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JAMDA xxx (2019) 1e2
JAMDA
journal homepage: www.jamda.com
Research Letter
Safety of Subcutaneous Piperacillin/
Tazobactam Administration Compared
to Intravenous Administration:
Propensity ScoreeMatched Cohort
Study
Currently, the subcutaneous administration of antibiotics is
considered to be an alternative route to intravenous administration
because of its safety and effectiveness in treating bacterial infec-
tion,1 leading to its widespread use, especially for palliative pur-
poses.2 Oral intolerance, poor venous access, refusal or
contraindication of central venous access, and refusal or contrain-
dication of intramuscular administration are common reasons for
choosing subcutaneous administration of antibiotics.1,3,4
According to earlier reviews, carbapenem, cephalosporines,
glycopeptide, penicillin, and aminoglycoside are safe for subcu-
taneous administration.5 We concluded that except for amino-
glycoside, these antibiotics are well tolerated and are
therapeutically effective. Piperacillin/tazobactam (PIPC/TAZ) is
currently one of the most commonly used broad-spectrum antibi-
otics to treat bacterial infection.6,7 However, PIPC/TAZ is usually
administered intravenously and rarely subcutaneously to patients
with bacterial infection, although some physicians and researchers
are interested in subcutaneous administration. As a result, almost
no research or reports have been published on the safety and effi-
cacy of subcutaneous PIPC/TAZ administration.
In this regard, our hospital has experience administering PIPC/
TAZ subcutaneously to infected patients formore than 10 years. The
aim of this study was to evaluate the safety of subcutaneous vs
intravenous administration of PIPC/TAZ among nonterminal
patients with propensity score matching.
We conducted a retrospective cohort study with propensity
score matching at a large teaching hospital in Tokyo, Japan,
from January 2005 to December 2018. We included all adult
inpatients who were treated with PIPC/TAZ as potential partic-
ipants. We excluded patients who were admitted to the hos-
pital’s palliative care unit. Our primary outcome was number of
adverse events due to PIPC/TAZ, and our secondary outcome
was in-hospital mortality due to infectious diseases. We
compared these outcomes between patients who were admin-
istered PIPC/TAZ subcutaneously and intravenously. The hospi-
tal’s ethics committee approved the study (approval number:
19-R010).
The authors declare no conflicts of interest.
https://doi.org/10.1016/j.jamda.2019.08.010
1525-8610/� 2019 Published by Elsevier Inc. on behalf of AMDA e The Society for Post
We included a total of 9226 potential patients in this study; 113
received PIPC/TAZ subcutaneously and 9113 received PIPC/TAZ
intravenously. Using logistic regression to calculate the propensity
score, we identified metastatic cancer, solid tumor without
metastasis, fluid and electrolyte disorders, hypothyroidism and
coagulopathy in Elixhauser comorbidity index, neoplasm in pri-
mary diagnosis, and albumin and hemoglobin in laboratory mea-
sures as the selected variables.
Finally, 112 patients who received PIPC/TAZ subcutaneously
were matched to 336 patients who received PIPC/TAZ intrave-
nously. During follow-up, 17 patients had adverse events (11 had
rash, 1 had fever, 1 had nausea, 1 had thrombocytopenia, 1 had
itchiness, and 1 had liver injury), but none of them were life-
threatening. Fisher exact test showed no significant differences in
adverse events between subcutaneous and intravenous adminis-
tration [subcutaneous vs intravenous: 1 (0.9%) vs 16 (4.7%), P¼ .08].
In terms of in-hospital mortality due to infectious diseases, 6
patients (5.4%) in the subcutaneous group and 28 patients (8.3%) in
the intravenous group died from infectious disease (P ¼ .30).
Multivariable logistic regression revealed that the subcutaneous
group still had a significantly higher odds ratio of in-hospital
mortality due to infectious diseases compared with the
intravenous group (adjusted odds ratio 0.73, 95% confidence in-
terval 0.27-2.01).
As to all-cause mortality, 99 patients (88.4%) in the subcutane-
ous group and 201 patients (59.8%) in the intravenous group died in
the hospital (P < .01). Our propensity scoreematched study
demonstrated that subcutaneous PIPC/TAZ administration had a
lower, rather than similar, incidence of adverse events due to an-
tibiotics compared with intravenous administration. In-hospital
mortality due to infectious diseases was also similar, but all-cause
mortality was significantly higher in the subcutaneous PIPC/TAZ
group compared with that in the intravenous PIPC/TAZ group.
To our knowledge, this study was the first to evaluate the safety
of subcutaneous PIPC/TAZ administration. In contrast to the drug
information in authorized secondary media,8 in our study, the pa-
tients who received intravenous PIPC/TAZ administration had a
relatively lower incidence of adverse events. In addition, those who
were administered PIPC/TAZ subcutaneously had much lower rates
of adverse events.
Furthermore, as stated by general theory and similar to other
antibiotics, subcutaneous PIPC/TAZ administration also may be
safe. Patients who received PIPC/TAZ subcutaneously had similar
in-hospital mortality due to infectious diseases compared with
those who received PIPC/TAZ intravenously after propensity score
matching. Although there were no datadeven in animal mod-
elsdon serum concentration after subcutaneous administration of
PIPC/TAZ, our findings may suggest that PIPC/TAZ is still effective
for infection even when administered subcutaneously. However, in
terms of all-cause mortality, patients who were administered PIPC/
-Acute and Long-Term Care Medicine.
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https://doi.org/10.1016/j.jamda.2019.08.010
Research Letter / JAMDA xxx (2019) 1e22
TAZ subcutaneously had higher all-cause in-hospital mortality
compared with those who received it intravenously.
Therefore, subcutaneous PIPC/TAZ administration can be used
safely, and it has a similar incidence of adverse events as other an-
tibiotics and similar in-hospital mortality due to infectious disease.
Acknowledgments
The authors express sincere thanks to Ms Aya Oizumi and Ms
Chika Horikawa for data extraction.
References
1. Noriega OD, Yarleque Leon SN. Antibiotics by subcutaneous route: A safe and
efficient alternative. J Am Med Dir Assoc 2018;19:553e554.
2. Gallardo R, Miguel Gamboa F. Feasibility of subcutaneous antibiotics for pallia-
tive care patients. Glob Drugs Therap 2017;2:1e5.
3. Roubaud-Baudron C, Forestier E, Fraisse T, et al. Tolerance of subcutaneously
administered antibiotics: A French national prospective study. Age Ageing 2017;
46:151e155.
4. Forestier E, Paccalin M, Roubaud-Baudron C, et al. Subcutaneously administered
antibiotics: A national survey of current practice from the French Infectious
Diseases (SPILF) and Geriatric Medicine (SFGG) society networks. Clin Microbiol
Infect 2015;21:370.e1e370.e3.
5. Farias Azevedo E, Augusto Barbosa L, Bortoli Cassiani SH. Administration of
antibiotics subcutaneously: An integrative literature review. Acta Paul Enferm
2012;25:817e822.
6. Yang H, Cui X, Ma Z, Liu L. Evaluation outcomes associated with alternative
dosing strategies for piperacillin/tazobactam: A systematic review and meta-
analysis. J Pharm Pharm Sci 2016;19:274e289.
7. Mah GT, Mabasa VH, Chow I, Ensom MH. Evaluating outcomes associated with
alternative dosing strategies for piperacillin/tazobactam: A qualitative system-
atic review. Ann Pharmacother 2012;46:265e275.
8. van der Steeg WA, Holme I, Boekholdt SM, et al. High-density lipoprotein
cholesterol, high-density lipoprotein particle size, and apolipoprotein A-I: Sig-
nificance for cardiovascular risk: The IDEAL and EPIC-Norfolk studies. J Am Coll
Cardiol 2008;51:634e642.
Daiki Kobayashi, MD, MPH, MBA, PhD
Division of General Internal Medicine
Department of Medicine
St. Luke’s InternationalHospital
Tokyo, Japan
Department of Epidemiology
St. Luke’s International University Graduate School of Public Health
Tokyo, Japan
Fujita Health University
Toyoake, Japan
Misuzu Cho, MD
Department of Palliative Care
St. Luke’s International Hospital
Tokyo, Japan
Kyoko Yokota, MD, MSc
Department of Infectious Disease
Kagawa Prefectural Central Hospital
Takamatsu, Japan
Takuro Shimbo, MD, PhD
Ohta Nishinouchi Hospital
Koriyama, Japan
http://refhub.elsevier.com/S1525-8610(19)30619-X/sref1
http://refhub.elsevier.com/S1525-8610(19)30619-X/sref1
http://refhub.elsevier.com/S1525-8610(19)30619-X/sref1
http://refhub.elsevier.com/S1525-8610(19)30619-X/sref2
http://refhub.elsevier.com/S1525-8610(19)30619-X/sref2
http://refhub.elsevier.com/S1525-8610(19)30619-X/sref2
http://refhub.elsevier.com/S1525-8610(19)30619-X/sref3
http://refhub.elsevier.com/S1525-8610(19)30619-X/sref3
http://refhub.elsevier.com/S1525-8610(19)30619-X/sref3
http://refhub.elsevier.com/S1525-8610(19)30619-X/sref3
http://refhub.elsevier.com/S1525-8610(19)30619-X/sref4
http://refhub.elsevier.com/S1525-8610(19)30619-X/sref4
http://refhub.elsevier.com/S1525-8610(19)30619-X/sref4
http://refhub.elsevier.com/S1525-8610(19)30619-X/sref4
http://refhub.elsevier.com/S1525-8610(19)30619-X/sref4
http://refhub.elsevier.com/S1525-8610(19)30619-X/sref5
http://refhub.elsevier.com/S1525-8610(19)30619-X/sref5
http://refhub.elsevier.com/S1525-8610(19)30619-X/sref5
http://refhub.elsevier.com/S1525-8610(19)30619-X/sref5
http://refhub.elsevier.com/S1525-8610(19)30619-X/sref6
http://refhub.elsevier.com/S1525-8610(19)30619-X/sref6
http://refhub.elsevier.com/S1525-8610(19)30619-X/sref6
http://refhub.elsevier.com/S1525-8610(19)30619-X/sref6
http://refhub.elsevier.com/S1525-8610(19)30619-X/sref7
http://refhub.elsevier.com/S1525-8610(19)30619-X/sref7
http://refhub.elsevier.com/S1525-8610(19)30619-X/sref7
http://refhub.elsevier.com/S1525-8610(19)30619-X/sref7
http://refhub.elsevier.com/S1525-8610(19)30619-X/sref8
http://refhub.elsevier.com/S1525-8610(19)30619-X/sref8
http://refhub.elsevier.com/S1525-8610(19)30619-X/sref8
http://refhub.elsevier.com/S1525-8610(19)30619-X/sref8
http://refhub.elsevier.com/S1525-8610(19)30619-X/sref8
	Safety of Subcutaneous Piperacillin/Tazobactam Administration Compared to Intravenous Administration: Propensity Score–Matc ...
	Acknowledgments
	References