The natural history of COVID-19 in vaccinated inflammatory bowel disease patients.

AIM: Assess the characteristics of break through COVID-19 in Inflammatory Bowel Disease (IBD) patients, despite complete vaccination. METHODS: Patients who reported a COVID-19 at least 3 weeks after complete vaccination were asked to answer an on-line anonymous questionnaire which included patient and disease characteristics, vaccination history, and the evolution of COVID-19. RESULTS: Among 3240 IBD patients who reported complete vaccination between 1st May 2021 and 30thJune 2022, 402 (12.4%) were infected by SARS Cov-2 [223 male, 216 Crohn's disease (CD), 186 Ulcerative Colitis (UC), mean (SD) age 42.3 (14.9) years, mean (SD) IBD duration 10.1 (9.7) years]. Three hundred and sixty-nine patients (91.8%) were infected once and 33 (8.2%) twice. The mean (SD) time between last vaccination and infection was 4.1 (1.6) months. Overall, 351 (87.3%) patients reported mild constitutional and/or respiratory symptoms, 34 (8.4%) were asymptomatic and only 17 patients (4.2%) required hospitalization. Of hospitalized patients, 2 UC patients died of COVID-19 pneumonia. The remaining hospitalized patients did not need high flow oxygen supply or ICU admission. CONCLUSIONS: A minority of completely vaccinated IBD patients developed COVID-19 which evolved with mild symptoms and a favorable outcome. These results reinforce the importance of vaccination especially in vulnerable populations.

Efficacy of switching from infliximab to golimumab in patients with ulcerative colitis in deep remission.

BACKGROUND-AIM: Intravenously administered biologicals are associated with a huge pressure to Infusion Units and increased cost. We aimed to assess the impact of switching infliximab to golimumab in ulcerative colitis (UC) patients in deep remission. Patients and method: In a prospective, single-centre pilot study UC patients on infliximab mono-therapy for = 2 years, whowere in deep remission, consented to switch to golimumab and were followed for 1 year with clinical assessment, serum and faecal biomarkers, work productivity, satisfaction with treatment and quality of life parameters. Endoscopic remission was assessed by colonoscopy at 1 year. Patients fulfilling the same inclusion criteria, who did not consent to switch to golimumab and continued to receive infliximab mono-therapy, for the same period, served as controls. PATIENTS AND METHODS: In a prospective, single-centre pilot study UC patients on infliximab mono-therapy for ≥ 2 years, who were in deep remission, consented to switch to golimumab and were followed for 1 year with clinical assessment, serum and faecal biomarkers, work productivity, satisfaction with treatment and quality of life parameters. Endoscopic remission was assessed by colonoscopy at 1 year. Patients fulfilling the same inclusion criteria, who did not consent to switch to golimumab and continued to receive infliximab mono-therapy, for the same period, served as controls. RESULTS: Between October 2015 and October 2017, 20 patients were recruited; however one patient stopped therapy because of pregnancy. All 19 patients who were switched to golimumab were still in clinical, biomarker and endoscopic remission at 1 year and maintained excellent quality of life without any complications. In the control group, 18 of 19 patients were also in deep remission, since only one patient had a flare which was managed with IFX dose intensification. During a median 3 years extension treatment with golimumab only 2 patients experienced a flare of colitis. CONCLUSIONS: This pilot study indicates that switching from in-fliximab to golimumab in UC patients in deep remission does not compromise treatment effectiveness or the course of disease; golimumab offers a valid alternative to intravenous infliximab infusions during the COVID-19 pandemic.

Validation of the dorsal air pouch model to predict and examine immunostimulatory responses in the gut.

AIMS: To validate the use of the air pouch system to predict and examine early immune responses induced by the presumptive probiotics Lactobacillus paracasei subsp. paracasei B112, DC205, DC215 and DC412 strains in the gut mucosa. METHODS AND RESULTS: Only the DC412 strain interacted strongly with the cells forming the air pouch lining tissue and induced early innate immune responses such as polymorphonuclear (PMN) cell recruitment, phagocytosis and tumour necrosis factor alpha (TNF-alpha) production that equal the respective responses induced by the probiotic Lactobacillus acidophilus NCFB 1748. The strains exhibiting strong immunoregulatory activity in the air pouch also interacted strongly with the gut-associated lymphoid tissue (GALT). The strain DC412 exerts its effect on the intestine through stimulation of Toll-like receptor (TLR)2/TLR4-mediated signalling events leading to secretion of a certain profile of cytokines in which gamma interferon (IFN-gamma), TNF-alpha, interleukin (IL)-6 and IL-10 are included. The probiotic Lact. acidophilus NCFB 1748 induces the same cytokine profile in addition to IL-12B, and this response is potentially mediated by the synergy of TLR2 and TLR9. CONCLUSION: The strain DC412 possesses the in vitro and in vivo characteristics of a probiotic micro-organism. SIGNIFICANCE AND IMPACT OF THE STUDY: The dorsal mouse or rat air pouch may be used as an alternative and rapid method for the initial discrimination and selection of potential probiotic Lactobacillus strains.

The dynamic relationship between antibiotic use and the incidence of vancomycin-resistant Enterococcus: time-series modelling of 7-year surveillance data in a tertiary-care hospital.

The role of antibiotics in the epidemiology of vancomycin-resistant Enterococcus (VRE) has been studied extensively, but controversies remain as to which, and to what extent, antibiotics facilitate the emergence and dissemination of VRE in hospitals. Aggregate data on the use of several antibiotic classes in terms of defined daily doses (DDD) per 100 patient-days (PD), and VRE incidence rates in terms of clinical isolates per 1000 PD, were evaluated during a 7-year period at a tertiary-care hospital. Time-series analysis (autoregressive integrated moving average (ARIMA) and transfer function models) was used to quantify the temporal effect of antibiotic use on VRE incidence and estimate effect-delays. The incidence rate of VRE observed in a specific bimester was found to be a function of its value during the preceding bimester and of prior changes in the volume of use of four antibiotic classes. In particular, an increase of one DDD/100 PD in the use of glycopeptides, fluoroquinolones, extended-spectrum cephalosporins and beta-lactam-beta-lactamase inhibitor combinations resulted, independently, in average changes of +0.024, +0.015, + 0.020 and -0.010 isolates per 1000 PD in the incidence of VRE, with average delays of 2, 4, 2 and 6 months, respectively, which explained 56% of the observed variation in VRE rates over time. Efforts to reduce VRE cross-transmission should be supplemented by targeted antibiotic control policies. The use of glycopeptides, broad-spectrum cephalosporins and fluoroquinolones in high amounts should be the targets of such policies. Penicillin-beta-lactamase inhibitor combinations might be suitable substitutes for extended-spectrum cephalosporins.

Long-term therapy with adefovir dipivoxil in hepatitis B e antigen-negative patients developing resistance to lamivudine.

BACKGROUND: The efficacy of long-term adefovir dipivoxil monotherapy or combination of adefovir and lamivudine in hepatitis B e antigen (HBe-Ag)-negative lamivudine-resistant chronic hepatitis B (CHB) patients is still under investigation. AIM: To assess the safety and efficacy of the long-term adefovir treatment alone or in combination with lamivudine in HBe-Ag-negative CHB patients who had developed breakthrough because of lamivudine-resistant mutants. METHODS: Fifty-nine patients received combination therapy, while 23 switched to adefovir alone after a 3-month course of combination therapy. RESULTS: The median follow-up after adefovir's onset was 31 (18-40) months. Baseline characteristics were similar between the two groups. At 12 and 24 months, 69% and 89% of patients receiving combination therapy and 73% and 82% of patients receiving adefovir monotherapy had serum HBV-DNA <10(4) copies/mL (P > 0.5). Normalization of alanine aminotransferase levels occurred in 81% and 79% of patients receiving combination vs. 61% and 53% receiving adefovir monotherapy at 12 and 24 months, respectively (P > 0.50). Virological breakthroughs because of adefovir-resistant mutants occurred in five patients under adefovir monotherapy and in none receiving combination therapy (P = 0.001). No one developed decompensated liver disease or hepatocellular carcinoma during follow-up. Re-introduction of lamivudine in adefovir-resistant patients achieved reduction in HBV-DNA and biochemical remission, but re-emergence of lamivudine mutants was observed in one patient after 7.5 months. CONCLUSION: In HBe-Ag-negative CHB patients with lamivudine resistance, adding adefovir to continuing lamivudine therapy maximizes anti-viral efficacy because of absence of viral resistance.

Emergence of vancomycin-resistant enterococci in a tertiary hospital in Crete, Greece: a cluster of cases and prevalence study on intestinal colonisation.

The aim of this study was to investigate the clinical and epidemiological characteristics of five consecutive cases of infection with vancomycin-resistant enterococci (VRE) and the prevalence of faecal carriage of VRE among patients admitted to a 700-bed university hospital where no VRE had been isolated previously. In a 2-month period, five consecutive patients infected with VRE were detected. Three VanB+ Enterococcus faecium isolates were obtained from three patients, while two VanA+ E. faecium isolates, one VanA+ Enterococcus faecalis isolate and one VanC1+ Enterococcus gallinarum isolate were obtained from the other two patients. Of 218 faecal specimens from all hospital wards, 41 (18.8%) were found to contain VRE. Forty-two isolates of VRE were obtained, comprising one (2%) E. faecalis, 11 (27%) E. faecium, 24 (57%) E. gallinarum and six (14%) Enterococcus casseliflavus/flavescens. Four isolates carried the vanA gene, eight carried vanB, 24 carried vanC1, and six carried vanC2/C3. Use of glycopeptides, the presence of central venous catheters and renal dialysis all correlated with VRE colonisation. The prevalence rates were among the highest reported in the literature.

A prospective randomized controlled trial of intravenous ciprofloxacin as an adjunct to corticosteroids in acute, severe ulcerative colitis.

BACKGROUND: The role of antibiotics in the treatment of ulcerative colitis is controversial. This study aims at assessing the therapeutic role of ciprofloxacin as an adjunct to corticosteroids in acute severe ulcerative colitis. METHODS: In this prospective, randomized, double-blind, placebo-controlled trial, 55 consecutive patients fulfilling the criteria of Truelove and Witts for severe ulcerative colitis were randomized on admission to the hospital to receive intravenously ciprofloxacin (400 mg b.i.d.) (n = 29) or placebo (n = 27). All patients received parenteral nutrition, intravenous hydrocortisone (100 mg q.i.d.) and hydrocortisone enemas (100 mg b.i.d.). Patients were assessed after 10 days of continuous treatment, or at any time a severe complication occurred. RESULTS: At study entry, there were no significant differences between treatment groups in any patient or disease-related parameter. Twenty-three of 29 patients (79.3%) treated with ciprofloxacin and 20 of 26 patients (77%) treated with placebo showed substantial improvement and were given oral steroids (P > 0.1). Six patients in each group did not improve (n = 10) or developed complications (n = 2). Nine of these 12 patients underwent emergency colectomy; three patients consented to receive intravenous cyclosporin but did not achieve remission of colitis and they underwent elective colectomy. There were no perioperative or late deaths. CONCLUSIONS: A short course of intravenous ciprofloxacin does not seem to augment the effect of corticosteroids for patients with acute, severe ulcerative colitis.

Antimicrobial resistance and serotype distribution of Streptococcus pneumoniae isolates from Crete, Greece.

Susceptibility to 14 antibiotics was determined for 125 clinical isolates of Streptococcus pneumoniae collected over a 3-year period in Crete, Greece. Twenty-three isolates (18.4%) showed intermediate resistance and 15 (12%) high-level resistance to penicillin. Erythromycin, chloramphenicol, tetracycline, trimethoprim-sulphamethoxazole and sparfloxacin resistance rates were 16.8, 10.4, 19.2, 24.8 and 9.6%, respectively. Multiple resistance was observed in 22 strains. Vancomycin and levofloxacin were the most active agents tested. The most prevalent serotype among penicillin-susceptible pneumococci was 14, followed by 9, 7 and 1, while among penicillin-intermediate or -resistant strains serotype 23 was predominant followed by 19 and 9. These results show that as well as a high level of penicillin resistance in this region, some strains are also resistant to other antibiotics and may show multi-drug resistance.

Antimicrobial susceptibilities and beta-lactamase production of Shigella isolates in Crete, Greece, during the period 1991-1995.

The susceptibility to 11 antibiotics was determined for 52 strains of Shigella isolated from patients with diarrheal disease in Crete, Greece, during the period 1991-1995. Forty-six percent of the isolates were resistant to ampicillin, 48% to tetracycline, 44.2% to chloramphenicol, and 28.8% to cotrimoxazole. Shigella flexneri was more resistant than S. sonnei to ampicillin (82 vs 4.3%), to tetracycline (82 vs 8.7%) and to cotrimoxazole (42.8 vs 13%). Overall, 82% of all S. flexneri isolates were resistant to the three or four antimicrobial agents tested. The beta-lactamases produced by shigellae were identified by isoelectric focusing and were found to be OXA-1, TEM-1, and a low-level beta-lactamase with a pI>8. The results from the present study, which is the first carried out in Crete, emphasize the need for continuous surveillance of resistance and control of antibiotic usage.

Gram-negative bacteremia in non-neutropenic patients: a 3-year review.

The causative organisms, clinical manifestations, factors influencing prognosis, and other epidemiological characteristics of 81 episodes of bacteremia due to gram-negative organisms, in non-neutropenic patients, were studied retrospectively during a 3-year period (1992-1994) at the Department of Internal Medicine of the University Hospital of Heraklion, Crete, Greece. The gram-negative bacteremia incidence was 2% and the overall mortality 12%. All 81 patients had fever; Escherichia coli was the most frequent organism isolated (from 47 patients--58%) and was associated with shock (9/47), disseminated intravascular coagulation (DIC) (8/47), anuria (5/47), adult respiratory distress syndrome (ARDS) (3/47), and pneumonia (1/47). Other less frequent gram-negative microorganisms were Klebsiella spp. (ten patients; 12%), Pseudomonas spp. (7; 7%), Salmonella spp. (5; 6%), Enterobacter spp. (5; 6%), Proteus spp. (3; 3.4%), Stenotrophomonas spp. (3; 3.4%), and Acinetobacter spp. (1; 1.2%). ARDS. shock, DIC, anuria, presence of central venous catheter, urinary catheter, unknown origin of infection and inappropriate treatment were significantly associated with a higher death rate. Early initiation of appropriate therapy was the most important intervention that favorably affected the outcome of gram-negative bacteremias in this patient population.

Bacterial pathogens associated with diarrhoea on the island of Crete.

Stool specimens from 3,600 diarrhoeal patients from the island of Crete, Greece, were examined for bacterial pathogens, during a three-year period (1992-1994). One or more pathogens were identified in 826 patients (22.9%), more often from children. Salmonella spp. were the most frequently isolated organisms in 13.6% of the patients, followed by Campylobacter in 4.7%, and enteropathogenic Escherichia coli (EPEC) in 3.9%. Yersinia enterocolitica was found in 0.7%, Shigella spp. in 0.7% and Aeromonas hydrophila in 0.05%. Vibrio spp. and enterohaemorragic E. coli were not identified in the stools tested. Resistance to ampicillin was observed in 36% of the Salmonella, 62% of the Shigella, and 27% of the EPEC isolates. Cotrimoxazole resistance was observed in 42% of the Shigella and 12% of the EPEC isolates, while tetracycline and the quinolones were inactive against almost half and erythromycin against 20% of the Campylobacter isolates. This is the first study investigating bacterial pathogens associated with diarrhoea on the island of Crete.