Antibiotics: SULF, CYCLINE, and (FL)OXACIN Flashcards
SULF (Sulfonamides)
- First effective chemotherapeutic agents used systemically for the prevention and cure of bacterial infections in humans (Prontosil (1932) => Nobel Prize in Medicine (1938))
- Development of penicillin (1940s) => diminished usefulness of
sulfonamides (except trimethoprim-sulfamethoxazole)
What is Sulfonamides drived from?
Para-aminobenzoic acid
MOA
Sulfonamides
Bacteriostatic
Competitive inhibitors of dihydropteroate synthase
- The bacterial enzyme responsible for incorporation of PABA into dihydropteroic acid, the immediate precursor of folic acid
- Competitive antagonism of PABA
Folic Acid Synthesis Inhibitor
SULF Types
Sulfamethoxazole
- Trimethoprim-Sulfamethoxazole (Bactrim, Septra, Cotrim): PO, and IV
Sulfadiazine: PO
Sulfacetamide: topical: cream, lotion, etc
Trimethoprim-Sulfamethoxazole (TMP-SMX)
Aka cotrimoxazole
- Wide variety of antimicrobial activity => range of clinical indications
Key spectrum of activity
- Staphylococcus aureus (including MRSA): Gram +
- E.coli, and other Enterobacteriaceae: Gram -
- Listeria monocytogenes (menagitis)
- Pneumocystitis jiroveci (most common)
- Taxoplasma gondii
- Nocaardia spp.
- Stenotrophomonas maltophilia
TMP-SMX: Indications
- Skin and soft tissue infections
- Urinary tract infections (UTIs)
- Meningitis
- Pneumocystis pneumonia
- Toxoplasma encephalitis
TMP-SMX: ADRs
- Gastrointestinal (nausea, vomiting, abdominal discomfort)
- Dermatologic/hypersensitivity
– (Rash, urticaria, Stevens-Johnson syndrome or toxic epidermal necrolysis) - Renal: Caution in renal impairment (dose adjustment needed),
– Crystalluria (need to maintain adequate hydration for prevention) - Hematologic (bone marrow suppression, e.g neutropenia)
TMP/SMX: Other Warning
- DDI: e.g warfaring; enhanced anticoagulant effect
- Cross-allergenicity with other sulfonamide drugs: glipizide, furosemide, hydrochlorothiazide
- Pregnancy catagory C: generally avoided in first trimester and near term
CYCLINE (Tetracyclines)
Introduced in late 1940s
- Basic four-ring chemcial structure with varying structural groups
MOA
Bacteriostatic
- Inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome => preventing access of aminoacyl tRNA to acceptor A site on the mRNA-ribosome complex
Protein synthesis inhibitor
Tetracyclines
Tetracycline (PO)
Doxycycline (Vibramycin, PO and IV)
Minocycline (Minocin, PO, IV):older
Tigecycline (Tygacil, IV): Glycylglycine (minocycline derivative)
Omadacycline (Nuzyra, PO and IV): aminomethylcycline
Eravacycline (Xerava, IV): fluorocycline (similar to tigecycline)
Demeclocyline (PO): NOT USED TO TREAT INFECTIONS
Tetracyclines
Topical indications
- Low-dose doxycycline (Oracea, PO): inflammatory pustules of rosacea
- Extended relase minocycline (Solodyn, PO): acne vugaris
- Sarecycline (Seysara, PO): acne vulgaris
Spectrum of Activity
- Borrelia burgdorferi (lime disease)
- Rickettsia (rocky mountain spotted fever)
- Treponema paallidum
- Chlamydia trachomatis
- Staphylococcus aureus (including MRSA)
- Atypicals: Mycoplasma pneumoniae, Chlamydia spp., Legionella spp.
- OTHER: Yersina pestis (plague), Bacillus anthracis (anthrax), Vibrio
cholerae (cholera), Bartonella henselae (cat scratch disease),
Plasmodium spp. (malaria), Coxiella burnetii (Q fever) - Tetracycline – Helicobacter pylori
- Tigecycline and eravacycline (add) – E. coli, other Enterobacteriaceae,
Bacteroides, and other drug-resistant bacterial strains - Omadacycline (adds) – Streptococcus pneumoniae (drug-resistant
strains), other streptococci, E. coli and other Gram-negative bacteria
Indication
Tetracyclines
- Lyme disease
- Rickettsial (RMSF) and other tickborne infections
- Syphilis
- Chlamydia
- Skin and soft tissue infections
- Community acquired pneumonia
- Complicatied intra abdominal infections
- Other zoonotic infections
Tigecycline BBW
- Increased all cause mortality versus comparators in phase 3 and 4 clinical trials
- Treaatment of hospital acquired pneumonia or ventilatory associated pneumonia
ADRs
cyclines
GI:
- Epigastric burning, abdominal discomfort, nausea, vomiting and diarrhea
- Esophagitis and esophageal ulcers
Photosensitivity:
- Avoid prolonged exposure to sunlight and use skin protection
Tooth enamel hypoplasia, permanent tooth discoloration
- Precaution in pediatrics
Other warning
cyclines
DDI: mutivalent cations (Ca2+, Mg2+, Al3+)
Pregnancy category D: only when benift outweight risk (RMSF)
(FL)OXACIN
Fluoroquinolones
- First quinolone: halidixic acid (treated UTIs)
- Broad antibacterial activity: treat wide vvariety of infectious disease
- Potentially fatal ADRs: many withdrawn from US market
– Lomefloxacin and sparfloxacin, Temafloxacin(immune hemolytic anemia), Trovafloxacin (hepatotoxicity), Grapafloxacin (cardiotoxicity), Clinafloxacin (phototoxicity)
MOA
- Bactericidal
- Inhibit topoisomerase II (gram (+)) (DNA gyrase) and IV (gram (-)) => inhibit relaxation of supercoiled DNA and promotes DNA breakage
Fluoroquinolones
- Ciprofloxacin (Cipro®, PO and IV)
- Ofloxacin
- Levofloxacin (Levaquin®, PO and IV)
- Moxifloxacin (Avelox®, PO and IV)
- Delafloxacin (Baxdela®, PO and IV)
Fluoroquinolones (ophthalmic/otic)
- Gatifloxacin (Zymaxid®, ophthalmic)
- Besifloxacin (Besivance®, ophthalmic)
- Ciprofloxacin (Ciloxan®, ophthalmic and Cetraxal®; Otiprio®, otic)
- Ofloxacin (Ocuflox®, ophthalmic and Floxin Otic®, otic)
- Levofloxacin
- Moxifloxacin (Moxeza®; Vigamox®, ophthalmic)
Spectrum of Activity
Fluoroquinolones
Broad spectrum antibiotics
- Gram-negative bacteria – E. coli, other Enterobacteriaceae,
Pseudomonas aeruginosa, and more
- Gram-positive bacteria – Streptococcus pneumoniae, other
streptococci, Staphylococcus aureus (delafloxacin; including MRSA)
- Atypicals - Mycoplasma pneumoniae, Chlamydia spp., Legionella spp.
- OTHER: Yersina pestis (plague), Bacillus anthracis (anthrax),
Mycobacterium tuberculosis (MDR tuberculosis), Salmonella, Shigella
Indications
Fluoroquinolones
Community acquired pneumonia
UTIs
Serious Systemic Gram Negative bacterial infections
- Hospital-acquired/ventilator-associated pneumonia
- Intra-abdominal infections
- Bloodstream infections
Bone/joint and skin/soft tissue infections
Sexually transmitted infections (chlamydia)
Acute sinusitis, COPD acute exacerbation
BBW
Fluoroquinolones
- CNS effects – seizures, tremors, dizziness
- Peripheral neuropathy
- Psychiatric reactions – nervousness, agitation, delirium,
hallucinations, confusion, etc. - Tendinopathy/tendon rupture – most frequently Achilles tendon
– Higher risk in older adults - Appropriate use - treatment of acute bacterial sinusitis, acute
bacterial exacerbation of chronic bronchitis, or uncomplicated UTI
should only happen if no alternatives - Myasthenia gravis - exacerbate muscle weakness
ADRs
Fluoroquinolones
- Gastrointestinal: Nausea, vomiting, and abdominal discomfort
- Clostridioides (formerly Clostridium) difficile-associated diarrhea
(CDAD) aka “C. diff infection” - QTc prolongation
- Rash and photosensitivity
- Dysglycemia (rare with quinolones currently on the market)
- Aortic aneurysm and dissection (relatively new FDA warning)
- Musculoskeletal disorders – concern in pediatrics
Other Warnings
Fluoroquinolones
DDI:
- Multivalent cations (Ca2+, Mg2+, AI3+)
- QTc prolongation
Pregnancy Category C: Avoided unless benefit outweight risk
