Antimicrobials

Question 1

List the 2 natural penicillins and route of administration
What class do they belong to?
What is their mechanism of action?

Answer 1

Penicillin G (IV)
Penicillin V (Oral)
Class: Penicillins (B-lactams)
Cell wall synthesis inhibitor-binds Penicillin binding protein (PBP)

Question 2

What are the three anti-staphylococcal or penicillinase-resistant penicillins?
What class do they belong to?

Answer 2

Oxacillin (IV)
Nafcillin (IV)
Dicloxacillin (PO)
Class: B-lactam (antistaph penicillin)

Question 3

What are the 2 natural penicillins and their primary clinical use?

Answer 3

Penicillin G (IV)
Penicillin V (Oral)
Primary clinical use: streptococcal infections (group A strep pharyngitis, cellulitis, endocarditis, syphyllis

Question 4

What are the 2 aminopenicillins?

Class?

Answer 4

Ampicillin (IV)
Amoxicillin (PO)
Class: B-lactam (aminopenicillins)

Question 5

What are the 2 aminopenicillins and what are the clinical uses?

Answer 5

Ampicillin (IV), Amoxicillin (PO)

Ampicillin is the drug of choice for enterococcal and Listeria infections

Question 6

What are the 2 anti-pseudomonal penicillins?
What class do they belong to?

Answer 6

Ticarcillin, Piperacillin

B-lactams (extended/broad spectrum penicillins

Question 7

The anti-pseudomonal extended/broad spectrum antibiotics are combined with what type of drug to improve effectiveness?

Answer 7

Ticarcillin or piperacillin are combined with B-lactamase inhibitors.

Pseudomonal infections are treated with a combination of piperacillin and tazobactam

Clavulanate is a common B-lactamase inhibitor combined with amoxicillin

Question 8

How is resistance to penicillin achieved by bacteria?

What are 3 drugs given in combination that protects against this?

Answer 8

bacteria can produce B-lactamase that cleaves B-lactam ring

B-lactamase inhibitors are often given with antipseudomonal penicillins (piperacillin, ticarcillin)…include clavulanate, tazobactam, sulbactam

Question 9

What three classes of drugs are B-lactams?

Answer 9

Penicillins, cephalosporins, carbapenems

Question 10

What are the two 1st generation cephalosporins?

What are their clinical uses?

Answer 10

Cefazolin (IV)-surgical prophylaxis to prevent staph aureus infections, UTI, MSSA
Cephalexin (PO)

Question 11

What are the four 2nd generation cephalosporins?

Clincial uses?

Answer 11

1. Cefuroxime (IV/PO)
2. Cefaclor (PO)
   Cephamycins: Used for colorectal and gyn surgical prophylaxis
3. Cefotetan (IV)
4. Cefoxitin (IV)

Question 12

What are the five 3rd gen cephalosporins

Answer 12

1. Cefdinir (PO)
2. Cefpodoxime (PO)
3. Ceftriaxone (IV)
4. Cefazidime (IV)
5. Cefotaxime (IV)

Question 13

What 3rd gen cephalosporin has activity against Pseudomonas?

Answer 13

Ceftazidime

Question 14

What is the one 4th generation cephalosporin?

Clinical uses?

Answer 14

Cefepime (IV)

Broad spectrum, crosses BBB, active against Pseudomonas and serious systemic infections

Question 15

What is the one 5th generation cephalosporin and what infection does it cover?

Answer 15

Ceftaroline (IV)-MRSA

Only B-lactam that covers MRSA

Question 16

What is a good antibiotic to use against MRSA?

Answer 16

Ceftaroline (IV)

MRSA is usually resistant to other drugs due to altered PBPs

Question 17

Which cephalosporins can be used to treat meningitis?

Answer 17

3rd gen: Ceftriaxone, cefotaxime
4th gen: cefepime

They cross BBB

Question 18

Which cephalosporins can be used to treat hospital acquired infections such as pseudomonas?

Answer 18

Ceftazadime and cefepime

Question 19

Which generation of cephalosporins are used to treat hospital acquired infections?

Answer 19

3rd generation:

1. Cefdinir (PO)
2. Cefpodoxime (PO)
3. Ceftriaxone (IV)
4. Cefazidime (IV)
5. Cefotaxime (IV)

Question 20

What cephalosporin is used to treat gonorrhea?

Answer 20

Ceftriaxone

3rd gen

Question 21

What cephalosporin is used to treat Lyme disease?

Answer 21

Ceftriaxone

3rd gen

Question 22

A 27-year-old man presents with complaints of a painless ulcer on his penis. He admits to having unprotected intercourse with a woman he met in a bar during a conference 2 weeks ago. A scraping of the lesion, visualized by dark field microscopy, demonstrates spirochetes, and a diagnosis of syphilis is made. Which of the following is the treatment of choice assuming the patient has no known allergies?
(A) Benzathine penicillin G
(B) Penicillin G
(C) Penicillin V
(D) Doxycycline
(E) Bacitracin

Answer 22

The answer is A. Patients with primary syphilis require a single intramuscular dose of benzathine penicillin G. Oral preparations of Pen G or Pen V are insufficient. Doxycycline for 14 days is an alternative treatment in penicillin-allergic patients. Bacitracin is only topical and insufficient for syphilis.

Question 23

2. A 19-year-old military recruit living in the army barracks develops a severe headache, photophobia, and a stiff neck, prompting a visit to the emergency room. A lumbar puncture reveals a diagnosis of bacterial meningitis. Which of the following cephalosporins is likely to be given to this
patient?
(A) Cefazolin
(B) Cefuroxime axetil
(C) Ceftriaxone
(D) Cefepime

Answer 23

The answer is C. Ceftriaxone is a third-generation cephalosporin that has excellent CNS penetration. All the third-generation cephalosporins enter the CNS. The first-and secondgeneration agents, cefazolin and cefuroxime, respectively, do not enter the CNS. There are limited data on the effectiveness of the fourth-generation agent, cefepime, in meningitis.

Question 24

3. A 27-year-old intravenous drug abuser is admitted for fever and shortness of breath. Multiple blood cultures drawn demonstrate S. aureus. The cultures further suggest resistance to methicillin. The attending physician also orders a transesophageal echocardiogram that shows tricuspid vegetations consistent with endocarditis. Which of the following is an appropriate antibiotic?
(A) Aztreonam
(B) Imipenem
(C) Gentamicin
(D) Vancomycin
(E) Ceftriaxone

Answer 24

The answer is D. Vancomycin is the drug of choice for serious infections due to methicillin-resistant S. aureus (MRSA). In the case of endocarditis, the treatment is usually 6 weeks. The resistance of MRSA is often due to altered penicillin-binding proteins, not β-lactamases, so aztreonam, imipenem, and ceftriaxone would not be useful. Gentamicin is often used in conjunction with penicillins in a non-MRSA setting.

Question 25

``` A patient is receiving piperacillin-tazobactam, tobramycin and vancomycin for hospital-acquired pneumonia. He complains of flushing and diffuse rash on his trunk. Which of the following is the most likely culprit of his symptoms? A. Piperacillin-tazobactam B. Tobramycin C. Vancomycin D. None of the above ```

Answer 25

Answer: C. Vancomycin Discussion: Piperacillin-tazobactam, like other β-lactams, is allergenic and can cause rash, but flushing would be abnormal. Vancomycin, however, can result in flushing and development of a temporary rash. This effect is commonly referred to as “redman syndrome”, and is due in part to histamine release. Slowing the infusion normally mitigates the reaction. Tobramycin is not often associated with rash.

Question 26

``` Which one of the following agents is the most acceptable for the treatment of MSSA bacteremia? A. Daptomycin B. Vancomycin C. Cefazolin D. Piperacillin-tazobactam ```

Answer 26

Discussion: Although daptomycin, vancomycin and piperacillin-tazobactam have activity against MSSA, there are various reasons for why they are not the most appropriate choices. Head-to-head studies evaluating β-lactams vs. vancomycin for the treatment of MSSA bacteremia show increased mortality when patients are given vancomycin. Daptomycin is effective against MSSA, MRSA, VRE and coagulase negative staph, and is usually reserved for vancomycin-resistant infections or when vancomycin is not tolerated. Daptomycin is also an expensive antibiotic (~$350-$700 per day). Piperacillin-tazobactam is a broad spectrum antibiotic with activity against gram-positives, gram-negatives and anaerobes, therefore the spectrum exceeds what is required for MSSA bacteremia. Cefazolin is a 1st generation cephalosporin with activity against MSSA and streptococci. It has a narrow spectrum of activity against gram-negatives, and is void of anaerobic activity.

Question 27

``` Which of the following antibiotics inhibits the last step in cell wall synthesis (transpeptidation)? A. Tigecycline B. Cephalexin C. Daptomycin D. Levofloxacin ```

Answer 27

Answer: B. Cephalexin Discussion: Cephalexin, a first generation cephalosporin, binds to penicillin-binding proteins (PBPs) which results in inhibition of transpeptidation. Tigecycline acts at the bacterial ribosome, daptomycin causes depolarization of the cell membrane, and levofloxacin inhibits DNA gyrase and topoisomerase IV

Question 28

``` Uncomplicated skin and soft tissue infections are treated by which of the following? Dicloxacillin Ceftaroline Aztreonam Tetracycline Gentamicin ```

Answer 28

Anti-Staphylococcal Penicillins for uncomplicated skin & soft tissue infections! dicloxacillin, oxacillin, nafcillin are very narrow-spectrum, B-lactamase resistant (bulky side chain), excellent for G+ cocci (MSSA but NOT MRSA), nafcillin: neutropenia + thrombophlebitis, oxacillin: neutropenia + hepatotoxicity

Question 29

In older patients it is important to think of Listeria infections...what drug covers listeria?

Answer 29

Ampicillin os DOC for listeria

Question 30

What is the empiric therapy for dog bites?

Answer 30

Amoxicillin/clavulanate

Question 31

What drug for c. diff?

Answer 31

Metronidazole is DOC but vancomycin can also treat

Question 32

what drug for neutropenic fever? (also has good pseudomonas coverage)

Answer 32

Cefepime-4th gen cephalosporin

Question 33

What is an important neruological side effect of carbapenems?

Answer 33

seizures

Question 34

What 2 drugs may result in nephrotoxicity AND ototoxicity?

Answer 34

Vancomycin and aminoglycosides (gentamycin, tobramycin, streptomycin, amikacin)

Question 35

What bacteria to think of with gram + rods?

Answer 35

Listeria

Question 36

What drug has no corss-allergenicity with penicillins or cephalosporins?

Answer 36

Monobactams-aztreonam

Question 37

A 44-year-old female is admitted with lethargy, fevers and chills. Three out of three blood cultures grow Pseudomonas aeruginosa. She is started on gentamicin. What other antimicrobial has the same binding site as this drug? ``` Chloramphenicol Doxycycline Clindamycin Erythromycin Linezolid ```

Answer 37

Doxycycline

Question 38

For protein synthesis inhibitors, which work on 30s and 50s ribosomes? buy AT 30, CEL at 50

Answer 38

``` buy AT 30, CEL at 50 30s A-aminoglycosides T-Tetracyclines 50s C-clindamycin E-erythromycin (macrolids) L-linezolid ```

Question 39

A 28-year-old male presents to his PCP with complaints of knee and hip pain. He has also noted multiple red lesions with central clearing over his popliteal and inguinal regions. He recalls being bit by a tick two months ago. The DOC for this infection would be a poor choice to treat which of the following organisms? ``` Chlamydia trachomatis Rickettsia rickettsii Pseudomonas aeruginosa Mycoplasma pneumoniae Streptococcus pneumoniae ```

Answer 39

Doxycycline does NOT treat pseudomonas

Question 40

What is an imporatnt side effect to condsider or expect with macrolids? (azithromycin)

Answer 40

GI distress binds 50s ribosome

Question 41

what drug has the side effect of pseudomembranous colitis?

Answer 41

clindamycin

Question 42

A 26-year-old male presents to the ED with a painful lesion on the inner surface of his right heel. On exam, there is a 5 by 4 cm abscess with foul-smelling, purulent drainage. An I & D is performed, and culture grows VRSA. What would be an appropriate outpatient therapy for this patient? ``` Methicillin Vancomycin Linezolid Aztreonam Ceftriaxone ```

Answer 42

Linezolid & Tedizolid: bind to 50S & inhibits initiation, spectrum: resistant G+ (VRSA & VRE!), side effects: bone marrow suppression (thrombocytopenia), SS, lactic acidosis ``` Methicillin: MSSA Vancomycin: MRSA Linezolid: Correct! Aztreonam: Only G- rods Ceftriaxone: No MRSA, VRSA, or VRE coverage! ```

Question 43

Which drug might cause QT prolongation (torsades de pointes)?

Answer 43

Fluoroquinolones and macrolides

Question 44

What do you use for uncomplicated cystitis?

Answer 44

TMP-SMX-bactrim

Question 45

A 22-year-old IV drug user presents to the ED with fevers, chills, myalgias, lethargy and lesions on the oral mucosa. An ELISA for HIV-1 Ab/Ag is positive. What would be an appropriate initial combination of therapy for this patient? ``` 2 NRTIs + Protease Inhibitor 2 NNRTIs + Integrase Inhibitor 2 NNRTIs + NRTI NRTI + NNRTI NRTI + Protease Inhibitor + Integrase Inhibitor ```

Answer 45

2 NRTIs + Protease Inhibitor Appropriate HIV HHART 2 NRTIs + Integrase Inhibitor 2 NRTIs + Protease Inhibitor 2 NRTIs + NNRTI

Question 46

An 18-year-old male presents to this PCP for a routine college physical. The patient states that he is sexually active with males and inquires about HIV pre-exposure prophylaxis with tenofovir-emtricitabine. What is the mechanism of action of these two drugs? A. Competitively inhibit nucleotide binding to reverse transcriptase B. Non-competitively inhibit reverse transcriptase C. Inhibit HIV genome integration via reversible inhibition of HIV integrase D. Inhibit HIV-1 protease E. Bind CCR-5 on T-cell and block interaction with HIV gp120

Answer 46

A. Competitively inhibit nucleotide binding to reverse transcriptase: Correct! B. Non-competitively inhibit reverse transcriptase: NNRTIs C. Inhibit HIV genome integration via reversible inhibition of HIV integrase: IIs D. Inhibit HIV-1 protease: PIs E. Bind CCR-5 on T-cell and block interaction with HIV gp120: Maraviroc

Question 47

A 28-year-old male who was recently diagnosed with HIV presents to his ID physician for a regular follow-up. His CD4 count on initial diagnosis was 43/mm3. At his last visit, the patient was started on HAART with efavirenz-emtricitabine-tenofovir and primary prophylaxis with TMP-SMX and azithromycin. He states he is tolerating the medications well, but he has noticed being able to recall several vivid, frightening dreams over the past few nights. Which drug might be responsible for this phenomenon? ``` Efavirenz Emtricitabine Tenofovir TMP-SMX Azithromycin ```

Answer 47

NNRTIs: Efavirenz, important side effects: rash, CYP450, CNS effects (efavirenz), teratogenic (efavirenz)

Question 48

What is the goal of HCV therapy in 12-24 weeks of therapy?

Answer 48

Sustained viral response of undetected HCV RNA

Question 49

A 16-year-old female presents to her PCP with painful genital lesions after her first sexual encounter. On exam, the patient has numerous clusters of erythematous vesicles on her labia. What would be an appropriate treatment for this patient? ``` Oseltamavir Zanamavir Foscarnet Acyclovir Ganciclovir ```

Answer 49

D. Acyclovir

Question 50

A 58-year-old male presents to the ED with complaints of a 2-week history of malaise, cough, and recent development of ulcerated skin lesions. His PMH includes rheumatoid arthritis currently treated with methotrexate. He recently returned from a trip to the SE United States where he visited Alabama, Mississippi, and Louisiana. A urine antigen test for Blastomyces is positive and the patient is started on appropriate antifungal therapy. What is the mechanism of action of this drug? ``` Form pores in fungal membranes to allow electrolyte leakage Inhibit ergosterol synthesis Inhibit fungal squalene epoxidase Inhibit DNA & RNA biosynthesis Inhibit synthesis of β-1,3-D-glucan ```

Answer 50

B. Inhibit lanosterol to ergosterol synthesis Azoles

Question 51

An 83-year-old male admitted for perforated diverticulitis is started on total parenteral nutrition (TPN) after 5 days of food intolerance. One week later, he develops fevers, chills, extreme fatigue, and erythematous pustules on his skin. Three out of three blood cultures grow Candida albicans. He is started on IV Amphotericin B. What side effect might occur in this patient as a result of this therapy? ``` Decreasing serum creatinine Hypertension Cardiac arrhythmias Infusion-related delirium Increasing hematocrit ```

Answer 51

C. Cardiac arrhythmias Amphotericin B: Form pores in fungal membranes to allow electrolyte leakage (K+ & Mg2+), used for life-threatening systemic infections, side effects: “shake & bake” (fev/ch w/ infusion), hypotension, nephrotoxicity, ↓ K+ & Mg2+  supplement to avoid cardiac arrhythmias, give as liposomal (lipid) form