Beta-Lactam Antibiotics (10)

2.

Questions 6–8. A 52-year-old man (weight 70 kg) is brought to the hospital emergency department in a confused and delirious state. He has had an elevated temperature for more than 24 h, during which time he had complained of a severe headache and had suffered from nausea and vomiting. Lumbar puncture reveals an elevated opening pressure, and cerebrospinal fluid findings include elevated protein, decreased glucose, and increased neutrophils. Gram stain of a smear of cerebrospinal fluid reveals gram-positive diplococci, and a preliminary diagnosis is made of purulent meningitis. The microbiology report informs you that for approximately 15% of S pneumoniae isolates in the community, the minimal inhibitory concentration for penicillin G is 20 mcg/mL. Treatment of this patient should be initiated immediately with intravenous administration of

Amoxicillin
Cephalexin
Ceftriaxone plus vancomycin
Nafcillin
Piperacillin

Correct Answer

A. Ceftriaxone plus vancomycin

Explanation

Pneumococcal isolates with a minimal inhibitory concentration for penicillin G of greater than 2 mcg/mL are highly resistant. Such strains are not killed by the concentrations of penicillin G or ampicillin that can be achieved in the cerebrospinal fluid. Nafcillin has minimal activity against penicillin-resistant pneumococci and piperacillin is mainly used for infections caused by gram-negative rods. Cefotaxime and ceftriaxone are the most active cephalosporins against penicillin-resistant pneumococci, and the addition of vancomycin is recommended in the case of highly resistant strains.

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3.

The primary mechanism of antibacterial action of the penicillins involves inhibition of

Beta-lactamases
Cell membrane synthesis
N-acetylmuramic acid synthesis
Peptidoglycan cross-linking
Transglycosylation

Correct Answer

A. Peptidoglycan cross-linking

Explanation

Penicillins (and cephalosporins) bind to PBPs acting at the transpeptidation stage of cell wall synthesis (the final step) to inhibit peptidoglycan cross-linking. The beta-lactam antibiotics also activate autolysins, which break down the bacterial cell wall. Synthesis of N-acetylmuramic acid is inhibited by fosfomycin. Vancomycin inhibits transglycolase, preventing elongation of peptidoglycan chains.
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4.

Immunofluorescent microscopic examination of fluid expressed from the penile chancre of this patient revealed treponemes. Because he appears to be infected with Treponema pallidum, the best course of action would be to

Administer a single oral dose of fosfomycin
Give no other antibiotics because drug treatment of gonorrhea provides coverage for incubating syphilis
Inject intramuscular benzathine penicillin G
Treat with oral tetracycline for 7 d
Treat with vancomycin

Correct Answer

A. Inject intramuscular benzathine penicillin G

Explanation

This patient with gonorrhea also has primary syphilis. The penile chancre, the enlarged nontender lymph nodes, and the microscopic identification of treponemes in fluid expressed from the lesion are essentials of diagnosis. Although a single dose of ceftriaxone may cure incubating syphilis, it cannot be relied on for treating primary syphilis. The most appropriate course of action in this patient is to administer a single intramuscular injection of 2.4 million units of benzathine penicillin G. For penicillin-allergic patients, oral doxycycline or tetracycline for 15 d (not 7 d) is effective in most cases (see Chapter 44). However, lack of compliance may be a problem with oral therapy. Fosfomycin and vancomycin have no significant activity against spirochetes.

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5.

A 36-year-old woman recently treated for leukemia is admitted to the hospital with malaise, chills, and high fever. Gram stain of blood reveals the presence of gram-negative bacilli. The initial diagnosis is bacteremia, and parenteral antibiotics are indicated. The records of the patient reveal that she had a severe urticarial rash, hypotension, and respiratory difficulty after oral penicillin V about 6 mo ago. The most appropriate drug regimen for empiric treatment is

Aztreonam
Ceftriaxone
Meropenem
Oxacillin
Ticarcillin plus clavulanic acid

Correct Answer

A. Aztreonam

Explanation

Each of the drugs listed has activity against some gram-negative bacilli. All penicillins should be avoided in patients with a history of allergic reactions to any individual penicillin drug. Cephalosporins should also be avoided in patients who have had anaphylaxis or other severe hypersensitivity reactions after use of a penicillin. There is partial cross-reactivity between penicillins and the carbapenems such as imipenem and meropenem, but no cross-reactivity between the penicillins and aztreonam.

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9

6.

Questions 2–3. A 33-year-old man was seen in a clinic with a complaint of dysuria and urethral discharge of yellow pus. He had a painless clean-based ulcer on the penis and nontender enlargement of the regional lymph nodes. Gram stain of the urethral exudate showed gram-negative diplococci within polymorphonucleocytes. The patient informed the clinic staff that he was unemployed and had not eaten a meal for 2 d. What is the most appropriate treatment of gonorrhoea in this patient?

A single intramuscular dose of ceftriaxone
Amoxicillin orally for 7 d
Procaine penicillin G intramuscularly as a single dose plus oral probenecid
Meropenem orally for 7 d
Vancomycin intramuscularly as a single dose

Correct Answer

A. A single intramuscular dose of ceftriaxone

Explanation

Treatments of choice for gonorrhea include a single dose of ceftriaxone (intramuscularly). Because of the high incidence of beta-lactamase-producing gonococci, the use of penicillin G or amoxicillin is no longer appropriate for gonorrhea. Similarly, many strains of gonococci are resistant to tetracyclines. Alternative drugs (not listed) for gonorrhea include cefixime, azithromycin (see Chapter 44) or spectinomycin (see Chapter 45).

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7.

Resistance of pneumococci to penicillin G is due to

Alterations in porin structure
Beta-lactamase production
Changes in chemical structure of target penicillin-binding proteins
Changes in the d-Ala-d-Ala building block of peptidoglycan precursor
Decreased intracellular accumulation of penicillin G

Correct Answer

A. Changes in chemical structure of target penicillin-binding proteins

Explanation

Pneumococcal resistance to penicillins is due to changes in the chemical structures of the target penicillin-binding proteins located in the bacterial cytoplasmic membrane. A similar mechanism underlies the resistance of staphylococci to methicillin (MRSA strains). A structural alteration in the d-Ala-d-Ala component of the pentapeptide side chains of peptidoglycans is the basis for a mechanism of resistance to vancomycin.
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8.

If this patient had been 82-years-old and the Gram stain of the smear of cerebrospinal fluid had revealed gram-positive rods resembling diphtheroids, the antibiotic regimen for empiric treatment would include

Ampicillin
Cefoxitin
Fosfomycin
Vancomycin

Correct Answer

A. Ampicillin

Explanation

Diphtheroid-like gram-positive rods in the cerebrospinal fluid smear of an elderly patient are indicative of L monocytogenes. Listeria infections are more common in neonates, elderly patients, and those who have been treated with immunosuppressive agents. Treatment consists of ampicillin with or without an aminoglycoside such as gentamicin. Trimethoprim-sulfamethoxazole can also be used (see Chapter 46).

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9.

A patient needs antibiotic treatment for native valve, culture-positive infective enterococcal endocarditis. His medical history includes a severe anaphylactic reaction to penicillin G during the last year. The best approach would be treatment with

Amoxicillin-clavulanate
Aztreonam
Ceftriaxone
Ticarcillin
Vancomycin

Correct Answer

A. Vancomycin

Explanation

In patients who have had a severe reaction to a penicillin, it is inadvisable to administer a cephalosporin or a carbapenem such as meropenem. Aztreonam has no significant activity against gram-positive cocci, so the logical treatment in this case is vancomycin, often with an aminoglycoside (eg, gentamicin) for synergistic activity against enterococci.

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10.

Which of the following statements about beta-lactam antibiotics is false?

Cephalexin and other first-generation cephalosporins do not cross the blood-brain barrier
Ceftriaxone and nafcillin are both eliminated mainly via biliary secretion
Instability of penicillins in gastric acid can limit their oral absorption
Renal tubular reabsorption of amoxicillin is inhibited by probenecid
Ticarcillin has activity against several gram-negative rods

Correct Answer

A. Renal tubular reabsorption of amoxicillin is inhibited by probenecid

Explanation

First- and second-generation cephalosporins are not effective in meningitis because they do not readily enter the cerebrospinal fluid. The elimination half-lives of many beta-lactam antibiotics are prolonged by probenecid, which inhibits their proximal tubular secretion.

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Beta-lactam Antibiotics (10)

Which statement about vancomycin is accurate?

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The primary mechanism of antibacterial action of the penicillins involves inhibition of

Immunofluorescent microscopic examination of fluid expressed from the penile chancre of this patient revealed treponemes. Because he appears to be infected with Treponema pallidum, the best course of action would be to

Resistance of pneumococci to penicillin G is due to

If this patient had been 82-years-old and the Gram stain of the smear of cerebrospinal fluid had revealed gram-positive rods resembling diphtheroids, the antibiotic regimen for empiric treatment would include

A patient needs antibiotic treatment for native valve, culture-positive infective enterococcal endocarditis. His medical history includes a severe anaphylactic reaction to penicillin G during the last year. The best approach would be treatment with

Which of the following statements about beta-lactam antibiotics is false?