High-dose tigecycline and colistin for successful treatment of disseminated carbapenem-resistant Klebsiella pneumoniae infection in a liver transplant recipient.

Solid organ transplantation (SOT) is a risk factor for the acquisition of carbapenem-resistant Klebsiella pneumoniae. This infection is associated with a high mortality rate given the limited armamentarium of antibiotics for multidrug-resistant organisms along with continued immunosuppression to prevent graft rejection. We report a case of carbapenem-resistant K. pneumoniae pneumonia, bacteraemia and intra-abdominal infection in a newly transplanted liver recipient. The patient was successfully treated with a long course of high-dose tigecycline and colistin, along with surgical drainage. We discuss SOT-relevant epidemiology, therapeutic options and the rationale for our treatment choice.

Lower than expected hepatitis B virus infection prevalence among first generation Koreans in the U.S.: results of HBV screening in the Southern California Inland Empire.

BACKGROUND: Hepatitis B virus (HBV) infection is prevalent in Asian immigrants in the USA. California's Inland Empire region has a population of approximately four million, including an estimated 19,000 first generation Koreans. Our aim was to screen these adult individuals to establish HBV serological diagnoses, educate, and establish linkage to care. METHODS: A community-based program was conducted in Korean churches from 11/2009 to 2/2010. Subjects were asked to complete a HBV background related questionnaire, provided with HBV education, and tested for serum HBsAg, HBsAb and HBcAb. HBsAg positive subjects were tested for HBV quantitative DNA, HBeAg and HBeAb, counseled and directed to healthcare providers. Subjects unexposed to HBV were invited to attend a HBV vaccination clinic. RESULTS: A total of 973 first generation Koreans were screened, aged 52.3y (18-93y), M/F: 384/589. Most (75%) had a higher than high school education and were from Seoul (62.2%). By questionnaire, 24.7% stated they had been vaccinated against HBV. The serological diagnoses were: HBV infected (3.0%), immune due to natural infection (35.7%), susceptible (20.1%), immune due to vaccination (40.3%), and other (0.9%). Men had a higher infection prevalence (4.9% vs. 1.7%, p = 0.004) and a lower vaccination rate (34.6% vs. 44.0%, p = 0.004) compared to women. Self-reports of immunization status were incorrect for 35.1% of subjects. CONCLUSIONS: This large screening study in first generation Koreans in Southern California demonstrates: 1) a lower than expected HBV prevalence (3%), 2) a continued need for vaccination, and 3) a need for screening despite a reported history of vaccination.

Use of ImPACT to diagnose minimal hepatic encephalopathy: an accurate, practical, user-friendly internet-based neuropsychological test battery.

BACKGROUND AND AIMS: An effective, user-friendly neurocognitive test to diagnose minimal hepatic encephalopathy (MHE) is needed. Immediate Post-concussion Assessment and Cognitive Testing (ImPACT) is a brief, validated, Web-based, neuropsychological test battery resulting in four composite scores [Verbal Memory (VrbM), Visual Memory, Visual Motor Speed (VMS), Reaction Time (RT)]. We compared ImPACT to traditional paper-and-pencil tests in patients at risk for MHE versus controls. METHODS: Ninety cirrhotic patients with no history of overt hepatic encephalopathy were compared with 131 controls on standard psychometric tests (SPT) [Trail Making Test-A, Trail Making Test-B, Digit Symbol Test], 4 ImPACT composite scores, and the Sickness Impact Profile (SIP). MHE+ was defined by a score 2 SD below the normative mean on at least one of the SPT. ImPACT (ImP+) scores of patients were defined as 2 SD from the control mean. RESULTS: Cirrhotic patients scored more poorly than controls on 3/4 of ImPACT scores: VrbM (78.88 vs. 71.37, p<0.001), VMS (26.47 vs. 22.68, p<0.001) and RT (0.89 vs. 1.00, p<0.01), as well as on all 3 SPT. Of the 90 cirrhotics, 16 (18%) were MHE+, who performed more poorly (p<0.001) than patients without MHE on VrbM (58.13 vs. 74.19), VMS (16.77 vs. 23.95) and RT (1.24 vs. 0.95). Of the 90 cirrhotics, 25 (27.8%) were ImP+. MHE+ and ImP+ patients had increased SIP scores versus controls (p<0.001). CONCLUSIONS: Compared to paper-and-pencil testing, ImPACT provides a brief, user-friendly, neuropsychological evaluation of MHE. ImPACT could become a new standard for MHE diagnosis.

A new highly sensitive point of care screen for spontaneous bacterial peritonitis using the leukocyte esterase method.

BACKGROUND & AIMS: Urine reagent strips measuring leukocyte esterase activity have been studied to screen spontaneous bacterial peritonitis (SBP) but are insensitive. We calibrated a strip specifically for ascitic fluid to achieve high sensitivity in this diagnosis. METHODS: Experiments were conducted on ascitic fluid from patients with cirrhosis. Samples with SBP were diluted with native acellular ascitic fluid to achieve PMN counts below, above, and close to the diagnostic threshold of 250 PMN/microl. A model of SBP was created by spiking negative ascitic fluid samples (<250 PMN/microl) with activated PMN from blood of patients with sepsis, and diluted to achieve a range of PMN. Aliquots were tested at 2, 3, 4, and 10 min with the Periscreen leukocyte esterase strip. PMN/microl was correlated to timings and color scales: white defined negative (PMN <250/microl); and shades of brown, purple, and pink defined positive. Ascitic fluid samples were obtained from 58 patients. Negative ascitic fluid was used from 32 to generate the model SBP. RESULTS: One thousand three hundred and four experiments were performed with a median PMN count of 492/microl (0-7510). After exclusion of uninterpretable colorimetric results, 1089 experiments were analyzed [PMN of 444/microl (0-7510)]. The best result was obtained at 3 min (n=299), with Se: 100%, Sp: 57.9%; NPV: 100%, PPV: 76.5%. The test was not interpretable in bloody, chylous or bilious ascitic fluid, or concurrent imipenem treatment. CONCLUSIONS: This new leukocyte esterase strip calibrated to an ascitic fluid PMN count 250/microl is a robust screening tool when the strip turns any hue of tan/brown at 3 min.

Proposal for a histological scoring and grading system for non-alcoholic fatty liver disease.

AIM/BACKGROUND: The spectrum of histopathological features in non-alcoholic fatty liver disease (NAFLD) has been well described. At least two scoring systems have been established. We propose here a system in which numerical scores are obtained using the different features. METHODS: Twenty-five cases of well-defined NAFLD were identified. Two pathologists blinded to identifiers and clinical data independently scored the liver biopsies twice for portal fibrosis (PF: 0-6), lobular inflammation and necrosis (LIN: 0-3), Mallory bodies (MB: 0-3), hepatocyte ballooning (HB: 0-3), perisinusoidal fibrosis (PSF: 0-3) and fatty change (FC: 1-4). The kappa statistic tested observer concordance. Non-parametric measures of correlation and hierarchical cluster analysis were used to elaborate a grading system. RESULTS: A broad spectrum of NAFLD was observed. Intra- and interobserver concordance was satisfactory. An activity score was created (AS: 0-12) as the sum of LIN, MB, HB and PSF, but not FC. A system for severity of NAFLD was developed: Grade 1 (PF: 0-2 and AS: 0-4), Grade 2 (PF: 3 or AS: 5-7) and Grade 3 (PF: 4-6 or AS: 8-12). Diabetes, elevated alkaline phosphatase and decreased platelets were associated with advanced grade. CONCLUSIONS: This simple, reproducible NAFLD score produces a three-tier severity grade. This numerical system may prove useful in assessing disease severity and interval changes.

Instant diagnosis of spontaneous bacterial peritonitis using leukocyte esterase reagent strips: Nephur-Test vs. MultistixSG.

BACKGROUND/AIM: Spontaneous bacterial peritonitis (SBP), defined by an ascites neutrophil count >250/mul, is a severe complication of cirrhosis and demands prompt diagnosis. Leukocyte esterase reagent strips can rapidly detect leukocytes in physiological fluids. We compared the performance of two leukocyte esterase reagent strips in the diagnosis of SBP. METHODS: Non-selected patients with cirrhosis and ascites were prospectively included in a Community Hospital. Manual ascites cytology, culture and BIOCHEMISTRY were compared with the Nephur-Test (read at 60 s: negative + 1 to + 3) and MultistixSG (read at 120 s: negative, trace, +1 to +3). Multiple investigators performed the tests with repeat readings by one nurse. RESULTS: Two hundred and forty five ascites fluid samples were obtained in 51 patients: 44% in conditions of SBP antibiotic prophylaxis, 64% in an ambulatory setting. Seventeen samples had an ascites polymorphonuclear count of > or =250/microl, associated with a positive ascites culture in seven, obtained in 12 patients (24%), 53% in an ambulatory setting. Sensitivity, specificity, and positive and negative predictive values were: Nephur-Test (88.2%, 99.6%, 93.8%, 99.1%); MultistixSG (64.7%, 99.6%, 91.7%, 97.4%). There was excellent agreement between the investigators and the nurse. CONCLUSIONS: Leukocyte esterase reagent strips may provide a rapid bedside diagnosis of SBP and thereby shorten time to appropriate management. The Nephur-Test appeared to out-perform MultistixSG. These tests might be particularly useful in ambulatory settings or whenever ascites fluid analysis is not rapidly available.

Rapid diagnosis of spontaneous bacterial peritonitis with leukocyte esterase reagent strips in a European and in an American center.

BACKGROUND: Timely diagnosis and treatment of spontaneous bacterial peritonitis (SBP) are essential to survival. The purpose of the present paper was to evaluate leukocyte esterase reagent strips (Nephur-Test and MultistixSG10) in the bedside diagnosis of SBP. METHODS: Patients with cirrhotic ascites were prospectively included in France (center 1) and in the USA (center 2). Paracenteses were performed on admission and repeated as indicated. Bedside reagent strip testing was performed on the ascitic fluid and compared to manual cell count with differential and ascitic fluid culture. In center 1, the Nephur-Test was tested in all cases, with dual testing with MultistixSG10 in a subgroup. In center 2, all cases had dual testing. Spontaneous bacterial peritonitis was defined as a polymorphonuclear ascites count > or =250/microL. RESULTS: A total of 184 samples was obtained in 76 patients. Center 1 included 151 samples from 53 patients. Seven samples had SBP, obtained in six patients. Center 2 included 33 samples from 23 patients. Six samples had SBP, obtained in five patients. The sensitivity, specificity, positive and negative predictive value of the reagent strips were as follows. Center 1/Nephur-Test: 86%, 100%, 100%, 99%; center 1/MultistixSG10: 100%, 100%, 100%, 100%; center 2/Nephur-Test: 100%, 92.5%, 75%, 100%; center 2/MultistixSG10: 83%, 96%, 83%, 96%. CONCLUSION: Leukocyte esterase reagent strips may provide a rapid bedside diagnosis of SBP.

HFE based re-evaluation of heterozygous hemochromatosis.

Homozygosity for the C282Y mutation in the HFE gene is strongly associated with hereditary hemochromatosis. More than one subject out of 10 in the general population is a heterozygote for the C282Y mutation. In this study, we address whether or not conclusions drawn from HLA-based family studies regarding the expression of heterozygous hemochromatosis are applicable to C282Y heterozygotes. The correlation between HLA-inferred and HFE genotypes and the variation of serum iron tests according to HFE genotype and other factors were studied in persons from well-characterized hemochromatosis pedigrees. Subjects were tested for both C282Y and H63D mutations. The following factors were studied: age, sex, alcohol consumption, body mass index, liver function tests, serum lipids and glucose, serum iron, transferrin saturation, and ferritin. HLA-inferred heterozygotes were C282Y heterozygotes in only 70% and compound heterozygotes (i.e., heterozygotes for both C282Y and H63D) in 20%. C282Y heterozygotes did not differ from wild type homozygotes in terms of serum iron tests. Only compound heterozygotes presented with slightly increased transferrin saturation. On the other hand, increased serum ferritin was strongly associated with overweight or lipidic or glucose abnormalities. C282Y heterozygotes selected from family studies do not have greater serum iron tests than wild type homozygotes, except for compound heterozygotes, and therefore should not require special followup. The discovery of abnormal iron tests in a C282Y heterozygote should lead to workup for other causes of iron overload.