Microbiology- a clinical approach by Anthony Strelkauskas et al Chapter 20: Antibiotic resistance

 The most important problem associated with infectious disease today is the rapid development of resistance to antibiotics.  Health care personnel has an immediate impact on the development of antibiotic resistance.

MRSA, VRSA, VRE, Acinetobacter baumannii, ESBL

 There are several factors in the development of antibiotic resistance: ◦ Bacteria have typically a short generation time and reach high numbers during infection. ◦ Considerable potential for rapid spontaneous mutation  Spontaneous mutation rate is 1 nucleotide per 10 6 to 1 nucleotide per base pairs ◦ Some of these mutations are for antibiotic resistance ◦ These mutations are selected for in the presence/use of an antibiotic.

 Bacterial cells that have developed resistance are not killed off. ◦ They continue to divide ◦ Resulting in a completely resistant population.  Mutation and evolutionary pressure cause a rapid increase in resistance to antibiotics.

 Modern technology and sociology further exacerbate development of resistant strains.  Travelers carry resistant bacteria.  They travel with several or many other people.  Other people infected with resistant bacteria.  These people continue traveling and infecting.  The process is repeated and the resistant bacteria spread.

 There are more large cities in the world today.  Large numbers of people in relatively small areas.  Passing antibiotic-resistant pathogens is easier.  Many large urban populations have poor sanitation.

 Bacteria pathogenic for humans colonize animals (used for consumption) without causing disease in the animal.  Widespread use of antibiotics in agriculture induces resistance in the pathogens before they even have infected humans.  Antibiotic residual that is eaten can trigger resistance in host microbiota

 An important social change is the increase in the number of people who are immunocompromised.  Necessitates increased use of antibiotics.  Fosters development of resistance.

 The most important contributing factor for resistance is overuse.  A good example is prescribing antibiotics that don’t kill viruses causing the common “cold.”  These antibiotics do destroy the normal bacteria flora.  Opportunistic pathogens that are resistant survive and can take hold.

 Hospitals are ideal reservoirs for the acquisition of resistance. ◦ A population of people with compromised health ◦ A high concentration of organisms, many of which are extremely pathogenic ◦ Large amounts of different antibiotics are constantly in use  Increased use of antibiotics leads to resistance. ◦ Hospital is a place where resistance can develop rapidly

 Gene transfer happens via transformation, transduction, and conjugation.  Resistance can be transferred by bacteria swapping genes. ◦ This can be easily accomplished in a hospital setting. ◦ Health care workers who don’t follow infection control protocols aid in increasing resistance.  Plasmids containing genes for resistance can integrate into the chromosome. ◦ Here they form resistance islands. ◦ Resistance genes accumulate and are stably maintained.

 Inactivation of the antibiotic  Keeping antibiotics out  Modification of the antibiotic target  Efflux pumps that remove the antibiotic (and disinfectants and antiseptics)  Alteration of a metabolic pathway originally inhibited by the antibiotic

 Extended spectrum beta lactamases.  Plasmid encoded  Found in Gram-negative bacteria such as Klebsiella.  Enzymes that inactivate all penicillins and cephalosporines.  Other resistances, such as aminoglycoside resistance, are often co-transferred on the same plasmid.

 Bacteria are considered clinically dangerous because of their antibiotic resistance.  MRSA (methicilin-resistant S. aureus)  VRSA (vancomycin-resistant S. aureus)  VRE (vancomycin-resistant Enterococcus)  VRSA strains are now found throughout the world. ◦ Developing new mechanisms for resistance. ◦ Cell walls for some increased in thickness.  There are no antibiotic treatments for some MRSA and VRSA strains. ◦ They are genetically flexible. ◦ They develop resistance to new antibiotics very quickly.

 Acinetobacter baumannii resistance is a new threat  World wide increase in resistance  Nosocomial infection  Also increased in war zones and natural disasters; Acinetobacter“iraqii”  Gram-negative rods  Form biofilm which contributes to antibiotic resistance  Wound infections and septicemia

 The doctor-patient-drug relationship leads to resistance.  Most clearly seen in the case of common viral infections. ◦ Patients expect to have antibiotics prescribed. ◦ There is over-prescription of antibiotics that are not required. ◦ Patients feel better and stop using the drug make the problem worse by allowing drug-resistant bacteria to survive and grow.

 The potential for global antibiotic resistance is due to: ◦ Overuse of antibiotics ◦ Improper adherence to hospital infection control protocols ◦ Ease of worldwide travel ◦ Difficulty finding new antibiotics  There are ways to lengthen the useful life of antibiotics.

 Mutations that confer resistance are selected for by bacteria.  Travel and modern technology have increased the spread of antibiotic-resistant pathogens.  One of the most important contributing factors to antibiotic resistance is the increase in the number of immunocompromised people.  The time it takes to develop resistance to antibiotics is relatively short.

 Resistance to an antibiotic can occur through inactivation of the antibiotic, pumping the antibiotic out of the cell, modifying the target of the antibiotic, or using alternative metabolic pathways.  Resistance can be reduced by rotational use or cyclical patterns of use for antibiotics as well as by using combinations of different antibiotics together, and completing the treatment.. Chapter 20 key concepts

A.Gram-positive bacteria only B.Gram-negative bacteria only C.Both gram- positive and gram-negative bacteria D.Ciprofloxacin is used for protozoan infections. E. Both c and d.

A.Heavy metals - inactivate enzymes B.Surfactants – DNA C.Alcohols – protein D.Oxidizing agents - nucleic acids E.Phenol- cell membrane

Quiz #3 – Wednesday, May 29, 12:50pm-1:20pm  Chapters 18, 19, 20, 21  Multiple Choice, T/F; 25 questions, 50 points  Lecture, Chapter Questions  Please bring Scantron, No. 2 pencil