Symbiosis and Clostridium Difficile Infections

• This is not a real exam, it is a creative adaptation of study material

Symbiotic Relationships Between Hosts and Microbes

• Avoiding red meat limits harmful metabolites produced by bacteria metabolizing choline.
• Rifaximin, an antibiotic inhibiting RNA polymerase, is an exogenous perturbation causing Host-Microbial Dysbiosis by promoting inflammation and eliminating beneficial bacteria.
• Host-Microbial Mutualism includes bacteria synthesizing short-chain fatty acids like butyrate, which serves as the primary energy source for human colonocytes.
• Immune system maturation and related cells are not independent of gut microbiota, as shown in gnotobiotic mice experiments.

Clostridium Difficile Infections (CDI)

• Clostridium difficile is a spore-forming, gram-positive bacterium, leading to 30,000 deaths annually, but infections are generally manageable with antibiotics
• The most significant preventative therapy against C. diff is a robust microbiome.
• Recurrence of CDI is associated with decreased microbial diversity and offending medications like PPIs
• Eliminating overuse of narrow-spectrum antibiotics is a modifiable risk factor for CDI.
• Introducing healthy donor fecal suspensions into the GI tract is a valid and highly efficacious CDI treatment

Prebiotics and Probiotics

• Probiotics are live microorganisms that have health benefits when consumed
• Prebiotics are non-digestible carbohydrates that stimulate the metabolism of healthy gut microbiota.
• Hempel et al. showed prebiotics as adjunct therapy reduces antibiotic-associated diarrhea risk by 58%.
• A prebiotic must resist mammalian metabolism/absorption in the upper gastrointestinal tract.

Inappropriate Antibiotic Therapy and Clinical Findings

• Inappropriate antibiotic therapy risks increased vulnerability to infectious diseases and resistance development
• Clinical findings that immediately support initiating antibiotic therapy include:
  • An obvious bacterial infection that requires urgent treatment
  • Labs indicating fever, severely low WBC count, and elevated ESR
  • A left-shift
  • Elevated procalcitonin levels

Hospital-Acquired Infections

• Patients prior antibiotic use in the hospital is helpful for identifying effective treatments.

Initial Steps for an ICU Patient with a Black Lesion

• Collect cultures from the patient

Incorrect Match of Infection and Suspected Organism

• Hospital Acquired Pneumonia (HAP) is caused by the often resistant M. catarrhalis, making it more serious than community-acquired pneumonia.

Anatomical Sterile Sites

• Anatomical Sterile Sites pertain to sites where if bacteria is found, it requires immediate treatment and it immediately considered a ‘True infection’

Presumed Diagnosis and Spectrum of Treatment Based on Gram Stain

• For a urinary tract sample with pink/red rod-shaped cells, the presumed diagnosis is Enterobacteraciae, to be treated with Gram(-) spectrum antibiotics

“Common Cold" and Influenza

• Inappropriate antibiotic treatment negatively impacts the microbiome, taking 1-2 years to reconstitute.
• Common Cold: A stuffy nose is common, the fever and cough are usually mild.
• Flu: A stuffy nose is rare, the fever and cough are usually severe.

Epidemiological Terms

• An inapparent infection is active and transmittable, but a latent infection is less likely to be transmitted and inactive until there is sufficient immune system perturbation.
• The secondary attack rate refers to the infection rate after exposure to an index case in a small population ex: school
• A pandemic is a world-wild epidemic, but an epidemic is one that is constantly present in a population while an endemic is one acquired by hosts in an area in a short time
• Prevalence calculates the number of people who newly develop a case during a particular time period while incidence calculates the total number of cases during a given time period.
• Herd immunity is a community's resistance to an infectious agent due to resistance inherent in a high number of individual members

Goal of Epidemiology

• The goal of epidemiology is to control or stop epidemics
• A major characteristic compared to other studies is that epidemiology deals with groups of people
• Not an application of epidemiology: To intermittently survey community members to detect changes in the prescribing patterns of antibiotics

The 5 D's of Antimicrobial Stewardship

• Objectives when treating an infection: To cure infection and minimize complications

Supporting Diagnosis or Treatment of a Patient

• Intramuscular therapy will not help support our diagnosis or treatment of a patient
• It should be switched from IV to PO therapy as [WBC] increases

Reasons for Receiving Unsatisfactory Response During Treatment

• Potential reasons include:
  • The patient has a large abscess that tests positive for infective agents
  • The IV fell out of the patients arm and is sitting on the floor
  • The bacterium is resistant to the previously administered empiric therapy based on susceptibility results
  • The patient has a severe infection and a bacteriostatic antibiotic is being used

Macrolide Antibiotics

• Macrolide antibiotics inhibit protein translation by interacting with residues within the nascent peptide channel near the catalytic center producing partial obstruction and protein-specific inhibition.

Linezolid and Oxazolidinone

• Linezolid works by clashing with incoming aminoacyl-tRNA to prevent polymerization.
• It is indicated for gram (+) MRSA.

Bacterial Ribosome

• The bacterial ribosome is a favored target for antibiotic therapy, key facts:
  • Responsible for the translation of essential proteins of the cell
  • Genes encoding for the ribosomal subunits are conserved in the prokaryotic domain
  • Genes encoding for the ribosomal subunits have a high copy number and are redundant

Antibiotic Resistance

• The following statements concerning antibiotic resistance are true:
  • cfr gene is often present on transposons and plasmids, associated with other resistance genes
• the cfr-mediated A2503 methylation confers resistance to Phenicols, Lincosamides, Oxazolidinones, Pleuromutilins, and Streptogramin A (PHLOPS
• the Erm-mediated A2058 methylation confers resistance to macrolides, Lincosamides, and Streptogramin B (MLSB)
• Clinically indicated choice for treat severe infections: Aminoglycosides

Sulfonamide Activity

• An inaccurate description is that mammals are tolerant of sulfonamide therapies because obtain folate diet

Peptidoglycan Structure

• The peptidoglycan structure is formed by cross-linking between stem peptide tails

Penicillin

• All of the Above:
  • In Penicillin, the amide group of the B-lactam ring is unstable to acidic conditions
  • Modifying the chemical structure of penicillin, such as adding an electron-withdrawing group Amoxicillin, will decrease the rate of acid hydrolysis
• The addition of polar groups, such as –NH2, can make B-lactams broad spectrum (- and +)
• Penicillin contains a thiazolidine ring

Televancin

• Televancin is a semi-synthetic derivative of Vancomycin with 10x the bactericidal activity

Second-Generation Quinolone Drugs

• Second-generation quinolone drugs:
  • They exhibit lower levels of toxicity and can be used long-term for extensive therapy, such as a 6-month anthrax regimen
  • Accumulate to high levels in the plasma and are effective in treating infections of the lower respiratory tract.
  • Target subunit A of DNA Gyrase

Synergistic Activity

• Novobiocin is frequently used with quinolones for its synergistic activity acting on DNA Gyrase subunit B

Daptomycin

• Cationic peptide side chains coordinated with Ca2+ interact with the negative charge of the cell wall components while another portion of the drug interacts with the lipid membrane

Azithromycin & Telithromycin

• False: Not all cases for Azithromycin is bacteriostatic and not all cases Telithromycin is bactericidal

Detecting Antibiotic Presence

• When bacteria are able to indirectly detect the presence of an antibiotic: Global regulators upregulate the production of virulence factors

C. difficile Infections

• Antibiotic activity against C. scindens will promote deoxycholic acid availability to support growth of C. difficile

Exploration of symbiotic relationships between hosts and microbes, including the role of bacteria in synthesizing essential compounds. Focus on Clostridium difficile infections (CDI), a spore-forming bacterium causing significant mortality annually, and preventative therapies.