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Biomedical subjects

E P Dellinger

Publications and source records attributed to E P Dellinger.

At least 55 records · Page 3Linked to original sources

Duration of preventive antibiotic administration for open extremity fractures.

The necessary duration of antibiotic administration after open fracture has not been established. In a double-blind prospective trial we randomized 248 patients with open fractures to receive one or five days of cefonicid sodium therapy or five days of cefamandole nafate therapy as part of the initial treatment. Rates of fracture-associated infections in the three groups were ten (13%) of 79, ten (12%) of 85, and 11 (13%) of 84, respectively. The 95% confidence limit for the difference in infection rates between the one-day group and the combined five-day groups was 0% to 8.3%. The actual difference was 0.2%. A brief course of antibiotic administration is not inferior to a prolonged course of antibiotics for prevention of postoperative fracture-site infections.

Adult↗

Hand infections. Bacteriology and treatment: a prospective study.

In a prospective, double-blind study, 193 patients hospitalized for established hand infections were randomized to receive either cefamandole intravenously followed by cephalexin by mouth or methicillin intravenously followed by dicloxacillin by mouth. Careful aerobic and anaerobic cultures were performed. Multiple organisms grew in cultures from 84% of the patients (over three isolates per infection on average). Human bite wounds contained anaerobes 43% of the time compared with 12% for other wounds. The majority of wounds (72%) required operative treatment. In 128 patients assessable for treatment outcome, results were unsatisfactory in 11 (9%). There was no difference in outcome between cefamandole (6/59, 10%) and methicillin (5/59, 8%). The presence of anaerobes, Eikenella corrodens, human bites, or an increasing number of organisms was associated with an unsatisfactory response. The presence of Staphylococcus aureus and/or beta-hemolytic streptococci was associated with a favorable response. The incidence of antibiotic-resistant isolates did not correlate with outcome.

Adolescent↗

Risk of infection after open fracture of the arm or leg.

Two hundred forty consecutive patients admitted for operative treatment of an open fracture of the arm or leg were followed up prospectively for the development of fracture infection. The independent risk of fracture infection was increased in patients with grade IIIB or IIIC fractures, internal or external fixation, lower-leg fracture, any blood transfusion, or injuries resulting from motorcycle accidents or motor vehicle-pedestrian accidents. By stepwise multivariate logistic regression, the most significant risk factors were the grade of the fracture, internal or external fixation, and fractures of the lower leg. These risk factors all represent local wound characteristics, and we conclude that the most important actions by the surgeon to prevent infection involve local wound care. There was no relation between the timing of antibiotic administration or duration of antibiotic therapy and infection risk.

Arm Injuries↗

Use of scoring systems to assess patients with surgical sepsis.

Several scoring systems for patients with severe surgical infections are described, compared, and contrasted. All show a strong relation between a high score and high mortality risk. Each has strengths and weaknesses. All of the systems need further refinement. Future investigations of patients with serious infections should incorporate one of the published severity scores as part of the patient description.

Critical Care↗

Design and conduct of antibiotic trials. A report of the Scientific Studies Committee of the Surgical Infection Society.

Several recent publications have identified important methodologic problems in the design and conduct of antimicrobial trials in surgery. Developed by consensus of the members of the Scientific Studies Committee of the Surgical Infection Society, this report provides broad guidelines for the construction of antimicrobial trials. The central issues identified include pretrial definition of study purpose, entry criteria, assignment device, and statistical analysis. These issues are fundamental in designing studies with an acceptable likelihood of finding differences among those antimicrobial regimens at least risk to the study subjects. The importance of stratifying patients on the basis of background condition, disease, and severity of illness is stressed. The inclusion in a study of variables that enhance the statistical power and, therefore, the believability of this study is stressed as an important means of clarifying substantial differences between therapies.

Abdomen↗

Nonoperative observation therapy for splenic injuries: a safe therapeutic option?

Combining these reported and estimated incidences of mortality from overwhelming postsplenectomy infection, splenic salvage with nonoperative observation therapy and operative therapy, and the incidence of posttransfusion hepatitis and related mortality provides a conditional probability estimation of the risks of death with nonoperative observation therapy and operative therapy (Figure 4). The combined mortality rates for nonoperative observation and operative therapies are based on the following measured and estimated statistics: The post-transfusion hepatitis death rate per unit of blood transfused is 0.14 percent. Forty percent of children and 20 percent of adults who have successful nonoperative observation therapy receive an average of 2 units of blood. One hundred percent of children and adults in whom nonoperative observation therapy is unsuccessful receive an average of 4 units of blood. Twenty percent of children and adults who undergo operation initially receive an average of 2 units of blood. Ten percent of observed children require laparotomy and 75 percent of these patients then undergo splenectomy. Forty percent of adults who have nonoperative observation initially later require laparotomy, 93 percent of whom also require splenectomy. Ten percent of children and adults treated with initial operation later require splenectomy. Death from overwhelming postsplenectomy infection occurs in 0.026 percent of adults who undergo splenectomy and 0.052 percent of children who undergo splenectomy. Given these assumptions, the conditional probability of death in a child who initially undergoes nonoperative observation therapy is 0.17 percent compared with 0.06 percent for initial operative therapy. In adults, 0.26 percent of the observed patients die compared with 0.06 percent for those operated on initially. As stated, many of the percentages or probabilities listed are estimations based on the best available clinical data. The inability to establish a mortality rate from overwhelming postsplenectomy infection remotely resembling that reported for otherwise healthy patients required an unsubstantiated estimate. However, even when mortality rates from overwhelming postsplenectomy infection of 0.43 percent and 0.6 percent were substituted, early laparotomy still produced lower mortality rates. This continues to be true if one assumes that early laparotomy will result in 50 percent or even 100 percent of patients undergoing splenectomy, although in these cases the statistical differences would be less. We acknowledge that these statistics may exceed or underestimate the true risk of either treatment plan.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Systemic absorption of endotracheally administered aminoglycosides in seriously ill patients with pneumonia.

A study was performed with 10 hospitalized patients to determine the percentage of an aminoglycoside dose (tobramycin or gentamicin) that is absorbed systemically after being instilled into the endotracheal tube at steady state. All patients were on respirators, had indwelling urinary catheters, and had creatinine clearances estimated to be greater than or equal to 40 ml/min. Tobramycin or gentamicin (40 mg) was instilled every 4 h directly into the endotracheal tube. Nine patients also received systemically a different aminoglycoside from that administered through the endotracheal tube. Urine was collected over a 4-h dosing interval at steady state (after at least 5 doses of the drug). The amount of aminoglycoside excreted over the 4-h interval was measured and expressed as percentage of the dose administered over that period. The range of percentage of dose absorbed was 1.5 to 34%, with a mean of 16.7 +/- 11.4% standard deviation and a median of 16.5%. The coefficient of variation was 68%. Levels of the endotracheally administered aminoglycoside in serum were measured, and all were less than 1.0 microgram/ml. While a large degree of variability in absorption was observed in this study, significant amounts of aminoglycosides could be absorbed in some patients. However, levels apparently did not accumulate in sera of patients with adequate renal function, and an empirical dosage reduction in intravenous aminoglycoside should not be necessary with the addition of endotracheally instilled aminoglycoside in patients with creatinine clearances greater than 40 ml/min.

Absorption↗

Efficacy of short-course antibiotic prophylaxis after penetrating intestinal injury. A prospective randomized trial.

Infection is the leading cause of morbidity and mortality occurring more than 48 hours after penetrating abdominal injury. Antibiotics are routinely administered to patients with penetrating intestinal injuries and are usually given for five days or more. We randomized 116 patients with confirmed penetrating injuries of the colon and/or small bowel to receive either 12 hours or five days of antibiotics. Age, sex, weapon, severity of injury, and other risk factors were evenly distributed between groups. Twenty-one patients (18%) developed trauma-related infections, 28 (24%) any infection, and three (2.6%) died. There were no significant differences between groups in any category of outcome. For patients with penetrating intestinal or colonic injury, a 12-hour course of antibiotics is as effective as a five-day course and has the advantage of lower cost and, theoretically, fewer side effects.

Adult↗

Enteral versus parenteral nutritional support following laparotomy for trauma: a randomized prospective trial.

Although enteral nutrition is considered more 'physiologic' than parenteral nutrition, there is greater published experience with parenteral nutrition in trauma patients. To compare the efficacy of these two techniques, we prospectively randomized multiple trauma patients during their admission laparotomy to receive either central venous parenteral nutritional (TPN: n = 23) or enteral nutrition by jejunostomy (Jej: n = 23). Nutritional support began on the first postoperative day; the study period continued a maximum of 14 days. There were no significant differences between the two groups in age, sex, injury severity, estimated caloric needs (3,322 TPN; 3,114 Jej), hours to achieve full prescription (77 PTN; 79 Jej), or the number of days on nutritional support (22 TPN; 25 Jej). Average daily caloric intakes, nitrogen balance results, and complication rates were also comparable. These results suggest that early postoperative jejunostomy feeding is a safe and efficacious choice for multiple trauma patients undergoing laparotomy.

Adult↗

Surgical infection stratification system for intra-abdominal infection. Multicenter trial.

One hundred eighty-seven patients treated for established intra-abdominal infection in five medical centers were studied using the surgical infection stratification system. This system combines an anatomic category with a numerical estimate (acute physiology score [APS]) of deviation from normal of 33 routine laboratory tests or physical findings. Overall mortality was 24% and the rate of treatment "success" with a single operation and single course of antibiotics was 48%. Eighty percent of deaths occurred with infection present. Multivariate analysis disclosed that APS, malnutrition, and age were most noteworthy for predicting survival or death. Intra-abdominal infection carries substantial mortality and morbidity despite advances in understanding the underlying pathophysiologic condition. Additional clinical studies are needed. Uniform reporting criteria, including the use of an objective severity scoring system, are suggested for future reports concerning intra-abdominal infection.

Abdomen↗

Stratified outcome comparison of clindamycin-gentamicin vs chloramphenicol-gentamicin for treatment of intra-abdominal sepsis.

A randomized, prospective trial was conducted of 93 patients with operatively confirmed intra-abdominal sepsis. The study compared clindamycin-gentamicin and chloramphenicol-gentamicin for treatment of carefully stratified patient groups. Malnutrition, age over 65 years, shock, alcoholism, gastrointestinal tract bleeding, steroid administration, diabetes, obesity, and organ malfunction were present with equal frequencies in each group. The duration of antibiotic treatment averaged 8 1/2 days, and the average length of postoperative hospitalization was 29 days. Study antibiotics were changed for bacteriologic reasons in 11 patients taking clindamycin-gentamicin and 12 patients taking chloramphenicol-gentamicin (25% of the total), and two patients in the clindamycin-gentamicin group had a minor adverse reaction. Initial satisfactory clinical responses were obtained in 59 (63%) patients. Twenty-five patients (27%) subsequently developed unsatisfactory courses, but 48 (52%) patients remained well through the 30-day period. Septic-related mortality occurred in 18 (19%) patients, and two (2%) patients had unrelated deaths. There were no significant differences between the study regimens by the outcome criteria evaluated.

Abdomen↗

Cimetidine clearance in the obese.

Six subjects with normal weight (mean weight = 62 kg) and six obese subjects (mean weight = 140 kg) were given a single intravenous cimetidine infusion of 600 mg over 10 to 15 minutes. Both groups of subjects had normal serum creatinine levels and were matched with respect to age, desirable body weight, height, renal function, and sex. Compared with subjects of normal weight, obese subjects had higher cimetidine systemic (1147 and 637 ml/min) and renal (808 and 318 ml/min) clearances. Volume of distribution at steady state was of the same order for the two groups (82 and 84 L), but the t 1/2 was shorter in the obese group (1.2 and 1.9 hr). Obese subjects had lower cimetidine sulfoxide serum concentrations and greater cimetidine sulfoxide renal clearance (856 and 509 ml/min). Cimetidine systemic clearance and cimetidine sulfoxide renal clearance values were of the same order in the two groups when normalized by the value of weight raised to the 0.76 and 0.5 powers. Under the assumptions of an average weight of 70 kg and that average serum concentrations produced by cimetidine, 300 mg iv every 6 hours, are appropriate, people with normal renal function and body weight usually receive 48 mg/day/weight0.76. This same dosage in obese individuals with normal serum creatinine values should result in the same average steady-state serum concentrations. In our obese subjects, the mean cimetidine dose would have been approximately 500 mg iv every 6 hours.

Adult↗

Risk of infection following laparotomy for penetrating abdominal injury.

We analyzed the occurrence of putative risk factors for postoperative infection in 338 patients who underwent emergency laparotomy for penetrating abdominal injury. Mortality was 3%, with nine of ten deaths directly related to infectious complications. Gunshot wounds and colon injuries occurred more frequently in the patients who died than in survivors. Stepwise discriminant analysis revealed that transfusion requirement, length of operation, age, and the penetrating abdominal trauma index were the most significant risk factors for any infection. Other risk factors examined (shock, number of organs injured, mode of injury, and chest injury) did not contribute any additional information. Colon injury was more prevalent in patients with trauma-related infections than in those with nosocomial infections.

Abdominal Injuries↗

A proposed classification of intra-abdominal infections. Stratification of etiology and risk for future therapeutic trials.

Serious studies of ultra-abdominal infections have yielded a mortality that ranges from 3.5% (a composite of antibiotic studies evaluating 1,275 patients) to more than 60% in studies of multiple-organ failure. In reviewing these studies, it is apparent that under the umbrella of "serious intra-abdominal infection," different diseases, processes, and patients are being studied. We define a binomial classification incorporating both an anatomic and a functional approach to intra-abdominal infection. There are ten etiologic classifications of intra-abdominal infections combined with an acute physiologic score (APS), measuring severity of illness, in three gradations. In the patient with undifferentiated intra-abdominal sepsis, the patient will be in class I, II, III, or IV, with a score, A, B, or C, added. Each of the groups V-X, defining a specific infectious category, can also use the APS, which has been verified in patients in intensive care and in those with intra-abdominal infection. It is anticipated that using this approach will provide a technique to evaluate patient groups uniformly in which drug or technical approaches to the management of intra-abdominal infections are being studied. The patients being studied will be more clearly defined, and studies will be comparable from one center to another.

Bacterial Infections↗

Antibiotic trials in intra-abdominal infections. A critical evaluation of study design and outcome reporting.

The introduction of several new antibiotics, including cephalosporins and ureido-penicillins, has been a stimulus for clinical trials with these agents for intra-abdominal infection. Despite marked differences in antibacterial spectra, substantial differences in treatment results have not been documented. We reviewed published trials of antibiotic therapy for intra-abdominal infection to determine factors in study design that might impair identification of clinically important differences between regimens. Sixteen articles were identified that provided sufficient numbers of cases and data for analysis. Eight were prospective comparative trials, the remainder "single-armed" studies. The mortality rate was 3.5%, and the overall success rate was 84% for aminoglycoside plus clindamycin (range 52%-96%), 89% (range 83%-93%) for aminoglycoside plus metronidazole, and 93% (range 61%-95%) for cephalosporin-based regimens. Several defects in study design were identified. (1) Exclusionary criteria employed generally prevented enrollment of seriously ill patients or infections associated with high failure rates: Patients were excluded if even mild renal impairment was present or if antibiotic therapy had been recently administered, thereby excluding patients with postoperative or recurrent infections. Several studies allowed entry of contaminated but not infected patients. (2) Criteria used for reporting infectious diagnosis, premorbid health status, severity of infection, and outcome were nonuniform, and few studies provided such information. (3) Despite the small number of treatment failures, data reported did not allow determination of the basis for failure. For example, only four studies provided information on the operations performed upon treatment failures. Whether treatment failures were due to inadequate antibiotic therapy could therefore not be determined. Enrollment of a variety of low mortality infections precluded demonstration of any differences in regimens. Use of stratified randomization, stratifying for site of infection and severity of infection, and inclusion of greater numbers of patients would increase the likelihood of identifying differences between regimens. Such study design would likely require a multicenter trial to enroll sufficient numbers of cases for statistical analysis.

Abdomen↗

Determinants of organ malfunction or death in patients with intra-abdominal sepsis. A discriminant analysis.

One hundred and six patients found at operation to have intra-abdominal sepsis were prospectively followed up to determine the incidence of organ malfunction and death. These outcomes were correlated with age, preexisting disease, underlying cause of sepsis, shock, nutritional status, and alcoholism. Organ malfunction occurred in 31 patients (29%), 19 (61%) of whom died. Two (3%) of 75 patients without organ malfunction died. Discriminant analysis revealed a significantly increased risk of death in patients with shock at any time, age greater than 65 years, alcoholism, bowel infarction, or malnutrition. A discriminant equation based only on preoperative variables correctly assigned the outcome of death or survival in 97 (92%) of the patients based on probabilities derived from this analysis. At present, this information is primarily of interest for researchers comparing outcomes in groups of patients, but with additional refinements it may become clinically useful for individual patients.

Abdomen↗