A COMPARISON OF INTRAPERITONEAL AND
INTRAVENOUS/ORAL ANTIBIOTICS IN CAPD
David Bennett-jones
Val Wass Penny
Mawson David Taube
Guy Neild Chisholm
Ogg j Stewart Cameron
and
D Gwyn Williams
ABSTRACT
Eighty patients with CAPD peritonitis
were randomised to receive either
intraperitoneal (IP) vancomycin and
tobramycin, or intravenous (IV) van-
comycin and tobramycin followed by oral
antibiotics, depending on the results of
culture and sensitivity. Five patients were
withdrawn, and, of the remaining patients,
39 were in the IP group and 36 in the IV
group.
When all episodes of bacterial
From Guy's Hospital, London SE1, UK.
Key Words: Intraperitoneal antibiotics,
Peritonitis, Peritonitis treatment, Anti-
biotics, Oral antibiotics, Vancomycin,
Tobramycin.
PERITONITIS
peritonitis are considered, the treatment
failure rate was higher in the IV group
(34.1% ) , than in the IP group (10.3% ) (p
< 0.02). This was also the case when gram-
positive organisms resistant to tobramycin
were considered separately (p < 0.05), but
not for vancoinycin-resistant organisms.
We conclude that vancomycin should be
administered by the intraperitoneal route:
the case for intraperitoneal tobramycin is
"not proven".
Current treatment of peritonitis compli-
cating continuous ambulatory peritoneal
dialysis (CAPO) evolved from that used in
intermittent peritoneal dialysis (IPD) (1).
Therapy is based on the addition of
antibiotics to peritoneal dialysis fluid and
continuing rapid exchanges (2-4), although
some prefer intravenous or oral routes (5,
6). However rapid exchanges may not be
the optimal mode for those on CAPO ,
because some studies have shown that
continuous rapid exchanges may delay
recovery (7) and may remove factors
important for host defence (8).
The intraperitoneal route has two
disadvantages: some patients find it
difficult to learn to add antibiotics to their
bags, and hence require inhospital
treatment; continuous administration
produces steady-state blood levels which,
particularly with aminoglycosides, may be
associated with ototoxicity (10).
For these reasons we did a prospective
randomised trial that managed CAPD
peritonitis using, as initial therapy,
vancomycin and tobramycin given by the
intraperitoneal (IP) or the intravenous (IV)
route.
METHODS
All patients from our CAPO program with
peritonitis (defined by a PD fluid leukocyte
count in excess of 100/mm3) were entered
with the following exclusions:
I. Associated catheter leak
2. Catheter-tract or severe exit-site
infection
3. Fungal peritonitis
4. Septicemia
5. Bowel perforation
6. Recurrence within 15 days of a
previous episode

Patients were randomised to be treated by
the IP or the IV/oral regime. Both groups
were given three rapid exchanges for
symptomatic relief. Then they returned to
their usual CAPD regime, and, in the IP
group, were shown how to add antibiotics
to the bags. Table I shows the antibiotic
regimes used. All patients received
vancomycin and tobramycin for the first
four days; in the light of sensitivities, the
appropriate antibiotic was continued to the
end of treatment (10 days) in the IP group.
In the IV/oral group, 55% of the patients
were treated with IV vancomycin and
tobramycin for 10 days because the
isolated microorganism was resistant to
oral antibiotics, the remaining 45% were
treated from day four with oral antibiotics:
flucloxacillin (eight pts), cotrimoxazole
(three), sodium fusidate, erythromycin,
amoxycillin (two each), pencillin V,
trimethoprim, cephalexin (one each).
At onset, samples of dialysate were sent
to the laboratory for microbiological
analysis and after two days and 10 days.
The following investigations were carried
out:
Dialysate leukocyte count
Gram stain
5 mls inoculated into Robertson's broth
Inoculation onto chocolate agar and
Wilkins Chagren agar
Antibiotic sensitivity testing
Serum levels of vancomyin and
tobramycin were measured at day two and
day five, and for those on intravenous
therapy, tobramycin levels were measured
on days four and six.
when they were proved to have fungal
peritonitis.
In the remaining 75 patients, 36 were in
the IV and 39 were in the IP group. The
results (Table II), demonstrate a
significantly better outcome for the IP
group (P < 0.02).
Because the higher failure rate in the IV
group may have been due to a
preponderance of tobramycin-resistant
organisms (generally Staphylococcus
epidermidis), we did a separate analysis of
episodes due to such organisms. Despite the
smaller number of cases the difference
between the two treatment regimes was still
significant (p < 0.05) (Table III).
The distribution of infecting organisms
Cure was defined as the resolution of
between the two treatment groups (Table
symptoms and signs of peritonitis, and a
IV) shows that nine of the 13 treatment
dialysate leukocyte count of less than
failures in the IV group had tobramycin-
100/mm3 within 10 days, in the absence of
resistant, gram-positive organisms.
a subsequent relapse. Relapse was defined
However, in both treatment groups, the
as a recurrence, with the same organism or
success rate against tobrarnycin-sensitive
no growth, within 15 days of completion of
organisms were similar (79% v 83%, p >
treatment of the previous episode.
0.5). We found no significant difference in
Treatment failure was defined as a clinical
outcome between those on the IV /oral
deterioration, or an increase in the dialysate
regime who had been changed to oral
leukocyte count, necessitating an alteration
antibiotics, and those who had received
in antibiotic administration, continuation of
vancomycin and tobramycin throughout the
treatment beyond 10 days or catheter
10-day course. There was no significant
removal.
difference, in the trough serum levels of
Statistical analysis used the chisquared
tobramycin or vancomycin, between
test with Yates correction, and Fisher's
treatment-successes and failures in either
exact test.
group.
Two patients in the IV group developed
RESULTS hypotension during the infusion of
vancomycin, a recognised side
Ninety-three patients developed peritonitis
during the course of the trial. Thirteen were
excluded for the following reasons:
Recurrence 7
Septicemia I
Tract infection 5
Five patients were withdrawn from the
trial. In three of these five, the catheter was
removed before completion of treatment
because of frequent attacks of peritonitis
before the current episode. We attributed
these to persistence of organisms on the
catheter , although these cases did not
satisfy the definition of recurrence within
15 days. Two of these withdrawals were IP,
the other being IV. Two more patients were
withdrawn from the IP group
 sumably was inadequate to eradicate the
infection. Our findings are in contrast to
those of Krothapalli et al (6), although this
may be explained by important differences
in the total dose of vancomycin
administered. Conversely, Gram-negative
organisms, all of which were vancomycin-
resistant, appeared to respond equally well
to IP and IV/oral regimes. There was no
evidence that those patients who changed
to oral antibiotics had a different
success-rate than those who had the 10-day
course of IV treatment.
In conclusion we recommend that
vancomycin be given by the intraperitoneal
route, although this may not be necessary
for tobramycin.

effect, and these patients were transferred
to the IP group. There was no clinical
evidence of ototoxicity in either group, and
serum tobramycin concentration did not
reach levels normally associated with toxic
side-effects. No patients suffered
pseudomembranous colitis .
DISCUSSION
We wished to examine a route of antibiotic
administration other than the intraperitoneal
for three main reasons . Firstly, many
patients do not find it easy to add
antibiotics aseptically to their bags, and
there is always a danger of inadvertent
overdosing which may be particularly
serious in the case of the aminoglycosides.
Secondly, when antibiotics are given in
every bag, a steady-state serum level is
achieved without any peaks or troughs;
some have suggested that this may be
associated with an increased risk of
aminoglycoside toxicity ( 10) .Finally, we
wanted to investigate the possibility
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