Anti-microbials Flashcards
What are the 4 ways microbes achieve resistance to anti-biotics?
- alterations in receptor target
- decreased entry or effleux of drug out of microbes
- alterations in metabolic pathways
- drug is inactive
When considering an anti-infective drug, what are the microbe factors to consider?
- identificaiton of organism
- susceptibility to concentration levels
What are the host factors to consider when selecting an anti-infective?
- drug allergies
- pharmacokinetic variables
- effect of food on drug absorption
- diseases affecting drug absorption
- effect of other drugs that alter biotransformation
- renal/hepatic function
- pregnancy/lactation
- site of infection
- signs and symptoms
- fever, malaise, leukocytosis, purulent drainage
Antibacterial agents work by 4 distinct major mechanism of action. name them
- inhibition of cell wall synthesis
- inhibition of protein synthesis
- inhibition of folic acid biosynthetic pathways
- inhibition of DNA/RNA synthesis
What are the drug classes that are cell wall synthesis inhibitors?
- penicillins
- cephalosporins
- carbapenems
- monobactams
WRT specificity and spectrum, what is the best use and why?
most specific narrow spectrum drug applicable
often more reactive and less alteration of normal GI microflora
What are the bactericidal antibiotics?
- penicillins
- cephalosporins
- imipenem
- vancomycin
- aminoglycosides
- bacitracin
- polymixins
- metronidazole
What are the bacteriostatic antibiotics?
- erythromycin
- tetracycline
- sulfonamides
- chloramphenicol
- clindamycin
- trimethoprim
Why are bactericidal antibiotics preferred?
- reduces number of microbes
- may be more rapid acting
- produce irreversible damage
- complete killing required in some cases
When choosing the correct antimicrobial therapy, the concentration of antibiotic at the site of infection is key. what are the 5 perameters associated with this?
- dosage and duration of therapy
- route of administration
- distribution, metabolism, excretion
- compliance
- protected sites (blood brain barrier, prostate)
What are some factors at the site of infection that can alter the microbial therapy?
- presence of pus
- presence of hemoglobin
- pH
- anaerobic conditions
- presence of foreign body
What are the 2 principles for antimicrobial development?
drugs can be found or developed that will specifically target site of action on parasites
sites of action should not be present in the organs and tissues of the host
What indications do you review for combination therapy of antibiotics?
- Treatment of mixed bacterial infections
- Treatment of severe infections of unknown etiology
- Enhancement of activity (drug synergy)
- Prevent emergence of resistant organisms
- Permit lower dose of one of the antibiotics
What are the 4 disadvantages of combination therapy?
- ** NOT usually necessary**=> Exceptions - more often treated with a combination of drugs – TB – Malaria – HIV
- Antagonism of therapy • Wrong combination of drugs, i.e. static plus cidal
- Increased toxicity • Avoid combining drugs with same site toxicity
- Increased cost
What are the 3 main adverse side effects?
Organ tissue toxicity
drug allergies
superinfections
Name the specific organ/tissue toxicity you would expect with different parts of ADME
GI => oral administration
Hepatotoxicity => primary site of drug metabolism
Nephrotoxicity => primary site of drug excretion
What are superinfections? How do they arise?
– Appearance of bacteriological and clinical evidence of a new infection during the chemotherapy of a primary infection.
Antibiotic-induced alterations of the normal GI flora
Incidence is greater with broad spectrum agents
What 2 general ways can antimicrobials demonstrate resistance?
intrinsic or natural resistance
acquired resistance
How does an organism get acquired resistance?
Occurs as a result of stable alterations in the genetic composition of the bacterial cell
Consequence of antibiotic therapy through selection of resistant organisms
NOT necessarily caused by the antibiotic
What are the mechanisms of drug resistance (antibiotic resistance?
– Alteration in receptors for drug
– Decreased transport of drug across cell wall
– Increased export of drug from cell
– Inactivation of drug
– Alternative and salvage metabolic pathways
– Defect in drug metabolism or activation
What are 5 failures of antibiotics?
- Inability to penetrate to site of infection
- Resistant organism
- Superinfections
- Drug reactions
- Competing treatment modalities
What are the indications of prophylactic use of antibiotics?
prevent infection by specific organism
prevent bacterial endocarditis or recurrence of rhematic fever
prevent infection resulting from rupture of viscus or a surgical procedure
patients with compromised host defense mechanisms
What are the inappropriate uses of prophylactic antibiotics?
prevent all potential secondary infections in patients ill with other diseases
What are the misuses of antibiotics?
• Treatment of insensitive infections
– viral infections
• Treatment of fever of undetermined
origin
- Treatment without adequate bacteriological data
- Un- or mis-diagnosed etiologic agent
- Improper dosage
What is the ideal antibiotic?
- Bactericidal
- Good antibacterial activity against usual organisms of infections
- Narrowest antibacterial spectrum possible
- No bacterial resistance
- Acid stable
WRT to ADME, what is the ideal antibiotic?
- Well absorbed orally
- No effect of food on absorption
- Good distribution to bones as well as soft tissues
- High tissue concentration – above MLC
- MLC achieved at reasonable dose
- Long half-life for optimal dosing
Considering the adverse reactions, what are other ideal characteristics of the right antibiotic?
- Nontoxic to mammalian cells
- Exhibits no side effects
- Creates no adverse drug interactions
- Readily excreted
- Ameliorates the infections in at least 5 to 7 days
