Biomedical subjects
Publications and source records attributed to C E Edmiston.
Specimens from 152 abdominal infections were examined to determine which groups of endogenous bacteria participate in infection emanating from different sites in the gastrointestinal tract. A notable finding was the predominance of anaerobic microflora from infections of ischemic versus perforated small bowel. Empiric antibiotic treatment for ischemic bowel should include focused coverage for anaerobes.
Sample-size determination is a crucial component of study design. Estimates of sample size are influenced by the amount of change that must occur between study groups and the degree of risk that the investigator is willing to accept in evaluating the null hypothesis. A complete understanding of the impact of sample size on the interpretation of study data is therefore a prerequisite for quality, innovative, valid research.
Peritonitis is associated clinically with paralytic ileus, but the physiologic mechanisms of the effects of peritonitis on bowel myoelectric activity have not been explored. Bipolar electrodes were inserted into the rats, and myoelectric control recordings were obtained for 4 h/d for 5 consecutive days. Peritonitis was then induced, and myoelectric recordings were again obtained. Each animal served as its own control. Prior to induction of peritonitis (control), phase I, II, and III myoelectric activity was present in all recordings. The cycle duration of the migrating myoelectric complex was 17.17 +/- 0.39 minutes, and the migration velocity of phase III was 0.61 +/- 0.02 cm/min. The most striking feature during peritonitis was the complete inhibition of phase II activity. Phase III activity, however, was present with a cycle duration of 16.69 +/- 0.42 minutes. This study shows that some features of intestinal myoelectric activity (phase III) are preserved during episodes of peritonitis, and others are changed (phase I) or lost (phase II). Disappearance of phase II activity in this type of ileus emphasizes its importance in normal small bowel motility.
Agar dilution and microbroth dilution methods appear equally acceptable for susceptibility testing of anaerobes against temafloxacin and ciprofloxacin. Most major discrepancies occurred with strains whose MIC was near the breakpoint. These results suggest that method variation will not be a significant factor in the susceptibility testing of anaerobic bacteria against other fluoroquinolone agents.
A double-blind trial was conducted in 385 patients with suspected bacterial intra-abdominal infections to compare the efficacy and safety of ampicillin-sulbactam with cefoxitin. Patients were randomized to receive either 3 g ampicillin-sulbactam (2 g ampicillin-1 g sulbactam), or 2 g cefoxitin, every 6 hours. To be evaluable, patients had to demonstrate positive culture evidence of peritoneal infection at the time of operation. A total of 197 patients were evaluable for clinical efficacy. The two treatment groups were comparable in demographic features and in the presence of risk factors for infection. Clinical success (absence of infection and of adverse drug reaction) was observed in 86% of patients in the ampicillin-sulbactam group and 78% in the cefoxitin group. Eradication of infection occurred in 88% of the ampicillin-sulbactam group and 79% of the cefoxitin group. There were no differences in the nature or frequency of side effects observed in the two groups. Ampicillin-sulbactam demonstrated no difference in safety or efficacy when compared with cefoxitin in the treatment of serious intra-abdominal infections of bacterial origin.
OBJECTIVE: To describe and test a method for temporary closure of the abdomen. DESIGN: Open laboratory and clinical studies. SETTING: Department of Surgery, Medical College of Wisconsin, USA. SUBJECTS: 11 patients who underwent planned relaparotomy. MATERIAL: The burr consists of two adherent sheets of polyamide and polypropylene, which may be trimmed to accommodate any wound. One sheet consists of micro-mushrooms, the second of multiple slings. The two sheets stick to each other upon pressure and can easily be separated to open the wound. INTERVENTION: Planned relaparotomy or staged abdominal repair. OUTCOME MEASURES: Measurements of tensile strength and microbiological cultures. RESULTS: The shearing force required to separate the burr is 150 +/- 27 N/5 cm2 when gas sterilized and 77 +/- 11 N/5 cm2 when used in five subsequent laparotomies. No adverse microbiological effects were seen. CONCLUSION: The artificial burr can be used for temporary closure of the abdomen. It circumvents the problems that occur with zip fasteners, Marlex mesh, slide fasteners, and towel clips.
Gastrointestinal dysfunction is a common secondary complication of insulin-dependent diabetes mellitus, yet its etiology is unclear. Enteric microbial overgrowth may play a role. To quantitate the changes in mucosal-adherent enteric microbial populations in untreated diabetes mellitus and to assess the impact of two forms of insulin replacement therapy upon enteric microbial populations, age-matched male Lewis rats were rendered diabetic by the administration of intravenous streptozotocin (55 mg/kg). After diabetes was confirmed (blood glucose level greater than 250 mg/dL), rats were divided into three groups: no treatment (no insulin), treatment with daily insulin to maintain normoglycemia (3 to 7 units of protamine zinc insulin subcutaneously), or transplantation with a vascularized heterotopic duct-ligated pancreatic isograft. After 1 month, rats were killed, and segments of the proximal, middle, and distal small bowel were obtained. Mucosal samples were rinsed in phosphate-buffered saline to remove nonadherent bacteria prior to aerobic and anaerobic culturing. Microbial recovery was expressed as the log10 colony-forming unit/mg tissue wet weight. Untreated diabetes resulted in an overgrowth of mucosal-associated small bowel aerobic and anaerobic microbial populations compared with populations in normal nondiabetic age-matched control rats. Insulin treatment and pancreatic transplantation prevented microbial overgrowth in the diabetic small intestine. Pancreatic transplantation resulted in strict normoglycemia equivalent to that in nondiabetic control rats, whereas insulin treatment resulted in slightly higher blood glucose levels at sacrifice and wide fluctuations in blood glucose levels compared with nondiabetic control rats. These data suggest that sustained normalization of glucose levels is not required to prevent microbial overgrowth in diabetic rats.
Fifty-four strains of Peptostreptococcus magnus (11 were recovered from abdominal infections, 18 were from nonpuerperal breast abscesses, and 21 were from diabetic foot infections; the type strain and three other strains were from the American Type Culture Collection, Rockville, Md.) and the type strain of Peptostreptococcus micros were tested for their ability to produce various enzymes, including catalase, hippurate hydrolase, serine dehydratase, threonine dehydratase, collagenase, gelatinase, alkaline phosphatase, and esterase C4. The data were analyzed by cluster analysis. The results showed that all but one strain could be assigned to either of two distinct, valid clusters. The first cluster of 11 strains was composed of strains that were relatively inactive, having produced one or two of the eight strain-dependent enzymes. The second was a large cluster of strains (n = 43) that were considerably more active, all having produced at least three enzymes; the vast majority of strains (89%) produced four or more enzymes. The unclustered strain produced one enzyme that was different from that produced by the strains in the first cluster. The chi 2 test of homogeneity applied to the clustering solution indicated that greater enzyme activity was significantly associated with the site of infection (P less than 0.001). The more enzymatically active P. magnus strains were recovered significantly more often from nonpuerperal breast abscesses and diabetic foot infections than they were from abdominal infections. These results may provide insight into the nature of certain polymicrobial soft tissue infections and suggest that (i) P. magnus may participate more in nonpuerperal breast and diabetic foot infections than in abdominal infections and that (ii) peptostreptococcal production of proteolytic enzymes may have an important adjunctive effect on the pathogenesis of certain soft tissue infections.
We explored the effects of prostaglandins (PG) F2 alpha and E2 on the motor and myoelectric activity of the small intestine using closed intra-arterial injections in conscious chronically instrumented dogs. PGF2 alpha (0.125-5 micrograms) and PGE2 (1-10 micrograms) were injected via a T tube into a branch of the superior mesenteric artery perfusing a 15-cm segment of jejunum. Experiments were performed on four dogs in which the recording devices had been implanted above, below, and within the perfused segment. PGF2 alpha given during phase I of the migrating myoelectric complex cycle induced phasic contractions in the perfused segment of intestine in a dose-dependent manner. Atropine (50-100 micrograms), hexamethonium (15 mg), or TTX (10-15 micrograms) administered before the injection of PGF2 alpha failed to inhibit the effects of PGF2 alpha. In contrast pretreatment of the perfused segment with verapamil (2.5 mg) or PGE2 (1-5 micrograms) abolished the effects of PGF2 alpha. Moreover, PGE2 injected 5 min after the administration of PGF2 alpha inhibited the PGF2 alpha-induced contractions. Administration of PGE2 alone (3-10 micrograms) before the arrival of phase III activity in the perfused segment abolished phase III from this segment of intestine. Our studies indicate opposing effects of PGF2 alpha and PGE2 on small intestinal myoelectric and contractile activities. PGF2 alpha has a direct excitatory effect on the intestinal smooth muscle, which is calcium channel dependent but independent of intrinsic nerves. PGE2 has an inhibitory effect both on the spontaneous and PGF2 alpha-induced small intestinal myoelectric and contractile activity.
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Alterations in the symbiotic relationship between immunocompromised hosts and their resident gut microflora may lead to serious complications following small bowel transplantation (SBT). This study examined the effects of SBT and cyclosporine (CsA) immunosuppression on gut bacterial populations and translocation to the mesenteric lymph nodes. Sixty adult male meat-fed Lewis rats were divided into six groups: normal controls, CsA alone (24 mg/kg im qod), CsA carrier vehicle alone, isografts, isografts given CsA, and allografts given CsA. Rats were killed after 3 weeks and segments of small bowel and colon were harvested for quantitative tissue culture. Mesenteric lymph nodes and blood were cultured to identify translocation. Transplantation alone led to an increase in gram-negative aerobes from 2.6 to 4.6 colony forming units/100 mg tissue (P less than 0.05) in the distal ileum (transplanted segment). Eighty-four percent of transplanted animals receiving CsA had bacteria recovered from their mesenteric lymph nodes compared to none in controls (P less than 0.001) and 20% in isografts not receiving CsA (P less than 0.02). Intestinal transplantation alone appears to promote gram-negative overgrowth while the addition of CsA therapy facilitates translocation to the mesenteric lymph nodes and may predispose to gut-associated sepsis following SBT.
Fifty isolates of Peptostreptococcus magnus from intraabdominal sepsis, nonpuerperal breast abscess, and diabetic foot infections were examined for collagenase activity using bovine type I collagen. Collagenase production was detected in a higher percentage of strains from nonpuerperal breast and diabetic foot specimens (P less than .001). This enzyme may be responsible for P. magnus playing a more central role in the pathogenesis of nonpuerperal breast abscess and diabetic foot disease than in intraabdominal sepsis.
The phenomenon of bacterial translocation, the movement of viable indigenous microorganisms across the intestinal epithelial barrier, has been recognized for almost 100 years. At the present time, the precise mechanism of microbial transport is unknown. Active epithelial uptake and phagocyte-mediated transport have been proposed as likely explanations for the extraintestinal movement of bacteria to mesenteric lymph nodes and distant organ sites. Translocation has been proposed as the pivotal process associated with intestinal origin portal sepsis in seriously ill and immunocompromised patients. While several etiologic factors can be implicated in the pathogenesis of bacterial translocation, the present clinical implications are based almost solely on studies of dogs, rats and mice. Present investigations continue to suggest a causal relationship between intestinal mucosal integrity and infection by indigenous gastrointestinal bacteria.
Parenteral antibiotics are used as an adjunct to amputation or operative debridement for patients with diabetes who require emergency surgery for a septic foot. In 26 patients with a diabetes-related foot infection, one dose of various intravenous antibiotic regimens (gentamicin and clindamycin, ticarcillin/clavulanate, ampicillin/sulbactam) was administered during the hour before the procedure, and assays were performed to measure the antibiotic serum and tissue levels at the time of surgical debridement. Aerobic and anaerobic cultures were performed on infected tissue. The 172 bacterial isolates, including 95 aerobes and 77 anaerobes, (6.6 isolates per patient) underwent antibiotic susceptibility testing. Antibiotic levels were calculated by biologic assay from serum and tissue biopsies from the viable margins of the surgical site, which subsequently healed primarily or supported a split-thickness skin graft. Sixteen of the patients achieved therapeutic serum levels, and therapeutic tissue levels were reached in six patients at the time of surgery. A significantly lower number of patients had therapeutic tissue levels compared to serum levels (p less than 0.01, chi square). Initial intravenous antibiotic administration provides inadequate tissue concentrations for treating foot infections in patients with diabetes. Adequate serum antibiotic levels do not reflect therapeutic tissue antibiotic levels at the surgical margins in this group of patients.
The brief exposure of bacteria to high antibiotic concentrations can result in prolonged suppression of bacterial growth termed postantibiotic effect (PAE). A pathogenic Staphylococcus epidermidis strain (RP-62) was exposed to 2X and 6X minimum inhibitory concentrations (MIC) of cefazolin, vancomycin, or rifampin for 1 hr and incubated for 2 to 24 hr in inhibitory-free broth. PAE was defined as the difference in time required for a 1.0 log increase in test (T) vs control (C) cultures (PAE = T-C). PAE was observed only for rifampin: 6 hr at 2X MIC and 8 hr at 6X MIC. Bacterial adherence to Dacron grafts was calculated in PAE vs control cultures by a quantitative culture technique for graft specimens incubated 2 to 24 hr. A demonstrable PAE and its impact on adherence were found to be both antimicrobial and concentration dependent. A significant decrease in staphylococcal adherence to velour-knitted Dacron was demonstrated by rifampin at 2X MIC (P less than 0.05) and 6X MIC (P less than 0.01). This phenomena may be useful in reducing bacterial adherence and colonization of bioprosthetics in the perioperative period. Preoperative suppression of staphylococcal skin flora by high dose antimicrobials can alter the capacity of these organisms to adhere to vascular prosthetic grafts and, if incorporated into antibiotic prophylaxis regimens, may reduce graft colonization.
Occult infection was investigated as an etiologic factor in the formation of femoral anastomotic pseudoaneurysms associated with prosthetic vascular grafts. Forty-five femoral pseudoaneurysms with no clinical evidence of infection 10 to 173 months after prosthetic graft placement were consecutively studied. The explanted Dacron or explanted polytetrafluoroethylene graft material was cultured in trypticase soy broth and ultrasonically oscillated to remove adherent bacteria. All patients were treated by excision of the pseudoaneurysm and surrounding perigraft capsule and in situ replacement with an interposition prosthetic graft. Thirty-two bacterial isolates were recovered from 27 (60%) of the specimens, with coagulase negative staphylococci (Staphylococcus epidermidis S. warneri, S. hominis, S. capitis) accounting for 24 of the recovered species. No infection of the replacement graft developed in any patient and no recurrent pseudoaneurysms were observed. Bacterial colonization may occur at implantation or during subsequent procedures when the prosthetic graft is exposed. This chronic infection can be diagnosed by means of sensitive culture techniques that dislodge adherent bacteria from the graft surface. On grounds of the observations reported in this study, there appears to be suggestive evidence that an occult infectious process may be one of the factors that play a role in the development of some femoral anastomotic pseudoaneurysms.
Sixty breast culture specimens were obtained by needle aspiration from 54 women and 2 men. A total of 221 microbial isolates were obtained from 52 culture-positive samples. Aerobes alone were recovered from 11 patients while 5 were culture-positive for anaerobes only. Thirty-six patients harbored mixed aerobic and anaerobic microbial flora, and the anaerobic gram-positive cocci were the predominant isolates recovered. The mean microbial recovery for patients with an acute abscess was 2.9 isolates, while in patients with chronic infections the mean microbial recovery was 5. The anaerobic populations outnumbered facultative isolates by two to one, and 34% of anaerobic isolates were recovered from subculture. These findings demonstrate that, contrary to previous reports, nonpuerperal breast infections involve a mixed infection that is primarily anaerobic.
Slime-producing coagulase-negative staphylococci are pathogens in vascular surgery by virtue of their ability to adhere to and persist on prosthetic graft material. Inguinal and abdominal skin sites were cultured in 41 patients upon hospitalization, and slime production and antimicrobial susceptibility were assessed in all recovered staphylococcal isolates. Twenty-one patients eventually underwent lower-extremity revascularization. In the operative population, cultures were also obtained on the day of surgery and fifth postoperative day. All 21 patients received perioperative cefazolin. Of 327 coagulase-negative staphylococci recovered, Staphylococcus epidermidis (47%), S. haemolyticus (21%), and S. hominis (10%) were the predominant isolates. Slime-producing coagulase-negative staphylococci were recovered from 17 of 21 patients at admission but only from 8 of 21 patients on day 5 postoperation (P less than 0.05). S. epidermidis isolates demonstrated increasing multiple resistance from admission to 5 days postoperation to methicillin, gentamicin, clindamycin, erythromycin, and trimethoprim-sulfamethoxazole (P less than 0.05). All coagulase-negative staphylococcal isolates were susceptible to ciprofloxacin and vancomycin. Slime-producing capability was not associated with increased methicillin resistance for the recovered isolates. The data demonstrate that patients enter the hospital colonized with slime-producing strains of coagulase-negative staphylococci and that during hospitalization the staphylococcal skin burden shifts from a predominately susceptible to a resistant microbial population, which may enhance the importance of slime production as a risk factor in lower-extremity revascularization.