22.3 Antimicrobial Stewardship, PK/PD Dosing Optimization & Hospital Infection Control
Key Takeaways
Critical illness can change both antimicrobial distribution and clearance. Review recent doses and organ function. Consider prolonged beta-lactam infusion and estimate vancomycin AUC for serious MRSA infection.
Reassess cultures, source control and clinical course daily. Use the 48–72 hour review to narrow, stop or set duration. Use age and symptoms when deciding whether to test a child for C. difficile.
Use Contact Precautions for suspected infectious diarrhea when indicated. During a norovirus outbreak, wash with soap and water after contact. Measles calls for Airborne Precautions and varicella calls for both Airborne and Contact.
Give qualifying meningococcal contacts prompt prophylaxis based on age, pregnancy and local resistance. For pertussis, exposure timing and contact with people at high risk guide prophylaxis.
In the PICU, effective empiric therapy and source control come first. At reassessment, ask whether a susceptible drug is reaching the infected site, whether the regimen can be narrowed, and which precautions will protect other patients.
Antimicrobial exposure in critical illness
Capillary leak and resuscitation can expand the apparent volume of distribution for hydrophilic drugs and lower early concentrations. Augmented renal clearance after major burns or in hyperdynamic illness can lower exposure to renally cleared drugs even when serum creatinine looks reassuring. Acute kidney injury can have the opposite effect. With continuous renal replacement therapy, both residual kidney function and circuit clearance matter. Review the initial dose and maintenance regimen separately, accounting for prior doses, renal trajectory, circuit settings and drug-specific safety. Pediatric cefepime pharmacokinetic study · 2026 pediatric cefepime target-attainment study
| Drug class | Exposure measure | How to use it |
|---|---|---|
| Beta-lactams | Time that free drug exceeds the minimum inhibitory concentration (MIC), expressed as a fraction of the dosing interval. | A longer infusion can improve target attainment for cefepime, meropenem or other suitable agents. The target varies with the drug, organism and severity. Check renal function, IV access, compatibility and dosing history with pharmacy. A patient already on treatment does not automatically need another loading dose. |
| Aminoglycosides | Peak-to-MIC exposure can be relevant to bacterial killing. Accumulation raises toxicity concerns. | Extended-interval dosing is appropriate in some settings, including age-specific neonatal protocols. Endocarditis synergy uses separate regimens. Monitor concentrations and renal function according to the drug, indication, dosing interval and clinical course. |
| Vancomycin for suspected or confirmed serious MRSA infection | The 24-hour area under the concentration–time curve (AUC). | Target an AUC over 24 hours of 400–600 mg·h/L, assuming a broth microdilution MIC of 1 mg/L. Use Bayesian estimation when available or an appropriate two-level pharmacokinetic method. Review the regimen if susceptibility or organ function changes. A single trough is insufficient to establish AUC. |
In a child with major burns on cefepime and vancomycin for suspected bloodstream infection, a high measured creatinine clearance raises concern for underexposure. Review the cefepime interval and consider a prolonged infusion to improve time above MIC. Estimate vancomycin AUC from measured concentrations and actual dose times before escalating. Follow cultures and source control as well as exposure. ASHP/IDSA/PIDS/SIDP vancomycin guideline · UCSF neonatal dosing pathway
Stewardship on rounds
- Reassess daily, with a structured review around 48–72 hours. Review culture quality and results, prior antibiotics, rapid diagnostics, suspected site, source control and clinical course. Narrow to an active agent, switch to oral therapy when the site, patient and susceptibility allow, and set a duration. Stop antibiotics if the course supports an alternative diagnosis. Negative cultures alone do not establish that a deep infection is absent.
- Clarify allergy histories. Ask about timing, manifestations, treatment and later tolerance. A child with a low-risk history such as a benign isolated rash may qualify for a supervised direct oral amoxicillin challenge. Anaphylaxis or a recent suspected immediate reaction needs a higher-risk evaluation. Cefazolin has a distinct side chain and is generally an option for patients with a penicillin allergy history when clinically indicated. Seek specialist guidance for severe delayed reactions such as SJS/TEN or DRESS, or a history implicating cefazolin itself.
CDC hospital stewardship core elements · AAAAI/ACAAI drug allergy practice parameter
Pediatric Clostridioides difficile infection
- Choose whom to test. Infants through 12 months frequently carry toxigenic organisms without illness. Avoid routine testing. In toddlers under 2 years, first exclude more likely infectious and noninfectious causes. From age 2 years, test compatible prolonged or worsening diarrhea when risk factors such as recent antibiotics or healthcare exposure are present. Send unformed stool and consider laxative effects before testing.
- Choose therapy by severity and episode. Oral vancomycin is an option for initial nonsevere disease, and fidaxomicin is FDA-labeled from age 6 months. The 2017 pediatric guideline also allows metronidazole for an initial nonsevere episode. Recurrence needs a regimen chosen for prior treatment and number of episodes. For severe disease use enteral vancomycin. For fulminant disease with shock, ileus or megacolon, obtain urgent specialist and surgical input, give enteral vancomycin with IV metronidazole as indicated, and consider rectal vancomycin if ileus limits delivery. IV vancomycin does not replace enteral treatment.
IDSA/SHEA pediatric CDI recommendations · Fidaxomicin U.S. label
Resistant bacteria and invasive fungi
- ESBL-producing Enterobacterales. For invasive infection outside the urinary tract, use a susceptible carbapenem. IDSA favors meropenem or imipenem-cilastatin initially in critical illness or hypoalbuminemia. Ertapenem can be appropriate in a stable patient with suitable susceptibility, site and albumin.
- Carbapenem-resistant Enterobacterales. Use susceptibility, site and the enzyme result. For invasive KPC producers, 2026 IDSA preferred agents include meropenem-vaborbactam, ceftazidime-avibactam and imipenem-cilastatin-relebactam. For invasive NDM producers, IDSA prefers aztreonam-avibactam or cefiderocol and gives ceftazidime-avibactam plus aztreonam as an alternative if aztreonam-avibactam is unavailable. Those recommendations describe organism-directed options. Pediatric ID and pharmacy must check age, formulation, evidence and dosing. U.S. labeling for aztreonam-avibactam has no established pediatric use.
- MRSA and VRE. For serious MRSA infection, choose an agent that fits the site and susceptibility, such as vancomycin with AUC monitoring when indicated. Daptomycin is unsuitable for pneumonia and does not replace gram-negative coverage. For invasive VRE, choose therapy with ID using species, susceptibility and site. Linezolid is a labeled option for susceptible vancomycin-resistant Enterococcus faecium, including infection with concurrent bacteremia. Monitor blood counts and review serotonergic drug interactions.
- Invasive candidiasis. An echinocandin is a common initial choice in older children. In neonates, IDSA recommends amphotericin B deoxycholate for disseminated disease and allows fluconazole in selected infants without prior fluconazole prophylaxis. The 2025 global guideline also supports liposomal amphotericin B or selected echinocandins in neonatal invasive disease. CNS and urinary disease require site-specific selection. In candidemia, document clearance and assess catheter removal with the treating team. IDSA and the 2025 global guideline support eye examination for neonates with Candida in blood or urine. For older children, consult local ID and ophthalmology guidance. IDSA favors screening after candidemia, whereas AAO advises against routine screening in asymptomatic patients.
- Invasive pulmonary aspergillosis. Voriconazole is a first-line option. Check pediatric formulation and dosing, measure trough concentrations, and review liver function, QT risk, visual adverse effects and drug interactions.
2026 IDSA resistant gram-negative guidance · Aztreonam-avibactam U.S. label · Daptomycin U.S. label · Linezolid U.S. label · IDSA candidiasis guideline · 2025 global pediatric candidiasis recommendations · AAO candidemia screening statement · IDSA aspergillosis guideline
Hospital infection prevention and exposure management
Apply Standard Precautions to every patient, including hand hygiene, protection from anticipated exposure to blood or body fluids, and safe injection practices. Add Transmission-Based Precautions when the presentation suggests a transmissible infection.
| Precautions | Bedside action | Pediatric examples |
|---|---|---|
| Contact | Gown and gloves on entry and dedicated or disinfected equipment. Prefer a single room when available. | RSV in infants and young children, rotavirus, major uncontained draining wounds and selected multidrug-resistant organisms under facility policy. |
| Contact for infectious diarrhea | For confirmed CDI, continue Contact at least 48 hours after diarrhea resolves and use EPA List K products. Soap and water is indicated when hands are visibly soiled and is encouraged after care during CDI outbreaks. During norovirus outbreaks, use soap and water after contact and an EPA-registered product effective against norovirus. | In norovirus outbreaks, continue Contact at least 48 hours after symptoms resolve. Consider longer precautions for infants and other patients with prolonged symptoms or shedding. |
| Droplet | Wear a medical mask on room entry. | Pertussis through five days of effective therapy, invasive meningococcal disease through 24 hours of effective therapy, and influenza according to facility guidance. |
| Airborne | Use a negative-pressure airborne infection isolation room with the door closed. Wear respiratory protection appropriate to the pathogen, such as a fit-tested N95 or PAPR. | Measles and infectious pulmonary or laryngeal tuberculosis. Add Contact for varicella and disseminated zoster. |
| Protective Environment | Use positive pressure and HEPA-filtered supply air. | Allogeneic hematopoietic stem cell transplant recipients. Continue Standard and any indicated Transmission-Based Precautions. |
CDC isolation recommendations and disease table · CDC healthcare hand hygiene · CDC CDI prevention · CDC norovirus recommendations
- Meningococcal exposure. Give prophylaxis as soon as possible, ideally within 24 hours of identifying the case, to household or childcare contacts and anyone with direct exposure to oral or airway secretions. For single-dose IM ceftriaxone, CDC lists 125 mg under age 15 years and 250 mg from age 15 years. Rifampin is another option with age-specific dosing. From age 1 month, single-dose ciprofloxacin 20 mg/kg up to 500 mg is an option where susceptibility and public health guidance permit. Coordinate agent choice for pregnancy, neonates and areas with resistance.
- Measles exposure. Consult public health promptly for susceptible contacts. For eligible contacts, MMR within 72 hours or immune globulin within six days can provide postexposure protection. Use eligibility and timing to choose the product. CDC measles prophylaxis
- Pertussis exposure. Offer prophylaxis to asymptomatic household contacts within 21 days of cough onset in the index case. Offer it within 21 days of exposure to infectious pertussis for those at high risk of severe disease and those who will have contact with them. Vaccination does not remove a qualifying exposure. Azithromycin is a common five-day regimen with age-specific dosing.
CDC meningococcal surveillance and prophylaxis · CDC pertussis prophylaxis
A 9-year-old with severe burns is receiving cefepime and vancomycin for suspected Pseudomonas and MRSA bloodstream infection. Measured creatinine clearance is 168 mL/min/1.73 m². The first vancomycin trough is 6.8 mcg/mL, and cefepime runs over 30 minutes every 8 hours. Which plan best addresses possible antimicrobial underexposure?
Review cefepime dosing and consider a prolonged infusion with pharmacy. Estimate vancomycin AUC and adjust to 400–600 mg·h/L over 24 hours, assuming an MRSA MIC of 1 mg/L by broth microdilution.
Reduce both cefepime and vancomycin maintenance doses by 50% to avoid drug accumulation during fluid resuscitation
Switch cefepime to once-daily extended-interval dosing and push vancomycin troughs above 20 mcg/mL
Replace cefepime with daptomycin for pulmonary and bloodstream coverage while holding vancomycin
A 5-month-old inpatient on ceftriaxone for pyelonephritis develops new watery diarrhea during a documented norovirus outbreak on the ward. What is the appropriate initial testing and infection-control plan?
Send C. difficile PCR immediately and start oral metronidazole if positive while using alcohol hand rub alone
Avoid routine C. difficile testing, assess for norovirus and other causes, and use Contact Precautions with soap-and-water hand hygiene after patient contact.
Place the infant in a negative-pressure Airborne Infection Isolation Room (AIIR) and order oral fidaxomicin empirically
Send C. difficile PCR and administer IV vancomycin if the assay returns positive
A 7-year-old unvaccinated child is admitted directly from the emergency department with fever, cough, coryza, conjunctivitis, Koplik spots on the buccal mucosa, and a blanching maculopapular rash spreading from the hairline down the neck and trunk. Which combination of isolation precautions and acute adjunctive treatment is indicated?
Droplet precautions for 24 hours after starting azithromycin plus oral zinc supplementation
Contact precautions with soap-and-water handwashing plus oral ribavirin
Airborne Precautions in a negative-pressure room with fit-tested N95 respirators, plus supervised oral vitamin A 200,000 IU daily for two days.
Protective Environment (positive-pressure HEPA room) plus IVIG 2 g/kg
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