chapter 12: antimicrobial treatment
drugs that target protein synthesis
(CATE) chloramphenicol, aminoglycosides, tetracyclines, erythromycin
how many children were expected to die from microbial disease 100 years ago?
1 out of 3 before the age of 5
what are the major modes of action for antiviral chemotherapeutic agents?
1. barring penetration of the virus into the host cell 2. blocking of nucleic acid synthesis 3. preventing the assembly or release of viral particle
how drugs affect nucleic acid synthesis?
1. block synthesis of nucleotides (no new DNA) 2. inhibit replication (no new DNA) 3. stop transcription (no RNA)
specific drug resistance mechanisms
1. drug inactivation 2. decreased drug permeability 3. drug is eliminated from cell 4. change of drug receptors 5. changes in metabolic patterns
preventing drug resistance
1. limit drug use 2. proper drug use 3. narrow range antibiotics 4. multiple drug treatments
why are drugs ineffective in biofilms?
1. penetration 2. when secured to surfaces, bacteria express different genes and therefore have different antibiotic susceptibility profiles
resistance mechanisms
1. prevent access of the drug to the target site 2. alter the nature of the target site
principles of antimicrobial therapy
1. selective toxicity 2. microbicidal 3. relatively soluble and functions when highly diluted 4. remains potent long enough to act 5. doesn't lead to development of antimicrobial resistance 6. assists host's defenses 7. remains active in tissues and bodily fluids 8. readily delivered to the site of infection 9. reasonably priced 10. does not harm host
microbes become resistant to a drug after:
1. spontaneous mutations in critical chromosomal genes 2. acquisition of entire new genes or sets of genes via transfer from another species
mechanisms of drug action
1. targets cell wall 2. targets cell or cytoplasmic membrane 3. targets nucleic acid structure and function (DNA/RNA) 4. targets protein synthesis (particularly ribosomes) 5. targets folic acid synthesis
what to know before starting treatment?
1. the identity of the microorganism causing the infection 2. the degree of an microorganism's susceptibility (sensitivity) to various drugs 3. the overall medical condition of the patient
what are the causes for antibiotic failure?
1. the inability of the drug to diffuse into the right body compartment 2. resistant microbes in the infection that did not make it into the sample collected for testing 3. an infection caused by more than one pathogen; some of which are resistant to the drug
interactions between drug and host
1. toxicity to organs 2. allergies 3. disruption of normal flora
test used for drug sensitivity/susceptibility of microorganisms
Kirby-Bauer Technique
what affect do drugs that target the cell membrane have?
a damaged cell membrane invariably results in death from disruption in metabolism or lysis
goal of antimicrobial chemotherapy
administer a drug to an infected person, which destroys the infective agent without harming the host's cells
shotgun antimicrobial therapy
administration of broad spectrum antibiotics versus narrow spectrum antibiotics for minor infections; practice led to superinfection
who was penicillin discovered by?
alexander fleming
antimicrobials
all inclusive term for any antimicrobial drug, regardless of what type of microorganism it targets
what is the primary problem when using penicillin therapy?
allergy and resistant strain of pathogens
drug resistance
an adaptive response in which microorganisms begin to tolerate an amount of drug that would ordinarily be inhibitory
narrow spectrum
antimicrobials effective against a limited array of microbial types; i.e. a drug effective mainly on gram-positive bacteria
broad spectrum
antimicrobials effective against a wide variety of microbial types; i.e. a drug effective against both gram-positive and gram-negative bacteria
anti-fungal drugs
azoles, griseofulvin
what drug is neosporon made up of?
bacitracin
where do antibiotics originate from?
bacteria and fungi in response to antagonism (competition for resources in their environment)
persister
bacteria produced by species that are so slow-growing that they are not affected by antibiotics
what does the largest number of antimicrobial drugs target?
bacterial infections
how do drugs that target cell membranes specify the antimicrobials they are trying to kill?
based on differences in types of lipids in their membrane
why is it difficult to achieve selective toxicity in antiviral drugs?
because a single metabolic system is responsible for both the virus and the host
why are there only a few drugs that affect nucleic acid synthesis?
because the mechanism is similar for eukaryotes and prokaryotes which leads to high drug toxicity
what do cephalosporins do?
block cross-linking of peptidoglycan/weaken cell wall
what does penicillin do?
blocks cross-linking of peptidoglycan, weakening the cell wall
are cephalosporins broad spectrum or narrow spectrum?
broad spectrum
what does the variable side chain/R group of penicillin do?
determine its microbicidal activity
Kirby-Bauer Test
disk diffusion test essential for groups of bacteria commonly showing resistance (drug susceptibility); place microorganism on agar plate with sheets of antibiotics on top; observe the growth/circle surrounding
goal of antimicrobial drugs
disrupt the cell processes (by interfering with function of enzymes) or structures of bacteria, fungi, and protozoa; or, inhibit virus replication
vancomycin
drug that targets the cell wall; used to treat MRSA and patients with penicillin allergies
synthetic drugs
drugs produced entirely by chemical reactions within a laboratory setting
semisynthetic drugs
drugs that are chemically modified in the lab after being isolated from a natural source
properties of the most effective drugs for helminths
drugs that immobilize, disintegrate, and inhibit the metabolism of all stages of live in helminths
penicillinase or beta-lactamase
enzyme produced by bacteria that deactivates penicillin
what is the problem with drugs for fungal infections?
fungal cells are eukaryotic and therefore similar to human cells leading to high toxicity
azoles
inhibit ergosterol synthesis (unique to fungal membrane)
how do drugs that target protein synthesis work?
inhibit translation by reacting with the ribosome-mRNA complex
bacitracin
inhibits cell wall synthesis; i.e. neosporon
griseofulvin
inhibits microtubules and prevents cell division; effective against athlete's foot
smaller circle on the Kirby Bauer Test
microbe is more resistant to the drug
large circle on the Kirby-Bauer Test
microbe is more susceptible/sensitive to drug
does the perfect drug exist?
no
are biofilms more or less sensitive to antibiotics?
no; biofilms are 1,000 times less sensitive to the same antimicrobials that work against them when they are free living
prebiotics
nutrients that encourage the growth of beneficial microbes in the intestine
what drugs target the cell wall?
penicillin and cephalosporins
most common antibiotics derived from molds
penicillium and cephalosporium
resistance factors (R factors)
plasmids that transfer drug resistance between cells
probiotics
preparations of live microorganisms fed to animals and humans to improve intestinal biota; can replace microbes lost during antimicrobial therapy
why are drugs that target protein synthesis less toxic?
prokaryotic and eukaryotic ribosomes are different
how do antimicrobial drugs affect the cell wall?
react with enzymes that synthesize peptidoclycans and transport it to its proper place; they weaken the cell wall which, in turn, can lead to lyses;
selective toxicity
selectively finding and destroying pathogens without damaging the host
most common antibiotics derived from bacteria
streptomyces and bacillus
antibiotics
substances produced by the natural metabolic processes of some organisms, or created by scientists, that can inhibit or destroy microorganisms; generally, the term is used for drugs targeting bacteria and not other types of microbes
history of penicillin
the drug was discovered, overused, and now (as of 2008) there are 532 enzymes that appeared in microbes to break down penicillin (drug resistance)
therapeutic index (TI)
the ratio of the dose of the drug that is toxic to humans to its minimum effective dose
what do the generic names of cephalosporin contain?
the root cef, ceph, or kef
minimum inhibitory concentration (MIC)
the smallest concentration (highest dilution) of drug that visibly inhibits growth
-cillin
the suffix of antimicrobial drugs containing penicillin
antimicrobial chemotherapy
the use of drugs to control infection
how does the structure of cephalosporins differ from that of penicillin?
they have a different ring structure (but still have a beta-lactum structure and a similar mode of action); cause fewer allergic reactions than penicillin; resistant to most penicillinases
structure of penicillin
thiazolidine ring, a beta-lactam, and a variable side chain/R group
how is resistance transferred?
through conjugation, transformation or transduction
prophylaxis
use of a drug to prevent imminent infection of a person at risk
superinfection
when beneficial resident species (normal biota) is destroyed through antibiotic therapy leading to an increase in microbes once smaller in number to overgrow and cause disease
probiotic sources
yogurt, sourdough bread, kombucha
