Questions and Answers
What is the primary mechanism of resistance against penicillins?
Which formulation of Penicillin G is contraindicated for intravenous use due to serious risks?
Which property affects the spectrum of penicillins?
What is a common side effect associated with high doses of Penicillin G?
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Which of the following statements is true regarding Penicillin G's CNS penetration?
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What adverse effect is noted with the IM formulation of Penicillin G Procaine?
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Which penicillin formulation is formulated for the treatment of tertiary syphilis?
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Which condition is a precaution associated with the use of all antibiotics, including penicillins?
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Which of the following statements regarding hapten complex allergy is correct?
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What adjustment is necessary for the dosing of penicillins in patients with renal impairment?
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Which aminopenicillin has a formulation that is more effective for gastrointestinal infections?
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What is a common side effect associated with the use of Amoxicillin/Clavulanic Acid?
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What is the primary reason for poor CNS penetration of aminopenicillins?
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Which formulation of ampicillin is designed to extend its effectiveness against beta-lactamase-producing strains?
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Why is amoxicillin typically preferred over ampicillin for oral administration?
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What should be done when prescribing ampicillin in patients with renal impairment?
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What is the effect of food on the gastrointestinal side effects of Amoxicillin/Clavulanic Acid?
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What is the combined purpose of Sulbactam and Durlobactam in their formulation?
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Which of the following side effects is NOT associated with the use of Sulbactam/Durlobactam?
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For what specific patient condition is renal dose adjustment for Sulbactam/Durlobactam required?
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What interaction should be monitored when using Sulbactam/Durlobactam?
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Which of the following is a potential warning associated with Sulbactam/Durlobactam use?
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What is the route of administration for Dicloxacillin?
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Which of the following side effects is specifically associated with Nafcillin and Oxacillin?
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Which type of bacteria are Anti-staphylococcal Penicillins primarily effective against?
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What is a unique characteristic of Dicloxacillin compared to Nafcillin and Oxacillin regarding dosage adjustments?
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How do Nafcillin and Oxacillin differ in terms of excretion?
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What is the primary mechanism of action of cephalosporins?
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Which factor does NOT affect the spectrum of cephalosporins?
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What describes the killing mechanism of cephalosporins?
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Which of the following factors is NOT relevant to cross-sensitivity of cephalosporins?
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Which statement accurately reflects cephalosporin use?
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Which cephalosporin is indicated for both IV and oral administration?
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What is a key characteristic of 2nd generation cephalosporins regarding Gram-negative bacteria?
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Which of the following is true about cefuroxime?
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What is a precaution associated with the use of 2nd generation cephalosporins?
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Which cephalosporin offers anaerobic coverage?
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Which cephalosporin has the greatest activity against Pseudomonas aeruginosa?
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What is the main reason ceftriaxone does not require renal dose adjustments?
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Which of the following statements about ceftriaxone is FALSE?
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What potential adverse effect is associated with prolonged use of cephalosporins?
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Which cephalosporin is NOT indicated for both intravenous and oral administration?
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Which cephalosporin is known for having renal dosing adjustments needed, unlike ceftriaxone?
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What is a crucial precaution when administering ceftriaxone in neonates?
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What describes the bacterial spectrum of cephalosporins compared to penicillins?
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Cefuroxime primarily targets which type of bacteria?
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What method of administration is Cefepime available in?
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Which of the following statements accurately describes Cefepime's activity?
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What is a necessary consideration when prescribing Cefepime?
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Which precaution must be taken when using Cefepime?
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What is a defining property of Cefepime?
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Which of the following drug options has coverage specifically for MRSA?
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What is a primary clinical indication for Ceftaroline?
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Which of the following statements about Ceftobiprole is true?
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What precaution should be taken when administering Ceftaroline or Ceftobiprole?
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Which characteristic is true regarding the elimination of Ceftaroline and Ceftobiprole?
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Which of the following describes the primary mechanism of action of monobactams?
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Which of the following factors does NOT determine the spectrum of activity of monobactams?
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What is a unique feature of Aztreonam regarding bacterial resistance?
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What common side effect may occur with the intravenous administration of Aztreonam?
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In which scenario might Aztreonam be safely used?
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What is the primary mechanism of action of carbapenems?
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Which carbapenem is specifically accompanied by cilastatin to prevent renal metabolism?
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Which carbapenem has the longest half-life allowing for once daily dosing?
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What distinguishes meropenem from other carbapenems regarding guidelines for CNS penetration?
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Which of the following statements about the cross-allergic reaction of carbapenems is accurate?
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Which combination is used in a formulation to inhibit beta-lactamase activity?
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What is the primary mechanism of action of lipopeptides?
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Which statement best describes the effect of lipopeptides on bacterial cells?
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What type of bacterial killing mechanism do lipopeptides exhibit?
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Which of the following outcomes is a consequence of lipopeptides' action?
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What element is primarily involved in the cell death mechanism caused by lipopeptides?
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What is the primary route of administration for Daptomycin?
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Which statement accurately describes the half-life and dosing frequency of Daptomycin?
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Which condition may occur approximately 2-4 weeks after starting Daptomycin treatment?
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What is a significant drug interaction associated with Daptomycin?
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Why should Daptomycin not be used to treat pneumonia?
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What is the primary mechanism of action of Glycopeptides like Vancomycin?
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Which type of killing mechanism is associated with Lipoglycopeptides?
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What is a major precaution associated with the use of Telavancin?
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Which of the following is a unique characteristic of Oritavancin?
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What mechanism allows some bacteria to resist Vancomycin?
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Which dosing strategy is recommended for Vancomycin in patients with normal renal function?
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Which of the following statements about the absorption of Vancomycin is correct?
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What type of bacterial coverage do Lipoglycopeptides provide?
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Why is careful dosing adjustment required for glycopeptides in patients with renal impairment?
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What is the maximum infusion rate for Televancin to avoid Red Man Syndrome?
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What should be avoided for 48 hours after administering Oritavancin?
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Which of the following is a precaution when administering Dalbavancin?
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What side effect is commonly associated with Televancin?
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What is a potential serious adverse effect associated with excessive usage of certain antibiotics mentioned?
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Which condition should be monitored when using Oritavancin, especially in patients on anticoagulants?
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What is the recommended infusion duration for Oritavancin?
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What is an adverse effect commonly associated with high levels of certain antibiotics that affects hearing?
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What is the primary mechanism of action of nitroimidazoles?
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Which condition is a contraindication for using metronidazole during pregnancy?
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What is the recommended dosing ratio for intravenous to oral administration of metronidazole?
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What serious side effect is associated with concurrent alcohol consumption while taking metronidazole?
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Which statement about benznidazole is true?
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What is the primary mechanism of action of Polymyxins?
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Which of the following is a common side effect associated with Polymyxins?
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When using colistimethate for treatment, which aspect requires careful consideration?
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What is a significant precaution when administering Polymyxin B?
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Which of the following statements about inhalation administration of Polymyxins is true?
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What is the mechanism by which pleuromutilin inhibits bacterial growth?
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Which of the following is a common side effect of Lefamulin?
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In which condition is dose adjustment necessary when using Lefamulin?
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What type of antibiotic activity is associated with pleuromutilin?
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Which statement correctly describes a serious side effect of Lefamulin?
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What is the primary mechanism through which Nitrofurantoin becomes active against bacteria?
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Which of the following describes one of the effects of Nitrofurantoin on bacterial cells?
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Which of the following is NOT true about the action of Nitrofurantoin?
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How does Nitrofurantoin's mechanism of action differ from traditional antibiotics?
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In which of the following scenarios would Nitrofurantoin likely be effective?
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Which of the following side effects is NOT associated with Nitrofurantoin?
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Under what condition should Nitrofurantoin not be used?
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What is the primary indication for the use of Nitrofurantoin?
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Which patient condition is NOT influenced by Nitrofurantoin's pharmacological properties?
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What unique effect can Nitrofurantoin have on urine?
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At what pH does methenamine mandelate and hippurate convert to formaldehyde?
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What is a significant reason for the slow reaction of methenamine mandelate and hippurate?
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Why are methenamine mandelate and hippurate contraindicated in cases of renal insufficiency?
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What adverse interaction should be avoided when administering methenamine mandelate and hippurate?
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What is the action of methenamine mandelate and hippurate in relation to bacteria?
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What is the primary mechanism of action of Fosfomycin?
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What is the recommended dosage form for Fosfomycin when treating uncomplicated UTIs?
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Which of the following statements about the pharmacokinetics of Fosfomycin is true?
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What limitation exists for the use of Fosfomycin regarding systemic infections?
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In what manner is Fosfomycin typically administered?
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What is the mechanism of action of rifaximin?
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Which condition is rifaximin NOT indicated for?
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What is a common side effect of rifaximin?
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How is rifaximin primarily absorbed in the body?
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Which of the following is an effect of rifaximin on the gut microbiota?
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What is the primary mechanism of action of fidaxomycin?
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For which condition is fidaxomycin primarily used?
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Which of the following is a common gastrointestinal side effect of fidaxomycin?
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What type of infections is fidaxomycin NOT indicated for?
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What structural similarity does fidaxomycin share with another antibiotic class?
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What is the primary mode of action of Taurolidine in Defencath?
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In what form is Taurolidine administered for its intended use?
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Which of the following statements best describes the mechanism of Taurolidine?
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What is a key reason for using Taurolidine in dialysis procedures?
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How does Taurolidine differ from other antimicrobial agents?
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What is the primary mechanism of action of Taurolidine in a dialysis catheter?
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What potential complication should be monitored for when using Heparin in conjunction with Taurolidine/Heparin?
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How does Taurolidine affect microorganisms?
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What is NOT a characteristic of Taurolidine's mechanism?
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In what formulation is Taurolidine typically used within a dialysis setting?
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Study Notes
Mechanism of Action and Properties
- Penicillins are bactericidal antibiotics that exert time-dependent killing effects.
- They bind to transpeptidase enzymes (PBPs), crucial for peptidoglycan cross-linking in bacterial cell walls.
- Spectrum of activity influenced by cell wall permeability, types of PBP, affinity for PBP, and concentration of PBP.
General Characteristics
- Most penicillins are susceptible to degradation by gastric acid; may require alternate formulations for oral use.
- Effectiveness in the central nervous system is limited and typically relies on the presence of inflamed meninges.
- Primarily eliminated renally, necessitating dose adjustments for renal impairment.
- Beta-lactamase expression is a major resistance mechanism, particularly in some strains of Streptococcus and Staphylococcus (MRSA).
- All penicillins carry a risk of pseudomembranous colitis and can cause hemolytic anemia, evidenced by a positive direct Coomb’s test.
Spectrum of Activity
- Generally effective against limited gram-positive and narrow gram-negative bacteria.
- Highly sensitive to beta-lactamase enzymes resulting in decreased efficacy.
Specific Formulations and Dosage
- Penicillin G Benzathine: used as an intramuscular (IM) formulation for treating tertiary syphilis.
- Penicillin G Procaine: another IM formulation for tertiary syphilis; may cause dizziness or paresthesia.
- Aqueous Crystalline Penicillin G: available in IV form as sodium or potassium salts; unstable under gastric conditions.
- Phenoxymethyl Penicillin (Penicillin V): oral formulation available as a potassium salt.
- Caution against using Penicillin G IM formulations intravenously due to risk of cardiac arrest and death; they are not formulated for IV use.
Side Effects and Contraindications
- Potential for allergic reactions associated with hapten complex formation.
- High doses of Penicillin G can induce seizures and serum sickness.
- Penicillin G Procaine carries a higher likelihood of allergic reactions and is contraindicated in individuals with procaine allergies.
Aminopenicillins Overview
- Amoxicillin (Amoxil®) is available as a PO formulation, while Ampicillin (Principen®) can be administered PO, IV, and IM.
- Both antibiotics have similar gram-positive coverage to penicillin but provide better gram-negative coverage and are more resistant to beta-lactamase.
Specific Formulations
- Amoxicillin/Clavulanic Acid (Augmentin): A PO formulation that broadens amoxicillin's spectrum to include beta-lactamase-producing strains.
- Ampicillin: Although available in PO form, it has poorer bioavailability (30-55%), making it more suitable for selected GI infections. The IV formulation is preferred for its efficacy.
Spectrum and Mechanism
- Ampicillin/Sulbactam: An IV formulation that also extends the spectrum of ampicillin to cover beta-lactamase-producing strains.
- Increased spectrum achieved through greater penetration of the outer membrane and higher affinity to penicillin-binding proteins (PBPs).
Pharmacokinetics and Dosage Adjustments
- Poor CNS penetration is noted unless the meninges are inflamed; thus, not ideal for CNS infections without inflammation.
- Renal dosage adjustments are required for ampicillin; dosage for Amoxicillin/Clavulanic Acid and Ampicillin/Sulbactam should consider the penicillin component.
Administration and Side Effects
- Amoxicillin is better absorbed orally compared to ampicillin, resulting in fewer gastrointestinal side effects, particularly diarrhea.
- Side effects of Ampicillin and Amoxicillin/Clavulanic Acid can include diarrhea and non-allergic rashes.
- Amoxicillin/Clavulanic Acid may cause nausea/vomiting; taking it with food can lessen gastrointestinal symptoms.
Beta-lactamase Inhibitors
- Beta-lactamase inhibitors irreversibly bind to certain enzymes, enhancing the efficacy of aminopenicillins against resistant bacteria.
Sulbactam/Durlobactam (XacDuro®) Overview
- Combination therapy using Sulbactam (a beta-lactam antibacterial) and Durlobactam (a beta-lactamase inhibitor).
- Specifically targets Acinetobacter baumannii calcoaceticus complex (ABC).
Indication
- Approved for the treatment of hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) caused by susceptible strains.
Pharmacology
- Sulbactam has a limited spectrum of action exclusively against ABC.
- Durlobactam enhances the effectiveness of Sulbactam by inhibiting beta-lactamases that would otherwise degrade it.
Dosage Considerations
- Renal dose adjustment is necessary to prevent accumulation and toxicity in patients with renal impairment.
Warnings and Precautions
- Risk of hypersensitivity reactions, including anaphylaxis.
- Potential for Clostridioides difficile-associated diarrhea (CDAD), which can occur following antibiotic use.
Side Effects
- Commonly reported side effects: liver test abnormalities, diarrhea, anemia, and hypokalemia (low potassium levels).
Drug Interactions
- May interact with Organic Anion Transporter 1 (OAT1) inhibitors, which could affect drug clearance and efficacy.
Anti-staphylococcal Penicillins Overview
- Include penicillinase-resistant penicillins such as Nafcillin, Oxacillin, and Dicloxacillin.
- Primarily effective against Gram-positive bacteria.
Nafcillin
- Brand names: Nafcil®, Unipen®.
- Administration: IV / IM.
- First choice drug for Methicillin-Sensitive Staphylococcus aureus (MSSA).
- Biliary excretion; no need for renal adjustment.
- Potential side effects include rash, nausea, vomiting, diarrhea, thrombophlebitis, and increased AST/ALT.
Oxacillin
- Brand names: Bactocil®, Prostaphlin®.
- Administration: IV / IM.
- Similar to Nafcillin regarding effectiveness against MSSA and excretion properties.
- Associated side effects are similar to those of Nafcillin.
Dicloxacillin
- Brand names: Dynapen®, Pathocil®.
- Administration: Oral (PO).
- Effective against MSSA; no activity against MRSA.
- Should be taken on an empty stomach for optimal absorption.
- Side effects include rash, nausea, vomiting, diarrhea.
General Notes
- Anti-staphylococcal penicillins are not effective against MRSA.
- Careful monitoring required for side effects, especially liver enzymes (AST/ALT) with Nafcillin and Oxacillin usage.
Cephalosporins Overview
- Class of antibiotics effective against a range of bacterial infections.
- Act primarily through binding to Penicillin Binding Proteins (PBPs), particularly transpeptidase enzymes.
Mechanism of Action (MOA)
- Bactericidal effect achieved by inhibiting the cross-linking of peptidoglycan, a crucial component of the bacterial cell wall.
- Killing activity is time-dependent, meaning effectiveness correlates with the duration of exposure to the drug.
Spectrum of Activity
- Determined by several factors:
- Cell Wall Penetration/Permeability: Ability of the antibiotic to penetrate the bacterial cell wall.
- Type of PBP: Different bacterial species have different types of PBPs with varying roles in cell wall synthesis.
- Affinity to PBP: The strength of the binding interaction between the cephalosporin and the PBP.
- Concentration of PBP: The amount of PBP present in the bacteria can influence susceptibility to cephalosporins.
Cross Sensitivity
- Cephalosporins may exhibit cross-reactivity with penicillins due to similar mechanisms of action and structure.
- Clinicians should consider potential allergic reactions when prescribing cephalosporins to patients with penicillin allergies.
2nd Generation Cephalosporins Overview
- Cephalosporins provide greater gram-negative coverage compared to first-generation, with a slight decrease in gram-positive efficacy.
Key Agents
- Cefoxitin (Mefoxin®): Administered intravenously (IV).
- Cefotetan (Cefotan®): Administered intravenously (IV).
- Cefuroxime (Zinacef®, Ceftin®): Available in IV, intramuscular (IM), and oral (PO) forms; notable for good central nervous system penetration.
- Cefaclor (Ceclor®): Only available in oral form (PO).
- Cefprozil (Cefzil®): Available in oral form (PO).
Coverage and Stability
- Cefotetan and Cefoxitin cover anaerobes and Neisseria gonorrhoeae.
- All IV agents are sensitive to gastric acid, leading to destruction if taken orally.
- Renally eliminated, requiring dosage adjustments.
- More stable against beta-lactamase compared to penicillins (PCNs).
Administration Notes
- Tablets and oral suspension of cefuroxime are not bioequivalent; do not substitute between forms.
- The oral suspension of cefuroxime should be taken with food for optimal absorption.
Precautions
- Possibility of cross-sensitivity with other beta-lactam antibiotics, necessitating caution in patients with known allergies.
3rd Generation Cephalosporins
- Key agents include Ceftazidime (Fortaz®, Tazicef®), Ceftriaxone (Rocephin®), and Cefotaxime (Claforan®).
- Broad spectrum antibiotics effective against various Gram-negative bacteria, with variable Gram-positive coverage.
Specific Medications
- Ceftazidime: Highest efficacy against Pseudomonas aeruginosa, limited Gram-positive activity.
-
Ceftriaxone:
- Administered IM or IV, does not require renal dose adjustment.
- Exhibits hepatic biliary excretion and a longer half-life allowing for once daily dosing.
- Superior CNS penetration compared to other cephalosporins.
- Cefotaxime: Similar CNS penetration as ceftriaxone.
- Oral Agents: Include Cefixime (Suprax®), Cefpodoxime proxetil (Vantin®), Cefdinir (Omnicef®), Cefditoren pivoxil (Spectracef®), and Ceftibuten (Cedax®).
Administration and Pharmacokinetics
- IV formulations are inactivated by gastric acid; appropriate dosing via IM or IV routes necessary.
- Most agents excreted through renal pathways; adjustments required with exceptions like ceftriaxone.
Safety and Precautions
- Prolonged use can lead to Clostridium difficile-associated diarrhea (CDAD) and pseudomembranous colitis.
- Avoid use of ceftriaxone in neonates to prevent kernicterus and biliary sludging.
- Contraindicated with calcium-containing IV products in neonatal patients (< 28 days) to prevent precipitation.
Drug Interactions
- Do not dilute or administer ceftriaxone with calcium-containing IV solutions through a Y-site due to precipitate formation.
Cross Sensitivity
- There may be cross-sensitivity among beta-lactam antibiotics, necessitating caution in patients with penicillin allergies.
Cefepime (Maxipime®) Overview
- Classified as a 4th generation cephalosporin antibiotic.
- Administered via Intramuscular (IM) or Intravenous (IV) routes.
- Exhibits broad-spectrum activity, effectively targeting a wide range of pathogens.
Pseudomonas Coverage
- Particularly notable for its strong efficacy against Pseudomonas aeruginosa.
- Valuable in treating infections caused by resistant strains of Pseudomonas.
Administration and Stability
- Available for IV use only due to vulnerability to destruction by gastric acid.
- Renally eliminated, necessitating dosage adjustments based on kidney function.
Precautions
- Cross-sensitivity may occur with other beta-lactam antibiotics, caution required in allergic patients.
Cephalosporins Overview
- Ceftaroline (Teflaro®) and Ceftobiprole (Zevtera®) are intravenous (IV) cephalosporins with MRSA coverage.
- Both agents are effective against specific infections such as skin and soft tissue infections (SSTIs) and community-acquired pneumonia (CAP).
Ceftaroline (Teflaro®)
- Approved for treating skin and soft tissue infections and CAP (excluding MRSA).
- Specifically designed to target MRSA, making it unique among cephalosporins.
Ceftobiprole (Zevtera®)
- Approved for treating Staphylococcus aureus bacteremia, CAP, and SSTIs.
- Demonstrates activity against penicillin-resistant Streptococcus pneumoniae (PRSP).
Key Characteristics
- Both Ceftaroline and Ceftobiprole are the only penicillin, cephalosporin, and carbapenem agents with confirmed coverage against MRSA.
- Administered IV due to instability in gastric acid, requiring careful handling.
Pharmacokinetics
- Both drugs are renally eliminated, necessitating dose adjustments based on renal function.
- Notable for their clinical utility in infections requiring effective MRSA management.
Precautions
- Cross-sensitivity with other beta-lactam antibiotics may pose risks for some patients.
Monobactams Overview
- Monobactams are a class of antibiotics designed to target bacterial cell walls.
- They exert their bactericidal effect through time-dependent killing mechanisms.
Mechanism of Action (MOA)
- Binds to penicillin-binding proteins (PBPs), specifically the transpeptidase enzyme.
- This binding inhibits the cross-linking of peptidoglycan polymers, weakening bacterial cell walls.
Spectrum of Activity
- Spectrum is determined by several factors:
- Cell wall penetration and permeability.
- Type of PBP present in bacteria.
- Affinity of the antibiotic to the PBP.
- Concentration of PBP in the organism.
Aztreonam (Azactam®)
- Aztreonam is the primary monobactam antibiotic available.
- Administered via intravenous (IV) route.
- Primarily effective against Gram-negative bacilli.
Resistance and Elimination
- Features a monocyclic ring that provides resistance to β-lactamases, enzymes that typically inactivate β-lactam antibiotics.
- Undergoes renal elimination; dose adjustments are necessary in patients with renal impairment.
Allergy Considerations
- Limited risk of cross-allergic reactions with other β-lactams, making it a suitable option for patients with penicillin allergies.
Formulation and Side Effects
- Available in an inhalational formulation for specific patients (e.g., cystic fibrosis).
- Common adverse effects include phlebitis and increased serum levels of ALT/AST.
Mechanism of Action
- Carbapenems bind to transpeptidase enzymes (Penicillin Binding Proteins), disrupting peptidoglycan cross-linking in bacterial cell walls.
- This action is bactericidal and exhibits time-dependent killing characteristics.
Famous Carbapenem Agents
- Doripenem (Doribax®): Administered intravenously.
- Ertapenem (Invanz®): Administered intravenously.
- Imipenem/Cilastatin (Primaxin®): Administered intravenously.
- Meropenem (Merrem®): Administered intravenously.
- Meropenem/Vaborbactam (Vabomere®): Administered intravenously.
- Imipenem/Cilastatin/Relebactam: Administered intravenously.
Clinical Indications and Usage
- Currently, the drug of choice (DOC) for treating infections caused by ESBL (Extended-Spectrum Beta-Lactamase) producing gram-negative bacteria.
- Noted for cross-allergic reactions with penicillins, exhibiting a higher risk than with cephalosporins.
- Offers broad-spectrum coverage, effectively targeting various bacterial species.
Pharmacokinetics and Considerations
- Agents administered intravenously are susceptible to degradation by gastric acid, necessitating parenteral delivery.
- Imipenem is specifically metabolized by renal dehydropeptidase I; cilastatin is co-administered to inhibit this metabolism.
- Renal elimination necessitates dosage adjustments in patients with renal impairment.
Unique Properties of Agents
- Ertapenem: Features the longest half-life among carbapenems, allowing for once-daily (q 24 h) dosing.
- Meropenem: Preferred in clinical guidelines due to good CNS penetration.
- Vaborbactam and Relebactam: Act as beta-lactamase inhibitors, enhancing the efficacy of carbapenems against resistant strains.
Lipopeptides Overview
- Class of antibiotics known for their unique cyclic structure.
- Primarily used to treat gram-positive infections, particularly those resistant to other treatments.
Mechanism of Action (MOA)
- Functions by inhibiting bacterial cell wall synthesis.
- Binds to the cell membrane, leading to depolarization.
- Depolarization causes potassium ions to be expelled from the bacterial cell.
- Results in cell death, categorizing lipopeptides as bactericidal agents.
- Exhibit concentration-dependent killing, meaning effectiveness increases with higher drug concentrations.
Daptomycin Overview
- Class: Lipopeptide antibiotic (trade name: Cubicin®)
- Administration: Intravenous (IV) only
- Spectrum: Effective against Gram-positive bacteria exclusively
Pharmacokinetics
- Half-life: Approximately 8 hours, allowing for once daily dosing
- Excretion: Primarily through renal pathways; dosage adjustments required in cases of renal failure
Clinical Considerations
- Contraindicated for pneumonia treatment due to inactivation by surfactant in the lungs
- Side effects may include elevated creatine phosphokinase (CPK) levels, potentially leading to myopathy or rhabdomyolysis; weekly monitoring of CPK is essential
- Risk of eosinophilic pneumonia can occur 2-4 weeks post initiation of treatment
Drug Interactions
- Co-administration with statins can increase the risk of rhabdomyolysis
- May cause a false elevation in prothrombin time/international normalized ratio (PT/INR) results
Mechanism of Action
- Glycopeptides and lipoglycopeptides inhibit cell wall synthesis by binding to the D-Ala-D-Ala terminus of murein monomers.
- This binding inhibits transglycosidase, preventing the growth of the polymer chain.
- Lipoglycopeptides also weaken the cell wall and damage the underlying cell membrane.
- Vancomycin exhibits time-dependent killing and is slowly cidal, while other lipoglycopeptides are concentration-dependent and bactericidal.
Key Drug Information
- Vancomycin (Vancocin®): Administered IV and PO.
- Telavancin (Vibativ®): Administered IV only; requires a MedGuide due to potential fetal risks.
- Oritavancin (Orbactiv®): Administered IV only, inhibits polymerization of peptidoglycan precursors.
- Dalbavancin (Dalvance®): Administered IV only; has a long half-life allowing for weekly dosing.
Black Box Warnings
- Telavancin:
- Fetal risk requires a pregnancy test prior to use.
- Increased mortality in hospital-acquired pneumonia (HAP) patients with moderate to severe renal impairment.
- Risk of nephrotoxicity.
Resistance Mechanisms
- Resistance in vancomycin is due to the use of D-lactate instead of D-Ala, associated with VanH and VanA genes.
- VRSA and VISA demonstrate thicker murein layers and increased free D-Ala-D-Ala as decoys.
Pharmacokinetics and Dosing
- Renal elimination necessitates dosage adjustments.
- Oritavancin and Dalbavancin should only be mixed in D5W; both have long half-lives (200 hours).
- Vancomycin has poor CNS and lung penetration; higher trough levels improve penetration.
- PO administration of vancomycin is only effective for severe antibiotic-associated colitis caused by Clostridium difficile.
Dosing Guidelines
- Vancomycin IV: 15-20 mg/kg every 8-12 hours, with adjustments for creatinine clearance.
- Vancomycin PO: 125-500 mg every 6 hours for 10-14 days for C. difficile.
- Trough levels for meningitis, pneumonia, and serious infections should be 15-20 mcg/mL, with AUIC >400.
Precautions and Adverse Effects
- Caution with nephrotoxins like Zosyn and avoid use if MIC of staphylococcus is ≥ 2 mcg/mL.
- Red Man Syndrome: Caused by rapid infusion of vancomycin, leading to flushing, rash, and hypotension. Maximum rate for infusion should be < 1 g/h.
- Risk of bone marrow suppression, nephrotoxicity, and ototoxicity with high levels.
Specific Drug Precautions
-
Telavancin:
- Precaution against prolonged QT intervals; avoid in patients with QT prolongation.
- May cause metallic taste, nausea, and vomiting.
-
Oritavancin:
- Avoid heparin within 48 hours to prevent interference with aPTT results.
- Warfarin co-administration can increase bleeding risk and alter PT/INR.
- Infusion-related reactions may occur; recommended infusion time is over 3 hours.
-
Dalbavancin:
- Precaution against Red Man Syndrome; infuse over 30 minutes.
- Monitor for elevated AST/ALT levels (> 3 times normal).
- Possible side effects include nausea, headache, diarrhea, and rash.
Coverage
- Effective against Gram-positive organisms exclusively.
Nitroimidazoles Overview
- Nitroimidazoles are a class of antibiotics that are effective against anaerobic bacteria and protozoa.
- Their mechanism of action involves the reduction of the nitro group in anaerobes, activating pyruvate-ferredoxin oxidoreductase, which results in the production of cytotoxic compounds that bind to proteins, membranes, and DNA.
- Exhibits bactericidal properties and relies on time-dependent killing to exert its effects.
CNS Penetration
- Nitroimidazoles demonstrate good penetration into the central nervous system, making them effective for treating CNS infections.
Specific Drugs and Uses
- Benznidazole: Exclusive availability from the CDC for treating Chagas Disease.
- Metronidazole (Flagyl®, Metro®): Available in IV, PO, topical, and vaginal forms. Known for its effectiveness against anaerobic infections and certain unusual pathogens.
Important Considerations
- Black Box Warning (BBW): Nitroimidazoles may be carcinogenic.
- Metronidazole: Not to be refrigerated when in IV form; features a 1:1 dosing ratio between IV and oral administration.
- Undergoes hepatic metabolism; no dose adjustments necessary for decreased creatinine clearance (CrCl).
Contraindications and Precautions
- Contraindicated during the first trimester of pregnancy.
- Breastfeeding warning applies specifically to Tinidazole.
- Alcohol should be avoided within three days of administration to prevent disulfiram-like reactions.
Side Effects
- Common gastrointestinal side effects include dysgeusia (altered taste) and nausea.
Mechanism of Action
- Functions as a cationic detergent, disrupting cytoplasmic membrane integrity.
- Causes alteration of the osmotic barrier, leading to bactericidal effects.
- Exhibits concentration-dependent killing, effective against Gram-negative organisms.
Types of Polymyxins
- Polymyxin E (Colistimethate): Administered IV or IM, branded as Coly-Mycin-M®.
- Polymyxin B Sulfate: Also delivered IV or IM.
Indications
- Primarily used for treating severe, life-threatening infections caused by Gram-negative bacilli.
- Due to potential toxicity, reserved for critical cases.
Black Box Warnings (BBW) for Polymyxin B
- Significant risk of nephrotoxicity (kidney damage).
- Potential neurotoxicity (nerve damage).
- Risk of respiratory muscle paralysis.
- Safety during pregnancy not established.
- Recommended for IM or intrathecal use in hospital settings only.
- Caution against using alongside other nephrotoxic agents.
Dosing and Administration
- Poor oral absorption necessitates IV administration for effectiveness.
- Colistimethate is typically the preferred option for IV dosing.
- Inhalation form available for both Polymyxin E and B.
- Polymyxin B is included in Neosporin GU irrigant for bladder irrigation with neomycin.
Pharmacokinetics
- Colistimethate acts as a pro-drug, which is converted to its active form after hydrolysis.
- Drug elimination is primarily renal; dosage adjustments are crucial for patients with renal impairment.
Side Effects
- Common adverse reactions include nephrotoxicity and neurotoxicity.
- The risk of respiratory muscle paralysis is a concern.
- Safety of use in pregnancy remains unvalidated.
- It's essential to restrict IM or intrathecal administration to hospital settings to monitor potential complications.
- Concurrent use with other nephrotoxins should be avoided to reduce cumulative risks.
Mechanism of Action
- Pleuromutilin inhibits bacterial protein synthesis by interacting with the A- and P-sites of the peptidyl transferase center in the 50S ribosomal subunit.
- Interactions include hydrogen bonds, hydrophobic forces, and Van der Waals forces.
- The binding pocket of the bacterial ribosome undergoes an induced fit around the mutilin core, blocking proper tRNA positioning.
- Exhibits bacteriostatic properties and is time-dependent, with efficacy measured by the AUC/MIC ratio.
Lefamulin (Xenleta®)
- Administered intravenously (IV) or orally (PO).
- Effective against Gram-negative bacilli.
- FDA-approved for the treatment of community-acquired pneumonia (CAP).
- Undergoes hepatic metabolism; dosage should be adjusted in patients with hepatic impairments.
Side Effects
- Common side effects include injection site reactions, diarrhea, and elevated AST/ALT levels.
- Serious side effects may include QT prolongation and Clostridium difficile-associated diarrhea (CDAD).
Drug Interactions
- Caution advised with CYP3A4 substrates that can prolong the QT interval.
Penicillins
- Bactericidal and time-dependent killing mechanism targets transpeptidase (PBP) in bacterial cell wall synthesis.
- Effectiveness influenced by cell wall permeability, PBP type and affinity, and PBP concentration.
- Most penicillins are destroyed by gastric acid; recommended for IV or IM use.
- Renally eliminated; beta-lactamase production in bacteria is a common resistance mechanism.
- Notable risks include pseudomembranous colitis and potential allergic reactions; hemolytic anemia may occur in patients.
Specific Penicillins
- Penicillin G Benzathine and Procaine: IM formulations for treating tertiary syphilis; not for IV use due to risk of severe reactions.
- Aqueous Crystalline Penicillin G: Available IV; sensitive to gastric acid.
- Amoxicillin / Clavulanic Acid: Extended spectrum to cover beta-lactamase-producing organisms.
- Ampicillin / Sulbactam: IV; augments ampicillin’s spectrum against resistant bacteria.
- Side effects include allergic reactions, diarrhea (more common with ampicillin), and potential myopathy.
Cephalosporins
- Bactericidal; binds to PBP, cross-sensitive with penicillins.
- 1st Generation: Good for gram-positive and some gram-negative bacteria.
- 2nd Generation (Cefoxitin, Cefotetan): Slightly less effective against gram-positive; anaerobic coverage.
- 3rd Generation (Ceftazidime, Ceftriaxone): Broad spectrum with improved gram-negative coverage; Ceftazidime effective against Pseudomonas.
- 4th Generation (Cefepime): Broad spectrum including Pseudomonas; requires renal dose adjustment.
- Ceftaroline: Only cephalosporin with MRSA coverage.
Monobactams
- Aztreonam: Gram-negative coverage; resistant to beta-lactamases; limited cross-reactivity with penicillin allergies.
Carbapenems
- Broad-spectrum agents; effective against ESBL+ gram negatives.
- Imipenem: Renal metabolism inhibited by cilastatin.
- Meropenem: Preferred for CNS penetration; used against resistant pathogens.
- Cross-sensitivity with penicillins; dose adjustments required for renal impairment.
Lipopeptides
- Daptomycin: Effective against gram-positive bacteria, not for pneumonia; renal adjustments needed; can cause myopathy.
- Side effect profile includes elevated creatine phosphokinase (CPK) and risk of eosinophilic pneumonia.
Glycopeptides
- Vancomycin: Bactericidal; used in serious infections like MRSA and C. difficile colitis; dose adjustments for renal function.
- Risk of nephrotoxicity and infusion-related reactions; requires careful monitoring.
Nitroimidazoles
- Metronidazole: Bactericidal against anaerobes; good CNS penetration; contraindicated in first trimester of pregnancy.
- Side effects include gastrointestinal issues and potential disulfiram-like reactions with alcohol.
Polymyxins
- Colistin and Polymyxin B: Effective against gram-negative bacilli in severe infections; significant nephrotoxicity and neurotoxicity risk.
- Often reserved for life-threatening infections due to their toxicity profile.
Pleuromutilins
- Lefamulin: Bacteriostatic against gram-negative bacteria; used for community-acquired pneumonia (CAP); caution with hepatic impairment.
General Considerations
- Renal adjustments are necessary for dosing in many antibiotic classes.
- Cross-reactivity between penicillins and other beta-lactams can occur.
- Caution against Clostridioides difficile-associated diarrhea with prolonged use of broad-spectrum antibiotics.
Nitrofurantoin (Macrodantin®) Overview
- Antibacterial agent primarily used for urinary tract infections (UTIs).
- Inadequate effectiveness for systemic infections; specifically targets urinary pathogens.
Pharmacology
- Optimal performance in acidic urine pH, enhancing drug activity against bacteria.
Side Effects
- Contraindicated in patients with renal impairment (Creatinine Clearance < 60 ml/min) due to decreased efficacy and increased risk of neurotoxicity.
- Neuropathy may occur, along with optic neuritis, highlighting potential neurotoxic effects.
- Associated with hemolytic anemia, especially in individuals with Glucose-6-phosphate dehydrogenase deficiency; a positive Coombs test can indicate this condition.
- Risk of acute pneumonitis, a rare but serious lung condition linked to long-term use.
- Can cause discoloration of urine, resulting in brown urine.
Clinical Uses
- Commonly prescribed for uncomplicated urinary tract infections, offering targeted treatment in non-complicated cases.
Methenamine Mandelate and Hippurate
- Converted to formaldehyde in acidic conditions (pH < 5.5), which also generates ammonia.
- Exhibits antibacterial properties, being toxic to a wide range of bacteria.
- Requires a slow reaction time; retention of urine in the bladder is essential for effectiveness, making catheter use inappropriate.
Side Effects and Contraindications
- Not recommended for patients with renal insufficiency as it may lead to precipitation of mandelic acid.
- Should not be administered concurrently with sulfonamides due to potential adverse interactions.
Fosfomycin (Monurol®)
- Works by inhibiting enolpyruvate transferase, a crucial cytoplasmic enzyme, leading to bactericidal effects.
- Typically administered mixed in 3-4 ounces of cold water for effective absorption.
- Renal excretion is the primary route, which is important to consider in patients with renal impairment.
- Primarily indicated for uncomplicated urinary tract infections (UTIs) and recommended as a single dose treatment.
Rifaximin Overview
- Rifaximin (Xifaxan®) is a bactericidal antibiotic.
- Classify it as a rifamycin, similar to rifampin.
Mechanism of Action
- Binds to bacterial DNA-dependent RNA polymerase.
- Inhibits the synthesis of RNA, preventing bacterial reproduction.
Pharmacokinetics
- Not absorbed through the gastrointestinal tract.
- Primarily used for localized gastrointestinal infections; ineffective for systemic infections.
Gastrointestinal Side Effects
- Potential side effects include:
- Flatulence
- Abdominal pain
- Urgency in defecation
Indications for Use
- Effective in treating travelers' diarrhea.
- Used in managing hepatic encephalopathy; reduces ammonia-producing bacteria in the gut.
- Indicated for irritable bowel syndrome (IBS) characterized by diarrhea.
Fidaxomycin Overview
- Fidaxomycin, marketed as Dificid®, is an antibacterial medication with a bactericidal effect.
- Its chemical structure is similar to macrolides, a class of antibiotics.
Mechanism of Action
- Inhibits RNA polymerase, an essential enzyme for RNA synthesis.
- Prevents the synthesis of bacterial RNA, ultimately leading to bacterial cell death.
Indications
- Specifically indicated for treating Clostridium difficile-associated diarrhea (CDAD).
- Not effective for systemic infections, highlighting its targeted use.
Side Effects
- Common gastrointestinal side effects include:
- Flatulence
- Abdominal pain
- Urgency in defecation
Penicillins
- Bactericidal agents exhibiting time-dependent killing.
- Mechanism of action involves binding to transpeptidase enzymes (PBPs) crucial for bacterial cell wall integrity.
- Resistance primarily due to beta-lactamase production and altered binding proteins, particularly in strains like MRSA.
- Limited gram-positive and narrow gram-negative coverage; highly sensitive to beta-lactamases.
- Penicillin G Benzathine and Procaine are IM formulations used for tertiary syphilis; not for intravenous use due to cardiac arrest risk.
- Aqueous crystalline Penicillin G available as IV formulations but degraded by gastric acid when taken orally.
- Allergic reactions are common, with potential hemolytic anemia a noted side effect.
Aminopenicillins
- Amoxicillin (Amoxil) and Ampicillin (Principen) cover similar gram-positive species as PCNs, with better gram-negative activity.
- Amoxicillin’s PO formulation has superior absorption, leading to less diarrhea compared to Ampicillin.
- Combination with beta-lactamase inhibitors (e.g., Amoxicillin/Clavulanic Acid) expands effectiveness against resistant strains.
- Ampicillin preferred for selected GI infections due to its IV formulation.
- Common side effects include diarrhea and a non-allergic rash.
Anti-staphylococcal Penicillins
- Include Nafcillin and Oxacillin; specifically target MSSA.
- Dicloxacillin is the oral formulation and must be taken on an empty stomach.
- Not effective against MRSA; excreted through biliary routes.
- Side effects include rash, nausea, and potential thrombophlebitis.
Cephalosporins
- Classified by generation, generally effective against gram-positive and gram-negative bacteria, with variable CNS penetration.
- Cross-sensitivity with penicillins might occur.
- 1st generation agents like Cefazolin are more gram-positive; later generations develop broader gram-negative coverage.
- Notable agents include Ceftriaxone, which is long-acting and hepatically excreted, avoiding renal adjustments.
Carbapenems
- Broad-spectrum with excellent CNS penetration; effective against ESBL-producing gram-negative bacteria.
- Includes Imipenem (with cilastatin) and Meropenem.
- Higher cross-reactivity noted with penicillins; used as a last-resort option.
- Renally eliminated and necessitate dose adjustments.
Monobactams
- Aztreonam specifically targets gram-negative bacilli; resistant to beta-lactamases.
- Minimal cross-reactivity with penicillins, suitable for patients with penicillin allergies.
- Administered IV and requires renal adjustments.
Lipopeptides
- Daptomycin targets gram-positive bacteria and requires careful CPK monitoring due to myopathy risks.
- Ineffective against pneumonia due to inactivation by lung surfactant.
Glycopeptides
- Vancomycin inhibits growth by binding to D-Ala-D-Ala in peptidoglycan; primarily for gram-positive infections, including MRSA.
- Renal adjustments required; use cautiously with nephrotoxins.
- Oritavancin and Dalbavancin offer long half-lives, allowing for less frequent dosing.
Metronidazole
- Bactericidal agent targeting anaerobic bacteria by inhibiting RNA synthesis.
- Effective for infections like Clostridioides difficile; good CNS penetration.
- Contraindicated in pregnancy and with alcohol.
Polymyxins
- Colistin and Polymyxin B target gram-negative bacteria; utilized for severe infections due to significant nephrotoxicity risks.
- Renal dosing adjustments are critical.
Pleuromutilin
- Lefamulin is effective for community-acquired pneumonia; its mechanism involves inhibiting bacterial protein synthesis.
- Hepatic metabolism necessitates dose adjustments in liver impairment.
General Notes
- Penicillin allergy and cross-reactivity are important considerations when prescribing.
- Resistance patterns influence choice of antibiotic; monitoring for renal function and side effects is essential across all classes.
Taurolidine/Heparin (Defencath®) Overview
- Combines taurolidine and heparin for use in dialysis catheters.
- Taurolidine has a non-specific mechanism of action (MOA) that damages cell walls of microorganisms.
- Inhibits adherence of microbes to biological surfaces, reducing infection risk.
Administration and Usage
- Instilled directly into dialysis catheters to provide antimicrobial protection.
- Important in preventing catheter-related infections during dialysis treatments.
Monitoring and Safety
- Heparin component requires monitoring for Heparin-induced thrombocytopenia (HIT), a condition characterized by low platelet count.
- Regular blood tests may be necessary to detect potential HIT early and manage it effectively.
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Explore the mechanisms of action, properties, and spectrum of Penicillins in this comprehensive quiz. Gain insights into how these bactericidal agents interact with bacterial cell walls and their characteristics, such as time-dependent killing and CNS penetration. Perfect for students studying pharmacology and microbiology.
