Surgical infection and the aging population.

With the general aging of the United States population we can expect to encounter increasing numbers of elderly patients with surgical infections. To further delineate this population, patient attributes, treatment characteristics, and outcomes were examined in elderly patients with surgical infection. All infections from December 1996 through May 2000 occurring on the inpatient, adult general, and trauma surgical services at a university hospital were studied prospectively. Characteristics, comorbidities, and outcomes were examined in patients > or = 70 years of age and compared with those of patients <70 years of age. Elderly patients had significantly higher Acute Physiology and Chronic Health Evaluation (APACHE) II scores (15.4 +/- 0.3 vs 11.2 +/- 0.2, P < 0.001) and greater numbers of comorbidities than the younger population. The Acute Physiology score; infecting organisms; and rates of pneumonia and intra-abdominal, central line, and bloodstream infection were similar between groups. Crude mortality (21.7% vs 8.1%, P < 0.001) and mortality associated with pneumonia (31.0% vs 17.2%, P = 0.005), central venous catheter infection (50.0% vs 17.4%, P < 0.001), bloodstream infection (32.3% vs 16.6%, P = 0.006), and intra-abdominal infection (23.2% vs 6.3%, P < 0.001) were significantly higher in the elderly. Logistic regression analysis identified APACHE II score, cerebrovascular disease, and fungal infection as independent predictors of mortality in the elderly population. Surgical infection in the elderly is associated with a high mortality and requires special consideration when treating this unique population.

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.

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.

Diagnosis of intra-abdominal infection in the critically ill patient.

Intra-abdominal infection continues to pose a significant threat to critically ill patients in the year 2000. A review of the current literature reveals that despite remarkable developments in critical care medicine and extensive study of patients with tertiary peritonitis, the associated mortality rate remains nearly 30%. Progress has been limited by the difficulty of comparing heterogeneous patient populations, groups that manifest a host of comorbid, potentially confounding illnesses. Additionally, debate persists regarding the definitions of secondary and tertiary peritonitis, resulting in varied study inclusion criteria, and further complicating data analysis and interpretation. Scoring systems developed to identify those patients at risk for progression to tertiary peritonitis, the more chronic, lethal form of intra-abdominal infection associated with multisystem organ failure, reflect the current emphasis in the literature on the importance of early diagnosis and early intervention. This has led to a renewed interest in conservative, data-dependent surgical management employing radiographic and microbiologic evidence to guide therapy.

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.

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.

Bacteremia associated with central venous catheter infection is not an independent predictor of outcomes.

BACKGROUND: Infection is the leading complication of central venous catheters. In the setting of suspected line infection, the CDC recognizes only catheter-related bloodstream infection but not catheter infection without bacteremia, which is designated "colonization." To evaluate the hypothesis that catheter-related bloodstream infection has worse outcomes than catheter infection without bacteremia, we compared demographics, clinical data, and outcomes. STUDY DESIGN: Analysis of catheter infections was performed on data collected prospectively for all episodes of infection occurring from December 1996 to September 1999 on the surgical services at a university hospital. Catheter tips were cultured only when infection was suspected. Catheter infection without bacteremia was defined as systemic evidence of infection, the presence of at least 15 colony-forming units on the catheter tip by a semiquantitative technique, and absence of bloodstream infection with the same organism as the catheter. Catheter-related bloodstream infection required the presence of bacteremia with the same organism as the catheter tip. RESULTS: The 59 patients with catheter-related bloodstream infection had more coexistent infections than the 91 patients with catheter infection without bacteremia (2.9+/-0.1 versus 1.7+/-0.1; p=0.0001), most commonly pneumonia (37.3% versus 16.5%, p = 0.004) and urinary tract infections (28.8% versus 8.8%, p = 0.001). Catheter-related bloodstream infection was associated with an increased proportion of gram-negative organisms compared with catheter infections without bacteremia (29.5% versus 16.9%, p = 0.04) and a trend toward fewer gram-positive organisms (61.5% versus 73.7%, p = 0.07). There were no differences in APACHE II score, WBC, length of hospital stay, time from admission to fever, time from fever to treatment, normalization of WBC, days of antibiotics, defervescence, gender, presence of comorbidities, occurrence of colonization while in an ICU, or mortality rate (18.6% with bacteremia, 24.2% without; p = 0.42). CONCLUSIONS: The presence of bloodstream infection in addition to catheter infection does not appear to alter outcomes. The definition of catheter infection perhaps should be extended to include catheter infections without bloodstream infection in the presence of systemic illness without another source.

Persistent occult hypoperfusion is associated with a significant increase in infection rate and mortality in major trauma patients.

OBJECTIVE: To investigate the hypothesis that occult hypoperfusion (OH) is associated with infectious episodes in major trauma patients. METHODS: Data were collected prospectively on all adult trauma patients admitted to the Surgical/Trauma Intensive Care Unit from November of 1996 to December of 1998. Treatment was managed by a single physician according to a defined resuscitation protocol directed at correcting OH (lactic acid [LA] > 2.4 mmol/L). RESULTS: Of a total of 381 consecutive patients, 118 never developed OH and 263 patients exhibited OH. Seventeen patients were excluded because their LA never corrected, and they all subsequently died. One hundred seventy-six infectious episodes occurred in 97 of the 364 patients remaining. The infection rate in patients with no elevation of LA was 13.6% (n = 118) compared with 12.7% (n = 110) in patients whose LA corrected by 12 hours, 40.5% (n = 79; p < 0.01 compared with all other groups) in patients whose LA corrected between 12 and 24 hours, and 65.9% (n = 57; p < 0.01 compared with all other groups) in patients who corrected after 24 hours. Among the patients with infections, there were 276 infection sites with 42% of infections involving the lung and 21% involving bacteremia. There was no difference in proportion of infections occurring at each site between groups. The mortality rate of patients who developed infections was 7.9% versus 1.9% in patients without infections (p < 0.05). Of the patients who developed infections, 69.8% versus 25.8% (p < 0.001) did not have their lactate levels normalized within 12 hours of emergency room admission. Logistic regression demonstrated that both the Injury Severity Score and OH > 12 hours were independently predictive of infection. CONCLUSION: A clear increase in infections occurred in patients with OH whose lactate levels did not correct by 12 hours, with an associated increase in length of stay, days in surgical/trauma intensive care unit, hospital charges, and mortality.

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.

Extremes of white blood cell count do not independently predict outcome among surgical patients with infection.

Historically patients with severely depressed or elevated white blood cell (WBC) counts during infection were felt to have worse outcomes. To test this assumption we prospectively analyzed all infections on the surgical services at the University of Virginia hospital between December 1, 1996 and April 1, 1999. Among 1737 infectious episodes 59 presented with leukopenia (WBC count < or = 3,000 cells/microL) whereas 66 presented with leukemoid responses (WBC count > or = 30,000 cells/microL). Compared with other infected patients leukopenic patients had higher Acute Physiology and Chronic Health Evaluation II (APACHE II) scores (18+/-0.9 vs 12+/-0.2, P < 0.0001) and mortality (23.7% vs 11.4%, P = 0.004). Patients with leukemoid responses also had higher APACHE II scores (21+/-1.0 vs 12+/-0.2, P < 0.0001) and mortality (30.3% vs 11.4%, P < 0.0001). Compared with a control group randomly matched (2:1) by age and APACHE II score, however, there was no significant difference in mortality associated with leukopenia or a leukemoid response. Furthermore logistic regression did not reveal leukopenia or leukemoid responses to be independent predictors of mortality (odds ratio for death with leukopenia = 1.57, 95% confidence interval = 0.63-3.91, P = 0.33; odds ratio for death with leukemoid response = 1.19, 95% confidence interval = 0.70-2.02, P = 0.53). Although very low or very high WBC counts may represent markers of severe illness in infected surgical patients they do not appear to be significant contributors to a worsened outcome.

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.

Waiting for microbiologic data to direct therapy against nosocomial infections in febrile surgical patients: are outcomes worsened?

HYPOTHESIS: Allowing adequate time for laboratory and culture results before initial treatment may be associated with a worse outcome in nosocomial infections. DESIGN: Cohort study of all episodes of nosocomial infection from December 10, 1996, to October 28, 1998. SETTING: Surgical services at a university hospital. PATIENTS AND METHODS: In surgical patients presenting with fever, 372 episodes of nosocomial infection were evaluated. Nosocomial infections were divided by time from fever to intervention (< or =12, 13-24, and >24 hours). These groups were subdivided by Acute Physiology and Chronic Health Evaluation II (APACHE II) scores into low (< or =10 [n = 114]), moderate (11-20 [n = 169]), and high severity of illness (>20 [n = 89]). Pneumonia and bloodstream infections were divided by APACHE II scores into low (< or =15 [n = 55 and n = 56, respectively]) or high severity of illness (>15 [n = 84 and n = 77, respectively]). MAIN OUTCOME MEASURES: Mortality, length of stay. RESULTS: No difference in outcome was seen between different time intervals from fever to intervention for nosocomial infections in patients with APACHE II scores of no more than 10. Patients treated more than 24 hours after fever were significantly younger than those treated at no more than 12 and 13 to 24 hours with APACHE II scores of 11 to 20 (P<.05) and more than 20 (P<.05). Mortality and length of stay for patients treated at later time intervals were comparable with those of patients treated earlier with similar APACHE II scores. There was no difference in outcome for patients with pneumonia or bloodstream infection. CONCLUSIONS: Episodes of infection in which treatment was withheld until initial microbiologic data were available (24 hours) did not have worse outcomes compared with those treated earlier. Waiting for laboratory and culture results to direct antibiotic therapy for nosocomial infections does not appear harmful and may be potentially beneficial.

Gender-dependent differences in outcome after the treatment of infection in hospitalized patients.

CONTEXT: While it is established that management strategies and outcomes differ by gender for many diseases, its effect on infection has not been adequately studied. OBJECTIVE: To investigate the role of gender among hospitalized patients treated for infection. DESIGN: Observational cohort study conducted during a 26-month period from December 1996 through January 1999. SETTING: University-affiliated hospital. PARTICIPANTS: A total of 892 patients in the surgical units of the hospital with 1470 consecutive infectious episodes (782 in men and 688 in women). MAIN OUTCOME MEASURES: Mortality during hospitalization by gender for infection episodes overall and for specific infectious sites, including lung, peritoneum, bloodstream, catheter, urine, surgical site, and skin/soft tissue. RESULTS: Among all infections, there was no significant difference in mortality based on gender (men, 11.1% vs women, 14.2%; P = .07). After logistic regression analysis, factors independently associated with mortality included higher APACHE (Acute Physiology and Chronic Health Evaluation) II score, older age, malignancy, blood transfusion, and diagnosis of infection more than 7 days after admission, but not gender (female odds ratio [OR] for death, 1.32; 95% confidence interval [CI], 0.90-1.94; P = .16). Mortality was higher in women for lung (men, 18% vs women, 34%; P = .002) and soft tissue (men, 2% vs women, 10%; P < or = .05) infection; for other infectious sites, mortality did not differ by gender. Factors associated with mortality due to pneumonia by logistic regression included higher APACHE II score, malignancy, diabetes mellitus, diagnosis of infection more than 7 days after admission, older age, transplantation, and female gender (OR for death, 2.25; 95% CI, 1.17-4.32; P = .02). CONCLUSIONS: Although gender may not be predictive of mortality among all infections, women appear to be at increased risk for death from hospital-acquired pneumonia, even after controlling for other comorbidities.

Prediction of poorer prognosis by infection with antibiotic-resistant gram-positive cocci than by infection with antibiotic-sensitive strains.

HYPOTHESES: Surgical patients with antibiotic-resistant gram-positive coccal (GPC) infections have a poorer prognosis than those with antibiotic-sensitive GPC infections, and colonization with resistant GPC predisposes to the development of resistant GPC infections. DESIGN: All infections among surgical patients from December 1, 1996, to December 1, 1998, were followed up prospectively. Patients with antibiotic-sensitive and antibiotic-resistant GPC infections were compared. Cohorts were also subdivided on the basis of GPC species, colonization status, and immunosuppression. SETTING: The surgical wards and intensive care units of a tertiary care, university hospital. MAIN OUTCOME MEASURES: In-hospital mortality, inhospital mortality during antibiotic therapy, length of stay, and length of stay from the time of initiation of antibiotics to discharge. RESULTS: Antibiotic-resistant GPC infection compared ki4th antibiotic-sensitive GPC infection was associated with a higher mortality and previous colonization rate (25.8% and 31.0% vs 17.6% and 8.8%, respectively; P = .04 and P<.001, respectively) and a markedly longer length of stay (55.0 +/- 3.3 vs 31.0 +/- 2.0 days; P<.001). Length of stay and treatment to discharge times were longer after resistant Staphylococcus aureus infections than after resistant Staphylococcus epidermidis infections. The mortality and length of stay of patients with gentamicin-resistant or vancomycin-resistant enterococcal infections were equivalently higher than those with antibiotic-sensitive enterococcal infections. Transplant recipients with resistant enterococcal infection had the highest mortality (41.9%). CONCLUSIONS: Surgical patients who develop antibiotic-resistant GPC infections have a significantly higher mortality rate, longer length of stay, and longer treatment to discharge time than patients with antibiotic-sensitive GPC infections. Colonization with resistant GPC predisposes to resistant GPC infection. Gentamicin-resistant enterococcus appears to be as virulent as vancomycin-resistant enterococcus.