JAMDA xxx (2019) 1e2

JAMDA
journal homepage: www.jamda.com

Research Letter

Safety of Subcutaneous Piperacillin/ We included a total of 9226 potential patients in this study; 113
received PIPC/TAZ subcutaneously and 9113 received PIPC/TAZ
Tazobactam Administration Compared intravenously. Using logistic regression to calculate the propensity
score, we identified metastatic cancer, solid tumor without
to Intravenous Administration: metastasis, fluid and electrolyte disorders, hypothyroidism and
Propensity ScoreeMatched Cohort coagulopathy in Elixhauser comorbidity index, neoplasm in pri-
mary diagnosis, and albumin and hemoglobin in laboratory mea-
Study 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
Currently, the subcutaneous administration of antibiotics is
rash, 1 had fever, 1 had nausea, 1 had thrombocytopenia, 1 had
considered to be an alternative route to intravenous administration
itchiness, and 1 had liver injury), but none of them were life-
because of its safety and effectiveness in treating bacterial infec-
threatening. Fisher exact test showed no significant differences in
tion,1 leading to its widespread use, especially for palliative pur-
adverse events between subcutaneous and intravenous adminis-
poses.2 Oral intolerance, poor venous access, refusal or
tration [subcutaneous vs intravenous: 1 (0.9%) vs 16 (4.7%), P ¼ .08].
contraindication of central venous access, and refusal or contrain-
In terms of in-hospital mortality due to infectious diseases, 6
dication of intramuscular administration are common reasons for
patients (5.4%) in the subcutaneous group and 28 patients (8.3%) in
choosing subcutaneous administration of antibiotics.1,3,4
the intravenous group died from infectious disease (P ¼ .30).
According to earlier reviews, carbapenem, cephalosporines,
Multivariable logistic regression revealed that the subcutaneous
glycopeptide, penicillin, and aminoglycoside are safe for subcu-
group still had a significantly higher odds ratio of in-hospital
taneous administration.5 We concluded that except for amino-
mortality due to infectious diseases compared with the
glycoside, these antibiotics are well tolerated and are
intravenous group (adjusted odds ratio 0.73, 95% confidence in-
therapeutically effective. Piperacillin/tazobactam (PIPC/TAZ) is
terval 0.27-2.01).
currently one of the most commonly used broad-spectrum antibi-
As to all-cause mortality, 99 patients (88.4%) in the subcutane-
otics to treat bacterial infection.6,7 However, PIPC/TAZ is usually
ous group and 201 patients (59.8%) in the intravenous group died in
administered intravenously and rarely subcutaneously to patients
the hospital (P < .01). Our propensity scoreematched study
with bacterial infection, although some physicians and researchers
demonstrated that subcutaneous PIPC/TAZ administration had a
are interested in subcutaneous administration. As a result, almost
lower, rather than similar, incidence of adverse events due to an-
no research or reports have been published on the safety and effi-
tibiotics compared with intravenous administration. In-hospital
cacy of subcutaneous PIPC/TAZ administration.
mortality due to infectious diseases was also similar, but all-cause
In this regard, our hospital has experience administering PIPC/
mortality was significantly higher in the subcutaneous PIPC/TAZ
TAZ subcutaneously to infected patients for more than 10 years. The
group compared with that in the intravenous PIPC/TAZ group.
aim of this study was to evaluate the safety of subcutaneous vs
To our knowledge, this study was the first to evaluate the safety
intravenous administration of PIPC/TAZ among nonterminal
of subcutaneous PIPC/TAZ administration. In contrast to the drug
patients with propensity score matching.
information in authorized secondary media,8 in our study, the pa-
We conducted a retrospective cohort study with propensity
tients who received intravenous PIPC/TAZ administration had a
score matching at a large teaching hospital in Tokyo, Japan,
relatively lower incidence of adverse events. In addition, those who
from January 2005 to December 2018. We included all adult
were administered PIPC/TAZ subcutaneously had much lower rates
inpatients who were treated with PIPC/TAZ as potential partic-
of adverse events.
ipants. We excluded patients who were admitted to the hos-
Furthermore, as stated by general theory and similar to other
pital’s palliative care unit. Our primary outcome was number of
antibiotics, subcutaneous PIPC/TAZ administration also may be
adverse events due to PIPC/TAZ, and our secondary outcome
safe. Patients who received PIPC/TAZ subcutaneously had similar
was in-hospital mortality due to infectious diseases. We
in-hospital mortality due to infectious diseases compared with
compared these outcomes between patients who were admin-
those who received PIPC/TAZ intravenously after propensity score
istered PIPC/TAZ subcutaneously and intravenously. The hospi-
matching. Although there were no datadeven in animal mod-
tal’s ethics committee approved the study (approval number:
elsdon serum concentration after subcutaneous administration of
19-R010).
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/
The authors declare no conflicts of interest.

https://doi.org/10.1016/j.jamda.2019.08.010
1525-8610/Ó 2019 Published by Elsevier Inc. on behalf of AMDA e The Society for Post-Acute and Long-Term Care Medicine.
2 Research Letter / JAMDA xxx (2019) 1e2

TAZ subcutaneously had higher all-cause in-hospital mortality 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-
compared with those who received it intravenously.
nificance for cardiovascular risk: The IDEAL and EPIC-Norfolk studies. J Am Coll
Therefore, subcutaneous PIPC/TAZ administration can be used Cardiol 2008;51:634e642.
safely, and it has a similar incidence of adverse events as other an-
tibiotics and similar in-hospital mortality due to infectious disease. Daiki Kobayashi, MD, MPH, MBA, PhD
Division of General Internal Medicine
Acknowledgments Department of Medicine
St. Luke’s International Hospital
The authors express sincere thanks to Ms Aya Oizumi and Ms Tokyo, Japan
Chika Horikawa for data extraction.
Department of Epidemiology
St. Luke’s International University Graduate School of Public Health
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