

doxycycline

minocycline

tetracycline

mechanism of action for tetracyclines

inhibit bacterial protein synthesis at the 30S ribosomal subunit

generally bacteriostatic

clinical role with tetracyclines

atypical respiratory infections

tick-borne infections

chlamydia

acne and rosacea

community-acquired MRSA skin infections

malaria prophylaxis, especially doxycycline

important limitations of doxycycline

avoid in pregnancy when possible

avoid in young children when alternative are appropriate

photosensitivity

GI irritation and esophagitis

absorption reduced by calcium, iron, magnesium, aluminum and zinc

high yield clinical uses for doxycycline

atypical respiratory infections

tick-borne infections

chlamydia

acne and rosacea

community-acquired MRSA skin infection

malaria prophylaxis

what is doxycycline commonly used

oral option

broad outpatient utility

good tissue penetration

covers organisms beta-lactams miss

classic patient counseling for doxycycline

photosensitivity: use sunscreen and avoid excess sun exposure

esophagitis risk: take with water and remain upright

separate from antacids, iron, calcium, magnesium, zinc, and dairy when possible

clinical caution in doxycycline treatment

avoid in pregnancy when possible

avoid in young children when alternatives are appropriate

use benefits vs. risk when treating serious infections such as tick-borne diseases

major do not miss risks with doxycycline

photosensitivity

esophagitis

GI upset

tooth discoloration and effect on bone growth with prolonged exposure in young children

avoid in pregnancy when possible

key monitoring/counseling for doxycycline

monitor clinical response and GI tolerance

take with a full glass of water

remain upright after taking

separate from mineral supplements and antacids

use sun protection

primary lincosamide agent

clindamycin

mechanism of action for lincosamides

inhibits bacterial protein synthesis at the 50S ribosomal subunit

generally bacteriostatic

clinical role of lincosamides

gram-positive cocci coverage

anaerobic coverage, especially oral/upper respiratory sources

skin and soft tissue infections

dental/oral infections

aspiration-related infections in selected cases

toin suppression in severe toxin-mediated infections

important limitations for lincosamides

significant C. difficile risk

resistance varies by region and organism

does not cover aerobic gram-negative organisms

clinical pearl for clindamycin

can be useful but it is not a benign antibiotic

coverage of clindamycin

anaerobes, toxin suppression, and C. difficile risk

where is clindamycin useful

skin and soft tissue infections

dental/oral infections

anaerobic infections above the diaphragm

aspiration-related infection in selected patients

community-acquired MRSA coverage when susceptible

toxin suppression role of clindamycin

can decrease toxin production in selected severe infections

clindamycin is often used as adjunctive therapy for:

invasive group A strep

necrotizing fasciitis

clostridial myonecrosis

major limitation of clindamycin

high association with antibiotic-associated diarrhea

high association with C. difficile infection

clinical pearl for clindamycin treatment

new severe diarrhea after clindamycin should raise concern for C. difficile

common oxazolidinones agents

linezolid

tedizolid

mechanism of action for oxazolidinones

inhibit bacterial protein synthesis at the 50S subunit

generally bacteriostatic

bactericidal against some streptococci

clinical role of oxazolidinones

resistant gram-positive infections

MRSA

VRE

Pneumonia caused by susceptible gram-positive organisms

complicated skin and soft tissue infections

advantages of oxazolidinones

excellent oral bioavailability

oral and IV dosing achieve similar systemic exposure

useful when resistant gram-positive coverage is needed

limitation of oxazolidinones

no gram-negative coverage

myelosuppression, especially thrombocytopenia

serotonin syndrome risk

peripheral and optic neuropathy with prolonged use

drug class/MOA of linezolid

oxazolidinone; inhibits 50S ribosomal subunit; generally bacteriostatic

best clinical use for linezolid

MRSA infections

VRE infections

Resistant gram-positive pneumonia

complicated skin and soft tissue infections

oral step-down option when appropriate

major do not risks for linezolid

thrombocytopenia and myelosuppression

serotonin syndrome

peripheral neuropathy with prolonged use

optic neuropathy with prolonged use

lactic acidosis, rare but serious

key interactions/barriers of linezolid

no gram-negative coverage

interacts with serotonergic drugs including SSRIs, SNRIs, TCAs, MAOIs, tramadol, and some migraine medications

cost and insurance coverage may be barriers

toxicity risk increases with prolonged therapy

monitoring/counseling for linezolid

monitor CBC, especially platelets

monitor for serotonin syndrome: agitation, confusion, fever, tremor, rigidity, diarrhea

monitor for vision changes or neuropathy symptoms with prolonged therapy

counsel patients to report unusual bruising, bleeding, numbness, tingling, or vision changes

common agents of sulfonamides & SMX

sulfamethoxazole/trimethoprim or SMX-TMP

sulfasalazine

silver sulfadiazine

mechanism of action for sulfonamides & SMX

blocks bacterial folate synthesis

sulfamethoxazole inhibits dihydropteroate synthase

trimethoprim inhibits dihydrofolate reductase

combination is usually bactericidal

clinical role of sulfonamides & SMX

uncomplicated UTI

community-acquired MRSA skin infections

Pneumocystitis jjrovecii pneumonia treatment or prophylaxis

nocardia infections

some opportunistic infections

high yield limitations of sulfonamides & SMX

rash and severe cutaneous reactions

hyperkalemia

renal effects

bone marrow suppression

avoid in patient with serious sulfa allergy

classic adverse effect of SMX-TMP

rash

stevens-johnson syndrome/toxic epidermal necrolysis

bone marrow suppression

renal dysfunction or increased creatinine

high-yield interaction patterns of SMX-TMP

increased bleeding risk with warfarin

increased hyperkalemia with ACE inhibitors, ARBs, and sprinolactone

increased marrow suppression risk with methotrexate

avoid in serious sulfa allergy

metronidazole drug class/MOA

nitroimidazole; causes DNA damage in anaerobic bacteria and certain protozoa

best clinical uses for metronidazole

anaerobic infections, especially intra-abdominal or pelvic sources

bacterial vaginosis

trichomoniasis

giardiasis

amebiasis

combination therapy for mixed aerobic/anaerobic infections

major do not miss risks for metronidazole

metallic taste and GI upset

peripheral neuropathy with prolonged use

rare CNS toxicity or seizures

alcohol counseling is traditionally emphasized

use caution with significant hepatic impairment

key interactions/barriers of metronidazole

may increase warfarin effect and bleeding risk

avoid alcohol during therapy and for at least 3 days after completion

does not cover aerobic gram-positive or aerobic gram-negative organisms

often paired with another antibiotic for polymicrobial infection

monitoring/counseling for metronidazole

monitor clinical response and GI intolerance

watch for numbness, tingling, weakness, or neurologic symptoms with prolonged therapy

counsel patients about metallic taste and alcohol avoidance

for trichomoniasis, sexual partners also need treatment

common agents of rifamycins

rifampin

rifabutin

rifapentine

mechanisms of action for rifamycins

inhibit bacterial RNA polymerase

block RNA synthesis

bactericidal

clinical role of rifamycins

tuberculosis treatment regimens

latent TB infection regimens

selected nontuberculosis mycobacterial infections

adjunctive therapy in prosthetic device or hardware associated infections

high-yield limitations of rifamycins

major drug interaction risk

hepatotoxicity risk

orange discoloration of body fluids

resistance develops quickly if used alone for active TB

clinical pearl for rifamycins

powerful TB drugs, but are also among the most interaction heavy antibiotics

best clinical uses for rifampin

active tuberculosis as part of combination therapy

latent TB infection regimens

selected nontuberculosis mycobacterial infections

adjunctive therapy for selected prosthetic device or hardware-associated infections

major do not miss risks of rifampin

hepatotoxicity

major drug interactions due to enzyme induction

orange discoloration of urine, sweat, saliva, and tears

resistance develops quickly if used alone for active TB

key interactions/barriers for rifampin

can reduce effectiveness of oral contraceptives

can reduce warfarin effect

interacts with many antiretrovirals, azole antifungals, anticonvulsants, and immunosuppressants

adherence is critical in TB therapy

monitoring/counseling for rifampin

monitor liver function when indicated

review medication list carefully before starting

counsel that orange body fluids are expected

counsel patient using hormonal contraception to use a backup method

do not stop TB therapy early without medical guidance

two major clinical categories of TB

latent TB infection

active TB disease

latent TB infection

patient is infected but asymptomatic and not contagious