Study guide
16.4 Antimicrobial Pharmacokinetics, Allergy, Toxicity & Infection Prevention
ABIM Critical Care Medicine Study Guide Exam
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1 Chapter 1: Exam Orientation: Format, Blueprint & Study Strategy
1.1 ABIM Critical Care Medicine Exam: Format, Blueprint & Study Strategy
2 Chapter 2: Acute Respiratory Failure & ARDS
2.1 ARDS Definition, Pathophysiology & Phenotypes 2.2 Lung-Protective Mechanical Ventilation 2.3 Refractory ARDS: Prone Positioning, Neuromuscular Blockade & VV-ECMO
3 Chapter 3: Obstructive Airways, Pulmonary Vascular & Pleural Emergencies
3.1 Severe Asthma & COPD Exacerbations in the ICU 3.2 Massive & Submassive Pulmonary Embolism 3.3 Pulmonary Hypertension & Right Ventricular Failure in the ICU 3.4 Massive Hemoptysis, Complex Pleural Effusions & Thoracic Drainage
4 Chapter 4: Airway, Parenchymal & Nonthrombotic Pulmonary Emergencies
4.1 Airway Management, Upper-Airway Obstruction & Artificial-Airway Complications 4.2 Diffuse Alveolar Hemorrhage, Interstitial Lung Disease, Pulmonary Vasculitis & Noncardiogenic Edema 4.3 Severe Community-Acquired & Viral Pneumonia 4.4 Nonthrombotic Embolism (Air, Fat, Amniotic Fluid, Tumor, Septic) & Acute Chest Syndrome
5 Chapter 5: Mechanical Ventilation Modes, Dyssynchrony & Liberation
5.1 Mechanical Ventilator Modes & Advanced Breath Delivery 5.2 Patient-Ventilator Dyssynchrony & Waveform Analysis 5.3 Ventilator Liberation, Spontaneous Breathing Trials & Post-Extubation Support
6 Chapter 6: Shock Syndromes & Hemodynamic Principles
6.1 Shock Classification, Cellular Pathophysiology & Biomarkers 6.2 Hemodynamic Monitoring: Arterial Lines, CVP & Pulmonary Artery Catheter 6.3 Dynamic Assessment of Fluid Responsiveness & Resuscitation Targets
7 Chapter 7: Vasoactive Therapies & Mechanical Circulatory Support
7.1 Vasopressors & Inotropes: Pharmacology & Clinical Titration 7.2 Temporary Mechanical Circulatory Support: IABP, Impella & TandemHeart 7.3 Venoarterial ECMO (VA-ECMO) & Differential Hypoxemia 7.4 Post-Cardiac Arrest Care, Targeted Temperature Management & Neuroprognostication
8 Chapter 8: Acute Kidney Injury & Renal Replacement Therapy
8.1 KDIGO AKI Classification, Etiologies & Diagnostic Evaluation 8.2 Continuous Renal Replacement Therapy (CRRT) vs Intermittent Hemodialysis 8.3 Indications & Timing for RRT in Critical Illness: AKIKI & STARRT-AKI
9 Chapter 9: Electrolyte, Acid-Base & Endocrine Emergencies
9.1 Severe Dysnatremias: Hyponatremia, Hypernatremia & Osmotic Demyelination 9.2 Potassium, Calcium, Magnesium & Phosphate Disorders 9.3 Complex & Mixed Acid-Base Disorders: Boston vs Copenhagen vs Stewart 9.4 Endocrine Crises: DKA, HHS, Thyroid Storm, Myxedema Coma & Adrenal Crisis
10 Chapter 10: Glycemic Control, Hyperammonemia, Pituitary & Adrenal Disorders
10.1 ICU Glycemic Control & Severe Hypoglycemia 10.2 Non-Hepatic Hyperammonemia & Metabolic Encephalopathy 10.3 Pituitary Emergencies, Adrenal Excess & Critical Illness-Related Corticosteroid Insufficiency
11 Chapter 11: Acute Coronary Syndromes & Cardiac Arrhythmias
11.1 Acute Coronary Syndromes & Mechanical Complications of Myocardial Infarction 11.2 Critical Tachyarrhythmias: Atrial Fibrillation with RVR, VT & VF 11.3 Critical Bradyarrhythmias, Conduction Blocks & Temporary Cardiac Pacing
12 Chapter 12: Acute Heart Failure, Valvular & Pericardial Emergencies
12.1 Acute Decompensated Heart Failure & Cardiogenic Pulmonary Edema 12.2 Acute Valvular Regurgitation & Prosthetic Valve Emergencies 12.3 Pericardial Tamponade & Acute Aortic Syndromes
13 Chapter 13: Myocardial Disease, Hypertensive & Cardiac Device Emergencies
13.1 Fulminant Myocarditis, Stress & Peripartum Cardiomyopathy, and Hypertrophic Cardiomyopathy 13.2 Hypertensive Emergencies & Ruptured Abdominal Aortic Aneurysm 13.3 Implanted Cardiac Devices, LVAD Emergencies & Electrical Storm
14 Chapter 14: Sepsis & Systemic Infectious Diseases
14.1 Sepsis-3 Definitions & Surviving Sepsis Campaign 2026 Guidelines 14.2 Refractory Septic Shock & Adjunctive Therapies 14.3 Multidrug-Resistant Pathogens & Antimicrobial Stewardship in the ICU
15 Chapter 15: ICU-Acquired & Severe Focal Infections
15.1 Hospital-Acquired & Ventilator-Associated Pneumonia 15.2 Central Line-Associated Bloodstream Infections & Catheter-Associated UTIs 15.3 Intra-Abdominal Sepsis, Necrotizing Soft Tissue Infections & CNS Infections
16 Chapter 16: Focal, Special-Host & Systemic Infections
16.1 CNS Infections Beyond Bacterial Meningitis: Encephalitis, Brain Abscess & Epidural Abscess 16.2 Infections in the Immunocompromised Host, Tropical & Bioterror Infections 16.3 Infective Endocarditis, Device Infections & Other Focal Cardiovascular Infections 16.4 Antimicrobial Pharmacokinetics, Allergy, Toxicity & Infection Prevention 16.5 Gastrointestinal & Hepatobiliary Infections: Fulminant C. difficile, Typhlitis, CMV Colitis & Abscesses
17 Chapter 17: Neurocritical Care & Coma
17.1 Coma, Altered Mental Status & Acute Delirium in the ICU 17.2 Status Epilepticus & Non-Convulsive Status Epilepticus 17.3 Acute Ischemic Stroke & Intracranial Hemorrhage
18 Chapter 18: Cerebrovascular Syndromes, Encephalopathy & Withdrawal States
18.1 Cerebral Venous Sinus Thrombosis, PRES & Reversible Cerebral Vasoconstriction Syndrome 18.2 Alcohol & Sedative Withdrawal, Wernicke Encephalopathy & Drug-Induced Encephalopathy
19 Chapter 19: Intracranial Hypertension & Neuromuscular Weakness
19.1 Intracranial Pressure Monitoring, Cerebral Perfusion & Tiered ICP Management 19.2 Acute Neuromuscular Respiratory Failure, ICU-Acquired Weakness & Brain Death Determination
20 Chapter 20: Traumatic Brain Injury, Spinal Cord Injury & Toxin-Mediated Paralysis
20.1 Traumatic Brain Injury Management & Paroxysmal Sympathetic Hyperactivity 20.2 Acute Spinal Cord Injury, Neurogenic Shock & Autonomic Dysreflexia 20.3 Toxin-Mediated Paralysis & Neuromuscular Crises: Botulism, Tetanus, Tick Paralysis & Myasthenic Crisis
21 Chapter 21: Gastrointestinal, Hepatic & Abdominal Emergencies
21.1 Acute Upper & Lower Gastrointestinal Bleeding in the ICU 21.2 Acute Liver Failure & Severe Acute Pancreatitis 21.3 Abdominal Compartment Syndrome & Acute Mesenteric Ischemia
22 Chapter 22: Luminal GI Emergencies & Complications of Cirrhosis
22.1 Esophageal, Gastric & Bowel Emergencies: Perforation, Obstruction, Ogilvie Syndrome & Colonic Ischemia 22.2 Complications of Cirrhosis: Alcohol-Associated Hepatitis, Hepatorenal Syndrome & Pulmonary Vascular Syndromes
23 Chapter 23: Trauma, Burns & Perioperative Critical Care
23.1 Polytrauma Resuscitation, Damage Control & Massive Transfusion 23.2 Severe Burn Injury, Inhalation Injury & Environmental Emergencies 23.3 Perioperative Critical Care for High-Risk Surgical Patients
24 Chapter 24: Thoracic Trauma, Environmental Injury & Obstetric Critical Care
24.1 Thoracic Trauma: Flail Chest, Pulmonary Contusion, Great Vessel & Tracheobronchial Injury 24.2 Environmental Injury: Drowning, Diving, Altitude, Heat, Cold, Electrical & Radiation 24.3 Obstetric & Genitourinary Emergencies and the Physiology of Pregnancy
25 Chapter 25: Transplantation, Donor Management & Post-Cardiac Surgery Care
25.1 Solid Organ Transplant Recipients & Deceased Donor Management 25.2 Post-Cardiac Surgery Critical Care: Bleeding, Tamponade, Low Output & Vasoplegia
26 Chapter 26: Hematologic Emergencies, Toxicology, Critical Ultrasound & ICU Liberation
26.1 Hematologic Emergencies in the ICU: HIT, DIC, TMA & Anticoagulant Reversal 26.2 Critical Care Toxicology, Toxidromes & Specific Antidotes 26.3 Critical Care Point-of-Care Ultrasound (POCUS) 26.4 ICU Liberation, Analgosedation, Goals of Care & Critical Care Ethics
27 Chapter 27: Transfusion Medicine, Hematologic & Oncologic Disorders
27.1 Transfusion Medicine: Products, Thresholds, Reactions & Apheresis 27.2 Red and White Cell Disorders, Hemoglobinopathies, Factor Deficiencies & Hypercoagulable States 27.3 Oncologic Emergencies, Hematopoietic Cell Transplant Complications & Cellular Therapy Toxicity
28 Chapter 28: Clinical Pharmacology, Adverse Drug Reactions & Specific Poisonings
28.1 Pharmacokinetic Principles, Dose Adjustment & Drug Interactions in Critical Illness 28.2 Adverse Drug Reactions: Anaphylaxis, Severe Cutaneous Reactions & Hyperthermic Syndromes 28.3 Specific Poisonings: Sodium-Channel Blockers, Lithium, Valproate, Theophylline, Iron, Sulfonylureas & Methemoglobinemia
29 Chapter 29: Ethics, Research Methods, Administration & Abdominal Ultrasound
29.1 Advance Care Planning, Nonbeneficial Treatment, Informed Consent & Confidentiality 29.2 Critical Care Research Methods, Statistics, IRB Oversight & Quality Improvement 29.3 Abdominal, Vascular & Procedural Point-of-Care Ultrasound
16.4 Antimicrobial Pharmacokinetics, Allergy, Toxicity & Infection Prevention
Key Takeaways Explain This Topic AI
Beta-lactams are time-dependent; the 2026 Surviving Sepsis Campaign recommends prolonged (extended or continuous) infusion for maintenance dosing after a loading dose.
Augmented renal clearance (creatinine clearance above about 130 mL/min) occurs in young trauma, burn, and sepsis patients and causes beta-lactam underdosing at standard doses.
Vancomycin dosing now targets an AUC/MIC of 400 to 600 rather than a trough of 15 to 20 mg/L, which reduces nephrotoxicity.
A PEN-FAST score of 0 to 2 indicates a very low risk of true penicillin allergy and supports direct oral challenge in appropriate settings.
Cefepime causes nonconvulsive status epilepticus and myoclonus when dosed without adjustment in kidney impairment, and carbapenems reduce valproate levels sharply.
Last updated: October 2026
Why Standard Doses Fail in Critical Illness
Change in critical illness Consequence
Capillary leak and aggressive fluid resuscitation Expanded volume of distribution for hydrophilic drugs (beta-lactams, aminoglycosides, vancomycin): subtherapeutic peaks unless a full loading dose is given
Hypoalbuminemia Higher free fraction of highly bound drugs (ceftriaxone, ertapenem, teicoplanin) with faster clearance
Augmented renal clearance (creatinine clearance above about 130 mL/min) Seen in younger trauma, burn, neurocritical and sepsis patients: standard doses undershoot
Acute kidney injury and kidney replacement therapy Accumulation if doses are not reduced; conversely, CRRT clears many antimicrobials substantially
ECMO circuits Sequestration of lipophilic and highly protein-bound drugs (fentanyl, propofol, voriconazole) in the oxygenator and tubing
Altered gut absorption and interrupted feeds Unreliable enteral absorption; use intravenous routes in shock
The rule : never reduce the loading dose for organ dysfunction, because it is determined by the volume of distribution; adjust the maintenance dose for clearance.
Pharmacodynamic Targets
Class Killing pattern Optimization
Beta-lactams Time-dependent (time above MIC) Extended (3 to 4 hour) or continuous infusion after a loading dose; higher frequency. The BLING III trial found no mortality difference but a favorable secondary signal, and meta-analysis supports continuous infusion; the 2026 SSC recommends prolonged infusion
Aminoglycosides Concentration-dependent (peak/MIC) High once-daily dosing (gentamicin 5 to 7 mg/kg, amikacin 15 to 20 mg/kg); monitor trough for toxicity
Vancomycin AUC-dependent AUC/MIC of 400 to 600 , using two-level or Bayesian estimation; the old trough target of 15 to 20 mg/L caused excess nephrotoxicity
Fluoroquinolones Concentration-dependent (AUC/MIC) Adequate single daily dose
Daptomycin Concentration-dependent 6 to 10 mg/kg daily; inactivated by pulmonary surfactant, so never use it for pneumonia ; monitor creatine kinase
Linezolid AUC-dependent Good lung penetration; causes thrombocytopenia, serotonin syndrome risk with serotonergic drugs, and lactic acidosis with prolonged use
Polymyxins (colistin) Concentration-dependent Loading dose required; nephrotoxic and neurotoxic; poor lung penetration
Drug-Specific Toxicity Traps
Cefepime neurotoxicity : myoclonus, encephalopathy, and nonconvulsive status epilepticus , usually from unadjusted dosing in kidney impairment. Stop the drug; dialysis helps in severe cases.
Vancomycin plus piperacillin-tazobactam : associated with a higher incidence of acute kidney injury (at least by creatinine-based definitions) than vancomycin with cefepime or meropenem.
Aminoglycosides : nephrotoxicity (nonoliguric, usually reversible) and irreversible ototoxicity and vestibulotoxicity ; avoid in myasthenia gravis.
Carbapenem plus valproate : carbapenems drop valproate levels dramatically and can precipitate seizures; choose another antibiotic or another antiepileptic.
Linezolid plus serotonergic drugs : serotonin syndrome risk, particularly with SSRIs.
Fluoroquinolones : QT prolongation, tendinopathy, aortic aneurysm association, glucose dysregulation, and delirium.
Trimethoprim-sulfamethoxazole : hyperkalemia (ENaC blockade), a creatinine rise from tubular secretion blockade without true injury, myelosuppression, and hypersensitivity.
Amphotericin B deoxycholate : infusion reactions, nephrotoxicity, and potassium and magnesium wasting; liposomal formulations are less nephrotoxic.
Voriconazole : visual disturbance, hepatotoxicity, encephalopathy, and extensive CYP interactions, which demand therapeutic drug monitoring.
Antibiotic Allergy Assessment
Up to 10% of hospitalized patients carry a penicillin allergy label, but fewer than 5% of those are truly allergic. The label drives use of broader, less effective, more toxic alternatives.
PEN-FAST scores the history:
PEN : penicillin allergy reported.
F : five years or less since the reaction (2 points).
A : anaphylaxis or angioedema, or S : severe cutaneous adverse reaction (2 points).
T : treatment required for the reaction (1 point).
A score of 0 to 2 indicates a very low risk of a positive penicillin allergy test and supports direct oral challenge in an appropriate setting.
Cross-reactivity : the shared R1 side chain, not the beta-lactam ring, drives most cross-reactivity. Cephalosporins with dissimilar side chains (cefazolin in particular) can usually be given to patients with a penicillin allergy history. Carbapenem cross-reactivity is well under 1%.
Never rechallenge after anaphylaxis to that same drug class without specialist input , or after severe cutaneous adverse reactions : Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS, or acute generalized exanthematous pustulosis.
Desensitization is an option when the drug is essential (for example, in neurosyphilis in pregnancy); it induces temporary tolerance only.
Vancomycin infusion reaction (flushing of the upper body) is a direct mast cell effect, not an allergy. Slow the infusion and give an antihistamine.
Resistance Patterns Worth Memorizing
MRSA : vancomycin, daptomycin (not for pneumonia), linezolid, ceftaroline.
VRE : linezolid or daptomycin (high dose).
ESBL-producing Enterobacterales : carbapenems are preferred over piperacillin-tazobactam for invasive infection (MERINO trial).
AmpC inducers ( Enterobacter , Serratia , Citrobacter , Providencia , Morganella ): avoid third-generation cephalosporins; use cefepime or a carbapenem.
Carbapenem-resistant Enterobacterales : ceftazidime-avibactam or meropenem-vaborbactam for KPC; cefiderocol or ceftazidime-avibactam plus aztreonam for metallo-beta-lactamase producers.
Difficult-to-treat Pseudomonas : ceftolozane-tazobactam, ceftazidime-avibactam, imipenem-relebactam, or cefiderocol.
Acinetobacter baumannii : ampicillin-sulbactam at high dose, sulbactam-durlobactam, cefiderocol, polymyxins.
Stenotrophomonas maltophilia : trimethoprim-sulfamethoxazole, minocycline, levofloxacin, cefiderocol.
Fungi : Candida glabrata and C. krusei have reduced azole susceptibility (an echinocandin is first-line for candidemia); Candida auris is multidrug-resistant and demands contact isolation; Aspergillus terreus is amphotericin-resistant; mucorales are voriconazole-resistant .
Stewardship and Infection Prevention
Stewardship basics : obtain cultures before antibiotics, start broad in septic shock then de-escalate on day 2 or 3 , use the shortest effective duration, and set a stop date at the time of ordering. Procalcitonin plus clinical assessment can shorten duration (the 2026 SSC supports this use) but should not delay initial therapy.
Short courses with evidence : 7 days for ventilator-associated pneumonia (most cases) and for gram-negative bacteremia (BALANCE and earlier trials), 4 days after source control in intra-abdominal infection (STOP-IT), and 5 to 7 days for community-acquired pneumonia with clinical stability.
Prevention bundles :
Hand hygiene remains the single highest-impact intervention.
Central line insertion bundle : hand hygiene, chlorhexidine skin preparation, full barrier precautions, avoiding the femoral site when possible, ultrasound guidance, and daily review of necessity.
Chlorhexidine bathing reduces bloodstream infection in ICU patients.
Ventilator bundle : head elevation, sedation interruption with daily extubation assessment, oral care, and subglottic secretion drainage.
Catheter-associated urinary tract infection : avoid placement, remove early, and do not treat asymptomatic bacteriuria.
Selective digestive decontamination reduced mortality in units with low antimicrobial resistance, and the 2026 SSC suggests it in that setting.
Isolation : contact precautions for resistant organisms and C. difficile (with soap and water rather than alcohol gel), droplet for influenza and plague, and airborne for tuberculosis, measles, varicella, and smallpox.