cefazolin
Regulatory sources consulted
Approved indications
- Susceptible respiratory, urinary, skin, biliary, and osteoarticular infections, septicemia, and endocarditis; perioperative prophylaxis.
Contraindications
Absolute
- Hypersensitivity to cefazolin or cephalosporins, or a history of a severe immediate reaction to another beta-lactam.
Clinical warnings
- Major warning · It may cause severe hypersensitivity or anaphylaxis. Review any history of immediate beta-lactam reactions before use and discontinue if an allergic reaction occurs. — FDA, set_id 00dd6da7-50a8-44c9-b2dc-7948973df392
- Major warning · It may cause Clostridioides difficile-associated diarrhea during or after treatment; assess significant diarrhea and avoid antiperistaltic drugs if colitis is suspected. — FDA, set_id 00dd6da7-50a8-44c9-b2dc-7948973df392
- Major warning · Excessive doses in renal impairment may cause seizures; adjust by creatinine clearance and monitor renal function. — FDA, set_id 00dd6da7-50a8-44c9-b2dc-7948973df392
- Major warning · It may reduce prothrombin activity and cause coagulopathy; monitor prothrombin time/INR in at-risk patients and give vitamin K when indicated. — FDA, set_id 00dd6da7-50a8-44c9-b2dc-7948973df392
Drug interactions
- HighOral anticoagulants
Mechanism: The antibiotic and infection may increase INR or bleeding risk.
Recommendation: Monitor INR and bleeding during and shortly after treatment.
FDA, set_id 00dd6da7-50a8-44c9-b2dc-7948973df392
- ModerateProbenecid
Mechanism: It reduces renal tubular secretion and may increase and prolong antibiotic exposure.
Recommendation: Avoid the combination unless deliberately indicated and monitor toxicity.
FDA, set_id 00dd6da7-50a8-44c9-b2dc-7948973df392
- HighAminoglycosides and other nephrotoxic drugs
Mechanism: The combination may increase nephrotoxicity.
Recommendation: Avoid the combination when possible and monitor renal function.
FDA, set_id 00dd6da7-50a8-44c9-b2dc-7948973df392
Adverse events
Common (≥1%)
Nausea, diarrhea, and rash
Rare but serious
Anaphylaxis, C. difficile colitis, and severe cytopenias
Pregnancy and lactation
Use during pregnancy only when clearly indicated. Small amounts pass into milk; monitor the infant for diarrhea, candidiasis, or sensitization and assess continuation according to the product.
Recent literature (PubMed)
Staphylococcus aureus, a gram-positive bacterium, is the leading cause of death from bacteremia worldwide, with a case fatality rate of 15% to 30% and an estimated 300 000 deaths per year. Staphylococcus aureus bacteremia causes metastatic infection in more than one-third of cases, including endocarditis (≈12%), septic arthritis (7%), vertebral osteomyelitis (≈4%), spinal epidural abscess, psoas abscess, splenic abscess, septic pulmonary emboli, and seeding of implantable medical devices. Patients with S aureus bacteremia commonly present with fever or symptoms from metastatic infection, such as pain in the back, joints, abdomen or extremities, and/or change in mental status. Risk factors include intravascular devices such as implantable cardiac devices and dialysis vascular catheters, recent surgical procedures, injection drug use, diabetes, and previous S aureus infection. Staphylococcus aureus bacteremia is detected with blood cultures. Prolonged S aureus bacteremia (≥48 hours) is associated with a 90-day mortality risk of 39%. All patients with S aureus bacteremia should undergo transthoracic echocardiography; transesophageal echocardiography should be performed in patients at high risk for endocarditis, such as those with persistent bacteremia, persistent fever, metastatic infection foci, or implantable cardiac devices. Other imaging modalities, such as computed tomography or magnetic resonance imaging, should be performed based on symptoms and localizing signs of metastatic infection. Staphylococcus aureus is categorized as methicillin-susceptible (MSSA) or methicillin-resistant (MRSA) based on susceptibility to β-lactam antibiotics. Initial treatment for S aureus bacteremia typically includes antibiotics active against MRSA such as vancomycin or daptomycin. Once antibiotic susceptibility results are available, antibiotics should be adjusted. Cefazolin or antistaphylococcal penicillins should be used for MSSA and vancomycin, daptomycin, or ceftobiprole for MRS
Staphylococcus aureus bacteremia is associated with high mortality. Whether cefazolin or an antistaphylococcal penicillin should be preferred for the treatment of methicillin-susceptible S. aureus bacteremia is unclear. In an ongoing international Bayesian adaptive platform trial, we conducted an open-label, randomized comparison of cefazolin with an antistaphylococcal penicillin (flucloxacillin or cloxacillin) in adult patients with penicillin-resistant, methicillin-susceptible S. aureus bacteremia. The primary outcome, which was evaluated with a hierarchical Bayesian logistic-regression model, was death from any cause within 90 days after enrollment in the platform. We assessed the posterior probability of the noninferiority of cefazolin to flucloxacillin or cloxacillin (with the criterion for noninferiority prespecified as an adjusted odds ratio of <1.2, which approximates an absolute difference in mortality of <2.5 percentage points if mortality in the antistaphylococcal-penicillin group is 15%), as well as the posterior probability of superiority (with the criterion of an adjusted odds ratio of <1.0). Secondary safety outcomes included the development of acute kidney injury within 14 days. This domain of the ongoing trial was conducted between February 17, 2022, and August 7, 2024, by which time the criterion for noninferiority had been met. Mortality at 90 days among adults who could be evaluated was 15.0% (97 deaths among 645 patients) in the cefazolin group and 17.0% (109 deaths among 642 patients) in the antistaphylococcal-penicillin group (adjusted odds ratio, 0.81; 95% credible interval, 0.59 to 1.12; probability of noninferiority, 99.2%; probability of superiority, 89.8%). Acute kidney injury occurred in 92 of 660 patients (13.9%) in the cefazolin group, as compared with 127 of 648 (19.6%) in the antistaphylococcal-penicillin group (adjusted odds ratio, 0.67; 95% credible interval, 0.50 to 0.89; probability of superiority, 99.7%). In patients with methic
To review recently published evidence relevant to Staphylococcus aureus bacteremia (SAB). Staphylococcus aureus is the most common pathogen causing co-infections and superinfections in patients with COVID-19. Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia ratios have sharply risen during the pandemic. SAB mortality is 18% at 1 month and 27% at 3 months but has gradually decreased over the last 30 years. Recurrences and reinfections are common (9%). Standardised items to define complicated SAB, and a new cut-off defining persisting bacteremia after 2 days with positive blood cultures have been proposed. Multiple antibiotic combinations have been trialled including vancomycin or daptomycin with β-lactams, fosfomycin, or clindamycin, without significant results. In the recently published guidelines, vancomycin remains the first line of treatment for MRSA bacteremia. For the management of methicillin-susceptible Staphylococcus aureus , cefazolin less frequently causes acute kidney injury than flucloxacillin, and when susceptibility is demonstrated, de-escalation to penicillin G is suggested. Our review confirms that Staphylococcus aureus represents a special aetiology among all causes of bloodstream infections. Pending results of platform and larger trials, its distinct epidemiology and determinants mandate careful integration of clinical variables and best available evidence to optimize patient outcomes.