What is the recommended IV dose of cefazolin (Ancef) for a 29-year-old patient with Methicillin-Sensitive Staphylococcus Aureus (MSSA) bacteremia, weighing 57 kg, with impaired renal function (serum creatinine 45) and a single kidney?

Cefazolin Dosing for MSSA Bacteremia in Patient with Single Kidney and SCr 45

Recommended Dosing Regimen

For this 29-year-old, 57 kg patient with MSSA bacteremia and a serum creatinine of 45 µmol/L (approximately 0.5 mg/dL), indicating preserved renal function despite having one kidney, administer cefazolin 2 grams IV every 8 hours for 4-6 weeks depending on source control and presence of complications. 1

Rationale for Cefazolin Selection

• Cefazolin is the preferred agent for MSSA bacteremia based on contemporary evidence showing superior outcomes compared to vancomycin and comparable or better efficacy than anti-staphylococcal penicillins (ASPs), with a more favorable safety profile 1

• Recent meta-analyses demonstrate that cefazolin is associated with 69-79% lower mortality hazards compared to vancomycin (adjusted HR: 0.21-0.31) and significantly reduced mortality compared to ASPs (OR: 0.69) 2, 3, 4

• Cefazolin causes significantly less nephrotoxicity than ASPs (OR: 0.36), which is particularly relevant for this patient with a single kidney 2, 4

Dose Calculation and Adjustment

Standard Dosing for Bacteremia

• For severe infections including bacteremia and endocarditis, the FDA-approved dosing is 1-1.5 grams every 6 hours, with doses up to 12 grams daily used in severe cases 5

• Weight-based dosing for this 57 kg patient would be approximately 30-35 mg/kg per dose, translating to 1.7-2 grams per dose 5

Renal Function Assessment

• With a serum creatinine of 45 µmol/L (0.5 mg/dL), this patient has normal to supranormal renal function despite having one kidney 5

• According to FDA labeling, no dose adjustment is required for patients with creatinine clearance ≥55 mL/min or serum creatinine ≤1.5 mg/dL 5

• The patient's estimated creatinine clearance using Cockcroft-Gault formula: [(140-29) × 57 × 0.85] / (72 × 0.5) = approximately 150 mL/min, confirming normal renal function 5

Recommended Regimen

Administer cefazolin 2 grams IV every 8 hours to achieve optimal bactericidal activity for serious MSSA infection 1, 5, 2

• This dosing provides adequate serum concentrations throughout the dosing interval for MSSA with typical MICs 5, 2

• Each dose should be administered over 30-60 minutes 5

Duration of Therapy

• Uncomplicated bacteremia with rapid source control: 14 days minimum, with 2 weeks being acceptable if blood cultures clear within 72 hours and no endocarditis or metastatic foci are identified 1

• Complicated bacteremia (persistent fever, delayed blood culture clearance >72 hours, or metastatic infection): 4-6 weeks of therapy 1

• If endocarditis is present: minimum 4-6 weeks for native valve endocarditis, ≥6 weeks for prosthetic valve endocarditis 1

Monitoring Parameters

Clinical Monitoring

• Repeat blood cultures 48-72 hours after initiating therapy to document clearance 1

• Daily assessment for clinical improvement (defervescence, hemodynamic stability, resolution of symptoms) 1

• Echocardiography (preferably TEE) should be performed to evaluate for endocarditis, particularly if bacteremia persists >72 hours 1

Renal Function Monitoring

• Monitor serum creatinine at baseline and every 2-3 days during therapy, particularly important given single kidney 2, 4

• Adjust dosing if renal function deteriorates: if creatinine clearance falls to 35-54 mL/min, maintain full doses but extend interval to every 12 hours 5

• If creatinine clearance falls to 11-34 mL/min, reduce to half the usual dose every 12 hours 5

Critical Pitfalls and Considerations

Cefazolin Inoculum Effect (CzIE)

• Some MSSA strains demonstrate the cefazolin inoculum effect, where MICs increase significantly with higher bacterial inocula 1

• However, large observational studies show cefazolin remains effective despite theoretical concerns about CzIE, with some data suggesting superiority over ASPs 1

• The preferable safety profile of cefazolin and availability of robust clinical data supporting efficacy justify its use in most MSSA bacteremia cases 1

Source Control

• Identify and remove infected foci (intravascular catheters, prosthetic devices, abscesses) as inadequate source control is the primary reason for treatment failure, not antibiotic choice 1

• Surgical consultation should be obtained for deep-seated infections, endocarditis, or osteomyelitis 1

Single Kidney Considerations

• While this patient currently has normal renal function, the absence of renal reserve necessitates vigilant monitoring throughout therapy 2, 4

• Avoid nephrotoxic combinations (aminoglycosides, vancomycin, NSAIDs) unless absolutely necessary 2, 4

• Cefazolin's lower nephrotoxicity profile compared to ASPs (36% reduction in nephrotoxicity risk) makes it particularly appropriate for this patient 2, 4

When to Consider Alternative Agents

• If clinical failure occurs despite adequate source control and appropriate dosing, consider switching to an ASP (nafcillin or oxacillin 2 grams IV every 4 hours) 1

• If severe penicillin/cephalosporin allergy exists, vancomycin 15-20 mg/kg every 8-12 hours with AUC monitoring targeting 400-600 is an alternative 1

• For prosthetic valve endocarditis, some experts recommend ASPs over cefazolin, though evidence is limited 1