Drug Action II EXAM 1 DRUG CHART -KUHL
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Questions and Answers

What is the primary mechanism of resistance against penicillins?

  • Alteration of binding proteins
  • Increased cell membrane permeability
  • Metabolic activation by bacteria
  • Beta-lactamase production (correct)

    • Which formulation of Penicillin G is contraindicated for intravenous use due to serious risks?

  • Penicillin G Aqueous Crystalline
  • Penicillin G Procaine
  • Phenoxymethyl penicillin
  • Penicillin G Benzathine (correct)

    • Which property affects the spectrum of penicillins?

  • Patient age and weight
  • Type of Beta-lactamase present
  • Route of administration
  • Affinity to Penicillin Binding Protein (PBP) (correct)

    • What is a common side effect associated with high doses of Penicillin G?

    <p>Seizures</p> Signup and view all the answers

    Which of the following statements is true regarding Penicillin G's CNS penetration?

    <p>CNS penetration occurs with inflamed meninges.</p> Signup and view all the answers

    What adverse effect is noted with the IM formulation of Penicillin G Procaine?

    <p>Dizziness and paresthesia</p> Signup and view all the answers

    Which penicillin formulation is formulated for the treatment of tertiary syphilis?

    <p>Penicillin G Benzathine</p> Signup and view all the answers

    Which condition is a precaution associated with the use of all antibiotics, including penicillins?

    <p>Pseudomembranous colitis</p> Signup and view all the answers

    Which of the following statements regarding hapten complex allergy is correct?

    <p>It is a common side effect noted with most beta-lactams.</p> Signup and view all the answers

    What adjustment is necessary for the dosing of penicillins in patients with renal impairment?

    <p>Decrease in dosing interval.</p> Signup and view all the answers

    Which aminopenicillin has a formulation that is more effective for gastrointestinal infections?

    <p>Ampicillin</p> Signup and view all the answers

    What is a common side effect associated with the use of Amoxicillin/Clavulanic Acid?

    <p>Nausea/Vomiting</p> Signup and view all the answers

    What is the primary reason for poor CNS penetration of aminopenicillins?

    <p>Inflammation of meninges</p> Signup and view all the answers

    Which formulation of ampicillin is designed to extend its effectiveness against beta-lactamase-producing strains?

    <p>Ampicillin/Clavulanic Acid</p> Signup and view all the answers

    Why is amoxicillin typically preferred over ampicillin for oral administration?

    <p>Better bioavailability and less diarrhea</p> Signup and view all the answers

    What should be done when prescribing ampicillin in patients with renal impairment?

    <p>Renally dose adjust</p> Signup and view all the answers

    What is the effect of food on the gastrointestinal side effects of Amoxicillin/Clavulanic Acid?

    <p>Food decreases side effects</p> Signup and view all the answers

    What is the combined purpose of Sulbactam and Durlobactam in their formulation?

    <p>To treat infections caused by Acinetobacter baumannii calcoaceticus complex</p> Signup and view all the answers

    Which of the following side effects is NOT associated with the use of Sulbactam/Durlobactam?

    <p>Acute kidney injury</p> Signup and view all the answers

    For what specific patient condition is renal dose adjustment for Sulbactam/Durlobactam required?

    <p>Renal impairment</p> Signup and view all the answers

    What interaction should be monitored when using Sulbactam/Durlobactam?

    <p>Interactions with Organic Anion Transporter 1 (OAT1) inhibitors</p> Signup and view all the answers

    Which of the following is a potential warning associated with Sulbactam/Durlobactam use?

    <p>Risk of hypersensitivity reactions</p> Signup and view all the answers

    What is the route of administration for Dicloxacillin?

    <p>Oral only</p> Signup and view all the answers

    Which of the following side effects is specifically associated with Nafcillin and Oxacillin?

    <p>Thrombophlebitis</p> Signup and view all the answers

    Which type of bacteria are Anti-staphylococcal Penicillins primarily effective against?

    <p>Gram-positive bacteria only</p> Signup and view all the answers

    What is a unique characteristic of Dicloxacillin compared to Nafcillin and Oxacillin regarding dosage adjustments?

    <p>Requires renal dose adjustment</p> Signup and view all the answers

    How do Nafcillin and Oxacillin differ in terms of excretion?

    <p>Biliary excretion</p> Signup and view all the answers

    What is the primary mechanism of action of cephalosporins?

    <p>Binds to transpeptidase enzyme for cell wall synthesis</p> Signup and view all the answers

    Which factor does NOT affect the spectrum of cephalosporins?

    <p>Method of administration</p> Signup and view all the answers

    What describes the killing mechanism of cephalosporins?

    <p>Bactericidal and time-dependent killing</p> Signup and view all the answers

    Which of the following factors is NOT relevant to cross-sensitivity of cephalosporins?

    <p>Genetic predisposition of the patient</p> Signup and view all the answers

    Which statement accurately reflects cephalosporin use?

    <p>Cephalosporin effectiveness varies based on PBP type and affinity.</p> Signup and view all the answers

    Which cephalosporin is indicated for both IV and oral administration?

    <p>Cefuroxime</p> Signup and view all the answers

    What is a key characteristic of 2nd generation cephalosporins regarding Gram-negative bacteria?

    <p>Slight decrease in Gram-positive coverage</p> Signup and view all the answers

    Which of the following is true about cefuroxime?

    <p>It has excellent CNS penetration.</p> Signup and view all the answers

    What is a precaution associated with the use of 2nd generation cephalosporins?

    <p>Increased chance of hypersensitivity reactions</p> Signup and view all the answers

    Which cephalosporin offers anaerobic coverage?

    <p>Cefotetan</p> Signup and view all the answers

    Which cephalosporin has the greatest activity against Pseudomonas aeruginosa?

    <p>Ceftazidime</p> Signup and view all the answers

    What is the main reason ceftriaxone does not require renal dose adjustments?

    <p>It is metabolized in the liver.</p> Signup and view all the answers

    Which of the following statements about ceftriaxone is FALSE?

    <p>It can be diluted with calcium-containing solutions safely.</p> Signup and view all the answers

    What potential adverse effect is associated with prolonged use of cephalosporins?

    <p>Pseudomembranous colitis</p> Signup and view all the answers

    Which cephalosporin is NOT indicated for both intravenous and oral administration?

    <p>Ceftriaxone</p> Signup and view all the answers

    Which cephalosporin is known for having renal dosing adjustments needed, unlike ceftriaxone?

    <p>Ceftazidime</p> Signup and view all the answers

    What is a crucial precaution when administering ceftriaxone in neonates?

    <p>It may lead to kernicterus.</p> Signup and view all the answers

    What describes the bacterial spectrum of cephalosporins compared to penicillins?

    <p>Cephalosporins offer better Gram-negative coverage.</p> Signup and view all the answers

    Cefuroxime primarily targets which type of bacteria?

    <p>Both aerobic Gram-positive and Gram-negative bacteria</p> Signup and view all the answers

    What method of administration is Cefepime available in?

    <p>IV only</p> Signup and view all the answers

    Which of the following statements accurately describes Cefepime's activity?

    <p>It provides broad-spectrum coverage and is effective against Pseudomonas aeruginosa.</p> Signup and view all the answers

    What is a necessary consideration when prescribing Cefepime?

    <p>It necessitates dose adjustments due to renal elimination.</p> Signup and view all the answers

    Which precaution must be taken when using Cefepime?

    <p>There is a risk of cross-sensitivity with penicillins.</p> Signup and view all the answers

    What is a defining property of Cefepime?

    <p>It is classified as a broad-spectrum antibiotic with specific activity against certain Gram-negative bacteria.</p> Signup and view all the answers

    Which of the following drug options has coverage specifically for MRSA?

    <p>Ceftobiprole</p> Signup and view all the answers

    What is a primary clinical indication for Ceftaroline?

    <p>Skin and soft tissue infections</p> Signup and view all the answers

    Which of the following statements about Ceftobiprole is true?

    <p>It provides coverage against MRSA infections.</p> Signup and view all the answers

    What precaution should be taken when administering Ceftaroline or Ceftobiprole?

    <p>Caution is needed due to potential cross-sensitivity.</p> Signup and view all the answers

    Which characteristic is true regarding the elimination of Ceftaroline and Ceftobiprole?

    <p>They are renally eliminated and dose adjustments are needed.</p> Signup and view all the answers

    Which of the following describes the primary mechanism of action of monobactams?

    <p>Inhibits the transpeptidase enzyme responsible for cell wall cross-linking</p> Signup and view all the answers

    Which of the following factors does NOT determine the spectrum of activity of monobactams?

    <p>Size of the bacterial cell membrane</p> Signup and view all the answers

    What is a unique feature of Aztreonam regarding bacterial resistance?

    <p>It has a monocyclic ring structure that resists β-lactamases.</p> Signup and view all the answers

    What common side effect may occur with the intravenous administration of Aztreonam?

    <p>Phlebitis</p> Signup and view all the answers

    In which scenario might Aztreonam be safely used?

    <p>In patients with a mild penicillin allergy</p> Signup and view all the answers

    What is the primary mechanism of action of carbapenems?

    <p>Binds to the transpeptidase enzyme involved in cell wall synthesis</p> Signup and view all the answers

    Which carbapenem is specifically accompanied by cilastatin to prevent renal metabolism?

    <p>Imipenem</p> Signup and view all the answers

    Which carbapenem has the longest half-life allowing for once daily dosing?

    <p>Ertapenem</p> Signup and view all the answers

    What distinguishes meropenem from other carbapenems regarding guidelines for CNS penetration?

    <p>It is preferred in treatment guidelines due to good CNS penetration.</p> Signup and view all the answers

    Which of the following statements about the cross-allergic reaction of carbapenems is accurate?

    <p>It has a risk of cross-allergic reaction with penicillins, higher than cephalosporins.</p> Signup and view all the answers

    Which combination is used in a formulation to inhibit beta-lactamase activity?

    <p>Vaborbactam and Meropenem</p> Signup and view all the answers

    What is the primary mechanism of action of lipopeptides?

    <p>Inhibition of cell wall synthesis</p> Signup and view all the answers

    Which statement best describes the effect of lipopeptides on bacterial cells?

    <p>They lead to cell depolarization and potassium efflux.</p> Signup and view all the answers

    What type of bacterial killing mechanism do lipopeptides exhibit?

    <p>Bactericidal and concentration-dependent</p> Signup and view all the answers

    Which of the following outcomes is a consequence of lipopeptides' action?

    <p>Cell death due to disrupted membrane integrity</p> Signup and view all the answers

    What element is primarily involved in the cell death mechanism caused by lipopeptides?

    <p>Potassium efflux</p> Signup and view all the answers

    What is the primary route of administration for Daptomycin?

    <p>Intravenous</p> Signup and view all the answers

    Which statement accurately describes the half-life and dosing frequency of Daptomycin?

    <p>8 hours; once daily dosing</p> Signup and view all the answers

    Which condition may occur approximately 2-4 weeks after starting Daptomycin treatment?

    <p>Eosinophilic pneumonia</p> Signup and view all the answers

    What is a significant drug interaction associated with Daptomycin?

    <p>Risk of rhabdomyolysis with statins</p> Signup and view all the answers

    Why should Daptomycin not be used to treat pneumonia?

    <p>It is inactivated by surfactant</p> Signup and view all the answers

    What is the primary mechanism of action of Glycopeptides like Vancomycin?

    <p>Inhibit cell wall synthesis by binding to D-Ala-D-Ala</p> Signup and view all the answers

    Which type of killing mechanism is associated with Lipoglycopeptides?

    <p>Bactericidal / Concentration-Dependent Killing</p> Signup and view all the answers

    What is a major precaution associated with the use of Telavancin?

    <p>Nephrotoxicity and fetal risk</p> Signup and view all the answers

    Which of the following is a unique characteristic of Oritavancin?

    <p>It has a long half-life allowing for weekly dosing</p> Signup and view all the answers

    What mechanism allows some bacteria to resist Vancomycin?

    <p>Use of D-lactate in place of D-Ala</p> Signup and view all the answers

    Which dosing strategy is recommended for Vancomycin in patients with normal renal function?

    <p>15-20 mg/kg every 8-12 hours</p> Signup and view all the answers

    Which of the following statements about the absorption of Vancomycin is correct?

    <p>Oral Vancomycin is used to treat C. difficile colitis due to poor systemic absorption.</p> Signup and view all the answers

    What type of bacterial coverage do Lipoglycopeptides provide?

    <p>Broad spectrum including gram-positive bacteria</p> Signup and view all the answers

    Why is careful dosing adjustment required for glycopeptides in patients with renal impairment?

    <p>To prevent accumulation and toxicity</p> Signup and view all the answers

    What is the maximum infusion rate for Televancin to avoid Red Man Syndrome?

    <p>1 hour</p> Signup and view all the answers

    What should be avoided for 48 hours after administering Oritavancin?

    <p>Heparin</p> Signup and view all the answers

    Which of the following is a precaution when administering Dalbavancin?

    <p>Infuse over 30 minutes</p> Signup and view all the answers

    What side effect is commonly associated with Televancin?

    <p>Metallic taste</p> Signup and view all the answers

    What is a potential serious adverse effect associated with excessive usage of certain antibiotics mentioned?

    <p>Renal failure</p> Signup and view all the answers

    Which condition should be monitored when using Oritavancin, especially in patients on anticoagulants?

    <p>Risk of bleeding</p> Signup and view all the answers

    What is the recommended infusion duration for Oritavancin?

    <p>3 hours</p> Signup and view all the answers

    What is an adverse effect commonly associated with high levels of certain antibiotics that affects hearing?

    <p>Hearing loss</p> Signup and view all the answers

    What is the primary mechanism of action of nitroimidazoles?

    <p>Reduction of nitro group by anaerobes</p> Signup and view all the answers

    Which condition is a contraindication for using metronidazole during pregnancy?

    <p>First trimester</p> Signup and view all the answers

    What is the recommended dosing ratio for intravenous to oral administration of metronidazole?

    <p>1:1</p> Signup and view all the answers

    What serious side effect is associated with concurrent alcohol consumption while taking metronidazole?

    <p>Disulfiram-like reaction</p> Signup and view all the answers

    Which statement about benznidazole is true?

    <p>It is exclusively available through the CDC.</p> Signup and view all the answers

    What is the primary mechanism of action of Polymyxins?

    <p>Acts as a cationic detergent altering cytoplasmic membrane</p> Signup and view all the answers

    Which of the following is a common side effect associated with Polymyxins?

    <p>Nephrotoxicity</p> Signup and view all the answers

    When using colistimethate for treatment, which aspect requires careful consideration?

    <p>Dose reduction is required in renal impairment</p> Signup and view all the answers

    What is a significant precaution when administering Polymyxin B?

    <p>IM administration in hospital settings only</p> Signup and view all the answers

    Which of the following statements about inhalation administration of Polymyxins is true?

    <p>Both Polymyxin E and B can be used for inhalation</p> Signup and view all the answers

    What is the mechanism by which pleuromutilin inhibits bacterial growth?

    <p>It inhibits bacterial protein synthesis by binding to the peptidyl transferase center in the ribosome.</p> Signup and view all the answers

    Which of the following is a common side effect of Lefamulin?

    <p>Injection site reaction</p> Signup and view all the answers

    In which condition is dose adjustment necessary when using Lefamulin?

    <p>Hepatic disease</p> Signup and view all the answers

    What type of antibiotic activity is associated with pleuromutilin?

    <p>Bacteriostatic and time-dependent</p> Signup and view all the answers

    Which statement correctly describes a serious side effect of Lefamulin?

    <p>QT prolongation</p> Signup and view all the answers

    What is the primary mechanism through which Nitrofurantoin becomes active against bacteria?

    <p>Reduced by the bacteria to active form</p> Signup and view all the answers

    Which of the following describes one of the effects of Nitrofurantoin on bacterial cells?

    <p>It inhibits enzyme activity by damaging DNA</p> Signup and view all the answers

    Which of the following is NOT true about the action of Nitrofurantoin?

    <p>It directly interferes with peptidoglycan synthesis</p> Signup and view all the answers

    How does Nitrofurantoin's mechanism of action differ from traditional antibiotics?

    <p>It is activated after being reduced by bacteria</p> Signup and view all the answers

    In which of the following scenarios would Nitrofurantoin likely be effective?

    <p>Uncomplicated urinary tract infections caused by sensitive bacteria</p> Signup and view all the answers

    Which of the following side effects is NOT associated with Nitrofurantoin?

    <p>Severe renal impairment</p> Signup and view all the answers

    Under what condition should Nitrofurantoin not be used?

    <p>In patients with renal impairment (CrCl &lt; 60 ml/min)</p> Signup and view all the answers

    What is the primary indication for the use of Nitrofurantoin?

    <p>Uncomplicated urinary tract infections</p> Signup and view all the answers

    Which patient condition is NOT influenced by Nitrofurantoin's pharmacological properties?

    <p>Severe renal impairment</p> Signup and view all the answers

    What unique effect can Nitrofurantoin have on urine?

    <p>Produces brown urine</p> Signup and view all the answers

    At what pH does methenamine mandelate and hippurate convert to formaldehyde?

    <p>pH &lt; 5.5</p> Signup and view all the answers

    What is a significant reason for the slow reaction of methenamine mandelate and hippurate?

    <p>Must retain urine in the bladder</p> Signup and view all the answers

    Why are methenamine mandelate and hippurate contraindicated in cases of renal insufficiency?

    <p>They precipitate mandelic acid</p> Signup and view all the answers

    What adverse interaction should be avoided when administering methenamine mandelate and hippurate?

    <p>Sulfonamides</p> Signup and view all the answers

    What is the action of methenamine mandelate and hippurate in relation to bacteria?

    <p>Toxic to most bacteria</p> Signup and view all the answers

    What is the primary mechanism of action of Fosfomycin?

    <p>Inhibition of enolpyruvate transferase</p> Signup and view all the answers

    What is the recommended dosage form for Fosfomycin when treating uncomplicated UTIs?

    <p>Single oral dose mixed in cold water</p> Signup and view all the answers

    Which of the following statements about the pharmacokinetics of Fosfomycin is true?

    <p>It is excreted renally.</p> Signup and view all the answers

    What limitation exists for the use of Fosfomycin regarding systemic infections?

    <p>Inadequate levels for systemic disease</p> Signup and view all the answers

    In what manner is Fosfomycin typically administered?

    <p>Orally as a powder mixed in water</p> Signup and view all the answers

    What is the mechanism of action of rifaximin?

    <p>Binds to bacterial DNA-dependent RNA polymerase</p> Signup and view all the answers

    Which condition is rifaximin NOT indicated for?

    <p>Septicemia</p> Signup and view all the answers

    What is a common side effect of rifaximin?

    <p>Flatulence</p> Signup and view all the answers

    How is rifaximin primarily absorbed in the body?

    <p>Poorly absorbed orally</p> Signup and view all the answers

    Which of the following is an effect of rifaximin on the gut microbiota?

    <p>Decreases ammonia-producing bacteria</p> Signup and view all the answers

    What is the primary mechanism of action of fidaxomycin?

    <p>Inhibits RNA polymerase</p> Signup and view all the answers

    For which condition is fidaxomycin primarily used?

    <p>Clostridium difficile-associated diarrhea (CDAD)</p> Signup and view all the answers

    Which of the following is a common gastrointestinal side effect of fidaxomycin?

    <p>Flatulence</p> Signup and view all the answers

    What type of infections is fidaxomycin NOT indicated for?

    <p>Systemic infections</p> Signup and view all the answers

    What structural similarity does fidaxomycin share with another antibiotic class?

    <p>Macrolides</p> Signup and view all the answers

    What is the primary mode of action of Taurolidine in Defencath?

    <p>Damages cell walls and inhibits microbial adherence</p> Signup and view all the answers

    In what form is Taurolidine administered for its intended use?

    <p>Instilled into the dialysis catheter</p> Signup and view all the answers

    Which of the following statements best describes the mechanism of Taurolidine?

    <p>It has a non-specific action that impacts cell walls</p> Signup and view all the answers

    What is a key reason for using Taurolidine in dialysis procedures?

    <p>To prevent bacterial infections in catheterized patients</p> Signup and view all the answers

    How does Taurolidine differ from other antimicrobial agents?

    <p>It has a broad-spectrum activity against multiple microorganisms</p> Signup and view all the answers

    What is the primary mechanism of action of Taurolidine in a dialysis catheter?

    <p>Damages cell walls and inhibits adherence</p> Signup and view all the answers

    What potential complication should be monitored for when using Heparin in conjunction with Taurolidine/Heparin?

    <p>Heparin-induced thrombocytopenia</p> Signup and view all the answers

    How does Taurolidine affect microorganisms?

    <p>Inhibits biofilm formation</p> Signup and view all the answers

    What is NOT a characteristic of Taurolidine's mechanism?

    <p>Only targets specific pathogens</p> Signup and view all the answers

    In what formulation is Taurolidine typically used within a dialysis setting?

    <p>Instilled into the dialysis catheter</p> Signup and view all the answers

    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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