Integrated Practice Quiz

6. JJ is a 25-year-old man with HIV/AIDS who presents to the infectious disease practice with a fever of 102F and complaint of severe headaches during the past week. He is given a work-up for a CNS fungal infection. Staining of his CSF with India ink reveals Cryptococcus neoformans. The patient is admitted and receives induction therapy with: A. Amphotericin B intrathecal B. Amphotericin B (IV) + flucytosine C. Amphotericin B (IV) + ketoconazole D. Fluconazole, oral E. Ketoconazole, oral

B. Amphotericin B (IV) + flucytosine*

Lincosamides

Clindamycin

11. A 6-month-old female is brought to the local emergency department by her mother, who reports that the child has a fever, irritability, lethargy, and doesn't want to eat since she awoke this morning about 8 hours ago. She has not been vomiting. Her family immigrated from Haiti one year ago. Family history reveals that the patient's mother suffered an "bad" reaction when she was treated for a urinary tract infection with "a sulfa drug" 6 years ago. She was told at the time that she has a G6PD deficiency. Urinalysis obtained by catheterization is positive for leukocyte esterases and urinary nitrites. Gram stain reveals gram-negative rods. A urine sample is sent to the microbiology lab for culture. Based on clinicalpresentation, the patient is given a diagnosis of uncomplicated urinary tract infection. In view of the family history, trimethoprim-sulfamethoxazole is contraindicated because it may induce an adverse drug reaction. What is the toxicity? A. Hemolytic anemia B. Neutropenia C. Sickle cell anemia D. Thalassemia E. Thrombocytopenia

Note: Severe hypersensitivity reactions to sulfonamide therapy can result in a constellation of effects, including agranulocytosis or aplastic anemia. This effect is not triggered by deficiency in G6PD.

5. A 16-year-old male presents to the ED with sudden onset of fever, chills, anorexia, and malaise. He also had a headache, chest soreness, abdominal pain and vomiting earlier today but these symptoms have abated. He went rabbit hunting 3 days ago with his dad. The patient was in charge of cleaning and preparing the rabbits for cooking. The patient's temperature is 104F; a chancre-like ulcer with raised margins is noted on the dorsum of his fourth digit of his right hand and regional axillary lymphadenopathy is noted. Blood samples are drawn for serology for suspicion of Francisella tularensis (an aerobic gram-negative coccobacillus). The patient is given empiric therapy for presumptive tularemia with a drug of choice for tularemia. He will be given an intramuscular injection twice daily, q12h, for at least 10 days. He is informed that his kidney function will be monitored. He is told that he might notice ringing in his ears, vertigo, tingling or numbness in his extremities, and diminished vision or a blind spot. Which of the following options fits the description of the administered drug? A. Amikacin B. Gentamicin C. Neomycin D. Paromomycin E. Streptomycin F. Tobramycin

The aminoglycosides include gentamicin, amikacin, tobramycin, neomycin, and streptomycin.

Tetracyclines

- Sumycin, Doxycycline (Vibramycin) - broad, rocky mtn fever, lyme disease, acne, GI infections by H. Pylori - bad GI discomfort - Don't give to kids ≤8; teeth permanently yellow - Bad photosensitivity- wear sunscreen! - Can't take with milk, iron, or antacids - Take on empty stomach with a full glass of water

Oxazolidinones

Linezolid

15. Where are the aminoglycosides' binding targets located?

Rationale: Aminoglycosides bind to the 30S ribosomal subunit.

What is the mechanism of the drug-drug interaction between itraconazole and the anti-rejection drug, tacrolimus? (Be precise.)

Rationale: Itraconazole is a strong CYP3A4 inhibitor; tacrolimus is a CYP3A4 substrate. Itraconazole inhibits tacrolimus metabolism and increases plasma concentrations of the immunosuppressant, thereby increasing the risk of the dose-related (concentration-related) tacrolimus toxicities, such as nephrotoxicity.

D-zone test

Which test is used for the determination of inducible clindamycin resistance in staphylococci and streptococci? modified Kirby-Bauer test determines the inducible clindamycin resistance in Staphylococcus sp. What test helps determine if inducible resistance is present in an erythromycin-resistant, clindamycin-sensitive organism (bacteria with erm gene)?

Macrolides

erythromycin, clarithromycin, azithromycin

5. A 26-year-old male was involved in a motorbike collision and suffered an open thigh fracture. The patient had a clear medical record before the accident. He required orthopedic surgery to insert an external osteosynthesis for fracture stabilization. The surgery was complicated by skin necrosis. Biopsies were submitted for culture. Surgical debridement was performed. Cultures and biopsies revealed a fungal infection (Rhizopus, Mucorales order). He is given intravenous treatment with the preferred antifungal agent and negative pressure wound therapy. The drug is a broad-spectrum antifungal agent with excellent activity in the treatment of mucormycosis. − Monitoring for drug-related adverse effects included renal function (SeCr, BUN, input and output), electrolytes (especially K+ and Mg2+), liver function tests, temperature, hematocrit, PT/PTT, CBC; signs of hypokalemia. − After one week, biopsies and cultures were negative and the patient underwent coverage of the skin loss (5% total body surface area) with split thickness skin grafts. − The patient eventually fully recovered. i) What is the name of the drug? Hints for recognizing the drug: The infection, the drug's spectrum of activity, the monitoring related to drug toxicities ii) Which one of the following best describes the mechanism of action of the drug described in the previous slide? A. Binds ergosterol; alters cell permeability B. Binds microtubules; inhibits fungal cell mitosis in metaphase C. Forms toxic metabolite; interferes with DNA, RNA synthesis D. Inhibits beta-1,3-D-glucan; disrupts fungal cell wall E. Inhibits a fungal CYP; impairs fungal cell membrane integrity and function

i) What is the name of the drug? Hints for recognizing the drug: The infection, the drug's spectrum of activity, the monitoring related to drug toxicities. ii) Which one of the following best describes the mechanism of action of the drug described in the previous slide? A. Binds ergosterol; alters cell permeability* B. Binds microtubules; inhibits fungal cell mitosis in metaphase C. Forms toxic metabolite; interferes with DNA, RNA synthesis D. Inhibits beta-1,3-D-glucan; disrupts fungal cell wall E. Inhibits a fungal CYP; impairs fungal cell membrane integrity and function Rationale: All the clues in the stem are indicative of amphotericin B. Clues: 1) Treatment of mucormycosis 2) Use of a broad-spectrum drug 3) Intravenous administration 4) Amphotericin is nephrotoxic. Monitoring for renal function / renal tubular acidosis - Input and output (IV fluids and fluids being consumed and urine volume being excreted) indicative of kidney function; serum creatinine and blood urea nitrogen indicative of glomerular filtration function; K+ and Mg2+ levels indicative of tubular dysfunction Signs of hypokalemia (including muscle weakness, cramping, drowsiness, ECG changes) 5) Monitoring for decreased red blood cell production/anemia (hematocrit and complete blood count) that would suggest erythropoietin deficiency. AMB therapy can also cause leukopenia and thrombocytopenia, which would be detected on a CBC. None of the other antifungal agents fit this profile. 6) Temperature: injection reaction can cause fever 7) Other tests: Liver function tests, elevations of serum aminotransferases can occur with therapy; PT/PTT, coagulopathy can occur during therapy

Aminoglycosides

ototoxicity, Renal toxicity, Can't take with PCN at all! - gentamicin, neomycin, streptomycin