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Safety of intravenous push administration of beta-lactams within a healthcare system Downloaded from https://academic.oup.com/ajhp/article-abstract/77/9/701/5824399 by Biblioteca Nacional de Salud y Seguridad social user on 09 July 2020

Kassandra Marsh, PharmD, BCIDP, Department of Pharmacy, NYU Langone Purpose. A critical shortage of small-volume parenteral solutions in late Health, New York, NY 2017 led hospitals to develop strategies to ensure availability for critical Nabeela Ahmed, PharmD, BCPS, patients, including administration of as intravenous push (IVP). Department of Pharmacy, NYU Langone Health–Brooklyn, Brooklyn, NY Minimal literature has been published to date that assesses the safety of Arnold Decano, PharmD, BCPS, administration of beta-lactams via this route. Therefore, the purpose of AAHIVP, Department of Pharmacy, NYU this study was to evaluate the safety of IVP administration of select beta- Langone Health–Brooklyn, Brooklyn, NY lactam antibiotics. Yanina Dubrovskaya, PharmD, BCPS, BCIDP, AAHIVP, Department of Methods. We performed a retrospective review of IVP administrations of Pharmacy, NYU Langone Health, New , , , and at two campuses of York, NY the New York University Langone Health system after October 2017. Pa- Shin-Pung (Polly) Jen, PharmD, BCPS (AQ-ID), AAHIVP, Department of tients receiving surgical prophylaxis or more than one IVP simul- Pharmacy, NYU Langone Health, New taneously were excluded. The primary endpoint was adverse events (ADE) York, NY following IVP administration of antibiotics. Justin Siegfried, PharmD, BCPS, Department of Pharmacy, NYU Langone Results. We evaluated 1000 patients who received IVP aztreonam (n = 43), Health, New York, NY ceftriaxone (n = 544), cefepime (n = 368) or meropenem (n = 45). There Xian Jie (Cindy) Chen, PharmD, were 10 (1%) ADE observed, 5 of which were allergic reactions. Four ADE BCPS, Department of Pharmacy, NYU Langone Health–Winthrop, Mineola, NY were neurotoxicity related to IVP cefepime. Based on the Naranjo score, 1 Cristian Merchan, PharmD, BCCCP, adverse event was “probably” and 3 were “possibly” related to cefepime Department of Pharmacy, NYU Langone IVP administration. Lastly, only 1 report of phlebitis was observed with the Health, New York, NY use of IVP ceftriaxone.

Conclusions. The use of IVP as an alternative to intravenous piggyback (IVPB) during times of drug shortage for select beta-lactam antibiotics ap- pears 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.

Keywords: antibiotics, beta-lactams, drug administration, drug safety, sterile products

Am J Health-Syst Pharm. 2020;77:701-708

rug shortages due to manufacturing poses the risk for an increase in dose- Dissues and natural disasters have dependent adverse effects. become an important issue in the de- Although the package insert for livery of medical care. In 2017, a critical some beta-lactam agents provide re- shortage of small-volume parenteral commendations for IVP, there is lim- solutions (SVPS) led many hospitals to ited published data which assesses the develop various strategies for rationing incidence of adverse reactions when these fluids, including the administra- using this method and rate of adminis- Address correspondence to Dr. Merchan tion of antibiotics as intravenous push tration.2-12 Literature describing ceph- ([email protected]). (IVP).1 Given the high concentration and alosporin administration as IVP found the fast rate of administration when ad- overall low rates of phlebitis or infusion © American Society of Health-System ministering an antibiotic as IVP over 5 reactions, with no differences com- Pharmacists 2020. All rights reserved. 6,8-11,13 For permissions, please e-mail: journals. minutes as compared to intravenous pared to IVPB. However, these [email protected]. piggyback (IVPB) over 30 minutes, the studies were limited to evaluations of DOI 10.1093/ajhp/zxaa044 higher maximum serum concentration phlebitis or injection site reactions,

AM J HEALTH-SYST PHARM | VOLUME 77 | NUMBER 9 | MAY 1, 2020 701 NOTE SAFETY OF I.V. PUSH BETA-LACTAM THERAPY without evaluations for cardiac disturb- in the EHR by the bedside nurse, with ances or neurotoxicity. KEY POINTS supplemental information provided by New York University Langone • During times of small-volume primary provider notes. Nursing docu-

Health (NYULH) implemented a health parenteral solution shortage, mentation per shift includes line flow- Downloaded from https://academic.oup.com/ajhp/article-abstract/77/9/701/5824399 by Biblioteca Nacional de Salud y Seguridad social user on 09 July 2020 system–wide IVP action plan for select utilization of intravenous push sheets, nursing shift flowsheets, and antibiotics as a solution to the shortage administration of antibiotics nursing notes for significant events re- of SVPS. Given the limited availability across a hospital system is quiring medical attention. of safety data, the main objective was to logistically feasible. Data collection. Electronic health evaluate the safety of IVP beta-lactam record queries were performed to gen- administration by examining the inci- • Multidisciplinary teams con- erate a list of patients who received dence of reported adverse events. sisting of pharmacists, nurses, IVP aztreonam, ceftriaxone, cefepime, physicians, and information or meropenem at NYULH–Tisch or Methods technologists play a vital role Brooklyn Hospitals during the des- Study design, setting, and pa- in implementation of strategies ignated study period. Patient demo- tient population. The study was a to combat drug shortages. graphics, past medical history, relevant retrospective cohort study conducted • Intravenous push administration concomitant medications, antibio­ at the Tisch and Brooklyn campuses over 5 minutes for aztreonam, tic administration including antibi- of NYULH, a health-system consisting ceftriaxone, cefepime, and otic agent, dose, frequency, number of approximately 1,500 beds. Due to meropenem is safe during of doses, indication and line access, the retrospective design of this obser- shortage of small-volume and adverse events were collected for vational project intended for quality ­parenteral solutions. each patient meeting inclusion criteria. assurance purposes, informed con- Adverse events were collected by re- sent was not required, and this pro- viewing provider notes, line flowsheets, ject was exempt from Institutional vitals graphs, and nursing flowsheets, Review Board review. The electronic alongside medication administration health records (EHR) of unique, con- records. secutively admitted patients 18 years of Medication records in the EHR were Study outcomes. The primary age or older who received at least two modified to the IVP formulation with outcome of the study was the incidence doses of IVP aztreonam, ceftriaxone, the appropriate diluent and admin- of adverse events (ADE), obtained cefepime, or meropenem from October istration instructions. Only the IVP from the nursing documentation in the to December 2017, the first 3 months medication records were available to EHR as well as supplemental pro- after IVP action plan implementation, order in the EHR for all indications vider documentation. Adverse events were evaluated for inclusion. Patients via an alternative use alert, however, that were assessed included phlebitis, were excluded if they received IVP anti- exceptions to IVP were allowed with allergic reactions, infusion-related re- biotics for surgical prophylaxis, were approval from a clinical pharmacy actions, gastrointestinal disturbances, pregnant, or received more than one manager. Education was provided to cardiac changes, and neurologic dis- IVP antibiotic on the same day. For all nursing staff prior to implementa- turbances. Phlebitis was graded ac- the majority of surgical procedures at tion of the IVP action plan. The select cording to the Visual Infusion Phlebitis NYULH, is the first-line agent antibiotics were supplied as vials in Scale.14 Infusion-related reactions in- recommended for prophylaxis, and the the automated dispensing cabinet for cluded flushing, alterations in blood safety of cefazolin IVP has been pre- nurses to reconstitute, or compounded pressure or heart rate, diaphoresis, and viously established.6,10,11,13 Patients re- and dispensed by pharmacy personnel. palpitations. Gastrointestinal disturb- ceiving and IVP Administration instructions within the ances included abdominal discomfort, were not included in this analysis given medication orders included directions , , and associ- the limited sample size of patients on on reconstitution and manual admin- ated with antibiotic administration in these agents during this time period. istration as a slow push over 5 minutes the absence of an alternate explanation. Although meropenem and aztreonam for nursing staff. Monitoring param- Cardiac changes included alterations in are FDA approved for IVP administra- eters included observing for injection blood pressure or heart rate, and palpi- tion, there is limited guidance on max- site reactions, changes in mental status, tations experienced within 1 hour of imum doses that can be administered changes in heart rate, palpitations, di- IVP administration. Finally, neurologic via this route. aphoresis, restlessness, gastrointestinal disturbances included altered mental Mandatory antibiotic IVP action disturbances, and -like status, restlessness, peripheral neurop- plan implementation. A manda- activity for one hour after administra- athy or seizures. For each ADE, the type tory antibiotic IVP action plan was im- tion. Adverse events were required by of management was documented and plemented in October 2017 (Table 1). institutional policy to be documented a Naranjo score, which standardizes

702 AM J HEALTH-SYST PHARM | VOLUME 77 | NUMBER 9 | MAY 1, 2020 SAFETY OF I.V. PUSH BETA-LACTAM THERAPY NOTE

Table 1. NYULH Mandatory Antibiotic IVP Action Plan

Drug Dosage Form Reconstitution Instructions Nursing Administration Instructions Downloaded from https://academic.oup.com/ajhp/article-abstract/77/9/701/5824399 by Biblioteca Nacional de Salud y Seguridad social user on 09 July 2020 Ceftriaxone 1-gram vial Reconstitute 1 gram with 10 mL 0.9% IVP over 5 minutes 2-gram vial sodium chloride Monitoring: within 1 hour of administration Reconstitute 2 grams with 20 mL 0.9% monitor for the following: sodium chloride • Injection site reactions • Changes in the following: Cefepime 1-gram vial Reconstitute 1 gram with 10 mL 0.9% ◦Mental status 2-gram vial sodium chloride ◦Heart rate 2-gram/20 mL syringe will be dispensed by • Palpitations pharmacy • Diaphoresis Meropenem 500-mg vial Reconstitute 500 mg with 10 mL sterile water • Restlessness 1-gram vial for injection • Seizures Reconstitute 1 gram with 20 mL sterile water for injection Aztreonam 1-gram vial Reconstitute 1 gram with 10 mL 0.9% 2-gram vial sodium chloride 2-gram/20 mL syringe will be dispensed by pharmacy Cefazolin 1-gram vial Reconstitute 1 gram with 10 mL 0.9% sodium chloride or sterile water for injection Daptomycin 500 mg vial Doses less than 500 mg will be prepared and dispensed by pharmacy Oxacillin 1-gram vial Reconstitute 1 gram with 10 mL NS or SWFI 2-gram vial Reconstitute 2 grams with 20 mL of NS or SWFI

Abbreviations: IVP, intravenous push; NS, 0.9% sodium chloride; NYULH, New York University Langone Health; SWFI, sterile water for injection. assessment of causality for adverse 34 (3%) patients were receiving di- patients (5%) received a median of 10 drug reactions, was calculated.15 alysis. Sixty-four (6%) patients had a (IQR 6, 16) doses of meropenem for a Statistical analysis. Descriptive history of seizures and 179 (18%) were median of 5 days (IQR 3, 7). Forty-three statistics were used to summarize dem- on at least 1 antiepileptic medication. patients (4%) received a median of 7 ographic and clinical characteristics. There was a median of 2 (1, 3) periph- (IQR 4, 11) doses of aztreonam IVP for Categorical variables were described eral lines placed per patient during a median of 3 days (IQR 2, 5). as frequencies and proportions, and IVP antibiotic administration. Three There were a total of 10 (1%) ADE continuous variables were described hundred seventy-nine (38%) patients seen among 10/1000 patients. Five as medians with interquartile ranges had a history of allergic reaction to a of these reactions were attributed to (IQRs). medication, 149 (15%) were receiving allergic reactions that were not cor- corticosteroids, and 199 (20%) were re- related with the IVP administration Results ceiving antihistamines during IVP an- of antibiotics. Allergic reactions in- A total of 1,134 consecutive pa- tibiotic administration. The majority of cluded 1 episode of drug reaction tients who received IVP aztreonam, patients (82%) were on anticoagulation with and systemic symp- ceftriaxone, cefepime, or meropenem for either prophylaxis or treatment of toms with ceftriaxone, 1 episode of between October 2017 and December thromboembolism. The most common rash with ceftriaxone, 1 episode of 2017 were reviewed. After excluding suspected or confirmed indications for hives with ceftriaxone, and two epi- 134 patients, primarily due to receipt receiving antibiotics were sodes of rash with cefepime. One ad- of multiple IVP antibiotics concom- (31%), urinary tract infections (28%), verse reaction was an infiltration of a itantly (82), missing documentation or intra-abdominal infections (19%). 20-gauge antecubital peripheral ve- (19), and receipt of only one dose of (Table 2) nous line after 6 doses of ceftriaxone the IVP antibiotic (18), we included Five hundred forty-four (54%) pa- IVP resulting in a grade 2 phlebitis. a total of 1,000 patients. The median tients received a median of 3 (IQR 2, The line was changed and ceftriaxone age was 70 years (IQR 56, 83) and 55% 5) doses of ceftriaxone for a median of IVP was continued without further were female, with a median body mass 3 days (IQR 2, 5). Three hundred sixty- ADE. The patient was not receiving index of 26 kg/m2 (IQR 22, 30). The me- eight patients (37%) received a median any other i.v. medications at the time dian clearance at the start of of 8 (IQR 4, 13) doses of cefepime for a of the ADE, and the calculated Naranjo IVP was 57 ml/min (IQR 33, 88), and median of 4 days (IQR 3, 6). Forty-five score was 1, indicating the ADE was

AM J HEALTH-SYST PHARM | VOLUME 77 | NUMBER 9 | MAY 1, 2020 703 NOTE SAFETY OF I.V. PUSH BETA-LACTAM THERAPY

“possibly” related to IVP ceftriaxone. Table 2. Characteristics of Antibiotic Administration Four (40%) adverse reactions were re- Variable Patients (n = 1000) lated to neurotoxicity with the use

of cefepime IVP. The neurotoxicity Downloaded from https://academic.oup.com/ajhp/article-abstract/77/9/701/5824399 by Biblioteca Nacional de Salud y Seguridad social user on 09 July 2020 Access characterized in these elderly patients Central line 125 (13) included altered mental status and my- Peripheral line 962 (96) oclonic jerking. Three of these patients Peripheral venous line 951 (99) had appropriate renal dose adjustment while one patient received a higher Midline 53 (6) dose than recommended. Three cases Number of lines per patient, median (IQR) 2 (1, 3) were graded as “possibly” and one case Indication for antibiotic therapya was graded as “probably” related to IVP Pneumonia 310 (31) administration of cefepime according to the Naranjo score. Details of these 275 (28) patients can be found in Table 3. Intra-abdominal infection 194 (19)

Skin/soft tissue infection 57 (6) Discussion Febrile 31 (3) Aztreonam, ceftriaxone, cefepime, Bacteremia 30 (3) and meropenem were safely adminis- 28 (3) tered via IVP during a shortage of SVPS 17 (2) at NYULH. In a total of 10 (1%) ADE, 15 (2) 5 were allergic reactions that were not correlated with IVP administration. Fever unknown origin 10 (1) Four ADE were neurotoxicity related to Endocarditis 7 (1) IVP cefepime and one report of phle- Spontaneous bacterial peritonitis 6 (1) bitis was observed with the use of IVP Non-meningeal central nervous system infection 2 (0.2) ceftriaxone. The existing evidence evaluating IVP Other indicationb 22 (2) beta-lactams has mainly assessed the Antibiotic therapy rates of phlebitis.8-10,13 Of the many fac- Ceftriaxone 544 (54) tors that can contribute to phlebitis, os- Every 12 hours 13 (2) molarity and rate of administration have 16– Every 24 hours 531 (98) been theorized to play significant roles. 18 Administration of a medication with Cefepime 368 (37) an osmolarity greater than 900 mOsm/L Every 8 hours 282 (77) through a peripheral line is thought to Every 12 hours 61 (17) put the patient at a higher risk for de- Every 24 hours 25 (7) velopment of phlebitis. The osmolarity Meropenem 45 (5) of IVP beta-lactams is determined by the individual beta-lactam and the dil- Every 6 hours 12 (27) uent used for its reconstitution.19 Based Every 8 hours 17 (38) on a review of the literature, the osmo- Every 12 hours 10 (22) larity of aztreonam and meropenem at Every 24 hours 6 (13) the concentrations used by NYULH has Aztreonam 43 (4) not been described. However, Gandhi and colleagues conducted osmolarity Every 8 hours 38 (88) testing of various beta-lactam anti- Every 12 hours 4 (9) biotics reconstituted in 10 mL of 0.9% Every 24 hours 1 (2) sodium chloride, and found that the os- Abbreviations: IQR, interquartile range. molarity of ceftriaxone 1 gram in 10 mL All values are expressed as n (%) unless otherwise noted. 0.9% sodium chloride was 658 mOsm/L, aPatients may have had more than one indication for antibiotic therapy. bOther indications include: Unknown (4), leukocytosis (3), bronchitis (2), foreign body and of cefepime 1 gram in 10 mL 0.9% prophylaxis (2), septic joint (2), transplant (1), catheter infection (1), COPD exacerbation sodium chloride was 1,040 mOsm/L.20 (1), Lemierre’s syndrome (1), parotitis (1), proctocolitis (1), cardiac arrest prophylaxis (1), suppurative sialadenitis (1), and surgical site infection (1). Despite the high osmolarity of cefepime

704 AM J HEALTH-SYST PHARM | VOLUME 77 | NUMBER 9 | MAY 1, 2020 SAFETY OF I.V. PUSH BETA-LACTAM THERAPY NOTE - Downloaded from https://academic.oup.com/ajhp/article-abstract/77/9/701/5824399 by Biblioteca Nacional de Salud y Seguridad social user on 09 July 2020 Description of Adverse Event 93-year-old M with ICH c/b seizures secondary to hyponatremia. secondary to hyponatremia. M with ICH c/b seizures 93-year-old Patient on cefepime 1 g every 8 hours (CrCl 55 ml/min) and with continued intermittent myoclonic for parotitis of hyponatremia. jerking after correction so patient Primary team concerned for cefepime neurotoxicity was changed to oral ciprofloxacin. PNA and UTI failure, F with acute hypoxic respiratory 89-year-old on cefepime 1 g every 24 hours (CrCl 8 ml/min, started dial - ysis) and with . changed cefepime to / on day 6 of Team therapy given concern for continued AMS due to cefepime neu - rotoxicity. AMS improved. Patient’s included cefepime, toxic-metabolic in setting of infec Differential and hypoglycemia. tion, hypoxia, uremia, SOB, cough, and hypoxia on M with increasing 84-year-old cefepime 1 g every 8 hours (CrCl 75 ml/min) and Patient also with acute confusion and AMS ID consult suggested discontinuation of cefepime due to concern for neurotoxicity. shock and obtunded in F with septic/cardiogenic 81-year-old fevers, and sepsis. setting of uremia, Cefepime dose not adjusted (every 12 hours) for declining renal function (CrCl < 10 ml/min) for 3 days until dialysis was initiated, at which point cefepime was changed to every 24 hours. with dialysis AMS did not improve change antibiotics to piperacillin/ ID consult recommended tazobactam with concern for cefepime neurotoxicity. • • • • • • • • • • • • • • 3 4 5 2 Score Naranjo Medications Other Concomitant history) Anticoagulant Anticoagulant Corticosteroid Anticoagulant Antihistamine Anticoagulant, Antiepileptic drug (seizure Type of i.v. access of i.v. Type Basilic 20-, 22-gauge PVL Cephalic, Basilic 20-gauge PVL Cubital, Metatarsal 20-, 22-gauge PVL Metacarpal, Basilic 20-, 22-gauge PVL Antecubital, Cephalic, 6 3 12 23 to Event # Doses Prior → every 24 hours n = 4) Adverse Reactions ( 3. Details of Cefepime Neurotoxicity Table IVP Antibiotic University Langone female; M, male; NYULH, New York intravenous push; IVPB, piggyback; F, IVP, mental status; c/b, complicated by; ICH, intracranial hemorrhage; AMS, altered Abbreviations: Health; PNA, pneumonia; PVL, peripheral venous line; UTI, urinary tract infection. the same antibiotic as IVPB at NYULH in past. All other cases of adverse events had not received The patient who experienced phlebitis had a history of tolerating ceftriaxone as IVPB. Cefepime every 24 hours Cefepime every 8 hours Cefepime every 12 hours Cefepime every 8 hours

AM J HEALTH-SYST PHARM | VOLUME 77 | NUMBER 9 | MAY 1, 2020 705 NOTE SAFETY OF I.V. PUSH BETA-LACTAM THERAPY at this concentration, we did not ob- rate of 0.4%. Despite the limited patient medical record by either nursing or serve any infusion site reactions with population and small sample sizes, the provider, and therefore the rate of cefepime administered as IVP via pe- these studies demonstrate that IVP ADE may have been underestimated.

ripheral lines. We hypothesize that this administration of and While our sample size for aztreonam Downloaded from https://academic.oup.com/ajhp/article-abstract/77/9/701/5824399 by Biblioteca Nacional de Salud y Seguridad social user on 09 July 2020 finding was due to the minimal duration has similar rates of phle- and meropenem IVP was small, these (5 minutes­ or less) of cefepime adminis- bitis as compared to IVPB. antibiotics are FDA approved for ad- tration through the line, a finding similar Our study expands on the existing ministration via this route, and our data to that of previously published literature literature for the safety of IVP adminis- supports the safety of this administra- evaluating ADE with 3% sodium chlo- tration of beta-lactam antibiotics. In the tion strategy. Finally, we did not directly ride (1,026 mOsm/L) administered pe- prior studies, patients received only the compare IVP to IVPB administration in ripherally for a mean duration of 47 first dose of antibiotic administration this study due to its nature as a quality minutes.21 as IVP, and the indication was mainly assurance project during the shortage. The rate of administration between limited to surgical prophylaxis.6,8-12 In Despite these limitations, the use of each individual beta-lactam has varied comparison, patients at our institution IVP administration was safe in this real- throughout the literature. Garrelts and received IVP for the duration of their world setting and can be considered as colleagues published a prospective, antibiotic course, regardless of indica- a fluid conservation strategy in times of randomized study comprised of 60 pa- tion. Furthermore, while prior studies shortage of SVPS. tients who received IVPB limited their evaluation to phlebitis, over 30 minutes vs IVP over 3 min- we included observation for cardiac, Conclusion utes for the purpose of surgical pro- neurologic, and gastrointestinal dis- phylaxis.8 No statistic­ally significant turbances.8-10 We found 4/368 (1%) The use of IVP as an alternative to difference in phlebitis was observed. cases of neurotoxicity associated with IVPB during times of drug shortage Another study evaluated cefepime the use of cefepime IVP, a finding sim- for select beta-lactam antibiotics ap- administration over 3-, 5-, 10-, or 15-mi- ilar or less than that reported in previous pears to be safe, and ADE are sim- nute periods, and found no serious literature with IVPB administration.23-25 ilar to those previously described for ADE, however, the total volume of solu- Similarly to Appa and colleagues, we IVPB administration. Future studies tion utilized was 50 mL.9 Additionally, found that cefepime neurotoxicity oc- evaluating clinical outcomes between in a prospective, observational study curred in elderly patients with varying IVP and IVPB administration may be consisting of 240 adult orthopedic sur- levels of renal function. Only one case of benefit. gical patients, there was no observed in our report was graded as “probably” differences in the rates of phlebitis related to IVP CEF administration ac- Disclosures in candidates who received cefazolin cording to the Naranjo score. The authors have declared no potential con- flicts of interest. IVPB over 30 minutes compared to Administration of beta-lactam anti- IVP over 3 to 5 minutes (3.4% vs 3.3%, biotics as IVP over 5 minutes may lead P = NS).13 The authors also conducted to suboptimal pharmacodynamic target Additional information a univariate analysis that highlighted attainment given their time-dependent The data have been presented in poster format at the ASHP Midyear Clinical Meeting that patients with more catheter days activity.7,26 As there was no evaluation of in Anaheim, CA, in December 2018 and at the (2 vs 1.36) were at a greater risk of phle- efficacy in our study, further literature Making a Difference in Infectious Diseases bitis.13 For IVP carbapenems, Norrby comparing IVP to IVPB is necessary to (MAD-ID) Annual Meeting in Orlando, FL, in and colleagues reviewed 2,457 admin- ensure this route of administration is not May 2019. istrations of meropenem i.v. given over associated with worse clinical response. 30 minutes vs 5 minutes, and found a Furthermore, the NYULH protocol re- References phlebitis occurrence rate of 0.7%.22 The commends administration of IVP over 1. Patiño AM, Marsh RH, Nilles EJ, authors reported 165 patients receiving 5 minutes, and as administration was Baugh CW, Rouhani SA, Kayden S. one or more doses of meropenem by completed manually by nursing staff Facing the shortage of IV fluids - A hospital-based oral rehy- bolus injection administered over ap- rather than via a syringe pump, there dration strategy. N Engl J Med. proximately 5 minutes, with no reports is no documentation of the actual rate 2018;378(16):1475-1477. of drug-related ADE specifically attrib- of infusion in this cohort. It was pos- 2. Loewenthal MR, Dobson PM. uted to the speed of administration. sible that administration of these IVP and gentamicin Overall, the reported rate of phlebitis in antibiotics occurred over a duration of can safely be given by slow push. J Antimicrob Chemother. prior studies of IVP beta-lactams ranges less than 5 minutes. Given the retro- 2010;65(9):2049-2050. 8-10,13 from 0–3.3%. In line with previous spective nature of this study, collection 3. Mendelson J, Portnoy J, Dick V, Black M. literature, we found an overall phlebitis of ADE relied on documentation in the Safety of the bolus administration

706 AM J HEALTH-SYST PHARM | VOLUME 77 | NUMBER 9 | MAY 1, 2020 SAFETY OF I.V. PUSH BETA-LACTAM THERAPY NOTE

of gentamicin. Antimicrob Agents intravenous piggyback administration dispensing. JPEN J Parenter Enteral Chemother. 1976;9(4):633-638. of antimicrobial agents. Clin Pharm. Nutr. 2014;38(3):334-377. 4. Meunier F, Van der Auwera P, 1988;7(10):760-765. 20. Gandhi RG, Steiger SN, Elshaboury RH, Schmitt H, de Maertelaer V, 11. Poole SM, Nowobilski-Vasilios A, Lund JT. I.V. push administra-

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