Phys · infectious
Antimicrobial Stewardship and Resistance
Also known as antimicrobial stewardship · antibiotic stewardship · antimicrobial resistance · AMR · multidrug resistance · MDR organism · MRSA · VRE · ESBL · carbapenem-resistant Enterobacteriaceae · CRE · carbapenemase · KPC · NDM · OXA-48 · Clostridioides difficile · Clostridium difficile · C. diff · fidaxomicin · bezlotoxumab · faecal microbiota transplant · procalcitonin · penicillin allergy delabeling · intrinsic resistance · acquired resistance
Consultant-physician-depth guide to antimicrobial stewardship and resistance — the central principle that every antibiotic prescription has consequences, captured by the five rights (right drug, right dose, right route, right duration, right indication). Covers the mechanisms of resistance (intrinsic versus acquired; enzymatic inactivation, target modification, reduced permeability and efflux, bypass; plasmids, transposons, integrons; rpoB mutations in TB), the key resistant organisms and their first-line, alternative and last-resort agents (MRSA, VRE, ESBL Enterobacteriaceae, CRE, MDR Pseudomonas and Acinetobacter), Clostridioides difficile infection (NAP1/027 hypervirulent strain, two-step diagnostic algorithm, fidaxomicin first-line, bezlotoxumab, faecal microbiota transplant), infection control (five moments of hand hygiene, contact precautions, screening), antibiotic allergy delabeling (90 per cent of penicillin allergy labels are wrong), and procalcitonin-guided antibiotic cessation — structured for FRACP DWE and DCE preparation.
On this page
Study tools
Your progress
Saved on this device.
Practise this topic
Target exams
Red flags
- Any inpatient who develops diarrhoea while on or within 8 weeks of antibiotics has Clostridioides difficile infection until a stool toxin assay proves otherwise; a WBC above 15 or creatinine 1.5 times baseline defines severe disease and changes the drug (oral vancomycin 500 mg four times daily) and the outcome
- A patient with carbapenem-resistant Enterobacteriaceae bacteraemia has a mortality of 40 to 50 per cent; carbapenemase type (KPC, NDM, OXA-48) drives therapy — KPC responds to ceftazidime-avibactam, NDM does not and requires aztreonam plus avibactam or colistin
- MRSA bacteraemia requires at least 14 days of therapy, echocardiography to exclude endocarditis, and removal of any removable focus (the line); a vancomycin MIC above 1.5 to 2 mg/L predicts vancomycin failure and prompts a switch to an alternative agent
- Daptomycin is inactivated by pulmonary surfactant and is NEVER used for pneumonia — if MRSA pneumonia fails vancomycin, the switch is to linezolid, not daptomycin
- Continuing surgical antibiotic prophylaxis beyond 24 hours (48 hours for cardiac surgery) is inappropriate and drives C. difficile and resistance — a single preoperative dose, repeated only for prolonged surgery or major blood loss, is the standard
- A penicillin allergy label denies the patient first-line beta-lactams and pushes therapy to vancomycin, fluoroquinolones or clindamycin — with worse outcomes in sepsis and endocarditis; 90 per cent of labels are wrong, and active delabeling is a stewardship priority
- Adding a single drug to a failing anti-tuberculous regimen creates functional monotherapy and selects resistance — every regimen change must add at least two (preferably three) new active agents, guided by susceptibility testing
Antimicrobial Stewardship and Resistance
[1]The one-minute consultant answer
Every antibiotic prescription has consequences — for the patient in front of you, for the ward they are on, and for the population that will need antibiotics after them. Antimicrobial stewardship is the discipline of prescribing so that those consequences are beneficial and not harmful. The 2016 IDSA/SHEA guideline frames it through the five rights — right drug, right dose, right route, right duration, right indication — delivered through two core programme interventions: pre-authorisation (restricting certain drugs to infectious diseases approval) and prospective audit with feedback (reviewing ongoing therapy and advising the treating team) [1]. The bedside moves are the 48-hour review (reassess the empiric choice against culture and sensitivity and de-escalate), the IV-to-oral switch (when the patient is stable and can absorb), and the defined stop date (written on every prescription at the start).
Resistance arises because bacteria acquire, exchange and accumulate resistance genes — by mutation (a spontaneous change in chromosomal DNA, the basis of rifampicin resistance in TB through rpoB mutation), and by horizontal gene transfer through plasmids, transposons and integrons. Four molecular mechanisms do the work: enzymatic inactivation (beta-lactamases, including ESBLs and carbapenemases such as KPC and NDM), target modification (PBP2a in MRSA; D-alanyl-D-lactate in VRE; altered DNA gyrase in fluoroquinolone resistance), reduced permeability and efflux (porin OprD loss in Pseudomonas conferring carbapenem resistance; AcrAB-TolC efflux pumps), and bypass pathways (alternative penicillin-binding proteins). Intrinsic resistance is species-inherent and chromosomal (Pseudomonas impermeability; Enterococcus intrinsically resistant to cephalosporins; Listeria intrinsically resistant to cephalosporins), while acquired resistance emerges under antibiotic pressure. [1]
The resistant organisms every physician must know — and the agents that treat them — are: MRSA (vancomycin, linezolid, daptomycin, ceftaroline), VRE (linezolid, daptomycin, tigecycline), ESBL Enterobacteriaceae (carbapenems — meropenem, ertapenem), CRE (colistin, tigecycline, ceftazidime-avibactam, meropenem-vaborbactam; aztreonam plus avibactam for NDM), multidrug-resistant Pseudomonas and Acinetobacter (ceftolozane-tazobactam, colistin), and Clostridioides difficile (fidaxomicin first-line with oral vancomycin an acceptable alternative, bezlotoxumab for recurrence prevention, faecal microbiota transplant for multiple recurrences) [2]. And the stewardship wins that change outcome the most are the unglamorous ones — stopping the antibiotic when the indication has resolved, narrowing it when the culture returns, switching from IV to oral when the patient can absorb, and delabeling the penicillin allergy that was never real (90 per cent of labels are wrong) [9].
References9ShowHide
- [1]Barlam TF, Cosgrove SE, Abbo LM, et al. Implementing an Antibiotic Stewardship Program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America Clin Infect Dis, 2016.PMID 27080992
- [2]McDonald LC, Gerding DN, Johnson S, et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) Clin Infect Dis, 2018.PMID 29462280
- [3]Schuetz P, Wirz Y, Sager R, et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections Cochrane Database Syst Rev, 2017.PMID 29025194
- [4]Wilcox MH, Gerding DN, Poxton IR, et al. Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection N Engl J Med, 2017.PMID 28121498
- [5]van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile N Engl J Med, 2013.PMID 23323867
- [6]Louie TJ, Miller MA, Mullane KM, et al. Fidaxomicin versus vancomycin for Clostridium difficile infection N Engl J Med, 2011.PMID 21288078
- [7]Loo VG, Poirier L, Miller MA, et al. A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality N Engl J Med, 2005.PMID 16322602
- [8]Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children Clin Infect Dis, 2011.PMID 21208910
- [9]Castells M, Khan DA, Phillips EJ Penicillin Allergy N Engl J Med, 2019.PMID 31826341