How long after completing IV ceftriaxone desensitization should the first therapeutic dose be given?

Comment by InpharmD Researcher

Literature directly addressing the timing of the first therapeutic ceftriaxone dose after intravenous (IV) desensitization is limited and relies largely on institutional protocols. These protocols describe ceftriaxone desensitization as a series of incremental doses administered every 15 minutes, followed by a 15- to 30-minute observation period, after which the full therapeutic dose is given if tolerated. Induced tolerance is temporary and maintained only with uninterrupted dosing, with some data suggesting that interruptions of roughly 24 hours or more generally require repeat desensitization. Overall, available evidence supports administering the first therapeutic ceftriaxone dose promptly after completing the desensitization sequence and the brief observation interval.

PubMed and Google Scholar were searched using combinations of keywords and Medical Subject Headings (MeSH), including ceftriaxone, cephalosporin, desensitization, drug desensitization, and hypersensitivity, combined with timing-related terms such as protocol, dose, therapeutic dose, and observation period. Reference lists of relevant review articles and institutional desensitization protocols were also screened to identify additional primary literature and guideline-based protocols describing post-desensitization dosing timing.

Background

A 2019 review on antimicrobial desensitization describes the process as inducing a temporary state of drug tolerance that reverses within hours to days after discontinuation, requiring repeat desensitization for future courses if therapy is interrupted. For ceftriaxone, the review references an intravenous cephalosporin desensitization protocol using incremental doses administered every 15 minutes, reaching completion in approximately 2 hours and 15 minutes, followed by a 30-minute observation period before administration of the full therapeutic dose. Refer to Table 1 for the full desensitization protocol. [1], [2]

According to a 2023 Baptist Health antibiotic graded dose challenge and desensitization protocol, intravenous ceftriaxone desensitization involves escalating doses administered every 15 minutes, each infused over 15 minutes and followed immediately by the next scheduled dose. After the final desensitization dose, the patient is observed for 15 to 30 minutes; if tolerated, the full therapeutic ceftriaxone dose is administered. The guideline also notes that desensitization induces a temporary state of tolerance that requires continued exposure, and if the antibiotic is not given for more than 24 hours, desensitization must be repeated. Refer to Table 2 for the full desensitization protocol. [3]

A 2019 review evaluated cephalosporin hypersensitivity and management approaches and describes rapid drug desensitization protocols using very low starting doses, typically 1/10,000th to 1/1,000,000th of the target dose, with dose escalation in doubling steps at minimum 15-minute intervals between steps. The review notes that desensitization is performed once for the treatment course, after which subsequent daily cephalosporin doses are administered as standard therapy without repeating the protocol, indicating that continued regular dosing is used to maintain the desensitized state. [4]

References: [1] Chastain DB, Hutzley VJ, Parekh J, Alegro JVG. Antimicrobial Desensitization: A Review of Published Protocols. Pharmacy (Basel). 2019;7(3):112. Published 2019 Aug 9. doi:10.3390/pharmacy7030112
[2] Win PH, Brown H, Zankar A, Ballas ZK, Hussain I. Rapid intravenous cephalosporin desensitization. J Allergy Clin Immunol. 2005;116(1):225-228. doi:10.1016/j.jaci.2005.03.037
[3] Baptist Health. Antimicrobial Stewardship Sub-Committee: Antibiotic graded dose challenge and desensitization guideline. Published June 21, 2023. Accessed February 24, 2026. https://www.baptisthealth.com/-/media/documents/care-and-services/infectious-diseases/antibiotic-gdc-and-desensitization-guideline__6-21-23.pdf?rev=1cfcd610e395423caa8611837969e89b&hash=515A4AC24FF6AD3E4C150496E3C49913
[4] Khan DA, Banerji A, Bernstein JA, et al. Cephalosporin Allergy: Current Understanding and Future Challenges. J Allergy Clin Immunol Pract. 2019;7(7):2105-2114. doi:10.1016/j.jaip.2019.06.001
Literature Review

A search of the published medical literature revealed 2 studies investigating the researchable question:

How long after completing IV ceftriaxone desensitization should the first therapeutic dose be given?

Level of evidence

B - One high-quality study or multiple studies with limitations  Read more→



Please see Tables 1-2 for your response.


Intravenous Cephalosporin Desensitization Protocol

 

Goal Therapeutic Dose – 1 gram IV cephalosporin

Goal Therapeutic Dose – 2 gram IV cephalosporin
Dose Number Dose (mg)

Cumulative Dose (mg)

Dose (mg) Cumulative dose (mg)
1 0.1

0.1

0.1 0.1
2 0.2

0.3

0.4 0.5
3 1.0

1.3

1.0 1.5
4 2.0

3.3

4.0 5.5
5 10.0

13.3

10.0 15.5
6 20.0

33.3

40.0 55.5
7 70.0

103.3

140.0 195.5
8 200.0

303.3

400.0 595.5
9 700.0

1003.3

1400.0 1995.5

Interval between doses was 15 minutes, with a total time of 2 hours and 15 minutes. Observation before the full therapeutic dose is 30 mins. IV cephalosporins used in this protocol included cefazolin, ceftriaxone, and cefepime.

References:
[1] [1] Adapted from: Chastain DB, Hutzley VJ, Parekh J, Alegro JVG. Antimicrobial Desensitization: A Review of Published Protocols. Pharmacy (Basel). 2019;7(3):112. Published 2019 Aug 9. doi:10.3390/pharmacy7030112

IV Ceftriaxone or Cefazolin Desensitization Protocol

Dose Number

Concentration (mg/mL) Volume (mL) Dose (mg) Cumulative Dose (mg)

1

0.01 1.5 0.015 0.015

2

0.01 3 0.03 0.045

3

0.01 6 0.06 0.105

4

0.1 1.25 0.125 0.23

5

0.1 2.5 0.25 0.48

6

0.1 5 0.5 1

7

0.1 10 1 2

8

0.1 20 2 4

9

0.1 40 4 8

10

10 0.75 7.5 15

11

10 1.5 15 30

12

10 3 30 60

13

10 6.25 62.5 123

14

10 12.5 125 250

15

100 2.5 250 500

16

100 5 500 1000

17

100 10 1000 2000
References:
[1] [1] Adapted from: Baptist Health. Antimicrobial Stewardship Sub-Committee: Antibiotic graded dose challenge and desensitization guideline. Published June 21, 2023. Accessed February 24, 2026. https://www.baptisthealth.com/-/media/documents/care-and-services/infectious-diseases/antibiotic-gdc-and-desensitization-guideline__6-21-23.pdf?rev=1cfcd610e395423caa8611837969e89b&hash=515A4AC24FF6AD3E4C150496E3C49913