Historical Context and Drug Metabolism

• 1940s: Penicillin so scarce scientists studied recycling from patients' urine
• Human body poorly metabolizes antibiotics/pharmaceuticals
• 25-75% of consumed antibiotics excreted in urine (average 70%)
• Poor metabolism due to drugs' solubility properties

Global Antibiotic Consumption Trends

• 2000-2015: World human antibiotic consumption increased 65%
• Projected 200% increase by 2030
• High/upper middle-income countries consume most antibiotics
• 2016: 270.2 million antibiotic prescriptions issued to Americans
• Contrast: Sub-Saharan Africa - treatable infectious diseases like pneumonia leading cause of death for children under 5
• 50-70% prescriptions for beta-lactam antibiotics (penicillin family, amoxicillin)

Unnecessary Prescriptions and Improvements

• 2010-2011: 30% of outpatient antibiotic prescriptions unnecessary
• US improvements: 5% decline in prescription rate from 2011-2016
  • From 877 per 10,000 people to 836 per 10,000
• China study (2014-2018): 51.4% of 18.8 million prescriptions inappropriate

Animal Antibiotic Usage

• Roughly 50% of world antibiotic production used for animals
• Farmers use antibiotics for:
  • Preventive measures
  • Improved nutrient uptake (saves feed costs)
• US data:
  • 2008: 88% of growing pigs received antibiotics in feed
  • 2017: 43% decline in antibiotic sales for animals since 2015 peak
• China 2013: 52% of 163,000 tons antibiotic consumption by animals
• Antibiotic use in farmed animals promotes resistant bacteria pockets
• Most resistant bacteria infecting humans come from other humans

Hospital Wastewater Concerns

• Hospitals consume 660-1,500L water per person daily
• 2001: 25% of all antibiotics administered in hospitals
• Hospital wastewater contains:
  • Up to 150x more antibiotics than regular municipal water
  • High concentrations of antibiotic-resistant bacteria and genes
• Horizontal gene transfer allows bacteria to acquire resistance genes
• 2017 assessment: Hospitals responsible for 40% of drugs entering wastewater treatment systems
• Hospital wastewater often dumped into local systems without additional treatment

Traditional Wastewater Treatment Process

• Three-stage process used for 100+ years:
  1. Mechanical filtration (sand filters) - removes solids
  2. Activated sludge process - eliminates organic matter, nitrogen, biodegradable items
     • Oxygen injection promotes microorganism growth
     • Produces recycled sludge and relatively clean water
  3. Final finishing - UV radiation and chlorination

Superbug Breeding Problem

• Modern synthetic antibiotics don't easily break down (vs. original naturally biodegradable antibiotics)
• Chemists engineer drugs for stability/effectiveness
• Wastewater treatment plants mix:
  • High antibiotic concentrations
  • Antibiotic-resistant bacteria
  • Mobile antibiotic-resistant genes
  • Heavy metals, detergents, hydrocarbons
• Warm, wet environment ideal for resistance development
• Studies show significantly higher antibiotic-resistant bacteria in treated water vs. incoming water
• One case: bacteria showed increased resistance to 21 out of 22 tested antibiotics

Water Re-entry Pathways

• Activated sludge used as agricultural fertilizer (varies by country)
• Treated water used for:
  • Irrigation
  • Groundwater recharge
  • Constructed wetlands
• Non-potable uses can contaminate food chain through irrigation

Detection and Concentration Challenges

• Six classes of antibiotics detected in wastewater
• Large regional disparities in concentrations
• Example: Hong Kong vs. Shenzhen
  • Cefotaxim: <15 nanograms/L vs. 1,100 nanograms/L
  • Cephalexin: reversed situation
• Concentrations depend on:
  • Watershed size
  • Seasonal variations
  • Patient ailments and prescriptions
• No established "correct" antibiotic levels for water

Removal Technologies

Biological Methods

• Longer sludge retention at second stage
• Membrane bioreactor option
• Highly variable and unreliable results

Membrane Filtration

• Nano-sized pores catch chemicals
• Similar to reverse osmosis
• 90% removal rates for quinolones, sulfonamides, tetracyclines
• 98.5% removal of amoxicillin
• Cost and fouling concerns

Absorption Methods

• Materials: activated carbon, bentonite, carbon nanotubes
• Accumulates antibiotics on surface
• Repurposed from organic contaminant removal

Ozonation

• Unstable molecule of three oxygen atoms
• Oxidizes chemicals creating removable particles
• Example: 7.1 micrograms ozone/L for 1+ minute removes 95% of some antibiotics
• Variable effectiveness requires different doses/exposure times

Other Promising Methods

• UV light treatment (expensive)
• Peracetic acid disinfection (environmentally friendly chlorine alternative)
• Best applied downstream of traditional biological processes

Current Crisis and Future Outlook

• 1930s-1960s: "Glory days" of antibiotic discovery
• Reduced new antibiotic discovery allows bacteria to catch up
• CDC estimates (annual):
  • 2.8+ million antibiotic-resistant infections
  • 35,000+ deaths
• Wastewater-grown superbugs part of the problem
• Need immediate action on wastewater treatment improvements