Emerging Infections Flashcards
Emerging Pathogens
A previously unknown organism that causes disease or a previously identified organism that developed the capacity to cause disease or previously identified PATHOGEN that can RESIST ANTIBIOTIC TREATMENT
Ex: ebola, raccoon rabies, malaria, E.coli, strep pneumoniae (penicillin resistance)
History of appearance of antimicrobial resistance
Huamn demographics and behavior: longer life spans, sexual behavior
Technology and industry: misuse of antibiotics in livestock
Economic development and land use: movement of populations, poor sewage control
International travel and commerce
Microbial adaptation and change
Breakdown of public health measure
Evolutionary forces driving antibiotic resistance
Antibiotic resistant pathogen has selective advantage of being able to grow and divide while others are killed
In a healthy host in the absence of drug, a resistant strain of pathogen might not reach a high enough titer (not enough growth advantage)
Variation in drug concentration throughout patient, tissue damage due to disease, levels of competitor bacteria
Why are sublethal doses of drug particularly effective in selecting for resistances?
Because a mutation able to provide resistance to a reduced level of drug is a more likely event
Multidrug efflux system
Can be transferred to non-pathogenic bacterium
Typically arises when the organism encounters multiple drugs
Transports drugs in a non-specific manner
Specific features of P.aeruginosa infection in a CF lung can lead to rapid evolution of resistance
In a normal lung selective pressures on the bacteria are equal across the epithelium
Later in the disease damages in the lung epithelium change the landscape and establish niches with WILDLY VARYING DEGREES OF SELECTION ON THE BACTERIA AT DIFFERENT LOCATIONS ACROSS THE EPITHELIUM
Hypermutation accelerates adaption to the range of niches. Variations in drug and the state of tissue at each location increases the chance of finding the “sweet spot” for antibiotic resistant bacteria to grab hold and multiply
Multiple ways in which physician can reduce the danger of emerging infections
Appropriately prescribing drugs (don’t misdiagnose)
Don’t over-prescribe or underestimate the length of treatment
Use effective concentration of drug
Stay informed of new drugs and treatments
Educate patients about proper dispensing of antibiotics
New drug development
Reductionist: identify molecular mechanisms of disease, target virulence factors
Genomic approach: sequence genome of pathogen and target all potential virulence factors
Attack intrinsic resistance: identify mechanisms of resistance (stationary phase, biofilms, efflux pumps), ensure candidate lead compounds work in spite of mechanisms of resistance BEFORE R&D, attack resistance mechanism (pheromone signaling in biofilm formation)
