Host-Microbe Symbiosis and C. diff Infections

• Exam includes multiple-choice and NAPLEX-style questions, check for completeness, mark answers, review, and verify with the last page

Host-Microbe Symbiosis

• Avoiding red meat is suggested due to harmful metabolites produced by bacteria metabolizing choline
• Rifaximin, an antibiotic inhibiting RNA polymerase, leads to inflammation and elimination of beneficial bacteria, an example of Host-Microbial Dysbiosis
• Short-chain fatty acids, such as butyrate, synthesized by bacteria, exemplify Host-Microbial Mutualism, butyrate is the primary energy source for human colonocytes
• Immune system maturation and related cells are independent from gut microbiota in gnotobiotic mice experiments

Clostridium difficile (C. diff) Infections (CDI)

• Clostridium difficile is a gram-positive, spore-forming bacteria causing 30,000 annual deaths
• A robust microbiome is a significant preventive therapy against C. diff with decreased microbial diversity
• Recurrence of CDI is frequently 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 effective CDI treatment

Prebiotics and Probiotics

• Probiotics are live microorganisms, such as non-pasteurized yogurt, with health benefits upon consumption
• Prebiotics are non-digestible carbohydrates stimulating the metabolism of healthy gut microbiota
• Hempel et al meta-analysis shows prebiotics as adjunct therapy reduce antibiotic-associated diarrhea risk by 58%
• A prebiotic must resist mammalian metabolism/absorption in the upper gastrointestinal tract

Initiating Antibiotic Therapy

• Inappropriate antibiotic therapy increases vulnerability to infections and resistance development
• Clinical findings immediately supporting antibiotics include bacterial infection requiring treatment, labs indicating fever + low WBC + elevated ESR, left-shift, and elevated Procalcitonin

Hospital-Acquired Infections

• Hospital-acquired infections aren't gram(-) bacilli resistant to penicillin, ampicillin, and erythromycin
• Severe nosocomial E. coli infections don't necessitate initial monotherapy
• The hospital environment isn't host to less harmful infectious agents than community settings
• A patients prior antibiotic use in the hospital is helpful for identifying what has worked in the past

Treating a Patient with a Black Lesion

• For a 45yo Asian American M in the ICU with a black lesion and severe pain, it is important to collect cultures from the patient first before treatment
• The patient was treated for MRSA a week prior and so he should be treated empirically for MRSA, using an antibiotic with a different mechanism of action than previously used.
• Consulting the Antibiogram is wrong

Infection and Organism Matching

• Patients with inflamed tracheas should be treated as a medical emergency with empiric therapy for H. influenzae
• Community-acquired Pneumonia is more serious and the most effective treatment due to the suspected M catarrhalis.
• Patients with Meningitis should receive age-based empiric therapy due to differing organisms by age group
• Amebiasis, is a protozoan disease linked to travelers/campers, from the amoeba Entamoeba histolytica
• Patients with Osteomyelitis (bone infection) needs treatment for common skin microflora inhabitant, S. aureus, until cultures/history indicate otherwise

Anatomical Sterile Sites

• Anatomical Sterile Sites are sites where bacteria require immediate treatment when found
• Examples include bones, the Upper Respiratory Tract, and the Cardiovascular and Central Nervous Systems
• It is immediately considered a “True infection"

Dysuria Diagnosis

• If a 16yo female patient presents with dysuria and a gram stain test reveals pink/red rod-shaped cells, the likely bug is E. coli which requires Gram(-) antibiotic treatment

"Common Cold" and Influenza

• Inappropriate antibiotic treatment negatively impacts the microbiome, with reconstitution taking 1-2 years
• Common cold symptoms are a stuffy nose, mild fever/cough, while flu symptoms are rare stuffy nose, severe fever/cough
• Both cold and flu result from viral infections, with no curative treatment for the common cold other than time

Epidemiological Terms

• Inapparent infections are active, can be transmitted, while latent infections are less transmissible and inactive until immune perturbation
• The rate of infection in a small population after exposure to an index case is the secondary attack rate
• A pandemic disease is a worldwide epidemic
• Prevalence refers to the total number of cases during a given time period. The incidence calculates the total number of new cases during a given time period
• Herd immunity is community resistance to the invasion and spread of infectious agents due to resistance in a high proportion of individuals

Epidemiology Goals

• Epidemiology aims to control/stop epidemics, dealing with groups rather than individuals
• Intermittently survey community members to detect changes in the prescribing patterns of antibiotics is not an application/goal

Antimicrobial Stewardship (Harnessing the 5 D's)

• With Antimicrobial Stewardship minimise costs and avoid discharging the patient with empiric therapy
• Cure infection and minimise complications
• Acquire specimens immediately following initiation of empiric therapy
• Improve creatinine clearance and avoid developing antibiograms

Patient Diagnosis

• The following will not help support our diagnosis or treatment of a patient:
• Using intramuscular therapy to decrease pain associated with injection

Potential Reasons for Unsatisfactory Treatment

• The following is a potential reason for receiving an unsatisfactory response during treatment of an infections:
• 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
• When culture susceptibility results come back, it is determined that the bacterium is resistant to your previously administered empiric therapy
• The patient has a severe infection and a bacteriostatic antibiotic is being used

Antibiotic Inhibition of Protein Translation

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

Linezolid Mechanism of Action

• Linezolid the oxazolidinone doesn't cause Homology between the human ribosome and bacterial ribosome which leads to suppression of mitochondrial translation

Bacterial Ribosome as Antibiotic Target

• The genes encoding for the ribosomal subunits have a high copy number
• Bacterial ribosome, a target for antibiotics, is responsible for translation of essential proteins
• Genes encoding ribosomal subunits are conserved in prokaryotes and have high copy numbers, not intracellular organelles only found in bacteria

Antibiotic Resistance

• Cfr-mediated A2503 methylation confers resistance to the PHLOPS family of antibiotics: Phenicols, Lincosamides, Oxazolidinones, Pleuromutilins, and those which have Streptogramin A
• The Erm-mediated A2058 methylation confers resistance to MLSB (macrolides, lincosamides, and Streptogramin B)

Antibiotic Class Indications

• Aminoglycosides are indicated to treat severe infections such as tuberculosis and bubonic plaque, cause ototoxicity

Sulfonamide Activity

• Sulfonamides aren't structural analogues of folate

Peptidoglycan Structure

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

Penicillin Structure

• Penicillin contains all of the above: amide group of the B-lactam ring is unstable to acidic conditions, modifying the chemical adding an electron-withdrawing group such as Amoxicillin will decrease the rate of acid hydrolysis, polar groups such as –NH2 can make B-lactams broad spectrum (- and +)

Televancin Characteristics

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

Quinolone Drugs

• Second-generation quinolones accumulate to high levels in the plasma and are effective in treating infections of the lower respiratory tract. Other quinolones include: Norfloxacin

Antibiotic Synergistic Activity with Quinolones

• Novobiocin is frequently used with quinolones for its synergistic activity and targeted at the DNA gyrase subunit B

Daptomycin Activity

• Daptomycin includes Catatonic 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 and Telithromycin

• The following is false: Azithromycin is bacteriostatic in all cases, AND Telithromycin is bactericidal in all cases

Bacteria and Antibiotic Detection

• When bacteria can indirectly detect antibiotics, global regulators (GR) upregulate the production of virulence factors

Answer based on correctness of statement

• Answer based on choice: Antibiotic activity against C. scindens promotes growth of C. difficile

Explore the delicate balance of host-microbe symbiosis, including the impact of dietary choices like red meat on bacterial metabolites. Learn about Clostridium difficile (C. diff) infections, their causes, and preventive strategies such as maintaining a robust microbiome. Also covered is the dysbiosis caused by antibiotics like Rifaximin.