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