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Activity of fleroxacin alone and in combination with clindamycin or metronidazole in experimental intra-abdominal abscesses.

To assess the potential efficacy of fleroxacin in combination with clindamycin or metronidazole in mixed aerobic and anaerobic infections, we used a rat model of intra-abdominal abscesses in which the inoculum consisted of pooled rat feces mixed with BaSO4. Two hours after bacterial challenge, antimicrobial therapy was begun intravenously with regimens designed to stimulate human pharmacokinetics. A combination of clindamycin and gentamicin was included as an established treatment regimen. After 8.5 days of therapy, final bacterial counts in abscesses showed that fleroxacin alone or combined with metronidazole or clindamycin effectively eradicated Escherichia coli, with bacterial densities of < or = 2.84 +/- 0.1, < or = 2.9 +/- 0.1, and < or = 2.9 +/- 0.1 (mean +/- standard error of the mean) log10 CFU/g, respectively. The addition of either clindamycin or metronidazole to fleroxacin substantially enhanced the effectiveness of the regimens against Bacteroides fragilis, with bacterial counts of < or = 3.0 +/- 0.1 or < or = 2.9 +/- 0.1 log10 CFU/g, respectively, versus 9.2 +/- 0.2 log10 CFU/g for fleroxacin alone. The combination of metronidazole and fleroxacin also resulted in a significantly greater reduction of peptostreptococci and Bacteroides thetaiotaomicron than fleroxacin alone (< or = 2.9 +/- 0.1 versus 6.1 +/- 0.9 log10 CFU/g and 3.3 +/- 0.4 versus 8.3 +/- 0.1 log10 CFU/g, respectively). Except for those of B. fragilis, counts of other anaerobes were reduced to a greater extent by metronidazole plus fleroxacin than by clindamycin plus fleroxacin, although differences were not always significant. Metronidazole plus fleroxacin was at least as active a clindamycin plus gentamicin against all species and was significantly more active against Clostridium spp. No regimen effectively eradicated enterococci from the abscesses. These results suggest that the addition of either metronidazole or clindamycin would effectively enhance the spectrum of fleroxacin for treatment of mixed aerobic and anaerobic infections.

Abdomen↗

Indium 111 labeled white blood cell scintigraphy for the diagnosis of upper abdominal abscesses in a child with Wiscott-Aldrich syndrome.

We report on a case of multiple hepatic abscesses in an immunodeficient patient where initial radiologic evaluation by ultrasonography and computed tomography confused early management by failing to demonstrate the abscesses and by suggesting other diagnoses. Indium 111 (In-111) white blood cell (WBC) scanning with Tc-99 liver-spleen scan subtraction accurately demonstrated subcapsular hepatic abscesses in four out of four sequential studies, and later confirmed resolution of the abscesses. We suggest that In-111 WBC scanning may be used as a highly specific method of diagnosing suspected upper abdominal abscesses in children.

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The effects of RU 41.740, a glycoprotein immunomodulating agent derived from Klebsiella pneumoniae, on intra-abdominal abscess formation in mice.

The prophylactic and therapeutic efficacies of the immunomodulating agent RU 41.740 (a glycoprotein extract from Klebsiella pneumoniae) were studied in a murine model of intra-abdominal abscess formation with Bacteroides fragilis, Escherichia coli, and bran as an abscess-potentiating agent. Parenteral injection of RU 41.740, either before or after injection of an abscess-inducing mixture (AIM), was associated with significantly diminished incidence and size of abscesses. Abscess incidence and size were significantly decreased by oral administration of RU 41.740 after, but not before, AIM injection. Abscess formation and resolution are the results of complex interactions of host defence mechanisms with bacteria and potentiating agent, and RU 41.740 has been shown previously to activate both macrophage and neutrophil function. These results indicate that activation of non-specific defences may protect against abscess development in chronic sepsis.

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Structure-function relationships for polysaccharide-induced intra-abdominal abscesses.

We have previously shown that in an animal model of sepsis positively and negatively charged groups on polysaccharide A of Bacteroides fragilis are essential for the induction of intra-abdominal abscess formation (A. O. Tzianabos, A. B. Onderdonk, B. Rosner, R. L. Cisneros, and D. L. Kasper, Science 262:416-419, 1993). By introducing chemical modifications into the structures of B. fragilis polysaccharide B as well as other abscess-inducing bacterial polysaccharides, we observed the following. (i) The presence of a nonacetylated free amino group on these polysaccharides appears to be required for abscess induction. (ii) No specific type of negatively charged group is essential to abscess induction by these polysaccharides. (iii) The density of free amino groups on these polysaccharides influences this pathobiologic host response.

Abdomen↗

Efficacy of abdominal computed tomography in evaluation of possible abdominal abscess.

A retrospective analysis was made of all abdominal computed tomography scans performed because of clinical suspicion of an abscess at our institution over a 12-month period. Of 130 patients examined, 45 patients had had abdominal surgery within the previous 2-week period. Of these patients, 14 were found to have abscesses on computed tomography, with three known false-negative studies. An additional nine patients had sterile postoperative collections. Nine patients had had an abdominal abscess previously diagnosed, and five of these had a residual abscess. A total of seven abscesses were found by computed tomography in 76 patients who had had no surgery in the previous 2 weeks, with one known false-negative study. High-risk categories of nonoperative patients were identified. Only one positive study occurred in a patient without a high clinical index of suspicion for an intraabdominal abscess, although a total of 50 patients fell into this low-risk, nonoperative category. The cost-effectiveness of computed tomography studies in such low-risk patients is questioned.

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Prevention of intra-abdominal abscesses with fibrinolytic agents.

Fibrin deposition during secondary peritonitis predisposes to abscess formation by protecting bacteria from host-defence mechanisms. To test the hypothesis that local fibrinolytic therapy can prevent the formation of intra-abdominal abscess, daily injections of the fibrinolytic enzymes trypsin and tissue plasminogen activator (t-PA) were administered intraperitoneally to Wistar rats inoculated intraperitoneally with infected fibrin clots. After 5 days, trypsin (1 mg/ml) had significantly (p less than 0.001) reduced abscess formation in animals inoculated with monomicrobial Bacteroides fragilis clots (20% versus 87%) or mixed Escherichia coli-B. fragilis clots (11% versus 91%). Bacteroides fragilis abscesses were also completely prevented with t-PA (0.25 mg/ml). The number of B. fragilis organisms present in residual abscesses in the trypsin-treated group was significantly (p less than 0.05) lower than in the control group (8.2 +/- 0.2, n = 7 versus 5.7 +/- 1.4, n = 4, log CFU/g abscess). In-vitro studies demonstrated that trypsin had no bactericidal effect on B. fragilis, suggesting enhanced clearance of bacteria. From these studies it appears that controlled fibrinolysis at operation may be a useful adjunct to surgery and systemic antibiotics in preventing abscess formation postoperatively.

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Use of lymphokines in treatment of experimental intra-abdominal abscess caused by Bacteroides fragilis.

The role of cell-free soluble factors (lymphokines) derived from mitogen-activated splenic cells of mice previously immunized against Bacteroides fragilis was evaluated in the treatment of B. fragilis intra-abdominal abscess (IAA). Neither clindamycin nor lymphokines alone were effective against an established B. fragilis IAA, but the combination of clindamycin and lymphokines decreased the abscess size and bacterial counts in the majority of animals. This suggests that the synergy of lymphokines with clindamycin effects cure of IAA caused by B. fragilis and that lymphokines might have an application as adjuncts to conventional antimicrobial therapy in this setting.

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Efficacy of different beta-lactams against an extended-spectrum beta-lactamase-producing Klebsiella pneumoniae strain in the rat intra-abdominal abscess model.

Although standard-inoculum MICs were within the susceptible range for all compounds, cefoperazone, cefotaxime, and cefpirome were significantly less effective than imipenem or the combination of cefoperazone and sulbactam in the treatment of rat intra-abdominal abscesses due to an extended-spectrum beta-lactamase-producing strain of Klebsiella pneumoniae.

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Efficacy of ampicillin-sulbactam versus that of cefoxitin for treatment of Escherichia coli infections in a rat intra-abdominal abscess model.

We examined the efficacy of ampicillin-sulbactam (2:1) and cefoxitin in the treatment of infections caused by Escherichia coli strains exhibiting increasing levels of beta-lactamase-mediated resistance to ampicillin-sulbactam in the rat intra-abdominal abscess model. Cefoxitin was superior to ampicillin-sulbactam in the treatment of infections caused by all strains. Treatment with ampicillin-sulbactam resulted in a statistically significant decrease in CFU per gram of abscess in comparison with treatment with ampicillin alone for both the moderately resistant and the resistant strains, with an inverse correlation between the MIC and the absolute decrease in CFU per gram of abscess.

Abdomen↗

Percutaneous catheter versus open surgical drainage in the treatment of abdominal abscesses.

In the past 3 years, percutaneous catheter drainage (PCD) was performed for 24 abdominal and retroperitoneal abscesses while open surgical drainage (OSD) was used for treatment of 24 similar abscesses at the affiliated hospitals of UMDNJ-Rutgers Medical School. Although the method of treatment was arbitrarily selected by the attending physician, the two groups were similar with respect to abscess location, underlying illnesses, and previous operations. In the PCD group, 17 of 24 abscesses developed after operations versus 16 of 24 in the OSD group. Location of abscesses were: PCD group: abdominal (9), renal (5), pelvic (4), subphrenic (3), hepatic (2), pancreatic (1); OSD group: abdominal (10), renal (4), subphrenic (4), pelvic (3), hepatic (2), pancreatic (1). With PCD, the abscesses were localized by ultrasound or computerized tomography scan; a 20- or 22-gauge needle passed into the cavity, followed by progressively larger guide wires, dilators, and catheters; the pus evacuated; and abscess cavity thoroughly irrigated with sterile saline. Percutaneous catheter drainage was successful in 22 of 24 cases. There were two inconsequential complications. The mean post-PCD hospital stay was 11.7 days. With OSD, five patients developed major complications, including three deaths from sepsis. The mean post-OSD stay for surviving patients was 21.2 days. The advantages of PCD versus OSD are: 1) precise noninvasive localization of abscesses, 2) avoidance of general anesthesia, 3) avoidance of major complications, and 4) shorter postdrainage hospital stay. Open surgical drainage should be reserved for cases where PCD fails to control sepsis, close fistulae, or when noninvasive scanning either fails to demonstrate a discrete abscess in the face of intra-abdominal sepsis or identifies an abscess that cannot be percutaneously drained without traversing the bowel.

Abdomen↗

Effects of muramyl dipeptide and clindamycin in a murine abdominal abscess model.

Peritonitis and subsequent local and remote complications are an important source of morbidity and mortality, which persist despite the best available treatment. Reasonable therapeutic efforts, therefore, have included stimulation of host defenses with immune adjuvants, recently typified by muramyl dipeptide (MDP). Murine abdominal abscesses were created by intraperitoneal injection of Bacteroides fragilis and autoclaved fecal suspensions, and the effects of MDP and clindamycin on these abscesses were evaluated. At 10(4) colony-forming units (CFU) per milliliter of Bacteroides fragilis, intraperitoneal clindamycin was effective in reducing both the incidence of abscess formation as well as the number of abscesses per mouse as compared with controls at doses of 5 mg/kg and 2 mg/kg (P less than 0.01). The effect was more significant when the drug was given 30 min prior than when given after injection of organisms (P less than 0.02). At 10(7) and 10(8) CFU/ml, pretreatment with MDP increased abscess formation (P less than 0.05, P less than 0.01), an effect that was obscured by clindamycin administration, which decreased number of abscesses from controls irrespective of pretreatment with MDP. Abscesses were present on the third day after injection, and MDP, paradoxically, had increased the number of abscesses by the fifth day. Clindamycin reduced abscess formation at all concentrations of bacteria and had a dose and time-dependent response. MDP increased abscess formation only at high concentrations of Bacteroides fragilis, but clindamycin abolished this effect and reduced the number of abscesses to similar levels in both the clindamycin alone and clindamycin + MDP groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗

Intraperitoneal irrigation with povidone-iodine solution for the prevention of intra-abdominal abscesses in the bacterially contaminated abdomen.

A prospective randomized investigation was undertaken, involving 168 consecutive patients undergoing laparotomy for conditions accompanying bacterially contaminated peritoneal cavities, to evaluate the effectiveness of povidone-iodine irrigation of the peritoneum in preventing the development of intra-abdominal abscesses. In the treatment group irrigated with povidone-iodine solution, 0.1 per cent available iodine, one of 80 patients had an abscess, 1.3 per cent, while, in the saline solution irrigated control group, nine of 88 patients had abscesses, 10.2 per cent, p less than 0.05. Although the serum iodine levels were elevated 24 hours after intraperitoneal irrigation with povidone-iodine solution, iodine levels returned to near normal by 72 hours. Thyroxine levels showed no major changes. No complications resulting from the use of povidone-iodine were recognized.

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Computed tomography and post-laparotomy intra-abdominal abscesses.

Thirty-one patients were prospectively studied and had abdominal computed tomography for post laparotomy sepsis. Computed tomography is of particular interest in seriously ill post-operative patients, 15 of our patients were on ventilators, and it enabled diagnosis and localization of abscesses in 15 patients. Drainage could therefore be achieved via a limited surgical approach, and extensive laparotomy was avoided. Of 16 patients without abscess, the abdominal computed tomogram was negative in 14 cases and there were two false positives. The overall accuracy was 0.94 with a sensitivity of 1 and a specificity of 0.88. The ability to screen the whole abdomen and exactly localize the lesion are the advantages of this non-invasive method.

Abdomen↗

Delayed administration of tissue plasminogen activator reduces intra-abdominal abscess formation.

Previous studies demonstrated that intraperitoneal fibrinolysis using tissue plasminogen activator (t-PA) prevented intraabdominal abscess formation in a rat fibrin clot infection model when administered simultaneously with the infecting inoculum. To more closely mimic the clinical setting, the efficacy of delayed administration of t-PA on intra-abdominal abscess formation was examined. A delay of 2, 6, and 18 hours had no effect on the rate of abscess formation but did reduce abscess size, indicating partial fibrinolysis. Since fibrin clots dehydrate in vivo, we hypothesized that a higher concentration of t-PA might be necessary to effect complete abscess resolution. High-dose t-PA (0.1 mg/mL) prevented abscess formation following a 6-hour delay and reduced mean weight following an 18-hour delay. Since heparin sodium may prevent new fibrin deposition and enhance t-PA activity, it was combined with t-PA to investigate potential synergistic effects. Despite adequate anticoagulation with heparin, no synergy with t-PA could be documented. In addition, the combination of antibiotics with t-PA did not affect its efficacy in vivo. We demonstrate that delayed administration of t-PA is effective in preventing abscess formation and may have implications for the clinical setting where initial surgical intervention is usually delayed.

Abdomen↗

Therapeutic evaluation of difloxacin (A-56619) and A-56620 for experimentally induced Bacteroides fragilis-associated intra-abdominal abscess.

Difloxacin (A-56619) and A-56620, two novel fluoroquinolones, were tested in comparison with ciprofloxacin, cefoxitin, and combined clindamycin and gentamicin in the treatment of experimentally induced intraabdominal abscess associated with Bacteroides fragilis. Difloxacin was found to be as effective as clindamycin-gentamicin. A-56620, despite achieving subtherapeutic levels in serum, was found to be as effective as cefoxitin. Both difloxacin and A-56620 were effective in vivo against experimentally induced intra-abdominal abscess in rats.

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