Christopher M. Moore

Virulence Associated with Outbreak-Related Strains of Burkholderia cepacia Complex among a Cohort of Patients with Bacteremia

The Burkholderia cepacia complex includes 9 genomovars. The relative virulence of each is unknown. Host and pathogen features associated with mortality were evaluated among patients with B. cepacia complex bacteremia. Cases were ascertained through review of blood culture results for the period of May 1996 through May 2002. Isolates were identified to species level with 16S rDNA and recA-based species-specific polymerase chain reaction analyses and recA restriction fragment-length polymorphism. Strain typing was performed with pulsed-field gel electrophoresis. Fifty-three patients with B. cepacia complex bacteremia were identified; only 9 (17%) had cystic fibrosis. Twenty-five patients (47%) died within 14 days of bacteremia. After controlling for comorbid conditions and therapeutic interventions, 2 outbreak-related strains of Burkholderia cenocepacia (genomovar III) were associated with 14-day mortality (odds ratio, 5.5; 95% confidence interval, 1.20-25.02). B. cenocepacia is an emerging nosocomial pathogen. Certain strains are associated with an enhanced capacity for interpatient spread and poor outcome.

Cirrhotic ascites review: Pathophysiology, diagnosis and management

Ascites is a pathologic accumulation of peritoneal fluidcommonly observed in decompensated cirrhotic states.Its causes are multi-factorial, but principally involve significant volume and hormonal dysregulation in the setting of portal hypertension. The diagnosis of ascites is considered in cirrhotic patients given a constellation of clinical and laboratory findings, and ultimately confirmed, with insight into etiology, by imaging and paracentesis procedures. Treatment for ascites is multi-modal including dietary sodium restriction, pharmacologic therapies, diagnostic and therapeutic paracentesis, and in certain cases transjugular intra-hepatic portosystemic shunt. Ascites is associated with numerous complications including spontaneous bacterial peritonitis, hepato-hydrothorax and hepatorenal syndrome. Given the complex nature of ascites and associatedcomplications, it is not surprising that it heralds increased morbidity and mortality in cirrhotic patients and increased cost-utilization upon the health-care system. This review will detail the pathophysiology of cirrhotic ascites, common complications derived from it, and pertinent treatment modalities.

Risk factors for Burkholderia cepacia complex bacteremia among intensive care unit patients without cystic fibrosis : A case-control study

BACKGROUND The Burkholderia cepacia complex is associated with colonization or disease in patients with cystic fibrosis (CF). For patients without CF, this complex is poorly understood apart from its presence in occasional point source outbreaks. OBJECTIVE To investigate risk factors for B. cepacia bacteremia in hospitalized, intensive care unit patients without CF. METHODS We identified patients with 1 or more blood cultures positive for B. cepacia between May 1, 1996, and March 31, 2002, excluding those with CF. Control patients were matched to case patients by ward, duration of hospitalization, and onset date of bacteremia. Matched analyses were used to identify risk factors for B. cepacia bacteremia. RESULTS We enrolled 40 patients with B. cepacia bacteremia into the study. No environmental or other point source for B. cepacia complex was identified, although horizontal spread was suspected. Implementation of contact precautions was effective in decreasing the incidence of B. cepacia bacteremia. We selected 119 matched controls. Age, sex, and race were similar between cases and controls. In multivariable analysis, renal failure that required dialysis, recent abdominal surgery, 2 or more bronchoscopic procedures before detection of B. cepacia bacteremia, tracheostomy, and presence of a central line before detection of B. cepacia bacteremia were independently associated with development of B. cepacia bacteremia, whereas presence of a percutaneous feeding tube was associated with a lower risk of disease. CONCLUSIONS B. cepacia complex is an important emerging group of nosocomial pathogens in patients with and patients without CF. Nosocomial spread is likely facilitated by cross-transmission, frequent pulmonary procedures, and central venous access. Infection control measures appear useful for limiting the spread of virulent, transmissible clones of B. cepacia complex.

Procalcitonin, and cytokines document a dynamic inflammatory state in non-infected cirrhotic patients with ascites

AIM To quantitate the simultaneous serum and ascitic fluid levels of procalcitonin and inflammatory markers in cirrhotics with and without ascites. METHODS A total of 88 consecutive severe cirrhotic patients seen in a large city hospital liver clinic were studied and divided into two groups, those with and without ascites. Group 1 consisted of 41 cirrhotic patients with massive ascites, as demonstrated by necessity for therapeutic large-volume paracentesis. Group 2 consisted of 47 cirrhotic patients without any clinically documented ascites to include either a recent abdominal computed tomography scan or ultrasound study. Serum and ascitic fluid levels of an array of inflammatory markers, including procalcitonin, were measured and compared to each other and a normal plasma panel (NPP). RESULTS The values for inflammatory markers assayed in the serum of Groups 1 and 2, and ascitic fluid of the Group 1. The plasma levels of the inflammatory cytokines interleukin (IL)-2, IL-4, IL-6, IL-8, interferon gamma (IFNγ) and epidermal growth factor (EGF) were all significantly greater in the serum of Group 1 as compared to that of the serum obtained from the Group 2 subjects (all P < 0.05). There were significantly greater serum levels of IL-6, IL-8, IL-10, monocyte chemoattractant protein-1, tumor necrosis factor-α, vascular endothelial growth factor and EGF when comparing Group 2 to the NPP. There was no significant difference for IL-1A, IL-1B, IL-2, IL-4 and IFNγ levels between these two groups. Serum procalcitonin levels were increased in cirrhotics with ascites compared to cirrhotics without ascites, but serum levels were similar to ascites levels within the ascites group. Furthermore, many of these cytokines, but not procalcitonin, demonstrate an ascites-to-serum gradient. Serum procalcitonin does not demonstrate any significant difference segregated by liver etiology in the ascites group; but ascitic fluid procalcitonin is elevated significantly in cardiac cirrhosis/miscellaneous subgroup compared to the hepatitis C virus and alcoholic cirrhosis subgroups. CONCLUSION Procalcitonin in the ascitic fluid, but not in the serum, differentiates between cirrhotic subgroup reflecting the dynamic interplay of ascites, bacterial translocation and the peri-peritoneal cytokine.

Fungal Infections: Their Diagnosis and Treatment in Transplant Recipients

Systemic fungal infections typically occur in individuals who are seriously ill with recognized risk factors such as those frequently found in transplant recipients. Unfortunately, they are often diagnosed late, when the efficacy of the available treatments is low, often less than 50%, and the cost in terms of lives lost, hospital length of stay, and total hospital costs is substantially increased. The application of antifungal therapies associated with reported efficacy rates greater than 50% are those used prophylactically. When used prophylactically, these infections are reduced in greater than 95% of the expected cases. The choice of a prophylactic agent should be based upon its ease of administration, lack of adverse effects, reduced likelihood of potential drug interactions, and its efficacy in patients with established risk factors and comorbid disease processes that include renal, hepatic, and chronic pulmonary disease. The indications for the use of currently available antifungal agents, their adverse effects, drug interactions, ease of dosing, and applicability in patients with preexisting disease states, and especially in liver transplant recipients, are presented in this paper.

Colonic diffuse large B-cell lymphoma in a liver transplant patient with historically very low tacrolimus levels.

Posttransplant lymphoproliferative disorders (PTLDs) comprise a wide spectrum of hematologic malignancies that are found increasingly in orthotopic liver transplant (OLT) patients given the rising frequency of these surgeries and their long-term success. PTLDs are highly correlated with both the Epstein-Barr virus (EBV) infection and the degree of immunosuppression involved. Herein is reported a case of a 53-year-old male with successfully treated hepatitis C virus genotype 4 and hepatocellular carcinoma who underwent OLT and developed symptoms of weakness and poor appetite 4 years later while on tacrolimus 3 mg b.i.d. with historically very low plasma levels. He was found to be anemic and colonoscopy revealed a 4.5 cm cecal diffuse large B-cell lymphoma (DLBCL). Further workup revealed mesenteric lymph node enlargement consistent and nodal DLBCL dissemination. He was treated with cyclophosphamide-hydroxyldaunorubicin-oncovin-prednisone-rituximab (CHOP-R) chemotherapy and his tacrolimus dose was lowered. Additionally, he manifested PTLD-associated cryoglobulinemia leading to acute kidney injury. After a prolonged hospitalization he was discharged with close followup.

Case Series of 10 Patients with Cirrhosis Undergoing Emergent Repair of Ruptured Umbilical Hernias: Natural History and Predictors of Outcomes

OBJECTIVES Ascites represents an important event in the natural history of cirrhosis, portending increased 1-year mortality. Umbilical herniation with rupture is an uncommon complication of large-volume ascites that is associated with significant morbidity and mortality. The aim of this study was to describe predictors of outcomes in patients undergoing emergent repair for spontaneous umbilical hernia rupture. MATERIALS AND METHODS We report a case series of 10 patients with decompensated cirrhosis (mean age 66 ± 9 years, mean Model for End-Stage Liver Disease score of 21 ± 7) who presented with a ruptured umbilical hernia and had emergent repair. RESULTS Thirty percent (3/10) of patients died or required liver transplant. Factors associated with death or transplant included the development of bacterial peritonitis (P = .03) and the presurgical 30-day Mayo Clinic Postoperative Mortality Risk in Patient with Cirrhosis Score (P = .03). CONCLUSIONS Emergent repair after umbilical hernia rupture in patients with decompensated cirrhosis carries a poor prognosis with 30% of patients developing poor postsurgical outcomes.

New models to enhance the assessment of mortality risk in low model for end-stage liver disease patients: “Objectifying” the subjective

Currently, approximately 3000 patients per year are removed from listing for liver transplantation (LT) in the United States because of the severity of their medical illness or death. In part, this outcome is a result of how health-care providers identify and manage the most suitable candidates before LT. Implemented in 2002, the Model for End-Stage Liver Disease (MELD) score is the current instrument broadly used to riskstratify and prioritize patients for the need for LT. Although reasonably successful in predicting shortterm mortality in all wait-listed patients, it may not adequately capture or identify high-mortality-risk subgroups with lower MELD scores. In this issue of Liver Transplantation, Wedd et al. seek to better characterize these potentially underserved populations, namely, patients with MELD scores 20 who have a higher than expected mortality risk. In particular, the authors examine a host of variables among 41 case subjects matched to 66 case controls with equivalent low MELD scores and other associated features. One key variable is “cirrhotic stage 1-5,” which was defined previously by D’Amico et al. but is conceptually new to the field: (1) cirrhosis without varices or ascites, (2) varices without bleeding, (3) variceal bleeding without ascites, (4) ascites with or without nonbleeding varices, and (5) ascites with variceal bleeding. Wedd et al. conclude that an increasing cirrhotic stage was the key variable associated with liver-related death more than other factors in this low-MELD cohort. This type of cirrhotic staging formally resurrects some level of subjectivity in our modern risk assessment, which traditionally was a concern with the Child-Turcotte-Pugh (CTP) score initially devised in the 1970s for reasons other than LT determination. The CTP score is limited by the following: (1) the explicitly subjective nature of 2 of the 5 parameters (ie, severity of ascites and encephalopathy); (2) the ceiling effect, which placed patients with greatly altered “objective” laboratory values into similar classes; and (3) the focus on a snapshot of disease, such as ascites improvement and subsequent CTP score reduction, which perhaps erroneously implied a reduced mortality risk. Indeed, in 1998, such concerns prompted the hybridization of the CTP score with patient location to create status levels (1, 2A, 2B, and 3) as the main instrument of risk assessment. Although this policy did reduce wait-list mortality, it was eventually plagued by the vagaries and potential wrongdoings of location placement. Ultimately, the transplant community had to develop a more purely objective system of risk assessment. This led directly to the implementation of the MELD score. However, there are persistent concerns with respect to the appropriateness of the objective parameters, the potential for interassay variability and manipulation, and, as mentioned previously, the underserving of lowscore, high-risk patients. Tinkering with the MELD score itself has thus persisted either through exception points [eg, for well-staged hepatocellular carcinoma (accepted)] or through modification of the equation itself (in testing). Examples of the latter include (1) serum sodium (MELD-Na), (2) integrated age and sodium (iMELD), (3) changes in the MELD score over time (DMELD), and (4) the alteration of the coefficients alone

An Esophagogastroduodenal Crohn’s-Like Disease in a Long-Standing Pan-Ulcerative Colitis Patient

Inflammatory bowel disease (IBD) comprises the principal subtypes Crohns disease (CD) and ulcerative colitis (UC), with a fraction remaining as IBD unclassified (IBDU). Given the complexity of IBD manifestations in a patient over time and our increasing understanding of IBD biology, a modification in subtype diagnosis can also occur. Herein is a case of a 27-year-old female with well-controlled and long-standing pan-UC, who developed Crohns-like esophagogastroduodenitis. The difficulty in classifying IBD into a single traditional subtype, and the debated presentation of a coexistent IBD will be discussed.