Basic Principles of Antimicrobial Therapy
A patient with pneumonia needs immediate antibiotic therapy, but culture results won't be available for 48 hours. What is the most appropriate approach?
a) Wait for culture results before starting any treatment
b) Start empiric therapy with a broad-spectrum antibiotic based on likely pathogens
c) Start with the narrowest spectrum antibiotic available
d) Give multiple antibiotics to cover all possible organisms
Answer: b) Start empiric therapy with a broad-spectrum antibiotic based on likely pathogens
Rationale: When a patient has a severe infection, treatment must begin before laboratory test results are available. Drug selection should be based on clinical evaluation and knowledge of which microbes are most likely to cause infection at that particular site. A broad-spectrum agent can be used for initial treatment, then switched to a more selective antibiotic once the identity and drug sensitivity of the infecting organism have been determined. It's essential that samples for culture are obtained before starting treatment, as antibiotics present during sampling can suppress microbial growth and confound identification.
How do penicillins cause bacterial cell death?
a) By inhibiting protein synthesis
b) By weakening the cell wall, causing bacteria to take up water and rupture
c) By damaging bacterial DNA
d) By inhibiting metabolic enzymes
Answer: b) By weakening the cell wall, causing bacteria to take up water and rupture
Rationale: Penicillins weaken the bacterial cell wall through two mechanisms: (1) inhibition of transpeptidases and (2) activation of autolysins. The bacterial cell wall is a rigid structure that prevents expansion against high internal osmotic pressure. When
penicillins weaken this wall, bacteria take up excessive amounts of water and rupture, making penicillins bactericidal. The drugs simultaneously disrupt synthesis of the cell wall and promote its active destruction, resulting in cell lysis and death.
How do cephalosporins compare to penicillins in terms of beta-lactamase resistance across generations?
a) All cephalosporins are equally susceptible to beta-lactamases
b) First-generation are destroyed; second-generation less sensitive; third-, fourth-, and fifth generation are highly resistant
c) Only fifth-generation cephalosporins are susceptible
d) Cephalosporins are completely immune to all beta-lactamases
Answer: b) First-generation are destroyed; second-generation less sensitive; third-, fourth-, and fifth-generation are highly resistant
Rationale: Not all cephalosporins are equally susceptible to beta-lactamases. Most first-generation cephalosporins are destroyed by beta-lactamases; second-generation cephalosporins are less sensitive to destruction; and third-, fourth-, and fifth-generation cephalosporins are highly resistant. Some beta-lactamases that act on cephalosporins (called cephalosporinases) can also cleave the beta-lactam ring of penicillins. This
progressive resistance to beta-lactamases is a key advantage of newer generation cephalosporins.
Why is matching the antimicrobial spectrum to the specific pathogen important?
a) It reduces healthcare costs only
b) It prevents all side effects
c) The drug should be active against the pathogen but no broader than required
d) Broad-spectrum antibiotics are always more effective
Answer: c) The drug should be active against the pathogen but no broader than required
Rationale: A prime rule of antimicrobial therapy is to match the drug with the bug. The antimicrobial should be active against known or suspected pathogens, but its spectrum should be no broader than required. Using unnecessarily broad-spectrum agents when narrower spectrum drugs would suffice can lead to resistance development and disruption of normal flora. The drug should be selected based on its effectiveness against the specific causative pathogen.
Why are penicillins active only against bacteria that are undergoing growth and division?
a) Dormant bacteria are naturally resistant to all antibiotics
b) Penicillin-binding proteins (PBPs) are expressed only during bacterial growth
c) The cell wall is thicker in dormant bacteria
d) Penicillins cannot penetrate non-dividing cells
Answer: b) Penicillin-binding proteins (PBPs) are expressed only during bacterial growth
Rationale: The molecular targets of penicillins are called penicillin-binding proteins (PBPs), which include transpeptidases, autolysins, and other bacterial enzymes. These PBPs are located on the outer surface of the cytoplasmic membrane. Bacteria express PBPs only during growth and division. Because PBPs must be present for penicillins to work, these drugs are active only when bacteria are growing and dividing.
A patient with severe immunocompromise develops a bacterial infection. What is the primary goal of antibiotic therapy in this patient?
a) To completely eliminate all bacteria without help from the immune system
b) To use rapidly bactericidal drugs since host defenses cannot adequately assist
c) To use only narrow-spectrum antibiotics
d) To wait for the immune system to recover before treating
Answer: b) To use rapidly bactericidal drugs since host defenses cannot adequately assist
Rationale: Host defenses (immune system and phagocytic cells) are critical for successful antimicrobial therapy. In most cases, drugs work in concert with host defense systems to subdue infection—the usual objective is to suppress microbial growth to the point where the balance tips in favor of the host. When treating immunocompromised patients (such as those with AIDS or undergoing cancer chemotherapy), the only hope lies with drugs that are rapidly bactericidal, as these patients' impaired defenses cannot adequately assist in fighting infection. Even bactericidal drugs may prove inadequate in severely immunocompromised hosts.
What is the primary mechanism by which bacteria develop resistance to penicillins?
a) Altered ribosomes
b) Production of beta-lactamases (penicillinases) that cleave the beta-lactam ring
c) Thickening of the cell wall
d) Increased efflux pumps
Answer: b) Production of beta-lactamases (penicillinases) that cleave the beta-lactam ring
Rationale: Beta-lactamases are enzymes that cleave the beta-lactam ring and thereby render penicillins inactive. Penicillinases are beta-lactamases that act selectively on penicillins. These enzymes are produced by both gram-positive and gram-negative bacteria. Gram-positive organisms produce large amounts and export them into the surrounding medium, while gram-negative bacteria produce smaller amounts and secrete
them into the periplasmic space. The genes for beta-lactamases can be transferred between bacteria via plasmids, promoting the spread of resistance.
When would an alternative antimicrobial agent be chosen instead of the drug of first choice?
a) When the first-choice drug is more expensive
b) When the patient is allergic to the drug of choice
c) When the patient prefers oral medication
d) When the pharmacy doesn't stock the first-choice drug
Answer: b) When the patient is allergic to the drug of choice
Rationale: For most infections, there is usually one drug that is superior to alternatives—the drug of first choice. This drug may be preferred for greater efficacy, lower toxicity, or narrower spectrum. Whenever possible, the drug of first choice should be employed. Alternative agents should be used only when the first-choice drug is inappropriate. Conditions that rule out a first-choice agent include: (1) allergy to the drug of choice, (2) inability of the drug to penetrate to the site of infection, and (3) heightened susceptibility of the patient to toxicity of the first-choice drug.
Why are penicillinase-resistant penicillins considered to have a narrow antimicrobial spectrum?
a) They only work against viral infections
b) They are used specifically against penicillinase-producing staphylococci
c) They cannot penetrate any bacterial cell walls
d) They are less effective than penicillin G against all bacteria
Answer: b) They are used specifically against penicillinase-producing staphylococci
Rationale: Penicillinase-resistant penicillins (nafcillin, oxacillin, and dicloxacillin) have a very narrow antimicrobial spectrum and are used only against penicillinase-producing strains of staphylococci (S. aureus and S. epidermidis). Because most strains of staphylococci produce penicillinase, these drugs are the drugs of choice for the majority of staphylococcal infections. However, they should not be used against infections caused by non-penicillinase-producing staphylococci because they are less active than penicillin G against these bacteria.
A patient with bacterial meningitis requires antibiotic therapy. What special consideration must be made regarding the site of infection?
a) Any antibiotic will work since bacteria are present
b) The antibiotic must be able to cross the blood-brain barrier to reach therapeutic concentrations
c) Oral antibiotics are preferred for meningitis
d) Lower doses are needed because the brain is small
Answer: b) The antibiotic must be able to cross the blood-brain barrier to reach therapeutic concentrations
Rationale: To be effective, an antibiotic must be present at the site of infection in a concentration greater than the minimum inhibitory concentration (MIC). At some sites, drug penetration may be hampered, making it difficult to achieve the MIC. In meningitis, the blood-brain barrier impedes drug access. Two approaches can be used: (1) select a drug that readily crosses the blood-brain barrier, or (2) inject an antibiotic directly into the subarachnoid space. The site of infection significantly impacts drug selection and route of administration to ensure adequate drug concentrations reach the infected area.
What does MRSA stand for, and what is the significance of this resistance?
a) Multiple-resistant Staphylococcus aureus; resistant to all antibiotics
b) Methicillin-resistant Staphylococcus aureus; lack of susceptibility to all penicillinase-resistant penicillins
c) Moderately resistant streptococcus; partially resistant to penicillins
d) Methicillin-responsive S. aureus; highly sensitive to penicillins
Answer: b) Methicillin-resistant Staphylococcus aureus; lack of susceptibility to all penicillinase-resistant penicillins
Rationale: MRSA refers to methicillin-resistant Staphylococcus aureus, indicating lack of susceptibility to methicillin (an obsolete penicillinase-resistant penicillin) and all other penicillinase-resistant penicillins. Resistance appears to result from the production of altered PBPs to which the penicillinase-resistant penicillins cannot bind. Vancomycin is
the treatment of choice for MRSA infections. This represents an increasing clinical problem in healthcare settings.
What is special about ceftaroline (a fifth-generation cephalosporin) compared to most other cephalosporins?
a) It is the only oral cephalosporin
b) It has demonstrated activity against MRSA
c) It has no side effects
d) It works against viral infections
Answer: b) It has demonstrated activity against MRSA
Rationale: Methicillin-resistant staphylococci produce altered PBPs that have a low affinity for cephalosporins, making most cephalosporins ineffective against MRSA. However, ceftaroline, a fifth-generation cephalosporin, has demonstrated activity against methicillin-resistant Staphylococcus aureus (MRSA). This makes ceftaroline unique among cephalosporins and provides an important treatment option for MRSA infections beyond vancomycin.