Morimoto et al.

Renal Replacement Therapy (2020) 6:19

https://doi.org/10.1186/s41100-020-00270-3

REVIEW Open Access

The impact of intraperitoneal antibiotic

administration in patients with peritoneal
dialysis-related peritonitis: systematic
review and meta-analysis
Kohkichi Morimoto1,2*, Hiroyuki Terawaki1,3, Naoki Washida1,4, Takahiro Kasai1,4, Yasushi Tsujimoto1,5,
Hidemichi Yuasa1,6, Munekazu Ryuzaki1,7, Yasuhiko Ito1,8, Masashi Tomo1,9, Hidetomo Nakamoto1,10 and on behalf
of Working Group on Revision of Peritoneal Dialysis Guidelines

Abstract
Background: Peritonitis is a common and clinically important complication in patients receiving peritoneal dialysis
(PD). Antibiotic administration is essential for PD-related peritonitis, but routes of administration have not been
established enough. Here, we performed a systematic review to assess the efficacy and safety of intraperitoneal (IP)
antibiotic administration compared to intravenous (IV) antibiotic administration in patients with PD-related peritonitis.
Methods: Cochrane CENTRAL, MEDLINE, and Ichushi-Web were searched in June 2017. Preferred Reporting Items for
Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed, and articles were screened by four
independent reviewers.
Results: Two randomized controlled trials (113 patients) were identified. IP antibiotic administration was more effective
than IV antibiotic administration. The pooled risk difference between IP and IV was 0.13 (95% CI − 0.17 to 0.43). Safety
assessment indicated less frequency of side effects in patients receiving IP antibiotic administration. The pooled risk
ratios of IV to IP regarding adverse drug reaction-related and administration route-related side effects were 5.13 (0.63 to
41.59) and 3.00 (0.14 to 65.90), respectively.
Conclusion: The systematic review and meta-analysis suggested that IP antibiotic administration is more effective and
safer in patients with PD-related peritonitis compared to IV antibiotic administration.
Keywords: Peritoneal dialysis, Peritonitis, Intraperitoneal antibiotics, Intravenous antibiotics

* Correspondence: [email protected]
1
Working Group on Revision of Peritoneal Dialysis Guidelines, Japanese
Society for Dialysis Therapy, Tokyo, Japan
2
Apheresis and Dialysis Center, School of Medicine, Keio University, Tokyo,
Japan
Full list of author information is available at the end of the article

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Morimoto et al. Renal Replacement Therapy (2020) 6:19 Page 2 of 6

Introduction because this study did not involve patient intervention

Peritoneal dialysis (PD) is a well-established modality of and confidential personal data collection.
renal replacement therapy for patients with end-stage renal
disease. The utilization and popularization of PD are rapidly Research question and eligibility criteria
growing, particularly in developing countries, where the The research question of this review was: “Is IP anti-
number of patients receiving PD has increased more than biotic administration superior in efficacy and safety to
2-fold during the last decade [1]. Although technical im- IV administration in patients with PD-related periton-
provements and innovations of PD-related clinical practice itis?” We included published randomized controlled tri-
have significantly decreased PD-associated infectious com- als (RCTs) comparing IP administration with IV, of any
plications including PD-related peritonitis and exit-site/tun- race and gender, in any language, and from any country.
nel infection, they are still one of the major barriers which We excluded observational studies, case reports, and
adversely affects both technical and patient survival in PD case series.
patients [2, 3].
The International Society for Peritoneal Dialysis (ISPD) Outcomes of interest
published guidelines and recommendations about PD- The outcomes were treatment success (cure of periton-
related peritonitis in 1983, which were revised in 1993, itis after antibiotic administration) and complication.
1996, 2000, 2005, 2010, and 2016 [3–8]. The most recent
recommendations published in 2016 are organized into the
Search strategy and study selection
following five sections: (1) peritonitis rate, (2) prevention of
We searched the Cochrane Central Register of Controlled
peritonitis, (3) initial presentation and management of peri-
Trials (CENTRAL), MEDLINE via PubMed, and NPO
tonitis, (4) subsequent management of peritonitis, and (5)
Japan Medical Abstracts Society (JMAS) databases. The
future research. In practical cases of PD-related peritonitis,
search was performed in June 2017 (Cochrane CENTRAL
proper initial management consists of diagnosis, subse-
and PubMed) and in April 2017 (JMAS) using the follow-
quent appropriate microbiological culture sampling, and
ing suitable search terms: peritoneal dialysis, peritonitis,
prompt empirical antibiotic therapy, followed by antibiotic
intraperitoneal injection/administration, intravenous in-
de-escalation in certain cases. Treatment intent of antibiotic
jection/administration. Four reviewers (KM, HT, NW, and
administration is a rapid resolution of inflammation to pro-
TK) independently screened the title and abstract of each
tect the peritoneal membrane. As an empirical regimen, a
study to select candidate studies, and the reviewers per-
proportional meta-analysis revealed that the combination
formed a full-text review to evaluate the eligibility of each
of a glycopeptide (vancomycin or teicoplanin) and ceftazi-
candidate study.
dime is considered to be superior to other regimens [9].
In terms of antibiotic administration, intraperitoneal
(IP) administration is preferred (GRADE 1B) in the most Assessment of risk of bias in included studies
recent ISPD recommendations, without cases presenting The selected studies were independently assessed by four
systemic sepsis [3]. In general, IP administration is con- authors (KM, HT, NW, and TK) using the risk of bias
sidered to bring about higher peritoneal drug concentra- assessment tool, as previously described (Cochrane
tion than intravenous (IV) administration [3]. Moreover, Handbook for Systematic Reviews of Interventions Ver-
IP administration is available without vascular puncture. sion 5.1.0; available at www.cochrane-handbook.org),
Several clinical studies comparing IP administration with and discrepancies were resolved by consultation with
IV administration for PD-related peritonitis revealed HY and YT: random sequence generation (selection
controversial results [10, 11], and the clinical advantage bias), allocation concealment (selection bias), blinding of
of the recommended IP administration has not been participants and personnel (performance and detection
established enough. Here, we performed a systematic re- bias), incomplete outcome data (attention bias), selective
view to assess the efficacy and safety of IP administration reporting (reporting bias), and other potential biases.
compared to IV administration in patients with PD-
related peritonitis. Measurement of treatment effect
Data from each trial was analyzed using the risk ratio
Methods with 95% confidence intervals (CI) for binary outcomes
Compliance with reporting guidelines and using the mean difference for continuous outcomes.
We conducted a systematic review of the relevant litera-
ture in agreement with the recommendations listed in Analysis and data synthesis
the Preferred Reporting Items for Systematic Reviews All analyses were conducted using Review Manager (Rev-
and Meta-Analysis (PRISMA) guidelines [12]. Exemption Man) Version 5.3 (Copenhagen: The Nordic Cochrane
from the review was granted by the Ethics Committee Centre, The Cochrane Collaboration).
Morimoto et al. Renal Replacement Therapy (2020) 6:19 Page 3 of 6

Table 1 Characteristics of the included studies

Literature Research design Participants Intervention Control Outcomes
Bailie et al. Nephron RCT 20 patients with PD-related IP administration, IV administration, VCM No difference in serum
1987 46 316 peritonitis, (GPC-positive) VCM 1 g, 1 g, as initial therapy VCM levels
1 hospital, the UK as initial therapy 3 cases of route-related
complication
Bennett-Jones et al. J RCT 93 patients with PD-related IP administration, IV administration, Success in therapy, 35 of
Antimicrob Chemother peritonitis, 1 hospital, the UK VCM 20 mg/L and VCM 0.5 or 1.0 g, TOB 39 cases (89.1%) vs. 23 of
1990 26 73 TOB 4 mg/L 1.0 mg/kg 36 cases (65.9%) (p < 0.02)
RCT randomized controlled trial, PD peritoneal dialysis, IP intraperitoneal, IV intravenous, VCM vancomycin, TOB tobramycin

Assessment of the certainty of evidence the removal of duplicates and the selection by the re-
We prepared a summary of findings table including an viewers, we identified two articles of RCT met the eligi-
overall grading of evidence certainty for the outcomes, bility criteria (Table 1).
which was evaluated using the Grading of Recommenda-
tion Assessment, Development and Evaluation (GRADE) Study characteristics
approach [13, 14]. The characteristics of the included studies are shown in
The recommendations follow the Grading of Recom- Table 2. A total of 113 patients from the two RCTs pub-
mendation Assessment, Development and Evaluation lished in 1987 and 1990 were included [16, 17]. Bailie
(GRADE) system for the classification of the level of evi- et al. compared IP with IV as the initial antibiotic ad-
dence and grade of recommendations in clinical guide- ministration (vancomycin 1 g/body as a loading dose)
line reports [15]. With each recommendation, the for PD-related peritonitis. The patients in both groups
strength of the recommendation is indicated as level 1 were treated with maintenance IP antibiotic administra-
(we recommend), level 2 (we suggest), or not graded, tion [16]. Bennett-Jones et al. compared IP (vancomycin
and the quality of the supporting evidence is shown as A 20 mg/L + tobramycin 4 mg/L in dialysate) with IV
(high quality), B (moderate quality), C (low quality), or (vancomycin 0.5–1.0 g/body + tobramycin 1.0 mg/kg
D (very low quality). body weight) as the initial and maintenance antibiotic
administration [17] (Table 1).
Results
Search results Risk of bias
The described electronic search of the databases identi- The assessment of risk of bias of the included studies is
fied 171 candidate studies via the Cochrane CENTRAL, shown in Table 2. In terms of “success in therapy,” “drug-
1094 via PubMed, and 463 via JMAS databases. After related complication,” and “route-related complication,”

Table 2 Risk of bias summary of the included studies

Morimoto et al. Renal Replacement Therapy (2020) 6:19 Page 4 of 6

the risk of bias domains of randomization, allocation con- pooled risk difference between IP and IV was 0.13 (95%
cealment, blinding of outcome assessors, and other CI − 0.17 to 0.43). Safety assessment indicated less fre-
sources in the two studies and of incomplete outcome quency of side effects in patients receiving IP adminis-
data in one study were considered “unclear” because we tration. The pooled risk ratios of IV to IP regarding
could not find enough information to assess the domains. adverse drug reaction-related and administration route-
Blinding of participants was considered “high risk” be- related side effects were 5.13 (0.63 to 41.59) and 3.00
cause blinding was limited in the two studies. Reporting (0.14 to 65.90), respectively (Fig. 1).
bias was also considered “high risk.” In one RCT, incom-
plete outcome data was considered “low risk” because all Discussion
participants were traced during the study. PD-related peritonitis is a major complication of PD
and is one of the leading causes of technical failure and
Effect and complication of interventions mortality in patients receiving PD. To prevent serious
We conducted a meta-analysis with the identified and clinical outcomes, proper management of peritonitis,
included two RCTs (113 patients). IP antibiotic adminis- including prompt diagnosis and empirical antibiotic
tration was more effective than IV administration. The therapy followed by subsequent management, is

A. Success in therapy
IV IP

B. Drug-related complication
IV IP

C. Administration route-related complication

IV IP

Fig. 1 Forest plot. The meta-analysis of the risk ratios of the success in therapy (a), drug-related complication (b), and administration route-related
complication (c)
Morimoto et al. Renal Replacement Therapy (2020) 6:19 Page 5 of 6

important. ISPD recommends empirical antibiotic ther- Authors’ contributions

apy with a center-specific regimen covering both KM, HT, NW, and TK mainly undertook this review. The literatures were
screened independently by KM, HT, NW, and TK. HY and YT participated in
Gram-positive and Gram-negative microorganisms, im- the design of the study and performed the statistical analysis. MR and YI
mediately after appropriate microbiological sampling conceived the study. MT and HN participated in its design and coordination
[3]. The current recommendations of antibiotics are and helped to draft the manuscript. All authors read and approved the final
manuscript.
vancomycin or first-generation cephalosporin for Gram-
positive organism coverage, and third-generation ceph- Funding
alosporin or aminoglycoside for Gram-negative organ- Not applicable.
ism coverage [3]. In terms of antibiotic administration
route, IP is preferred in ISPD recommendations, un- Availability of data and materials
Please contact the authors for data requests.
less there are clinical presentations of systemic sepsis
or a foreseeable delay (e.g., combination of catheter
Ethics approval and consent to participate
obstruction) in IP administration [3, 18]. Not applicable.
While IP is a less common route than IV, oral or
topic use of antibiotic administration in general clinical Consent for publication
situations of infectious diseases, IP is regarded as a Not applicable.
common and established antibiotic administration
Competing interests
route in patients with PD-related patients. The usability
The authors declare that they have no competing interests.
of PD catheter as peritoneal access and the relative
easiness of drug administration in outpatient clinics Author details
1
Working Group on Revision of Peritoneal Dialysis Guidelines, Japanese
would contribute to the uniqueness. Oral antibiotic ad-
Society for Dialysis Therapy, Tokyo, Japan. 2Apheresis and Dialysis Center,
ministration is also compatible with outpatient medical School of Medicine, Keio University, Tokyo, Japan. 3Department of Internal
service, but it would be difficult to cover possible Medicine, Nephrology, Teikyo University Chiba Medical Center, Chiba, Japan.
4
Department of Nephrology, International University of Health and Welfare,
causative pathogens enough only with oral antibiotics.
Chiba, Japan. 5Department of Healthcare Epidemiology, School of Public
In addition, antibiotic treatment should aim for rapid Health in the Graduate School of Medicine, Kyoto University, Kyoto, Japan.
6
resolution of inflammation to preserve the peritoneal Department of Dental and Oral Surgery, National Hospital Organization
Toyohashi Medical Center, Aichi, Japan. 7Department of Nephrology, Saiseikai
membrane function, but oral administration generally
Central Hospital, Tokyo, Japan. 8Department of Nephrology and
requires additional time in drug absorption and intra- Rheumatology, Aichi Medical University, Aichi, Japan. 9Faculty of Medicine,
corporeal drug delivery compared to IP and IV [19, 20]. Clinical Engineering Research Center, Oita University, Oita, Japan.
10
Department of General Internal Medicine, Saitama Medical University,
IP antibiotic administration is an effective and practicable
Saitama, Japan.
therapeutic approach to PD-related peritonitis. Efficacy
and practical dosage of IP antibiotic administrations are Received: 22 January 2020 Accepted: 31 March 2020
recommended with published clinical experiences rather
than pharmacokinetic studies, closely described in the
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