ID Part 2 Flashcards
VK is a 67-year-old female with diabetes, overactive bladder and hypothyroidism who has been started on Cipro for treatment of a urinary tract infection, based on susceptibility testing. All of the following counseling points are appropriate for VK EXCEPT:
A. This medication can cause tendon rupture.
B. Separate this medication from antacids such asMaalox.
C. This medication is associated with a risk of myelosuppression.
D. Thismedication can make the skin more sensitive to the sun. Use sunscreen and protective clothing.
E. Monitor blood glucose carefully while taking this medication if you have diabetes.
This medication is associated with a risk of myelosuppression.
Quinolones can cause many CNS toxicities (including seizures) and muscle toxicities (including tendon rupture).
They cause photosensitivity.
They should be separated from divalent cations to avoid chelation and reduced absorption.
Quinolones can cause hypoglycemia or hyperglycemia, so patients with diabetes should monitor blood glucose closely during therapy.
Extended infusion piperacillin-tazobactam is a dosing strategy that optimizes which of the following pharmacodynamic parameters?
A. Peak:MIC ratio
B. AUC:MIC ratio
C. Peak concentration
D. Time above MIC (T > MIC)
E. Minimum bactericidal concentration
Time above MIC (T > MIC)
As a beta-lactam antibiotic, piperacillin/tazobactam kills or inhibits bacterial growth when drug concentrations exceed the minimum inhibitory concentration (MIC).
Extending the infusion (from the traditional 30 minutes to infusing over 4 hours) results in greater T > MIC and is one way to optimize the activity of beta-lactams and effectively treat more resistant (higher MIC) organisms.
KD is a 35-year-old female with no known past medical history. She is married to an HIV-positive man. She has received a prescription for pre-exposure prophylaxis. Which labs must be performed before beginning therapy? (Select ALL that apply.)
A. TB skin test
B. CD4+ count
C. HIV test
D. Hepatitis B test
E. Hepatitis A test
HIV test
Hepatitis B test
Patients eligible for pre-exposure prophylaxis (PrEP) must be screened and test negative for HIV prior to initiation and then every 3 months after starting PrEP. It is important to evaluate this information, as the 2-drug NRTI PrEP regimen is not adequate for treatment of a patient diagnosed with HIV.
Patients must also be screened for hepatitis B and STI’s. Abrupt discontinuation of PrEP in patients with hepatitis B can exacerbate the condition.
PrEP
Before starting
Confirm the patient is HIV negative (blood test)
Screen for recent symptoms of HIV
Lab tests: SCr, hepatitis B serologies
PrEP
Treatment options
Oral Truvada or Descovy, 1 tablet once daily (≤ 90-day supply)
IM cabotegravir (Apretude) monthly x 2 doses, then Q2 months
PrEP
Follow-up
Test for HIV every 3 months (if negative, continue PrEP)
Screen for STIs, monitor renal function and other potential adverse effects PRN (schedule varies)
PEP
Before starting
Obtain HIV test, SCr, and hepatitis B serologies
PEP
Treatment
Start ASAP (ideally within 72 hours) of exposure
Complete 3-drug regimen x 28 days:
Truvada (if CrCl ≥ 60)
+
Dolutegravir (Tivicay) or raltegravir (Isentress)
PEP
Follow-up
Follow-up HIV testing
Commonly Used Drugs for Specific Pathogens
Methicillin-susceptible Staphylococcus aureus (MSSA)
Dicloxacillin, nafcillin, oxacillin
Cefazolin, cephalexin (and other 1 and 2nd generation cephalosporins)
Amoxicillin/clavulanate, ampicillin/sulbactam (Unasyn)
Commonly Used Drugs for Specific Pathogens
Methicillin-resistant Staphylococcus aureus (MRSA)
Ceftaroline
Daptomycin (not in pneumonia)
Linezolid
Vancomycin (consider using alternative if MIC ≥ 2)
SMX/TMP (CA-MRSA SSTIs)
Clindamycin (CA-MRSA SSTIS)
Doxycycline, minocycline (CA-MRSA SSTIs)
Commonly Used Drugs for Specific Pathogens
Vancomycin-resistant Enterococcus (VRE)
Pen G or ampicillin (E. faecalis only)
Linezolid
Daptomycin
Cystitis only: nitrofurantoin, fosfomycin (Monurol), doxycycline (Vibramycin)
Commonly Used Drugs for Specific Pathogens
Atypical Organisms
Azithromycin, clarithromycin
Doxycycline, minocycline
Quinolones
Commonly Used Drugs for Specific Pathogens
HNPEK
Haemophilus, Neisseria, Proteus, E Coli, Klebsiella
Beta-lactam/beta-lactamase inhibitor
Cephalosporins (except 1st generation)
Carbapenems
Aminoglycosides
Quinolones
SMX/TMP
Commonly Used Drugs for Specific Pathogens
Pseudomonas aeruginosa
Aztreonam
Cefepime
Ceftazidime
Ceftazidime/avibactam
Ceftolozane/tazobactam (Zerbaxa)
Carbapenems (except ertapenem)
Ciprofloxacin, levofloxacin
Piperacillin/tazobactam (Zosyn)
Tobramycin
Colistimethate, polymyxin B
Commonly Used Drugs for Specific Pathogens
CAPES
Citrobacter, Acinetobacter, Providencia, Enterobacter, Serratia
Aminoglycosides
Cefepime
Carbapenems
Colistimethate, polymyxin B
Piperacillin/tazobactam
Commonly Used Drugs for Specific Pathogens
Extended-spectrum beta- lactamase (ESBL) producing gram-negative rods (E. coli, K. pneumoniae, P. mirabilis)
Carbapenems
Ceftazidime/avibactam
Ceftolozane/tazobactam (Zerbaxa)
Commonly Used Drugs for Specific Pathogens
Carbapenem-resistant gram-negative rods (CRE)
Ceftazidime/avibactam
Colistimethate, polymyxin B
Meropenem/vaborbactam (Vabomere)
Imipenem/cilastatin/relebactam (Recarbrio)
Commonly Used Drugs for Specific Pathogens
Gram-negative anaerobes (Bacteroides fragilis)
Beta-lactam/beta-lactamase inhibitor
Cefotetan, cefoxitin
Carbapenems
Metronidazole
Moxifloxacin (reduced activity)
Commonly Used Drugs for Specific Pathogens
C. difficile
Vancomycin (oral)
Fidaxomicin (Dificid)
Metronidazole
Refrigeration Required After Reconstitution
Penicillin VK
Ampicillin
Amoxicillin/Clavulanate
Cephalexin
Cefadroxil
Cefpodoxime
Cefprozil
Cefuroxime
Cefaclor
Vancomycin oral
Valganciclovir
Antibiotics
That do not require renal adjustment
Antistaphylococcal penicillins (e.g., dicloxacillin, nafcillin)
Ceftriaxone
Clindamycin
Doxycycline
Macrolides (azithromycin and erythromycin only)
Metronidazole
Moxifloxacin
Linezolid
How should efavirenz be administered to decrease CNS side effects?
A. In the morning with a large meal
B. At bedtime on an empty stomach
C. Twice a day with a pharmacokinetic booster
D. 30 minutes before breakfast
E. With the largest meal of the day
At bedtime on an empty stomach
NNRTI; Brand: Sustiva
NNRTIs Meds
REDEN
Rilpivirine (Edurant)
Efavirenz (Sustiva)
Doravirine (Pifeltro)
Etravirine (Intelence)
Nevirapine
NNRTIs MOA
Non-competitively inhibit the reverse transcriptase enzyme, preventing the conversion of HIV RNA to HIV DNA in stage 3 (reverse transcription) of the HIV life cycle
NNRTIs SE
Hepatotoxicity
Severe rash, including SJS/TEN
Which NNRTI has the highest risk of SJS/TEN?
nevirapine
NNRTI Drug Intxn
Is a 3A4 substrate
Efavirenz & etravirine are moderate 3A4 inducers
Rilpivirine needs an acidic environment for absorption
Efavirenz SE
=
Psychiatric symptoms (depression, suicidal thoughts)
CNS effects (impaired concentration, abonormal/vivid dreams, confusion): usually resolve after 2-4 weeks
↑ TC & TGC
Rilpivirine SE
Depression
Artificial ↑ SCr (no effect on GFR)
Not rec if preTx VL > 100,000 or CD4 ct < 200 (higher failure rate)
How do you take rilpivirine?
Take with a meal and water (do not substitute with a protein drink)
Requires an acidic environment for absorption; do not use with PPIs and separate from H2RAs and antacids
Chlamydia Tx
Azithromycin 1 g PO x 1 OR
Doxycycline 100 mg PO BID 7d
Rifaximin maybe used in managementof all of the following EXCEPT:
A. Hepatic encephalopathy
B. IBS with diarrhea
C. Refractory C. difficile
D. Spontaneous bacterial peritonitis
E. Travelers’ diarrhea
Spontaneous bacterial peritonitis
PO only
Rifaximin (Xifaxin) is an antibacterial agent that is structurally related to rifampin.
It is indicated for the treatment of non-invasive E. colitravelers’ diarrhea, for reduction in the risk of overt hepatic encephalopathy and for IBS-D.
Since systemic drug absorption is minimal, it is not useful for spontaneous bacterial peritonitis (SBP).
Acute Cystitis
Empiric treatment
Nitrofurantoin 100 mg BID × 5 days
Fosfomycin 3 grams × 1 dose
Sulfamethoxazole/trimethoprim DS 1 tablet BID × 3 days (if no sulfa allergy)
Nitrofurantoin CI CrCl < 60
Treatment of Pyelonephritis
Bactrim
Urinary quinolones (ciprofloxacin, levofloxacin)
Which of the following statements are correct with regard to sulfamethoxazole/trimethoprim? (Select ALL that apply.)
A. It is a potent hepatic enzyme inducer resulting in reduced drug concentrations.
B. It has excellent bioavailability, thus can transition from intravenous to oral formulations in a 1:1 fashion.
C. It is active against Gram-positive pathogens, including Staphylococci, Gram-negative pathogens and opportunistic pathogens.
D. It should be avoided in a patient with a G6PD deficiency.
E. A negative Coombs test with sulfamethoxazole/trimethoprim indicates hemolytic anemia.
It has excellent bioavailability, thus can transition from intravenous to oral formulations in a 1:1 fashion.
It is active against Gram-positive pathogens, including Staphylococci, Gram-negative pathogens and opportunistic pathogens.
It should be avoided in a patient with a G6PD deficiency.
TMP/SMX is a potent CYP2C9 inhibitor (not inducer). It has 1:1 conversion from IV:PO dosing.
It is a broad spectrum agent with excellent Gram-positive, Gram-negative (not Pseudomonas) and opportunistic pathogen coverage.
It is partially cleared by the kidney and should be dosed reduced for CrCl < 30 mL/min.
A positive Coombs test in the labs (along with decreasing hemoglobin/hematocrit) would indicate the presence of hemolytic anemia and Bactrim should be discontinued.
Bactrim CI
Sulfa Allergy
Pregnant or breastfeeding
Bactrim Warnings
Skin Reactions (SJS/TEN)
G6PD deficiency
Bactrim SE
Photosensivity
↑ K
hemolytic anemia (+ Coombs test)
crystalluria
Bactrim Common Uses
Ca-MRSA
UTI
Pneumocystis pneumonia
Bactrim Drug Intxn
2C9 inhibitor → ↑ INR w/ warfarin
Ciprofloxacin IV:PO
80%
Which azole antifungal requires an acidic environment for absorption?
A. Fluconazole
B. Voriconazole
C. Ketoconazole
D. Isavuconazonium
E. Posaconazole
Ketoconazole
Ketoconazole requires an acidic environment for absorption.
If a PPI or H2RA must be used while on ketoconazole, taking an acidic beverage (such as non-diet soda) can improve absorption by providing an acidic environment.
Azole Class Effects
↑ LFTs
Risk for QT prolongation (except isavuconazonium)
What is the DOC for Aspergillus
Voriconazole
Which azole is mostly used for onychomycosis?
Itraconazole
Meningitis Empiric Tx
Ceftriaxone + vancomycin ± Ampicillin (> 50 y/o)
Neisseria meningitidis (Meningococcus) close contacts vaccine & antibiotics prophylaxis
Rifampin 600 mg PO BID for 2 days OR
Cipro 500 mg PO single dose OR
Ceftriaxone 250 mg single IM inj (most effective)
Which of the following statements are accurate with regard to aminoglycosides? (Select ALL that apply.)
A. Active against most aerobic Gram-negative pathogens
B. Active against most Gram-positive pathogensas monotherapy
C. Demonstrate post-antibiotic effect
D. Cause hepatotoxicity
E. Demonstrate concentration-dependent bacterial killing
Active against most aerobic Gram-negative pathogens
Demonstrate post-antibiotic effect
Demonstrate concentration-dependent bacterial killing
Aminoglycosides are concentration-dependent killers and are active against Pseudomonas.
They are cleared by the kidney and associated with nephrotoxicity and ototoxicity, especially when trough levels remain high or when given for prolonged treatment courses.
When used in complicated Gram-positive infections (Staphylococcus and Enterococcus) they are used for synergy, which means that they must be given in combination with beta-lactams or vancomycin.
Aminoglycosides Coverage
Gram-negatives, including Pseudomonas
Synergy for Gram-positives (Staphylococci/Enterococci) w/ beta-lactams
Low resistance & Cost
Aminoglycosides Monitoring
Renal Functions
Serum Levels
Renal Damage & Ototoxicity
Aminoglycosides Dosing
Gentamicin/tobramycin
Traditional (1-2.5 mg/kg IV Q8H)
* Peaks and troughs
Extended-interval: (4-7 mg/kg IV Q24H)
* Draw a random level and use nomogram
Concentration-dependent killing → give larger doses less frequently (extended interavl dosing) → allow the kidneys to recover
Aminoglycosides: Traditional Dosing: Target Drug Concentations
When to draw trough and peak?
Draw trough 30 mins before 4th dose
Draw peak 30 mins after the end of the 4th dose infusion
Aminoglycosides: Traditional Dosing: Target Drug Concentations
Gentamicin/tobramycin Peak/Trough Range
Peak: 5-10 mcg/mL
Trough: < 2 mcg/mL
A hospitalized patient with no known drug allergies has cellulitis and the physician ordered vancomycin 1,000 mg IV Q12H and imipenem-cilastatin 1,000 mg IV Q8H. The medications were administered at the same time over 30 minutes. During the infusion, the patient experienced a profound drop in blood pressure. Her upper body, mostly in the trunk area, was covered with an erythematous rash. What is the likely cause of the patient’s symptoms?
A. Rhabdomyolysis
B. Vancomycin flushing reaction
C. Drug-induced lupus erythematosus
D. CYP2C9 drug interaction
E. Photosensitivity reaction
Vancomycin flushing reaction
The patient has experienced symptoms of vancomycin flushing, an infusion reaction due to a rapid administration of vancomycin.
Symptoms can include rash, pruritus, erythema and, less frequently, hypotension or angioedema.
Infusions should be limited to no more than 1 gram per hour.
Vancomycin Coverage
Gram-positives (MRSA),
Streptococci,
Enterococci,
C. difficile (PO only)
Vancomycin Dosing
IV: 15-20 mg/kg Q8-12H, using TBW
Dose/interval adjustment in renal failure
Vancomycin Monitoring
SCr and avoid other nephrotoxic or ototoxic drugs (e.g., furosemide, aminoglycosides, cisplatin)
What is 1st line for MRSA infections?
Vancomycin
e.g., pneumonia, meningitis, bacteremia, some skin infections
Vancomycin Target Trough
15-20 mcg/mL
Vancomycin C. difficile
PO only for C. difficile infections (125 mg QID x 10 days)
Which antibiotic cause Red Man Syndrome?
Vancomycin
Infuse 1 g over 1 hr
43 y/o Male
Physical Exam / Vitals:
Height: 5’9” Weight: 209pounds
BP: 102/59 mmHg HR: 100 BPM RR: 28 BPM Temp: 102°F Pain: 6/10
Plan: Acetaminophen per feeding tube for fever, empiric antibiotics for ventilator-associated pneumonia, to include meropenem + vancomycin + gentamicin (extended-interval dosing).
What dose of gentamicin should be initiated in MV as part of the empiric antibiotic regimen?
A. 95 mg
B. 160 mg
C. 560mg
D. 665 mg
E. 1125 mg
560mg
MV is obese, so his adjusted body weight (~80 kg) should be used for aminoglycoside dosing.
The dose used most commonly for extended interval dosing is 7 mg/kg (but may range from 4-7 mg/kg).
When to use an alternative to vancomycin?
MIC ≥ 2
Echinocandins Covers
Candida glabrata & krusei
Echinocandins Forms
IV only
Warning for infusion reactions
Echinocandins MOA
Blocks Beta-glucans synthesis
Few drug intxn
No renal dose adjustment
Which antifungal is CI in pregnancy?
Griseofulvin
Can cause contraceptive failure
Treatment Of Opportunistic Infections
Candidiasis (oropharyngeal/ esophageal)
Fluconazole
Alternatives: Itraconazole Posaconazole
Treatment Of Opportunistic Infections
Cryptococcal meningitis
Induction: Amphotericin B (deoxycholate or liposomal) + flucytosine
Alternative: Fluconazole + flucytosine
Secondary PPx: Fluconazole (low dose)
Treatment Of Opportunistic Infections
Cytomegalovirus (CMV)
Valganciclovir (PO) or Ganciclovir (IV)
If toxicities to ganciclovir or resistant strains: foscarnet, cidofovir
Secondary PPx: No agents recommended Maintain CD4+ count> 100 cells/mm³
Foscarnet & cidofovir - nephrotoxicity
Treatment Of Opportunistic Infections
Mycobacterium avium complex infection
(Clarithromycin or azithromycin) + ethambutol
Add a 3rd or 4th agent using rifabutin, amikacin or streptomycin, moxifloxacin or levofloxacin
Secondary PPx: Same as treatment regimens
Ethambutol - ototoxicity
BJ is on tobramycin IV every 8 hours for treating a gram-negative infection and his levels are reported as a peak of 8.3 mcg/mL and a trough of 2.5 mcg/mL. Which of the following recommendations should the pharmacist make to the medical team?
A. Increase the dose of tobramycin
B. Decrease the dose of tobramycin
C. Extend the dosing interval of tobramycin
D. Shorten the dosing interval of tobramycin
E. Continue the current regimen
Extend the dosing interval of tobramycin
The peak of tobramycin is within range, but the trough level is above the goal level(it should be less than 2 mcg/mL and ideally less than 1.5 mcg/mL).
By extending the dosing interval, the trough level will decrease and the toxicity risk is lowered without decreasing the peak for this concentration-dependent drug.
Protease Inhibitors Meds
Atazanavir (Reyataz)
Darunavir (Prezista)
Fosamprenavir
Lopinavir/ritonavir (Kaletra)
Tipranavir (Aptivus)
“navir”
All PIs
Rec w/ a PK booster (ritonavir or cobicistat)
No renal dose adjustments
Which PIs do you take w/ food?
Darunavir (Prezista)
Atazanavir (Reyataz)
Reduces GI upset
Which PI needs an acidic gut for absorption?
Atazanavir (Reyataz)
Avoid PPIs w/ unboosted atazanavir
Separate boosted atazanavir w/ PPI by 12 hours
No more than 20 mg of omeprazole or equivalent
Which PI is used only for PK boosting?
Ritonavir
Low doses
PIs SE
Diarrhea, nausea
Hyperglycemia/insulin resistance, dyslipidemia, lipodystrophy
Hepatotoxicity (eg, ↑ LFTs, hepatitis)
Hypersensitivity reactions (eg, rash, SJS/TEN)
Atazanvir SE
Hyperbilirubinemia (reversible)
Yellow appearance to the skin or scleral icterus (yellow eyes)
Which PIs should not be taken if the pt has a sulfa allergy?
Darunavir (Prezista)
Fosamprenavir
Tipranavir (Aptivus)
Which PI contatins alcohol?
Lopinavir/ritonavir (Kaletra) Sol
Disulfiram rxn w/ metronidazole
PK Boosters Med
Cobicistat (Tybost)
Ritonavir (Norvir)
Take w/ food
Which PK Booster can artificially ↑ SCr?
Cobicistat (Tybost)
PI & PK Booster Drug interactions
CI or should be avoided
Alpha-1A blockers: alfuzosin, silodosin, tamsulosin
Amiodarone, dronedarone
Anticoagulants/antiplatelets: apixaban, rivaroxaban, ticagrelor
Azole antifungals: voriconazole, posaconazole, itraconazole, isavuconazole
Protease inhibitors for hepatitis C (eg, grazoprevir, glecaprevir)
Lovastatin & simvastatin
PDE-5 inhibitors used for pulmonary hypertension: sildenafil, tadalafil
Strong CYP3A4 inducers (eg, carbamazepine, rifampin, St. John’s wort)
Systemic, inhaled & intranasal steroids (except beclomethasone)
Which of the following antimicrobialshas arisk foradditive QT prolongation when combined with amiodarone?
A. Zithromax
B. Penicillin V potassium
C. Invanz
D. Nitrofurantoin
E. Cleocin
Zithromax
All macrolides have a risk for QT prolongation and should be used cautiously in patients with cardiovascular disease or those taking other QT prolonging drugs.
Macrolides Meds
Azithromycin (Zithromax)
Clarithromycin (Biaxin)
Erythromycin (E.E.S.)
Macrolides Coverage
Atypical pathogens (Legionella, Chlamydia, Mycoplasma, Mycobacterium avium)
H. influenzae
S. pneumoniae
Azithromycin covers traveler’s diarrhea
Common Uses
Macrolides
CAP, Strep throat
Common Uses
Azithromycin
COPD exacerbations
Chlamydia
Gonorrhea
MAC PPx
And Traverlers’ diarrhea
Common Uses
Clarithromycin
H. pylori
Common Uses
Erythromycin
↑ gastric motility
e.g. gastroparesis
Macrolides Safety Issues
QT prolongation: caution w/ CVD ↓ K/Mg, use of other QT-prolong drugs
Drug intxn:
Clarithromnycin/erythromycin Strong 3A4 inhibitors
CI w/ simvastatin/lovastatin
JPhas a blood culture report showing Gram-positive cocci resembling Streptococci, Klebsiella pneumoniaeand anaerobes. Which of the following medications would provide adequate coverage for these organisms?
A. Ertapenem
B. Rifaximin
C. Metronidazole
D. Fosfomycin
E. Ciprofloxacin
Ertapenem
Carbapenems are very broad-spectrum antibiotics.
They cover gram positives, gram negatives and anaerobes.
Rifaximin, metronidazole and fosfomycin have a much narrower spectrum.
Ciprofloxacin does not have reliable strep coverage, nor does it cover anaerobes.
Carbapenem Meds
Doripenem
Imipenem/Cilastatin (Primaxin I.V.)
Meropenem
Meropeneme/Vaborbactam (Vabomere)
Ertapenem (Invanz)
Carbapenems Class Effects
All active against ESBL-producing organisms and (except ertapenem) Pseudomonas
Do not use with penicillin allergy
Seizure risk (with higher doses, failure to dose adjust in renal dysfunction, or use of imipenem/cilastatin)
Carbapenems Coverage
Broad coverage, so remember what is not covered:
Atypicals, VRE, MRSA, C. difficile, Stenotrophomonas
ErtAPenem does not cover PEA: Pseudomonas, Enterococcus, Acinetobacter
Carbapenems Common Uses
Polymicrobial infections (e.g., severe diabetic foot infection)
Empiric therapy when resistant organisms are suspected
ESBL-positive infections
Resistant Pseudomonas or Acinetobacter infections (except ertapenem)
Carbapenems Form
IV only
Ertapenem must be diluted in?
NS
