pharma infections

• Causes of Gastrointestinal infections


  • Viral
  • Bacterial
  • Parasitic

  
• Symptoms of Gastrointestinal infections

  • Diarrhea
  • Nausea
  • Vomiting
  • Abdominal pain
  • Dehydration

  
• Dehydration is the main danger of gastrointestinal infections, so rehydration is important
• Most gastrointestinal infections are self-limited and resolve within a few days
• In specific populations (newborns/infants, immuno-compromized patients or elderly populations), gastrointestinal infections are potentially serious

  
• Rapid diagnosis and appropriate treatment are particularly important in specific populations
• Oral rehydration therapy (ORT)

  Replace water, salt, sugars lost due to diarrhea, vomiting

  
• WHO-ORS (low-osmolar ORS or reduced-osmolarity ORS)


  Formula per liter of fluid
• Super ORS


  Special kinds of ORS where instead of mono sugars it comprises of more complex sugars or aminoacids and trace amounts of zinc
• Enteric viral infections


  • Rotavirus
  • Norovirus: infants
  • Astrovirus: children , adults
  • Enteric adenovirus: adults, children
• Enteric viral infections


  • Most common cause of gastrointestinal viral infections
  • Characterized by moderate to severe vomiting followed by watery diarrhea and fever
  • Transmitted from water, vegetables contaminated by feces

  
• No specific antiviral drug for enteric viral infections, just conservative treatment with antipyretics for fever, antiemetics for vomiting and ORS for dehydration
• Antibiotics not recommended for bacterial gastrointestinal infections unless infection causes bacteremia and septicemia or in debilitating patients
• Common sources of bacterial GI infections

  • Salmonella enterica (S. typhi, S paratyphi)
  • E.coli (enterotoxigenic, enteropathogenic)
  • Shigella spp (Bacillary dysentery)
  • Campylobacter jejuni
  • Vibrio cholera
  • Clostridium difficile: antibiotic associated diarrhea
• Pseudomembranous colitis (antibiotic-associated diarrhea or C. difficile colitis)


  Can occur following antibiotic treatment when normally harmless C. difficile grow rapidly due to lack of competition with other flora, and produce toxins that damage the inner wall of the intestines
• Treatment of Pseudomembranous colitis

  1. Stop all antibiotics whenever possible

  2. Oral metronidazole 250 mg /6 hr (1st choice)

  3. If metronidazole failed, give oral vancomycin solution 125 mg/6 hr
• Antibiotics likely cause diarrhea

  • ampicillin
  • amoxicillin
  • cephalosporins
  • clindamycin
• Antibacterial for Treatment of Cholecystitis

  • Meropenem, imipenem/cilastatin
  • Piperacillin/ tazobactum: effective mainly against ? Org.
  • Tigecycline
  • Cefazolin, cefepime ?
  • Ciprofloxacin, levofloxacin
• Antibacterial for Treatment of Liver abscess & peritonitis


  • Piperacillin/ tazobactum
  • Tigecycline
  • Meropenem
• Azithromycin


  • MOA: Inhibit protein synthesis
  • Rapidly absorbed from GIT
  • Food delays absorption
  • Extensive tissue distribution, except CSF
  • Major route of elimination: Biliary route
  • Half- life approx. 68 hr
  • Advantage: once daily dosing
• Indications for Azithromycin


  • E.coli (enterotoxigenic, enteropathogenic)
  • Shigella spp (Bacillary dysentery)
  • Campylobacter jejuni
  • Vibrio cholera

  
• Fluoroquinolone Levofloxacin and Ciprofloxacin


  • MOA: inhibit bacterial ? synthesis
  • Attain excellent tissue penetration
  • Kill S. typhi in its intracellular stationary stage in monocytes/macrophages
  • Achieve higher active drug levels in the gall bladder
• Adverse effects of Fluoroquinolones


  • N/V, diarrhea
  • Risk of aortic aneuryrsm and dissection
  • Photo toxicity
  • Peripheral neuropathy and glucose dysregulation
  • Predispose to seizers in pts with history of epilepsy
  • Articular cartilage erosion (arthropathy)
• Fluoroquinolones should be avoided in pregnancy, lactation, and children under 18 years of age
• Ciprofloxacin (enzyme inhibitor) can increase serum levels of warfarin, and cyclosporine
• Indications for Fluoroquinolones


  • Salmonella enterica (S. typhi, S paratyphi)
  • E.coli
  • Shigella spp (Bacillary dysentery)
  • Vibrio cholera

  
• Rifaximin


  • MOA: inhibition of bacterial RNA synthesis
  • Effective against both gram-positive and G-ve bacteria, including aerobes and anaerobes
  • Given Orally, poorly absorbed
  • Associated to a very low side-effect incidence
• Indications for Rifaximin


  • Traveler's diarrhea caused by noninvasive strains of E.coli (diarrheagenic E. coli) in adults and pediatric patients 12 years of age and older
  • Irritable bowel syndrome with diarrhea

  
• Doxycycline


  • MOA: Inhibit protein synthesis (? S)
  • Cornerstone of successful antibiotic regimens for the treatment of brucellosis (zoonosis)
  • Exhibits excellent activity in the acidic environment of the infected macrophages
  • Could be combined with rifampicin or streptomycin for better therapy
• Doxycycline adverse effect: Moderate to severe diarrhea
• Indications for Doxycycline


  • Treatment of Vibrio cholera (>8 years)

  
• Cephalosporins


  • Ceftriaxone, cefotaxime: (Parenteral), Cefixime (Oral) : ?G
  • 3rd G Cephalosporins: for G-ve infection
  • Cefazolin:? G, Parenteral, Drug of choice for surgical prophylaxis
  • Cefepime: ?G, extended-spectrum antibiotics, resistant to beta-lactamases
• Cephalosporins


  • Bactericidal, inhibit bacterial ? synthesis
  • Highly effective against G –ve org.: Salmonella typhi and Non-typhoidal Salmonella, Shigella
• Adverse effects of Cephalosporins

  • Hypersensitivity
  • Disulfiram-like Reaction
  • Increase Nephrotoxicity of Aminoglycosides
  • Vitamin K Deficiency
• Tigecycline


  • Is a tetracycline derivative
  • MOA: Inhibit bacterial ? synthesis
• Indications for Tigecycline


  • Management of intraabdominal infection resistant to Beta-lactam, fluoroquinolones
  • Cholecystitis
  • Liver abscess
• Carbapenems: Meropenem, Ertapenem, Imipenem/cilastatin


  • MOA: inhibit bacterial ? synthesis
  • Coverage: broad spectrum (G+ve/ -ve, resistant, anaerobes)
  • Given by injection
  • Dosage should be adjusted for altered kidney function
• Indications for Carbapenems


  • intra-abdominal infections (caused by E.coli, Bacteroides fragilis, clostridium)
  • Biliary tract infections, cholecystitis
  • Liver abscess
  • Secondary peritonitis/GI perforation
• Adverse effects of Carbapenems

  • Diarrhea
  • Nausea
  • Phelibitis
  • Headache