Antimicrobials and Resistance Quiz

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Questions and Answers

What is the recommended action for patients with known severe Penicillin allergy regarding cephalosporins?

Cephalosporins should always be administered as the first line treatment.

Cephalosporins should be avoided unless skin tests are negative. (correct)

Cephalosporins can be safely used regardless of allergy.

Cephalosporins should only be used in emergencies.

Which of the following bacteria is NOT effectively targeted by tetracyclines?

Mycoplasma

Rickettsia

Escherichia coli (correct)

Staphylococcus

Which macrolide is known to be a structural analogue of erythromycin?

Clarithromycin (correct)

Doxycycline

Minocycline

Penicillin

What effect do tetracyclines have on growing bones and teeth?

They cause discoloration of teeth. Signup and view all the answers

What is a limitation of macrolides in treating infections?

They do not cross the blood-brain barrier. Signup and view all the answers

What defines the therapeutic index of an antimicrobial drug?

The ratio of the lowest toxic dose to the typical treatment dose Signup and view all the answers

What is the primary role of bacteriostatic drugs?

To inhibit bacterial growth while relying on host immunity Signup and view all the answers

Which statement accurately describes broad-spectrum antimicrobials?

They may disrupt normal flora due to their wide range of activity. Signup and view all the answers

What is the purpose of using a combination of antimicrobial drugs?

To enhance the effectiveness of treatment through synergistic effects. Signup and view all the answers

Which of the following is an adverse effect of antimicrobial drugs?

Suppression of normal flora Signup and view all the answers

What does selective toxicity in antimicrobial drugs mean?

They cause more harm to bacteria than to human cells. Signup and view all the answers

What characterizes an antagonistic drug interaction?

One drug reduces the effectiveness of the other. Signup and view all the answers

How can bacteria develop resistance to antimicrobials?

Via spontaneous mutations or acquiring new genes. Signup and view all the answers

What was the significant discovery made by Alexander Fleming in 1929?

The mold Penicillium produced a bactericidal substance Signup and view all the answers

Which antimicrobial drug was first mass-produced during WWII?

Penicillin Signup and view all the answers

Which of the following statements about streptomycin is accurate?

It was isolated from the soil bacterium Streptomyces griseus Signup and view all the answers

What does the lowest MIC indicate when comparing antibiotics?

The drug has the highest potency Signup and view all the answers

What is the primary source of most modern antibiotics?

Species of microorganisms that live in the soil Signup and view all the answers

Which term describes an organism that is inhibited by the usual dosage of a drug?

Sensitive Signup and view all the answers

Which of the following types of antimicrobial drugs does NOT belong to the initial classifications mentioned?

Antiviral drugs Signup and view all the answers

Which of the following factors is NOT considered when selecting an antibiotic?

Patient's age Signup and view all the answers

What is a primary action of sulfonamides?

They inhibit folic acid synthesis Signup and view all the answers

What was a consequence of the initial treatment with penicillin on a patient with Staphylococcus aureus?

The supply of penicillin ran out before the infection was controlled Signup and view all the answers

In which trimester of pregnancy are sulfonamides contraindicated?

First trimester Signup and view all the answers

What significant change occurred in the availability of antimicrobial drugs?

Many previously fatal illnesses became easy to treat Signup and view all the answers

Which of the following conditions can sulfasalazine treat?

It helps with ulcerative colitis Signup and view all the answers

What is the first step in the process of commercially producing antibiotics?

Choosing a strain and growing it in broth Signup and view all the answers

What is a common adverse effect of sulfonamides related to G6PD deficiency?

Hemolytic anemia Signup and view all the answers

Which organisms are sulfonamides NOT effective against?

Both A and C Signup and view all the answers

Which condition would not be treated with Moxifloxacin?

Tendonitis Signup and view all the answers

Which of the following agents is known for its anti-anaerobic properties?

Metronidazole Signup and view all the answers

Which factor is NOT considered when selecting an antibiotic?

Color of the medication Signup and view all the answers

What is a potential side effect of Rifampin?

Orange discoloration of body fluids Signup and view all the answers

Which medication is used solely for treating urinary tract infections?

Nitrofurantoin Signup and view all the answers

How do antacids affect the absorption of fluoroquinolones?

They decrease absorption. Signup and view all the answers

What is a concern when using fluoroquinolones in older adults?

Increased risk of tendonitis and rupture Signup and view all the answers

Which of the following interactions is a significant concern with fluoroquinolones?

Increase the effects of theophylline Signup and view all the answers

What is the primary approach used in antibiotic therapy when the infection is not well defined?

Empiric Therapy Signup and view all the answers

Why is there often a reliance on empiric therapy?

Prompt therapy is needed for life-threatening infections Signup and view all the answers

Which of the following best describes the characteristics of directed therapy?

Often has stronger supporting evidence Signup and view all the answers

What is the first step recommended before starting antibiotic therapy in outpatients?

Obtain cultures Signup and view all the answers

When considering treatment for a patient with pneumonia, which consideration is emphasized?

Identifying and treating the infection rather than colonization Signup and view all the answers

Which of the following is NOT a reason for patients to be treated with antibiotics?

Asymptomatic bacteriuria Signup and view all the answers

Which antibiotic is commonly used for Group A Streptococcal pharyngitis?

Penicillin Signup and view all the answers

What misconception might lead to unnecessary antibiotic use?

Patients should receive more antibiotics if they seem very sick Signup and view all the answers

Study Notes

Antimicrobial Therapy - History

Quinine used for malaria in the 1600s
Emetine used for amebiasis (Entamoeba histolytica) in the 1600s
Arsphenamines used for syphilis between 1900 and 1910
A red dye discovered in 1935 with antibacterial properties; sulfonamides were broadly active.
Initial marketing in the US did not go well
A chemical analogue of antifreeze
Penicillin discovered in 1929 by Alexander Fleming (Scottish)
Nobel Prize for Penicillin in 1945
Penicillin was knighted in 1944
Penicillin produced by the fungus Penicillium chrysogenum
In 1941, penicillin was tested on humans with life-threatening Staphlylococcus aureus infections; treatment was initially effective.
Supply of penicillin ran out before the infection could be controlled

Antimicrobial Drugs - History and Development

Alexander Fleming discovered penicillin while working with Staphylococcus.
He noticed no Staph colonies grew near a mold contaminant.
The colonies appeared to be melting.
The mold was identified as Penicillium.
It produced a bactericidal substance effective against a wide range of microbes.
In 1943, Selman Waksman (Nobel prize winner) isolated streptomycin from a soil bacterium (Streptomyces griseus).

Antimicrobial Drugs

Chemicals used to treat microbial infections
Before antimicrobials, many people died from common illnesses.
Now many illnesses are easily treated with antimicrobials
Antimicrobial drugs are now becoming less useful
Different types of antimicrobial drugs include antibacterial, antifungal, antiprotozoan, and antihelminthic.

Acquired resistance: Resistance that develops through mutation or acquisition of new genes.
Antibacterial drug: An antimicrobial drug specifically used to treat diseases caused by bacteria.
Antibiotic: A compound naturally produced by certain molds and bacteria that inhibits the growth of or kills other microorganisms.
Antimicrobial drug/antimicrobial: A chemical that inhibits the growth of or kills microorganisms, encompassing antibiotics and chemically synthesized drugs.
Antiviral drug: A drug that interferes with viral replication, all chemically synthesized, none are antibiotics.
Bactericidal drug: An antimicrobial drug that kills bacteria.
Bacteriostatic drug: An antimicrobial drug that inhibits bacterial growth.
Broad-spectrum antimicrobial: An antimicrobial effective against a wide range of microorganisms (Gram-positive and Gram-negative).
Chemotherapeutic agent: A chemical used to treat a disease.
Intrinsic resistance: Resistance due to an inherent characteristic of the microorganism.
Narrow-spectrum antimicrobial: An antimicrobial effective against a limited range of microorganisms
R plasmid: A plasmid that encodes resistance to one or more antimicrobial drugs.
Therapeutic index: The ratio of the lowest dose of a drug that is toxic to the patient, divided by the dose typically used for therapy. Indicates whether a drug is less or more toxic to the patient.

Features of Antimicrobial Drugs

Most modern antibiotics originate from soil microorganisms.
Steps for commercial antibiotic production.

Select a specific strain of mold.
Grow the mold in a nutrient solution.
Separate and purify the antibiotic from the mold.
Alter the chemical structure of the antibiotic to make it more stable.

Selective toxicity - antibiotics harm microorganisms more than human hosts.
Usually achieved by interfering with biological structures or biochemical processes common in bacteria but not in humans.
Drug toxicity is measured by the therapeutic index, which is the ratio of the lowest toxicity dose to the dose used for therapy.
A higher therapeutic index results in a less toxic drug
Antimicrobial action - drugs may kill or inhibit microbial growth.
- Inhibit = bacteriostatic
- Kill = bacteriocidal
- Bacteriostatic drugs rely on host immunity to eliminate the pathogen.
- Bacteriocidal drugs are helpful when host immunity cannot control the pathogen.

Resistance to Antimicrobials

Some microorganisms are inherently resistant to the effects of a particular drug.
Other microorganisms that were previously sensitive to an antimicrobial can develop resistance through genetic mutations or acquiring new genes.
Mechanisms of Resistance:
- Drug inactivating enzymes - some organisms produce enzymes that chemically alter or modify a drug, making it inactive.
- Alteration of target molecule - minor structural changes in the target molecule of the drug can prevent binding. Example: penicillinase breaks down the beta-lactam ring, making penicillin ineffective.
Acquisition of resistance can occur by spontaneous mutation of existing genes (vertical evolution) or via transfer of new genes (horizontal transfer)
Drug resistance limits use of all known antimicrobials, leading to more resistant bacteria.

Resistance - Staphylococcus Aureus

A common cause of nosocomial infections.
Increasingly resistant to penicillin over the past 50 years.
Development of penicillinase genes.
Many strains are resistant to Methicillin (effective against penicillinase resistant organisms)
MRSA is a methicillin-resistant Staphylococcus aureus.

Resistance - Streptococcus pneumoniae

Has remained sensitive to penicillin.
Some strains have acquired resistance, possibly due to modification in genes coding for penicillin-binding proteins.
Changes may be due to the acquisition of chromosomal DNA from other strains of Streptococcus ( via DNA-mediated transformation).

Factors Contributing to the Spread of Antibiotic Resistance

Transmission of resistant organisms between patients in hospitals or healthcare settings
Use of antibiotics in animals raised for commercial food
Incorrect antibiotic prescriptions
- Antibiotics given for conditions unlikely to be bacterial.
- Antibiotics given for self-limiting conditions.
- Narrow spectrum antibiotics instead of broad spectrum ones, when possible
- Using unnecessary high doses or prolonged treatment periods.
- Incorrect dosing or treatment duration (non-compliance).

Slowing the Emergence and Spread of Antimicrobial Resistance

Responsibilities of Providers: identify the microbe, prescribe the appropriate antimicrobial, educate patients.
Responsibilities of Patients: follow prescribed instructions.
Educate the Public: understand the appropriateness and limitations of antibiotics; antibiotics are not effective against viruses.
Global Impacts: organisms can quickly travel to different countries, and in some places, are available without prescription. Antibiotics fed to animals select for drug resistant organisms.

Current Major Antibiotic Resistance Problems: Community Infections

Respiratory Tract: Penicillin resistance in pneumococci increasing.
Gastrointestinal: Quinolone resistance in Campylobacter.
Sexually transmitted: Penicillin and quinolone resistance in gonococci.
Urinary tract: Beta-lactam resistance in E. coli.
MRSA and MDR-TB.
Tropical: Multi-drug resistance in Salmonella typhi, Shigella spp, malaria

So, The Criteria of the Ideal Antibiotic

Selectively toxic to the microbe, but non-toxic to the host.
Soluble in body tissue (blood-brain barrier).
Remains in the body long enough to be effective, resisting excretion and breakdown.
Shelf life.
Does not lead to resistance.
Cost is not excessive.
Hypoallergenic.
Microbiocidal, rather than microbiostatic (kills rather than inhibits).
Doesn't suppress normal flora (does not trigger antibiotic-associated colitis with Clostridium difficile and/or Candida albicans).

Mechanisms of Action of Antibacterial Drugs

Inhibit cell wall synthesis (e.g., penicillins).
Inhibit protein synthesis (e.g., tetracyclines).
Inhibit nucleic acid synthesis (e.g., sulfonamides, quinolones).

Cellular Targets of Antimicrobial Drugs

Describes specific cellular targets for various antimicrobial drugs.

Mechanisms of Antibiotics

Cell Wall Inhibitors: Inhibit cell wall synthesis (e.g., penicillins, cephalosporins, vancomycin).
Protein Synthesis Inhibitors: Prevent protein synthesis in bacteria (e.g., aminoglycosides, tetracyclines, macrolides).
Inhibit Nucleic Acid Synthesis: Inhibit nucleic acid synthesis (e.g., quinolones, rifampin).

Cell Wall Inhibitors

Bacteria cell walls are made from peptidoglycan
Antimicrobials that interfere with cell wall do not interfere with eukaryotic cells
These drugs have a very high therapeutic index, meaning they are less toxic to humans

Protein Synthesis Inhibitors

Most interfere with bacteria ribosomes
Inhibit protein synthesis.
Compounds which inhibit protein synthesis include aminoglycosides (e.g., streptomycin), tetracyclines, macrolides, chloramphenicol, lincosamides and oxazolidinones.

Nucleic Acid Synthesis Inhibitors

DNA/RNA polymerase inhibitors, quinolones, sulfonamides, and other similar compounds.

Determining Susceptibility of Bacteria to Antimicrobial Drug - Conventional Disc Diffusion

Kirby-Bauer disc diffusion method is commonly used to qualitatively determine susceptibility of a bacterial strain to specific antibiotic.
Standard concentration of the bacterial strain is spread uniformly across a plate.
Discs containing specific concentrations of antibiotics are placed on the plates.
The plates are incubated and observed for zones of inhibition around the discs.

Determining Susceptibility of Bacteria to Antimicrobial Drug - Minimum Inhibitory Concentration (MIC)

MIC is the smallest quantity of antibiotic required to inhibit the growth of a bacterial organism.
Determined by measuring how bacteria grow in broth containing various concentrations of test drugs
The lowest concentration of an antibiotic that stops bacterial growth is the MIC.

Susceptibility Determination

Provides examples of specific susceptibility data.
Includes a table which shows the MIC results for several antimicrobials.

Antibiotic Choice

Factors besides susceptibility and resistance include: infection location (e.g., lipid-soluble vs. water-soluble drugs) and excretion properties (e.g., drug excreted by kidneys reaching higher bladder levels than serum levels).
Gram-positive vs gram-negative organisms considerations.

Remember

Selective toxicity
Spectrum of activity
Antimicrobial action
Adverse effects
Resistance

Antimicrobial Classes

Lists various classes of antimicrobial drugs, e.g., sulfonamides, penicillins, cephalosporins, tetracyclines, macrolides, glycopeptides, aminoglycosides, fluoroquinolones, nitroimidazoles, and other drugs.

Sulfonamides

First group of antibiotics.
Bacteriostatic effect by inhibiting folic acid synthesis.
Broad spectrum.

Penicillins

Part of a large group of chemically related antibiotics.
Derived from fungus or mold.
Inhibits the synthesis of the bacterial cell wall, most effective on newly forming and actively growing cell walls.

Cephalosporins

Chemically and pharmacologically related to penicillins.
Action: prevents bacterial cell wall synthesis, but binds to different proteins.
All are bactericidal.
Include several generations
- First: good gram-positive coverage
- Second: good gram-positive coverage; some gram-negative coverage
- Third: less gram-positive coverage, more gram-negative coverage
- Fourth: good gram-negative coverage, pseudomonas
- Fifth: MRSA
Has no activity against LAME; Listeria, atypicals (including mycoplasma & chlamydia), MRSA (except 5th generation), enterococci.

Tetracyclines

Action: inhibits protein synthesis in bacterial cells; bacteriostatic.
Broad spectrum (gram+ and gram-).
Effective against several types of bacteria, including protozoa, Mycoplasma, Rickettsia, Chlamydia, syphilis, and Lyme disease infections.
Tetracyclines (TCNs) bind to calcium in growing bones and teeth and can discolor teeth.
Should be avoided in children below 8 years old.

Macrolides and Ketolides

Structural analogues of erythromycin.
Include erythromycin, azithromycin, clarithromycin.
Bacteriostatic; inhibit protein synthesis in bacterial cells.
Very effective against organisms that typically cause CAP (community-acquired pneumonia), including atypical infections like mycoplasma and chlamydia.
Can be used as an alternative in patients who are sensitive to penicillin.
Treat both Gram+ (some Gram -) bacteria.

Ketolides

Only ketolide on market - telithromycin.
Can be used for respiratory infections, those resistant to macrolides.
Initial safety concerns were ignored, fraudulent research indicated safety; later significant liver injury and hepatotoxicity has occurred.

Vancomycin - Glycopeptides

Bactericidal
Poorly absorbed orally.
Inhibits peptidoglycan formation.
Active against most Gram+ organisms.
IV administration used in severe infections (e.g. septicemia, or endocarditis).
Oral vancomycin administered commonly for Clostridium difficile infections.
Inhibits cell wall synthesis.
Other glycopeptides include oritavancin and dalabavancin

Aminoglycosides

Effective against many Gram- and some Gram+ organisms.
Bactericidal, inhibiting cell wall protein synthesis.
Narrow therapeutic index - potentially very toxic
VIIIth cranial nerve (ototoxicity) and kidney damage are significant adverse side effects.

Fluoroquinolones

Bactericidal, altering DNA.
Effective against Gram- organisms and some Gram+ organisms.
Well-absorbed orally and intravenously.
Include levofloxacin, ofloxacin, ciprofloxacin, moxifloxacin, gemifloxacin.
Used to treat many infections, such as lower respiratory tract infections, bone and joint infections, infectious diarrhea, and urinary tract infections.
Significant drug-drug interactions, including increased effects of theophylline, warfarin, propranolol, and antacids.
Prolongs QT intervals; use with steroids increases the risk of tendonitis and rupture, especially in older adults.

5-Nitroimidazoles

Anti-anaerobic agents.
Wide-spectrum and bactericidal.
Metronidazole - useful against anaerobic bacteria and protozoan infections.
Tinidazole - longer duration of action than metronidazole.
Inhibits DNA synthesis and/or damages DNA.

Other- Rifampin

Inhibits DNA-dependent RNA synthesis.
Active against Gram+ bacteria, some Gram- bacteria, and MRSA.
Effective against Mycobacterium tuberculosis; often given in combination with other drugs for synergistic effect and to reduce resistance.
Side effects include headache, nausea and vomiting, and fever; body fluids turn orange.

Other - Nitrofurantoin

Structurally similar to quinolones.
Used only to treat and prevent UTIs.
Serum concentrations are very low; not suitable for complex UTIs and sepsis.
Renal excretion, contraindicated in renal insufficiency.

Principles of Antibiotic Therapy

Empiric therapy: Best guess therapy, broad-spectrum, multiple drugs when the infection isn't well defined.
Directed therapy: A narrow-spectrum, single drug approach when the infection is well-defined. Directed therapy relies on evidence for optimal treatment.

Why So Much Empiric Therapy

Need for rapid therapy in life-threatening infections with limited time for cultures or definitive diagnosis.
Difficult to perform cultures for some infections (e.g., pneumonia, sinusitis, cellulitis.)
Potential provider bias that patients with serious illness need more antibiotics.
Patients respond to prior, empirically chosen therapies and providers often continue on the same drug.

Therapy for Outpatients

Define the infection (anatomically, microbiologically, pathophysiologically.)
Obtain cultures before starting antibiotics.
Narrow-spectrum antibiotics are often effective for many illnesses with good supporting evidence.
Medications commonly used in outpatient settings include amoxicillin, penicillin, cephalosporin, trimethoprim/sulfamethoxazole or nitrofurantoin.

Tenet 1: Treat Bacterial Infection, not Colonization

Many patients are colonized with bacteria (often asymptomatic).
Treat ONLY confirmed infections to avoid unnecessary use of antibiotics.

Tenet 2: Treat Patient, Not the X-ray

It's critical to evaluate symptoms over just X-rays.
Confirm the symptoms indicate an infection.
Non-infectious issues could be present, such as atelectasis, malignancy, hemorrhage, or pulmonary edema.

Community-Acquired Pneumonia (CAP)

Not all patients with chest x-rays showing pneumonia actually have an infection.
Do not treat if no evidence of systemic inflammatory response.

Tenet 3: Do not Treat Viral Infections with Antibiotics

Antibiotics are ineffective against viruses; treating viral infections with antibiotics provides no benefit.

Tenet 4: Limit Duration of Antibiotic Therapy to the Appropriate Length

Specific treatment durations for infections like community-acquired pneumonia, cystitis, pyelonephritis, intra-abdominal infections, and cellulitis. - Appropriate duration is based on clinical response and not simply on an arbitrary time frame.

Other Tenets of Antibiotic Stewardship

Re-evaluate, de-escalate, and stop therapy based on diagnosis and microbiologic results.
Do not give two antibiotics with overlapping activity.
Use rapid diagnostics.
Solicit expert advice.
Strategies to prevent infections.

Sensitivity

Negative test rules out the issue
SNOut

Specificity

Positive test rules in the issue
SPin

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Test your knowledge on antimicrobial drugs and their mechanisms. This quiz covers various aspects including drug classifications, effects on bacteria, and resistance development. Perfect for students and professionals in pharmacology and microbiology.