Microbiology UTA Exam 3

chemotherapy

drugs that target living cells and tissues; known as antimicrobial drugs--obtained through consumption of plants and fermented products

Paul Ehrlich

went through 600 ARSENIC compounds to find a cure for SYPHILIS (Treponema pallidum) without killing host

Klarer, Mietzch, & Domagk

used synthetic dye (Prontosil) to treat strep infections; first SYNTHETIC antimicrobial

Alexander Flemming

discovered penicillin in 1928 as the first NATURAL antibiotic; mass production started in the 1940s

Dorothy Hodgkin

used X-RAYS to analyze the structure of penicillin; which was used to create modified penicillins (SEMISYNTHETIC antimicrobial)

Selman Waksman

discovered that Actinomycetes (SOIL microbes) are the source of more than 50% of natural antibiotics

narrow spectrum drugs

targets specific group of microbes (best choice)

broad spectrum drugs

targets wide variety of microbes; can cause SUPERINFECTION

dosage

concentration given in a certain time period; based on mass for children (12+)

optimal dosage

high drug efficacy and low adverse effects

routes of administration

oral, topical, intravenous, intramuscular

synergistic drug

drug-to-drug interaction INCREASES action of drug(s)
ex: Trimethoprim + Bactrim

antagonistic drug

drug-to-drug interaction DECREASES action of drug(s)
ex: Rifampin + birth control

selective toxicity

inhibiting/killing microbe but not harming host

B-lactams

presence of lactam ring that blocks cross-linking of peptide chains in a new peptidoglycan

Penicillins

MOA: inhibits transpeptidase activity (cell wall synthesis)
Narrow spectrum
Pathogens targeted: mostly G+, some G-

Cephalosporins

MOA: inhibits transpeptidase activity (cell wall synthesis)
Narrow spectrum
Pathogens targeted: resistant to B-lactamases

Carbapenems

MOA: inhibits transpeptidase activity (cell wall synthesis)
Broad spectrum
Pathogens targeted: Both G+ and G-

Monobactams

MOA: inhibits transpeptidase activity (cell wall synthesis)
Narrow spectrum
Pathogens targeted: G- only

Vancomycin

Class: Glycopeptides
MOA: binds to end of peptide chain to block subunits from adding to peptidoglycan backbone
Narrow spectrum
Pathogens targeted: G+ only

Bacitracin

MOA: blocks transport of peptidoglycan precursors
Broad spectrum
Pathogens targeted: both G+ and G-

Aminoglycosides

MOA: binds to 30S subunit of ribosome and impairs "proofreading" ability
Broad spectrum
--CIDAL
ex: streptomycin, gentamicin, neomycin

Tetracyclines

MOA: binds to 30S subunit and blocks association of tRNA with ribosome
Broad spectrum
--STATIC

Macrolides

MOA: binds to 50S subunit and inhibits peptide bond formation in specific combos of amino acids
Broad spectrum
--STATIC
ex: erythromycin, azithromycin

Lincosamides

MOA: binds to 50S subunit and inhibits peptide bond formation in specific combos of amino acids
Narrow spectrum
Pathogens targeted: streptococcal and staphylococcal infections
--STATIC

Chloramphenicol

MOA: binds to 50S subunit and inhibits peptide bond formation in specific combos of amino acids
Broad spectrum \-- SIDE EFFECTS
--STATIC

Oxazolidinone

MOA: binds to the 50S ribosomal subunit and interferes with association of 30S subunits
Broad spectrum
--STATIC
ex: linezolid

Polymyxins

MOA: lipophilic and interacts with LPS to disrupt outer and inner membrane
Narrow spectrum
Pathogens targeted: G-

Daptomycin

Class: Lipopeptide
MOA: cyclic lipopeptide that inserts and disrupts membrane
Narrow spectrum
Pathogens targeted: G+

Metronidazole

MOA: interferes with DNA replication; not selective in toxicity
Broad spectrum
--CIDAL
Pathogens targeted: anaerobic bacteria and protozoa

Rifampin

MOA: blocks RNA polymerase activity; can be antagonistic and hepatotoxic
Narrow spectrum
--CIDAL
Pathogens targeted: mainly G+, some G-

Fluoroquinolone

MOA: inhibits DNA gyrase enzyme; selective toxicity and has many side effects
Broad spectrum
--CIDAL
Pathogens targeted: both G+ and G-

Antimetabolites

competitive inhibitors of enzymes to stop certain pathways

Sulfonamides (sulfa drugs)

MOA: halts folic acid synthesis and production of pyrimidines and purines; often used with Trimethoprim
Broad spectrum
--STATIC
Pathogens targeted: both G+ and G-

Trimethoprim

MOA: inhibits later stage of folic acid synthesis
Broad spectrum
Pathogens targeted: both G+ and G-

Isoniazid

MOA: specific toxicity for mycobacteria to block synthesis of mycolic acid
Narrow spectrum
Pathogens targeted: Mycobacterium spp. including M. Tuberculosis

Diarylquinolines

MOA: inhibits mycobacterial growth; exact mechanisms unknown but evidence shows interference with ATP synthase and reducing available ATP

Imidazoles

MOA: disrupts ergosterol biosynthesis
Pathogens targeted: treats infections caused by dermatophytes aka ringworm, tinea pedis, tinea cruris
Commonly used in medical and agriculture

Triazoles

MOA: inhibits ergosterol biosynthesis
Pathogens targeted: systemic yeast infections aka oral thrush, cryptococcal meningitis
Administered orally or IV

Allylamines

MOA: inhibits earlier step in ergosterol biosynthesis
Pathogens targeted: same dermatophytic skin infections as Imidazoles
ex: Terbinafine (Lamisil)

Polyenes

antifungal drug that binds to ergosterol and creates pores in the membrane

Flucytosine

antifungal drug that interferes with DNA replication and protein synthesis

Echinocandins

antifungal drug that inhibits B(1-3) glucan synthesis aka "penicillin for fungi"

Polyoxins & Nikkomycins

antifungal drug that inhibits chitin synthesis

Griseofulvin

antifungal drug that interferes with microtubules involved in spindle formation during mitosis

Atovaquone (AF)

antifungal drug that acts as an antimetabolite for fungal AND protozoal mitochondrial cytochrome function

Atovaquone (AP)

antiprotozoan drug that inhibits electron transport
Pathogens targeted: Malaria, babesiosis, toxoplasmosis

Proguanil

antiprotozoan drug that inhibits folic acid synthesis

Metronidazole (AP)

antiprotozoan drug that inhibits DNA synthesis
Pathogens targeted: dysentery, Giardia, trichomoniasis

Pentamidine

antiprotozoan drug that cleaves DNA within kinetoplasts; binds tRNA
Pathogens targeted: African sleeping sickness, leishmaniasis

Artemisinin (antimalarial)

antiprotozoan drug whose MOA is unclear, but likely damages target cells by ROS
Pathogens targeted: malaria

Quinolines

antiprotozoan drug that interferes with heme detoxification
Pathogens targeted: Malaria, dysentery

Mebendazole

antihelminthic drug that inhibits microtubule formation

Ivermectin

antihelminthic drug that blocks neuronal transmission in invertebrates causing starvation, paralysis, and death
Pathogens targeted: round worms and parasitic insects

Niclosamide

antihelminthic drug that inhibits ATP formation under anaerobic conditions
Pathogens targeted: intestinal tapeworms

Praziquantel

antihelminthic drug that induces the influx of Calcium into the worm leading to paralysis
Pathogens targeted: tapeworms, liver flukes, schistosomiasis

Acyclovir

antiviral drug that activates viral enzymes and affinity for viral DNA polymerase

Amantadine & Rimantadine

antiviral drug that binds to transmembrane protein which prevents RNA release into host cells; treats influenza A

Oseltamivir (Tamiflu)

antiviral drug that inhibits neuraminidase that aids in release of viral particles from host cell

reverse transcriptase inhibitors

blocks RNA --\> DNA

protease inhibitors

blocks processing of viral proteins

integrase inhibitors

prevents integration of viral DNA into host chromosome

fusion inhibitors

prevents binding of virus to host cell and merging of envelope and membrane

HIV

1. targets CD4 and WBC
2. retrovirus; incorporates into host genome
3. rapid development of antiviral drug resistance

selective pressure

increases through misuse and inappropriate use of antimicrobials, subtherapeutic dosage, & patient noncompliance

multidrug-resistant microbes (MDRs)

"superbugs"
2 million infections per yr
cross resistance
ESKAPE pathogens

cross resistance

one mechanism confers resistance to multiple drugs

ESKAPE pathogens

Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, & Enterobacter spp.

vancomycin-resistant enterococci (VRE)

target modification of peptide component in cell wall; prevents binding

vancomycin-resistant S.aureus (VRSA)

horizontal gene transfer from patients infected with VRE and MRSA

vancomycin-intermediate S.aureus (VISA)

increase in targets; binding to outer cell wall

methicillin-resistant S.aureus (MRSA)

acquisition of new low-affinity PBP; resistance to all B-lactams

extended-spectrum B-lactamases (ESBLs)

resistance to penicillins, cephalosporins, monobactams, B-lactamase inhibitors

carbapenem-resistant enterobacteriaceae (CRE)

produces carbapenemases (B-lactamases that inactivate all B-lactams)

multidrug-resistant mycobacterium tuberculosis (MDR-TB)

resistant to both rifampin and isoniazid

extensively drug-resistant mycobacterium tuberculosis (XDR-TB)

additionally resistant to any fluoroquinolone and at least 1 of 3 others

kirby-bauer method

disk diffusion test to examine degree of susceptibility/resistance
- contains zones of inhibitions: area of antibacterial activity around drug impregnated disk

minimal inhibitory concentration (MIC)

lowest concentration of drug that inhibits visible bacterial growth

minimal bactericidal concentration (MBC)

lowest drug concentration that kills more than 99.9%

E test

combo of Kirby Bauer assay and dilution method; a strip with antibacterial gradient is placed on agar plate

sterilization

removal/killing of ALL microbes from fomite (inanimate object)
- aseptic technique

disinfection

inactivation/killing of microbes on fomites
ex: vinegar and bleach

antiseptic

inactivation/killing of microbes; acts on microbes but not organism/tissue
ex: hydrogen peroxide & rubbing alcohol

sanitization

decreasing microbial load on fomite
ex: heat or chemicals

degerming

reduce microbial load on living tissue
ex: washing hands, wiping with paper towel, soap

BSL-1

microbes are not known to cause diseases in healthy hosts and pose minimal risk to workers and the environment
ex: E.coli & B.subtilis

BSL-2

UTA microbio labs
microbes are typically indigenous and are associated with diseases of varying severity. they pose moderate risk to workers and the environment
ex: S.aureus & Salmonella spp.

BSL-3

microbes are indigenous or exotic and cause serious or potentially lethal diseases through respiratory transmission
ex: M. tuberculosis & B.anthracis

BSL-4

microbes are dangerous and exotic; posing a high risk of aerosol-transmitted infections, which are frequently fatal without treatment or vaccines. few labs are at this level
ex: ebola & Marburg viruses

critical

must be sterile; items used inside the body
ex: surgical instruments, catheters, IV fluids

semicritical

do not require high level sterilization; items might contact non-sterile tissue but not penetrate tissue
ex: GI endoscope, respiratory therapy equipment

noncritical

do not require sterilization; items contact but do not penetrate intact skin
ex: stethoscopes, bed linens, blood pressure cuffs

CIDAL

to kill

STATIC

inhibit growth

microbial death curve

measure of percentage of kill

decimal reduction time (DRT)

how much time it takes to kill 90% (1 log reduction) of the population

physical means of control

6 types:
- temperature
- pressure
- desiccation
- radiation
- sonication
- filtration

heat sterilization

oldest and most common; alters membranes and denatures proteins

thermal death point

lowest temp that will kill in 10 minutes

thermal death time

length of time to kill at a certain temperature