Drug Treatments for Infectious Diseases

why are ppl with egg allergies unable to get many vaccine types?

because some vaccines, such as flu, are produced in eggs

celiac disease

• not directly an allergy

• hypersensitivity to gluten protein

• triggers immune system into making antibdies against tissue-transglutaminase in small intestine

• leads to malnutrition

• makes you more likely to develop additional disorders later in life

when are antibiotics used?

for bacterial infections (not viral or fungal) when other interventions such as vaccines and non-medical treatments such as OTC drugs aren’t enough

abx can disrupt the human __________

gut microbiome

what is recommended to take when on antibiotics to replace good bacteria?

probiotics

why is abx-resistance such a rapidly growing concern?

• overuse (prescribing for viral infections, common in kids)

• prescribing the wrong class/dosage

• use in agriculture to hasten growth of livestock (banned in US and EU)

side effect of tetracycline in abx

binds calcium, staining teeth (especially in children)

side effects of (fluoro)quinolones including ciprofloxacin

tendon rupture (achilles) and hearing damage (unknown mech)

common side effect after taking broad-spectrum abx

GI upset and subsequent C. difficile

bacteriostatic abx

prevents pathogen from further growth

• if abx is removed, growth continues

bactericidal abx

directly kills pathogen

common targets of abx

• Central Dogma

• stopping synth of building blocks of cell

broad spectrum abx

acts on both gram + and - (wide range of disease-causing bacteria)

• used when bacterial infection is suspected but specific bacteria is unknown

narrow spectrum abx

targeted - only able to kill/inhibit limited species of bacteria

what abx target cell wall synthesis?

1. cycloserine

2. vancomycin

3. bacitracin

4. penicillins

5. cephalosporins

6. monobactams

7. carbanenems

8. teixobactin

what abx target the cytoplasmic membrane structure/function?

1. polymixins

2. daptomycin

what abx target DNA gyrase?

1. quinolones: nalidixic acid, ciprofloxacin

2. novobiocin

what abx targets DNA-dep RNApol?

1. rifamin

2. streptovaricins

what abx targets RNA elongation?

actinomycin

what abx targets protein synthesis/inhibits 50S?

1. erythromycin

2. chloramphenicol

3. clindamycin

4. lincomycin

what abx target protein synth/inhibit 30S?

1. tetracyclines

2. spectinomycin

3. streptomycin

4. gentamicin

5. kanamycin

6. amikacin

7. nitrofurans

what abx target protein synth (tRNA)?

1. mupirocin

2. puromycin

what abx target lipid biosynthesis?

platensimycin

why are plymyxins and daptomycin last resort abx?

target cytoplasmic membrane (all cells have this, including ours— would damage our cells not just bacterial)

most abx are derivatives of…

natural things— fungi, baceria

from the late 1960s to mid 20210s the vast majority of new abx relied on …

chemical modification of existing classes

• modifications were aimed at broadening/narrowing/targeting scope of antibiotic

what has led to a population vulnerable to death from otherwise treatable infections?

• lack of discovery of new abx/focus on chemical modification of existing classes

• rise of abx resistance

benefit of modifying existing abx

combat abx resistance mechs

what is the most promising hope for abx that maximizes potential targets & phyicochemical properties and/or structural diversity?

microbiota-based therapeutics

list alternatives to current abx

• antisense therapeutics (SRNA of bacteria)

• natural products (discovered in nature)

• antimicrobial peptdies (hard to synth)

• antibodies and AACs (ex. rabies)

• bacteriophages

• microbiota-based therapeutics

describe BSL-4

• most dangerous

• death ~ certain

• pathogen is new to human, effects maay be unknown

• require complete isolation procedures

• must protect public from accidental release

• only ~17 facilities have this designation

• used for space samples

why do we study BSL3-4 pathogens?

• drug and vaccine development

• epidemiology (disease tracing)

BSL-1 controls

1. controlled access

2. hand-washing

3. sharp hazards warning policy

4. PPE

5. lab bench

6. autoclave optional

BSL-2 controls

1. controlled access

2. hand-washing sink

3. sharp hazards warning policy

4. physical contaminent device

5. PPE

6. lab bench

7. autoclave

BSL-3 controls

1. self-closing double door access

2. controlled access

3. personal shower out optional

4. sharp hazards warning policy

5. hand-washing sink

6. sealed penetrations

7. physical containment device

8. powered air purifying respirator optional

9. lab bench

10. autoclave

11. exhaust HEPA filter

12. effluent decontamination system

BSL-4 controls

1. self-closing double door access

2. controlled access

3. sharp hazards warning policy

4. hand-washing sink

5. sealed penetrations

6. physical containment device

7. positive pressure protective suit

8. lab bench

9. autoclave

10. chemical shower out

11. supply & exhaust HEPA filters

12. effluent decontamination system

hospital-acquired infections (HAI)

• 10-30% of hospitalized pations develop an infection secondary to reason for concern

• serious & growing threat

• often due to human error/oversight

what are the most concerning & fastest growing HAI causitive agents?

ESKAPE pathogens

list ESKAPE pathogens

1. Enteroccocus faecium

2. Staphylococcus aureus

3. Klebsiella pneumoniae

4. Acinetobacter baumannii

5. Pseudomonas aeruginosa

6. Enterobacter spp.

Enteroccocus faecium

• endocarditis

• UTI

• prostatitis

• cellulitis

• wound infection and concurrent bacteremia

Staphylococcus aureus

• skin infections

• pneumonia endocarditis

• osteomyelitis infections

• arthritis

Klebsiella pneumoniae

• bacteria

• pneumonia

• endocarditis

• osteomyelitis

• GI tract infection

Acinetobacter baumannii

• ventilator-associated pneumonia

• bloodstream infection

• wound infections

• meningitis

Pseudomonas aeruginosa

• endocarditis

• pneumonia

• urinary tract

• CNS

• wounds

• eyes

• bones

• muscle

• ears

• skin infections

Enterobacter spp.

• UTI

• respiratory infections

• soft tissue infections

• osteomyelitis

• endocarditis

list causes of HAI from most to least

1. respiratory tract infections

2. surgical site infections

3. GI infections

4. other

5. UTI

6. blood-stream infections

list risk factors for HAI

• patients (already ill or immunocompromised)

• newborn infants/elderly (not fully immune competent

• infectious disease patients (pathogen reservoirs— typhoid mary)

• patient proximity (increases cross-infection)

• healthcare personnel (can transfer pathogens among patients, may be asymptomatic carriers)

• medical procedures (breaching skin barrier can introduce pathogens)

• surgery (exposes internal organs, may induce pathogens, causes stress lowering resistance to infection)

what 3 things are vital to stop infections?

1. fast treatment

2. identification

3. contact tracing

what is the first step when a patient is suspected to have an infectious disease?

• immunological assays (blood sample to search for antibodies/antigens)

• other assays (blood, feces, urine, tissue biopsy, mucosal swab)

growth-dependent microbiology

• use selectie/differential media (enrichment)

• isolate w pure culture

• identify using growth-dependent, biochemical, immunollogical or molecular assays

molecular assays

search for pathogen genes by gene amplification

antigen assay

search for microbial or virus antigens using fluorescent antibodie, EIA, and so on

endemic disease

always present

epidemic disease

has pretty predictable cycles

pandemic disease

• about every 100 yrs

• steep exponential growth curve (almost vertical line)

airborne infections can travel…

great distances

droplets can travel…

a few feet

fomites

when infection is transferred thru contact with an infected object

• ex. norovirus

list modes of transmission

1. direct contact

2. indirect contact

3. airborne droplets

4. waterborne

5. foodborne

6. airborne

7. soilborne

8. arthropods/insects (vector)