Incidence of Early and Late-Onset Clostridioides difficile Infection following Appendectomy Compared to Other Common Abdominal Surgical Procedures.

Introduction: Clostridioides difficile associated diarrhea (CDAD) is a major public health issue. The appendix may function as a reservoir for the intestinal microbiome, which may repopulate the intestine following enteric infections including CDAD. Patients/Methods. This retrospective cohort study includes a total of 12,039 patients undergoing appendectomy, hemicolectomy, and cholecystectomy at a single center between 1992 and 2011 who were diagnosed with early and late-onset CDAD and were followed for a minimum of two years. Results: Cumulative CDAD rates were 2.3% after appendectomy, 6.4% after left and 6.8% after right hemicolectomy, and 4% after cholecystectomy with a median onset of 76 (range 1-6011) days after the procedure. Median time to CDAD onset was 76 days after appendectomy, 23 days after left, 54 days after right hemicolectomy, and 122 days after cholecystectomy (p < 0.05). Late-onset CDAD (>1 year) was significantly more common following appendectomy (37%) and cholecystectomy (39%) than after left (17%) and right (21%) hemicolectomy. Significant differences in age, gender, complication rate, and length of hospitalization between the four groups need to be considered when interpreting the results. Conclusion: The incidence of CDAD after various abdominal surgeries ranged between 2% and 7% in this study. Whereas, hemicolectomy patients had predominantly early onset CDAD, and appendectomy and cholecystectomy may increase the risk for late-onset CDAD. Appendectomy per se does not seem to increase the risk for late-onset CDAD.

Erratum to: Antimicrobials: a global alliance for optimizing their rational use in intra-abdominal infections (AGORA).

[This corrects the article DOI: 10.1186/s13017-016-0089-y.].

Laparoscopic gastric banding in a kidney-pancreas transplant recipient with new onset type II diabetes mellitus associated with morbid obesity.

Combined kidney-pancreas transplantation is the treatment of choice for end-stage diabetic nephropathy. Post-transplant weight gain increases the risk for post-transplant complications and death owing to cardiovascular events. Gastric banding is an established treatment for moderate morbid obesity. We report on a patient who experienced significant weight gain and developed type II diabetes mellitus following successful kidney-pancreas transplantation. He underwent laparoscopic gastric banding and initially had good weight loss. However, lack of compliance with dietary guidelines led to transient failure of weight loss therapy. With further adjustment of the gastric band good weight loss was achieved.

Morning report: combining education with patient handover.

INTRODUCTION: The advent of resident work hour restrictions has challenged us to train residents within a shorter working week, while ensuring continuity of patient care. We instituted morning report (MR) at the University of Virginia primarily as a means to accomplish these objectives. Serendipitously MR has become an integral educational tool for the surgical residents. The rationale for the format and instructional design are discussed in the context of learning theory. METHODS: The chief residents as primary stakeholders were strongly encouraged to play a leadership role in designing MR. A faculty- led didactic format was rejected because of the importance of focusing on resident team building, and leadership, but poor faculty participation was also an issue. RESULTS: The initial obstacles included timing, and designing the format. CONCLUSIONS: MR is an opportunity for residents to exercise and improve their knowledge, leadership, presentation and problem-solving skills. We would hypothesise that the advantages for teaching are many and include that residents are prepared for actual clinical problems in a supportive environment with opportunities for immediate feedback and assessment. Reports of educational effectiveness of MR are mostly anecdotal and further studies are needed to characterise the types of learning and teaching that occur during MR and to document educational effectiveness.

A nutrition support team led by general surgeons decreases inappropriate use of total parenteral nutrition on a surgical service.

The purpose of this study was to decrease the number of inappropriate orders for total parenteral nutrition (TPN) in surgical patients. From February 1999 through November 2000 and between July 2001 and June 2002, the surgeon-guided adult nutrition support team (NST) at a university hospital monitored new TPN orders for appropriateness and specific indication. In April 1999, the NST was given authority to discontinue inappropriate TPN orders. Indications, based on the American Society for Parenteral and Enteral Nutrition (ASPEN) standards, included short gut, severe pancreatitis, severe malnutrition/catabolism with inability to enterally feed > or =5 days, inability to enterally feed >50 per cent of nutritional needs > or =9 days, enterocutaneous fistula, intra-abdominal leak, bowel obstruction, chylothorax, ischemic bowel, hemodynamic instability, massive gastrointestinal bleed, and lack of abdominal wall integrity. The number of inappropriate TPN orders declined from 62/194 (32.0%) in the first 11 months of the study to 22/168 (13.1%) in the second 11 months (P < 0.0001). This number further declined to 17/215 (7.9%) in the final 12 months of data collection, but compared to the second 11 months, this decrease was not statistically significant (P = 0.1347). The involvement of a surgical NST was associated with a reduction in inappropriate TPN orders without a change in overall use.

The "July phenomenon" and the care of the severely injured patient: fact or fiction?

BACKGROUND: The "July phenomenon," a common belief in medical academia, refers to purported errors, inefficiency, and negative outcomes during the summertime transition of the house staff. We hypothesized that care in a trauma service is consistent throughout the year and that the July phenomenon therefore is a myth. METHODS: The records of adults admitted to a trauma service between July 1994 and September 1999 were evaluated. The care of and outcomes for patients admitted in July and August were compared with those of patients admitted in April and May. RESULTS: Nine hundred seventeen patients were evaluated over 5 years. Patients were well matched by the Injury Severity Score, the Glasgow Coma Score, by mechanism, and by survival probability. Patients admitted in the spring were significantly older, by a mean of 5.1 years. Length of stay and intensive care unit stay were similar. Emergency department times were similar, as were resuscitation times, infection rates, and hospital costs. The mortality of patients was similar between the 2 times. CONCLUSIONS: There was no evidence of an increase in negative outcomes early in the academic year compared with the end of the academic year. We believe that a systematic approach to the diagnosis, resuscitation, and treatment of trauma prevented a July phenomenon.

Impact of a rotating empiric antibiotic schedule on infectious mortality in an intensive care unit.

OBJECTIVE: The development of antibiotic-resistant bacteria is associated with significant morbidity and mortality in critically ill patients. We postulated that quarterly rotation of empirical antibiotics could decrease infectious complications from resistant organisms in an intensive care unit (ICU). DESIGN: Prospective cohort study. SETTING: An ICU at a university medical center. SUBJECTS: All patients admitted to the general, transplant, or trauma surgery services who developed pneumonia, peritonitis, or sepsis of unknown origin. INTERVENTIONS: A 2-yr study consisting of 1 yr of nonprotocol-driven antibiotic use and 1 yr of rotating empirical antibiotic assignment. MEASUREMENTS AND MAIN RESULTS: Over 100 variables were recorded for each infectious episode, including patient characteristics (e.g., Acute Physiology and Chronic Health Evaluation [APACHE] II score, age, comorbidities), infection characteristics (e.g., site, organism), treatment characteristics (e.g., antibiotic, treatment duration) and outcome measures (e.g., mortality, length of stay, antibiotic cost). Of 1456 consecutive admissions to the ICU, 540 episodes of infection were treated. No differences were noted in age, APACHE II score, race, overall antibiotic utilization or duration of therapy between the 2 yrs of study. Outcome analysis revealed significant reductions in the incidence of antibiotic-resistant Gram-positive coccal infections (7.8 infections/100 admissions vs. 14.6 infections/100 admissions, p <.0001), antibiotic-resistant Gram-negative bacillary infections (2.5 infections/100 admissions vs. 7.7 infections/100 admissions, p <.0001), and mortality associated with infection (2.9 deaths/100 admissions vs. 9.6 deaths/100 admissions, p <.0001) during rotation. Logistic regression identified age (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01-1.06), APACHE II score (OR, 1.06; 95% CI, 1.01-1.13), solid organ transplantation (OR, 9.50; 95% CI, 2.01-52.21), and malignancy (OR, 10.16; 95% CI, 4.11-26.96) as independent predictors of mortality. Antibiotic rotation was an independent predictor of survival (OR 6.27, 95% CI 2.78-14.16). CONCLUSION: Rotation of empirical antibiotic therapy seems to be a promising method to reduce infectious mortality in an ICU.

Uni- and multi-variate analysis of risk factors for early and late hepatic artery thrombosis after liver transplantation.

BACKGROUND: Hepatic artery thrombosis (HAT) is a significant cause of morbidity after liver transplantation. The aims of this study are to identify and compare risk factors that might contribute to HAT. METHODS: A total of 424 liver transplants performed at the University of Virginia were reviewed. HAT was defined as complete disruption of arterial blood flow to the allograft and was identified in 29 cases (6.8%). HAT was classified as early (less than 1 month posttransplant, 9 cases: 2.1%) or late (more than 1 month posttransplant, 20 cases: 5.4%). Possible risk factors for HAT were analyzed using Pearson chi2 test for univariate analysis and logistic regression for multivariate analysis. RESULTS: Multiple transplants, recipient/donor weight ratio >1.25, biopsy-proven rejection within 1 week of transplant, recipient negative cytomegalovirus (CMV) status, arterial anastomosis to an old conduit (defined as a previously constructed aorto-hepatic artery remnant using donor iliac artery), and CMV negative patients receiving allograft from CMV positive donors were found to be significant risk factors for developing early HAT. After logistic regression, factors independently predicting early HAT included arterial anastomosis to an old conduit [odds ratio (OR)=7.33], recipient/donor weight ratio >1.25 (OR=5.65), biopsy-proven rejection within 1 week posttransplant (OR=2.81), and donor positive and recipient negative CMV status (OR=2.66). Female donor, the combination of female donor and male recipient, recipient hepatitis C-related liver disease, donor negative CMV status, and the combination of recipient CMV negative and donor CMV negative were found to be significant risk factors for late HAT. Factors independently predicting late HAT by logistic regression included negative recipient and donor CMV status (OR=2.26) and the combination of a female donor and male recipient (OR=1.97). CONCLUSION: Therefore, in nonemergency situations attention to these factors in donor allocation may minimize the possibility of HAT.

Cohort study of fever and leukocytosis as diagnostic and prognostic indicators in infected surgical patients.

The presence of fever and leukocytosis have traditionally been utilized as important diagnostic markers of infection despite some who question their reliability. To examine this point, the role of fever and leukocytosis as diagnostic and prognostic indicators for surgical infections was evaluated. A prospective observational study was performed on all patients with suspected infection in 1997 on the general surgical services at a university hospital. Fever was defined as maximum temperature (Tmax) > or = 38.5 degrees C, and leukocytosis was defined as a white blood cell (WBC) count > or = 11,000/microl. Among all infections, patients presenting with a Tmax > or = 38.5 degrees C were younger (51.3 +/- 1.1 vs. 53.8 +/- 0.9 years, p = 0.005) and had a higher APACHE II score (15.1 +/- 0.5 vs. 11.4 +/- 0.4; p < 0.001). By logistic regression analysis chronic renal insufficiency was associated with a Tmax < 38.5 degrees C [odds ratio (OR) 0.371, 95% confidence interval (CI) 0.195-0.704], and chronic steroid therapy was associated with a WBC count < 11,000/microl (OR 0.556, 95% CI 0.335-0.921). In addition, infected transplant patients were more likely to present with a Tmax < 38.5 degrees C and a WBC count < 11,000/microl (OR 0.195, 95% CI 0.075-0.502). Mortality rates for infected patients with a Tmax < 38.5 degrees C or > 38.5 degrees C were 11.6% and 12.9%, respectively (p < 0.7), and the lengths of stay were 14 +/- 1 and 18 +/- 1 days, respectively (p < 0.03). Mortality rates for patients with a WBC count < 11,000/microl or > 11,000/microl were 4.7% and 18.6%, respectively (p < 0.001), and the lengths of stay were 14 +/- 1 and 19 +/- 1 days, respectively (p < 0.001). In the setting of infection, chronic renal insufficiency and chronic steroid therapy are associated with suppression of fever and leukocytosis, respectively. Transplantation is an independent predictor of infection in patients presenting without fever or leukocytosis. Leukocytosis, but not fever, may be predictive of hospital mortality in infected surgical patients.

Implications of 2,457 consecutive surgical infections entering year 2000.

OBJECTIVE: To assess the demographics and characteristics of infections in surgical patients to define areas that deserve emphasis in surgical education. SUMMARY BACKGROUND DATA: As a result of evolving technology and diseases, the complexity of diagnosing and treating infections has increased during the past three decades for all patients, including those treated primarily by surgeons. No comprehensive analysis of these conditions in a single surgical cohort has been recently published. METHODS: The authors conducted a prospective, observational study of all infections occurring on the general and trauma surgery services at a single university hospital during a 3.5-year period. RESULTS: The authors identified 2,457 infections: 608 community-acquired, 1,053 occurring on the wards, and 796 occurring in the intensive care unit. Although dependent on patient location, the most common sites were abdomen, lung, and wound; the most common isolates were Staphylococcus epidermidis, Staphylococcus aureus, and Candida albicans; and the most commonly used antibiotics were ciprofloxacin, vancomycin, and metronidazole. The overall death rate was 13%, ranging from 5% after community-acquired infections to 25% after infections acquired in the intensive care unit. CONCLUSIONS: Most infections treated by surgeons are hospital-acquired. Infections with gram-positive cocci and fungi are common, with pulmonary infections becoming more common. Fluoroquinolones have become important therapeutic agents. Depending on the type of practice, these data should be helpful to direct educational efforts so that surgeons can remain knowledgeable and active in the nonsurgical care of their patients.

Impact of bloodstream infection on outcomes among infected surgical inpatients.

OBJECTIVE: To assess the importance of bloodstream infection (BSI) to outcomes among infected surgical patients. BACKGROUND: Bloodstream infection complicating infection is thought to connote a more serious condition compared with a primary infection alone. The authors recently reported, however, that BSI does not alter outcomes with central venous catheter colonization in the presence of sepsis. The significance of BSI with other infections has been incompletely evaluated. METHODS: Data on all episodes of infection among surgical patients were collected prospectively during a 38-month period at a single hospital, then analyzed retrospectively to determine the independent prognostic value of BSI for all infections by logistic regression analysis, and for abdominal infections and pneumonia using matched control groups. RESULTS: During the study period, 2,076 episodes of infection occurred, including 363 with BSI. Patients with BSI had a greater severity of illness and a greater death rate. After logistic regression, however, BSI did not independently predict death. After matching patients with abdominal infections and pneumonia with BSI to patients without BSI but with a similar site of infection, severity of illness, age, and causative organism, no difference in outcome was seen. CONCLUSIONS: Bloodstream infection is associated with critical illness and death but appears to be a marker of severe primary disease rather than an independent predictor of outcome.

Preexposure of murine macrophages to CpG oligonucleotide results in a biphasic tumor necrosis factor alpha response to subsequent lipopolysaccharide challenge.

Bacterial DNA and synthetic oligonucleotides containing CpG sequences (CpG-DNA and CpG-ODN) provoke a proinflammatory cytokine response (tumor necrosis factor alpha [TNF-alpha], interleukin-12 [IL-12], and IL-6) and increased mortality in lipopolysaccharide (LPS)-challenged mice via a TNF-alpha-mediated mechanism. It was hypothesized that preexposure of macrophages to CpG-ODN would result in an increased TNF-alpha response to subsequent LPS challenge in vitro. Using the murine macrophage cell line RAW 264.7, we demonstrated both a rapid proinflammatory cytokine response (TNF-alpha) and a delayed inhibitory cytokine response (IL-10) with CpG-ODN. Preexposure of macrophages to CpG-ODN for brief periods (1 to 3 h) augmented TNF-alpha secretion and mRNA accumulation following subsequent LPS challenge (1 microg/ml). However, prolonged preexposure to CpG-ODN (6 to 9 h) resulted in suppression of the TNF-alpha protein and mRNA response to LPS. The addition of anti-IL-10 antibody to CpG-ODN during preexposure resulted in an increase in the LPS-induced TNF-alpha response over that induced by CpG-ODN preexposure alone. Thus, while brief preexposure of macrophages to CpG-ODN augments the proinflammatory cytokine response to subsequent LPS challenge, prolonged preexposure elicits IL-10 production, which inhibits the TNF-alpha response. Although the initial proinflammatory effects of CpG-DNA are well established, the immune response to CpG-DNA may also include autocrine or paracrine feedback mechanisms, leading to a complex interaction of proinflammatory and inhibitory cytokines.

Tertiary peritonitis (recurrent diffuse or localized disease) is not an independent predictor of mortality in surgical patients with intraabdominal infection.

BACKGROUND: It is well documented that tertiary peritonitis is associated with different microbiological flora and worse outcomes than secondary peritonitis. It is unknown, however, if these differences can be explained simply by the nosocomial nature of tertiary peritonitis and underlying severity of illness. METHODS: We reviewed all episodes of intraabdominal infection on the inpatient surgical services at a university hospital over a 46-month period. Univariate analysis and logistic regression were used to compare 91 episodes of secondary peritonitis that progressed to tertiary peritonitis (recurrent diffuse or localized intraabdominal infection) to all episodes of secondary peritonitis (n = 453) to identify predictors for developing tertiary peritonitis. Logistic regression was also used to identify predictors of mortality among patients with secondary (n = 473) or tertiary peritonitis (n = 129). RESULTS: Of 602 episodes of intraabdominal infection identified, there were 473 episodes of secondary peritonitis, including 20 patients who died within seven days of diagnosis. A total of 129 episodes of tertiary peritonitis were identified, of which 91 were preceded by a single episode of secondary peritonitis, and 38 were preceded by an episode of secondary peritonitis and at least one prior episode of tertiary peritonitis. Tertiary peritonitis was associated with a high APACHE II score (14.9 +/- 0.7), pancreatic or small bowel source, drainage only at initial intervention, gram-positive and fungal pathogens, and a high mortality rate (19%). Increasing APACHE II score (OR 1.07, 95% CI 1.03-1.16, p = 0.0009) independently predicted progression from secondary to tertiary peritonitis while increasing age (OR 0.98, 95% CI 0.97-0.99, p = 0.01) and appendiceal source (OR 0.12, 95% CI 0.02-0.68, p = 0.02) predicted non-progression to tertiary peritonitis. Independent predictors of mortality in this population included increasing age (OR 1.06, 95% CI 1.03-1.1, p < 0.001), increasing APACHE II score (OR 1.18, 95% CI 1.11-1.3, p < 0.001), and four comorbidities: cerebrovascular disease (OR 4.3, 95% CI 1.4-13.1, p = 0.01), malignant disease (OR 2.9, 95% CI 1.3-6.5, p = 0.01), hemodialysis dependency (OR 3.8, 95% CI 1.3-11.2, p = 0.02), and liver disease (OR 4.2, 95% CI 1.6-15.1, p = 0.03). Tertiary peritonitis was not an independent predictor of mortality. CONCLUSIONS: We were unable to demonstrate, when compared to secondary peritonitis, that tertiary peritonitis is a significant independent predictor of mortality when other variables are taken into account. This suggests that the high mortality associated with tertiary peritonitis is more a function of the patient population in which it occurs than the severity of the pathologic process itself.

Enhanced murine macrophage TNF receptor shedding by cytosine-guanine sequences in oligodeoxynucleotides.

The immunomodulatory role of unmethylated cytosine-guanine sequences (CpG) in bacterial DNA has been well documented. We have previously demonstrated that murine macrophage-like RAW 264.7 cells respond to CpG DNA with an increase in the proinflammatory cytokine, TNF-alpha, in both a dose-dependent and time-dependent manner. In addition, CpG DNA stimulates a significant, though delayed, secretion of the anti-inflammatory cytokine IL-10. Because TNF-alpha and TNFR (TNFRI and II) expression are tightly regulated responses, we hypothesized that CpG containing oligodeoxynucleotide (CpG ODN) would also affect TNFRI and II shedding. Using both murine peritoneal macrophages and RAW 264.7 cells, we demonstrated a significant, time-dependent increase in soluble TNFRI and TNFRII production with CpG ODN stimulation. RAW 264.7 cells treated with CpG ODN had a transient increase in membrane TNFRII expression, but not TNFRI. Both types of TNFR mRNA were also up-regulated by CpG ODN, and addition of the transcriptional inhibitor actinomycin D abrogated the effect of CpG ODN on TNFR mRNA and protein expression. Addition of anti-IL-10 and anti-TNF-alpha Abs did not change these results. The addition of plate-bound anti-TNF receptor Abs to this system increased the amount of bioactive TNF, implying that these receptors are acting as inhibitors of TNF activity. These results suggest that the de novo, non-IL-10- and non-TNF-alpha-dependent transcription, translation, and shedding of TNFRs are additional potential counterinflammatory effects of CpG DNA.

Characteristics of infectious complications associated with mortality after solid organ transplantation.

Infection remains a common source of morbidity and mortality after solid organ transplantation. The purpose of this study was to characterize the continuously changing patterns of post-transplantation infections, analyze early post-transplantation infections, and evaluate characteristics associated with mortality. A secondary analysis was performed on prospectively collected data for all episodes of infection occurring between 10 December 1996 and 28 October 1998 on the surgery services at a university medical center. Post-transplantation infections were compared with those in non-transplantation patients randomly matched by severity of illness. Further analysis was performed on post-transplantation infections occurring during the admission of transplantation compared with those in subsequent admissions. To evaluate factors associated with mortality, episodes occurring in survivors and non-survivors were compared. The results demonstrated that infections in transplantation recipients (n = 303) were associated with a younger age and had significantly lower white blood cell counts (WBC) compared with non-transplantation patients. There was no difference in mortality (15.5 vs. 16.5%, p = 0.74). Post-transplantation infectious complications during the initial hospitalization (n = 105) occurred at 38+/-6 compared with 695+/-66 d (p<0.0001) after transplantation and were associated with a longer length of stay (LOS) and increased mortality (30.5 vs. 7.6%, p<0.0001) compared with those occurring in subsequent admissions (n = 198). Although multiple characteristics of post-transplantation infections were associated with mortality, only the Acute Physiology and Chronic Health Evaluation (APACHE) II score was an independent predictor of mortality. Post-transplantation infections remain a significant source of morbidity and mortality. The leukocyte response to infection was suppressed in the transplantation population. Post-transplantation infections which occur during the admission for transplantation have a markedly increased mortality.

Pretransplantation hepatitis C virus quasispecies may be predictive of outcome after liver transplantation.

The evolution of hepatitis C virus (HCV) envelope variation was studied using a liver-transplant model to evaluate the role of HCV quasispecies for hepatocyte infection. Twelve HCV polymerase chain reaction (PCR)-positive liver-transplant recipients (6 with posttransplantation biochemical hepatitis and 6 without hepatitis [controls]) were prospectively evaluated and underwent detailed quasispecies analysis of pre- and postoperative serum samples. HCV amino acid sequence diversity and complexity at the first hypervariable region (HVR1) of the second envelope protein (E2) was correlated with outcome. Recurrence of HCV-induced allograft injury was defined by persistently elevated serum alanine transaminase (ALT) levels. The major variant (sequences >10% of all clones) of recipients with hepatitis accounted for a significantly smaller percent of all preoperative clones compared with controls (41% +/- 6% vs. 69% +/- 8%; P <.015). Recipients with hepatitis had an increased number of pretransplantation major variants (2.5 +/- 0.3 vs. 1.1 +/- 0.2; P <.006). Eighty-three percent of controls had a predominant variant (accounting for >50% of clones) compared with 17% of those with recurrence (P <.05). These differences did not persist postoperatively. In addition, recipients without a pretransplantation predominant variant demonstrated an increased allograft fibrosis score (2.3 +/- 0.3 vs. 0.5 +/- 0.3; P <.015) at 181 to 360 days posttransplantation compared with those in whom a predominant variant was present. Increased HCV envelope complexity may act as a stronger antigenic stimulus or improve hepatocyte receptor binding and lead to allograft hepatitis and fibrosis. Although pretransplantation differences in HCV quasispecies did not persist postoperatively, pretransplantation quasispecies may be a predictor of HCV-induced hepatitis and graft fibrosis after liver transplantation.

Hepatitis C-induced hepatic allograft injury is associated with a pretransplantation elevated viral replication rate.

Hepatitis C virus (HCV) allograft infection after liver transplantation follows a variable but accelerated course compared with the nontransplantation population. Predictors of outcome and mechanisms of reinfection remain elusive. The accelerated HCV-induced allograft injury associated with a 10- to 20-fold increase in serum viral quantity posttransplantation was hypothesized to be the result of elevated intrahepatic viral replication rates. Patients (N = 23) with HCV-induced end-stage liver disease who underwent liver transplantation between October 1995 and December 1998 were prospectively studied. HCV-induced allograft injury was defined by posttransplantation persistent biochemical hepatitis or allograft fibrosis not explained by other diagnoses. Liver biopsies (N = 92) were obtained by protocol and when clinically indicated. Negative-strand HCV RNA (putative intermediate for replication) was detected by a strand-specific reverse-transcription polymerase chain reaction (RT-PCR) assay and semiquantatively compared with constitutively expressed 18S rRNA. Recipients with increased pretransplantation replication were at increased risk for the development of posttransplantation biochemical hepatitis (P =.03), an increased rate of allograft fibrosis (P =.006), and increased mortality rate (40.0% vs. 0.0%; P =.02). There was no correlation with quantities of genomic HCV RNA in the serum with relative intrahepatic viral replication either before or after liver transplantation. The relative rate of HCV replication within the allograft was not elevated in the posttransplantation period compared with that seen within the explanted liver. Accelerated allograft injury caused by HCV may be predicted by viral replication rates within the explanted liver. The stable intrahepatic replication rate after transplantation suggests that elevated serum viral loads are the result of decreased viral clearance, possibly secondary to immunosuppressive therapy.

Prediction of liver allograft fibrosis after transplantation for hepatitis C virus: persistent elevation of serum transaminase levels versus necroinflammatory activity.

Recurrence of hepatitis C virus (HCV) after orthotopic liver transplantation (OLT) remains a significant source of morbidity and mortality. Factors that reliably predict allograft injury from HCV have not been identified. Demographics, clinical data, and histopathological characteristics of recipients with and without persistently elevated serum transaminase levels (PEST) were compared. Twenty-four patients with HCV-induced end-stage liver disease who underwent OLT between October 1995 and December 1998 were entered into a longitudinal, prospective evaluation for identification of parameters associated with graft injury. Liver biopsies were performed preoperatively and between posttransplantation days 1 to 28, 29 to 60, 61 to 180, 181 to 360, and then every 6 to 12 months thereafter. Biopsy specimens were reviewed in a blinded fashion and scored for rejection, necroinflammatory activity, extent of fibrosis, and infiltrating cell type, location, and magnitude. Transplant recipients with PEST (alanine transaminase level >1.5 times normal for 3 consecutive months) and cholestatic hepatitis showed an increased viral load compared with their own preoperative values (16-fold and 256-fold, respectively). Compared with control transplant recipients, PEST was associated with macrovesicular steatosis within 28 days after OLT (P <.05) and showed an increased rate of fibrosis (P <.003) despite similar degrees of rejection and necroinflammatory activity. There was no difference in demographics or immunosuppression. Macrovesicular steatosis may be the earliest predictor of graft fibrosis. Despite similar degrees of necroinflammatory activity, transplant recipients with PEST had an increased rate of fibrosis that could be predicted on average within 6 months posttransplantation.

Contribution of Escherichia coli alpha-hemolysin to bacterial virulence and to intraperitoneal alterations in peritonitis.

Alpha-hemolysin (Hly) is a common exotoxin produced by Escherichia coli that enhances virulence in a number of clinical infections. The addition of hemolysin production to laboratory bacterial strains is known to increase the lethality of E. coli peritonitis. However, the mechanisms involved have not been determined and the contribution of hemolysin to the alterations in the host intraperitoneal environment and the leukocyte response is not known. Utilizing a rat peritonitis model, we show that wild-type hemolytic E. coli strains have a significant competitive advantage over nonhemolytic strains within the peritoneum. To examine the specific contribution of Hly to E. coli-induced virulence and alterations within the peritoneum, a mixed peritonitis model of E. coli, Bacteroides fragilis, and sterile fecal adjuvant was used. Three transformed E. coli strains were utilized: one strongly secretes active hemolysin (WAF 270), a second secretes active hemolysin but a reduced amount (WAF 260), and the third does not produce hemolysin (WAF 108). After an equal inoculum of each of the three strains, WAF 270 produced a markedly increased lethality and an increased recovery of both E. coli and B. fragilis from the host relative to the other strains. Changes in the intraperitoneal pH, degree of erythrocyte lysis, and recruitment and viability of leukocytes within the peritoneum following the induction of peritonitis differed significantly between the strongly hemolytic and nonhemolytic strains. Induction of peritonitis with WAF 270 caused a pronounced decrease in intraperitoneal pH, lysis of most of the intraperitoneal erythrocytes, and a marked decrease in recoverable viable leukocytes compared to WAF 108. Thus, hemolysin production by E. coli within the peritoneum may alter not only the host's ability to control the hemolytic strain itself but also other organisms.

Analysis of aminoglycosides in the treatment of gram-negative infections in surgical patients.

HYPOTHESIS: Antibiotic regimens containing aminoglycosides result in a similar outcome compared with non-aminoglycoside regimens in the treatment of gram-negative infections in surgical patients. DESIGN: An inception cohort study of hospitalized surgical patients from December 1, 1996, through September 30, 1998. Patients were observed from the time of diagnosis of infection to discharge. SETTING: University hospital. PATIENTS: Two hundred fifty-eight consecutive gram-negative infections occurring in general surgical and trauma patients and patients undergoing transplantation. Sixty-six patients received aminoglycosides as a component of their treatment regimen, whereas 192 received other agents. RESULTS: Patients treated with aminoglycosides were younger (mean +/- SEM age, 48+/-2 vs 53+/-1 years; P = .04 by univariate analysis) and had a similar APACHE II (Acute Physiology and Chronic Health Evaluation II) score (mean +/- SEM, 17+/-1 vs 15+/-1; P = .10), yet had a significantly higher mortality vs patients treated with other agents (29% vs 14%; P = .02). A larger proportion of patients requiring hemodialysis were treated with aminoglycosides (33% vs 13%; P = .001). Although there was no difference in the sites of infection between groups, surgical patients with gram-negative pneumonia had a higher mortality when treated with aminoglycosides (37% vs 18%; P = .04), despite similar APACHE II scores (mean +/- SEM, 20+/-1 vs 18+/-1; P = .40). CONCLUSIONS: Despite a younger age and similar severity of illness, patients with gram-negative infections treated with aminoglycosides were associated with a higher mortality rate, although this may be related to selection bias in the use of aminoglycoside agents. The mortality rate associated with gram-negative pneumonia was also higher in patients treated with aminoglycosides, despite a similar severity of illness. Future randomized studies are necessary to reanalyze the role of aminoglycosides in treating surgical patients with gram-negative infections, particularly pneumonia.