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Katzung Pharm-Antimicrobials Pt. 1

Terms in this set (50)

The primary mechanism of antibacterial action of the penicillins involves inhibition of
(A) Beta-lactamases
(B) Cell membrane synthesis
(C) N-acetylmuramic acid synthesis
(D) Peptidoglycan cross-linking
(E) Transglycosylation
(D) Peptidoglycan cross-linking
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.
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.
The most appropriate treatment of gonorrhea in this patient is
(A) A single intramuscular dose of ceftriaxone
(B) Amoxicillin orally for 7 d
(C) Procaine penicillin G intramuscularly as a single dose plus oral probenecid
(D) Meropenem orally for 7 d
(E) Vancomycin intramuscularly as a single dose
(A) A single intramuscular dose of ceftriaxone
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 or spectinomycin.
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.
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
(A) Administer a single oral dose of fosfomycin
(B) Give no other antibiotics because drug treatment of
gonorrhea provides coverage for incubating syphilis
(C) Inject intramuscular benzathine penicillin G
(D) Treat with oral tetracycline for 7 d
(E) Treat with vancomycin
(C) Inject intramuscular benzathine penicillin G
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. However, lack of compliance may be a problem with oral therapy. Fosfomycin and vancomycin have no significant activity against spirochetes.
Which of the following statements about beta-lactam antibiotics is false?
(A) Cephalexin and other first-generation cephalosporins do not cross the blood-brain barrier
(B) Ceftriaxone and nafcillin are both eliminated mainly via biliary secretion
(C) Instability of penicillins in gastric acid can limit their oral absorption
(D) Renal tubular reabsorption of amoxicillin is inhibited by probenecid
(E) Ticarcillin has activity against several gram negative rods
(D) Renal tubular reabsorption of amoxicillin is inhibited by probenecid
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.
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
(A) Aztreonam
(B) Ceftriaxone
(C) Meropenem
(D) Oxacillin
(E) Ticarcillin plus clavulanic acid
(A) Aztreonam
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.
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
(A) Amoxicillin
(B) Cephalexin
(C) Ceftriaxone plus vancomycin
(D) Nafcillin
(E) Piperacillin
(C) Ceftriaxone plus vancomycin
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.
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.
Resistance of pneumococci to penicillin G is due to
(A) Alterations in porin structure
(B) Beta-lactamase production
(C) Changes in chemical structure of target penicillin-binding
proteins
(D) Changes in the d-Ala-d-Ala building block of peptido-glycan precursor
(E) Decreased intracellular accumulation of penicillin G
(C) Changes in chemical structure of target penicillin-binding proteins
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.
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.
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) Ampicillin
(B) Cefoxitin
(C) Ceftriaxone
(D) Fosfomycin
(E) Vancomycin
(A) Ampicillin
Diphtheroid-like gram-positive rods in the cerebrospinal fluid smear of an elderly patient are indicative of L mono- cytogenes. 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.
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
(A) Amoxicillin-clavulanate
(B) Aztreonam
(C) Ceftriaxone
(D) Ticarcillin
(E) Vancomycin
(E) Vancomycin
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.
Which statement about vancomycin is accurate?
(A) Active against methicillin-resistant staphylococci
(B) Bacteriostatic
(C) Binds to PBPs
(D) Hepatic metabolism
(E) Oral bioavailability
(A) Active against methicillin-resistant staphylococci
Vancomycin is a bactericidal glycoprotein. It inhibits cell wall synthesis but does not bind to PBPs and is not susceptible to beta-lactamases. Vancomycin is not absorbed after oral administration and is used by this route in the treatment of colitis caused by C difficile and staphylococci. It undergoes renal elimination. Vancomycin is commonly considered the drug of first choice for parenteral use against methicillin-resistant staphylococci.
A 4-year-old child is brought to the hospital after ingesting pills that a parent had used for bacterial dysentery when traveling outside the United States. The child has been vomiting for more than 24 h and has had diarrhea with green stools. She is now lethargic with an ashen color. Other signs and symptoms include hypothermia, hypotension, and abdominal distention. The drug most likely to be the cause of this problem is
(A) Ampicillin
(B) Azithromycin
(C) Chloramphenicol
(D) Doxycycline
(E) Erythromycin
(C) Chloramphenicol
Chloramphenicol is commonly used outside the United States for treatment of bacillary dysentery. The drug causes a dose-dependent (reversible) suppression of erythropoiesis. Although the gray baby syndrome was initially described in neonates, a similar syndrome has occurred with overdosage of chloramphenicol in older children and adults, especially those with hepatic dysfunction.
The mechanism of antibacterial action of tetracycline involves
(A) Antagonism of bacterial translocase activity
(B) Binding to a component of the 50S ribosomal subunit
(C) Inhibition of DNA-dependent RNA polymerase
(D) Interference with binding of aminoacyl-tRNA to bacterial ribosomes
(E) Selective inhibition of ribosomal peptidyl transferases
(D) Interference with binding of aminoacyl-tRNA to bacterial ribosomes
Tetracyclines inhibit bacterial protein synthesis by interfering with the binding of aminoacyl-tRNA molecules to bacterial ribosomes. Peptidyl transferase is inhibited by chloramphenicol.
Clarithromycin and erythromycin have very similar spectra of antimicrobial activity. The major advantage of clarithromycin is that it
(A) Does not inhibit hepatic drug-metabolizing enzymes
(B) Eradicates mycoplasmal infections in a single dose
(C) Has greater activity against H pylori
(D) Is active against methicillin-resistant strains of staphylococci
(E) Is active against strains of streptococci that are resistant to erythromycin
(C) Has greater activity against H pylori
Clarithromycin can be administered less frequently than erythromycin, but it is not effective in single doses against susceptible organisms. Organisms resistant to erythromycin, including pneumococci and methicillin-resistant staphylococci, are also resistant to other macrolides. Drug interactions have occurred with clarithromycin through its ability to inhibit cytochrome P450. Clarithromycin is more active than erythromycin against M avium complex, T gondii, and H pylori.
The primary mechanism of resistance of gram-positive organisms to macrolide antibiotics including erythromycin is
(A) Changes in the 30S ribosomal subunit
(B) Decreased drug permeability of the cytoplasmic membrane
(C) Formation of drug-inactivating acetyltransferases
(D) Formation of esterases that hydrolyze the lactone ring
(E) Methylation of binding sites on the 50S ribosomal subunit
(E) Methylation of binding sites on the 50S ribosomal subunit
Methylase production and methylation of the receptor site are established mechanisms of resistance of gram-positive organisms to macrolide antibiotics. Such enzymes may be inducible by macrolides or constitutive; in the latter case, cross-resistance occurs between macrolides and clindamycin. Increased expression of efflux pumps is also a mechanism of macrolide resistance. Esterase formation is a mechanism of macrolide resistance seen in coliforms.
A 26-year-old woman was treated for a suspected chlamydial infection at a neighborhood clinic. She was given a prescription for oral doxycycline to be taken for 14 d. Three weeks later, she returned to the clinic with a mucopurulent cervicitis. On questioning she admitted not having the prescription filled. The best course of action at this point would be to
(A) Delay drug treatment until the infecting organism is identified
(B) Rewrite the original prescription for oral doxycycline
(C) Treat her in the clinic with a single oral dose of azithromycin
(D) Treat her in the clinic with an intravenous dose of amoxicillin
(E) Write a prescription for oral erythromycin for 10 d
(C) Treat her in the clinic with a single oral dose of azithromycin
Cervicitis or urethritis is often caused by C trachomatis. Such infections may develop slowly because of the long incubation period of chlamydial infection. Treatment with oral doxycycline for 14 d (as originally prescribed) would have eradicated C trachomatis and most other organisms commonly associated with nongonococcal cervicitis or urethritis. Given the limited compliance of this patient, the best course of action would be the administration (in the clinic) of a single oral dose of azithromycin.
A 55-year-old patient with a prosthetic heart valve is to undergo a periodontal procedure involving scaling and root planing. Several years ago, the patient had a severe allergic reaction to procaine penicillin G. Regarding prophylaxis against bacterial endocarditis, which one of the following drugs taken orally is most appropriate?
(A) Amoxicillin 10 min before the procedure
(B) Clindamycin 1 h before the procedure
(C) Erythromycin 1 h before the procedure and 4 h after the procedure
(D) Vancomycin 15 min before the procedure
(E) No prophylaxis is needed because this patient is in the negligible risk category
(B) Clindamycin 1 h before the procedure
This patient is in the high-risk category for bacterial endocarditis and should receive prophylactic antibiotics before many dental procedures. The American Heart Association recommends that clindamycin be used in patients allergic to penicillins. Oral erythromycin is not recommended because it is no more effective than clindamycin and causes more gastrointestinal side effects. Intravenous vancomycin (not oral), sometimes with gentamicin, is recommended for prophylaxis in high-risk penicillin-allergic patients undergoing genitourinary and lower gastrointestinal surgical procedures. Complete cross-allergenicity must be assumed between individual penicillins.
A 24-year-old woman comes to a clinic with complaints of dry cough, headache, fever, and malaise, which have lasted 3 or 4 d. She appears to have some respiratory difficulty, and chest examination reveals rales but no other obvious signs of pulmonary involvement. However, extensive patchy infiltrates are seen on chest x-ray film. Gram stain of expectorated sputum fails to reveal any bacterial pathogens. The patient mentions that a colleague at work had similar symptoms to those she is experiencing. The patient has no history of serious medical problems. She takes loratadine for allergies and supplementary iron tablets, and she drinks at least 6 cups of caffeinated coffee per day. The physician makes an initial diagnosis of community-acquired pneumonia.
Regarding the treatment of this patient, which of the following drugs is most suitable?
(A) Ampicillin
(B) Clindamycin
(C) Doxycycline
(D) Linezolid
(E) Vancomycin
(C) Doxycycline
It is often difficult to establish a definite cause of community-acquired pneumonia (CAP). More than 80% of cases are caused by typical pathogens such as S pneumoniae, H influenzae, or M catarrhalis, and 15% are due to the nonzoonotic atypial pathogens such as Legionella species, Mycoplasma species, or C pneumoniae. Currently, monotherapy coverage of both typical and atypical pathogens in CAP is preferred to double-drug therapy. Preferred initial therapy includes a macrolide, doxycycline, or a quinolone active against respiratory pathogens. Ampicillin, clindamycin, and vancomycin have low activity against atypical pathogens in CAP.
A 24-year-old woman comes to a clinic with complaints of dry cough, headache, fever, and malaise, which have lasted 3 or 4 d. She appears to have some respiratory difficulty, and chest examination reveals rales but no other obvious signs of pulmonary involvement. However, extensive patchy infiltrates are seen on chest x-ray film. Gram stain of expectorated sputum fails to reveal any bacterial pathogens. The patient mentions that a colleague at work had similar symptoms to those she is experiencing. The patient has no history of serious medical problems. She takes loratadine for allergies and supplementary iron tablets, and she drinks at least 6 cups of caffeinated coffee per day. The physician makes an initial diagnosis of community-acquired pneumonia.
If this patient were to be treated with erythromycin, she should
(A) Avoid exposure to sunlight
(B) Avoid taking supplementary iron tablets
(C) Decrease her intake of caffeinated beverages
(D) Have her plasma urea nitrogen or creatinine checked before treatment
(E) Temporarily stop taking loratadine
(C) Decrease her intake of caffeinated beverages
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 of cytochrome P450, which metabolizes methylxanthines.. Consequently, cardiac and/or CNS toxicity may occur with excessive ingestion of caffeine. Unlike the tetracyclines, the oral absorption of erythromycin is not affected by cations and the drug does not cause photosensitivity. Because erythromycin undergoes biliary excretion, there is little reason to assess renal function before treatment.
A 24-year-old woman comes to a clinic with complaints of dry cough, headache, fever, and malaise, which have lasted 3 or 4 d. She appears to have some respiratory difficulty, and chest examination reveals rales but no other obvious signs of pulmonary involvement. However, extensive patchy infiltrates are seen on chest x-ray film. Gram stain of expectorated sputum fails to reveal any bacterial pathogens. The patient mentions that a colleague at work had similar symptoms to those she is experiencing. The patient has no history of serious medical problems. She takes loratadine for allergies and supplementary iron tablets, and she drinks at least 6 cups of caffeinated coffee per day. The physician makes an initial diagnosis of community-acquired pneumonia.
A 5-d course of treatment for community-acquired pneumonia would be effective in this patient with little risk of drug interactions if the drug prescribed were
(A) Azithromycin
(B) Clindamycin
(C) Doxycycline
(D) Erythromycin
(E) Vancomycin
(A) Azithromycin
Azithromycin has a half-life of more than 70 h, which allows for once-daily dosing and a 5-d course of treatment for community-acquired pneumonia. Unlike other macrolides, azithromycin does not inhibit cytochrome P450 enzymes involved in drug metabolism.
Concerning quinupristin-dalfopristin, which statement is accurate?
(A) Active in treatment of infections caused by E faecalis
(B) An effective drug in treatment of multidrug-resistant streptococcal infections
(C) Bacteriostatic
(D) Hepatotoxicity has led to FDA drug alerts
(E) Increase the activity of hepatic drug-metabolizing enzymes
(B) An effective drug in treatment of multidrug-resistant streptococcal infections
Quinupristin-dalfopristin is bactericidal against many drug- resistant gram-positive cocci, including multidrug-resistant streptococci, MRSA, and vancomycin-resistant enterococci. The streptogramins have activity against E faecium (not E faecalis). The drugs are potent inhibitors of CYP3A4 and interfere with the metabolism of many other drugs. The streptogramins are not hepatotoxic.
Regarding the mechanism of action of aminoglycosides, the drugs
(A) Are bacteriostatic
(B) Bind to the 50S ribosomal subunit
(C) Cause misreading of the code on the mRNA template
(D) Inhibit peptidyl transferase
(E) Stabilize polysomes
(C) Cause misreading of the code on the mRNA template
Aminoglycosides are bactericidal inhibitors of protein synthesis binding to specific components of the 30S ribosomal subunit. Their actions include block of the formation of the initiation complex, miscoding, and polysomal breakup. Peptidyl transferase is inhibited by chloramphenicol, not aminoglycosides.
A 72-kg patient with creatinine clearance of 80 mL/min has a gram-negative infection. Amikacin is administered intramuscularly at a dose of 5 mg/kg every 8 h, and the patient begins to respond. After 2 d, creatinine clearance declines to 40 mL/min. Assuming that no information is available about amikacin plasma levels, what would be the most reasonable approach to management of the patient at this point?
(A) Administer 5 mg/kg every 12 h
(B) Decrease the dosage to daily total of 200 mg
(C) Decrease the dosage to 180 mg every 8 h
(D) Discontinue amikacin and switch to gentamicin
(E) Maintain the patient on the present dosage and test
auditory function
(C) Decrease the dosage to 180 mg every 8 h
Monitoring plasma drug levels is important when aminoglycosides are used. In this case, the patient seems to be improving, so a decrease of the amikacin dose in proportion to decreased creatinine clearance is most appropriate. Because creatinine clearance is only one half of the starting value, a dose reduction should be made to one half of that given initially.
All of the following statements about the clinical uses of the aminoglycosides are accurate except
(A) Effective in the treatment of infections caused by anaerobes such as Bacteroides fragilis
(B) Gentamycin is used with ampicillin for synergistic effects in the treatment of enterococcal endocarditis
(C) In the treatment of a hospital-acquired infection caused by Serratia marcescens, netilmicin is more effective than streptomycin
(D) Often used with cephalosporins in the empiric treatment of life-threatening bacterial infections
(E) Owing to their polar nature, aminoglycosides are not absorbed after oral administration
(A) Effective in the treatment of infections caused by anaerobes such as Bacteroides fragilis
Aminoglycoside antibiotics act at the ribosomal level and their intracellular accumulation by bacteria is oxygen dependent. Anaerobic bacteria including B fragilis are innately resistant.
Which statement is accurate regarding the antibacterial action of the aminoglycoside amikacin?
(A) Antibacterial activity is often reduced by the presence of an inhibitor of cell wall synthesis
(B) Antibacterial action is not concentration-dependent
(C) Antibacterial action is time-dependent
(D) Efficacy is directly proportional to the duration of time that the plasma level is greater than the minimal inhibitory concentration
(E) The drug continues to exert antibacterial effects even after plasma levels decrease below detectable levels
(E) The drug continues to exert antibacterial effects even after plasma levels decrease below detectable levels
The antibacterial action of aminoglycosides is concentration dependent rather than time dependent. The activity of amikacin continues to increase as its plasma level rises above the minimal inhibitory concentration (MIC). When the plasma level falls below the MIC, aminoglycosides continue to exert antibacterial effects for several hours, exerting a post-antibiotic effect. Inhibitors of bacterial cell wall synthesis often exert synergistic effects with aminoglycosides, possibly by increasing the intracellular accumulation of the aminoglycoside.
An adult patient (weight 80 kg) has bacteremia suspected to be due to a gram-negative rod. Tobramycin is to be administered using a once-daily dosing regimen, and the loading dose must be calculated to achieve a peak plasma level of 20 mg/L. Assume that the patient has normal renal function. Pharmacokinetic parameters of tobramycin in this patient are as follows: Vd =30L;t1/2 =3h;CL=80mL/min. What loading dose should be given?
(A) 100 mg
(B) 200 mg
(C) 400 mg
(D) 600 mg
(E) 800 mg
(D) 600 mg
The loading dose of any drug is calculated by multiplying the desired plasma concentration (mg/L) by the volume of distribution (L).
A 76-year-old man is seen in a hospital emergency department complaining of pain in and behind the right ear. Physical examination shows edema of the external otic canal with purulent exudate and weakness of the muscles on the right side of the face. The patient informs the physician that he is a diabetic. Gram stain of the exudate from the ear shows many polymorphonucleocytes and gram-negative rods, and samples are sent to the microbiology laboratory for culture and drug susceptibility testing. A preliminary diagnosis is made of external otitis. At this point, which of the following is most appropriate?
(A) Amikacin should be injected intramuscularly and the patient should be sent home
(B) Analgesics should be prescribed, but antibiotics should be withheld pending microbiological results
(C) Oral cefaclor should be prescribed together with analgesics, and the patient should be sent home
(D) The patient should be hospitalized and treatment started with imipenem-cilastatin
(E) The patient should be hospitalized and treatment started with gentamicin plus ticarcillin
(E) The patient should be hospitalized and treatment started with gentamicin plus ticarcillin
The diabetic patient with external otitis is at special risk because of the danger of spread to the middle ear and possibly the meninges, so hospitalization is advisable, especially in the elderly. Likely pathogens include E coli and Pseudomonas aeruginosa, and coverage must be provided for these and possibly other gram-negative rods. The combination of an aminoglycoside plus a wider spectrum penicillin is most suitable in this case and is synergistic against many pseudomonas strains. Imipenem-cilastatin is also possible, but resistant strains of P aeruginosa have emerged during treatment. Cefaclor lacks antipseudomonal activity.
Regarding the toxicity of aminoglycosides which statement is accurate?
(A) Gentamicin and tobramycin are the least likely to cause renal damage
(B) Ototoxicity due to amikacin and gentamicin includes vestibular dysfunction, which is often irreversible
(C) Ototoxicity is reduced if loop diuretics are used to facilitate the renal excretion of aminoglycoside antibiotics
(D) Reduced blood creatinine is an early sign of aminoglycoside nephrotoxicity
(E) Skin reactions are very rare following topical use of neomycin
(B) Ototoxicity due to amikacin and gentamicin includes vestibular dysfunction, which is often irreversible
Gentamicin and tobramycin are the most nephrotoxic aminoglycosides. The incidence of nephrotoxic effects with gentamicin is 2 to 3 times greater than the incidence of ototoxicity. With traditional dosage regimens, the first indication of potential nephrotoxicity is an increase in trough serum levels of aminoglycosides, which is followed by an increase in blood creatinine. Although aminoglycoside ototoxicity usually involves irreversible effects on vestibular function, hearing loss can also occur. Ototoxicity is enhanced by loop diuretics. Skin reactions are common with topical use of neomycin.
This drug has characteristics almost identical to those of gentamicin but has much weaker activity in combination with penicillin against enterococci.
(A) Amikacin
(B) Erythromycin
(C) Netilmicin
(D) Spectinomycin
(E) Tobramycin
(E) Tobramycin
Tobramycin is almost identical to gentamicin in both its pharmacodynamic and pharmacokinetic properties. However, for reasons that are unclear, it is much less active than either gentamicin or streptomycin when used in combination with a penicillin in the treatment of enterococcal endocarditis.
Your 23-year-old female patient is pregnant and has gonorrhea. The medical history includes anaphylaxis following exposure to amoxicillin. The most appropriate drug to use is
(A) Azithromycin
(B) Cefixime
(C) Ceftriaxone
(D) Ciprofloxacin
(E) Doxycycline
(A) Azithromycin
All of the listed drugs have been used for the treatment of gonorrhea. Cephalosporins should be avoided in patients with a history of severe hypersensitivity to penicillins, and fluoroquinolones should be avoided in pregnancy. Tetracyclines including doxycycline have been used in the past for gonorrhea, but not as single doses, and they too should be avoided in pregnancy.
Which statement about "once-daily" dosing with aminoglycosides is not accurate?
(A) Dose adjustment is less important in renal dysfunction
(B) It is convenient for outpatient treatment
(C) Less nursing time is required for drug administration
(D) Often less side effects than multiple (conventional) dosing regimens
(E) Underdosing is less of a problem
(A) Dose adjustment is less important in renal dysfunction
In "once-daily dosing" with aminoglycosides, the selection of an appropriate dose is particularly critical in patients with renal insufficiency. The aminoglycosides are eliminated by the kidney in proportion to creatinine clearance. Knowledge of the degree of insufficiency, based on plasma creatinine (or BUN), is essential for estimation of the appropriate single daily dose of an aminoglycoside.
Trimethoprim-sulfamethoxazole is established to be effective against which of the following opportunistic infections in the AIDS patient?
(A) Cryptococcal meningitis
(B) Herpes simplex
(C) Oral candidiasis
(D) Toxoplasmosis
(E) Tuberculosis
(D) Toxoplasmosis
Trimethoprim-sulfamethoxazole is not effective in the treatment of infections caused by viruses, fungi, or mycobacteria. However, the drug combination is active against certain protozoans, including Toxoplasma, and can be used for both prevention and treatment of toxoplasmosis in the severely immunocompromised AIDS patient.
A 65-year-old woman has returned from a vacation abroad suffering from traveler's diarrhea, and her problem has not responded to antidiarrheal drugs. A pathogenic gram-negative bacillus is suspected. Which drug is most likely to be effective in the treatment of this patient?
(A) Ampicillin
(B) Ofloxacin
(C) Sulfadiazine
(D) Trimethoprim
(E) Vancomycin
(B) Ofloxacin
The second-generation fluoroquinolones are very effective in diarrhea caused by bacterial gram-negative pathogens, including E coli, Shigella, and Salmonella. None of the other drugs listed would be appropriate. Many coliforms are now resistant to amoxicillin and ampicillin. Although trimethoprim is available as a single drug, resistance emerges rapidly during treatment unless it is used for urinary tract infections, in which high concentrations can be achieved. Vancomycin has no activity against gram-negative bacilli.
Which statement about the clinical use of sulfonamides is false?
(A) Active against C trachomatis and can be used topically for treatment of chlamydial infections of the eye
(B) Are not effective as sole agents in the treatment of prostatitis
(C) Effective in Rocky Mountain spotted fever
(D) In some bacterial strains resistance occurs via increased PABA formation
(E) Reduced intracellular uptake is a mechanism of sulfonamide resistance in some bacterial strains
(C) Effective in Rocky Mountain spotted fever
Sulfonamides have minimal therapeutic actions in rickettsial infections. Chloramphenicol may be used for Rocky Mountain spotted fever in patients with established allergy or other contraindication to tetracyclines. All of the other statements about sulfonamide antimicrobial drugs are accurate.
A 31-year-old man has gonorrhea. He has no drug allergies, but a few years ago acute hemolysis followed use of an anti-malarial drug. The physician is concerned that the patient has an accompanying urethritis caused by C trachomatis, although no cultures or enzyme tests have been performed. Which of the following drugs will be reliably effective against both gonococci and C trachomatis and safe to use in this patient?
(A) Cefixime
(B) Ciprofloxacin
(C) Spectinomycin
(D) Sulfamethoxazole-trimethoprim
(E) None of the above
(E) None of the above
Cefixime in a single oral dose is effective in gonorrhea, but it has no activity against organisms causing nongonococcal urethritis. Spectinomycin is active against most gonococci, but does not eradicate a uro-genital chlamydial infection. Although ciprofloxacin might be effective in both gonorrhea and chlamydial urethritis, it is no longer recommended for treatment of gonorrhea in the United States, since resistance is now common. This patient could be treated by single oral doses of cefixime plus azithromycin (not listed). Sulfamethoxazole or TMP-SMZ would not be useful and may cause acute hemolysis in this patient.
Which statement about the fluoroquinolones is accurate?
(A) Antacids increase their oral bioavailability
(B) Contraindicated in patients with hepatic dysfunction
(C) Fluoroquinolones are drugs of choice in a 6-year-old child with a urinary tract
(D) Gonococcal resistance to fluoroquinolones may involve changes in DNA gyrase
(E) Modification of moxifloxacin dosage is required in patients when creatinine clearance is less than 50 mL/ min
(D) Gonococcal resistance to fluoroquinolones may involve changes in DNA gyrase
Antacids can decrease oral bioavailability of fluoroquinolones. Neither hepatic or renal dysfunction is a contraindication to the use of fluoroquinolones. Most fluoroquinolones undergo renal elimination and dosage should be modified with creatinine clearance <50 mL/min. Moxifloxacin elimination occurs mainly via the liver. The fluoroquinolones should not be used to treat uncomplicated first-time urinary tract infections in children because of possible effects on cartilage development. Uncomplicated urinary tract infections in children are usually due to a strain of E coli that is sensitive to many other drugs, including beta-lactam antibiotics.
A 40-year-old man complains of periodic bouts of diarrhea with lower abdominal cramping and intermittent rectal bleeding. Seen in the clinic, he appears well nourished, with blood pressure in the normal range. Examination reveals moderate abdominal pain and tenderness. His current medications are limited to loperamide for his diarrhea. Sigmoidoscopy reveals mucosal edema, friability, and some pus. Laboratory findings include mild anemia and decreased serum albumin. Microbiologic examination via stool cultures and mucosal biopsies do not reveal any evidence for bacterial, amebic, or cytomegalovirus involvement. The most appropriate drug to use in this patient is
(A) Ampicillin
(B) Doxycycline
(C) Norfloxacin
(D) Sulfasalazine
(E) Trimethoprim-sulfamethoxazole
(D) Sulfasalazine
In the absence of any evidence pointing toward a definite microbial cause for the colitis in this patient, a drug that decreases inflammation is indicated. Sulfasalazine has significant anti-inflammatory action, and its oral use results in symptomatic improvement in 50-75% of patients suffering from ulcerative colitis. The drug is also used for its anti-inflammatory effects in rheumatoid arthritis.
Which adverse effect is most common with sulfonamides?
(A) Fanconi's aminoaciduria syndrome
(B) Hematuria
(C) Kernicterus in the newborn
(D) Neurologic dysfunction
(E) Skin rash
(E) Skin rash
The most common adverse effect of the sulfonamides is a skin rash caused by hypersensitivity. Neurologic dysfunction and hematuria occur less frequently. Sulfonamides are usually avoided in the third trimester of pregnancy or in neonates, so kernicterus is rare. Fanconi's syndrome is associated with the use of outdated tetracyclines.
Which drug is effective in the treatment of nocardiosis and, in combination with pyrimethamine, is prophylactic against Pneumocystis jirovecii infections in AIDS patients?
(A) Amoxicillin
(B) Erythromycin
(C) Levofloxacin
(D) Sulfadiazine
(E) Trimethoprim
(D) Sulfadiazine
Sulfadiazine and TMP-SMZ are drugs of choice in nocardiosis. In combination with pyrimethamine (an effective dihydrofolate reductase inhibitor in protozoa), sulfadiazine is effective in toxoplasmosis and is prophylactic against pneumocystis pneumonia in the AIDS patient. However, TMP-SMZ is more commonly used for the latter purpose.
Which statement about ciprofloxacin is accurate?
(A) Antagonism occurs if used with dihydrofolate reductase inhibitors
(B) Ciprofloxacin is active against MRSA strains of staphylococci
(C) Most "first-time" urinary tract infections are resistant to ciprofloxacin
(D) Organisms that commonly cause ear infections are highly resistant
(E) Tendinitis may occur during treatment
(E) Tendinitis may occur during treatment
Ciprofloxacin is commonly used for the treatment of urinary tract infections and is active against most strains of common causative agents of otitis media, including H influenzae and pneumococci. However, up to 50% of strains of MRSA are now resistant to ciprofloxacin. No clinical antagonism has been reported between fluoroquinolones and inhibitors of folic acid synthesis. Fluoroquinolones are not recommended for use in pregnancy or for children less than 10 years of age because they may damage growing cartilage. Tendonitis and tendon rupture are adverse effects of the fluoroquinolones.
Supplementary folinic acid may prevent anemia in folate-deficient persons who use this drug; it is a weak base achieving tissue levels similar to those in plasma
(A) Ciprofloxacin
(B) Levofloxacin
(C) Linezolid
(D) Sulfamethoxazole
(E) Trimethoprim
(E) Trimethoprim
Trimethoprim is the only weak base listed (fluoroquinolones and sulfonamides are acidic compounds), and its high lipid solubility at blood pH allows penetration of the drug into prostatic and vaginal fluid to reach levels similar to those in plasma. Leukopenia and thrombocytopenia may occur in folate deficiency when the drug is used alone or in combination with sulfamethoxazole. Fluoroquinolones and linezolid do not exacerbate symptoms of folic acid deficiency.
The primary reason for the use of drug combinations in the treatment of tuberculosis is to
(A) Delay or prevent the emergence of resistance
(B) Ensure patient compliance with the drug regimen
(C) Increase antibacterial activity synergistically
(D) Provide prophylaxis against other bacterial infections
(E) Reduce the incidence of adverse effects
(A) Delay or prevent the emergence of resistance
Although it is sometimes possible to achieve synergistic effects against mycobacteria with drug combinations, the primary reason for their use is to delay the emergence of resistance.
A 21-year-old woman from Southeast Asia has been staying with family members in the United States for the last 3 mo and is looking after her sister's preschool children during the day. Because she has difficulty with the English language, her sister escorts her to the emergency department of a local hospital. She tells the staff that her sister has been feeling very tired for the last month, has a poor appetite, and has lost weight. The patient has been feeling somewhat better lately except for a cough that produces a greenish sputum, sometimes specked with blood. With the exception of rales in the left upper lobe, the physical examination is unremarkable and she does not seem to be acutely ill. Laboratory values show a white count of 12,000/μL and a hematocrit of 33%. Chest x-ray film reveals an infiltrate in the left upper lobe with a possible cavity. A Gram-stained smear of the sputum shows mixed flora with no dominance. An acid-fast stain reveals many thin rods of pinkish hue. A preliminary diagnosis is made of pulmonary tuberculosis. Sputum is sent to the laboratory for culture.
At this point, the most appropriate course of action is to
(A) Hospitalize the patient and start treatment with 4 anti-tubercular drugs
(B) Hospitalize the patient and start treatment with rifampin
(C) Prescribe isoniazid for prophylaxis and send the patient home to await culture results
(D) Provide no drugs and send the patient home to await culture results
(E) Treat the patient with isoniazid plus rifampin
(A) Hospitalize the patient and start treatment with 4 anti-tubercular drugs
Despite the fact that this patient does not appear to be acutely ill, she would in most cases be treated with 4 drugs that have activity against M tuberculosis. This is because organisms infecting patients from Southeast Asia are commonly INH-resistant, and coverage must be provided with 3 other antituberculosis drugs in addition to isoniazid. This patient should be hospitalized for several reasons, including potential difficulties with compliance regarding the drug regimen and the fact that young children are in the home where she is living.
A 21-year-old woman from Southeast Asia has been staying with family members in the United States for the last 3 mo and is looking after her sister's preschool children during the day. Because she has difficulty with the English language, her sister escorts her to the emergency department of a local hospital. She tells the staff that her sister has been feeling very tired for the last month, has a poor appetite, and has lost weight. The patient has been feeling somewhat better lately except for a cough that produces a greenish sputum, sometimes specked with blood. With the exception of rales in the left upper lobe, the physical examination is unremarkable and she does not seem to be acutely ill. Laboratory values show a white count of 12,000/μL and a hematocrit of 33%. Chest x-ray film reveals an infiltrate in the left upper lobe with a possible cavity. A Gram-stained smear of the sputum shows mixed flora with no dominance. An acid-fast stain reveals many thin rods of pinkish hue. A preliminary diagnosis is made of pulmonary tuberculosis. Sputum is sent to the laboratory for culture.
Which drug regimen should be initiated in this patient when treatment is started?
(A) Amikacin, isoniazid, pyrazinamide, streptomycin
(B) Ciprofloxacin, cycloserine, isoniazid, PAS
(C) Ethambutol, isoniazid, pyrazinamide, rifampin
(D) Isoniazid, pyrazinamide, rifampin, streptomycin
(E) PAS, pyrazinamide, rifabutin, streptomycin
(C) Ethambutol, isoniazid, pyrazinamide, rifampin
Sputum cultures will not be available for several weeks, and no information is available regarding drug susceptibility of the organism at this stage. For optimum coverage, the initial regimen should include INH, rifampin, pyrazinamide, and ethambutol. INH-resistant organisms are usually sensitive to both rifampin and pyrazinamide. Streptomycin is usually reserved for use in severe forms of tuberculosis or for infections known to be resistant to first-line drugs. Likewise, amikacin and ciprofloxacin are possible agents for treatment of multidrug-resistant strains of M tuberculosis. Cycloserine, PAS, and rifabutin are alternative second-line drugs that may be used in cases of failed response to more conventional agents.
A 21-year-old woman from Southeast Asia has been staying with family members in the United States for the last 3 mo and is looking after her sister's preschool children during the day. Because she has difficulty with the English language, her sister escorts her to the emergency department of a local hospital. She tells the staff that her sister has been feeling very tired for the last month, has a poor appetite, and has lost weight. The patient has been feeling somewhat better lately except for a cough that produces a greenish sputum, sometimes specked with blood. With the exception of rales in the left upper lobe, the physical examination is unremarkable and she does not seem to be acutely ill. Laboratory values show a white count of 12,000/μL and a hematocrit of 33%. Chest x-ray film reveals an infiltrate in the left upper lobe with a possible cavity. A Gram-stained smear of the sputum shows mixed flora with no dominance. An acid-fast stain reveals many thin rods of pinkish hue. A preliminary diagnosis is made of pulmonary tuberculosis. Sputum is sent to the laboratory for culture.
Which statement concerning the possible use of isoniazid (INH) in this patient is false?
(A) Dyspnea, flushing, palpitations, and sweating may occur after ingestion of tyramine-containing foods
(B) In patients from Southeast Asia, lower maintenance doses are necessary
(C) Peripheral neuritis may occur during treatment
(D) The patient should take pyridoxine daily
(E) The risk of the patient developing hepatitis from INH is less than 2%
(B) In patients from Southeast Asia, lower maintenance doses are necessary
Patients from Pacific Rim countries do not require lower doses of INH! Fast acetylators, including Native Americans, may require higher doses of the drug than others. Peripheral neuropathy caused by INH is due to pyridoxine deficiency. It is more common in the diabetic, malnourished, or AIDS patient and can be prevented by a daily dose of 25-50 mg of pyridoxine. INH can inhibit monoamine oxidase type A and has caused tyramine reactions. Hepatotoxicity is age-dependent, with an incidence of 0.3% in patients aged 21-35 yr and greater than 2% in patients older than 50 yr.
A 21-year-old woman from Southeast Asia has been staying with family members in the United States for the last 3 mo and is looking after her sister's preschool children during the day. Because she has difficulty with the English language, her sister escorts her to the emergency department of a local hospital. She tells the staff that her sister has been feeling very tired for the last month, has a poor appetite, and has lost weight. The patient has been feeling somewhat better lately except for a cough that produces a greenish sputum, sometimes specked with blood. With the exception of rales in the left upper lobe, the physical examination is unremarkable and she does not seem to be acutely ill. Laboratory values show a white count of 12,000/μL and a hematocrit of 33%. Chest x-ray film reveals an infiltrate in the left upper lobe with a possible cavity. A Gram-stained smear of the sputum shows mixed flora with no dominance. An acid-fast stain reveals many thin rods of pinkish hue. A preliminary diagnosis is made of pulmonary tuberculosis. Sputum is sent to the laboratory for culture.
On her release from the hospital, the patient is advised not to rely solely on oral contraceptives to prevent pregnancy because they may be less effective while she is being maintained on antimycobacterial drugs. The agent most likely to interfere with the action of oral contraceptives is
(A) Amikacin
(B) Ethambutol
(C) Isoniazid
(D) Pyrazinamide
(E) Rifampin
(E) Rifampin
Rifampin induces the formation of several microsomal drug-metabolizing enzymes, including cytochrome P450 isoforms. This action increases the rate of elimination of a number of drugs, including anticoagulants, ketoconazole, methadone, and steroids that are present in oral contraceptives. The pharmacologic activity of these drugs can be reduced markedly in patients taking rifampin.
A patient with AIDS and a CD4 cell count of 100/μL has persistent fever and weight loss associated with invasive pulmonary disease due to M avium complex (MAC). Optimal management of this patient is to
(A) Choose an antibiotic based on drug susceptibility of the cultured organism
(B) Initiate a two-drug regimen of INH and pyrazinamide
(C) Prescribe rifabutin because it prevents the development of MAC bacteremia
(D) Start treatment with the combination of azithromycin, ethambutol, and rifabutin
(E) Treat with trimethoprim-sulfamethoxazole
(D) Start treatment with the combination of azithromycin, ethambutol, and rifabutin
Combinations of antibiotics are essential for suppression of disease caused by M avium complex in the AIDS patient, and treatment should be started before culture results are available. Although rifabutin is prophylactic against MAC bacteremia when it is used as sole therapy in active disease, resistant strains of the organism emerge rapidly. MAC is much less susceptible than M tuberculosis to conventional antimycobacterial drugs. Currently, the optimum regimen consists of azithromycin (or clarithromycin) with etham- butol and rifabutin.
A 10-year-old boy has uncomplicated pulmonary tuberculosis. After initial hospitalization, he is now being treated at home with isoniazid, rifampin, and ethambutol. Which statement about this case is accurate?
(A) A baseline test of auditory function test is essential before drug treatment is initiated
(B) His mother, who takes care of him, does not need INH prophylaxis
(C) His 3-year-old sibling should receive INH prophylaxis
(D) Polyarthralgia is a potential adverse effect of the drugs the boy is taking
(E) The potential nephrotoxicity of the prescribed drugs warrants periodic assessment of renal function
(C) His 3-year-old sibling should receive INH prophylaxis
A baseline test of ocular (not auditory) function may be useful before starting ethambutol. None of the drugs prescribed is associated with nephrotoxicity. Polyarthralgia is a common adverse effect of pyrazinamide that was not prescribed in this case. Periodic tests of liver function may be advisable in younger patients who are treated with INH plus rifampin, especially if higher doses of these drugs are used. Prophylaxis with INH is advisable for all household members and very close contacts of patients with active tuberculosis, especially young children.
Which statement about antitubercular drugs is accurate?
(A) Antimycobacterial actions of streptomycin involve inhibition of arabinosyltransferases
(B) Cross-resistance of M tuberculosis to isoniazid and pyrazinamide is common
(C) Ocular toxicity of ethambutol is prevented by thiamine
(D) Pyrazinamide treatment should be discontinued immediately if hyperuricemia occurs
(E) Resistance to ethambutol involves mutations in the emb gene
(E) Resistance to ethambutol involves mutations in the emb gene
Arabinosyltransferase is inhibited by ethambutol (not streptomycin) and resistance involves alterations in the emb gene. Ocular adverse effects of ethambutol are dose-dependent and usually reversible when the drug is discontinued. Thiamine is not protective. There is minimal cross-resistance between pyrazinamide and other antimycobacterial drugs. Pyrazinamide uniformly causes hyperuricemia, but this is not a reason to halt therapy even though the drug may provoke gouty arthritis in susceptible persons.
Once-weekly administration of which of the following antibiotics has prophylactic activity against bacteremia caused by M avium complex in AIDS patients?
(A) Acedapsone
(B) Azithromycin
(C) Clarithromycin
(D) Kanamycin
(E) Rifabutin
(B) Azithromycin
Because of its long elimination half-life (3-4 d), weekly administration of azithromycin has proved to be equivalent to daily administration of clarithromycin when used for prophylaxis against M avium complex in AIDS patients. Acedapsone is a repository form of dapsone used in leprosy.
Risk factors for multidrug-resistant tuberculosis include
(A) A history of treatment of tuberculosis without rifampin
(B) Recent immigration from Asia and living in an area of over 4% isoniazid resistance
(C) Recent immigration from Latin America
(D) Residence in regions where isoniazid resistance is known to exceed 4%
(E) All of the above
(E) All of the above
Multi drug-resistant tuberculosis (MDR-TB) is defined as resistance to 2 or more drugs. All the risk factors are relevent. In the case of resistance to both INH and rifampin, initial regimens still include both drugs, plus ethambutol, pyrazinamide, streptomycin (or other aminoglycoside), and a fluoroquinolone. Continuation therapy should include at least 3 drugs shown to be active in vitro against the infecting strain. The appropriate duration of therapy has not been established.
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