Chapter 7 anti-infective agents - general info Flashcards
selective toxicity
1) penicillins have few side effects b/c they attack bacterial structures that are absent in human cells (good therapeutic index)
2) e.g amphotericin – attack less unique features in fungi, are toxic to human cells at therapeutic doses (poor selective toxicity)
gram positives
- Nafcillin (IV)
- Docloxacillin (PO)
- both provide coverage of most gram + and are not destroyed by penicillinases
- 1st gen cephalosporins (cephalexin, cefazolin) effective against most skin and skin strucccutre infections
gram negatives
- 3rd gen cephalosporins are effective against many gram (-) and are not destoryed by cephalosporinases (penetrate brain well)
- additionally, cephalosporins + penicillins can enhance aminglycoside antibiotic class against gram (-)
- combo of amp + gent or ampicillin and gentamicin (aminoglycoside antibiotics) provides good coverage against both gram (+) and gram (-)
- trimethoprim-sulfamethoxazole (bactrim/septra) is active against most UTIs
- Amoxicillin for otitis media (middle ear infection) + bacterial upper resp infection
pseudomonas
- ticarcillin or ceftazidime (cephalosporin antibiotics) cover most gram negatives, including pseudomonas [fail to tx some gram (+)]
- Imipenem and meropenem (beta-lactam antibiotics) good against pseudomonas
anaerobes
- metronidazole (nitroimidazole antimicrobials) and clindamycin cover most anerobic bacteria
- mouth anaerobes covered by penicillin
mycoplasma
- macrolides (erythromycin, clarithomycin, azithromycin) treat presume micoplasma pneumonia — along with other organisms that cause community acquired pneumonia
systemic fungi
- amphotericin (antifungal) drug of choice
- these infections common amongst pt taking broad spectrum AB’s that destroyed their endogenous bacteria allowing this fungal growth
To prevent resistance?
- use two AB drugs
How to achieve synergy?
- combination of penicillins or cephalosporing with aminoglycosides?
- aminoglycosides work intracellularlt but have difficulty entering the cell
- penciilins + cephalosporins prevent repair of holes in bacterial cells making aminoglycosides easier to enter
bacericidal antibotics
- kill bacteria (cidal)
bacteriostatic agents
- inihbit bacterial proliferation while host’s immune sys destroys bacteria
How to ensure AB get to infection site?
- brain, testes, eye are protected sites in body
- few drugs penetrate those barriers
- abscess walls form an effective barrier to AB’s — must be incised and drained!
enemies: gram (+) cocci
- most developed resistance to basic penicillins and some strains may be resistant to specialized penicillins
- peptidoglycan (polypeptide + sugar) cell wall surrounds it — impermeable (compared to gram (-) bacteria) responsible for retaining blue dye during gram staining
- penicillins, cephalosporins, bacitracin, vancomycin and cycloserine inhibit this wall production
common entry
* staph aureus & staph epidermidis ==> skin, wounds, surgical site, and indwelling catheters (particularly catheter can cause endocarditis)
* strep pneumoniae cause of community-acquired penumonia and adult bacterial meningitis
* group a beta-hemolytic streptococcus => strep throat (untreated can cause immuno rxn in heart, joints, and other tissues => rheumatic fever)
enemies: anaerobes
- common - bacterioides fragilis, clostridium difficile and fuscobacterium
- c botulinum and c tetani => make toxins that cause botulism and tetanus respectively
- metronidazole (nitroimidazole antimicrobials) + chloramphenicol (broad spectrum for +/-) + clindamycin effective against anaerobic infections
- mixed gram + and - make up most of these anaerobic infections /// freq encased in an abcess wall w/ production of foul smelling gas
common entry
* mouth, GI tract, skin of all persons
* infection starts when anaerobes get into poor oxygenated tissues (diabetic foot) or otherwise sterile area (peritoneum lining the abdominal cavity + organs)
* broad spectrum => l/t c diff proliferating
enemies gram-negative pathogens
common gram (-) into 4 groups
1) enterics, consisting of organisms that normally inhabit the GI tract [escherichia, shigella, salmonella, klebsiella, enterobacter, serratia, proteus + acinetobacter, others]
2) haemophilus influenzae
3) neisseria
4) pseudomonas
* enteries are not responsible for most nosocomial infections
structure
* plasma membrane of gram (-) is protected by an adjacent rigid petidoglycan wall (site of action for penicillin + cephalosporin) which is encased by an outer membrane
* penicillins must cross outer membrane in order to act at inner cell wall — this outmembrane is made of lipopolysaccharides interrupted by transmembrane protein pores that stop entry of most penicillins and cephalosporins
* BROAD spectrum penicillins and 3rd gen cephalosporins are more hydrophilic than previous drugs (allowing passage through these selective pores)
* even so, some gram neg strains are resistant to penicillins b/c they produce b-lactamases that are concentraed in space between outer membrane + cell wall
sites of invasion
* enterics — UTIs + aspiration pneumonia d/t GI tract close to urethra + lungs
* neisseria gonorrhea (ceftriaxone now replaced penicillin as drug of choice) for STD
* n. meningits (penicillin G) and h influenze cause meningitis (influenze more commonly cause penumonia)
* pseudomonas aeruginoas — HA infections
* pseudomonal infections can occur at any site (especially if immunocompromised)
* also if enough moisture, pseudomonas may colonize any surface in the hosptial (include workers) and is resistant to many disinfectants
* psuedomonas have extra cellular polysaccharide slime layer and unipolar flagella
