Antibacterials 6 Flashcards
Describe Cotrimoxazole? MOA?
- Combination of trimethoprim & sulfamethoxazole
- Bactericidal
Mechanism of action:
• Synergistic: inhibition of sequential steps in
tetrahydrofolic acid synthesis
Cotrimoxazole Clinical Applications?
• Uncomplicated UTI’s (drug of choice)
• Commonly used in treatment of opportunistic
infections (in immunocompromised)
• Upper respiratory, ear and sinus infections
Cotrimoxazole PK?
- Oral admin. generally (can be given IV)
* Well distributed (including CSF)
Cotrimoxazole AE?
- Dermatologic (common)
- GI
- Hematologic (hemolytic anemia)
- AIDS patients = higher incidence
- Contraindicated in pregnancy (esp. 1st trimester)
Describe Metronidazole
- Antimicrobial, amebicide & antiprotozoal
- Activity against anaerobic bacteria
- Bactericidal
Metronidazole MOA?
• Anaerobic conditions are vital for optimal activity
• Undergoes reductive bioactivation of its nitro group by
ferredoxin
• Forms cytotoxic products that interfere with nucleic acid
synthesis -> damage DNA
Metronidazole Clinical Applications?
- Pseudomembranous colitis
- Anaerobic or mixed intra-abdominal infections
- Vaginitis
- Brain abscesses
- H.pylori eradication (in combination)
Metronidazole PK?
- Oral, IV, rectal or topical
- Wide distribution (including CSF)
- Elimination = hepatic metabolism
Metronidazole AE?
• Disulfiram-like effect (avoid alcohol)
• Headache, dark coloration of urine, metallic taste
• GI irritation, stomatitis, peripheral neuropathy (prolonged
use)
• Leukopenia, dizziness, ataxia (rarer)
• Opportunistic fungal infections
• Use generally not advised in 1st trimester
Describe Polymyxin B?
- Basic peptides
- Activity against Gram-negative bacteria
- Gram-positive bacteria are resistant
- Bactericidal
MOA of Polymyxin B?
- Act as cationic detergents
- Attach to and disrupt bacterial cell membranes
- Also, bind to and inactivate endotoxin
Polymyxin B Clinical Applications?
• Mostly topical treatment for infected superficial skin
lesions
• Possible emerging role as parenteral agent for salvage
therapy of infections caused by resistant Acinetobacter
baumannii, P.aeruginosa and Enterobacteriaceae strains
Polymyxin AE?
- Few when used topically
* Given systemically = extremely nephrotoxic
Describe Urinary antiseptics and use?
- Oral agents with antibacterial activity in urine but little or no systemic effect
- Use is limited to prophylaxis and treatment of lower UTI’s
Describe Nitrofurantoin?
• Bacteriostatic & bactericidal
• Active against many Gram-positive and Gram-negative
bacteria
Nitrofurantoin MOA?
• Reduction of nitrofurantoin by bacteria in the urine leads
to formation of reactive intermediates that subsequently
damage bacterial DNA
• Slow emergence of resistance and no cross-resistance
Nitrofurantoin PK and AE?
Pharmacokinetics
• Rapid elimination (only achieves adequate concentrations
in urine)
Adverse Effects
• Anorexia, nausea & vomiting.
•Neuropathies, hemolytic anemia (G6PD deficient patients)
•Pulmonary injury (rare)
Nitrofurantoin Contraindications?
- Significant renal insufficiency
- Pregnancy at term (38-42 weeks)
- Infants <1 month (risk of hemolytic anemia)
Antimicrobial effect on fetus and neonate? Aminoglycoside? Tetracycline,Glycilines? Sulfonamides? Choramphenicol? Fluoroquinolones? Nitrofurantion? Trimethoprim? Metronidazole?
Aminoglycosides -Possible damage to the eighth
cranial nerve of the fetus
Tetracyclines, Glycylcyclines -Tooth enamel dysplasia, inhibition
of bone growth
Sulfonamides Kernicterus (displacement of bilirubin from serum albumin)
Chloramphenicol Gray baby syndrome
Fluoroquinolones Tendon rupture/damage
Nitrofurantion Hemolytic Anemia
Trimethoprim Folate deficiency
Metronidazole Unknown safety
Surgical Antimicrobial Prophylaxis Cardiothoracic?
Antimicrobials:
Routine: Cefazolin
MRSA: Cefazolin +
vancomycin
Penicillin-allergic patient:
Vancomycin + aztreonam (routine & MRSA)
Surgical Antimicrobial Prophylaxis Colorectal?
Antimicrobials:
Ampicillin/sulbactam
Penicillin-allergic patient: Ciprofloxacin + metronidazole or ciprofloxacin + clindamycin
Surgical Antimicrobial Prophylaxis General Surgery?
Antimicrobials: Cefazolin
Penicillin-allergic patient:
Vancomycin or
clindamycin
Surgical Antimicrobial Prophylaxis Neurosurgical?
Antimicrobials: Cefazolin
Penicillin-allergic patient: Vancomycin
Surgical Antimicrobial Prophylaxis Orthopedics?
Antimicrobials: Cefazolin
Penicillin-allergic patient:
Vancomycin or
clindamycin
Surgical Antimicrobial Prophylaxis Vascular Surgery?
Antimicrobials: Cefazolin or cefuroxime
Penicillin-allergic patient:
Vancomycin or
clindamycin
Anti-staphylococcal penicillins used against which bacteria?
beta-lactamase producing bacteria
Gram +ve
Carbapenems used against which bacteria?
beta-lactamase producing bacteria
Gram +ve and –ve
Aztreonam used against which bacteria?
beta-lactamase producing bacteria
Gram –ve
Vancomycin used against which bacteria?
MRSA, enterococci
Daptomycin used against which bacteria?
MRSA, enterococci, VRE
Tigecycline used against which bacteria?
MDR Gram +ve and some Gram –ve bacteria
Streptogramins used against which bacteria?
MRSA, VRE
Linezolid used against which bacteria?
MRSA, VRE
Rifampin used against which bacteria?
MRSA
