BMS2037 Antibiotics Part 2.pdf

BMS2037 Treatment case studies Antimicrobial susceptibility testing Dr Alison Cottell Preserve and conserve what we already have Despite Staph. aureus resistance, penicillin remains important for the treatment of: Listeriosis Meningitis Streptococcal infections...

BMS2037 Treatment case studies Antimicrobial susceptibility testing Dr Alison Cottell Preserve and conserve what we already have Despite Staph. aureus resistance, penicillin remains important for the treatment of: Listeriosis Meningitis Streptococcal infections Syphilis Neisseria gonorrhoea is generally resistant Treatment Meningococcal disease Gonnococcal disease IV antibiotics – benzyl penicillin or Developed resistance rapidly to all amoxicillin. antibiotics introduced for treatment. – 3rd generation cephalosporins First line treatments now extended – Drug resistance is rare spectrum e.g. cefixime or IM Maintenance therapy for shock ceftriaxone (fluids, etc.) Gonococcal superbugs now id’ed Vasoactive treatments IV adrenaline which have R to ceftriaxone Steroids (preferably before first of Dual treatments now recommended – Ceftriaxone and Azithromycin antibiotic – why?) Experimental therapies, such as anti-cytokine and anti-endotoxin have been investigated. The drugs don’t work  Urinary tract infection (UTI) – basic overview Ascending infection Secondary spread: can cause fever and renal abscess loin pain bacteraemia Pyelonephritis Cystitis: exacerbated by urinary stasis Prostatitis Urethritis Contamination Epididymitis from faecal / perineal flora Aetiological agents of urinary tract infection Causative organism Comments E. coli From gut microflora; very common Klebsiella / Proteus spp. From gut microflora: less common Pseudomonas aeruginosa Usually hospital-associated Staphylococcus epidermidis Often associated with catheterisation or Enterococcus faecalis instrumentation Chlamydia trachomatis In sexually active people Neisseria gonorrhoea Treatment guidelines and precautions Clinical case BNF recommendations Uncomplicated lower UTI Trimethoprim; nitrofurantoin (adults, and children >3 months old. These drugs become concentrated in the urine, and N.B. variations in dose for different remain in an active state in the bladder patient groups) Pregnancy – clinical, rather than Avoid quinolones. Avoid trimethoprim. microbiological considerations Nitrofurantoin: avoid at term. Use amoxicillin or cephalosporin instead E. coli with ESBL enzymes Increasing prevalence. Nitrofurantoin remains sensitive Renal impairment Caution, as for any drug given to patients in this group Upper UTI (acute Antibiotics usually initially administered via IV route due pyelonephritis) to risk of septicaemia. Cephalosporin; quinolone; gentamicin. Pseudomonas aeruginosa – intrinsic resistance Consequences for treatment: Only a few members of the beta-lactam group are effective Increasing resistance among members of the aminoglycoside and fluoroquinolone group Specialist anti- pseudomonal antibiotics are often used Summary of spectrum of activity of antibiotics (from Brock Biology of Microorganisms) Aminoglycosides Introduction of antimicrobial agent First recorded case of antimicrobial resistance  Stepwise proliferation of antimicrobial-tolerant strains can lead to resistance Red dots represent bacterial mutants In the presence of an antimicrobial Sustained presence of the antibiotic that have raised tolerance to antibiotics most cells are killed, but a small sub- causes the small population of tolerant population of tolerant cells remain cells to replicate. Grey dots represent fully sensitive cells. Further antimicrobial exposure adds to the selective pressure that can precede [Link to stepwise tolerance timelapse video full resistance https://news.harvard.edu/gazette/story/2016/09/a- cinematic-approach-to-drug-resistance/]  Measuring antibiotic susceptibility and resistance Quantitative methods for measuring the minimum inhibitory concentration (MIC) The broth dilution test: Broths contain different antimicrobial concentrations Inoculated and incubated Lowest concentration with no turbidity is the MIC 1.6 mcg/ml in the example below  Measuring antibiotic susceptibility and resistance Tolerance – bacteria have a higher-than-expected MIC Resistance – bacterial have an MIC higher than the therapeutic dose of an antibiotic Source: EUCAST: European Committee in Antimicrobial Sensitivity Testing Disc-diffusion: The antibiotic diffuses into the agar producing a radial concentration gradient, Antibiotic breakpoints: An empirical prediction of resistance is preventing the growth of interpreted based on whether the zone falls above or below a sensitive organisms in that area. specified diameter (the breakpoint). Molecular methods for ascertaining resistance These involve molecular and genetic methods. Presence of specific resistance gene negates the need to identify the MIC via phenotypic methods. Digital PCR-High Resolution Melt analysis (HRM)-based bacterial identification from mixed bacterial samples (Khan et al, 2019)  Broader consequences of antimicrobial resistance According to WHO, AMR compromises the following: Organ transplant Cancer chemotherapy Diabetes management Routine surgery, e.g.: ~5000 transplants ~350 000 new cancer Hip-replacements per year cases / year; ~100 000 Caesarians receive chemotherapy Other impacts: Longer stays in hospital Longer time intubated Longer duration of antibiotic treatment Greater financial costs ~4.5 M surgical 6% of UK population admissions in the UK have diabetes per year.  Projected total global antibiotic consumption (billions of DDDs): 2000–2030. Eili Y. Klein et al. PNAS 2018;115:15:E3463-E3470 ©2018 by National Academy of Sciences Predicted deaths attributable to antimicrobial resistance, compared to other causes of deaths. Source: Antimicrobial Resistance: Tackling a crisis for the health and wealth of nations – The Review on Antimicrobial Resistance Chaired by Jim O’Neill Further Reading: The main textbook for the module (available on Bibliu) Microbiology – An introduction. Tortora, GJ. 2021. Pearson. General Textbooks: Antimicrobial Chemotherapy, Fifth Edition, By Greenwood et al. ( Open University Press, ISBN: 0198570163). [Any recent edition] Antibiotics and Chemotherapy: anti-infective agents and their use in therapy, Eighth Edition, By Finch et al.: Churchill Livingstone, ISBN: 0443071292). [Any recent edition]