Antimicrobials (by Class) — Mechanisms, Spectrum & Resistance

Meet the patient

A 72-year-old man arrives with septic shock from a urinary source — lactate 4.2 mmol/L, MAP 58 on noradrenaline 0.3 mcg/kg/min, two courses of antibiotics in the last three months, recent hospitalisation in India. Blood cultures and broad-spectrum anti-pseudomonal cover are started within the hour of recognition, source control follows, and therapy is narrowed once cultures and susceptibilities return.^[21][22]

The exam question and the bedside question are the same: which target, which PK/PD index, which resistance mechanism, which toxicity, de-escalated when? The four international impératifs — give effective antibiotics within one hour in septic shock, source control within 6–12 hours, de-escalate on culture, and dose for the patient's PK — are non-negotiable.^[2]

References28ShowHide

1. [1]Karnad DR, Nor MBM, Richards GA, et al. Intensive care in severe malaria: Report from the task force on tropical diseases by the World Federation of Societies of Intensive and Critical Care Medicine. Journal of critical care, 2018.PMID 29132978
2. [2]Evans L, Rhodes A, Alhazzani W, et al Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Crit Care Med, 2021.PMID 34605781
3. [3]Dulhunty JM, Roberts JA, Davis JS, et al A Multicenter Randomized Trial of Continuous versus Intermittent Beta-Lactam Infusion in Severe Sepsis (BLING II). Am J Respir Crit Care Med, 2015.PMID 26200166
4. [4]Liu C, Bayer A, Cosgrove SE, et al Clinical practice guidelines by the IDSA for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis, 2011.PMID 21217178
5. [5]Bartlett JG Clostridium difficile Infection. Infectious disease clinics of North America, 2017.PMID 28779831
6. [6]Endimiani A, Paterson DL Optimizing therapy for infections caused by enterobacteriaceae producing extended-spectrum beta-lactamases. Semin Respir Crit Care Med, 2007.PMID 18095228
7. [7]Triplett JD, Lawn ND, Chan J, et al Cephalosporin-related neurotoxicity: metabolic encephalopathy or non-convulsive status epilepticus? J Clin Neurosci, 2019.PMID 31201049
8. [8]Pappas PG, Kauffman CA, Andes DR, et al Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the IDSA. Clin Infect Dis, 2016.PMID 26810419
9. [9]Patterson TF, Thompson GR 3rd, Denning DW, et al Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the IDSA. Clin Infect Dis, 2016.PMID 27481947
10. [10]Kalil AC, Metersky ML, Klompas M, et al Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 IDSA Clinical Practice Guidelines. Clin Infect Dis, 2016.PMID 27418577
11. [11]Harris PNA, Tambyah PA, Lye DC, et al (MERINO) Effect of Piperacillin-Tazobactam vs Meropenem on 30-Day Mortality for Patients With E coli or Klebsiella pneumoniae Bloodstream Infection and Ceftriaxone Resistance (MERINO). JAMA, 2018.PMID 30208454
12. [12]Kumarasamy KK, Toleman MA, Walsh TR, et al Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study (NDM-1). Lancet Infect Dis, 2010.PMID 20705517
13. [13]Boucher HW, Talbot GH, Bradley JS, et al Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin Infect Dis, 2009.PMID 19035777
14. [14]Rybak MJ, Le J, Lodise TP, et al Executive Summary: Therapeutic Monitoring of Vancomycin for Serious Methicillin-Resistant Staphylococcus aureus Infections: A Revised Consensus Guideline and Review. Pharmacotherapy, 2020.PMID 32227354
15. [15]Pagkalis S, Mantadakis E, Mavros MN, et al Pharmacological considerations for the proper clinical use of aminoglycosides. Drugs, 2011.PMID 22085385
16. [16]Fowler VG Jr, Boucher HW, Corey GR, et al Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus. N Engl J Med, 2006.PMID 16914701
17. [17]Silverman JA, Mortin LI, Vanpraagh AD, et al Inhibition of daptomycin by pulmonary surfactant: in vitro modeling and clinical impact. J Infect Dis, 2005.PMID 15898002
18. [18]Maan G, Keitoku K, Kimura N, et al Cefepime-induced neurotoxicity: systematic review. J Antimicrob Chemother, 2022.PMID 35971666
19. [19]Pan K, Li R, Li Y, et al Vancomycin combined with piperacillin/tazobactam increases the risk of acute kidney injury compared with vancomycin plus other anti-pseudomonal beta-lactams: a systematic review and network meta-analysis. J Antimicrob Chemother, 2025.PMID 39533846
20. [20]Dulhunty JM, Brett SJ, De Waele JJ, et al Continuous vs Intermittent β-Lactam Antibiotic Infusions in Critically Ill Patients With Sepsis: The BLING III Randomized Clinical Trial. JAMA, 2024.PMID 38864155
21. [21]Kumar A, Roberts D, Wood KE, et al Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med, 2006.PMID 16625125
22. [22]Seymour CW, Gesten F, Prescott HC, et al Time to Treatment and Mortality during Mandated Emergency Care for Sepsis. N Engl J Med, 2017.PMID 28528569
23. [23]Pongchaidecha M, Changpradub D, Bannalung K, et al Vancomycin Area under the Curve and Pharmacokinetic Parameters during the First 24 Hours of Treatment in Critically Ill Patients using Bayesian Forecasting. Infect Chemother, 2020.PMID 33263245
24. [24]Nakamura A, Takasu O, Sakai Y, et al Development of a teicoplanin loading regimen that rapidly achieves target serum concentrations in critically ill patients with severe infections. J Infect Chemother, 2015.PMID 25726436
25. [25]Forrest A, Nix DE, Ballow CH, et al Pharmacodynamics of intravenous ciprofloxacin in seriously ill patients. Antimicrob Agents Chemother, 1993.PMID 8517694
26. [26]Taylor SD, Palmer M The action mechanism of daptomycin. Bioorg Med Chem, 2016.PMID 27288182
27. [27]Serio AW, Keepers T, Andrews L, et al Aminoglycoside Revival: Review of a Historically Important Class of Antimicrobials Undergoing Rejuvenation. EcoSal Plus, 2018.PMID 30447062
28. [28]Zeng D, Debabov D, Hartsell TL, et al Approved Glycopeptide Antibacterial Drugs: Mechanism of Action and Resistance. Cold Spring Harb Perspect Med, 2016.PMID 27663982