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February '26 Infectious Diseases Update

Posted by Doug Black, PharmD., Ann Lloyd, PharmD. on Feb 10th 2026

Article of the Month (Editors' Choice)

Anti-staphylococcal Penicillin or Cefazolin for Methicillin-susceptible Staphylococcus aureus Bacteremia? 

By Henry F. Chambers, MD

  • Which agent is better for the treatment of bacteremia due to methicillin-susceptible Staphylococcus aureus (MSSA), an anti-staphylococcal penicillin or cefazolin? Observational studies (Ther Adv Infect Dis 2025;12:20499361251384146; Clin Microbiol Infect 2025;31:1272) have suggested that the two have similar efficacy and that the latter is better tolerated. A randomized controlled trial confirming or refuting these impressions has been lacking. Until now. Burdet and colleagues (Lancet 2025;406:2349) conducted an open-label, non-inferiority, randomized controlled trial in 21 medical centers in France in which patients with MSSA bacteremia were allocated to receive cefazolin (25-50 mg/kg IV q8h, maximum 6 gm/day) or cloxacillin (25-50 mg/kg IV q4-6h, between 8 gm/day and a maximum of 12 gm/day) for the first seven days of therapy. Patients with intravascular implants or suspected CNS infection were excluded. The non-inferiority margin was 12%.
  • The primary efficacy outcome was a composite of sterile blood cultures at day 3 (day 5 for endocarditis), no relapse of bacteremia or death, and clinical success, defined as resolution of signs and symptoms of infection, assessed at day 90 after randomization. One hundred forty-six participants were enrolled into the intention-to-treat (ITT) population in each arm. 30% of participants met criteria for immunosuppression, 16% had diabetes requiring medication, 8% had a prosthetic joint, and only 3% had a history of injection drug use. The most common infections were catheter-related (37%), bacteremia of unknown origin (30%), bone or joint infection (25%), and skin and soft tissue infection (22%). Rates of urinary infection, respiratory infection, deep abscess, and endocarditis were 8% or less.
  • Cefazolin was non-inferior to cloxacillin for the primary composite outcome in the ITT population, 109 participants (75%) in the cefazolin group and 108 participants (74%) in the cloxacillin group (95% confidence interval -11 to 9%), as well as for all secondary efficacy outcomes. Cefazolin was better tolerated than cloxacillin with fewer serious adverse events by day 7, 14/146 versus 30/146 (p=0.009), acute kidney injury (AKI) by day 7, 1/134 versus 15/128 (p=0.0002), and AKI by end of study treatment, 4/111 versus 19/99 (p=0.0008).
  • Because of the non-inferiority trial design it is not possible to conclude which is the more efficacious treatment for MSSA bacteremia (an anti-staphylococcal penicillin or cefazolin), or to conclude (because of the small number of participants enrolled) which might be better for specific infections, such as endocarditis or more serious or complicated infections.
  • One area where an anti-staphylococcal penicillin might be preferred is initial therapy of high inoculum infections, such as endocarditis. Cefazolin is less stable than anti-staphylococcal penicillins to hydrolysis by some staphylococcal beta-lactamase subtypes, A and C. In vitro this is manifested as an inoculum effect such that the minimum inhibitory concentration (MIC) is within the susceptible range at the standard inoculum (105 CFU/mL), but is ≥16 μg/mL at a 100-fold higher inoculum (≥107 CFU/mL). Anecdotal reports and in vivo models (Antimicrob Agents Chemother 2009;53:3437; J Antimicrob Chemother 2025;80:1287; Infect Dis Ther 2026;15:417) suggest an association between the inoculum effect and treatment failure, but are far from conclusive.
  • This randomized trial comparing cefazolin to cloxacillin presented an opportunity to shed light on the inoculum effect question by assessing whether outcomes for cloxacillin and cefazolin differed for those strains that produced type A staphylococcal beta-lactamase, a type most strongly associated with the inoculum effect. Alas, results were inconclusive. While non-inferiority of cefazolin to cloxacillin was not shown for any outcome for participants whose S. aureus strain carried type A beta-lactamase (except for the absence of relapse by day 90), the numbers are too small to allow for a robust assessment. Moreover, rates of microbiological failure were not statistically significantly different for participants infected with a S. aureus strain carrying the type A beta-lactamase, 6/58 (10%) compared to those whose bacterial strain did not, 9/194 (5%), p=0.12.
  • To summarize, overall efficacies for cefazolin and cloxacillin were quite similar, without red flags one way or the other, and confirmatory of a rather large body of observational evidence indicating that cefazolin and anti-staphylococcal penicillins are probably interchangeable. Where cefazolin was clearly better than cloxacillin was safety, with significantly low rates of adverse events and AKI. Given what at this point is a largely theoretical advantage of an anti-staphylococcal penicillin over cefazolin in efficacy, and the clear safety signal favoring the latter, cefazolin may be the better choice for many patients with MSSA bacteremia.

New or Updated Guidelines

Chikungunya Vaccine Update

  • Valneva has voluntarily withdrawn the biologics license application (BLA) and Investigational New Drug (IND) application for its chikungunya vaccine, IXCHIQ, in the United States following suspension of the BLA by the US FDA in August 2025. The vaccine continues to be widely available outside the US.
  • Vimkunya, a non-live recombinant virus-like particle vaccine, was approved by the FDA in February 2025 in persons ≥12 years of age and remains available.

Antimicrobial Stewardship

Antibiotic De-Escalation

  • A newly published target trial emulation study assessed the clinical impact of antibiotic de-escalation in patients with community-onset sepsis. 
  • The study evaluated the de-escalation of anti-MRSA antibiotics and antipseudomonal antibiotics on hospital day 4 in patients who had no evidence of multidrug-resistant organisms. Patients receiving de-escalation were compared to those who received continued broad-spectrum antibiotic therapy for the primary outcome of 90-day mortality. 
  • Based on a weighted analysis, 90-day mortality was similar between groups. There were no differences between the groups in in-hospital mortality, 30-day mortality, the composite of in-hospital mortality or hospice discharge, and Clostridioides difficile infection. 
  • De-escalation of both anti-MRSA and anti-pseudomonal therapy was associated with fewer days of antibiotics and shorter hospital length of stay. Anti-pseudomonal de-escalation was associated with lower 90-day readmission. For patients that were clinically stable, de-escalation of anti-MRSA agents was associated with a lower 90-day mortality. 
  • Antimicrobial stewardship  teams may consider using the data from this study to reinforce guideline recommendations to safely de-escalate antibiotic therapy in patients hospitalized with community-onset sepsis (JAMA Intern Med 2026;186:192).

Antimicrobial Shortages (US)

  • New shortages:
    • Moxifloxacin injection (13 Jan 2026)
  • Resolved shortages:
    • Metronidazole injection (23 Dec 2025)
  • Antimicrobial drugs recently discontinued: 
    • Bezlotoxumab injection (31 Jan 2025, by Merck)
  • Antimicrobial drugs or vaccines in continued reduced supply or unavailable due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons: 
    • Antibacterial drugs:
      • Aminoglycosides:
        • Gentamicin injection (22 Feb 2021)
      • Cephalosporins:
        • Cefazolin injection (4 Jun 2018)
        • Cefdinir, all formulations (29 Jun 2023)
        • Cefotaxime injection (10 Jun 2015)
          • FDA is allowing temporary importation of product from SteriMax in Canada, in conjunction with Provepharm Life Solutions and its distributor Direct Success.
      • Fluoroquinolones:
        • Levofloxacin injection in D5W (29 May 2024)
        • Levofloxacin oral solution, 25 mg/mL (15 Sep 2023)
        • Moxifloxacin 400 mg tablets (6 Dec 2023)
      • Glycopeptides, glycolipopeptides, lipopeptides:
        • Vancomycin injection (1 Jun 2015)
      • Lincosamides:
        • Clindamycin phosphate injection (25 Jun 2015)
      • Macrolides, azalides:
        • Azithromycin injection (6 Jan 2026)
        • Azithromycin oral suspension, 1 gm packets (20 Nov 2024)
        • Erythromycin lactobionate injection (21 Apr 2025)
      • Miscellaneous
        • Bacitracin ophthalmic ointment 500 units/gm (12 Sep 2024)
        • Chloramphenicol injection (9 Oct 2023)
        • Neomycin and Polymyxin B sulfates GU irrigant (25 Jun 2023)
        • Nitrofurantoin oral suspension (5 Jun 2018)
        • Rifaximin 200 mg tablets (11 Apr 2024)
      • Oxazolidinones:
        • Linezolid injection (16 Oct 2024)
      • Penicillins:
        • Amoxicillin, all oral formulations (18 Oct 2022)
        • Amoxicillin-clavulanate, all oral formulations (17 Nov 2022)
        • Dicloxacillin 250 mg, 500 mg capsules (18 Aug 2021)
        • Oxacillin injection (4 Nov 2025)
        • Penicillin G benzathine injection (1 Feb 2023) Availability update
        • Penicillin G benzathine/Penicillin G procaine (31 Mar 2023) Availability update
        • Penicillin VK, all oral formulations (17 May 2023)
    • Antifungal drugs: 
      • Amphotericin B Lipid Complex (5 Aug 2022)
      • Ibrexafungerp 150 mg tablets (3 Dec 2024)
    • Antimycobacterial drugs: 
      • No current shortages
    • Antiparasitic drugs:
      • Nitazoxanide oral susp 100 mg/5 mL (15 Feb 2024)
    • Antiviral drugs: 
      • Acyclovir injection (16 Dec 2025)
      • Oseltamivir, all formulations (1 Nov 2022)
      • Peginterferon alfa-2a (Pegasys) (8 Jan 2025)
      • Ribavirin for inhalation solution (23 May 2023)
  • For more information including estimated resupply dates, see ASHP Drug Shortages website.
  • Data shown are current as of 9 February 2026.
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