Antimicrobial culture and susceptibility testing has little value for routine management of secondary bacterial peritonitis.

The traditional surgical practice of routinely culturing specimens from patients with community-acquired intraabdominal infections, such as appendicitis, contributes little to the management of the individual patient, either initially or later when infectious complications have developed. Instead of performing routine cultures for peritonitis, a modified approach that still facilitates hospital surveillance for microbial resistance patterns should be used.

Ticarcillin/clavulanate compared with clindamycin/gentamicin (with or without ampicillin) for the treatment of intra-abdominal infections in pediatric and adult patients.

Combinations of penicillins with beta-lactamase inhibitors have become acceptable treatments for mixed bacterial infections. The objective of this multicenter, randomized, open-label study was to compare the efficacy, safety, and tolerance of ticarcillin/clavulanate with clindamycin/gentamicin (with or without ampicillin) when administered to adult and pediatric patients with intra-abdominal infections. A total of 993 patients 2 years of age or older were entered in this trial if they had suspected or bacteriologically documented intra-abdominal infection. Of these, 341 were determined at the time of operation to have intra-abdominal infection. Cure rates at the time of final assessment were 79%, 80%, and 82% for ticarcillin/clavulanate, and clindamycin/gentamicin without or with ampicillin, respectively (P = 0.829, Cochran-Mantel-Haenszel). The most frequent reason for failure was development of an intra-abdominal abscess (6% of patients overall), followed by wound infections (4%), and persistent fever (3%). Two patients who had received ticarcillin/clavulanate and five who had received clindamycin/gentamicin required discontinuation of the study regimen because of adverse drug reactions. The bacteria isolated most frequently from study failures were E. coli, B. fragilis, Pseudomonas, and Streptococci. In this study, ticarcillin/clavulanate was as effective as the combination of clindamycin/gentamicin for the treatment of intra-abdominal infections.

Assessment of hepatitis B virus immunization status among North American surgeons.

OBJECTIVE: We hypothesized that many surgeons have not been vaccinated against hepatitis B virus (HBV), despite the existence of effective recombinant vaccines. Prevalence of HBV vaccination among surgeons, attitudes of those not vaccinated, estimated HBV infection rates, and respondents' knowledge of the epidemiology of HBV exposure were determined. DESIGN: Survey conducted by mail just before implementation of mandatory HBV vaccination for health care workers. SETTING: Private and academic general surgical, trauma and transplantation practices. PARTICIPANTS: Two thousand one hundred twenty-five surgeons received the survey. Response rates are as follows: in the Surgical Infection Society, 196 (50%) of 393 surgeons; in the American Association for the Surgery of Trauma, 223 (52%) of 433 surgeons; in the American Society of Transplant Surgeons, 194 (44%) of 438 surgeons; and among the Fellows of the American College of Surgeons, 403 (47%) of 861 surgeons. MAIN OUTCOME MEASURES: Prevalence of HBV exposure and active immunization by specialty and society. RESULTS: Prevalence of HBV exposure was 19.6%, was higher among trauma and transplantation surgeons compared with general surgeons (P < .0001), and increased significantly with age in all groups (P < .05). Despite greater exposure, probable immunity was lower at an older age because young surgeons (age, < 46 years) are more likely to be vaccines (P < .05). Most surgeons (55%) were vaccinated more than 5 years ago; many recipients of recombinant vaccines (26%) received an inadequate amount of vaccine or were improperly vaccinated. Knowledge of the epidemiology was uniformly poor, with rates of correct responses to the three questions below 50%. CONCLUSIONS: Vaccination does not equal immunity. Between 38% and 50% of practicing surgeons may not have adequate immunity to HBV.

Single dose cephalosporin prophylaxis in high-risk patients undergoing surgical treatment of the biliary tract.

During June 1985 through October 1986, 292 patients considered to be at high risk for having postoperative complications develop underwent cholecystectomy and were evaluated in a multicenter, randomized, prospective, double-blind study. Risk factors included age greater than 70 years, acute cholecystitis within the previous six months, obstructive jaundice, obesity and diabetes mellitus. One gram of cefamandole was administered intravenously to 144 patients and 148 patients received 1 gram of cefotaxime intravenously 30 minutes prior to skin incision. Culture-proved bactibilia was found in 55 patients and 11 of the patients had choledocholithiasis. Of the risk factors considered to place patients at high risk for postoperative infectious complications, obesity and acute cholecystitis proved to be the more common. However, age greater than 70 years, diabetes mellitus and obstructive jaundice were more significant risk factors predisposing to bactibilia. The most common organisms isolated from the bile and gallbladder intraoperatively were Staphylococcus, Streptococcus and Klebsiella species along with enterococcus, Escherichia coli and diphtheroids. Clinically significant postoperative infections occurred in eight patients, including six patients in the cefamandole group and two patients in the cefotaxime group. Antibiotic concentrations were measured in the serum, muscle, subcutaneous fat, gallbladder and bile, with cefamandole showing statistically significant greater concentrations in bile, gallbladder and muscle tissue. There was no statistical significance between the postoperative infection rates, total period of hospitalization or total hospital charges for each group. Therefore, there is no significant advantage between a single prophylactic dose of cefamandole versus cefotaxime for high-risk patients undergoing biliary tract operation.

Outpatient open cholecystectomy.

A prospective study to evaluate discharge of patients from the hospital the day of open cholecystectomy was performed. Patients were selected for outpatient operation if they were less than 55 years of age, did not undergo exploration of the common bile duct and had no significant co-morbidity. During a six month period, 94 consecutive patients underwent cholecystectomy. Forty-four of 64 eligible patients were discharged the day of operation. Patients were walking and receiving oral liquids soon after operation. Marcaine (bupivacaine hydrochloride) was injected subfascially in all patients and vertical incisions were used in 34 of 44. One patient required readmission for 12 hours, three days after operation. The satisfaction rate was high and the patients returned to their usual activity in seven to 21 days. Outpatient open cholecystectomy is safe, and appropriate therapy and the data established a standard with which to compare that of laparoscopic cholecystectomy.

Twenty-four hour hospitalization after cholecystectomy.

To evaluate the likelihood that patients can be discharged from the hospital the day after open cholecystectomy, a prospective study of 500 consecutive patients undergoing cholecystectomy was undertaken. The study group included patients with associated acute and gangrenous cholecystitis, biliary pancreatitis and choledocholithiasis as well as those with diabetes, hypertension and obesity. Approximately one-fourth of the total group were discharged within 24 hours and over one-half in 48 hours. There was a significant correlation between advancing age and increasing length of stay. Almost one-half of the patients less than 35 years of age without acute or complicated disease were discharged within 24 hours, more than 80 per cent within 48 hours, and the mean length of postoperative stay (MLS) for these patients was 1.9 days. The presence of choledocholithiasis and fever greater than 101 degrees F. increased MLS, while acute cholecystitis, hyperamylasemia and leukocytosis did not. Early discharge from the hospital after open cholecystectomy, even in sick patients, is safe and cost-effective.

Perforated or gangrenous appendicitis treated with aminoglycosides. How do bacterial cultures influence management?

To study the influence of bacterial culture data on the clinical management of gangrenous or perforated appendicitis, we reviewed records of 104 patients who had been treated empirically with aminoglycoside antibiotics. Culture results appeared to influence antibiotic therapy in only 7 patients (7%). The routine cultures obtained at appendectomy affected therapy in only 2 patients. Discriminant analysis identified postoperative infectious complications and related factors as the principal determinants of culture utility. We conclude that, in patients with perforated appendicitis treated empirically with aminoglycoside combination regimens, culture results were seldom used for clinical management except in instances of postoperative infectious complication. Routine cultures and Gram's stains of perforated appendicitis, however, should still be obtained (1) to allow epidemiologic tracking in the hospital; (2) to identify organisms that are recovered infrequently but may cause serious disease (eg, Clostridium); and (3) because newer antibiotics are replacing aminoglycosides in the treatment of perforated appendicitis.

Individualized pharmacokinetic versus standard dosing of amikacin: a comparison of therapeutic outcomes.

We compared the therapeutic outcome in patients with normal renal function managed with either individualized pharmacokinetic (PK) dosing or standard (every 12 h) dosing of amikacin. A total of 82 patients with confirmed or suspected infectious processes were entered into the study. There was no difference in therapeutic outcomes (P = 0.47) with one patient from each group dying. The duration of hospital stay (15.8 days vs 11.3 days, P = 0.052) and the mean duration of therapy (8.9 days vs 7.4 days, P = 0.20) were not significantly different, although a trend was seen towards longer time periods in the PK group. The incidence of nephrotoxicity (3 vs 1, P = 0.61), and calculated PK parameters were not different between the PK and standard groups, respectively. Upon evaluation of amikacin serum concentrations in individual patients, we found that five of 82 patients (6.1%) were or might have been at risk for toxicity with standard, unmonitored doses of amikacin, when compared to published literature. Although equivalent therapeutic outcomes may be achieved with standard or individualized PK dosing, the risk of toxicity with standard dosing is substantial. The routine use of standard dosing regimens cannot be recommended. Definition of specific patients subtypes in whom standard regimens utilizing lower doses can safely and effectively be used is necessary.

Endogenous factors contributing to prosthetic device infections.

Although there is a direct association between the tissue reactivity of implants and their ability to potentiate infection, bacterial slime production and adherence to implant surfaces (generation of the biofilm) appear to play a primary role in the pathogenesis of most prosthesis infections.

Pathobiology of infection in prosthetic devices.

Because of the growing use of implants, infections in prosthetic devices are probably becoming commoner, even though the risk of infection remains low. Multiple factors appear to be involved in the development of these infections, including foreign body-associated tissue damage, impairment of host defenses, bacterial trapping by fibrin, sequestration of bacteria in implant interstices, and the generation of a biofilm on implant surfaces. Although there is a direct association between the tissue reactivity of implants and their ability to potentiate infection, bacterial slime production and adherence to implant surfaces (generation of the biofilm) appear to play a primary role in the pathogenesis of device infections, contemporary prosthetic devices generally being quite nonreactive with respect to host tissues. While virtually any organism can cause these infections, gram-positive bacteria, especially staphylococci, predominate. Infections due to gram-negative organisms and fungi, however, tend to be more serious, often requiring prompt removal of the implant.

Cefamandole versus cefoxitin prophylaxis in patients undergoing cholecystectomy.

A prospective, randomized, double-blind study of three different antibiotic prophylaxis regimens in 150 patients undergoing cholecystectomy was conducted. Group I patients received a 1-gram preoperative dose of cefamandole followed by 4 additional postoperative doses at 6-hour intervals. Group II received a similar regimen except that 2-gram doses of cefamandole were used. Group III received a comparable cefoxitin regimen in 2-gram doses. The patients were deemed to be at high risk for postoperative infection by virtue of the fact that most (almost 70%) were obese and all had had a recent attack of cholecystitis. There were no significant differences among the 3 groups with respect to postoperative infectious complications. It is concluded that perioperative cefamandole and cefoxitin are both effective in reducing the postoperative infectious complications of cholecystectomy. A 5-gram course of cefamandole is as effective as either a 10-gram course of cefamandole or a 10-gram course of cefoxitin and could provide a substantial savings in cost.

Rapid resolution of high level hyperamylasemia as a guide to clinical diagnosis and timing of surgical treatment in patients with gallstones.

We reviewed the charts of 78 patients with acute hyperamylasemia (25 with gallstones, 38 alcoholic patients and 15 other), looking for early patterns of serum amylase flux that could distinguish gallstone associated disease. Patients with gallstones had average serum amylase levels of 1,848 +/- 289 International units per liter and 911 +/- 233 International units per liter at hospital admission and on hospital day 2, respectively; these levels were significantly greater than those in either the alcoholic or other patients. In the group of patients with gallstones, there were also dramatic decreases in serum levels of amylase at 24 hours (1,425 +/- 286 International units) after hospital admission; these decreases were not seen in the other groups of patients. At operation, the patients with gallstones had mild or no pancreatitis. All of them underwent uneventful cholecystectomy within 48 hours of hospitalization; only three patients required exploration of the common duct, and only one patient had ampullary obstruction. We conclude that rapid resolution of high level hyperamylasemia within 24 hours of hospitalization in symptomatic patients with gallstones can help to identify patients whose amylase fluctuations are indeed gallstone related, who have either mild pancreatitis or none at all, are good candidates for early cholecystectomy and are not likely to have common duct stones.

Impact of LY146032 on Streptococcus (Enterococcus) faecalis translocation in mice.

The susceptibility of Swiss White mice to colonization with Streptococcus (Enterococcus) faecalis was greatly increased when the animals were given 5 mg of streptomycin sulfate per ml in their drinking water. One week after initiation of streptomycin treatment, the mice were challenged orogastrically with graded doses of streptomycin-resistant S. faecalis. The number of S. faecalis cells required to implant the intestinal tract of 50% of untreated mice was 2.9 X 10(9), but was only 4.8 X 10(3) for streptomycin-treated animals. When both groups of mice were challenged orogastrically with 4.6 X 10(6) viable S. faecalis cells, the cecum and small intestine of 100% of the streptomycin-treated animals, but only 10% of the untreated animals, were colonized with the organism. Similarly, translocation of S. faecalis to extraintestinal sites occurred in a majority of streptomycin-treated mice, but in only a small number of untreated mice. Subcutaneous administration of the experimental antibiotic LY146032 (Eli Lilly & Co., Indianapolis, Ind.) to streptomycin-treated mice concomitant with orogastric challenge with 5.5 X 10(5) viable S. faecalis cells resulted in a significant decrease in the incidence of intestinal colonization by the organism, a significant reduction in S. faecalis populations, and the absence of the organism in the liver, spleen, and heart. However, once intestinal colonization had occurred and extraintestinal infections were established, LY146032 did not significantly reduce S. faecalis populations or ameliorate the infections. We conclude that LY146032 effectively prevents translocation of S. faecalis from the intestinal tract of mice but does not resolve established extraintestinal infections.

Effects of soil infection potentiating factors on neutrophils in vitro.

Although the ability of soil silicate fractions to potentiate infection is well recognized, the precise mechanisms by which they do so remain unexplained. This study was carried out to investigate the effects of montmorillonite clay, the most potent of these soil infection potentiators, on human neutrophils, erythrocytes, and serum complement in vitro. Using phase microscopy, rapid neutrophil lysis was observed when cells were exposed to untreated clay. After lysis, the cytoplasmic marker enzyme lactate dehydrogenase rapidly adsorbed to the surface of the clay. Both enzyme surface adsorption and cell lysis could be blocked, however, by pretreatment of the clay with human albumin. Likewise, neutrophil chemiluminescence could be stimulated by untreated clay, but not by clay pretreated with 5 percent albumin or 10 percent pooled human serum. Maximal chemiluminescence was stimulated by clay pretreated with 0.1 percent albumin, probably because the partially protective albumin coating delayed cell lysis. Compared with the effect on neutrophils, clay lysis of erythrocytes was incomplete. When zymosan-activated serum samples were exposed to clay, complement activity as measured by neutrophil chemotaxis was suppressed in a dose-dependent fashion. We conclude that montmorillonite clay may potentiate infection by a direct cytotoxic effect on the neutrophil, making it unavailable for bacterial phagocytosis, by local reduction in bacterial opsonization due to depletion of activated complement, and by the release of toxic tissue substances, such as lysosomal enzymes and oxygen free radicals, from leukocytes which may damage host tissue and thus create an environment favorable for bacterial survival.

Role of amikacin in the management of intra-abdominal sepsis.

Controversy has developed regarding the antibiotic management of intra-abdominal sepsis because of the recent availability of the third-generation cephalosporins and ureidopenicillins as alternatives to traditional combination therapy (aminoglycosides plus clindamycin). Most observers now acknowledge the need to provide anti-anaerobic as well as anti-aerobic gram-negative drug coverage. Although most of the newer agents do provide such broad-spectrum coverage, doubt remains regarding their efficacy because of flaws in comparative study design and the observation that resistance to the newer agents, which may even extend to the aminoglycosides, can emerge in individual patients during single courses of antibiotic therapy. Indeed, such resistance is most likely to occur during the treatment of seriously ill, immunodepressed patients who have undergone multiple reoperation for persistent or recurrent intra-abdominal sepsis--the precise group for which the new drugs were most desired as less toxic alternatives to the aminoglycosides. On the basis of such observations, combination therapy with the aminoglycosides, appears to remain the most logical choice. In the setting of nosocomial sepsis and pathogen resistance to other aminoglycosides, amikacin may be especially effective. Recent surveillance data indicate that the use of amikacin under such circumstances not only may provide effective antibiotic therapy, but also may actually reduce the level of microbial resistance to the other aminoglycosides. Past concern regarding the development of resistance to amikacin has probably been excessive and should not deter the use of this agent under appropriate clinical circumstances.