Clin Med - antimicrobials I (complete)

patient factors that affects antimicrobial selection:

allergy history

renal and hepatic function

cost, access, and adherence barriers

infection factors that affect antimicrobial selection

site of infection

severity of illness

pathogen factors that influence antimicrobial selection

likely pathogen

prior culture and resistance history

local antibiogram

context factors that influence antimicrobial selection

community-acquired vs. healthcare-associated infection

operational factors what influence antimicrobial selection

route of therapy

key steps in pathogen identification

1. collect cultures from the suspected site of infection when

appropriate

2. obtain cultures before antibiotics when feasible

3. use gram stain to classify bacteria by cell wall structure and morphology

4. use culture results to identify the organism

5. use susceptibility testing to guide targeted therapy

6. narrow therapy when possible based on result

characteristics of gram-positive bacteria

thick peptidoglycan cell wall

no outer membrane

common examples: Staphylococcus, streptococcus, enterococcus

characteristics of gram-negative bacteria

thin peptidoglycan cell wall

outer lipopolysaccharide membrane

prophylactic therapy

prevents infection before it occurs

empiric therapy

initial therapy before organism is confirmed

based on likely pathogens, infection site, severity, and resistance risk

targeted therapy

narrowed treatment once organism and susceptibilities are known

suppressive therapy

long-term therapy when infection risk cannot be fully eliminated

core stewardship actions for abx

use antibiotics only when bacterial infection is likely

choose the narrowest effective therapy

reassess once culture data return

avoid unnecessarily long treatment courses

narrow-spectrum therapy

targets a smaller group of organisms

preferred when the pathogen is known

lower resistance and adverse-effect pressure

broad spectrum therapy

covers a wide range of organisms

useful for severe infection or uncertain pathogen

higher risk of collateral damage

clinical principle of narrow vs. broad coverage

start broad when needed and narrow when possible

bactericidal antibiotics

kill bacteria directly

often preferred for severe or deep-seated infections

bacteriostatic abx

inhibit bacterial growth

rely partly on host immune response

examples of bactericidal abx

penicillins

cephalosporins

carbapenems

aminoglycosides

fluoroquinolones

vancomycin

examples of bacteriostatic abx

macrolides

tetracyclines

sulfonamides

clindamycin

linezolid

time dependent killing pattern

efficacy depends on time above the minimum inhibitory

aka: how long can we give at MIC or above MIC

concentration dependent killing pattern

efficacy depends on achieving a high peak concentration

exposure-dependent killing pattern

efficacy depends on total drug exposure over time

common resistance mechanisms

enzymatic drug destruction

altered drug target

reduced antibiotic entry

increased antibiotic removal

metabolic bypass

examples of enzymatic drug destruction mechanisms

beta-lactamases

carbapenemases

examples of altered drug target mechanism

changed penicillin-binding proteins

altered ribosomal binding sites

examples of the reduced antibiotic entry mechanism

outer membrane changes

porin loss

examples of increased antibiotic removal mechanisms

efflux pumps

examples of metabolic bypass mechanisms

altenative pathway avoids drug effect

risk factors for resistant infections

recent abx exposure

recent or prolonged hospitalization

residence in a long-term facility

prior resistant organism or abnormal culture history

immunosuppression

indwelling lines, drains, or urinary catheters

hemodialysis

recurrent infection or treatment failure

Key questions to ask for abx allergies

what abx caused the reaction?

what symptoms occurred?

how long ago did it happen?

was treatment required?

has the patient tolerated related abx since?

high-risk allergy features

anaphylaxis

angioedema

respiratory compromise

severe cutaneous reaction

organ injury

clinical principle of abx allergies

avoid the allergy label becoming broader than the true risk

why does penicillin allergy and beta-lactam cross reactivity matter

penicillin allergy is commonly reported

many reported allergies are not true IgE-mediated allergies

Avoiding all beta-lactams may lead to broader or less effective therapy

cross-reactivity considerations for PCN and beta-lactams

risk depends partly on similar side chains

1st generation cephalosporins have more overlap with some PCNs

later generation cephalosporins are often tolerated in low-risk histories

severe delayed reaction require avoidance and specialist input

clinical principle of PCN allergy and beta-lactam cross-reactivity

clarify the reaction before excluding an entire drug class

major MOAs of abx

cell wall synthesis inhibitors

protein synthesis inhibitors

DNA/RNA or metabolic pathway inhibitors

cell wall synthesis inhibitor abx

PCNs

cephalosporins

carbapenems

gylcopeptides

protein synthesis inhibitors

macrolides

tetracyclines

aminoglycosides

lincosamides

oxazolidinones

DNA/RNA or metabolic pathway inhibitors abx

fluoroquinolones

Rifamycins

sulfonamides

metronidazole

key features of cell wall inhibitors abx

generally bactericidal

most useful for gram-positive organisms, but some have broad gram-negative activity

do not cover atypical bacteria

allergy history and renal function are major considerations

beta-lactam abx

PCNs

cephalosporins

carbapenems

monobactams

shared characteristics of beta-lactam abxs

bactericidal

inhibit bacterial cell wall synthesis

time-dependent killing

commonly require renal dose adjustment

allergy hx is clinically important

what are beta-lactamases

bacterial enzymes that inactivate beta-lactam abx

common combinations for beta-lactamase inhibitors

amoxicillin/clavulanate

ampicillin/sulbactam

piperacillin/tazobactam

ceftazidime/avibactam

meropenem/vaborbactam

imipenem/cilastatin/relebactam

clinical role of beta-lactamase inhibitors

expands coverage against beta-lactamase producing organisms

useful for polymicrobial infections

important for some resistant gram-negative infections

major subgroups of PCNs

natural PCNs

Anti-staphylococcal PCNs

Aminopenicillins

extended-spectrum PCNs

natural PCNs

Penicillin G

Penicillin VK

key clinical themes of penicillins

strong gram-positive activity

some agents add gram-negative or anaerobic coverage

no atypical coverage

allergy hx is a major consideration

clinical use of natural PCNs

Streptococcal pharyngitis

Syphilis

Dental/oral infections

rheumatic fever prophylaxis

key limitations of natural penicillins

not stable against beta-lactamases

limited gram-negative coverage

no atypical coverage

allergy hx is a major consideration

anti-staphylococcal penicillins

Nafcillin - IV

Oxacillin - IV

Dicloxacillin - PO

clinical role of anti-staphylococcal PCNs

methicillin-susceptible S. aureus or MSSA

Methicillin-susceptible S. epidermidis or MSSE

skin and soft tissue infections

bacteremia, endocarditis, or osteomyelitis when MSSA is confirmed

key limitations of anti-staphylococcal PCNs

do not cover MRSA

limited gram-negative coverage

no atypical coverage

allergy hx is a major consideration

aminopenicillin examples

amoxicillin - PO

Ampicillin - PO or IV

clinical role of aminopenicillins

streptococcal infections

enterococcus infections

otitis media

sinusitis

respiratory tract infections

listeria meningitis, especially ampicillin

key limitations of aminopenicillins

not stabe against beta-lactamases

limited S. aureus coverage unless paired with a beta-lactamase inhibitor

no atypical coverage

rash may occur, especially with epstein-barr virus infectious mononucleosis

examples of aminopenicillins + beta-lactamase inhibitors

amoxicillin/clavulanate - PO

ampicillin/sulbactam - IV or IM

clinical role of aminopenicillins + beta-lactamase inhibitors

repsiratory infections when beta-lactamase coverage is needed

bite wounds

dental/oral infections

aspiration pneumonia

polymicrobial skin and soft tissue infections

some intra-abdominal or pelvic infections

key limitations to aminopenicillins + beta-lactamase inhibitors

broader than amoxicillin or ampicillin alone

more GI adverse effects, especially diarrhea

no atypical coverage

allergy hx remains important

class for amoxicillin/clavulanate

aminopenicillin + beta-lactamase inhibitor

MOA for amoxicillin/clavulanate

inhibits bacterial cell wall synthesis

clavulanate inhibits beta-lactamase enzymes

indications for amoxicillin/clavulanate

acute bacterial sinusitis

otitis media

bite wounds

dental/oral infections

polymicrobial skin and soft tissue infections

contraindications for amoxicillin/clavulanate

serious PCN allergy

prior cholestatic jaundice or hepatic dysfunction with amoxicillin/clavulanate

barriers/limitations of amoxicillin/clavulanate

GI intolerance

diarrhea

twice-daily dosing

allergy hx

drug interactions of amoxicillin/clavulanate

warfarin may have increased anticoagulant effect, allopurinol may increase rash risk

dosing for amoxicillin/clavulanate

common adult dose: 875/125 mg PO twice daily

dose varies by infection type and renal function

monitoring for amoxicillin/clavulanate

clinical response, rash, diarrhea, hepatic symptoms, renal function when appropriate

patient education for amoxicillin/clavulanate

take with food

complete the prescribed course

report severe diarrhea or rash

do not use leftover abx

examples of extended-spectrum PCNs

piperacillin/tazobactam - IV

Piperacillin alone - IV, rarely used alone

clinical role of extended-spectrum PCNs

broad gram-negative coverage

pseudomonas coverage

anaerobic coverage when paired with tazobactam

polymicrobial infections

intra-abdominal infections

hospital-acquired or ventilator-associated pneumonia

severe skin and soft tissue infections when broad coverage is needed

key limitations of extended-spectrum PCNs

IV only

broad-spectrum therapy with resistance and C. difficile risk

requires renal dose adjustment

allergy hx is important

does not cover MRSA

drug class of piperacillin/tazobactam

extended-spectrum PCN + beta-lactamase inhibitor

MOA of piperacillin/tazobactam

inhibits bacterial cell wall synthesis

tazobactam inhibits beta-lactamase enzymes

indications for piperacillin/tazobactam

severe polymicrobial infections

intra-abdominal infections

hospital acquired pneumonia

ventilator associated pneumonia

complicated skin/soft tissue infections

suspected pseudomonas infections

contraindications for piperacillin/tazobactam

serious penicillin allergy

barriers/limitations for piperacillin/tazobactam

IV only

broad spectrum resistance pressure

C. difficile risk

renal dose adjustment

no MRSA coverage

drug interactions for piperacillin/tazobactam

may increase bleeding risk with anticoagulants

increased nephrotoxicity risk when combined with vancomycin

dosing for piperacillin/tazobactam

common adult dose: 3.375-4.5 g IV every 6-8 hours

dose varies by infection, severity, infusion strategy, and renal function

monitoring for piperacillin/tazobactam

renal function

clinical response

culture results

diarrhea

hypersensitivity reactions

patient education for piperacillin/tazobactam

explain need for IV therapy

report rash or severe diarrhea

therapy may be narrowed once cultures return

shared features of the cephalosporins

beta-lactam abx

bactericidal

time-dependent killing

generally tolerated well

most require renal dose adjustment

no reliable enterococcus coverage

generation patterns for cephalosporins

earlier generations: more gram-positive coverage

later generations: more gram-negative coverage

some later agents add psuedomonas or MRSA coverage

examples of 1st generation cephalosporins

cefazolin - IV

cephalexin - PO

Cefadroxil - PO

clinical role of 1st generation cephalosporins

methicillin-susceptible Staphylococcus aureus or MSSA

streptococcal infections

skin and soft tissue infections

surgical prophylaxis, especially cefazolin

key limitations of 1st generation cephalosporins

limited gram-negative coverage

no MRSA coverage

no enterococcus coverage

no atypical coverage

examples of 2nd gen cephalosporins

Cefuroxime - PO or IV

Cefoxitin - IV

Cefotetan - IV

clinical role of 2nd gen cephalosporins

respiratory tract infections

otitis media and sinusitis

haemophilus influenzae and moraxella catarrhalis coverage

intra-abdominal or pelvic infections when anaerobic coverage is needed

surgical prophylaxis for selected abdominal or gynecological procedures

key limitations of 2nd gen cephalosporins

less gram-positive activity than 1st generation

no MRSA coverage

no enterococcus coverage

no atypical coverage

examples of 3rd gen cephalosporins

ceftriaxone - IV or IM

cefotaxime - IV or IM

Ceftazidime - IV or IM

Cefdinir, cefpodoxime, cefixime - PO

clinical role of 3rd gen cephalosporins

expanded gram-negative coverage

community-acquired pneumonia

pyelonephritis and complicated UTI

gonorrhea, especially ceftriaxone

meningitis, especially ceftriaxone or cefotaxime

pseudomonas coverage only ceftazidime

key limitations of 3rd gen cephalosporins

less MSSA activity than 1st gen agents

no enterococcus coverage

no atypical coverage

most do not cover pseudomonas

ceftriaxone is avoided in neonates

drug class of ceftriaxone

3rd generation cephalosporin

MOA for ceftriaxone

inhibits bacterial cell wall synthesis by binding penicillin-binding proteins

indications for ceftriaxone

community-acquired pneumonia

gonorrhea

meningitis

pyelonephritis

sepsis

selected intra-abdominal infections when combines with anaerobic coverage

contraindications of ceftriaxone

serious cephalosporin allergy

neonates with hyperbilirubineremia

neonates receiving calcium-containing IV solutions

barriers/limitations of ceftriaxone

IV or IM only

no pseudomonas coverage

no enterococcus coverage

no atypical coverage

drug interactions of ceftriaxone

calcium-containing IV solutions in neonates

possible anticoagulant effect with warfarin

dosing for ceftriaxone

common adult dose: 1-2g IV/IM once daily

meningitis dosing commonly 2g IV every 12 hours

monitoring for ceftriaxone

clinical response

allergy symptoms

diarrhea

CBC and hepatic/renal function with prolonged therapy