Page 1 of 8 Peritoneal Dialysis International

Peritoneal Dialysis International, inPress 0896-8608/17 $3.00 + .00

www.PDIConnect.com Copyright © 2017 International Society for Peritoneal Dialysis

OUTCOMES OF CORYNEBACTERIUM PERITONITIS: A MULTICENTER REGISTRY ANALYSIS

Htay Htay,1,2,3,4 Yeoungjee Cho,1,2,3 Elaine M. Pascoe,3 Darsy Darssan,3 Carmel Hawley,1,2,3,5 Philip A. Clayton,1,6,11
Monique Borlace,6 Sunil V. Badve,1,7 Kamal Sud,1,8,9 Neil Boudville,10 Stephen P. McDonald,1,6,11
and David W. Johnson1,2,3,5

Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry;1 Department of Nephrology,2 Princess Alexandra
Hospital, Brisbane, Australia; Australasian Kidney Trial Network,3 Diamantina Institute, University of Queensland,
Brisbane, Australia; Department of Renal Medicine,4 Singapore General Hospital, Singapore; Translational
Research Institute,5 Brisbane, Australia; Central Northern Adelaide Renal and Transplantation Service,6
Royal Adelaide Hospital, Adelaide, Australia; Department of Nephrology,7 St George Hospital, Sydney,

Downloaded from http://www.pdiconnect.com/ at Fudan University on August 31, 2017

Australia; Departments of Renal Medicine,8 Nepean and Westmead Hospitals, Sydney, Australia;
University of Sydney Medical School,9 Sydney, Australia; School of Medicine and Pharmacology,10
University of Western Australia, Australia; and School of Medicine,11 Faculty of
Health Sciences, University of Adelaide, Adelaide, Australia

♦♦ Background: Corynebacterium is a rare cause of peritonitis
that is increasingly being recognized in peritoneal dialysis (PD)
patients. The aims of this study were to compare Corynebacterium
peritonitis outcomes with those of peritonitis caused by other
organisms and to examine the effects of type and duration of
antibiotic therapy on outcomes of Corynebacterium peritonitis.
♦♦ Methods: Using Australia and New Zealand Dialysis and
Transplant Registry (ANZDATA) data, we included all PD patients
who developed peritonitis in Australia between 2004 and 2014.
The primary outcome was peritonitis cure by antibiotic therapy,
defined as resolution of a peritonitis episode with antibiotics alone
and without being complicated by recurrence, relapse, catheter
removal, hemodialysis transfer, or death. Peritonitis outcomes
were analyzed using multivariable logistic regression.
♦♦ Results: A total of 11,122 episodes of peritonitis in 5,367
patients were included. Of these, 162 episodes (1.5%) were due to
Corynebacterium. Compared with Corynebacterium peritonitis, the
odds of cure were lower in peritonitis due to Staphylococcus aureus
(odds ratio [OR] 0.66, 95% confidence interval [CI] 0.45 – 0.97),
Pseudomonas (OR 0.22, 95% CI 0.14 – 0.33), other gram-negative
organisms (OR 0.52, 95% CI 0.35 – 0.75), fungi (OR 0.02, 95%
CI 0.01 – 0.03), polymicrobial organisms (OR 0.32, 95% CI 0.22
– 0.47), and other organisms (OR 0.66, 95% CI 0.44 – 0.99) but
similar for culture-negative and other gram-positive peritonitis.
Similar results were observed for hemodialysis transfer and death.
The outcomes of Corynebacterium peritonitis were not associated
with the type of initial antibiotic selected (vancomycin vs cefazolin)
or the duration of antibiotic therapy (≤ 14 days vs > 14 days).
♦♦ Conclusions: Outcomes for Corynebacterium peritonitis are
generally favorable compared with other forms of peritonitis. Cure
Correspondence to: David Johnson, Department of Nephrology,
Level 2, ARTS Building, Princess Alexandra Hospital, 199 Ipswich
Road, Woolloongabba, Brisbane Qld 4102, Australia.
david.johnson2@health.qld.gov.au
Received 12 February 2017; accepted 9 May 2017.
Supplemental material available at www.pdiconnect.com
rates did not appear to differ if peritonitis was treated initially with
vancomycin or cefazolin or if treatment duration was prolonged
beyond 14 days.
Perit Dial Int: inPress
https://doi.org/10.3747/pdi.2017.00028
KEY WORDS: Antibiotic; Corynebacterium infections;
end-stage kidney disease; outcomes; peritoneal dialysis;
peritonitis; treatment.
P eritoneal dialysis-associated peritonitis can be acquired
through either touch contamination or catheter-related
infection (1), leading to skin bacteria gaining access to the
peritoneal cavity. Corynebacterium, a gram-positive bacil-
lus, forms a part of the normal skin flora (2,3) and has
uncommonly been associated with peritonitis in peritoneal
dialysis (PD) patients (4–6). Although its isolation in clinical
samples has historically been disregarded as a contaminant,
Corynebacterium has more widely been recognized as a patho-
gen causing peritonitis, and management of Corynebacterium
peritonitis has been included as an entity in the International
Society for Peritoneal Dialysis (ISPD) peritonitis management
guideline since 2010 (7,8).
To date, very few studies have investigated the outcomes of
Corynebacterium peritonitis in PD patients. A previous study
by Barraclough et al. using data from the Australia and New
Zealand Dialysis and Transplant (ANZDATA) Registry reported
that outcomes of Corynebacterium peritonitis and all non-
Corynebacterium peritonitis were comparable (4). However,
the outcomes of Corynebacterium peritonitis have not been
directly compared with those of peritonitis caused by other
specific organisms. The aforementioned study also reported
that the majority (67%) of patients with Corynebacterium

PDI in Press. Published on July 11, 2017. doi:10.3747/pdi.2017.00028

 Peritoneal Dialysis International
HTAY et al.
peritonitis were cured with antibiotic therapy and that the type
of antibiotic had no impact on the outcomes (4). However, in
a retrospective study of Corynebacterium peritonitis outcomes
in Hong Kong, Szeto et al. reported that relapses were com-
mon with Corynebacterium peritonitis and that vancomycin
was the preferred antibiotic (5). Similarly, in 3 case reports
of peritonitis due to different species of Corynebacterium, the
majority reported achieving a cure with vancomycin (9–11).
The present study aimed to compare the outcomes of
Corynebacterium peritonitis with those of peritonitis caused by
other micro-organisms and also examine associations between
type and duration of antibiotic therapy and the outcomes of
Corynebacterium peritonitis.
METHODS
All PD patients who developed peritonitis in Australia during
the period of 2004 to 2014 were included in the study, using
data from the ANZDATA Registry. The methods of data collec-
tion and validation are described in detail on the Registry
website (12).
DATA COLLECTION
The covariates recorded and examined in the study were age
at initiation of PD therapy, gender, race, body mass index (BMI,
subcategorized into 4 groups according to the World Health
Organization classification), smoking status (non-smokers,
current smokers, former smokers), comorbidities including
presence of diabetes mellitus, cardiovascular disease (defined
as composite of coronary artery disease, cerebrovascular
disease, and peripheral vascular disease), and chronic lung
disease, primary renal disease, late referral to a nephrolo-
gist (defined as < 3-month follow-up before commencement
of renal replacement therapy [RRT]), initial RRT modality,
initial PD modality, and socioeconomic position, reported as
Index of Relative Socioeconomic Advantage and Disadvantage
(IRSAD) scores (13). Each peritonitis episode was attributed
to 1 of 9 categories of causative organism: Corynebacterium,
Staphylococcus aureus, other gram-positive organism, culture-
negative, Pseudomonas, other gram-negative organism,
fungal, polymicrobial, other organisms. Pseudomonas perito-
nitis was defined as Pseudomonas aeruginosa, Pseudomonas
maltophilia, Pseudomonas cepacia, Pseudomonas stutzer, and
other or unknown Pseudomonas species. A relapsed episode
was considered as part of the original episode. The duration of
antibiotic treatment for Corynebacterium peritonitis was cal-
culated as the time difference between the dates of the initial
and final doses of antibiotics. For episodes of peritonitis which
required changing to other antibiotic therapy, the duration of
treatment was calculated as the difference between the first
day of the last antibiotic regimen and the final day of antibiot-
ics. In the case of vancomycin therapy, an additional 5 days was
added to account for its prolonged duration of action following
a dose. The duration of antibiotic therapy was categorized as
≤ 14 days or > 14 days of therapy.
2
Page 2 of 8
inPress PDI
STUDY OUTCOMES
The primary outcome was peritonitis cure by antibiotic
therapy, defined as resolution of a peritonitis episode with
antibiotics alone and without the complication of recurrence,
relapse, catheter removal, transfer to hemodialysis (HD) for
≥ 30 days, or death (4,14,15). The secondary outcomes were
relapse/recurrent peritonitis (16), peritonitis-related catheter
removal, transfer to HD ≥ 30 days (17), peritonitis-related
hospitalization, and death (18). For all outcomes, the odds of
cure of Corynebacterium peritonitis were compared with those
of other organisms. In addition, the associations of type and
duration of antibiotic therapy with Corynebacterium peritonitis
outcomes were examined.
STATISTICAL ANALYSIS
Downloaded from http://www.pdiconnect.com/ at Fudan University on August 31, 2017
Baseline characteristics are presented as frequency (percent-
age) for categorical variables, mean ± standard deviation for
normally distributed continuous variables, and median and inter-
quartile range for non-normally distributed continuous variables.
The outcomes of peritonitis cure, catheter removal, transfer
to HD, relapsed/recurrent peritonitis, hospitalization, and
death were analyzed using multivariable logistic regression
with participating centers and patients fitted as random effects
to accommodate clustering due to episodes of peritonitis
nested within patients and patients nested within centers.
Causative organism was included in all logistic regression
models as the covariate of primary interest. Other covariates
with p values < 0.2 in univariable analyses were also included
as fixed effect covariates in the multivariable logistic regres-
sion analyses. There was no biologically meaningful first-order
interaction between covariates. Data were analyzed using Stata
version 14.0 (StataCorp LP, College Station, TX, USA). P values
< 0.05 were considered statistically significant.
RESULTS
A total of 11,256 episodes of peritonitis occurred in 5,441
patients in Australia from 2004 to 2014. Of these, 134 (1%) epi-
sodes of peritonitis in 74 patients had missing information on
outcomes and so were excluded from analyses. Consequently,
the study included a total of 11,122 episodes of peritonitis in
5,367 PD patients from 51 centers. The number of episodes of
peritonitis ranged from 1 to 17 per patient, with the majority
of patients (n = 2,725, 51%) developing only 1 episode. There
were 162 (1.5%) episodes of Corynebacterium peritonitis,
1,124 (10%) episodes of Staphylococcus aureus peritonitis,
3,859 (35%) episodes of other gram-positive peritonitis, 1,760
(16%) episodes of culture-negative peritonitis, 365 (3.3%)
episodes of Pseudomonas peritonitis, 1,781 (16%) episodes
of other gram-negative peritonitis, 307 (2.7%) episodes of
fungal peritonitis, 1,261 (11%) episodes of polymicrobial
peritonitis, and 503 (4.5%) episodes of peritonitis caused by
other organisms. The demographic data of study participants
are presented in Table 1.
Page 3 of 8 Peritoneal Dialysis International

PDI inPress OUTCOMES OF CORYNEBACTERIUM PERITONITIS

TABLE 1 lower odds of cure by antibiotic therapy were observed with

Baseline Characteristics of Study Participants Staphylococcus aureus peritonitis, Pseudomonas peritonitis,
other gram-negative peritonitis, fungal peritonitis, polymicro-
Descriptive statistics bial peritonitis, and peritonitis caused by other organisms after
Characteristics (n = 5,367) adjusting for other confounders (Table 2, Figure 1). There was no
significant difference in the odds of cure by antibiotic therapy
Male 3,060 (57) between Corynebacterium peritonitis and culture-negative peri-
Age (years) 61.2±14.9 tonitis or other gram-positive peritonitis. Age was significantly
Race
and inversely associated with odds of cure by antibiotics.
Caucasian 3,869 (72)
Asian 593 (11)
ATSI 547 (10) PERITONITIS-RELATED CATHETER REMOVAL
Maori-Pacific Islanders 190 (4)
Other 168 (3) There was a statistically significant association between
Body mass index (kg/m2) 27.0±6.0 causative micro-organism and catheter removal (p < 0.01).
<18.5 177 (3) Compared with Corynebacterium peritonitis, significantly
18.5–24.9 1,960 (37) higher odds of peritonitis-related catheter removal were
25–29.9 1,823 (34) observed with Pseudomonas peritonitis, other gram-negative

Downloaded from http://www.pdiconnect.com/ at Fudan University on August 31, 2017

≥30 1,407 (26) peritonitis, fungal peritonitis, polymicrobial peritonitis, and
Primary renal disease peritonitis caused by other organisms (Table 2, Figure 2),
Glomerulonephritis 1,400 (26)
whereas other gram-positive peritonitis had significantly lower
Diabetes mellitus 1,824 (34)
Hypertension 751 (14)
odds of peritonitis-related catheter removal. There was no
Polycystic kidney disease 288 (5) significant difference in the odds of catheter removal between
Other 1,104 (21) Corynebacterium peritonitis and culture-negative peritonitis or
Comorbidities Staphylococcus aureus peritonitis. Patients who commenced PD
Diabetes mellitus 2,316 (43) as their initial RRT modality were associated with lower odds
Cardiovascular disease 2,541 (47) of peritonitis-related catheter removal (Table 2).
Chronic lung disease 781 (15)
Smoking status HEMODIALYSIS TRANSFER DUE TO PERITONITIS
Non-smoker 2,480 (46)
Current smoker 733 (14) Compared with Corynebacterium peritonitis, the odds of
Former smoker 2,154 (40)
peritonitis-related HD transfer were significantly higher in
Late nephrology referral 1,174 (22)
Initial modality of PD (CAPD) 4,149 (77)
Pseudomonas peritonitis (OR 5.49, 95% CI 3.35 – 8.99), other
PD as first RRT modality 704 (13) gram-negative peritonitis (OR 1.94, 95% CI 1.22 – 3.06), fungal
IRSAD scores (socioeconomic position) 974±83 peritonitis (OR 26.5, 95% CI 15.6 – 44.8), polymicrobial peri-
tonitis (OR 3.87, 95% CI 2.44 – 6.12), and peritonitis caused
ATSI = Aboriginal and Torres Strait Islander; PD = peritoneal dialysis; by other organisms (OR 1.65, 95% CI 1.00 – 2.71).There was
CAPD = continuous ambulatory peritoneal dialysis; RRT = renal no significant difference in HD transfer in Corynebacterium
replacement therapy; IRSAD = Index of Relative Socioeconomic peritonitis compared with culture-negative peritonitis
Advantage and Disadvantage. (OR 0.76, 95% CI 0.47 – 1.21), other gram-positive organisms
Data are presented as number (%) or mean±standard deviation. (OR 0.65, 95% CI 0.41 – 1.03), or Staphylococcus aureus peri-
tonitis (OR 1.47, 95% CI 0.92 – 2.36) (Supplemental Table 1).
A total of 162 episodes of Corynebacterium peritonitis
occurred in 126 patients. One hundred and twenty-one (75%) PERITONITIS RELAPSED/RECURRENT
of the 162 episodes of Corynebacterium peritonitis were
cured by antibiotic therapy alone. The remaining 41 (25%) Causative micro-organism was not statistically significantly
Corynebacterium peritonitis episodes were not cured because associated with odds of relapsed or recurrent episodes of peri-
of 1 or more of the following complications: relapsed/recurrent tonitis (p = 0.33) (Table 2).
peritonitis (n = 25), catheter removal (n = 24), HD transfer (n =
23), and/or death (n = 2). A total of 109 episodes of peritonitis PERITONITIS-RELATED MORTALITY
(67%) required hospitalization.
Compared with Corynebacterium peritonitis, the odds of
PERITONITIS CURE WITH ANTIBIOTIC THERAPY (MEDICAL CURE) peritonitis-related death were significantly and indepen-
dently higher in Pseudomonas peritonitis, other gram-negative
There was a statistically significant association between peritonitis, fungal peritonitis, polymicrobial peritonitis,
causative micro-organism and cure by antibiotic therapy and Staphylococcus aureus peritonitis (Table 2, Figure 3).
(p < 0.01). Compared with Corynebacterium peritonitis, Corynebacterium peritonitis had similar peritonitis-related

3
 Peritoneal Dialysis International Page 4 of 8

HTAY et al. inPress PDI

TABLE 2
Multivariable Logistic Regression of Outcomes of Peritonitis

Medical cure Catheter removal Relapse/recurrent Peritonitis-related death

Variables OR 95% CI p OR 95% CI p OR 95% CI p OR 95% CI p

Age (decades) 0.95 0.92–0.98 <0.01 0.99 0.95–1.03 0.73 0.97 0.92–1.02 0.22 1.75 1.60–1.91 <0.01
Male 1.06 0.97–1.17 0.21 0.94 0.84–1.04 0.23 1.08 0.93–1.26 0.29 0.65 0.54–0.79 <0.01
Race 0.16 0.42 0.15 0.50
Caucasian 1.0 reference 1.0 reference 1.0 reference 1.0 reference
Asian 1.17 1.00–1.37 0.05 0.88 0.73–1.06 0.16 0.88 0.68–1.13 0.30 0.83 0.61–1.14 0.25
ATSI 0.98 0.83–1.15 0.76 0.93 0.76–1.14 0.50 1.18 0.91–1.52 0.20 0.88 0.62–1.26 0.48
Maori-Pacific Islanders 1.21 0.95–1.55 0.13 0.86 0.64–1.16 0.33 0.95 0.64–1.38 0.77 1.28 0.77–2.14 0.34
Other 1.13 0.85–1.50 0.40 1.14 0.83–1.56 0.42 0.61 0.36–1.01 0.06 0.81 0.43–1.53 0.52
Body mass index (kg/m2) 0.26 0.70 0.61 0.36
<18.5 0.84 0.65–1.09 0.20 0.95 0.71–1.29 0.75 1.05 0.69–1.59 0.83 1.35 0.84–2.15 0.21
18.5–24.9 1.0 reference 1.0 reference 1.0 reference 1.0 reference
25–29.9 0.96 0.86–1.06 0.42 0.98 0.86–1.10 0.69 1.06 0.89–1.25 0.54 0.90 0.73–1.11 0.32

Downloaded from http://www.pdiconnect.com/ at Fudan University on August 31, 2017

≥30 0.90 0.80–1.01 0.08 1.05 0.92–1.21 0.45 1.14 0.94–1.36 0.18 0.94 0.74–1.19 0.60
Smoking status 0.07 0.99 0.07 0.21
Non–smoker 1.0 reference 1.0 reference 1.0 reference 1.0 reference
Current smoker 0.85 0.74–0.98 0.03 0.99 0.84–1.18 0.94 1.29 1.03–1.59 0.02 1.28 0.94–1.74 0.12
Former smoker 0.94 0.85–1.03 0.22 1.00 0.89–1.12 0.99 1.11 0.95–1.30 0.19 1.15 0.94–1.40 0.19
Diabetes mellitus 0.94 0.85–1.04 0.26 0.97 0.86–1.09 0.58 1.01 0.87–1.19 0.86 1.37 1.12–1.67 <0.01
Cardiovascular disease 0.96 0.86–1.05 0.40 0.99 0.88–1.13 0.91 0.97 0.83–1.14 0.70 1.19 0.98–1.45 0.08
Chronic lung disease 0.93 0.81–1.05 0.27 0.98 0.84–1.14 0.81 1.02 0.83–1.25 0.88 1.24 0.98–1.57 0.08
Initial modality of RRT (PD) 1.14 1.00–1.31 0.06 0.82 0.69–0.97 0.02 1.00 0.80–1.24 0.98 0.96 0.72–1.26 0.76
Causative micro-organism <0.01 <0.01 0.33 <0.01
Corynebacterium species 1.0 reference 1.0 reference 1.0 reference 1.0 reference
Staphylococcus aureus 0.66 0.45–0.97 0.04 1.53 0.96–2.43 0.07 0.79 0.46–1.34 0.38 4.40 1.05–18.4 0.04
Other gram-positive 1.21 0.84–1.76 0.31 0.60 0.39–0.95 0.03 0.79 0.48–1.31 0.36 1.92 0.47–7.94 0.37
Culture-negative 1.08 0.74–1.57 0.71 0.71 0.45–1.14 0.16 0.74 0.44–1.24 0.26 3.51 0.85–14.6 0.08
Pseudomonas 0.22 0.14–0.33 <0.01 5.97 3.68–9.71 <0.01 0.58 0.31–1.09 0.09 10.6 2.49–44.8 <0.01
Other gram-negative 0.52 0.35–0.75 <0.01 1.97 1.26–3.10 <0.01 0.83 0.49–1.38 0.47 7.01 1.71–28.8 <0.01
Fungi 0.02 0.01–0.03 <0.01 43.0 24.9–74.5 <0.01 0.94 0.51–1.73 0.84 19.3 4.58–81.2 <0.01
Polymicrobial 0.32 0.22–0.47 <0.01 3.90 2.48–6.14 <0.01 0.69 0.41–1.18 0.18 8.11 1.97–33.4 <0.01
Other organisms 0.66 0.44–0.99 0.05 1.70 1.04–2.77 0.04 0.98 0.56–1.73 0.96 3.47 0.79–15.3 0.10

ATSI = Aboriginal and Torres Strait Islander; CI = confidence interval; OR = odds ratio; PD = peritoneal dialysis; RRT= renal replacement therapy.

mortality compared with other gram-positive peritonitis, THERAPEUTIC PREDICTORS OF OUTCOMES IN

culture-negative peritonitis, and peritonitis caused by other
organisms (Table 2).
PERITONITIS-RELATED HOSPITALIZATION
Compared with Corynebacterium peritonitis, the odds of
peritonitis-related hospitalization were higher in Pseudomonas
peritonitis (OR 3.83, 95% CI 2.18 – 6.72), other gram-negative
peritonitis (OR 2.93, 95% CI 1.82 – 4.73), fungal peritonitis
(OR 28.9, 95% CI 13.3 – 62.6), and polymicrobial peritonitis
(OR 2.92, 95% CI 1.79 – 4.74). There was no significant differ-
ence in the odds of peritonitis-related hospitalization between
Corynebacterium peritonitis and Staphylococcus aureus peri-
tonitis (OR 1.41, 95% CI 0.87 – 2.30), other gram-positive
peritonitis (OR 0.92, 95% CI 0.58 – 1.46), culture-negative
peritonitis (OR 0.70, 95% CI 0.44 – 1.13), or peritonitis
caused by other organisms (OR 1.11, 95% CI 0.66 – 1.87)
(Supplemental Table 1).
CORYNEBACTERIUM PERITONITIS
Seventy-four episodes (46%) of Corynebacterium peritonitis
were initially treated with vancomycin therapy, 71 episodes
(44%) were treated with cefazolin, 13 (8%) were treated with
other antibiotics, and 4 (2%) were treated with both cefazolin
and vancomycin initially. Of the 74 peritonitis episodes initially
treated with a vancomycin-based regimen, 66 episodes (89%)
remained on vancomycin at the end of therapy. Of these 66 epi-
sodes, 45 (68%) achieved cure (Figure 4). Of the71 peritonitis
episodes initially treated with a cefazolin-based regimen,
24 episodes (34%) remained on cefazolin at the end of therapy,
of which 19 (79%) achieved cure. Of the 71 episodes initially
treated with cefazolin, 47 episodes were eventually converted
to vancomycin (n = 32) and other antibiotics (n = 15), and 38
(81%) of these 47 episodes were cured by antibiotics (Figure 4).
When the outcomes of Corynebacterium peritonitis were
examined according to the initial empirical vancomycin-based

4
Page 5 of 8 Peritoneal Dialysis International
PDI inPress
Figure 1 — Forest plot comparing the odds of cure by antibiotics
among peritonitis due to different organisms, after adjusting for age,
gender, race, smoking status, body mass index, diabetes mellitus,
cardiovascular disease, chronic lung disease, and initial modality of
renal replacement therapy. Corynebacterium peritonitis is used as a
reference group. The x-axis is in logarithmic scale. OR = odds ratio;
CI = confidence interval.
Figure 2 — Forest plot comparing the odds of catheter removal
among peritonitis due to different organisms, after adjusting for age,
gender, race, smoking status, body mass index, diabetes mellitus,
cardiovascular disease, chronic lung disease, and initial modality of
renal replacement therapy. Corynebacterium peritonitis is used as a
reference group. The x-axis is in logarithmic scale. OR = odds ratio;
CI = confidence interval.
regimen (n = 74), 52 episodes of peritonitis (70%) were cured
by antibiotics. The episodes of peritonitis treated initially with
vancomycin were associated with catheter removal (n = 15,
20%), HD transfer (n = 14, 19%), relapsed/recurrent peritonitis
(n = 13, 18%), and death (n = 1, 1%). When the outcomes of
Corynebacterium peritonitis were examined according to the
initial empirical cefazolin-based regimen (n = 71), 57 epi-
sodes of peritonitis (80%) were cured by antibiotics. The
episodes of peritonitis treated initially with cefazolin were
OUTCOMES OF CORYNEBACTERIUM PERITONITIS
Figure 3 — Forest plot comparing the odds of peritonitis-related death
Downloaded from http://www.pdiconnect.com/ at Fudan University on August 31, 2017
among peritonitis due to different organisms, after adjusting for age,
gender, race, smoking status, body mass index, diabetes mellitus,
cardiovascular disease, chronic lung disease, and initial modality of
renal replacement therapy. Corynebacterium peritonitis is used as a
reference group. The x-axis is in logarithmic scale. OR = odds ratio;
CI = confidence interval.
associated with catheter removal (n = 7, 10%), HD transfer
(n = 7, 10%), relapsed/recurrent peritonitis (n = 8, 11%), and
death (n = 1, 1%).
When examining the outcomes of episodes of peritonitis
which eventually converted to vancomycin (n = 38; 32 episodes
initially treated with cefazolin and 6 episodes initially treated
with other antibiotics), 30 episodes (79%) were cured by
antibiotics. The episodes of peritonitis eventually converted
to vancomycin were associated with catheter removal (n = 1,
3%), transfer to HD (n = 1, 3%), relapsed/recurrent peritonitis
(n = 6, 16%), and death (n = 1, 3%).
There were 30 episodes of peritonitis (18%) with missing
data on the duration of antibiotic therapy. Among 60 episodes
of peritonitis treated with ≤ 14 days of antibiotics, 46 episodes
(77%) were cured by antibiotics. Of 72 episodes of peritonitis
treated with > 14 days of antibiotics, 52 episodes (72%) were
cured by antibiotics. The episodes of peritonitis treated with
≤ 14 days of antibiotics were associated with catheter removal
(n = 8, 13%), HD transfer (n = 7, 12%), relapsed/recurrent
peritonitis (n = 8, 13%), and death (n = 2, 3%). The episodes of
peritonitis treated with >14 days of antibiotics were associated
with catheter removal (n = 11, 15%), HD transfer (n = 11, 15%),
relapsed/recurrent peritonitis (n = 13, 18%), and death (n = 0).
DISCUSSION
This study demonstrated that Corynebacterium peritonitis
was significantly and independently associated with higher
odds of cure with antibiotic therapy than peritonitis episodes
caused by Staphylococcus aureus, Pseudomonas, other gram-
negative organisms, fungi, polymicrobial organisms, or
peritonitis caused by other organisms and similar odds of
5
 Peritoneal Dialysis International Page 6 of 8

HTAY et al. inPress PDI

Downloaded from http://www.pdiconnect.com/ at Fudan University on August 31, 2017

Figure 4 — Flow chart describing the association between antibiotics used and achievement of cure in Corynebacterium peritonitis. ‡ = cephalo-
thin (n=8), ceftazidime (n=1), ciprofloxacin (n=1), gentamicin (n=2), rifampicin (n=1); † = gentamicin (n=3), ciprofloxacin (n=1), cephalothin
(n=2), cefoxitin (n=1); @ = gentamicin (n=4), ticarcillin (n=2), ciprofloxacin (n=3), cephalexin (n=3), ceftazidime (n=1), doxycycline (n=1),
other antibiotics (n=1); * = cephalothin (n=4), gentamicin (n=2), amoxicillin/clavulanic (n=1).

cure as culture-negative peritonitis and other gram-positive
peritonitis. Corynebacterium peritonitis also had significantly
lower odds of peritonitis-related catheter removal, HD transfer,
and death than Pseudomonas peritonitis, other gram-negative
peritonitis, fungal peritonitis, and polymicrobial peritonitis.
There was no significant difference in peritonitis relapse/
recurrence between peritonitis due to Corynebacterium spe-
cies and other organisms. The outcomes of Corynebacterium
peritonitis did not appear to differ according to whether
peritonitis episodes were treated initially with a vancomycin-
or cefazolin-based antibiotic regimen or whether treatment
duration was prolonged beyond 14 days.
These findings both contrast with and extend those of a
previous smaller study by Barraclough et al., in which the
outcomes of Corynebacterium peritonitis were observed to be
similar to those caused by all other organisms analyzed as a
single group (4).The much larger number of cases in the present
study (162 vs 82) allowed a more detailed comparison of the
outcomes of Corynebacterium peritonitis with those of perito-
nitis episodes caused by individual organisms. Consequently,
outcomes for Corynebacterium peritonitis were found to be
directly comparable with culture-negative peritonitis and
superior to most other organism-specific peritonitis. It is also
worth noting that the outcomes of Corynebacterium peritonitis
in this contemporary Australian PD patient cohort (2004 –
2014) were generally better than those observed in the earlier
cohort described by Barraclough et al. (2003 – 2006): cure 75%
vs 67%, catheter removal 15% vs 21%, hospitalization 67%
vs 70%, and death 1% vs 2%. Although the numbers in the
present study were too small to determine whether there was
a true improvement in outcomes over time, it is possible that
outcomes may have improved due to the recent implementation
of national quality improvement activities targeting peritonitis
prevention and treatment (19).
The only other previously published, substantive study of
Corynebacterium peritonitis was that conducted by Szeto et al.
(5), who reported that, although 20 (74%) of their 27 patients
with Corynebacterium peritonitis in a single Hong Kong center
achieved a primary response to antibiotic therapy, only 10
(37%) achieved a complete cure. This observed cure rate was
less than half that observed in the current investigation and
was appreciably influenced by a much higher observed rate of
relapse/recurrence (48% vs 15%). The apparent disparity in
findings may be potentially explained by the smaller sample
size, earlier era (1995 – 2002) and single-center nature of
the Hong Kong study. It is also possible that the causative
Corynebacterium species may have differed between Hong Kong
and Australia. For example, some Corynebacterium species,
such as Corynebacterium jeikeium, are multi-drug resistant
and more difficult to treat effectively (20,21). Unfortunately,
information regarding the causative Corynebacterium species
was unavailable in both studies. However, given that nearly half
the episodes of peritonitis (n = 32, 45%), initially treated with
a cefazolin-based regimen required a change to vancomycin in
the early course of therapy in this study, one can speculate that
the reason for such change might be related to drug-resistant
Corynebacterium species.
Another notable finding of the present study was that
regardless of initial antibiotic therapy (vancomycin- or
cefazolin-based regime), the outcomes of Corynebacterium
peritonitis were comparable, taking into account that antibi-
otic regimens were adjusted appropriately. Though information
on the reasons for changing antibiotics was unavailable, such
changes were most probably based on antibiotic sensitivity

6
Page 7 of 8 Peritoneal Dialysis International
PDI inPress
results and/or clinical response. The study demonstrated that
episodes of Corynebacterium peritonitis that were eventually
changed to vancomycin therapy were also able to achieve rea-
sonable outcomes. Although there were significant amounts
of missing data on the duration of the antibiotic treatment,
the study demonstrated that the outcomes of Corynebacterium
peritonitis were acceptable, whether episodes of peritonitis
were treated with ≤ or > 14 days of antibiotics. This reinforced
the previous findings by Barraclough et al. (4), but contrasted
sharply with those of Szeto et al. (5), which found that relapsed
Corynebacterium peritonitis was common (48%) and generally
required 3 weeks’ therapy with intraperitoneal vancomycin.
It should be noted, however, that only 3 peritonitis episodes
were treated with cephalosporin for the entire antibiotic course
and that approximately 30% of Corynebacterium isolates were
penicillin-resistant. Data on antimicrobial susceptibilities
were not collected by the ANZDATA Registry, so it is uncertain
whether there is a difference in antibiotic resistance patterns
between Hong Kong and Australia. However, a considerable
number (45%) of patients initially treated with cefazolin in the
present study eventually changed to vancomycin. Whether this
change in antibiotic therapy was due to a failure to respond
to cefazolin, antibiotic sensitivity results or other reasons was
uncertain, as the ANZDATA Registry did not record the reasons
for such changes. Previous case studies of peritonitis with dif-
ferent Corynebacterium species reported that most species of
Corynebacterium peritonitis responded to vancomycin therapy
(9–11,22,23). However, the present study demonstrated that
the outcomes of Corynebacterium peritonitis were compa-
rable regardless of initial antibiotic therapy (vancomycin- or
cefazolin-based regime). Taken together, the choice of anti-
biotic should ideally be based on antibiotic-sensitivity results.
This is the largest study of Corynebacterium peritonitis to
date, comprising 162 episodes. It is also the first study compar-
ing the outcomes of Corynebacterium peritonitis with those of
other varieties of organism-specific peritonitis.
The strengths of this study should be balanced against its
limitations. The limited data collected by the ANZDATA registry
prevented inclusion and analysis of important information,
including the exact species of Corynebacterium, antibiotic-
sensitivity results, and reasons for changing antibiotic therapy.
The non-availability of this information limited the ability to
compare outcomes between different treatment regimens and
durations due to possible indication bias. The possibility of
coding/classification bias also cannot be excluded. Although
attempts were made to account for center effects by using
multi-level, multivariable logistic regression to accommodate
clustering due to episodes of peritonitis nested within patients
and patients nested within centers, the possibility of residual
confounding cannot be excluded.
In conclusion, the present study demonstrated that the
outcomes of Corynebacterium peritonitis were comparable with
those of culture-negative peritonitis and superior to those of
Staphylococcus aureus peritonitis, Pseudomonas peritonitis,
other gram-negative peritonitis, fungal peritonitis, and poly-
microbial peritonitis. The study was unable to demonstrate
OUTCOMES OF CORYNEBACTERIUM PERITONITIS
any difference in outcomes according to the type or duration
of antibiotic treatment. Initial empiric selection of either
vancomycin or cephalosporin for gram-positive cover resulted
in comparable final outcomes. Future studies that incorporate
precise species identification and antimicrobial susceptibilities
may help to further inform and refine ISPD Peritonitis Guideline
recommendations regarding the duration and type of antibiotic
therapy for Corynebacterium peritonitis.
ACKNOWLEDGMENTS
The authors gratefully acknowledge the contributions of the entire
Australia and New Zealand nephrology community (physicians, sur-
geons, database managers, nurses, renal operators, and patients)
in providing information for and maintaining the ANZDATA registry
database. The interpretation and reporting of these data are the
responsibility of the authors and in no way should be seen as an
official policy or interpretation of the Australia and New Zealand
Downloaded from http://www.pdiconnect.com/ at Fudan University on August 31, 2017
Dialysis and Transplant Registry.
DISCLOSURES
DWJ has received consultancy fees, research grants, speaker’s hono-
raria and travel sponsorships from Baxter Healthcare and Fresenius
Medical Care. He is supported by a National Health and Medical
Research Council Practitioner Fellowship. YC has received research
grants from Fresenius Medical Care. She is supported by a National
Health and Medical Research Council Early Career Fellowship. CH
has previously received research grants and travel sponsorships
from ­Baxter Healthcare and Fresenius Medical Care. KS has received
speaker’s honoraria from Baxter Healthcare, Roche, Amgen, and
Boehringer Ingelheim and conference or meeting sponsorships from
Shire, Roche, Boehringer Ingelheim, Amgen, Sanofi, and Novartis.
All other authors have no conflicts of interest to declare.
REFERENCES
1. Piraino B, Bernardini J, Sorkin M. The influence of peritoneal catheter
exit-site infections on peritonitis, tunnel infections, and catheter loss in
patients on continuous ambulatory peritoneal dialysis. Am J Kidney Dis
1986; 8(6):436–40.
2. Cogen AL, Nizet V, Gallo RL. Skin microbiota: a source of disease or
defence? Br J Dermatol 2008; 158(3):442–55.
3. Davis CP. Normal flora. In: Baron S, ed. Medical Microbiology. 4th ed.
Galveston (TX): University of Texas Medical Branch at Galveston; 1996.
Available from: http://www.ncbi.nlm.nih.gov/books/NBK7617/
4. Barraclough K, Hawley CM, McDonald SP, Brown FG, Rosman JB, Wiggins
KJ, et al. Corynebacterium peritonitis in Australian peritoneal dialysis
patients: predictors, treatment and outcomes in 82 cases. Nephrol Dial
Transplant 2009; 24(12):3834–9.
5. Szeto CC, Chow KM, Chung KY, Kwan BCH, Leung CB, Li PKT. The clinical
course of peritoneal dialysis-related peritonitis caused by Corynebacterium
species. Nephrol Dial Transplant 2005; 20(12):2793–6.
6. Leung AC, Orange G, Henderson IS, Kennedy AC. Diphtheroid peritonitis
associated with continuous ambulatory peritoneal dialysis. Clin Nephrol
1984; 22(4):200–5.
7. Li PKT, Szeto CC, Piraino B, de Arteaga J, Fan S, Figueiredo AE, et al. ISPD
peritonitis recommendations: 2016 update on prevention and treatment.
Perit Dial Int 2016; 36(5):481–508.
8. Li KTP, Szeto CC, Piraino B, Bernardini J, Figueiredo AE, et al. Peritoneal
dialylsis-related infections recommendations: 2010 update. Perit Dial Int
2010; 30(4):393–423.
7
 Peritoneal Dialysis International
HTAY et al.
9. Franklin DB, Yium JJ, Hawkins SS. Corynebacterium equi peritonitis in a
patient receiving peritoneal dialysis. South Med J 1989; 82(8):1046–7.
10. Pierard D, Lauwers S, Mouton MC, Sennesael J, Verbeelen D. Group JK
Corynebacterium peritonitis in a patient undergoing continuous ambula-
tory peritoneal dialysis. J Clin Microbiol 1983; 18(4):1011–4.
11. Altwegg M, Záruba K, von Graevenitz A. Corynebacterium group JK peri-
tonitis in patients on continuous ambulatory peritoneal dialysis. Klin
Wochenschr 1984; 62(16):793–4.
12. ANZDATA Australia and New Zealand dialysis and transplant registry [Online].
Available from: http://www.anzdata.org.au/v1/data_collection.html.
13. SEIFA. 2016. [Online]. Available from: http://www.abs.gov.au/websitedbs/
censushome.nsf/home/seifa.
14. Tang W, Grace B, McDonald SP, Hawley CM, Badve SV, Boudville NC, et al.
Socio-economic status and peritonitis in Australian non-indigenous
peritoneal dialysis patients. Perit Dial Int 2015; 35(4):450–9.
15. Johnson DW, Clayton P, Cho Y, Badve SV, Hawley CM, Mcdonald S, et al.
Weekend compared with weekday presentations of peritoneal dialysis-
associated peritonitis. Perit Dial Int 32:516–24.
16. Li PKT, Szeto CC, Piraino B, de Arteaga J, Fan S, Figueiredo AE, et al. ISPD
peritonitis recommendations: 2016 update on prevention and treatment.
Perit Dial Int 2016; 36(5):481–508.
17. Lan PG, Clayton PA, Johnson DW, McDonald SP, Borlace M, Sud K, et al.
Page 8 of 8
inPress PDI
Duration of hemodialysis following peritoneal dialysis cessation in
­Australia and New Zealand: proposal for a standardized definition of
technique failure. Perit Dial Int 2016; 36(6):623–30.
18. Lan PG, Johnson DW, McDonald SP, Boudville N, Borlace M, Badve SV, et al.
The association between peritoneal dialysis modality and peritonitis. Clin
J Am Soc Nephrol 2014; 9(6):1091–7.
19. Nataatmadja M, Cho Y, Johnson DW. Continuous quality improvement
initiatives to sustainably reduce peritoneal dialysis-related infections in
Australia and New Zealand. Perit Dial Int 2016; 36(5):472–7.
20. Tauch A, Kaiser O, Hain T, Goesmann A, Weisshaar B, Albersmeier A, et al.
Complete genome sequence and analysis of the multiresistant nosocomial
pathogen Corynebacterium jeikeium k411, a lipid-requiring bacterium of
the human skin flora. J Bacteriol 2005; 187(13):4671–82.
21. Tauch A, Trost E, Tilker A, Ludewig U, Schneiker S, Goesmann A, et al.
The lifestyle of Corynebacterium urealyticum derived from its complete
genome sequence established by pyrosequencing. J Biotechnol 2008;
136(1–2):11–21.
22. Bhandari S, Meigh JA, Sellars L. CAPD peritonitis due to Corynebacterium
striatum. Perit Dial Int 1995; 15(1):88–9.
23. Fernández Girón F, Saavedra Martín JM, Benítez Sánchez M, Fernández
Downloaded from http://www.pdiconnect.com/ at Fudan University on August 31, 2017
Mora F, Rodríguez Gómez E. Corynebacterium minutissimum peritonitis
in a CAPD patient. Perit Dial Int 1998; 18(3):345–6.