Laura S. Trachtenberg

Effects of interferon-γ treatment on surgically simulated wound infection in mice

Interferon-γ (IFN-γ) has been shown to have immunoregulatory properties and is able to modulate resistance to several microbial infections. This study was designed to determine the efficacy of IFN-γ treatment in a mouse model of infection that simulates many clinical conditions associated with surgical wound infection: viz, a bacteria laden suture and tissue injury. The test bacteria were Klebsiella pneumoniae. Groups of CBA/J mice received either IFN-γ or RPMI1640 medium (controls) subcutaneously. IFN-γ was administered daily at a dose of 7500 units for 5 days prior to bacterial challenge. Mice treated with IFN-γ survived significantly longer than controls. Systemic bacterial recovery was significantly reduced in the IFN-γ treated group but local bacterial recovery was unaffected.

A randomized, double-blind trial of single dose piperacillin versus multidose cefoxitin in alimentary tract operations

For elective alimentary tract operations in which contamination is moderate, single dose prophylaxis with piperacillin is equivalent to triple dose cefoxitin, a well established and effective regimen. Both methods failed to control infection arising in the perineal wound after abdominoperineal resection. Just as is the case with drain site infection, such infection often evolves from postoperative contamination and, indeed, is in theory and in fact unlikely to be controlled by perioperative prophylaxis. This study is among the first of several examining the issue of single dose prophylaxis and will be the harbinger of other studies from other groups examining whether or not the course of therapeutic antibiotics can be safely shortened in patients with peritoneal contamination.

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)

Evaluation of Copovithane as a Nonspecific Immunomodulator in Surgically Simulated Sepsis

Copovithane (CPV), a synthetic polymer, has been shown to have antitumor activity and also to reduce mortality in experimental murine peritonitis. The purpose of this study was to compare CPV with muramyl dipeptide (MDP), an immunomodulator of proven efficacy in simulated surgical infection. Six groups of CBA/J mice were compared; they received intramuscular injections of normal saline (controls), MDP (100 micrograms), or CPV (100, 200, and 400 mg/kg) 24 h prior to bacterial challenge. The challenge consisted of a Klebsiella-impregnated thigh suture. The first experiment assessed survival after bacterial challenge. The MDP and the CPV groups both had median survival times of 3 days, significantly longer than the control group (1 day, p less than .05). In the second experiment, animals were sacrificed at 6, 24, and 48 h following bacterial challenge, and blood and infected muscle were taken for quantitative bacteriology. At 6 h, there was no difference between groups. Both the MDP and CPV groups had significantly (p less than .05) lower blood bacterial counts than the control group at 24 and 48 h. Both the MDP and CVP groups had significantly lower local bacterial recovery than controls at 48 h (p less than .05), and local bacterial recovery of the MDP group was significantly lower than the control group at 24 h (p less than .05). CPV improved survival and reduced local and systemic bacterial recovery compared with controls. Although the effect of CPV was similar to MDP in this model, it consistently was of lower magnitude and had a narrow dose range.