ANSWERS

1. Penicillins (and cephalosporins) bind to PBPs acting at the transpeptidation

stage of cell wallsynthesis (the final step) to inhibit peptidoglycan cross-linking.
The beta-lactam antibiotics alsoactivate autolysins, which break down the
bacterial cell wall. Synthesis of N-acetylmuramic acidis inhibited by fosfomycin.
Vancomycin inhibits transglycolase, preventing elongation ofpeptidoglycan
chains. The answer is D

2. 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 oramoxicillin is no longer appropriate for gonorrhea. Similarly,
many strains of gonococci areresistant to tetracyclines. Alternative drugs (not
listed) for gonorrhea include cefixime,azithromycin (see Chapter 44) or
spectinomycin (see Chapter 45). The answer is A

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

4. First- and second-generation cephalosporins are not effective in meningitis

because they do notreadily enter the cerebrospinal fluid. The elimination half-
lives of many beta-lactam antibioticsare prolonged by probenecid, which inhibits
their proximal tubular secretion. The answer is D

5. Each of the drugs listed has activity against some gram-negative bacilli. All
penicillins should beavoided 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 severehypersensitivity reactions after use of a penicillin. There is partial
cross-reactivity betweenpenicillins and the carbapenems such as imipenem and
meropenem, but no cross-reactivitybetween the penicillins and aztreonam. The
answer is A
6. Pneumococcal isolates with a minimal inhibitory concentration for penicillin G
of greater than 2mcg/mL are highly resistant. Such strains are not killed by the
concentrations of penicillin G orampicillin that can be achieved in the
cerebrospinal fluid. Nafcillin has minimal activity againstpenicillin-resistant
pneumococci and piperacillin is mainly used for infections caused by
gramnegative rods. Cefotaxime and ceftriaxone are the most active
cephalosporins against penicillinresistant pneumococci, and the addition of
vancomycin is recommended in the case of highlyresistant strains. The answer is
C

7. Pneumococcal resistance to penicillins is due to changes in the chemical

structures of the targetpenicillin-binding proteins located in the bacterial
cytoplasmic membrane. A similar mechanismunderlies the resistance of
staphylococci to methicillin (MRSA strains). A structural alteration inthe d-Ala-d-
Ala component of the pentapeptide side chains of peptidoglycans is the basis for
amechanism of resistance to vancomycin. The answer is C

8. Diphtheroid-like gram-positive rods in the cerebrospinal fluid smear of an

elderly patient areindicative of L monocytogenes. Listeria infections are more
common in neonates, elderlypatients, and those who have been treated with
immunosuppressive agents. Treatment consistsof ampicillin with or without an
aminoglycoside such as gentamicin. Trimethoprimsulfamethoxazole can also be
used (see Chapter 46). The answer is A

9. In patients who have had a severe reaction to a penicillin, it is inadvisable to

administer acephalosporin or a carbapenem such as meropenem. Aztreonam
has no significant activityagainst gram-positive cocci, so the logical treatment in
this case is vancomycin, often with anaminoglycoside (eg, gentamicin) for
synergistic activity against enterococci. The answer is E

10. Vancomycin is a bactericidal glycoprotein. It inhibits cell wall synthesis but

does not bind toPBPs and is not susceptible to beta-lactamases. Vancomycin is
not absorbed after oraladministration and is used by this route in the treatment of
colitis caused by C difficile andstaphylococci. It undergoes renal elimination.
Vancomycin is commonly considered the drug offirst choice for parenteral use
against methicillin-resistant staphylococci. The answer is A
ANSWERS
1. Chloramphenicol is commonly used outside the United States for treatment of
bacillarydysentery. The drug causes a dose-dependent (reversible) suppression
of erythropoiesis

Although the gray baby syndrome was initially described in neonates, a similar
syndrome hasoccurred with overdosage of chloramphenicol in older children and
adults, especially those withhepatic dysfunction. The answer is C

2. Tetracyclines inhibit bacterial protein synthesis by interfering with the binding

of aminoacyl-tRNAmolecules to bacterial ribosomes. Peptidyl transferase is
inhibited by chloramphenicol. Theanswer is D

3. Clarithromycin can be administered less frequently than erythromycin, but it is

not effective insingle doses against susceptible organisms. Organisms resistant
to erythromycin, includingpneumococci and methicillin-resistant staphylococci,
are also resistant to other macrolides. Druginteractions have occurred with
clarithromycin through its ability to inhibit cytochrome P450

Clarithromycin is more active than erythromycin against M avium complex, T

gondii, and Hpylori. The answer is C

4. Methylase production and methylation of the receptor site are established

mechanisms ofresistance of gram-positive organisms to macrolide antibiotics.
Such enzymes may be inducibleby macrolides or constitutive; in the latter case,
cross-resistance occurs between macrolides andclindamycin. Increased
expression of efflux pumps is also a mechanism of macrolide resistance

Esterase formation is a mechanism of macrolide resistance seen in coliforms.

The answer is E

5. Cervicitis or urethritis is often caused by C trachomatis. Such infections may

develop slowlybecause of the long incubation period of chlamydial infection.
Treatment with oral doxycycline for14 d (as originally prescribed) would have
eradicated C trachomatis and most other organismscommonly associated with
nongonococcal cervicitis or urethritis. Given the limited compliance ofthis patient,
the best course of action would be the administration (in the clinic) of a single
oraldose of azithromycin. The answer is C

6. This patient is in the high-risk category for bacterial endocarditis and should
receive prophylacticantibiotics before many dental procedures. The American
Heart Association recommends thatclindamycin be used in patients allergic to
penicillins. Oral erythromycin is not recommendedbecause it is no more effective
than clindamycin and causes more gastrointestinal side effects

Intravenous vancomycin (not oral), sometimes with gentamicin, is recommended

for prophylaxisin high-risk penicillin-allergic patients undergoing genitourinary
and lower gastrointestinalsurgical procedures. Complete cross-allergenicity must
be assumed between individualpenicillins. The answer is B

7. It is often difficult to establish a definite cause of community-acquired

pneumonia (CAP). Morethan 80% of cases are caused by typical pathogens
such as S pneumoniae, H influenzae, or Mcatarrhalis, and 15% are due to the
nonzoonotic atypial pathogens such as Legionella species,Mycoplasma species,
or C pneumoniae. Currently, monotherapy coverage of both typical andatypical
pathogens in CAP is preferred to double-drug therapy. Preferred initial therapy
includesa macrolide, doxycycline, or a quinolone active against respiratory
pathogens (Chapter 46)

Ampicillin, clindamycin, and vancomycin have low activity against atypical

pathogens in CAP

The answer is C

8. The inhibition of liver cytochrome P450 by erythromycin has led to serious

drug interactions

Although erythromycin does not inhibit loratadine metabolism, it does inhibit the
CYP1A2 form ofcytochrome P450, which metabolizes methylxanthines.
Consequently, cardiac and/or CNStoxicity may occur with excessive ingestion of
caffeine. Unlike the tetracyclines, the oralabsorption of erythromycin is not
affected by cations and the drug does not causephotosensitivity. Because
erythromycin undergoes biliary excretion, there is little reason toassess renal
function before treatment. The answer is C

9. Azithromycin has a half-life of more than 70 h, which allows for once-daily

dosing and a 5-dcourse of treatment for community-acquired pneumonia. Unlike
other macrolides, azithromycindoes not inhibit cytochrome P450 enzymes
involved in drug metabolism. The answer is A

10. Quinupristin-dalfopristin is bactericidal against many drug-resistant gram-

positive cocci,including multidrug-resistant streptococci, MRSA, and vancomycin-
resistant enterococci. Thestreptogramins have activity against E faecium (not E
faecalis). The drugs are potent inhibitorsof CYP3A4 and interfere with the
metabolism of many other drugs. The streptogramins are nothepatotoxic. The
answer is B