Antibiotic resistance

End of the antibiotic era?

  • This would mean people start dying younger due to infection because bacteria have become resistant to antibiotics

  • This means common antibiotics are unable to be used and more toxic antibiotics must be given as last line.

 

Effects of antimicrobial agents on bacteria

  • Bacteriostatic- growth inhibition

  • Bactericidal - cell killing

 

What are the four main classes of antibiotic targets?

  • Cell wall synthesis

  • Protein synthesis

  • Metabolic pathways

  • Nucleic acid synthesis

 

Reasons for resistance to antibiotics

Natural:

  • Lack target structure

  • Impermeable to antibiotic

  • Lactobacilli are intrinsically resistant to vancomycin

Acquired:

  • Enzymic inactivation

  • Modification of target

  • Acquisition of Efflux mechanism to pump out antibiotics

Different antibiotics target different cellular sites/ processes Cell wall s Cycloserine Va ncomycin Bacitracin Pe nicillins thesis DNA ase Nalidixic acid Quinolones Ciprofloxacin Novobiocin THF DHF rase RNA elongation Actinomyci n Ribosomes DNA-directed RNA 01 Rifampin Streptovaricins Protein synthesis (50S inhibitors) Monobactams Carbapenems Folic acid nwtabolism Trimethoprim Sulfonamides mRNA 30 30 Cytoplasnic rTErrbrane structure and function Polymyxins Daptomycin PABA 0 2012 Pearson Educatön, Inc. Cytoplaynic membrane 30 Lipid bios thesis Platensimycin Cell wall Erythromycin (macrolides) Chloramphenicol Clindamycin Lincomycin Protein synthesis (30S inhibitors) Tetracyclines Spectinomycin Stre ptomycin Ge nta micin Ka mycin Amikacin Nitrofurans Proteins thesis tRIÅ) Mupirocin Puromycin 8

Antibiotics- Gram-negative Mycobacteria bacteria Tobramycin spectrum of activity Gram-positive bacteria Penicillins Chlamydias Isoniazid Sulfonamides Cephalosporins Streptomycin Tetracyclines Polymyxins Figure 13-1 Microbiology,6/e @ 2005 John Wiley & Sons Rickettsias 9 Antibiotic resistance:

  • When treating patient with antibiotic it is both pathogen and microbiota of body (oral cavity, nasal and small intestine) which are exposed

  • Antibiotic resistance is the acquired ability of microorganism to resist the effects of chemotherapeutic agent which it is normally sensitive to

 

Why does antibiotic resistance develop?

  • Selection pressure

  • Transfer of resistant genes (species to species; genus to genus)

  • Rapid cell division

  • Antibiotic selection pressure norrnal bacterium dead bacterium resistant bacterium

Causes of antibiotic resistance:

  • Overuse of antibiotics

  • Improper disposal

  • Travelling (spreading resistant bacteria)

  • Lack of hand washing

 

  • Antibiotic resistance increases with

    • Antibiotic use

    •  time

Biochemical mechanisms of antibiotic resistance

  • Overproduction/ alternation of target

  • Alternative pathway

  • Decreased influx/ increased efflux

  • Drug modification

  • Drug destruction

How do microorganisms acquire the ability to become resistant to antibiotics?

Horizontal gene transfer:

  • Transformation

    • one mode of horizontal gene transfer (HGT) in bacteria, wherein extracellular naked DNA is taken up by cells that have developed genetic competence

  • Conjugation

    • a gene transfer process in which a recipient bacterium receives DNA from a donor bacterium by cell-to-cell contact through conjugative pili. Conjugation is mediated by certain plasmids or transposons.

  • Transduction

    • Transduction is the process by which foreign DNA is introduced into a cell by a virus or viral vector.

    • An example is the viral transfer of DNA from one bacterium to another

What are biofilms?

  • Bacteria which are much less susceptible to antimicrobials than planktonic bacteria

Antimicrobial stewardship:

  • Don't start antibiotics id bacterial infection is not evident

  • Use local guidelines for antibiotic treatment

  • Document antibiotic use on drug chart/medical notes

  • Obtain cultures before giving out (use professional judgement)

  • Single dose antibiotics for surgical prophylaxis

  • Review need for antibiotics by 48 hours

  • Figure I: Antimicrobial Stewardship (AMS) — Treatment algorithm ANTIMICROBIAL STEWARDSHIP Treatment algorithm Start Smart DO NOT START ANTIBIOTICS IN THE ABSENCE OF CLINICAL EVIDENCE OF BACTERIAL INFECTION Then Focus CLINICAL REVIEW & DECISION AT 48-72 HOURS Clinical review, check microbiology and make a clear plan. Document this decision 2. 3. 4. 5. 6. Take thorough drug allergy history Initiate prompt effective antibiotic treatment within one hour of diagnosis (or as soon as possible) in patients with severe sepsis or life-threatening infectionsa Comply with local antimicrobial prescribing guidance Document clinical indication (and disease severity if appropriate), doseß and route* on drug chart and in clinical notes Include review/stop date or duration Obtain cultures prior to commencing therapy where possible (but do not delay therapy) 2. 3. 4. 5. STOP IV to oral switch Change antibiotic Continue OPAT* Document Decision & Next Review Date or Stop Date DOCUMENT ALL DECISIONS o In sepsis pÖert safety Ottp england nhs conterWupIoads,QO to weigw.ge in children refer to local formu.•y BNFC QJse "propriate route in ine wit' seve%ieri factors Parenteral Theroy Advocating patient safety and auditing of antimicrobial stewardship in hospitals should be based around the principles stated in thi AMS algorithm. Examples of audit tools are shared in Appendix I https://www.gov.uk

  • Figure 2: Antimicrobial Stewardship (AMS) — Surgical prophylaxis algorithm ANTIMICROBIAL STEWARDSHIP Surgical prophylaxis algorithm Clean surgery Clean contaminated Involving placement of surgery a prosthesis or implant Surgical Prophylaxis ONE DOSE*I Contaminated surgery Within 60 minutes before knife to skin2 Redose for long surgical procedures Intraoperative redosing is needed to ensure adequate serum and tissue concentrations of the antimicrobial if the duration of the procedure exceeds two half-lives of the antimicrobial or there is excessive blood loss (i.e., >1500 mL in adults3 or >25mVkg in children). A treatment course of antibiotics may also need to be given (in addition to appropriate prophylaxis) in cases of dirty surgery or infected wounds3. The appropriate use and choice of antibiotics should be discussed with infection specialists for each case. DOCUMENT ALL DECISIONS References: 1. NICE cir-iCal %ideine 74: •.r•cal site infection — Prevertion and of sur#al site infection http nice oro 2 Workl aliance for Patiert Safety. WHO sugical safety check'st 2008 Ntp resources,'SSSL Checkist final-Jun080df7ua=1 3. Bratzier DW, De'nger EP, Olsen KM etal_ (2013). CiNcal practice *idérws in svwy_ Am' Heath syst Pharm 2013: 70(3): 195-283 Advocating patient safety and auditing of antimicrobial stewardship in hospitals should be based around the principles stated in this AMS algorithm. Examples of audit tools are shared in Appendix 1. Deviations from the NICE guideline should be evidence based, with prolonged prophylaxis needing evidence of benefit. 30 https://www.gov.uk