Microbiology Chapter 14

True

(T/F) Echinocandins, known as "penicillin for fungi," target β(1→3) glucan in fungal cell walls.

B-lactam antibiotics

(presence of lactam ring, similar to peptidoglycan subunit. Blocks cross linking of peptide chains in new peptidoglycan) penicillins: (narrow) derived from fungi: mostly against G+ but some G- cephalosporins: similar to penicillin but resistant to b- lactamase carbaponems: broad spectrum against G+/G- Monobactems: narrow spectrum G- only

Etest

The method that can determine the MICs of multiple antimicrobial drugs against a microbial strain using a single agar plate is called the ________.

False

(T/F) If drug A produces a larger zone of inhibition than drug B on the Kirby-Bauer disk diffusion test, drug A should always be prescribed.

False

(T/F) Narrow-spectrum antimicrobials are commonly used for prophylaxis following surgery.

True

(T/F) The rate of discovery of antimicrobial drugs has decreased significantly in recent decades.

False

(T/F) β-lactamases can degrade vancomycin.

Inhibitors of membrane function

(plasma membrane) polymyxins: (Neosporin) lipophilic lipids and interact with lps to disrupt outer and inner membrane of gram - also targets host membranes (selective toxicity) daptomycin: cyclic lipopeptide that inserts and disrupts gram + membrane (fatty)

HIV difficult to treat because

1. targets CD4+ WBC 2. retrovirus; incorporates into host genome (hides) 3. Rapid development of antiviral drug resistance

Neuraminidase inhibitors

Antiviral drugs, like Tamiflu and Relenza, that are effective against the influenza virus by preventing viral escape from host cells are called ________.

-inhibits ATP formation under anaerobic conditions -inhibits oxidative phophorylation in mitochondria of targeted pathogen -non absorbable allows for high localized intestinal concentration -starves paralysis and death of worm

Niclosamide is insoluble and thus is not readily absorbed from the stomach into the bloodstream. How does the insolubility of niclosamide aid its effectiveness as a treatment for tapeworm infection?

Prokaryotic

Selective toxicity antimicrobials are easier to develop against bacteria because they are ________ cells, whereas human cells are eukaryotic.

Nasal

Staphylococcus aureus, including MRSA strains, may commonly be carried as a normal member of the ________ microbiota in some people.

Clostridium difficile

The bacterium known for causing pseudomembranous colitis, a potentially deadly superinfection, is ________.

Actinomycetes

The group of soil bacteria known for their ability to produce a wide variety of antimicrobials is called the ________.

MIC: the lowest concentration of drug that inhibits the visible bacterial growth MBC: the lowest drug concentration that kills>99.9% of the starting inoculum

What is the difference between MIC and MBC?

MDR's: carry one or more resistance mechanism=resistance to multiple antimicrobials Cross resistance: a single resistance mechanism refers resistance to multiple antomicrobial drugs

What is the difference between multidrug resistance and cross-resistance?

-targets variety of bacterial pathogens(g+/-), empiric therapy for potential pathogens, polymicrobic infections, prophylactic preventions of infections, treat infection when narrow spectrum drug fails becuase of drug resistance

When is using a broad-spectrum antimicrobial drug warranted?

Mold, plant derived medicines

Where do antimicrobials come from naturally? Why?

​C. treatment of strep throat caused by culture identified Streptococcus pyogenes

Which clinical situation would be appropriate for treatment with a narrow-spectrum antimicrobial drug? ​A. treatment of a polymicrobic mixed infection in the intestine ​B. prophylaxis against infection after a surgical procedure ​C. treatment of strep throat caused by culture identified Streptococcus pyogenes ​​D. empiric therapy of pneumonia while waiting for culture results

A. sulfanilamide

Which of the following antimicrobial drugs is synthetic? ​A. sulfanilamide ​B. penicillin ​C. actinomycin ​​D. neomycin

C. nalidixic acid

Which of the following antimicrobials inhibits the activity of DNA gyrase? ​A. polymyxin B ​B. clindamycin ​C. nalidixic acid ​​D. rifampin

D. soil

Which of the following has yielded compounds with the most antimicrobial activity? A. water B. air C. volcanoes ​​D. soil

​​D. selective toxicity

Which of the following terms refers to the ability of an antimicrobial drug to harm the target microbe without harming the host? ​A. mode of action ​B. therapeutic level ​C. spectrum of activity ​​D. selective toxicity

Inhibitors of metabolic pathways

antimetabolites: competitive inhibitors of enzymes to stop certain pathways sulfonamides: (sulfa drugs) halts folic acid synthesis (pregnant) and production of pyrimidines and purines (DNA cannot build up) often used with trimethoprim: synergicicidal broad spectrum and static trimethoprim: inhibits later stage of folic acid synthesis (sulfomethoxazale and trimethoprim) commonly used in combination to boost effect (cidal) isoniazid: specific toxicity for mycobacteria to block synthesis of mycolic acid (tuberculosis)

Antimicrobial drug resistance

arises from increased selective pressure (evolution) selective pressure increased thru: misuse and inappropriate use of antimicrobials sub-therapeutic dosage patient noncompliance resistant genes are obtained thru horizontal and vertical transfer

Neosporin made of

bacitracin ( cell wall) polymyxin (membrane) neomisin ( protein inhibitors)

Too often patients will stop taking antimicrobial drugs before the prescription is finished. What are factors that cause a patient to stop too soon, and what negative impacts could this have?

before finishing prescription patients feel better and think they can stop taking it-they will get sick again and can build resistance to the treatment

History of Chemotherapy

chemotherapy: drugs that target living cells and tissues antimicrobial drugs: target (kill) microbe (kill the pathogen save the host)

Fundamentals of Antimicrobial Therapy

cidal= kill static= inhibit growth narrow spectrum: (best choice) target specific groups of microbes broad spectrum: (avoid) targets wide variety (efflux pump) non specifc downside= superinfection dosage: concentration given in certain time period optimal dosage= high drug efficacy but low adverse effects synergistic: (increase action) trimethoprim+ bactrim antagonist: (decrease action) rifampin+ birth control

inhibition of atp synthase

diaryquinolines: inhibits mycobacterial growth: exact mechanism unknown but evidence shows interference with atp synthase and reducing available atp

Antifungal drugs

disruption of sterol synthesis and membrane integrity human: cholesterol fungi: ergosterol imidazoles: disrupt ergosterol biosynthesis commonly used in medical and agriculture treat infections caused by dermatophytes: ringworms (athletes foot), tinea cruris, jock itch triazoles: inhibit ergosterol biosynthesis administer orally or intravenously systemic yeast infection: oral thrush and cryptococcal meningitis allylamines: (topical) inhibit earlier step in ergosterol biosynthesis treat dermatophytic skin infection: athletes foot, ringworm, jock itch, lamisil polyenes: bind to ergosterol and create pores in membranes

antifungal continued

flucytosine: interferes w dna replication and protein synthesis echinocandins: inhibit b(1-3) glucan synthesis penicillin= fungi polyoxins and nikkomycins: inhibit chitin synthesis griseofulvin: interferes microtubules involved in spindle formation during mitosis atovoquore: (cross boundaries) antimetabolite for fungal and protozoal mitochondrial cytochrome function (ATP)

testing effectiveness of antimicrobials

kirby bauer method: disk diffusion test to examine degree of susceptibility/ resistance (cannot determine minimum inhibitory concentrations) zone of inhibition: area of antibacterial activity around drug- impregnated disk (bigger = more susceptible)

multidrug resistant microbes MDR (superbug)

untreatable 2 mil infected, 23,000 dead yearly cross resistance: one mechanism confers resistance to multiple drugs difficult to treat because of large number of nosocomial infections ESKAPE pathogens: enterococcus facium, staphylococcus aureus, klebsiella pneumuniae, actinobacter baumanii, pseudomas aureginosa, enterobacter

prominent cell wall drugs

vancomycin: binds to end of peptide chain to block subunit from adding to peptidoglycan back bone G+ only bacitracin: derived from b. subtilis and blocks transport of peptidoglycan precursors (amazon truck delivery mess up) Neosporin

What bacterial structural target would make an antibacterial drug selective for gram-negative bacteria? Provide one example of an antimicrobial compound that targets this structure.

β-Lactam antibiotics are a broad class of antibiotics that includes penicillin derivatives (penams), cephalosporins (cephems), monobactams, and carbapenems. β-Lactam antibiotics are bacteriocidal and act by inhibiting the synthesis of the peptidoglycan layer of bacterial cell walls.

In considering the cell structure of prokaryotes compared with that of eukaryotes, propose one possible reason for side effects in humans due to treatment of bacterial infections with protein synthesis inhibitors.

The ribosomes in prokaryotes differ from eukaryotes.Side effects can be phototoxicity and liver toxicity.This could be because certain proteins are blocked from being made or they altered and unable to do their normal job.

HIV is a virus with complex life cycles: -targets CD4-postive white blood cells (immune system) -is a retrovirus - reverse transcriptase lacks proofreading activity and allows mutations and rapid development for antiviral drug resistance

How does the biology of HIV necessitate the need to treat HIV infections with multiple drugs?

-diameter of the zone of inhibition (in mm) is compared to a standardized chat and that determine the susceptibility/resistance of the bacterial pathogen to the drug

How is the information from a Kirby-Bauer disk diffusion test used for the recommendation of the clinical use of an antimicrobial drug?

Rifamycins: functions by blocking RNA polymerase activity in bacteria, RNA polymerase enzymes in bacteria are different from those in Eukaryotes, providing selective toxicity against bacterial cells

If human cells and bacterial cells perform transcription, how are the rifamycins specific for bacterial infections?

​B. glycopeptides

Which of the following is not a type of β-lactam antimicrobial? ​A. penicillins ​B. glycopeptides ​C. cephalosporins ​​D. monobactams

​C. cholesterol

Which of the following is not an appropriate target for antifungal drugs? ​A. ergosterol ​B. chitin ​C. cholesterol ​​D. β(1→3) glucan

​C. drug inactivation

Which of the following resistance mechanisms describes the function of β-lactamase? ​A. efflux pump ​B. target mimicry ​C. drug inactivation ​​D. target overproduction

A. efflux pump

Which of the following resistance mechanisms is commonly effective against a wide range of antimicrobials in multiple classes? ​A. efflux pump ​B. target mimicry ​C. target modification ​​D. target overproduction

​​D. efflux pump

Which of the following resistance mechanisms is the most nonspecific to a particular class of antimicrobials? ​A. drug modification ​B. target mimicry ​C. target modification ​​D. efflux pump

A.oral

Which of the following routes of administration would be appropriate and convenient for home administration of an antimicrobial to treat a systemic infection? ​A. oral ​B. intravenous ​C. topical ​​D. parenteral

C. Kirby-Bauer disk diffusion test

Which of the following techniques cannot be used to determine the minimum inhibitory concentration of an antimicrobial drug against a particular microbe? ​A. Etest ​B. microbroth dilution test ​C. Kirby-Bauer disk diffusion test ​​D. macrobroth dilution test

A. MRSA

Which of the following types of drug-resistant bacteria do not typically persist in individuals as a member of their intestinal microbiota? ​A. MRSA ​B. VRE ​C. CRE ​​D. ESBL-producing bacteria

Because tuberculosis is recommended to be treated for 6 months to a year and many people don't actually take their antibiotics for the whole time and that leads to antibiotic resistance

Why does the length of time of antimicrobial treatment for tuberculosis contribute to the rise of resistant strains?

-It was found to work after screening 600 arsenic containing compounds, remedy for the disease in humans Resulted in a now common strategy for discovery of new antibmicrobial agents

Why was Salvarsan considered to be a "magic bullet" for the treatment of syphilis?

​B. semisynthetic

A scientist discovers that a soil bacterium he has been studying produces an antimicrobial that kills gram-negative bacteria. She isolates and purifies the antimicrobial compound, then chemically converts a chemical side chain to a hydroxyl group. When she tests the antimicrobial properties of this new version, she finds that this antimicrobial drug can now also kill gram-positive bacteria. The new antimicrobial drug with broad-spectrum activity is considered to be which of the following? ​A. resistant ​B. semisynthetic ​C. synthetic ​D. natural

antihelminthic drugs

Achieving selective toxicity is very challenging multicellular eukaryotes (full organ system) (avermactin) mebendazole: (broad) inhibition of microtubule formation ivermectin: blocks neuronal transmission in invertebrates causing starvation, paralysis, and death. (covid= people used horse ivermectin) (roundworms and parasitic insects) lices and flees niclosamide: inhibits atp formation under anaerobic conditions intestinal tape worms (GI distress) praziquantel: induce influence of ca into worm: paralysis tapeworms, liver flukes, schistomiasis (blood flukes)

Etest: used to determine MIC because it is a combination of Kirby-Bauer disk diffusion and dilution method test However the MBC cannot be determined by the Etest unlike macrobroth and microbrorh dilutions

Can an Etest be used to find the MBC of a drug? Explain.

Mechanisms of Resistance

Enzymatic modification or inactivation of the drug: Modification of the antimicrobial target: Overproduction of antimicrobial target: Enzymatic bypass of antimicrobial target: mimicry of antimicrobial target prevention of drug penetration or accumulation (scariest)

A.diameter

In the Kirby-Bauer disk diffusion test, the _______ of the zone of inhibition is measured and used for interpretation. ​A. diameter ​B. microbial population ​C. circumference ​​D. depth

Why can't drugs used to treat influenza, like amantadines and neuraminidase inhibitors, be used to treat a wider variety of viral infections?

Influenza-specific antiviral drugs are an important adjunct to vaccine but are not a substitute for vaccine. In the United States, four antiviral agents are approved for preventing or treating influenza: amantadine, rimantadine, zanamivir, and oseltamivir.

Why are yeast infections a common type of superinfection that results from long-term use of broad-spectrum antimicrobials?

The risk associated with using broad-spectrum antimicrobials is that they will also target a broad spectrum of the normal microbiota, increasing the risk of a superinfection, a secondary infection in a patient having a preexisting infection. A superinfection develops when the antibacterial intended for the preexisting infection kills the protective microbiota, allowing another pathogen resistant to the antibacterial to proliferate and cause a secondary infection

D. in a localized population.

The utility of an antibiogram is that it shows antimicrobial susceptibility trends ​A. over a large geographic area. ​B. for an individual patient. ​C. in research laboratory strains. ​​D. in a localized population.

-age, weight(mass), patient history regarding how the drugs will be metabolized and eliminated

When prescribing antibiotics, what aspects of the patient's health history should the clinician ask about and why?

​C. short-term use of narrow-spectrum antimicrobials

Which of the following combinations would most likely contribute to the development of a superinfection? ​A. long-term use of narrow-spectrum antimicrobials ​B. long-term use of broad-spectrum antimicrobials ​C. short-term use of narrow-spectrum antimicrobials ​​D. short-term use of broad-spectrum antimicrobials

​A. tetracyclines

Which of the following does not bind to the 50S ribosomal subunit? ​A. tetracyclines ​B. lincosamides ​C. macrolides ​​D. chloramphenicol

​B. avermectins

Which of the following drug classes specifically inhibits neuronal transmission in helminths? ​A. quinolines ​B. avermectins ​C. amantadines ​​D. imidazoles

​​D. azidothymidine

Which of the following is a nucleoside analog commonly used as a reverse transcriptase inhibitor in the treatment of HIV? A. acyclovir ​B. ribavirin ​C. adenine-arabinoside ​​D. azidothymidine

​A. artemisinin

Which of the following is an antimalarial drug that is thought to increase ROS levels in target cells? ​A. artemisinin ​B. amphotericin b ​C. praziquantel ​​D. pleconaril

mechanism resistance examples

drug modification: b- lactamase hydrolyzed lactam bond traget modification: lps structure alteration to affect polymyxins rna polymerase alteration to affect rifampin target overproduction: (visa) vancomycin (sugar cell wall) resistance in s. aureus by decreased cross linkage of peptide chains in cell wall (increase in targets) target mimicry: m tuberculosis produces pentapeptide to mimic dna and binds to floroquinolones (fake protein dna) mimic prevent accumulation: pathogens produce efflux pump to transport drugs out of cell and prevent accumulation (pump out drug)

antiviral drugs

inhibiting nucleic acid synthesis not many targets= protein/ nucleic acid acyclovir: viral enzyme activation and affinity for viral dna polymerase (chickenpox & herpes) amentanline and rimantidine: treatment for influenza A binds to transmembrane protein blocks escape from endosome prevents rna release into host cell (prevent uncoat)

Antiprotozoan drugs

inhibition various metabolites inhibition dna synthesis alovaquore: inhibits electron transport (malaria, babesiosis, toxoplasmosis) proguanil: inhibits folic acid synthesis metronidazole: (anaerobic and protozoan) inhibits dna synthesis dysentery, giardia, trichonomoniasis (std), carcinogen pentamidine: cleaves dna within kinetoplasts: binds trna african sleeping sickness, leishmaniasis ( vacation) arteminisin: (plant derived) moc unclear but likely damages target cells by ros and antimaterial quinolines: interferes w heme detoxification ( malaria and dysentry)

Inhibitors of nucleic acid synthesis

metronidazole: (cross boundary) interferes w dna replication, not very selective in toxicity. (targets anaerobic bacteria and protozoa) broad spectrum & cidal rifampin: blocks rna polymerase activity, can treat semi dormant m. tuberculosis but can be antagonistic and hepatoxic narrow spectrum (mainly G+ some G-) cidal & liver toxic fluoroquinolones: inhibits dna gyrase (unwind) enzyme, selective toxicity but mainly side effects broad spectrum & cidal

In nature, why do antimicrobial-producing microbes commonly also have antimicrobial resistance genes?

microbes are constantly evolving in order to overcome the antimicrobial compounds produced by other microorganisms. Human development of antimicrobial drugs and their widespread clinical use has simply provided another selective pressure that promotes further evolution.

dilution tests

minimum inhibitory concentration (MIC): lowest concentration of drug that inhibits visible bacterial growth minimal bactericidal concentration (MBC): lowest drug concentration that kills >99.9% Etest: combo of kirby bauer assay and dilution method: strip with antibacterial gradient placed on agar plate (MIC and Kirby): MIC multiple antimicrobial drugs

vancomycin

only effective against G+ treat wounds and septic infections, endocarditis and meningitis caused by pathogens and resistant to other antibiotics last line of defense (icluding mrsa) s. aureus excessive use in 1970s and 80s resulted in resistance emergence

antibiotics founders

paul enrilch: scanned through 600 arsenic compounds to find cure for syphyllis without killing host (trapenema pallidium) josef klaren, fitz melrich, & gerhard domagk: used synthetic dye to treat step infections. first synthetic antimicrobial: "sulfa" and other synthetic antimicrobials alexander fleming: accidentally discovered antibiotic from penicillin ( 1st natural antibiotic) from staphylococcus dorothy hodgen: used xrays to analyze structure of penincillin resulting structures= semisynthetic antimicrobials selmen waksman: studied soil microbes (actinomycetes) >50% of natural antibiotics

inhibition of neuramindase (spike)

red protein found on influenza envelope aids in release of viral particles from host cell (osertamivir)= drink for tamifu zanamivir= nasal relenza: neuraminidase inhibitors

ART (antiretroviral therapy) for HIV COCKTAIL

reverse transcriptase inhibitors: Blocks RNA - DNA (azidothymidine) Protease inhibitors: blocks processing of viral proteins (prevent RNA) Integrase inhibitors: prevents integration of viral dna into host chromosomes (prevent hiding) fusion inhibitors: prevents binding of virus to host cells and merging of envelope and membrane

protein synthesis drugs

ribosomes (30+50=70s) 30s: aminoglycosides: binds to 30s subunit of ribosome and impair proofreading ability (faulty protein) (streptomycin, gentamicin, neomycin) tetracyclines: binds to 30s, blocks association of trna with ribosomes (stop trna) inhibit protein synthesis very liver toxic 50s: inhibit protein synthesis and stop peptide bond formation macrolides: broad spectrum (static) erythromycin (Neosporin) and azithromycin chloramphenicol: broad spectrum (static) rarely used because of severe side effects (liver and bone marrow toxic) lincosamides: narrow spectrum (static) particularly active against streptococcal and staphylococcal infections oxazolidinone: 30& 50s binds to 50s ribosome unit and interferes with association of 30s and other factors broad spectrum, static, linezoid

mechanism of antibacterial drugs

selective toxicity: (prokaryotic antimicrobials) b lactams: presence of lactam ring, similar to peptidoglycan subunit blocks cross linking of peptide chains in new peptidoglycan natural= penicillin g: G+ & few G- (parenteral) penicillin v: similar but oral synthetic= ampicillin: G+ & more G- then penicillin (parenteral & oral) amoxicillin: similar but oral (better) semisynthetic= methicillin: G+ only (b lactamase producers) parenteral (penincillase)

current strategies for antimicrobial discovery

tfixobactin: targets 2 distinct steps in G+ cell wall synthesis development of more effective semisynthetic derivatives: (resistance develops rapidly) check large #'s of soil and microbial products by high throput screening ichip: grown on situ instead of cultured clovoic acid inhibits resistance mechanisms: restore efficiacy of old drugs marine environments?

vancomycin drugs

vancomycin resistant enterococci (VRE): targets modification of peptide components in cell wall preventing binding Vancomycin resistance s. aures: (VRSA): horizontal gene transfer from patients infected with VRE and MRSA Vancomycin intermediate s. aureus (VISA): increase in targets: binds to outer cell wall Methicillin resistant s. aureus (MRSA): (nasal microbiota) acquisition of new low affinity PBP resistant to all B-lactams (modification) do not persist intestinal microbiota Extended spectrum B- lactamases (ESBLS): resistance to penicillins, cephalosporins, manobactems, B-lactamase inhibitors, but not carbapenems (ESBL found on plasmid that have other drug resistance) Carbepenem resistant enterobacteriace (CRE): produce carbapenemases (b lactamases that inactivate all b lactams) efflux pump: (non specific) uptake prevention (pain resistance) effective wide range some have developed resistance to all antibacterials multidrug resistant mycobacterium tuberculosis (MDR-TB): resistant to both rifampin and isoniazid extensively drug resistant mycobacterium tubercolosis: (XDR-TB) additionally resistant to any fluroquinole and at least 1 of 3 others