Therapeutics III: Introduction to Infectious Disease

What is the difference between empiric and targeted/definitive therapy?

Empiric: patient has general signs/symptoms of infection, so we use broad therapy to cover all potential pathogens

Targeted/Definitive: pathogen and susceptibilities are known and thus are able to narrow spectrum to best option for the pathogen

In targeted or definitive therapy, ______ should be clearly defined.

Duration

How long does it usually take to get cultures and full susceptibility information?

it takes about 2-3 days to get cultures and susceptibility information. Cultures need to be on the agar plate for 24 hours and then it takes 2-3 days to get known susceptibilities

Do you always get results from cultures?

No, you might not always get results since it is not always possible for cultures to reveal susceptibilities

What are the bacterial skin flora that are often considered contaminants in cultures?

S. epidermis, bacillus rod, corynebacterium (diphtheroids)

Which bacterias are aerobic, gram positive and cocci shaped?

s. aureus, s. epidermis

Where does s. aureus tend to colonize? and what type of infections do we see?

skin, upper respiratory tract; leukocytosis, bacteremia, endocarditis, and nosocomial pneumonias

Where does s. epidermis tend to colonize? and what type of infections do we see?

skin flora contaminant, blood; leukocytosis, pneumonia

What type of bacteria is aerobic, gram positive, and pairs-shapeed?

s. pneumoniae

Where does s. pneumoniae tend to colonize? and what type of infections do we see?

upper respiratory tract; pneumonia (most common), MRSA, sepsis, URIs/otic infections, meningitis

What types of bacteria are aerobic, gram positive, and chains-shaped?

viridans streptococcus, s. pyogenes (GAS), s. agalactiae (GBS)

Where does viridans streptococcus tend to colonize? and what type of infections do we see?

mouth; bacteremia, endocarditis

Where does s. pyogenes (GAS) tend to colonize? and what type of infections do we see?

skin, upper respiratory tract, stomach; skin infection, strep throat, rheumatic fever, post-infectious glomerulonephritis, toxic shock syndrome (when in blood)

Where does s. agalactiae (GBS) tend to colonize? and what type of infections do we see?

female reproductive tract; neonatal infections, meningitis, bacteremia, pneumonia

What type of bacteria is aerobic, gram positive, and pairs/chains shaped?

enterococcus spp

Where does enterococcus spp tend to colonize? and what type of infections do we see?

ileum, duodenum/jejunum, large intestine; UTIs, intraabdominal infections, endocarditis (3rd most common cause), VRE

What are the two types of enterococcus spp?

enterococcus faecalis (more common, less resistant), enterococcus faecium (less common, more resistant)

What type of bacteria is aerobic, gram negative, and diplococci shaped?

neisseria spp

Where does neisseria spp tend to colonize? and what type of infections do we see?

upper respiratory tract; traveler's diarrhea, meningitis, gonorrhea

What types of bacteria are aerobic, gram negative and coccobacilli (oval) shaped?

haemophilus influenzae, moraxella catarrhalis

Where does haemophilus influenzae tend to colonize? and what type of infections do we see?

upper respiratory tract; pnuemonia, URIs, meningitis (rare)

Where does moraxella catarrhalis tend to colonize? and what type of infections do we see?

upper respiratory tract; URIs in smokers/COPD exacerbations, otitis media

What types of bacteria are aerobic, gram negative, and rod-shaped?

E. coli, klebsiella spp, enterobacter spp, salmonella/shigella/campylobacter/vibrio spp, proteus spp, pseudomonas aeruginosa

Where does E. coli tend to colonize? and what type of infections do we see?

ileum, duodenum/jejunum, large intestine; acute intestinal illness, food poisoning (most common), intraabdominal infections, UTIs

Where does klebsiella spp tend to colonize? and what type of infections do we see?

GI tract; pneumonia, UTIs

Where does enterobacter spp tend to colonize? and what type of infections do we see?

GI tract; UTIs, intraabdominal infections, nosocomial pneumonias

Where does salmonella/shigella/campylobacter/vibrio spp tend to colonize? and what type of infections do we see?

GI tract; acquired intestinal illness through contaminated food/water

Where does proteus spp tend to colonize? and what type of infections do we see?

GI tract; acquired intestinal illness through contaminated food/water

Where does pseudomonas aeruginosa tend to colonize? and what type of infections do we see?

GI tract, colonization in chronic lung diseases; respiratory infections, blood stream pathogen, nosocomial infections

What types of bacteria are neither gram positive or gram negative, atypical, and have a really small cocci form?

chlamydia pneumoniae, chlamydia trachomatis, mycoplasma pneumoniae, legionella pneumophilia

Where does chlamydia pneumoniae tend to colonize? and what type of infections do we see?

upper respiratory tract; community acquired pneumonia (walking pneumonia)

Where does chlamydia trachomatis tend to colonize? and what type of infections do we see?

vaginal, oral, anal areas; sexually transmitted infection

Where does mycoplasma pneumoniae tend to colonize? and what type of infections do we see?

upper respiratory tract; community acquired pneumonia

Where does legionella pneumophilia tend to colonize? and what type of infections do we see?

upper respiratory tract; severe pneumonia (spread through water features and ventilation systems)

What type of bacteria is gram positive, anaerobic, and rod-shaped?

clostridoides difficile

Where does clostridoides difficile tend to colonize? and what type of infections do we see?

GI tract; severe antibiotic associated diarrhea

What type of bacteria is gram negative, anaerobic, and rod shaped?

bacteroides fragilis

Where does bacteroides fragilis tend to colonize? and what type of infections do we see?

GI tract (ileum, colon); intraabdominal infections, abcesses

What types of bacteria does natural penicillins (penicillin G/VK) cover?

Drugs of choice for: s. pyogenes, s. pneumoniae, syphilis;

can be used for e. faecalis

What types of bacteria do oxacillin/nafcillin and dicloxacillin cover?

Drug of choice: MSSA; covers MRSA, s. pyogenes, s. pneumoniae

What types of bacteria do ampicillin and amoxicillin cover?

s. pyogenes, s. pneumoniae, e. faecalis

What types of bacteria do amox-clavulanate, amp-sulbactam cover?

MSSA, s. pyogenes, s. pneumoniae, e. faecalis, h. influenzae, m. catarrhalis, e. coli, klebsiella, bacteroides

What types of bacteria does piperacillin-tazobactam cover?

MSSA, s. pyogenes, s. pneumoniae, e. faecalis, h. influenzae, m. catarrhalis, e. coli, klebsiella, pseudomonas, bacteroides

What types of bacteria do the 1st gen cephalosporins (cefazolin, cephalexin) cover?

Drug of choice: MSSA; covers s. pyogenes, s. pneumoniae, e. coli, klebsiella,

What types of bacteria does the 2A gen cephalosporins (cefuroxime) cover?

MSSA, s. pyogenes, s. pneumoniae, h. influenzae, m. catarrhalis, e. coli, klebsiella

What types of bacteria does the 2B gen cephalosporins (cefotetan) cover?

MSSA, s. pyogenes, s. pneumoniae, h. influenzae, m. catarrhalis, e. coli, klebsiella, bacteroides

What types of bacteria does the 3A gen cephalosporins (ceftriaxone, cefdinir, cefpodoxime) cover?

MSSA, s. pyogenes, s.pneumoniae, h. influenzae, m. catarrhalis, e. coli, klebsiella

What types of bacteria does the 3B gen cephalosporins (ceftazidime) cover?

m. catarrhalis, e. coli, klebsiella, pseudomonas

What types of bacteria does the 4th gen cephalosporins (cefepime) cover?

MSSA, s. pneumoniae, h. influenzae, m. catarrhalis, e. coli, klebsiella, pseudomonas

What types of bacteria does the 5th gen cephalosporins (ceftaroline) cover?

MSSA, s. pneumoniae, h. influenzae, m. catarrhalis, e. coli, klebsiella

What types of bacteria do ceftazidime-avibactam cover?

sometimes MSSA, s. pyogenes, s. pneumoniae, h. influenzae, m. catarrhalis, e. coli, klebsiella, pseudomonas (reserved for carbapenem resistant)

What types of bacteria do imipenem and meropenem cover?

MSSA, s. pyogenes, s.pneumoniae, e. faecalis (imipenem only), h. influenzae, m. catarrhalis, e. coli, klebsiella, pseudomonas, bacteroides

What types of bacteria does ertapenem cover?

MSSA, s. pyogenes, s. pneumoniae, h. influenzae, m. catarrhalis, e. coli, klebsiella, bacteroides

What types of bacteria does mero/vaborbactam and imi/relbactam cover?

MSSA, s. pyogenes, s. pneumoniae, e. faecalis imipenem only), h. influenzae, m. catarrhalis, e. coli, klebsiella, pseudmonas (imi works against resistance), bacteroides

What types of bacteria does aztreonam (monobactam) cover?

h. influenzae, m. catarrhalis, e. coli, klebsiella, pseudmonas

What types of bacteria does ciprofloxacin cover?

MSSA, h. influenzae, m. catarrhalis, e. coli, klebsiella, pseudmonas, mycoplasma, chlamydia, legionella

What types of bacteria does levofloxacin cover?

MSSA, s. pyogenes, s. pneumoniae, e. faecalis, h. influenzae, m. catarrhalis, e. coli, klebsiella, pseudmonas, mycoplasma, chlamydia, legionella

What types of bacteria does moxifloxacin cover?

MSSA, s. pyogenes, s. pneumoniae, e. faecalis, h. influenzae, m. catarrhalis, e. coli, klebsiella, mycoplasma, chlamydia, legionella

What types of bacteria do clarithromycin, azithromycin (macrolides) cover?

h. influenzae, m. catarrhalis, mycoplasma, chlamydia, legionella

What types of bacteria do doxycycline, minocycline (tetracyclines) cover?

MSSA, MRSA, s. pneumoniae, h. influenzae, m. catarrhalis, bacteroides (minimal for fragilis), mycoplasma, chlamydia, legionella

what types of bacteria does TMP-SMX (sulfonamides) cover?

MSSA, MRSA, h. influenzae, m. catarrhalis, regionally e. coli and klebsiella, legionella

what types of bacteria does vancomycin (glycopeptide) cover?

drug of choice: MRSA; covers all gram positive bacteria except VRE, c. difficile

what types of bacteria does daptomycin (cyclic lipopeptide) cover?

MSSA, MRSA, s. pyogenes, e. faecalis, VRE

what types of bacteria does dalbavancin, oritavancin (lipoglycopeptides) cover?

MSSA, MRSA, all gram positive bacteria

what types of bacteria does clindamycin (lincosamide) cover?

MSSA, community acquired MRSA sometimes, s. pyogenes, s. pneumoniae, gram positive bacteroides

what types of bacteria does metronidazole (nitroimidazoles) cover?

drug of choice for anaerobes (gram negative) aka bacteroides

what types of bacteria does nitrofurantoin (urinary agent) cover?

e. faecalis, VRE, e. coli, klebsiella, sometimes pseudomonas

what types of bacteria does fosfomycin (urinary agent) cover?

e. coli, klebsiella, sometimes pseudomonas

what types of bacteria does linezolid (oxazolidinones) cover?

MSSA, MRSA, all gram positive bacteria

what types of bacteria does gentamicin, tobramycin (aminoglycosides) cover?

sometimes covers MSSA, MRSA, VRE, e.faecalis (gentamicin only), covers e. coli, klebsiella, pseudomonas

What adverse drug reactions can be seen with all beta lactams?

hypersensitivity reactions (rash, fever, anaphylaxis), nausea, vomiting, diarrhea, LFT elevations, c. difficile

describe the risk of allergic cross-reactivity between cephalosporins and penicillins

cross reactivity is about 5% with 1st gen cephalsporins and penicillins, but otherwise negligible once you get to 3rd gen cephalosporins

Which cephalosporins have a warning about severe neurological reactions? and what may increase the risk of reaction?

3b gen (ceftazidime): warning about rare neurotoxicity like myoclonus and ataxia in renal dysfunction

4th gen (cefepime): warning about neurotoxicity like myoclonus and seizures in renal dysfunction

What cephalosporin overs MRSA? aka ONLY beta lactam to cover MRSA

ceftaroline

which class (and specific drug) is most commonly associated with seizures?

carbapenems (imipenem)

what are the "respiratory" fluoroquinolones? Why are they called that?

levofloxacin and moxifloxacin since they have expanded streptococcal coverage compared to other fluoroquinolones

What are the common and serious ADRs of fluoroquinolones?

tendinitis, tendon rupture, myopathy/arthropathy, peripheral neuropathy, CNS effects (delirium), myasthenia gravis, DO NOT USE FOR UNCOMPLICATED UTI, BRONCHITIS, OR SINUSITIS

Which fluoroquinolone does not achieve good urine concentrations?

moxifloxacin (cannot be used in UTIs) and has increased pseudomonal resistance

What is the only class of oral antibiotics that covers pseudomonas aeruginosa?

fluoroquinolones

What are the common ADRs of macrolides?

GI intolerance, diarrhea, prolonged QTc, cholestatic hepatitis, reversible ototoxicity, torsades de pointes, rash, hypothermia, exacerbation of myasthenia gravis

What is different about the drug interactions between azithromycin and other macrolides?

azithromycin doesn't have any CYP3A4 interactions

What are the ADRs associated with tetracyclines?

GI upset, N/V/D, hepatotoxicity, esophageal ulcerations, photosensitivity, azotemia, visual disturbances, vertigo, hyperpigmentation, hemolytic anemia, pseudotumor cerebri, pancreatitis, c. difficile

What 3 classes of drugs that are reliable against atypical bacteria?

fluoroquinolones, macrolides, tetracyclines

What are the ADRs associated with TMP/SMZ?

GI intolerance, rash, hyperkalemia, bone marrow suppression, serum sickness, hepatitis, photosensitivity, crystalluria with azoternia, methemoglobinemia, SJS, toxic epidermal necrolysis, pancreatitis, interstitial nephritis

What monitoring parameters are associated with vancomycin?

Goal trough: 10-20 mcg/mL or 15-30 mcg/mL for Meningitis, Osteomyelitis, Pneumonia, Septicemia

AUC: >400

What unique ADRs are associated with daptomycin? What drug interaction results from this?

myalgias/rhabdomyolysis (need to follow creatine phosphokinase at least weekly, discontinue if >1000 u/L with symptoms or >2000 u/L without symptoms)

Drug interaction: HMG-CoA reductase inhibitors (statins)

What is unique about dalbavancin and oritavancin dosing?

once weekly dosing

What is a D-test in relation to clindamycin?

positive D-test = potential for inducible resistance to s.aureus during treatment

What ADRs are associated with metronidazole?

N/V/D, headache, metallic taste, dark urine, peripheral neuropathy, disulfiram reactions with alcohol, insomnia, stomatitis, dysarthria

Nitrofurantoin and fosfomycin are limited to which infections?

cystitis (only gram negative and positive bacteria)

What are the ADRs associated with oxazolidinones? What drug interactions are possible?

myelosuppression (thrombocytopenia, leukopenia, anemia), peripheral neuropathy, optic neuropathy, lactic acidosis, diarrhea, nausea, serotonin syndrome

Drug interactions: increased incidence of serotonin syndrome (weak MAOI)

What are the ADRs associated with aminoglycosides?

tubular necrosis and renal failure (reversible), vestibular and cochlear toxicity, anemia, hypersensitivity

Which agents have activity against extended spectrum beta lactamase (ESBL) producers?

imipenem, meropenem, ertapenem, beta-lactamase inhibitor combos (ceftolozane-tazo, ceftazidime-avi)

Which agents have activity against klebsiella pneumoniae carbapenemases (KPCs)?

beta lactamase inhibitor combos (ceftolo-tazo, ceftazi-avi), meropenem-vaborbactam

What are four reasons why multiple antibiotics might be used at the same time?

1. Synergistic activity (combined kill effect greater than independent activities)

2. Empiric therapy for suspected bacteria typically resistant to multiple antibiotics (have to double cover some bacteria, an additional agent might be added to decrease the chances of missing the suspected bacteria)

3. Extend antimicrobial spectrum beyond that of a single agent for treatment of polymicrobial infections (have one antibiotic make up the hole of another antibiotic)

4. Prevent emergence of resistance

What are the 4 moments of antibiotic prescribing?

1. make the diagnosis

2. empiric therapy and appropriate cultures

3. narrow or stop therapy

4. duration of therapy

What is the question we need to ask to make the diagnosis?

does the patient have an infection that requires antibiotics?

What are the questions we need to ask for empiric therapy and appropriate cultures?

a. Were appropriate cultures ordered before antibiotics were started?

b. Were empiric antibiotics compliant with guidelines?

c. Were specific reactions (allergies or other patient features) considered?

What are the questions we need to ask for narrow or stop therapy?

a. Are antibiotics still needed? If not, will you stop them today?

b. Can antibiotics be narrowed based on microbiology or other clinical data? If so, will you change to narrower agents today?

c. Can antibiotics be changed from IV to PO? If so, will you change to oral therapy today?

What are the questions we need to ask for duration of therapy?

a. Has a planned duration been documented in the medical record?

b. Is the planned duration consistent with guidelines?