Is there any data to suggest worse outcomes with IV push antibiotics versus IVPB? Please also note if there is any data from the operating room.

Comment by InpharmD Researcher

Generally, IV push (IVP) antibiotics in the acute care setting are considered to be as safe and effective when compared to IVPB; with benefits to IVP including faster administration time, decreased fluid volume, reduced time to receive treatment, reduced reliance on small-volume parenteral solutions, enhanced nursing satisfaction, and cost savings. There have not been explicit data suggesting worse outcomes with IVP antibiotics, but comparative efficacy is limited to retrospective studies, and the overall evidence is of low quality, making it difficult to draw definitive conclusions from available data. There appears to be a general lack of data specific to the operating room.

Background

A 2018 review discussing the administration of antibiotics via intravenous (IV) push suggests that IV push administration can provide clinical and practical advantages over longer IV infusions in multiple clinical scenarios. In such settings, conversion to IV push administration may provide a practical solution. Intravenous push administration allows for the administration of an antibiotic in a minimal fluid volume, which can be particularly useful in patients who are fluid-restricted, such as patients with acute volume overload. The faster administration time may also provide advantages in the emergency department (ED), making it so the time-to-first-dose can be minimized. Additionally, in the setting of drug or fluid shortages, IV push administration may help to conserve supplies. [1]

With the many benefits of administering antibiotics via IV push, one of the primary advantages is that, in cases where immediate administration is required for medication stability or for clinical necessity, preparation and dilution of the medication can occur in patient care areas. Additionally, for agents that are concentration-dependent, IV push administration allows for maximizing the area under the curve (AUC) per unit of time in relation to the bacterial minimum inhibitory concentration (MIC), increasing the rapidity of bacterial killing and the likelihood of a good clinical outcome. It should be noted, however, that several studies have found extended and continuous infusion strategies to be associated with improved clinical cure and survival, particularly in severely ill patients, compared with shorter infusion durations. Thus, current data do not support the substitution of IV push for extended or continuous infusion schemes in patients who are critically ill, immunocompromised, or infected with organisms with MICs at or above the clinical breakpoint for susceptibility. In general, precautions should be taken to ensure safe IV push administration, including clear labeling and staff education. Additionally, pharmacodynamic changes due to IV push administration should be considered, such as effects on time above MIC when administering antibiotics via IV push that are normally administered via extended or continuous infusions. [1]

Ceftriaxone IV push administration has been studied in different settings, including in hospitalized patients, in the ED, and with outpatient parenteral antibiotic therapy; reports of concerns with IV push administration were minimal in the literature. Rapid ceftriaxone administration (2 grams over 5 minutes) was reported to be associated with palpitation, tachycardia, restlessness, shivering, and diaphoresis in an adult patient. In the pediatric population, ceftriaxone has been associated with ​​increased biliary pseudolithiasis (ceftriaxone given over 3 to 5 minutes) and with the formation of a calcium-ceftriaxone precipitate in neonates receiving concurrent calcium-containing solutions, which led to adverse cardiopulmonary events (ceftriaxone given over 2 to 4 minutes). Description of how IV push administration of ceftriaxone may affect the efficacy of the drug was not discussed. [1]

Another commentary published in 2021 states that time to antibiotic administration is an important parameter for ED patients, particularly in the case of sepsis and septic shock. Notably, two large retrospective cohort studies found that shorter time to antibiotics was associated with a reduction in mortality in patients with sepsis and septic shock. However, there is still a lack of data to support improved outcomes with IV push antibiotics compared to IV piggyback administration. Due to septic patients frequently requiring multiple antibiotics and concomitant interventions, IV push antibiotics make an attractive option, especially within the first several hours of care. While faster administration is one of the primary benefits of IV push administration, it also requires less total fluid volume, making it an ideal modality in patients with fluid restrictions. Additionally, IV push antibiotics are easily stored in automated dispensing cabinets and do not require small-volume parenteral solutions, which are commonly in short supply. One study found that 87% of ED nurses favored IV push administration due to less time spent gathering equipment and infusion supplies, entering nursing orders for carrier fluids, and documenting secondary infusions. [2]

A potential benefit of IV push antibiotic administration is cost savings. Use of intravenous tubing, diluent bags, and staff time (e.g., preparation, pharmacist review, nurse administration) is reduced by reconstituting antibiotics with 10 to 20 mL of diluent at the bedside. The expiration date is also extended when compared to the IV piggyback route, minimizing drug waste. With respect to safety, IV push beta-lactams appear to be as safe as IV piggyback/infusion, with no study to date demonstrating a significantly increased risk of adverse effects. However, IV push antibiotics generally have higher sodium concentrations and osmolalities compared to IV piggyback, which may lead to infiltration, local irritation, and phlebitis. Despite this caveat, available data have typically found IV push antibiotics to be well tolerated; use of sterile water for injection instead of 0.9% sodium chloride or 5% dextrose may minimize the osmolality to mitigate the risk of phlebitis. Overall, IV push antibiotics appear to be as safe and effective compared to IV infusions, with potential benefits including decreased time to antimicrobial administration, enhanced nursing satisfaction, and lower healthcare costs. [2]

Several retrospective studies have investigated IV push and IV piggyback cephalosporins. A 2024 retrospective study 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 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 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; IV piggyback: 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 IV piggyback administration. However, given that only the abstract was available, a comprehensive analysis of the study could not be conducted. [3]

A 2021 abstract describes a retrospective study aimed to evaluate the incidence of infusion-related complications in patients receiving cefazolin, ceftriaxone, and cefepime administered via IV push versus short infusion IV piggyback. IVP or IV piggyback administration complications were evaluated from a chart review of electronic medical records. A total of 366 therapy sessions from 355 individual patients were included for analysis. In the IV push group, complications occurred in 13 of 183 treatment episodes (7.1%) compared to 18 of 183 (9.8%) in the IV piggyback group (p = 0.35). For both groups, the median time to complications was two days. The median time to the first dose of vancomycin in the ED was 25 minutes shorter with IV push 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. Cefazolin, ceftriaxone, and cefepime administered as IV push were found to be as safe as IV piggyback while lowering the time to the first dose of vancomycin in the ED and cost. [4]

Finally, a 2019 retrospective analysis assessed the safety and efficacy of transitioning from intermittent 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. 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. [5]

A 2024 multicenter, retrospective practice research report compared IVP versus IVPB antibiotic administration across six emergency departments within a 1,250-bed healthcare system. The investigation focused on adult patients (≥18 years) who received a single dose of IVP or IVPB ceftriaxone, cefepime, cefazolin, or meropenem. IVP administration protocols were implemented alongside educational handouts and order set modifications that included bedside reconstitution and administration instructions. The study population included 43 patients in each group, selected based on matched antibiotic dosing and emergency department location, with the IVPB cohort identified in January 2022 and the IVP cohort between November and December 2022. According to the report, IVP antibiotics significantly reduced the median time from order placement to administration initiation—31 minutes (IQR, 21–52) versus 74 minutes (IQR, 29–114) with IVPB (p = 0.003). Moreover, the median cost per dose was notably lower for IVP agents when compared to IVPB preparations: $3.31 vs $20.59 for ceftriaxone (p <0.001), $7.11 vs $45.84 for cefepime (p <0.001), and $2.37 vs $7.03 for meropenem (p = 0.029). Annual cost savings were estimated to exceed $227,000 across the emergency departments due to reduced reliance on expensive IVPB premixes and associated materials. A nursing satisfaction survey revealed widespread acceptance, with 76% of respondents preferring IVP over IVPB and 87% reporting perceived reductions in time to administration. These results highlight that IVP antibiotic protocols can improve timeliness of care, enhance resource utilization, and support sepsis treatment guidelines that emphasize antibiotic administration within one hour of recognition. [6]

Lastly, a 2012 prospective, quasi-experimental study evaluated postinfusion phlebitis rates in 240 adult orthopedic surgical patients receiving cefazolin prophylaxis via two different infusion methods, IVP and IVPB. Patients were divided into two sequential groups of 120; the first group received cefazolin via IVPB over 30 minutes, while the second group received the same medication via IVP over 3 to 10 minutes, contingent upon the dosage. All patients received between 1 and 5 doses of IV cefazolin and had IV lines in place for 1 to 4 days. Results indicated no statistically significant difference in phlebitis rates between the two methods, with incidences reported at 3.4% for the IVPB cohort and 3.3% for the IVP cohort. Phlebitis cases in the IVP group were all grade 1, whereas the IVPB group observed two grade 2 cases. Although a multivariate analysis was not feasible given the limited number of phlebitis cases, univariate analysis highlighted the total catheter-days as the sole significant predictor (p<0.01). Despite variances in adjuvant IV analgesics, such as morphine and hydromorphone being more common in the IVP cohort compared to ketorolac and prochlorperazine in the IVPB group, these differences did not affect phlebitis outcomes. Overall, these findings highlight that administering cefazolin via IVP is a cost-effective alternative that does not compromise patient safety or vascular access site integrity. [7]

References:

[1] Spencer S, Ipema H, Hartke P, et al. Intravenous Push Administration of Antibiotics: Literature and Considerations. Hosp Pharm. 2018;53(3):157-169. doi:10.1177/0018578718760257
[2] Rech MA, Gottlieb M. Intravenous Push Antibiotics Should be Administered in the Emergency Department. Ann Emerg Med. 2021;78(3):384-385. doi:10.1016/j.annemergmed.2021.03.021
[3] Branan T, Bland C, Smith S. 486: intravenous push versus iv piggyback ceftriaxone in critically ill obese patients with sepsis. Critical Care Medicine. 2024;52(1):S217-S217. doi:10.1097/01.ccm.0001000124.28023.b0
[4] Lee R, Tran T, Tan S, Chun P. 602. Intravenous Push Versus Intravenous Piggyback Administration of Cephalosporin Antibiotics: Impact on Safety, Workflow, and Cost. Open Forum Infect Dis. 2021;8(Suppl 1):S403-S404. Published 2021 Dec 4. doi:10.1093/ofid/ofab466.800
[5] Baize P, Smith T, Faust A. 1831: intermittent iv infusion versus slow iv push beta-lactam administration. Critical Care Medicine. 2019;47:889. doi:10.1097/01.ccm.0000552569.08640.4b
[6] 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
[7] Biggar C, Nichols C. Comparison of postinfusion phlebitis in intravenous push versus intravenous piggyback cefazolin. J Infus Nurs. 2012;35(6):384-388. doi:10.1097/NAN.0b013e3182706719

Literature Review

A search of the published medical literature revealed 7 studies investigating the researchable question:

Is there any data to suggest worse outcomes with IV push antibiotics versus IVPB? Please also note if there is any data from the operating room.

Level of evidence

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



Please see Tables 1-7 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 Survival Sepsis Campaign guidelines. Administration of medications such as vasoactive agents, corticosteroids, and insulin was based on the discretion of the attending physician.

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.

InpharmD Researcher 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. 

References:

Lim SY, Baek S, Jo YH, et al. Effect of intravenous push and piggyback administration of ceftriaxone on mortality in sepsis. The Journal of Emergency Medicine. Published online December 2023:S0736467923005954. 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 shortage of small-volume parenteral solutions led to a hospital-wide implementation of a mandatory antibiotic IVP action plan. The electronic health records (EHR) of patients were reviewed to identify patients eligible for inclusion in the study based on health chart information from this period. 

Although IVP formulations were made available for ordering the EHR, exceptions to IVP were allowed with approval from a clinical pharmacy manager. Antibiotics were supplied as vials in the automated dispensing cabinet for nurses to reconstitute or were compounded and dispensed from the pharmacy. Medication orders included instructions for reconstitution and manual administration as a slow push over 5 minutes. Patients were monitored for adverse reactions for one hour after administration; adverse reactions monitored included injection site reactions, changes in mental status, changes in heart rate, palpitations, diaphoresis, restlessness, gastrointestinal disturbances, seizures, and seizure-like activity. 

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, n

Every 12 hours (Q12H)

Q24H

Cefepime, n

Q8H

Q12H

Q24H

Meropenem, n

Q6H

Q8H

Q12H

Q24H

Aztreonam, n

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.

InpharmD Researcher 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. 
References:

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 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. 

InpharmD Researcher 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. 

References:

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

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.
References:

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

Intravenous Push Versus Intravenous Piggyback Beta-Lactams for the Empiric Management of Gram-Negative Bacteremia

Design

Retrospective cohort

N= 213

Objective

To evaluate and compare clinical and microbiological outcomes between empiric cefepime (FEP) and meropenem (MEM) administered as intravenous push (IVP) compared to intravenous piggyback (IVPB) in Gram-negative bacteremia (GNB)

Study Groups

IVPB (n= 105)

IVP (n= 108)

Inclusion Criteria

Unique adult patients with first episode of GNB during study period that was susceptible to the study drug and received FEP or MEM IVPB or IVP empirically for at least two days of therapy

Exclusion Criteria

No repeat blood cultures drawn; concomitant Gram-positive bacteremia or fungemia; empiric combination Gram-negative coverage longer than 48 h; extended infusion used as empiric treatment; patients who died, were discharged, or were transitioned to hospice within 48 h of culture collection 

Methods

Due to a critical shortage of small-volume parenteral solutions (SVPS), a mandatory IVP action plan was implemented in October 2017; FEP 1 g and 2 g and MEM 500 mg and 1 g doses were reconstituted by nursing or pharmacy staff with 10-20 mL of normal saline or sterile water for injection and administered by nursing as IVP over a period of 5 min. Antimicrobials were dosed according to local guidelines. MEM was allowed to be administered as extended infusion over 3 h in critically ill patients with septic shock or in patients with minimum inhibitor concentrations of 4-16 mg/L.

A retrospective review of patients with GNB at two academic centers in the New York Metropolitan area was conducted. A list of patients with GNB who received FEP or MEM at any time point during their hospitalization was generated using microbiology laboratory reports and pharmacy database of medication administration. Empiric antibiotic selection and escalation of therapy were at the discretion of the primary team. 

Duration

July 1, 2016 to September 30, 2018

Outcome Measures

Primary: need for escalation of therapy (change in empiric antibiotic to a broader spectrum agent, the addition of a second Gram-negative agent, or a change to extended infusion over 3 hours at any time during the course of bacteremia treatment); 

Change to broader spectrum agent defined as: escalation from FEP to piperacillin/tazobactam (TZP), carbapenem, ceftazidime/avibactam (CZA), or ceftolozane/tazobactam (C/T); or from MEM to CZA or C/T

Secondary: microbiological clearance; recurrence of bacteremia during hospitalization; time to defervescence; time to white blood cell (WBC) normalization; time to vasopressor discontinuation; in-hospital and 90-day mortality; hospital and intensive care unit (ICU) length of stay; time to antibiotic administration; neurologic adverse events; any infection-related readmission within 90 days 

Baseline Characteristics

 

IVPB (n= 105)

IVP (n= 108)

 

Median age, years (IQR)

70 (62-81) 72 (62-83)  

Male

54% 53%  

Median BMI, kg/m2 (IQR)

27 (24-30) 26 (22-30)  

Median Charlson Comorbidity Index (IQR)

3 (1-4) 2 (1-3)  

Past medical history

Diabetes mellitus

Immunocompromising condition

Heart failure

End-stage renal disease

Chronic obstructive pulmonary disease

Cirrhosis

 

32%

22%

13%

10%

9%

6%

 

34%

32%

16%

15%

8%

6%

 

Severity of illness

Sepsis at time of culture collection

Febrile at time of blood culture collection

CrCl, median, mL/min (IQR)

CRRT at time of culture collection

Pitt Bacteremia Score, median (IQR)

WBC at start of therapy, median, x 109 cells/L (IQR)

ICU admission

ICU length of stay, median, days (IQR)

Mechanical ventilation

Vasopressor use

Length of hospital stay, median, days  (IQR)

 

87%

79%

37 (27-68)

0

2 (0-3)

14 (8-19)

40%

4 (3-7)

4%

19%

9 (5-17)

 

81%

73%

39 (25-64)

1%

2 (0-3)

14 (10-19)

40%

3 (2-5)

0

17%

7 (5-11)

 

Empiric treatment prior to FEP/MEM

Number of doses, median, IQR

Received empiric combination therapy

Susceptible to empiric combination therapy

Patients treated with FEP

Total daily dose, median, g (IQR)

Duration of therapy, median, days (IQR)

Patients treated with MEM

Total daily dose, median, g (IQR)

Duration of therapy, median, days (IQR)

FEP/MEM duration of therapy, median, days (IQR)

57%

2 (1-2)

25%

75%

50%

3 (3-6)

4 (3-4.25)

50%

2 (1.5-2)

4 (3-8)

4 (3-5)

45%

1 (1-2)

19%

84%

67%

3 (3-3)

3 (3-5)

33%

1.5 (1-2)

5 (3-7)

4 (3-5)

 

Source of bacteremia

Urine

Intra-abdominal

Pneumonia

Catheter

Skin and soft tissue infection

Osteomyelitis

Central nervous system

Joint

Endocarditis

Sternal wound

Surgical

Unknown

Removable source

Source control achieved

Time to source control, median, days (IQR)

 

49%

18%

11%

6%

4%

2%

3%

2%

1%

1%

1%

6%

32%

76%

2 (1-6)

 

53%

31%

5%

3%

3%

2%

0

0

0

0

0

8%

21%

83%

2 (1-5)

 

Isolated pathogen

Escherichia coli

Klebisella pneumoniae

Proteus mirabilis

Enterobacter cloacae

Pseudomonas aeruginosa

Serratia marcescens

Other

 

44%

29%

8%

4%

5%

5%

12%

 

60%

21%

5%

6%

3%

2%

6%

 

ESBL organism identified

Patients who received FEP empirically

Patients who received MEM empirically

30%

19%

40%

19%

7%

44%

 

IQR: interquartile range; CrCl: creatinine clearance; CRRT: continuous renal replacement therapy; ESBL: extended-spectrum beta-lactamase

Results

Endpoint

IVPB (n= 105)

IVP (n= 108)

p-Value

Escalation of therapy

Broader spectrum agent

Addition of aminoglycoside

Change to extended infusion MEM

Time to escalation from culture collection, median, days (IQR)

14%

87%

13%

7%

3 (3-5)

10%

100%

0

0

3 (2-4)

0.36

 

 

 

0.68

Microbiological clearance

Empiric FEP

Empiric MEM

Recurrence of bacteremia

Time to defervescence, median, days (IQR)

WBC normalization

Duration of vasopressor, median, h (IQR)

Neurologic adverse events

Transitioned to hospice during hospital admission

In-hospital mortality

Non-ICU patients

ICU patients

90-day mortality

90-day infection-related readmission

95%

97%

92%

1%

2 (1-2)

57/75 (76%)

25 (14-56)

1%

4%

9%

1/63 (2%)

8/42 (19%)

11%

20%

96%

98%

94%

1%

1 (1-2)

62/81 (77%)

24 (13-47)

0

5%

3%

3%

2%

7%

32%

1

1

0.68

1

0.24

0.94

0.63

0.49

1

0.07

1

0.02

0.21

0.08

Adverse Events

See results section

Study Author Conclusions

Our findings suggest no differences in clinical response with the use of IVP compared to IVPB FEP and MEM for treatment of GNB. This form of administration may be considered as a fluid conservation strategy in times of shortage. 

InpharmD Researcher Critique

Limitations of the study are the retrospective design and inclusion of two centers in the same geographic area, possibly limited generalizability of the results. Limited deep-seated infections (i.e., meningitis, osteomyelitis, endocarditis) were included in the study and limited number of patients had P. aeruginosaisolated; as these infections may be more difficult to eradicate, the results of the study may not be applicable to these infections/organism. Adverse events other than neurologic events were not evaluated, limiting the safety evaluation in this study. 

References:

Marsh K, Dubrovskaya Y, Jen SP, et al. Intravenous push versus intravenous piggyback beta-lactams for the empiric management of gram-negative bacteremia. J Clin Pharm Ther. 2021;46(2):373-381. doi:10.1111/jcpt.13291

Outcomes of Intravenous Push versus Intermittent Infusion Administration of Cefepime in Critically Ill Patients

Design

Single center, retrospective, observational, pre/post-protocol change study

N= 285

Objective

To examine the effects of cefepime administration strategies on antibiotic treatment failure and safety

Study Groups

Intravenous piggyback (IVPB) (n= 87)

Intravenous push (IVP) (n= 198)

Inclusion Criteria

At least 18 years of age; admitted to the intensive care unit (ICU) who received cefepime either IVPB or IVP

Exclusion Criteria

Infected with a pathogen intermediate or resistant to cefepime (including susceptible-dose-dependent); pregnant patients; received cefepime for < 72 h; received cefepime both through IVP and IVPB

Methods

The standard empiric dose of cefepime was 2 g IV every 8 h for critically ill patients, and adjusted per manufacturer's recommendations when calculated creatinine clearance < 60 mL/min. IVPB doses were prepared in a total volume of 100 mL and administered by infusion pump over 30 min; IVP doses were reconstituted with 10 mL of sterile water for injection and administered by the patient's bedside nurse as a slow IVP over 5 min. Patients were identified by pharmacy dispensing logs of cefepime. The institution changed its standard practice for cefepime infusion after August 14, 2018, after which cefepime was administered by IVP. 

Duration

IVPB: 2015 to August 13, 2018

IVP: August 14, 2018 to 2021

Outcome Measures

Primary: treatment failure (composite of inpatient mortality and/or switching from cefepime to a broader Gram-negative antibiotic [i.e., carbapenem] due to clinical worsening, as documented by the electronic medical record)

Secondary: adverse drug events; days of cefepime therapy; total days of antibiotic therapy; ICU and hospital length of stay; ICU and hospital mortality 

Baseline Characteristics

 

IVPB (n= 87)

IVP (n= 198)

p-Value

Age, years*

73 (63-81) 67 (58-76) 0.004

Male

53% 59%  

White

African-American

82%

18%

72%

26%

 

CrCl, mL/min*

37 (16-64) 49 (27.1-84.5) 0.049

SOFA score*

6 (3-8) 5 (2.75-7)  

Source of infection

Pneumonia

Intraabdominal

Urinary tract

Severe**

Skin and soft tissue

Multiple sources

 

55%

1%

8%

8%

5%

23%

 

51%

7%

5%

10%

8%

20%

 

Sepsis

Septic shock

83%

17%

69%

31%

0.044

0.044

Isolated pathogen(s)

Pseudomonas aeruginosa

Methicillin-resistant Staphylococcus spp.

Methicillin-sensitive Staphylococcus spp.

Streptococcus spp.

Klebsiella spp.

Escherichia coli

Proteus spp.

Enterobacter spp.

Serratia spp.

Bacteroides

Citrobacter spp.

Haemeophilus spp.

Other bacteria

Polymicrobial

 

16%

5%

3%

5%

3%

2%

3%

6%

5%

2%

2%

1%

6%

10%

 

17%

5%

5%

4%

5%

3%

3%

1%

1%

1%

1%

1%

6%

9%

 

*Data presented as median (interquartile range [IQR])

**Severe infections defined as bacteremia, central nervous system infection, osteomyelitis, or endocarditis 

CrCl: creatinine clearance; SOFA: sequential organ failure assessment

Results

Endpoint

IVPB (n= 87)

IVP (n= 198)

p-Value

Treatment failure

Escalation of therapy

All-cause mortality

18%

2%

18%

27%

9%

22%

0.109

0.093

0.339

Adverse drug event

Therapy change due to ADE

1%

1%

1%

1%

0.915

Average cefepime daily dose, g*

Duration of cefepime, days*

Duration of antibiotics, days*

3.33 (2-4)

6 (4-8)

9 (6-12)

3.785 (2.65-5)

6 (5-8)

10 (7-14)

< 0.001

0.314

0.194

ICU LOS, days*

Hospital LOS, days*

6 (2-10)

11 (8-22)

7 (4-14)

13 (9-22)

0.06

0.148

*data presented as median (interquartile range [IQR])

ADE: adverse drug event; LOS: length of stay 

Binary logistic regression: longer duration of antibiotics (odds ratio [OR] 1.057; 95% confidence interval [CI] 1.013 to 1.103; p= 0.011), higher SOFA score (OR 1.274; 95% CI 1.157 to 1.404; p< 0.001), and IVP administration fo cefepime (OR 2.4; 95% CI 1.149 to 5.017; p= 0.02)

Adverse Events

N/A

Study Author Conclusions

Critically ill patients had a similar rate of treatment failure with IVPB and IVP administration of cefepime. Treatment failure was more likely with IVP administration of cefepime in an adjusted analysis. Current practice of IVP administration of cefepime should be further evaluated in the critically ill population.

InpharmD Researcher Critique

Limitations of the study include the single-center and retrospective design, which may introduce the risk for selection bias and limit ability to control for confounding variables. As data was collected by chart review, adverse events may be underreported. The higher incidence of sepsis in the IVPB group and septic shock in the IVP group may have affected the outcome results. Additionally, there were substantially more patients in the IVP group than the IVPB group. As the study interventions took place during different time periods, antimicrobial resistance, antibiotic prescribing patterns, and standard of ICU care may have varied between time periods. 

References:

Smith SE, Halbig Z, Fox NR, Bland CM, Branan TN. Outcomes of Intravenous Push versus Intermittent Infusion Administration of Cefepime in Critically Ill Patients. Antibiotics (Basel). 2023;12(6):996. Published 2023 Jun 1. doi:10.3390/antibiotics12060996

 

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 intensive care unit (ICU) who received empiric ceftriaxone for ≥72 hours

Exclusion Criteria

Receipt of both IVP and IVPB ceftriaxone, pregnancy

Methods

Patients admitted from March 2016 to April 2018 received ceftriaxone via IVPB, while those admitted from May 2018 to January 2021 received IVP ceftriaxone, reflecting a system-wide protocol change. Ceftriaxone doses administered in the emergency department were included in the 72-hour minimum if the patient was directly admitted to the ICU.

Data collected on the intervention included the route of administration (IVP or IVPB), average daily dose, and duration of ceftriaxone therapy. In the primary cohort, the average daily dose was 1.33 grams in the IVP group and 1.40 grams in the IVPB group. The average duration of ceftriaxone therapy was 5.8 days in both groups.

Duration

IVPB administration: March 2016 to April 2018

IVP administration: May 2018 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

BMI, kg/m2

31.6 ± 9.4 30.6 ± 10.4 0.311

SCr, mg/dL at initiation

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

Urinary tract infection

Other/unknown

 

107 (53.2%)

27 (13.4%)

24 (11.9%)

 

80 (40.0%)

47 (23.5%)

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

Abbreviations: BMI= Body Mass Index; SCr= serum creatinine; CrCl= creatinine clearance; SOFA= Sequential Organ Failure Assessment

Results

Endpoint

IVP (n= 201)

IVPB (n= 200)

p-value

Treatment failure

Escalation of therapy

All-cause hospital mortality

76 (37.8%)

51 (25.4%)

43 (21.4%)

39 (19.5%)

23 (11.5%)

19 (9.5%)

<0.001

<0.001

<0.001

All-cause ICU mortality

35 (17.4%) 18 (9%) 0.013

ICU LOS, days

10.3 ± 9.2 9 ± 8 0.143
Hospital LOS, days 18.6 ± 16.8 14.9 ± 10.2 0.009

Multivariate logistic regression analysis identified several factors independently associated with treatment failure. IVP administration of ceftriaxone was associated with increased odds of treatment failure compared to IVPB, with an OR of 2.121 (95% CI, 1.304 to 3.448; p= 0.002). Higher SOFA scores were also associated with treatment failure (OR 1.191; 95% CI 1.106 to 1.283; p< 0.001).

In contrast, longer duration of ceftriaxone therapy was associated with reduced odds of treatment failure (OR 0.875; 95% CI 0.792 to 0.968; p= 0.009). The source of infection was not significantly associated with treatment failure; compared to respiratory infections (reference category), intra-abdominal (OR 0.817; p= 0.649), urinary tract (OR 0.649; p= 0.226), severe infections (OR 1.436; p= 0.331), and other/unknown sources (OR 0.756; p= 0.470) did not show statistically significant associations.

Abbreviations: OR= Odds Ratio; CI= Confidence Interval; 

Adverse Events

Although the methods section of the study states that adverse drug reactions and changes in tolerability were collected from provider notes in the electronic health record (EHR), the study did not report specific adverse events. 

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.

InpharmD Researcher 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, was not collected. Despite these limitations, the study suggests a possible benefit with IVPB administration of ceftriaxone in ICU patients.



References:

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