What literature is there about the use of ceftriaxone as an IV push? Is there evidence of increased reactions with the use of ceftriaxone given IV push versus intermittent infusion? Or is there specific evidence of the safe administration of ceftriaxone as IV push?

Comment by InpharmD Researcher

Available literature evaluating ceftriaxone intravenous (IV) push includes primarily retrospective studies and one small randomized trial of beta-lactam antibiotics in which ceftriaxone was the most common agent. Overall, ceftriaxone IV push was commonly administered over approximately 1 to 5 minutes and was associated with faster administration, operational/cost advantages, and generally low or comparable reported adverse-event rates versus IV piggyback/intermittent infusion in the emergency department (ED), outpatient parenteral antimicrobial therapy (OPAT), and health-system shortage settings. However, the evidence is limited by mostly retrospective designs, small sample sizes, inconsistent reporting of dose/preparation/administration details, and incomplete ceftriaxone-specific safety reporting; one intensive care unit (ICU) retrospective cohort found higher treatment failure with IV push ceftriaxone versus IV piggyback, though safety events were not specifically reported. Thus, available data support that ceftriaxone IV push has been used in practice with a low reported frequency of adverse reactions, but the literature does not definitively establish equivalent safety versus intermittent infusion across all patient populations, particularly critically ill patients.

Background

A 2018 comprehensive review evaluated the literature and clinical considerations regarding intravenous (IV) push administration of antibiotics in adults, including cephalosporins such as cefazolin and ceftriaxone. Cefazolin is FDA-approved for IV push administration, and available literature supports its feasibility when reconstituted with sterile water for injection (e.g., 1–2 g diluted in approximately 10 mL) and administered over short time frames, typically 1–5 minutes depending on the source. Ceftriaxone, while not FDA-approved for IV push administration, has been evaluated in several clinical settings—including emergency departments, outpatient parenteral antimicrobial therapy (OPAT), and hospitalized patients—with studies generally reporting similar rates of phlebitis and other complications compared with short infusions. Evidence describing IV push ceftriaxone administration is somewhat limited by inconsistent reporting of preparation and administration details, though available data have not identified major safety concerns. However, rapid IV administration of certain cephalosporins has been associated with rare adverse events in the literature; for example, very rapid ceftriaxone administration (e.g., 2 g over ~5 minutes) has been associated with symptoms such as palpitations, tachycardia, restlessness, shivering, and diaphoresis in isolated cases. Overall, the literature suggests that cefazolin IV push administration is well supported, while ceftriaxone IV push use remains off-label but has been used in practice with generally comparable safety to short infusions when administered over several minutes. [1]

A 2024 retrospective study conducted across six emergency departments in a large multicenter health system evaluated the impact of implementing intravenous push (IVP) antibiotics—ceftriaxone (1 and 2 grams), cefepime (1 and 2 grams), cefazolin (1 and 2 grams), and meropenem (500 mg)—administered over 3 to 5 minutes, compared with traditional intravenous piggyback (IVPB) formulations. The study included 86 adult patients with a median age of 66 years and a balanced gender distribution, most commonly presenting with pneumonia, urinary tract infections, or sepsis. The primary objective was to compare order-to-administration time between IVP and IVPB, with secondary outcomes assessing cost differences and nursing satisfaction. The study found a significant reduction in order to the start of administration time with IVP (median 31 minutes) versus IVPB (74 minutes), along with substantial monthly cost savings for IVP ceftriaxone, cefepime, and meropenem. No adverse events with IVP administration were reported. Nursing survey data demonstrated high confidence, preference for IVP, and perceived workflow benefit. The study also detailed standardized preparation steps, including instructions for preparing ceftriaxone 1 g by adding 9.6 mL sterile water for injection (SWFI) and withdrawing approximately 10 mL into a syringe, ceftriaxone 2 g by adding 19.2 mL SWFI and withdrawing approximately 20 mL, cefazolin 1 g by adding 9.5 mL SWFI and withdrawing approximately 10 mL, and cefazolin 2 g using two 1-g vials each reconstituted with 9.5 mL SWFI and combined into a single syringe (approximately 20 mL total). Overall, IVP antibiotics significantly improved administration efficiency, reduced costs, and were well accepted by staff, supporting expanded adoption of IVP antibiotic protocols in emergency departments. See Table 4 for additional study details. [2]

A 2019 retrospective analysis, published as an abstract, assessed the safety and efficacy of transitioning from intermittent intravenous (IV) infusion to slow IV push administration of cefepime, ceftriaxone, and meropenem. A total of 108 patients were included in the analysis specifically evaluating clinical improvement, with 57 patients in the intermittent IV infusion group and 51 in the slow IV push group. Dosing of the included antibiotics were not reported. Notably, the analysis revealed no significant differences between the intermittent IV infusion and slow IV push groups in terms of clinical improvement 48 hours after antibiotic initiation (43.3% vs. 47.8%; p= 0.79), antibiotic duration (6.07+2.90 days vs. 5.57+2.52 days; p= 0.34), peripherally inserted central catheter or midline placement (59.6% vs. 47.1%; p= 0.25), or death (1.8% vs. 3.9%; p= 0.60). These results suggest that transitioning from intermittent IV infusion to slow IV push administration of cefepime, ceftriaxone, and meropenem did not yield statistically significant differences in the assessed endpoints, indicating comparable outcomes between the two administration methods. However, it is important to note that only the abstract of this study was available for scrutiny. [3]

Another retrospective study, published in 2021 as an abstract, evaluated the administration of ceftriaxone, cefepime, or cefazolin via IV push versus IVPB. A total of 366 treatment episodes were evaluated for 355 unique patients. Similarly, the doses of ceftriaxone, cefepime, and cefazolin were not reported within the published abstract. In the IVP group, complications occurred in 13 of 183 treatment episodes (7.1%) compared to 18 of 183 (9.8%) in the IVPB group (p= 0.35). For both groups, the median time for complications was two days. The median time to the first dose of vancomycin in the ED was 25 minutes shorter with IVP cefepime and ceftriaxone. Additionally, the use of cefazolin, ceftriaxone, and cefepime as IV push yielded quarterly cost savings of $38,890.04. Notably, 55% of nursing staff and 85% of pharmacy staff preferred IV push administration for cefazolin, ceftriaxone, and cefepime. Overall, cefazolin, ceftriaxone, and cefepime administered as IVP were found to be as safe as IVPB while lowering the time to the first dose of vancomycin in the ED and cost; efficacy evaluations were not within the scope of this study. [4]

A recent retrospective study, also published as an abstract, compared the rate of treatment failure in obese (n= 206) and non-obese (n= 187) intensive care unit patients receiving IV push and IV piggyback (IVPB) ceftriaxone. The primary outcome, treatment failure, was defined as a composite of antibiotic escalation and all-cause mortality. Among the included non-obese and obese patients, 47% and 55% received IV push ceftriaxone, respectively. The specific dose of ceftriaxone was also not reported within this published abstract. The primary outcome of treatment failure showed no significant difference between non-obese and obese patients (28% vs. 30%; p= 0.696). Additionally, subgroup analyses based on the administration method revealed no significant differences (IV push: non-obese 38% vs. obese 38%; p= 0.967; IVPB: non-obese 19% vs. obese 20%; p= 0.866). Notably, secondary outcomes encompassing the individual components of the composite outcome, costs of therapy, and length of stay also did not exhibit any significant differences. Overall, these findings suggest that obesity did not contribute to worse outcomes with either IV push or IVPB administration. However, given that only the abstract was available, a comprehensive analysis of the study could not be conducted. [5]

A 2020 publication, presented findings from a retrospective chart analysis exploring the effects of ceftriaxone administered by intravenous push (IVP) on adverse drug reactions within an emergency department setting. The analysis included adult patients, 18 years and older, who received ceftriaxone between January and March 2018. Due to a critical shortage of saline bags following Hurricane Maria, ceftriaxone administration was transitioned from the traditional intravenous infusion (IVI) to IVP. Ceftriaxone was provided in 1 g/10 ml vials that were reconstituted in 10 ml of sterile water for injection and Internal nursing guidelines recommend pushing over 1–2 minutes. Research assistants meticulously extracted relevant data from patient records, focusing on demographics, antibiotic administration details, and any recorded adverse reactions. The study's primary outcome was the rate of adverse reactions associated with the IVP method. Among the 831 encounters initially identified, 753 were deemed valid for analysis after excluding those with missing or erroneous data. The 2020 analysis revealed that only one adverse reaction was definitively linked to ceftriaxone administered via IVP, resulting in a notably low adverse event rate of 0.13%. This singular case involved a patient reporting vomiting shortly after the administration of the antibiotic, as confirmed by an ADR probability scale and the consensus of a panel of emergency medicine clinicians. These findings pointed towards significant implications for ED practices, advocating for the continued use of IVP even after the saline bag shortage had abated. [6]

Relevant Prescribing Information

For intramuscular injection of cefazolin by Sandoz Inc., intravenous direct (bolus) injection or intravenous infusion, reconstitute with Sterile Water for Injection. Direct (bolus) injection: Following reconstitution according to the above table, further dilute vials with approximately 5 mL Sterile Water for Injection. Inject the solution slowly over 3 to 5 minutes, directly or through tubing for patients receiving parenteral fluids. This includes cefazolin 500 mg diluted in 2 mL. [7]

For intravenous bolus injection of cefazolin 2 g by Hikma Pharmaceuticals, For 2 g dose, inject the solution intravenously slowly over 7 to 11 minutes. [8]

Literature Review

A search of the published medical literature revealed 9 studies investigating the researchable question:

Level of evidence

C - Multiple studies with limitations or conflicting results Read more→

Please see Tables 1-9 for your response.

Effect of Intravenous Push and Piggyback Administration of Ceftriaxone on Mortality in Sepsis
Design	Retrospective analysis N= 939
Objective	To compare the effects of administering ceftriaxone via intravenous push (IVP) and intravenous piggyback (IVPB) on 28-day mortality in patients with sepsis
Study Groups	IVP (n= 299) IVPB (n= 640)
Inclusion Criteria	Adults with sepsis or septic shock who visited an emergency department (ED) and were treated with ceftriaxone as an initial antibiotic
Exclusion Criteria	Patients who had not received ceftriaxone initially, pregnant women, patients who refused life-sustaining treatment, patients with missing data, and patients who were transferred from other medical institutions because their history of antibiotic administration could not be confirmed.
Methods	Patients were treated according to the Surviving Sepsis Campaign guidelines. Administration of medications such as vasoactive agents, corticosteroids, and insulin was based on the discretion of the attending physician. In the IVP group, ceftriaxone was mixed in 10-20 mL of 0.9% sodium chloride injection and given over 2-4 minutes.
Duration	Between March 2010 and February 2019.
Outcome Measures	If the primary outcome measure isn’t explicit from the study, all outcome measures applicable to the inquiry can be listed in this section. If the primary outcome measure is explicit, then make separate sections for ‘Primary’ and ‘Secondary’ Outcome Measures. The administration method was determined according to the preference of the physician. In the IVP group, ceftriaxone in vials was mixed in 10 to 20 ml of 0.9% sodium chloride for injection over 2 to 4 minutes. The IVPB group received ceftriaxone either by mixing with 50 ml normal saline or using a premixed form, typically needed approximately 30 minutes The initial administration of antibiotics within 1 hour and within 3 hours was delineated.
Baseline Characteristics		IVP (n= 299)	IVPB (n= 640)	p-Value
	Age, years (IQR)	72.0 (64.5-78.0)	74.0 (66.0-80.0)	0.052
	Male	174 (58.2%)	367 (57.3%)	0.861
	BMI, kg/m² (IQR)	22.4 (19.3-25.2)	22.4 (19.6-24.9)	0.732
	Comorbidity Hypertension Diabetes mellitus Chronic liver disease Chronic heart failure Chronic lung disease Chronic renal failure Malignancy	133 (44.5%) 99 (33.1%) 20 (6.7%) 19 (6.4%) 33 (11.0%) 29 (9.7%) 108 (36.1%)	314 (49.1%) 230 (35.9%) 37 (5.8%) 22 (3.4%) 71 (11.1%) 57 (8.9%) 237 (37.0%)	0.215 0.440 0.692 0.062 1.000 0.786 0.844
	Initial vital sign (IQR) Systolic blood pressure, mmHg Heart rate, beat/min Respiratory rate, breath/min Temperature, ℃	103.0 (84.5-127.0) 111.0 (92.5-128.0) 20.0 (18.0-25.0) 37.9 (36.9-38.8)	89.0 (79.0-116.0) 103.0 (86.5-119.5) 21.0 (18.0-25.0) 37.7 (36.7-38.6)	<0.001 <0.001 0.727 0.059
	Initial laboratory finding (IQR) White blood cell, x10³/μL Hemoglobin, g/dL Platelet, x10³/μL Creatinine, mg/dL Albumin, g/dL C-reactive protein, mg/dL Lactate, mmol/L	11.4 (7.0-17.1) 12.0 (10.6-13.4) 167.0 (113.5-238.5) 1.4 (0.9-2.1) 3.4 (3.0-3.8) 15.7 (5.9-23.0) 3.5 (2.0-5.5)	11.3 (7.0-16.3) 11.9 (10.3-13.5) 169.0 (113.0-237.5) 1.4 (1.0-2.2) 3.3 (2.8-3.7) 12.8 (5.6-20.0) 2.6 (1.6-4.5)	0.560 0.557 0.804 0.687 0.003 0.025 <0.001
	Infection site Pulmonary Genitourinary Intra-abdominal Other	98 (32.8%) 66 (22.1%) 108 (36.1%) 27 (9.0%)	237 (37.0%) 143 (22.3%) 208 (32.5%) 52 (8.1%)	0.232 0.993 0.308 0.734
	Initial SOFA score (IQR)	7.0 (5.0-9.5)	6.0 (5.0-8.0)	0.025
	Abbreviations: BMI= body mass index; IQR= interquartile range
Results	Endpoint	IVP (n= 299)	IVPB (n= 640)	p-Value
	28-day mortality	38 (12.7%)	77 (12.0%)	0.851
	Antibiotics Administration time, min Administration within 1hr Administration within 3hr	160.0 (100.0-242.5) 19 (6.4%) 178 (59.5%)	186.5 (129.0-256.0) 15 (2.3%) 300 (46.9%)	<0.001 0.004 <0.001
	Allergic reaction	1 (0.3%)	0 (0.0%)	0.697
	Appropriate antibiotics	220 (73.6%)	507 (79.2%)	0.065
	Septic shock	180 (60.2%)	366 (57.2%)	0.423
	ICU admission	88 (29.4%)	188 (29.4%)	1.000
Adverse Events	See Results
Study Author Conclusions	IVP administration of ceftriaxone reduced the time of antibiotic administration compared to IVPB, but there was no difference in 28-day mortality.
Critique	The data presented only represents a single institution's retrospective experience, and notably, the study found no significant difference in 28-day mortality between the two groups. The authors noted that 61.9% of subjects were administered ceftriaxone with other antibiotics and thus could not evaluate the effect of antibiotic combination therapy, which may have influenced the results.

Table 1 References:
[9] Lim SY, Baek S, Jo YH, et al. Effect of Intravenous Push and Piggyback Administration of Ceftriaxone on Mortality in Sepsis. J Emerg Med. 2024;66(5):e632-e641. doi:10.1016/j.jemermed.2023.12.008

Safety of intravenous push administration of beta-lactams within a healthcare system
Design	Retrospective observational cohort study N= 1,000
Objective	To evaluate the safety of intravenous push (IVP) administration of select beta-lactam antibiotics
Study Groups	Aztreonam (n= 43) Ceftriaxone (n= 544) Cefepime (n= 368) Meropenem (n= 45)
Inclusion Criteria	18 years of age or older and received at least two doses of IVP aztreonam, ceftriaxone, cefepime, or meropenem within the specified period
Exclusion Criteria	Received IVP antibiotics for surgical prophylaxis, pregnancy, received more than one IVP antibiotic on the same day
Methods	A medication shortage of small-volume parenteral solutions prompted hospital-wide implementation of a mandatory intravenous push (IVP) antibiotic action plan. A retrospective review of electronic health records (EHR) was conducted to identify eligible patients based on chart data from the implementation period. Although IVP formulations were incorporated into the EHR as standard ordering options, exceptions to IVP administration were permitted with approval from a clinical pharmacy manager. Antibiotics were supplied either as vials in automated dispensing cabinets for nurse reconstitution or as pharmacy-compounded preparations. Medication orders included standardized instructions for reconstitution and manual administration as a slow IV push over approximately 5 minutes. The study evaluated use of multiple antibiotics administered via IVP, including ceftriaxone (1 and 2 g), cefepime (1 and 2 g), meropenem (500 mg and 1 g), aztreonam (1 and 2 g), daptomycin (500 mg), and oxacillin (1 and 2 g).
Duration	October to December 2017
Outcome Measures	Incidence of adverse events (ADE)
Baseline Characteristics		All patients (N= 1,000)
	Median age, years	70 (56 to 83)
	Female	55%
	Body mass index, kg/m²	26 (22 to 30)
	Kidney function Creatinine clearance, mL/min Dialysis	57 (33 to 88) 34 (3%)
	Seizure history	64 (6%)
	History of a medication allergic reaction Concomitant corticosteroid use Concomitant antihistamine use	379 (38%) 149 (15%) 199 (20%)
	Anticoagulation (treatment or prophylaxis)	82%
	Most common indications Pneumonia Urinary tract infection Intra-abdominal infection Skin/soft tissue infection	310 (31%) 275 (28%) 194 (19%) 57 (6%)
	Antibiotic therapy Ceftriaxone Q12H Q24H Cefepime Q8H Q12H Q24H Meropenem Q6H Q8H Q12H Q24H Aztreonam Q8H Q12H Q24H	544 (54%) 13 (2%) 531 (98%) 368 (37%) 282 (77%) 61 (17%) 25 (7%) 45 (5%) 12 (27%) 17 (38%) 10 (22%) 6 (13%) 43 (4%) 38 (88%) 4 (9%) 1 (2%)
Results	Adverse reactions	Incidence
	Ceftriaxone Allergic reactions, n Rash Hives Reaction with eosinophilia and systemic symptoms Phlebitis, n	1 1 1 1
	Cefepime Allergic reactions, n Rash Neurotoxicity, n	2 4
	A total of 10 adverse events were reported including allergic reactions, however, allergic reactions were not correlated with IVP administration. The phlebitis adverse reaction occurred due to the infiltration of a 20-gauge antecubital peripheral venous line after 6 doses of ceftriaxone IVP resulting in a grade 2 reaction. The line was changed and ceftriaxone IVP was continued without further ADEs.
Adverse Events	See Results
Study Author Conclusions	The use of IVP as an alternative to intravenous piggyback (IVPB) over 30 minutes during times of drug shortage for select beta-lactam antibiotics appears to be safe, and ADE are similar to those previously described for IVPB administration. Future studies evaluating clinical outcomes between IVP and IVPB administration may be of benefit.
Critique	The study is limited by its retrospective observational design which may be a source of recall bias. There was no direct comparison to an IVPB group for safety and efficacy. The IVP administration over 5 minutes was done manually which could have led to variation in the true administration rate.

Table 2 References:
[10] Marsh K, Ahmed N, Decano A, et al. Safety of intravenous push administration of beta-lactams within a healthcare system. Am J Health Syst Pharm. 2020;77(9):701-708. doi:10.1093/ajhp/zxaa044

Intravenous Push Cephalosporin Antibiotics in the Emergency Department
Design	Practice improvement project, retrospective review N= 2,256
Objective	To determine whether the implementation of an intravenous push (IVP) cephalosporin antibiotic protocol would improve time from provider order to administration for all emergency department (ED) patients who were ordered a cephalosporin antibiotic
Study Groups	Preintervention arm (intravenous piggyback [IVPB]) (n= 1,146) Postintervention arm (IVP) (n= 1,110)
Inclusion Criteria	Received IV cephalosporins either by 30 min IV infusion or 2-5 min IVP
Exclusion Criteria	Received antibiotics prior to arrival to ED (i.e., transferred from another facility)
Methods	An interprofessional team designed an IVP cephalosporin antibiotic protocol which allowed providers to order the cephalosporin class of antibiotics including 1 and 2 grams of cefazolin, cefepime, ceftriaxone, and ceftazidime via the IVP route for the first dose. IVP medication kits that included the antibiotic plus the diluent were added to the automated medication dispensing system. The electronic medical record was searched to identify patients who presented to the ED and were given an IV cephalosporin antibiotic for any indication in the preintervention and postintervention period. All patients who received IV cephalosporins by infusion over 30 min were included in the preintervention group; the postintervention group included patients who received IVP antibiotic over 2-5 min.
Duration	Preintervention: November 1, 2015 to January 31, 2016 Postintervention: March 1, 2016 to May 30, 2016
Outcome Measures	Primary: time from order to cephalosporin administration Secondary: crude in-hospital mortality (subgroup analysis of patients with sepsis); cost analysis for supplies associated with cephalosporin administration
Baseline Characteristics		Preintervention (n= 1,146)	Postintervention (n= 1,110)
	Sepsis, n	458 (40%)	637 (57%)
Results	Endpoint	Preintervention (n= 1,146)	Postintervention (n= 1,110)	p-Value
	Median time from order to administration, min (IQR) Ceftriaxone, min Ceftazidime, min Cefepime, min Cefazolin, min	31 (18-49) 42 (26-63) 42 (29-65) 30 (17-49)	23 (12-42) 30 (15-52) 28 (17-46) 17 (7-35)	< 0.0001 0.0064 < 0.0001 0.0007
	In-hospital mortality (subgroup)	7.21%	7.06%	0.9
	IQR: interquartile range Cost of infusion supplies: almost 11.5 times higher for IVPB ($9.53) vs. IVP ($0.83); approximately $10,000 in savings to the institution in a 3-month period and $40,000 annually 87% of nurses favored switching to IVP administration
Adverse Events	No reports of adverse effects regarding IVP antibiotics were filed during the study period
Study Author Conclusions	Administering the first dose of cephalosporin antibiotic as an IVP instead of an IV infusion resulted in faster treatment times for patients. Adverse effects and crude mortality were not different between the two groups. In addition, cost savings were realized and nursing time was decreased.
Critique	The study is limited by its single-center, retrospective design. Baseline demographics were not reported in the study, limiting the evaluation of any differences between groups. The only efficacy outcome evaluated was in-hospital mortality. Only patients who received the first dose were included, and subsequent doses or antibiotic therapy after the first dose were not included or evaluated, limiting the association of the effect of IVP administration on mortality in the subgroup analysis.

Table 3 References:
[11] McLaughlin JM, Scott RA, Koenig SL, Mueller SW. Intravenous Push Cephalosporin Antibiotics in the Emergency Department: A Practice Improvement Project. Adv Emerg Nurs J. 2017;39(4):295-299. doi:10.1097/TME.0000000000000160

Intravenous push antibiotics in the emergency department: Education and implementation
Design	Retrospective study conducted at a multifacility healthcare system with over 1,250 licensed hospital beds N= 86
Objective	To determine whether intravenous push antibiotics could decrease the time from an order to the start of administration compared to piggyback antibiotics in emergency departments, measure the cost savings of antibiotic preparation and administration, and assess nursing satisfaction when using intravenous push antibiotics
Study Groups	IVP group (n= 43) IVPB group (n= 43)
Inclusion Criteria	Patients 18 years of age or older who received at least a single dose of intravenous push or piggyback ceftriaxone, cefepime, cefazolin, or meropenem in one of the institution’s emergency departments
Exclusion Criteria	Patients <18 years old, antibiotic administration occurred outside the institution’s EDs, dose was discontinued, or the antibiotic dose or administration route was incorrect
Methods	IVP antibiotic order sets were created, including a one-time IVP dose followed by use of IVPB. Preparation and administration instructions were provided. Ceftriaxone (1 and 2 grams), cefepime (1 and 2 grams), cefazolin (1 and 2 grams), and meropenem (500 mg) were administered over 3 to 5 minutes. Pharmacists verified orders, and nurses prepared, administered, and charted administration. Data collection included age, gender, ED, time of admission, diagnosis, antibiotic, dose, preparation, location, order time, pharmacy verification time, administration start time, and cost per dose
Duration	IVPB group: January 2022 IVP group: November 15 to December 31, 2022
Outcome Measures	Primary: Time from order to start of administration of IVP vs IVPB antibiotics Secondary: Cost of IVP and IVPB antibiotic preparation
Baseline Characteristics		IVP (n= 43)	IVPB (n= 43)
	Age, years	66 (55-84)	70 (49-76)
	Female	26 (60%)	22 (51%)
	Diagnosis Pneumonia Diabetic foot infection Sepsis Urinary tract infection Intrabdominal infection Cellulitis	13 (30%) 3 (7%) 7 (16%) 12 (28%) 2 (5%) 2 (5%)	15 (35%) 3 (7%) 7 (16%) 8 (19%) 0 1 (2%)
Results		IVP (n= 43)	IVPB (n= 43)	p-value
	Time from order to start of administration, median (IQR), minutes	31 (21-52)	74 (29-114)	0.003
Adverse Events	No specific adverse events were reported in the study
Study Author Conclusions	Intravenous push antibiotics decrease the time from ordering to the start of administration and result in significant cost savings. Encouraging institutions to implement additional IVP antibiotic protocols will enhance time and cost savings as well as optimize patient care.
Critique	The study's strengths include its inclusion of multiple facilities and relevant objectives based on sepsis guidelines. However, limitations include the retrospective design, potential selection and performance bias due to the small sample size, and the impact of IVPB fluid shortages on results. Additionally, the study only included fall/winter months, which may not represent other seasons.

Table 4 References:
[12] Brady RE, Giordullo EL, Harvey CA, Krabacher ND, Penick AM. Intravenous push antibiotics in the emergency department: Education and implementation. Am J Health Syst Pharm. 2024;81(12):531-538. doi:10.1093/ajhp/zxae039

Implementation of IV Push Antibiotics for Outpatients During a National Fluid Shortage Following Hurricane Maria
Design	Retrospective study N= 218
Objective	To evaluate the implementation of IV push antibiotics as an alternative to IV drip infusion during a national fluid shortage and assess its impact on efficiency, cost, and patient outcomes
Study Groups	IVP group (n= 113) IV drip group (n= 102)
Inclusion Criteria	Patients discharged to the OPAT clinic using all methods of parenteral drug delivery from November 2016 to June 2018
Exclusion Criteria	Not specified
Methods	Parkland pharmacists evaluated self-administered antimicrobials for IVP viability. Cefazolin, ceftriaxone, cefepime, and daptomycin were transitioned to IVP. Data on patient demographics, satisfaction, clinical outcomes, and cost were collected. Statistical analysis was performed using SPSS. The rate of IV push was administered over 5 to 10 minutes. Antibiotic doses were not provided.
Duration	November 2016 to June 2018
Outcome Measures	Primary: Hospital length of stay, patient satisfaction, cost savings Secondary: 30-day readmission rate, mortality
Baseline Characteristics		Pre (n= 95)	Post (n= 105)
	Male	75 (79%)	82 (78%)
	Race/ethnicity White Non-Hispanic Black Non-Hispanic Hispanic Other	15 (16%) 11 (12%) 68 (72%) 1 (1%)	18 (17%) 11 (10%) 72 (69%) 4 (4%)
	Payor group - Charity/self-pay	93 (98%)	101 (96%)
	Diabetic	72 (76%)	71 (68%)
	Age, years	47 ± 13	51 ± 12
	BMI, kg/m²	28.6 (25.3–32.6)	27.4 (24.1–32.9)
	Antibiotic Cefazolin Ceftriaxone Daptomycin Cefepime	5 (5%) 41 (43%) 52 (55%) 0 (0%)	14 (13%) 51 (49%) 41 (39%) 4 (4%)
Results		Pre (n= 95)	Post (n= 105)	p-value
	Hospital length of stay before S-OPAT visit, d	12 (9–17)	11 (8–15)	0.03
	All-cause readmission rate within 30 d of S-OPAT visit	10 (11%)	11 (11%)	0.99
	All-cause readmission rate within 1 y of S-OPAT visit	31 (33%)	35 (33%)	0.92
	ED visit within 30 d of S-OPAT visit	21 (22%)	25 (24%)	0.78
	ED visit within 1 y of S-OPAT visit	42 (44%)	45 (43%)	0.85
	CLABSI	0 (0%)	0 (0%)	-
	Mortality	4 (4%)	7 (6%)	0.75
	Abbreviations: CLABSI, central line–associated bloodstream infection; ED, emergency department; IV, intravenous; S-OPAT, self-administered outpatient parenteral antimicrobial therapy
Adverse Events	No central line bloodstream infection in either group
Study Author Conclusions	The implementation of IV push antibiotics during a fluid shortage improved efficiency, reduced costs, and maintained safety and efficacy. The IV push model is a viable alternative to standard IV drip infusion, providing high-value care.
Critique	The study effectively demonstrated cost savings and improved efficiency with the IV push method. However, the retrospective design and focus on a single institution may limit the generalizability of the findings. Additionally, the study did not explore long-term outcomes beyond the immediate post-discharge period.

Table 5 References:
[13] Yagnik KJ, Brown LS, Saad HA, et al. Implementation of IV Push Antibiotics for Outpatients During a National Fluid Shortage Following Hurricane Maria. Open Forum Infect Dis. 2022;9(5):ofac117. Published 2022 Mar 21. doi:10.1093/ofid/ofac117

Evaluation of the Efficacy of Intravenous Push and Intravenous Piggyback Ceftriaxone in Critically Ill Patients
Design	Single-center, retrospective cohort study N= 401
Objective	To compare the safety and efficacy of intravenous push (IVP) and intravenous piggyback (IVPB) ceftriaxone in critically ill patients
Study Groups	IVP (n= 201) IVPB (n= 200)
Inclusion Criteria	Adults admitted to an ICU from 2016 to 2021 who received empiric ceftriaxone for ≥72 h
Exclusion Criteria	Receipt of both IVP and IVPB ceftriaxone, pregnancy
Methods	Retrospective analysis of adults in ICU receiving ceftriaxone for ≥72 h. IVPB administration from March 2016 to April 2018, IVP from May 2018 to January 2021. Primary outcome was treatment failure, defined as inpatient mortality or escalation of antibiotics. Secondary outcomes included length of stay and mortality. Chi-squared and independent-sample t-tests were used. Multivariate logistic regression evaluated treatment failure.
Duration	March 2016 to January 2021
Outcome Measures	Primary: Treatment failure (inpatient mortality or escalation of antibiotics) Secondary: Length of stay (LOS), mortality
Baseline Characteristics		IVP (n= 201)	IVPB (n= 200)	p-value
	Age, years	61.7 ± 13.8	60.5 ± 16.3	0.458
	Female	85 (42.3%)	92 (46%)	0.454
	Body mass index, kg/m²	31.6 ± 9.4	30.6 ± 10.4	0.311
	SCr, mg/dL	1.7 ± 1.7	1.8 ± 1.7	0.951
	CrCl, mL/min at initiation	94.3 ± 75.3	86.7 ± 70.7	0.302
	Race African American Caucasian	55 (27.4%) 141 (70.1%)	43 (21.5%) 148 (74%)	0.437 - -
	Organ dysfunction SOFA score Sepsis Septic shock	6.4 ± 3.5 113 (56.2%) 59 (29.4%)	5.4 ± 2.9 61 (30.5%) 21 (10.5%)	0.002 <0.001 <0.001
	Source of Infection Respiratory Intra-abdominal/SBP prophylaxis Urinary tract infection Severe infection^† Other/unknown	107 (53.2%) 21 (10.4%) 27 (13.4%) 22 (10.9%) 24 (11.9%)	80 (40.0%) 16 (8.0%) 47 (23.5%) 25 (12.5%) 32 (16.0%)	0.023 - - - - -
	Interventions Duration of ceftriaxone, days Average daily dose, g Duration of antibiotic(s), days	5.8 ± 2.4 1.33 ± 0.49 10.3 ± 6.2	5.9 ± 3.5 1.40 ± 0.91 9.9 ± 5.9	0.726 0.335 0.538
	^† Severe infection = meningitis, endocarditis, pericarditis, or osteomyelitis. IVPB = intravenous piggyback; IVP = intravenous push; SOFA = Sequential Organ Failure Assessment; SCr = serum creatinine; CrCl = creatinine clearance; SBP = spontaneous bacterial peritonitis.
Results		IVP (n= 201)	IVPB (n= 200)	p-value
	Treatment failure	76 (37.8%)	39 (19.5%)	<0.001
	Escalation of therapy	51 (25.4%)	23 (11.5%)	<0.001
	All-cause hospital mortality	43 (21.4%)	19 (9.5%)	<0.001
	All-cause ICU mortality	35 (17.4%)	18 (9.0%)	0.013
	ICU length of stay, days	10.3 ± 9.2	9 ± 8	0.143
	Hospital length of stay, days	18.6 ± 16.8	14.9 ± 10.2	0.009
Adverse Events	Not specifically provided
Study Author Conclusions	Compared to IVPB, IVP ceftriaxone was associated with higher treatment failure in critically ill patients. Both safety and efficacy should be considered before implementing novel antibiotic administration strategies in practice based primarily on convenience.
Critique	The study's retrospective, single-center design and the higher incidence of sepsis and septic shock in the IVP group are limitations. The lack of demographic diversity and potential confounding variables such as comorbidities and concomitant medications were not collected. Despite these limitations, the study suggests a possible benefit with IVPB administration of ceftriaxone in ICU patients.

Table 6 References:
[14] Sherman ER, Ta NH, Branan TN, et al. Evaluation of the Efficacy of Intravenous Push and Intravenous Piggyback Ceftriaxone in Critically Ill Patients. Antibiotics (Basel). 2024;13(10):921. Published 2024 Sep 26. doi:10.3390/antibiotics13100921

The Effects of Ceftriaxone by Intravenous Push on Adverse Drug Reactions in the Emergency Department
Design	Retrospective chart analysis N= 753
Objective	To explore the switch from intravenous infusion (IVI) to intravenous push (IVP) in adult patients admitted to the emergency department
Study Groups	Study patients (N= 753)
Inclusion Criteria	Age 18 years or older, administered ceftriaxone by IVP in the emergency department
Exclusion Criteria	N/A
Methods	Data were collected from a single institution where ceftriaxone 1 g/10 mL was reconstituted in 10 mL of sterile water for injection then pushed over 1-2 minutes per internal nursing guidelines. Adverse events were defined as any noxious or unintended response to a drug given at therapeutic dose. Adverse drug reactions were assessed using the Naranjo ADR likelihood scale.
Duration	January 2018 to March 2018
Outcome Measures	Potential adverse event, possibly related to ceftriaxone
Baseline Characteristics		Study patients (N= 753)
	Age, years	52.8
	Female	54.2%
	Race Black White Other Asian/Pacific islander American Indian/Native Alaskan	41.5% 38.6% 14.1% 3.1% 2.5%
	Hispanic ethnicity	45.3%
Results	Endpoint	Study patients (N= 753)
	Potential adverse reactions Pneumonia Urinary tract infection	24 8 5
	Possibly related to ceftriaxone	1*
	*Patient developed vomiting soon after ceftriaxone was administered. Only ceftriaxone was administered and there were no prior documentation of nausea or vomiting.
Study Author Conclusions	Our study demonstrates that the rate of adverse reactions for IVP is lower than previously reported. Given the demonstrated safety of IVP administration, future studies are warranted to determine the implications for ED efficiency and cost benefits from this change in drug delivery.
InpharmD Researcher Critique	The study lacked a comparison between IVP and IV piggyback administration of ceftriaxone. While only one adverse event was deemed possibly related to IVP of ceftriaxone, an adequately powered comparison study is needed to support these findings.

Table 7 References:
[15] Agunbiade A, Routsolias JC, Rizvanolli L, Bleifuss W, Sundaresan S, Moskoff J. The effects of ceftriaxone by intravenous push on adverse drug reactions in the emergency department. Am J Emerg Med. 2021;43:245-248. doi:10.1016/j.ajem.2020.03.022

Antibiotics Administered via Intravenous Push Versus Intravenous Piggyback to Adult Patients in the Emergency Department: a Randomized Trial
Design	Single-center, double-blinded, double-dummy, randomized controlled trial N= 71
Objective	To compare the safety and efficacy of intravenous (IV) push to intravenous piggyback (IVPB) antibiotics in emergency department (ED) patients
Study Groups	IV push (n= 37) IVPB (n= 34)
Inclusion Criteria	Patients aged 18 years or older who presented to the ED and for whom an IV β-lactam antibiotic was ordered, including aztreonam, cefazolin, cefoxitin, ceftriaxone, cefepime, ertapenem, or meropenem
Exclusion Criteria	Pregnant, breastfeeding, non-English-speaking, unable to provide consent, prisoners, or history of an adverse reaction to the ordered antibiotic
Methods	Patients were randomized 1:1 to receive the ordered β-lactam antibiotic by either IV push or IVPB. A double-dummy design was used: patients in the IV push group also received IVPB placebo with 50 mL 0.9% sodium chloride, and patients in the IVPB group also received IV push placebo with 10 mL 0.9% sodium chloride. Only study pharmacists had access to randomization assignments; treating clinicians and research assistants assessing outcomes were blinded. IV push antibiotics were administered by syringe over 2–3 minutes, while IVPB antibiotics were infused over 30 minutes by infusion pump. The syringe and IVPB were administered at the same time. Patients completed symptom surveys immediately before antibiotic administration and every 15 minutes for 90 minutes after administration to identify possible adverse drug reactions (ADRs). Any new symptom during the 90-minute observation period was considered a possible ADR and was graded by the treating physician on a 1-to-5 severity scale adapted from the Common Terminology Criteria for Adverse Events. Baseline characteristics and clinical outcomes were collected by research assistants using chart review.
Duration	April 2018 to June 2019
Outcome Measures	Primary: Percentage of patients experiencing a possible ADR within 90 minutes Secondary: Hospital length of stay, severity of ADRs, types of adverse reactions, ED disposition, in-hospital mortality
Baseline Characteristics		IVPB (n= 34)	IV push (n= 37)
	Median age in years (IQR)	45.5 (31.5 to 59.3)	52 (31 to 65)
	Female	20 (58.8%)	16 (43.2%)
	Median weight in kg (IQR)	78.4 (68.2 to 95.2)	72.7 (65.9 to 84.6)
	No known drug allergies	18 (52.9%)	22 (59.5%)
	Antibiotic received Ceftriaxone Cefepime Cefazolin Cefoxitin Ertapenem Meropenem Aztreonam	22 (64.7%) 7 (20.6%) 0 1 (2.9%) 0 3 (8.8%) 1 (2.9%)	25 (67.6%) 6 (16.2%) 1 (2.7%) 0 1 (2.7%) 4 (10.8%) 0
	Median lowest SBP, mmHg (IQR)	120 (109.2 to 132.5)	122.5 (112 to 138.2)
	Median initial lactate, mmol/L (IQR)	1.06 (0.96 to 1.47)	1.11 (1.00 to 1.82)
	Other medication administered	17 (50%)	18 (48.6%)
	Abbreviations: IQR, interquartile range.
Results		IVPB (n= 34)	IV push (n= 37)	Difference (95% CI)
	Any possible ADR within 90 minutes	4 (11.8%)	7 (18.9%)	7.1% (−9.5 to 23.8%)
	Possible ADR grades Grade 1 Grade 2 Grade 3 or higher	4 (11.8%) 0 0	5 (13.5%) 2 (5.4%) 0	1.7% (−17.2 to 13.7%) 5.4% (−1.9 to 12.7%) -
	Admitted to the hospital	31 (91.2%)	30 (81.1%)	10.1% (−5.7 to 25.9%)
	Median hospital length of stay, hours (IQR)	68.1 (42.1 to 121)	68.6 (25.3 to 122)	0.5 (−30.8 to 45.1)
	In-hospital deaths	0	1 (2.7%)	2.7% (−2.5 to 7.9%)
Adverse Events	There were no statistically significant differences in ADRs between IV push and IVPB antibiotic administration. However, there was a signal of harm in the IV push group, with 18.9% experiencing possible ADRs compared to 11.8% in the IVPB group. Two patients in the IV push group had grade 2 reactions, and one patient died in the IV push group.
Study Author Conclusions	In this double-blinded, double-dummy, randomized trial, we found no statistically significant difference in the rates of adverse drug reactions in patients who received β-lactam antibiotics by IV push as compared to IVPB, but our sample size was too small to draw conclusions about safety. There was a signal of increased adverse events in the IV push group, which should be further explored in a larger randomized trial. We found no reduction in hospital length of stay or other evidence of improved outcomes in patients who received IV push antibiotics as compared to IVPB.
Critique	This randomized, double-blinded, double-dummy trial directly compared IV push versus IVPB β-lactam administration in adult ED patients with active infections, making it highly relevant to the inquiry; however, ceftriaxone represented only a subset of antibiotics administered, and results were not reported separately for ceftriaxone-treated patients. The study did not show a statistically significant increase in ADRs with IV push administration, but the small sample size, convenience sampling, broad definition of possible ADRs, and signal of numerically higher ADRs in the IV push group limit conclusions regarding comparative safety.

Table 8 References:
[16] Rahbar A, Promlap J, Patel J, David J, Phan L, Lee P, Zitek T. Antibiotics administered via intravenous push versus intravenous piggyback to adult patients in the emergency department: a randomized trial. SN Compr Clin Med. 2023;5:186. doi:10.1007/s42399-023-01523-y

Real-World Evaluation of Ceftriaxone-Related Safety Events: A Stewardship Call to Action
Design	Retrospective evaluation N= 211 events
Objective	To identify ceftriaxone-related safety events as recommended by Georgia Department of Public Health (GA DPH) and the Centers for Disease Control and Prevention (CDC) and to characterize the rates of ceftriaxone-related events compared to other cephalosporins
Study Groups	Ceftriaxone group (n= 90) Non-ceftriaxone group (n= 121)
Inclusion Criteria	Events occurring within six hours after receipt of injectable ceftriaxone in a non-intensive care unit (ICU) setting that resulted in death or required CPR and was not attributed by the provider(s) to a cause other than ceftriaxone administration
Exclusion Criteria	Events occurring in an ICU
Methods	A “Code Narrator” documentation tool within the electronic health record was used to retrospectively identify rapid response and cardiac arrest events occurring within 4 hours after administration of an IV cephalosporin, including cefazolin, cefuroxime, ceftriaxone, ceftazidime, or cefepime, across 7 hospitals in urban and suburban Georgia. Manual chart review was performed for identified events. Extracted variables included hospital, department/location of event, administration type, event time, time from cephalosporin administration to event, event type, and documented beta-lactam allergy. For the ceftriaxone group only, concomitant proton pump inhibitor use and QTc interval on the date of event were collected. Frequencies of rapid response and cardiac arrest events were calculated per number of non-ICU inpatient IV cephalosporin administrations, and ceftriaxone events were compared with non-ceftriaxone cephalosporin events using descriptive statistics and chi-squared or Fisher exact tests.
Duration	October 1, 2022, to June 30, 2025
Outcome Measures	Frequency of rapid response and cardiac arrest events per number of administrations for each cephalosporin; details of events specifically documented as related to a cephalosporin by the treating providers
Baseline Characteristics		Ceftriaxone group (n= 90)	Non-ceftriaxone group (n= 121)	p-value
	Location of event Emergency department Imaging Wards OR/Procedural	38 (42.2%) 11 (12.2%) 39 (43.3%) 2 (2.2%)	16 (13.2%) 8 (6.6%) 60 (49.6%) 37 (30.6%)	<0.01 0.22 0.01 <0.01
	Administration IV Push Intermittent IV Infusion	89 (98.9%) 1 (1.1%)	116 (95.9%) 5 (4.1%)	0.24 0.21
	Beta-lactam allergy, yes	12 (13.3%)	24 (19.8%)	0.21
	Penicillin allergy	11 (91.7%)	22 (91.7%)	0.81
	Cephalosporin allergy	1 (8.3%)	3 (12.5%)
	Concomitant PPI use, yes	20 (22.2%)	-	-
Results	During the study period, 90 significant events were identified among patients who received ceftriaxone and 121 events were identified among patients who received other IV cephalosporins. Cardiac arrest occurred in 59 ceftriaxone events (65.6%) versus 70 non-ceftriaxone cephalosporin events (57.9%), while rapid response events occurred in 31 (34.4%) versus 51 (42.1%) events, respectively; these differences were not statistically significant (p= 0.26). Among rapid response events, altered mental status was less frequent in the ceftriaxone group compared with the non-ceftriaxone group (3.2% vs 17.6%; p= 0.03), while rates of arrhythmia, hypotension, hypoxia, seizure, stroke, chest pain, and hyperglycemia were not significantly different between groups. Relative to total non-ICU inpatient IV cephalosporin administrations, the overall frequency of events was similarly low with ceftriaxone versus non-ceftriaxone cephalosporins (0.047% vs 0.041%; p= 0.33), including cardiac arrest events (0.031% vs 0.024%; p= 0.14) and rapid response events (0.016% vs 0.017%; p= 0.77). Three cardiac arrest events were attributed to ceftriaxone by the clinical team in the medical record, compared with no events attributed to a cephalosporin in the non-ceftriaxone group.
Adverse Events	Three cardiac events attributed to ceftriaxone occurred in patients with multiple co-morbidities, within 15 mins of administration. Kounis syndrome should be considered as a potential cause.
Study Author Conclusions	Due to the low frequency of events and comparable rates to other cephalosporins, avoidance of ceftriaxone was not recommended by our antimicrobial stewardship team. Given the broad use of ceftriaxone and a small number of cases related to significant adverse effects identified, the public health alert issued by the CDC and state departments can be challenging for healthcare systems to address. As there are no recommendations from the CDC to withhold or recommend alternatives to ceftriaxone while the investigation is ongoing, stewardship teams must employ their own strategies to help guide optimal antibiotic use while trying to minimize unintended consequences.
Critique	This retrospective, multi-hospital evaluation is directly relevant because it assessed real-world rapid response and cardiac arrest events after IV ceftriaxone exposure and compared event frequencies with other IV cephalosporins. However, it does not robustly answer whether IV push ceftriaxone increases reactions versus intermittent infusion because nearly all ceftriaxone administrations associated with events were IV push, with only 1 ceftriaxone event after intermittent infusion; therefore, the study supports a low observed frequency of serious events after ceftriaxone use but cannot establish comparative safety by administration method.

Table 9 References:
[17] Paciullo K, Suchindran S, Hojat LS, et al. Real-world evaluation of ceftriaxone-related safety events: a stewardship call to action. Antimicrob Steward Healthc Epidemiol. 2026;6:e7. doi:10.1017/ash.2025.10258