186: Systemic and Topical Antibiotics Flashcards
What are the indications for penicillin therapy in treating skin and soft tissue infections (SSTIs)?
Penicillin therapy is indicated for:
- Syphilis and nonvenereal treponematoses
- Empiric treatment of mild or moderate nonpurulent SSTIs
- Infections caused by Streptococcus spp., Clostridium spp., spirochetes, Pasteurella multocida, Eikenella corrodens, and Erysipelothrix rhusiopathiae
What are the common side effects and precautions associated with penicillin use?
Common side effects and precautions include:
- Hypersensitivity reactions ranging from mild to severe
- Penicillin is a leading cause of drug-induced anaphylaxis, accounting for approximately 1% to 10% of all cases
- 5% to 10% of the general population reports an allergy to penicillin, which is likely overreported
- Skin prick testing can detect Type I hypersensitivity, followed by intradermal testing if negative
- Desensitization is recommended for patients with a positive skin test if a B-lactam is necessary
What is the mechanism of action of B-lactam antibiotics, including penicillins?
B-lactam antibiotics, including penicillins, work by:
- Binding to specific penicillin-binding proteins
- Inhibiting cell wall peptidoglycan synthesis
- Inactivating an inhibitor of autolytic enzymes present on bacterial cell walls
What steps should be taken to confirm penicillin allergy in a patient requiring treatment for a severe purulent SSTI?
Skin prick testing followed by intradermal testing if negative. If the tests are negative, a challenge dose of oral penicillin under observation may be administered. If positive, desensitization or alternative antibiotics like vancomycin may be used.
What are the characteristics of extended-spectrum penicillins and their activity against Pseudomonas spp.?
Extended-spectrum penicillins, such as carboxypenicillins (carbenicillin, ticarcillin) and ureidopenicillins (piperacillin), have a broad spectrum and susceptibility to B-lactamase. They exhibit some activity against Pseudomonas spp. and Proteus spp. Ureidopenicillins are derived from ampicillin and have greater activity against Gram-negative organisms, including Pseudomonas.
What is the significance of antistaphylococcal penicillins in treating infections?
Antistaphylococcal penicillins, such as oxacillin, dicloxacillin, and nafcillin, are B-lactamase resistant and are effective against S. aureus. They are the drug of choice (DOC) for methicillin-sensitive S. aureus SSTIs but have no activity against enterococci or Gram-negative organisms. They are important for empiric therapeutic use in treating certain infections.
How should oral penicillins be administered to ensure proper absorption?
Most oral penicillins should be taken at least 1 hour before or after meals to avoid food binding. However, amoxicillin is unaffected by food. Other penicillins like penicillin G, nafcillin, carbenicillin, ticarcillin, and piperacillin are unstable at low pH and poorly absorbed, thus requiring careful administration.
What are the metabolic and excretion characteristics of penicillins?
Penicillins are typically excreted renally, with free penicillin being excreted in the urine. Nafcillin, oxacillin, and ureidopenicillins are excreted via the hepatobiliary system. They are generally poorly absorbed and can be degraded by colonic bacteria. Additionally, they do not typically cross the blood-brain barrier, although meningitis can enhance permeability.
What is the pregnancy category of penicillins and their safety during breastfeeding?
Penicillins are classified as Pregnancy Category B, indicating they are excreted in breast milk in low quantities and are considered safe during breastfeeding.
What are the indications for using first-generation cephalosporins in treating SSTIs?
First-generation cephalosporins, such as Cephalexin and Cefazolin, are indicated for uncomplicated SSTIs caused by Staphylococcus aureus and Streptococcus pyogenes. They are effective for mild or moderate nonpurulent SSTIs (cellulitis) where community-acquired MRSA is not suspected.
What is the expanded Gram-negative activity of second-generation cephalosporins compared to first-generation cephalosporins?
Second-generation cephalosporins, such as Cefprozil and Cefoxitin, have expanded Gram-negative activity over first-generation agents, particularly against H. influenzae and Moraxella catarrhalis.
What are the side effects and precautions associated with first and second-generation cephalosporins?
First and second-generation cephalosporins cross-react with penicillin in approximately 10% of penicillin-allergic patients. It is important to assess for penicillin allergy before prescribing these medications.
How do third-generation cephalosporins differ in their effectiveness against Gram-positive organisms compared to earlier generations?
Third-generation cephalosporins, such as Cefdinir and Ceftriaxone, have expanded Gram-negative activity but are less effective against Gram-positive organisms compared to first and second-generation cephalosporins.
What is the significance of cross-reactivity between cephalosporins and penicillin?
Cross-reactivity between cephalosporins and penicillin is significant as it can lead to allergic reactions in patients with a penicillin allergy. First and second-generation cephalosporins cross-react in 10% of cases, while third-generation cephalosporins cross-react in 2% to 3% of cases.
Which cephalosporins are safer options for a patient with a history of penicillin allergy?
Cefdinir, cefpodoxime, and cefuroxime are safer options because they lack side chain similarity to penicillin, ampicillin, or amoxicillin.
Which cephalosporin generation is least likely to cross-react in a patient with a history of penicillin allergy?
3rd-generation cephalosporins are least likely to cross-react, with a cross-reactivity rate of 2% to 3%.
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B-lactam antibiotics inhibit bacterial cell wall synthesis by blocking peptidoglycan incorporation.
What are the indications for Ceftaroline in the treatment of SSTIs?
Ceftaroline is indicated for complicated SSTIs, including those caused by MRSA, and is an option for empiric therapy for severe purulent SSTIs.
How does the spectrum of activity of 4th generation cephalosporins compare to 3rd generation cephalosporins?
4th generation cephalosporins, such as Cefepime, have increased activity against Gram (+) organisms compared to 3rd generation cephalosporins and are also active against Gram (-) organisms like Pseudomonas and Enterobacteriaceae.
What is the significance of the dihydrothiazine ring in B-lactam antibiotics?
The dihydrothiazine ring in B-lactam antibiotics provides resistance to some, but not all, B-lactamases, affecting their efficacy against resistant bacteria.
What are the dietary considerations for taking esterified cephalosporins like cefuroxime and cefpodoxime?
Esterified cephalosporins require food to extend mucosal contact time and allow enzymatic cleavage; medications that lower gastric pH can reduce their absorption.
What drug is used for a severe SSTI caused by MRSA, and what is its spectrum of activity?
Ceftaroline is used. It has a broad spectrum of activity against Gram-positive organisms, including MRSA, and some Gram-negative organisms.
What generation and specific drug should be used for a severe SSTI caused by Pseudomonas aeruginosa?
A 4th-generation cephalosporin like cefepime should be used due to its activity against Pseudomonas aeruginosa.
What is the mechanism of action of tetracyclines in bacterial treatment?
Tetracyclines inhibit bacterial protein synthesis by binding to the 30S ribosomal subunit and blocking transfer RNA binding to the messenger RNA-ribosome complex.
What are the indications for using doxycycline in treatment?
Doxycycline is preferred for treating infections caused by:
- Borrelia spp.
- Chlamydia spp.
- Ehrlichia spp. (monocytic and granulocytic ehrlichiosis)
- Coxiella burnetii (Q fever)
- Leptospira spp.
- Mycoplasma spp.
- Rickettsia spp.
It is also used for infections caused by:
- Actinomyces spp.
- Bacillus anthracis
- Mycobacterium marinum
- Klebsiella granulomatis (granuloma inguinale)
- Vibrio vulnificus
Additionally, it is an acceptable treatment for animal bites and syphilis (if allergic to penicillin).
What are the side effects and precautions associated with tetracyclines?
Common side effects and precautions for tetracyclines include:
- Skin and nail hyperpigmentation (minocycline)
- Dental hyperpigmentation (in infants and children)
- Gastrointestinal irritation
- Photosensitivity (doxycycline)
- Esophageal erosion/stricture
- Skeletal hypoplasia
- Renal toxicity
- Pancreatitis
- Blood dyscrasias (long-term use)
- Pseudomembranous colitis
Pregnancy Category D: Should be avoided during pregnancy, while nursing, and throughout childhood as they can cross the placenta and appear in high concentrations in breast milk.
How do the pharmacokinetics of doxycycline differ from tetracycline?
Doxycycline and minocycline are unaffected by the presence or absence of food and have longer half-lives than tetracycline, requiring less frequent dosing. They also have:
- Greater lipid solubility than tetracycline, allowing for good tissue penetration.
- Doxycycline is excreted in the feces and does not require dose adjustments, while tetracycline requires adjustments due to renal excretion.
What dietary restrictions should a patient prescribed doxycycline follow?
The patient should avoid concurrent ingestion of iron preparations, aluminum hydroxide gels, calcium and magnesium salts, or milk products as they lower the absorption of doxycycline.
Which tetracycline should be avoided in a pregnant patient and why?
Tetracyclines, including doxycycline, should be avoided during pregnancy as they are Pregnancy Category D and can cross the placenta, affecting developing bone and teeth.
What is the mechanism of action of Clindamycin?
Clindamycin is a lincosamide antibiotic that binds to the bacterial 50S ribosomal subunit, inhibiting protein synthesis through blockade of peptide chain initiation. It also facilitates opsonization and phagocytosis, decreases bacterial adhesion to host cells, and has antiparasitic activity by targeting protein synthesis of the apicoplast.
What are the common side effects associated with Clindamycin therapy?
Common side effects of Clindamycin include gastrointestinal upset and diarrhea, occurring in 20% to 35% of patients. It can also lead to C. difficile-associated diarrhea and pseudomembranous colitis, which are life-threatening complications (though infrequent).
What are the indications for Macrolide therapy?
Indications for Macrolide therapy include:
- Granuloma inguinale
- Chlamydia
- Uncomplicated non-purulent skin and soft tissue infections
- Lyme disease
- Non-tuberculous mycobacterial skin disease
- Lymphogranuloma venereum (alternative)
What are the common side effects of Macrolides?
The most common side effects of Macrolides include:
- Abdominal pain
- Nausea
- Vomiting
- Diarrhea
Additionally, Macrolides may produce cardiac conduction defects and arrhythmias, and there is a potential association with increased risk of sudden cardiac death or ventricular tachyarrhythmias.
How do Clindamycin and Macrolides differ in their mechanism of action?
Clindamycin and Macrolides both bind to the 50S ribosomal subunit, but Clindamycin is a lincosamide that inhibits protein synthesis through blockade of peptide chain initiation, while Macrolides inhibit RNA-dependent protein synthesis and also affect neutrophil chemotaxis and interleukin-8 secretion.
What is Clindamycin’s unique mechanism of action against abscesses?
Clindamycin preferentially accumulates in polymorphonuclear leukocytes, facilitating its impact on abscesses by enhancing opsonization and phagocytosis.
What are the primary uses of clarithromycin and azithromycin in treating infections?
Clarithromycin and azithromycin are effective against a variety of pathogens including:
- H. influenzae
- Neisseria gonorrhoeae
- M. catarrhalis
- Chlamydia
- Mycoplasma pneumoniae
- Helicobacter pylori
- T. gondii
- T. pallidum
- Borrelia burgdorferi
- Nontuberculous mycobacteria.
What are the key pharmacological properties of fluoroquinolones?
Fluoroquinolones are characterized by:
- Inhibition of bacterial topoisomerase II (DNA gyrase) and topoisomerase IV, disrupting DNA replication and repair.
- Broad-spectrum activity against many Gram-negative organisms, including Salmonella, Shigella, Enterobacter, and Campylobacter.
- Effective against some Mycobacterium species, including M. tuberculosis.
- Rapid absorption and large volume of distribution, with most excreted by the kidneys, except for moxifloxacin.
What are the contraindications and precautions associated with fluoroquinolone therapy?
Key contraindications and precautions for fluoroquinolone therapy include:
- Decreased bioavailability when taken with antacids (aluminum, magnesium, iron, and calcium).
- Risk of tendon rupture in patients with renal disease, hemodialysis, or steroid use.
- Seizure disorder exacerbation
- Excretion of breastmilk in negligible amounts
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Key contraindications and precautions include decreased bioavailability with antacids, risk of tendon rupture in certain patients, exacerbation of seizure disorders, and excretion in breast milk in negligible quantities.
What is the significance of the resistance observed in group A strep isolates to erythromycin?
Approximately 50% of group A strep isolates are resistant to erythromycin, highlighting the need for alternative treatments and monitoring resistance patterns.
Which macrolide is most active against Mycobacterium leprae?
Clarithromycin is the most active macrolide against Mycobacterium leprae.
What is the mechanism of action of Trimethoprim-Sulfamethoxazole (TMP-SMX)?
TMP-SMX inhibits bacterial nucleic acid synthesis by Trimethoprim inhibiting dihydrofolate reductase and Sulfamethoxazole inhibiting dihydropteroate synthetase.
What are the indications for using Trimethoprim-Sulfamethoxazole in treating SSTIs?
Indications include community-acquired MRSA infections, empiric therapy for moderate purulent SSTIs, uncomplicated SSTIs, and granuloma inguinale (alternative treatment).
What are the contraindications for using Trimethoprim-Sulfamethoxazole?
Contraindications include severe reactions in HIV/AIDS patients, prolonged prothrombin time in warfarin users, and contraindication in patients on methotrexate.
What are the common side effects associated with Trimethoprim-Sulfamethoxazole?
Common side effects include erythema, photosensitivity, nausea, vomiting, anorexia, glossitis, stomatitis, skin reactions, and blood dyscrasias.
What is the role of Vancomycin in treating skin and soft tissue infections?
Vancomycin is used for treating Gram (+) infections resistant to B-lactams, first-line therapy for complicated SSTIs caused by MRSA, and empiric therapy for severe SSTIs.
What precautions should be considered when administering Vancomycin?
Precautions include renal function monitoring, risk of nephrotoxicity, ototoxicity, phlebitis, hypersensitivity reactions, and risk of ‘Red man syndrome’.
What is the first-line treatment for a severe purulent SSTI caused by hospital-acquired MRSA?
Vancomycin is the first-line treatment. Monitor for nephrotoxicity, ototoxicity, and ‘Red Man Syndrome’.
Which fluoroquinolones are effective against chlamydia and chancroid?
Ciprofloxacin and levofloxacin are effective against chlamydia and chancroid.
What is the recommended dose of Vancomycin and what monitoring is required?
The recommended dose is 15 to 20 mg/kg. Renal function monitoring is required during therapy.
What are the primary uses of lipoglycopeptides such as dalbavancin, oritavancin, and telavancin?
They disrupt bacterial cell wall integrity and are used for empiric therapy for severe purulent SSTIs, with long half-lives allowing for infrequent dosing.
How does tedizolid compare to linezolid in terms of efficacy against Gram-positive bacteria?
Tedizolid is 2-fold to 8-fold more potent against Gram-positive bacteria compared to linezolid.
What are the common side effects associated with quinpristin-dalfopristin?
Common side effects include phlebitis, arthralgia, and myalgia, with potential elevation of hepatic transaminases.
What is the primary mechanism of action of daptomycin?
Daptomycin disrupts bacterial cell wall function and is approved for treating complicated SSTIs caused by MRSA, penicillin-resistant S. pneumoniae, and VRE.
What are the key characteristics of ertapenem in treating complicated SSTIs?
Ertapenem is a β-lactam antibiotic with broad antimicrobial activity, comparable to piperacillin-tazobactam, but has poor activity against Pseudomonas, Acinetobacter, and enterococci.
What are the advantages of tigecycline over traditional tetracyclines?
Tigecycline has better activity against tetracycline-resistant organisms and improved efficacy against Streptococcus spp.
What alternative antibiotic can be used for a patient allergic to vancomycin?
Linezolid can be used as an alternative, offering a broader spectrum of coverage and better safety profile.
Which lipoglycopeptide should be avoided in a patient with a history of QT prolongation?
Telavancin should be avoided due to its increased risk of QT prolongation.
What serious adverse event should be monitored for in a patient prescribed daptomycin?
Monitor for myopathy, which is a transient and reversible serious adverse event.
What are the limitations of ertapenem?
Ertapenem has poor activity against Pseudomonas, Acinetobacter, and enterococci and should be used cautiously in renal impairment.
What precautions should be taken regarding tigecycline’s side effects?
Tigecycline shares a similar side effect profile to tetracyclines, including photosensitivity and gastrointestinal upset.
Which lipoglycopeptide has the longest half-life?
Oritavancin has the longest half-life, allowing for infrequent dosing.
Which oxazolidinone is more potent and what is its dosing schedule?
Tedizolid is more potent with a dosing schedule of 200 mg once daily.
What is the mechanism of action of quinopristin-dalfopristin?
Quinopristin-dalfopristin irreversibly inhibits bacterial protein translation by binding to different sites of the 50S ribosomal subunit.
What is the dosing schedule and excretion route for daptomycin?
The dosing schedule is 4 mg/kg IV every 24 hours for 7 to 14 days, primarily excreted by the kidneys.
What is the dosing schedule for ertapenem and its limitations?
The dosing schedule is 1 g/day IV for 7 to 14 days. Limitations include poor activity against Pseudomonas, Acinetobacter, and enterococci.
What is the dosing schedule for tigecycline and its advantages?
The dosing schedule is 50 mg IV twice daily following a 100-mg loading dose. It has better activity against tetracycline-resistant organisms.
What are the considerations for using topical antibiotics after minor surgical procedures?
Topical antibiotics may decrease postoperative infections but can be unnecessary and counterproductive due to expense and allergy risks.
What is the significance of benzoyl peroxide in relation to clindamycin?
Benzoyl peroxide may slow the development of antibiotic resistance when added to clindamycin.
What is mupirocin and how is it used?
Mupirocin is a topical agent used intranasally BID for 5 days to eradicate MRSA colonization.
What are the properties and uses of bacitracin?
Bacitracin is effective against impetigo, furunculosis, and pyodermas, often combined with polymyxin B and neomycin.
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Neomycin has a high risk of allergic contact dermatitis, while gentamicin is used for prophylaxis against malignant otitis externa.
What preparation is available for fusidic acid and can it be used for atopic dermatitis?
Fusidic acid is available at 2% and can be combined with steroids for treating atopic dermatitis.
Which aminoglycoside is suitable for a patient undergoing surgery for a periorbital wound?
Gentamicin is suitable and can be used as an ophthalmic formulation.
Which broad-spectrum antibiotic is commonly used for burn wounds?
Silver sulfadiazine is commonly used for burn wounds due to its broad-spectrum activity.
Which topical antibiotic is commonly used for atopic dermatitis combined with steroids?
Fusidic acid is commonly used due to its low risk of allergic contact dermatitis.
How should mupirocin be applied for MRSA colonization?
Mupirocin ointment should be applied intranasally twice daily for 5 days.
What antibiotic derived from Bacillus subtilis is used for treating impetigo?
Bacitracin is derived from Bacillus subtilis and is used for treating impetigo.
What is the mechanism of action of mupirocin?
Mupirocin reversibly binds to isoleucyl-transfer RNA synthetase, inhibiting protein synthesis.
Which antibiotic is derived from Micromonospora purpurea, and what is its use?
Gentamicin is derived from Micromonospora purpurea and is used for the treatment of minor skin infections and prophylaxis against malignant otitis externa.
What is the application frequency for mupirocin ointment (based on the table)?
Mupirocin ointment is applied 3 times per day.
What is the safety category of retapamulin?
Retapamulin is classified as Category B for safety.
What type of bacteria does bacitracin target?
Bacitracin targets Gram-positive cocci, specifically staphylococci and streptococci.
What is the recommended application frequency for polymyxin B ointment?
Polymyxin B ointment is applied 1 to 3 times per day.
What is the primary use of silver sulfadiazine?
Silver sulfadiazine is primarily used in the treatment of burns.
What is the common adverse effect associated with clindamycin (topical)?
Clindamycin can cause allergic contact dermatitis as an adverse effect.
What is the application frequency for fusidic acid ointment?
Fusidic acid ointment is applied 2 to 3 times per day for up to 2 weeks.
What is the risk associated with the use of clindamycin in terms of skin reactions?
The risk of allergic contact dermatitis (ACD) with clindamycin is high, affecting 9% of patients who undergo patch testing.
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Mupirocin is a broad spectrum antibiotic commonly used in the treatment of burns.
What is the mechanism of action of Penicillin in bacterial treatment?
Penicillin inhibits cell wall peptidoglycan synthesis.
Which class of systemic antibiotics disrupts bacterial cell wall integrity and/or inhibits bacterial cell wall synthesis?
Vancomycin is known to disrupt bacterial cell wall integrity and/or inhibit bacterial cell wall synthesis.
What is the role of Tetracyclines in bacterial protein synthesis?
Tetracyclines inhibit bacterial protein synthesis by binding to the 30S ribosomal subunit.
How do Macrolides function in inhibiting bacterial growth?
Macrolides reversibly bind to the 50S ribosomal subunit and inhibit protein synthesis.
What is the primary action of Clindamycin in bacterial treatment?
Clindamycin binds to the 50S ribosomal subunit and inhibits protein synthesis.
What is the mechanism of action of Daptomycin?
Daptomycin disrupts bacterial cell wall integrity and/or inhibits bacterial cell wall synthesis.
Which antibiotic class is known to inhibit bacterial nucleic acid synthesis?
Fluoroquinolones inhibit bacterial nucleic acid synthesis by inhibiting dihydrofolate reductase and dihydropteroate synthetase.
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Mupirocin binds to the 30S ribosomal subunit and inhibits protein synthesis.
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TMP-SMX inhibits bacterial nucleic acid synthesis by inhibiting dihydrofolate reductase and dihydropteroate synthetase.
How does Neomycin function as a topical antibiotic?
Neomycin inhibits protein synthesis by binding to the 30S ribosomal subunit.
What are the first-line therapies for Lyme disease caused by Borrelia burgdorferi?
Doxycycline or amoxicillin are the first-line therapies for Lyme disease caused by Borrelia burgdorferi.
Which antibiotic is recommended for treating human bite infections caused by Eikenella corrodens?
The first-line therapy for human bite infections caused by Eikenella corrodens is Penicillin or ampicillin.
What is the alternative therapy for Chlamydia trachomatis infections?
The alternative therapy for Chlamydia trachomatis infections includes erythromycin, ofloxacin, or levofloxacin.
What is the recommended first-line therapy for cutaneous anthrax caused by Bacillus anthracis?
The first-line therapy for cutaneous anthrax caused by Bacillus anthracis is doxycycline, ciprofloxacin, or levofloxacin.
What are the first-line and alternative therapies for gas gangrene caused by Clostridium perfringens?
The first-line therapy for gas gangrene caused by Clostridium perfringens is Penicillin G or clindamycin. The alternative therapy includes doxycycline, chloramphenicol, and metronidazole.
What is the first-line therapy for Q fever caused by Coxiella burnetii?
The first-line therapy for Q fever caused by Coxiella burnetii is doxycycline.
What is the first-line therapy for necrotizing wound infections caused by Vibrio vulnificus?
The first-line therapy for necrotizing wound infections caused by Vibrio vulnificus is doxycycline plus ceftazidime.
What is the recommended treatment for Staphylococcus aureus infections?
For Staphylococcus aureus infections, the first-line therapy for MSSA is oxacillin or nafcillin, while for HA-MRSA, it is vancomycin, cefazolin, or oritavancin.
