Predictors of Thiopurine Treatment Failure in Biologic-Naïve Ulcerative Colitis Patients.

INTRODUCTION: Thiopurines (azathioprine and 6-mercaptopurine) have been used in the management of UC patients for over three decades. Nearly half of patients with UC treated with thiopurines fail to achieve remission or lose remission during treatment. Factors associated with thiopurine failure are poorly understood. The primary aim of our study was to investigate patient-related factors which are associated with thiopurine failure. METHODS: TNF-alpha antagonist-naïve patients with histological diagnosis of UC, receiving thiopurine therapy, with follow-up data from 1 to 3 years were included in the study. Data regarding demographics, laboratory results, and disease characteristics were collected. The primary endpoint was failure of thiopurine therapy, defined as treatment with steroids, therapeutic escalation to TNF-alpha antagonist therapy, or need for surgery. RESULTS: Of the 563 patients identified using ICD-9 codes, 78 TNF-alpha antagonist-naïve patients with a histological diagnosis of UC, receiving thiopurine treatment, were identified. Over the three-year follow-up period, 38 patients failed thiopurine treatment. On adjusted Cox regression, BMI < 25 kg/m(2) (HR 3, 95 % CI 1.55-5.83; p value = 0.001) was significantly associated with thiopurine failure. Furthermore, although not statistically significant, there was a strong trend toward thiopurine failure among patients with serum albumin level < 4 g/dL (HR 1.98, 95 % CI 0.97-4; p value = 0.06), non-smoking status (HR 2.2, 95 % CI 0.96-5.06; p value = 0.06), and higher degree of colon inflammation (HR 1.49, 95 % CI 0.96-2.32; p value = 0.08). DISCUSSION: Our results show that low body mass index is associated with increased risk of failure of thiopurine treatment. Furthermore, there was a strong trend toward thiopurine failure among patients with low serum albumin level (<4gm/dL). These factors should be considered as markers of non-response to thiopurine monotherapy for patients with moderately severe ulcerative colitis.

Persistent Reactive Thrombocytosis May Increase the Risk of Coronary Artery Disease Among Inflammatory Bowel Disease Patients.

BACKGROUND: IBD patients are at increased risk of coronary artery disease in the absence of traditional risk factors. However, the disease-related risk factors remain poorly understood although increased inflammation seems to increase cardiovascular disease risk in IBD. Thrombocytes are involved in the pathogenesis of coronary artery disease, and a subset of IBD patients have reactive thrombocytosis. AIM: The aim of our study was to investigate the effect of persistent reactive thrombocytosis on the development of coronary artery disease in IBD. METHODS: We evaluated a retrospective cohort of 2525 IBD patients who were evaluated at the Henry Ford hospital from 2000 to 2004. We performed a case-control study comparing patients with persistent thrombocytosis and patients without persistent thrombocytosis. Cases (n = 36) and controls (n = 72) were matched for age and gender. Coronary artery disease incidence was compared between the two groups. RESULTS: Cases (n = 36) and controls (n = 72) were matched for age and gender. Cases and controls were similar in age at onset of IBD (41.5 vs. 35.5, p value 0.11) and smoking status (33.3 vs. 27.8%, p value 0.66). Persistent thrombocytosis was less common among Caucasian patients (44.44 vs. 62.5%, p value 0.09) and more common in patients who had exposure to steroids during the study follow-up period. Coronary artery disease occurred in 13 (36.1%) patients with persistent thrombocytosis compared to only seven (9.7%) patients in the control group. CONCLUSIONS: Persistent reactive thrombocytosis among IBD patients is associated with increased risk of coronary artery disease. Further studies should characterize the clinical and molecular associations of this phenomenon and determine appropriate therapeutic measures.

Gatifloxacin versus ofloxacin for the treatment of uncomplicated enteric fever in Nepal: an open-label, randomized, controlled trial.

BACKGROUND: Fluoroquinolones are the most commonly used group of antimicrobials for the treatment of enteric fever, but no direct comparison between two fluoroquinolones has been performed in a large randomised trial. An open-label randomized trial was conducted to investigate whether gatifloxacin is more effective than ofloxacin in the treatment of uncomplicated enteric fever caused by nalidixic acid-resistant Salmonella enterica serovars Typhi and Paratyphi A. METHODOLOGY AND PRINCIPAL FINDINGS: Adults and children clinically diagnosed with uncomplicated enteric fever were enrolled in the study to receive gatifloxacin (10 mg/kg/day) in a single dose or ofloxacin (20 mg/kg/day) in two divided doses for 7 days. Patients were followed for six months. The primary outcome was treatment failure in patients infected with nalidixic acid resistant isolates. 627 patients with a median age of 17 (IQR 9-23) years were randomised. Of the 218 patients with culture confirmed enteric fever, 170 patients were infected with nalidixic acid-resistant isolates. In the ofloxacin group, 6 out of 83 patients had treatment failure compared to 5 out of 87 in the gatifloxacin group (hazard ratio [HR] of time to failure 0.81, 95% CI 0.25 to 2.65, p = 0.73). The median time to fever clearance was 4.70 days (IQR 2.98-5.90) in the ofloxacin group versus 3.31 days (IQR 2.29-4.75) in the gatifloxacin group (HR = 1.59, 95% CI 1.16 to 2.18, p = 0.004). The results in all blood culture-confirmed patients and all randomized patients were comparable. CONCLUSION: Gatifloxacin was not superior to ofloxacin in preventing failure, but use of gatifloxacin did result in more prompt fever clearance time compared to ofloxacin. TRIAL REGISTRATION: ISRCTN 63006567 (www.controlled-trials.com).

Risk factors for and epidemiology of community-onset vancomycin-resistant Enterococcus faecalis in southeast Michigan.

BACKGROUND: Given the known link between vancomycin-resistant Enterococcus faecalis (VREF) and vancomycin-resistant Staphylococcus aureus (VRSA), the recent increase in prevalence of VREF in southeast Michigan has raised concerns about the presence of a large "community" reservoir of VREF. Efforts to control its spread face some important challenges. METHODS: Patients with clinical isolates of community-onset (CO) VREF (cases) were compared with matched uninfected controls (study 1) and patients with hospital-onset (HO) VREF (study 2). Here, CO was defined as a hospital stay of ≤2 days before VRE isolation. RESULTS: Independent predictors for the isolation of CO-VREF compared with uninfected controls were nonhome residence; chronic skin ulcers; previous invasive procedures/surgery; exposure to cephalosporin, penicillin, and/or vancomycin; immunosuppressive status; and the presence of indwelling devices. Independent predictors for isolation of CO-VREF compared with HO-VREF included no stay in an intensive care unit in the previous 3 months and recent hospitalization. VREF isolation from wounds and aminoglycoside exposure were inversely associated with isolation of CO-VREF. CONCLUSIONS: Health care-related exposures and antimicrobial exposures are risk factors for the isolation of CO-VREF. Regional infection control practices are imperative in controlling CO-VREF, in addition to the emergence and spread of VRSA.

Aetiologies of central nervous system infections in adults in Kathmandu, Nepal: a prospective hospital-based study.

We conducted a prospective hospital based study from February 2009-April 2011 to identify the possible pathogens of central nervous system (CNS) infections in adults admitted to a tertiary referral hospital (Patan Hospital) in Kathmandu, Nepal. The pathogens of CNS infections were confirmed in cerebrospinal fluid (CSF) using molecular diagnostics, culture (bacteria) and serology. 87 patients were recruited for the study and the etiological diagnosis was established in 38% (n = 33). The bacterial pathogens identified were Neisseria meningitidis (n = 6); Streptococcus pneumoniae (n = 5) and Staphylococcus aureus (n = 2) in 13/87(14%). Enteroviruses were found in 12/87 (13%); Herpes Simplex virus (HSV) in 2/87(2%). IgM against Japanese encephalitis virus (JEV) was detected in the CSF of 11/73 (15%) tested samples. This is the first prospective molecular and serology based CSF analysis in adults with CNS infections in Kathmandu, Nepal. JEV and enteroviruses were the most commonly detected pathogens in this setting.

Highly resistant Salmonella enterica serovar Typhi with a novel gyrA mutation raises questions about the long-term efficacy of older fluoroquinolones for treating typhoid fever.

As a consequence of multidrug resistance, clinicians are highly dependent on fluoroquinolones for treating the serious systemic infection typhoid fever. While reduced susceptibility to fluoroquinolones, which lessens clinical efficacy, is becoming ubiquitous, comprehensive resistance is exceptional. Here we report ofloxacin treatment failure in typhoidal patient infected with a novel, highly fluoroquinolone-resistant isolate of Salmonella enterica serovar Typhi. The isolation of this organism has serious implications for the long-term efficacy of ciprofloxacin and ofloxacin for typhoid treatment.