Infectious Disease

What is empiric therapy?

Used when a patient has signs/symptoms of infection and uses broad-spectrum antibiotics to cover likely pathogens

What is definitive/targeted therapy?

used when the pathogen and susceptibilities are known

• Duration should be clearly defined (shortest possible for that disease state)

• Definitive is not always possible (cultures often reveal nothing)

In targeted or definitive therapy, what should be clearly defined?

Duration of therapy

How long does it usually take to get cultures and full susceptibility information, and do you always get results?

• Cultures take about a day to grow

• Identifying an organism takes 3 days (gram stain)

• Sometimes do not have adequate culture or nothing grows (stuck with empiric therapy for the course)

• 48-72 hours time from + cultures

Name some bacterial skin flora commonly considered contaminants in cultures

• Staphylococcus epidermidis

• Bacillus species - Corynebacterium species

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

• Hypersensitivity Rxns (i.e., rash, drug fever, acute interstitial nephritis, anaphylaxis)

• Diarrhea/Nausea

• C. Diff

• Thrombocytopenia

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

~5% with 1st-generation cephalosporins in type I IgE-mediated reactions

Which cephalosporins have a warning about severe neurological reactions and what increases the risk?

• Ceftazidime (3B): myoclonus, ataxia in renal dysfxn

• Cefepime (4): myoclonus, seizures in renal dysfxn

Which cephalosporin covers MRSA (the only beta-lactam that does)?

Ceftaroline (5th generation)

Which class and specific drug is most commonly associated with seizures?

Carbapenems, especially imipenem

What are the respiratory fluoroquinolones and why are they called that?

• Moxifloxacin

• levofloxacin

What are the common and serious ADRs of fluoroquinolones?

• Tendonitis/tendon rupture

• myopathy/arthropathy

• peripheral neuropathy

• CNS effects

• myasthenia gravis exacerbation

• More common when used for uncomplicated UTIs, bronchitis, sinusitis → AVOID USING

Which fluoroquinolone does not achieve good urine concentrations?

Moxifloxacin—poor urine penetration, avoid in UTIs

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

Fluoroquinolones (except moxifloxacin)

What are the common ADRs of macrolides?

• QTc prolongation

• nausea

• vomiting

• diarrhea

What is different about azithromycin drug interactions compared to other macrolides?

Azithromycin avoids CYP3A4 interactions

What adverse reactions are associated with tetracyclines?

• Abdominal pain (take with food)

• esophageal ulceration

• photosensitivity

• rash

• SJS/TEN

• permanent tooth discoloration (avoid <8 years)

• pregnancy category D

What three antibiotic classes reliably cover atypical bacteria?

• Tetracyclines

• fluoroquinolones

• macrolides

What are the ADRs associated with trimethoprim/sulfamethoxazole?

• GI upset

• Hypersensitivity (i.e., rash, fever)

• Renal (i.e., “false” AKI, interstitial nephritis)

• Hyperkalemia

• Bone marrow suppression (at high doses)

• Hemolysis risk

• C/I in pregnancy

• Risk with ACE/ARBs

What monitoring parameters are associated with vancomycin?

Goal trough 10–20 mcg/mL (15–20 for severe infections - meningitis, osteomyelitis, pneumonia, or septicemia) or AUC > 400

• watch for “red man” syndrome and nephrotoxicity

What unique ADRs are associated with daptomycin and what interaction occurs?

• Myalgias/rhabdomyolysis (monitor CK weekly, hold statins)

• rare eosinophilic pneumonia

What is unique about dalbavancin and oritavancin dosing?

Once-weekly dosing for skin infections

What is a D-test in relation to clindamycin?

Detects inducible clindamycin resistance in S. aureus

What adverse reactions are associated with metronidazole?

• GI intolerance

• HA

• Metallic taste

• Dark urine

• Peripheral neuropathy

• Disulfiram rxn with alcohol

• Stomatitis

• Aseptic Meningitis

• Dysarthria

• Rash (SJS)

• Neurotoxicity (may limit duration): neuropathy to encephalopathy

Nitrofurantoin and fosfomycin are limited to which infections?

UTIs only

What are the ADRs and drug interactions associated with oxazolidinones?

• Myelosuppression (i.e., thrombocytopenia, leukopenia, anemia)

• Peripheral and optic neuropathy

• Blindness

• Lactic Acidosis

• Diarrhea/NA

• Serotonin Syndrome

• Interstitial Nephritis

• Drug Interactions: prior or concomitant serotonergic agents

What are the ADRs associated with aminoglycosides?

• Tubular necrosis and renal failure

• Vestibular and cochlear toxicity

• Neuromuscular blockade

• Vertigo 

• Anemia

• Hypersensitivity

• Fetal harm

Which agents have activity against Extended spectrum Betal lactamase (ESBL) -producing organisms?

• Carbapenems (DOC)

• Ceftolozane - Tazobactam

• Ceftazidime - Avibactam

• Nitrofurantoin

• Fosfomycin

• Cefepime (not first choice)

Pip - Tazo (inconsistent)

Which agents have activity against Klebsiella pneumoniae carbapenemases (KPCs… also referred to as carbapenem resistant enterobacterales - CRE) organisms?

• Ceftazidime - Avibactam

• Ceftolozane - Tazobactam

What are reasons for using multiple antibiotics simultaneously?

• Synergistic Activity: combined kill effect is greater than monotherapy

• Empiric TX for suspected bacteria that is typically resistant to multiple abx

  • Can narrow once susceptibilities are known

  • Done to ensure at least 1 abx will be given

• Extend antimicrobial spectrum beyond a single agent to treat polymicrobial infxns

• Prevent emergence of resistance (TB)

What are the four moments of antibiotic prescribing and key questions at each?

1. Make the Diagnosis: does the patient have an infxn requiring abx?

2. Empiric Therapy + Appropriate Cultures: were appropriate cultures ordered before abx were started? Were the empiric abx compliant with guidelines? Were specific rxns considered?

3. Narrow / Stop Therapy: 1+ day has passed… Are abx still necessary? Will we stop abx today? Can abx be narrowed? Can abx be changed from IV → PO

Duration of Therapy: has a planned duration been documented? Is the planned duration consistent with guidelines?