COMPARISON OF CONCENTRATIONS OF SULBACTAM-AMPICILLIN ADMINISTERED BY BOLUS INJECTIONS OR BOLUS PLUS CONTINUOUS-INFUSION IN TISSUES OF PATIENTS UNDERGOING COLORECTAL SURGERY
C. Martin et al., COMPARISON OF CONCENTRATIONS OF SULBACTAM-AMPICILLIN ADMINISTERED BY BOLUS INJECTIONS OR BOLUS PLUS CONTINUOUS-INFUSION IN TISSUES OF PATIENTS UNDERGOING COLORECTAL SURGERY, Antimicrobial agents and chemotherapy, 42(5), 1998, pp. 1093-1097
The concentrations of sulbactam and ampicillin were determined in sera
and different abdominal tissues of 16 patients who underwent elective
colorectal surgery. Patients were randomly allocated to two groups. A
t the time of induction of anesthesia, patients in group 1 (eight pati
ents) were given 1,000 mg of sulbactam with 2,000 mg of ampicillin by
intravenous bolus injection (3 min). This dose was administered again
after 2 h by bolus injection by the same route, Patients in group 2 (e
ight patients) were given the same initial dose of sulbactam-ampicilli
n by bolus injection (3 min), Then, a continuous infusion of 1,000 mg
of sulbactam with 2,000 mg of ampicillin in normal saline was immediat
ely started and was administered over a 4-h period, Blood samples were
collected to determine peak (10 min) and trough tend of surgery) anti
biotic levels. Serial blood samples were also collected at predetermin
ed periods (at the time of opening and closing of the abdominal cavity
and at the time of surgical anastomosis). Abdominal wall fat, epiploi
c fat, and colonic wall tissue samples were collected simultaneously.
Antibiotic concentrations were determined by high-performance liquid c
hromatography, Similar levels of the drugs in serum were observed for
the two regimens of administration, with trough sulbactam levels of 33
+/- 16 and 37 +/- 22 mu g/ml in groups 1 and 2, respectively, and tro
ugh ampicillin levels of 72 +/- 55 and 79 +/- 47 mu g/ml in groups 1 a
nd 2, respectively. Similar sulbactam concentrations were observed in
abdominal tissues whichever regimen of administration was used; in fat
ty tissues the sulbactam concentrations ranged from 2.7 to 3.8 mu g/g
for group 1 and from 1.7 to 4.0 mu g/g for group 2, and sulbactam conc
entrations in the colonic wall were 5.6 +/- 7.7 and 6.8 +/- 3.2 mu g/g
in groups 1 and 2, respectively (not significant). Again, no influenc
e of the regimen of administration was observed on tissue ampicillin c
oncentrations; in fatty tissues ampicillin concentrations ranged from
4.1 to 5.4 mu g/g for group 1 and from 3.2 to 5.8 mu g/g for group 2,
and sulbactam concentrations in the colonic wall were 7.0 +/- 2.8 and
11.0 +/- 4.7 mu g/g for groups 1 and 2, respectively (not significant)
. In most patients, the concentrations of ampicillin-sulbactam were gr
eater than the MIC at which 50% of isolates are inhibited (MIC50) for
Bacteroides fragilis in the fatty tissues. In the colonic wall, for mo
st patients the concentrations of ampicillin-sulbactam were greater th
an the MIG,, for B. fragilis. No influence of the regimen of administr
ation was observed on the ratio of the two components in the tissues i
nvestigated and in sera. In conclusion, a second intraoperative bolus
injection or a continuous infusion were equally effective in maintaini
ng sulbactam-ampicillin concentrations in abdominal tissues, The first
method of administration can be recommended since it is easier to han
dle.