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Purpose: Even with nearly 100% compliance with prophylactic antibiotic protocols, many surgical patients (> 5%) develop surgical site infections, some caused by pathogens transmitted from the anesthesia workspace (e.g., anesthesia machine), including multidrug-resistant Staphylococcus aureus. Reducing contamination of the anesthesia workspace substantively reduces the risk of surgical site infections. We estimated the percentage of hospital patients at risk for health care-associated infections who may benefit from the application of basic preventive measures under the control of anesthesia practitioners (e.g., their hand hygiene)., Methods: We conducted a retrospective cohort study which included every patient admitted to the University of Miami Health System from April 2021 through March 2022 for hospitalization, surgery, emergency department visits, or outpatient visits. Lists were created for the start date and times of every parenteral antibiotic administered and every anesthetic., Results: Among 28,213 patient encounters including parenteral antibiotic(s), more than half (64.3%) also included an anesthetic (99% confidence interval, 62.2 to 66.6). The hypothesis that most antibiotics were administered during encounters when a patient underwent an anesthetic was accepted (P < 0.001). This observation may seem counterintuitive because parenteral antibiotics were administered for fewer than half of the 53,235 anesthetics (34.2%). The result was a consequence of most anesthetics (63.5%) at the health system being conducted in nonoperating room locations, and only 7.2% of such patients received a parenteral antibiotic., Conclusions: Because approximately two-thirds of patients who receive an intravenous antibiotic also undergo an anesthetic, greater use of effective infection control measures in the anesthesia operating room workspace has the potential to substantively reduce overall rates of hospital infections., (© 2023. Canadian Anesthesiologists' Society.)

Contemporary data on infections after intensive chemotherapy for acute myeloid leukemia (AML) are scarce. Cladribine, high-dose cytarabine, G-CSF, and dose-escalated mitoxantrone ("CLAG-M") may result in higher remission rates than standard-dose cytarabine plus anthracycline ("7 + 3") but may result in more infections. We compared moderate to severe infections occurring up to 90 days after the first induction cycle for AML or other high-grade myeloid neoplasms in patients receiving CLAG-M for newly diagnosed (n = 196) or relapsed/refractory disease (n = 131) or 7 + 3 for newly diagnosed disease (n = 115). For newly diagnosed disease, microbiologically documented infections were more frequent after CLAG-M compared to 7 + 3 (adjusted rate ratio, 1.65 [95% CI, 1.06-2.58]; P = 0.03), with a cumulative incidence of 27.8% and 16.5% by day 90, respectively. Patients receiving CLAG-M for relapsed/refractory disease had the highest cumulative incidence of 50.7%. Bacterial bloodstream infections were the most frequent followed by respiratory tract infections. Among 29 patients (7%) who died, infection was a primary or contributing cause of death in 59%. These data indicate that infections continue to cause substantial morbidity in patients treated for AML, especially those treated for relapsed/refractory disease, and are more common with newer, more myelosuppressive regimens such as CLAG-M. Improved strategies for infection prevention are needed., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Urinary tract infections account for one of the most bacterial infectious diseases worldwide., Objectives: The primary aim of this pilot project was to identify the relative percentage of antibiotic use in comparison to all patients in a university medical center for the better establishment of antibiotic stewardship (ABS) programs., Material and Methods: This is an epidemiological pilot project. In the time period of three months it was evaluated which relative percentage of the patients was treated with antibiotics for bacterial urinary tract infection in comparison to all patients., Results: In summary, about 40% of all urological patients received an antibiotic treatment against urinary tract infections or as perioperative prophylaxis against bacterial infection in the operating room (OR). The antibiotic use at the urological ward is highest in comparison to ambulance or OR., Conclusion: Infectious diseases, especially bacterial infections, account for a significant part of urology. This knowledge is essential to establish ABS programs and to tackle the progression of antibiotic resistance. Detailed studies are necessary to understand antibiotic prescription practice in urology to develop targeted ABS interventions., (© 2022. The Author(s).)

Background: Genitourinary tract infections, mycotic as well as bacterial, as defined by clinical symptoms, are one of the common adverse effects associated with the use of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in type 2 diabetes mellitus (T2DM) patients in clinical trials. However, Indian data in terms of the prevalence of culture-proven bacterial type of urinary tract infection (UTI), and the causative organism is limited., Objective: This study aimed to determine the prevalence and causative agents of bacterial UTI among patients with T2DM on SGLT2i., Methodology: This was a prospective longitudinal study involving all patients with T2DM who were prescribed with SGLT2i, uncontrolled on other oral anti-diabetic medications, from June 2019 to February 2020. Prevalence of bacterial UTI was evaluated at baseline and 12 weeks after initiation of SGLT2i., Results: A total of 80 patients were started on SGLT2i. One female patient on canagliflozin had significant asymptomatic bacteriuria and the causative agent was Acinetobacter baumannii . One male patient on dapagliflozin had symptomatic UTI with negative urine culture study. Four patients developed genital mycotic infection., Conclusion: In this real-world study, SGLT2i as a class, was well tolerated with favorable safety profile, and risk of developing significant bacteriuria and/or symptomatic UTI was minimal., Competing Interests: All authors certified fulfillment of ICMJE authorship criteria., (© 2022 Journal of the ASEAN Federation of Endocrine Societies.)

Tocilizumab decreases inflammatory response in the cytokine storm which is one of the mechanisms behind the development of ARDS in COVID-19 patients. The objective of our study was to determine response of tocilizumab in patients suffering from COVID-19 by analyzing clinical parameters and inflammatory markers. A single-arm observational retrospective study was conducted from March 15, 2020 to March 15, 2021. Clinical outcomes in terms of mortality, weaning from mechanical ventilator, improvement in laboratory parameters including inflammatory cytokines, and length of hospital stay were documented. Reduction in values of inflammatory markers, and patients discharged home in stable condition were defined as an improvement after tocilizumab administration. A total of 514 patients received tocilizumab, majority of whom were critically sick 333 (64.8%). Out of the total sample 363 (70.6%) patients were discharged home in stable condition. Overall mean length of stay was 11.50 ± 8.4 days. There was significant difference in length of stay of patients who required invasive mechanical ventilation as compared to those who were kept only on supplemental oxygen (p < 0.05). Patients who were discharged home showed significant improvement in inflammatory markers and neutrophil to lymphocyte ratio as compared to those who expired (p < 0.05). A total of 21 (4.1%) patients had positive blood culture while 57 (11.1%) had positive culture of tracheal aspirate. Hence, tocilizumab is found to be a reasonable therapeutic option for worsening COVID-19 pneumonia by decreasing the need for mechanical ventilation. However, it is associated with adverse events including bacterial and fungal infections., (Copyright © 2021. Published by Elsevier B.V.)

Complications of cirrhosis and portal hypertension (PH) can be reduced by statin therapy. The common loss-of-function variant p.V174A in the solute carrier organic anion transporter gene 1B1 (SLCO1B1) gene encoding the organic anion transporting polypeptide 1B1 results in decreased hepatic uptake of statins. Our specific aim was to assess the impact of this variant in patients with cirrhosis and statin treatment while controlling for the stage of cirrhosis and other potential confounders with propensity score matching (PSM), availing of a large cohort of genotyped study patients. In total, from 1,088 patients with cirrhosis in two German academic medical centers, PSM yielded 154 patients taking statins and 154 matched controls. The effect on PH was assessed by the liver stiffness-spleen size-to-platelet score (LSPS), and complications of cirrhosis were retrospectively recorded applying consensus criteria. As hypothesized, patients on statin treatment presented less frequently with signs of PH: Esophageal varices (41% vs. 62%; P < 0.001) were less common, and LSPS (4.8 ± 11.5 vs. 5.6 ± 6.4; P = 0.01) was reduced. Correspondingly, decompensation events were also reduced in patients on statins (odds ratio [OR] = 0.54, 95% confidence interval [CI] 0.32-0.90; P = 0.02). When the variant in SLCO1B1 was present in patients on statins, esophageal varices (OR = 2.68, 95% CI 1.24-5.81; P = 0.01) and bacterial infections (OR = 2.50, 95% CI 1.14-5.47; P = 0.02) were more common as compared with wild type carriers on statins. Conclusion: In this cohort, signs and complications of PH were reduced in patients with cirrhosis treated with statins. Notably, this effect was diminished by the common loss-of-function variant in SLCO1B1. Further prospective studies in independent cohorts are warranted to confirm these genotype-specific observations., (© 2021 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of the American Association for the Study of Liver Diseases.)

We describe the opportunistic infections occurring in 362 patients with lymphoproliferative disorders treated with ibrutinib and idelalisib in clinical practice. Overall, 108 of 362 patients (29·8%) developed infections, for a total of 152 events. Clinically defined infections (CDI) were 49·3% (75/152) and microbiologically defined infections (MDI) were 50·7% (77/152). Among 250 patients treated with ibrutinib, 28·8% (72/250) experienced one or more infections, for a total of 104 episodes. MDI were 49% (51/104). Bacterial infections were 66·7% (34/51), viral 19·6% (10/51) and invasive fungal diseases (IFD) 13·7% (7/51). Among the 112 patients treated with idelalisib, 32·1% (36/112) experienced one or more infections, for a total of 48 episodes. MDI were 54·2% (26/48). Bacterial infections were 34·6% (9/26), viral 61·5% (16/26) and IFD 3·8% (1/26). With ibrutinib, the rate of bacterial infections was significantly higher compared to idelalisib (66·7% vs. 34·6%; P = 0·007), while viral infections were most frequent in idelalisib (61·5% vs. 19·6%; P < 0·001). Although a higher rate of IFD was observed in patients treated with ibrutinib, the difference was not statistically significant (13·7% vs. 3·8% respectively; P = 0·18). Bacteria are the most frequent infections with ibrutinib, while viruses are most frequently involved with idelalisib., (© 2020 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Bacterial infection caused cell pyroptosis and gingival inflammation contributes to periodontitis progression, and lipopolysaccharide (LPS) is the main infectious agent of gram-negative bacteria, which is reported to be closely associated with gingival inflammation and periodontitis. In this study, the primary human periodontal ligament cells (PDLCs) were isolated, cultured, and exposed to LPS treatment, and the results suggested that LPS suppressed cell viability and promoted pro-inflammatory cytokines' (IL-1β, IL-18, IL-6, and TNF-α) generation and secretion in the PDLCs and its supernatants in a time- and concentration-dependent manner. Also, we noticed that LPS upregulated NLRP3, Gasdermin D, and cleaved caspase-1 to trigger pyroptotic cell death in the PDLCs. Further experiments identified that glycogen synthase kinase-3β (GSK-3β) was upregulated by LPS treatment, and inhibition of GSK-3β by its inhibitor (GSKI) or GSK-3β downregulation vectors was effective to restore normal cellular functions in LPS-treated PDLCs. Mechanistically, blockage of GSK-3β restrained NLRP3-meidated cell pyroptosis and inflammation, resulting in the recovery of cell viability and inhibition of cell death in PDLCs treated with LPS, which further ameliorated periodontitis progression. Finally, we collected the serum from periodontitis patients and healthy volunteers, and the clinical data supported that those pro-inflammatory cytokines were also upregulated in patients' serum but not in the healthy participants. Taken together, we concluded that targeting the GSK-3β/NLRP3 pathway mediated cell pyroptosis was effective to attenuate LPS-induced cell death and inflammation in PDLCs, and this study firstly investigated this issue, which broadened our knowledge in this field.

Background: Dupilumab is an effective treatment for moderate to severe atopic dermatitis (AD) with limited safety data in clinical practice., Objective: To assess the 6-month risk of conjunctivitis and serious infections in patients with AD who initiated dupilumab., Methods: In a cohort study using US claims data, we compared the risk of conjunctivitis and serious infections in patients with AD who initiated either dupilumab, methotrexate (MTX), cyclosporine, or mycophenolate. Relative risks (RRs) were computed after 1:1 propensity score matching., Results: We identified 1775 dupilumab, 1034 MTX, 186 cyclosporine, and 257 mycophenolate users. The 6-month risk for any conjunctivitis was 6.5% for dupilumab, 3.3% for MTX, 4.8% for cyclosporine, and 1.2% for mycophenolate initiators. After PS matching, the RR of any conjunctivitis was increased in dupilumab users versus MTX (RR, 2.45; 95% confidence interval [CI], 1.47-4.08), versus cyclosporine (RR, 1.56; 95% CI, 0.69-3.50), and versus mycophenolate (RR, 7.00; 95% CI, 2.12-23.2). The risk of serious infection was 0.6% in dupilumab and 1.0% in MTX initiators (RR, 0.90; 95% CI, 0.37-2.20)., Limitations: Analyses were based on few events, and differential surveillance is a concern., Conclusions: Although dupilumab shows a low risk of serious infections, it is associated with a clinically meaningful increase in conjunctivitis that needs to be managed in practice., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

There is evidence that intake of proton pump inhibitors (PPI) increases the risk for spontaneous bacterial peritonitis (SBP) in patients with liver cirrhosis. However, data regarding the impact of PPI intake on occurrence of infections other than SBP are still lacking.We hypothesized that PPI use is associated with a higher rate of infections other than SBP in patients with liver cirrhosis.The current case-control study sample included patients with liver cirrhosis from the Disease Analyzer database (IQVIA), which compiles data such as risk factors, drug prescriptions and diagnoses obtained from general practitioners and specialists in Germany. In total, 2,823 patients with infections were matched with 2,823 patients without infections by propensity scores. For quantification of PPI use the prescribed quantity of PPI during the past 12 months before index date was analyzed.Frequency of PPI users was significantly higher in patients with infections than in patients without infections (47.9% vs 37.9%). In regression analysis, PPI use was significantly associated with the occurrence of infections overall (OR 1.55, 95% CI 1.39-1.72, P < .001), and associated with the occurrence of lower respiratory tract infections, urinary tract infections and infectious gastroenteritis. There was no association between PPI use and skin infections. Pantoprazole and omeprazole were the most frequently prescribed PPIs and were both independently associated with the occurrence of infections.PPI use may be associated with infections other than SBP in patients with liver cirrhosis. Prescription of PPI should be limited to patients with a clear indication.

An estimated 1 million people in the United States have functional or anatomic asplenia or hyposplenia. Infectious complications due to encapsulated organisms such as Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae can lead to fulminant sepsis and death, particularly in young children, in the period shortly after splenectomy, and in immunocompromised patients. Patients with asplenia are also at risk for less common infections due to Capnocytophaga, Babesia, and malaria. Antibiotic prophylaxis, vaccines, and patient and family education are the mainstays of prevention in these at-risk patients. Recommendations for antibiotic prophylaxis typically target high-risk periods, such as 1 to 3 years after splenectomy, children ≤5 years of age, or patients with concomitant immunocompromise. However, the risk for sepsis is lifelong, with infections occurring as late as 40 years after splenectomy. Currently available vaccines recommended for patients with asplenia include pneumococcal vaccines (13-valent pneumococcal conjugate vaccine followed by the 23-valent pneumococcal polysaccharide vaccine), meningococcal vaccines (meningococcal conjugate vaccines for serogroups A, C, Y and W-135 and serogroup B meningococcal vaccines), H. influenzae type b vaccines, and inactivated influenza vaccines. Ongoing booster doses are also recommended for pneumococcal and meningococcal vaccines to maintain protection. Despite the availability of prevention tools, adherence is often a challenge. Dedicated teams or clinics focused on patient education and monitoring have demonstrated substantial improvements in vaccine coverage rates for individuals with asplenia and reduced risk of infection. Future efforts to monitor the quality of care in patients with asplenia may be important to bridge the know-do gap in this high-risk population., Competing Interests: Conflict-of-interest disclosure: The author declares no competing financial interests., (© 2020 by The American Society of Hematology.)

Our aim was to compare the efficacy and safety of two recently developed biosimilars of pegfilgrastim, a pegylated form of the recombinant human granulocyte-colony stimulating factor (G-CSF) analog filgrastim with those of the reference pegfilgrastim. We retrospectively analyzed data from patients diagnosed with diffuse large B-cell lymphoma (DLBCL) who were treated with first-line R-CHOP chemotherapy and received pegylated G-CSF for primary prophylaxis. The following pegylated G-CSFs were analyzed in this study: reference pegfilgrastim (Neulasta ® ) and two of its biosimilars (tripegfilgrastim; Dulastin ® and pegteograstim; Neulapeg ® ). In total, 296 patients were enrolled. The number of patients with at least one episode of neutropenia during R-CHOP chemotherapy was the lowest in the reference cohort (pegfilgrastim: 127 of 193 patients, 65.8%; tripegfilgrastim: 64 of 69 patients, 92.8%; pegteograstim: 28 of 34 patients, 82.4%, P < .001). The number of patients with at least one episode of febrile neutropenia was also lowest in the reference cohort (pegfilgrastim: 67 of 193 patients, 34.7%; tripegfilgrastim: 38 of 69 patients, 55.1%; pegteograstim: 16 of 34 patients, 47.1%, P = .009). There were no differences in the duration of neutropenia and febrile neutropenia or treatment outcomes (rate of complete response or relapse and survival). There were no reports of grade 3 or higher adverse events requiring discontinuation of prophylactic pegylated G-CSF in any group. The safety of the pegfilgrastim biosimilars for prophylactic purposes was comparable to that of the reference pegfilgrastim; however, in terms of their efficacy, the incidence of neutropenia and febrile neutropenia tended to be higher than that when using pegfilgrastim. The clinical relevance of these results in the biosimilar cohorts should be explored., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

The monocationic quaternary surfactant DOTAP has been used for the delivery of nucleic acids and peptides into mammalian cells. This study tested the applicability of DOTAP for the enhancement of adhesion and invasion frequencies of Yersinia (Y.) similis to enable the analysis of the effects of low-pathogenic bacteria on intestinal epithelial cells. Incubation of Y. similis with DOTAP ahead of infection of C2BBe1 intestinal epithelial cells increased invasion and adhesion frequency four- and five-fold, respectively, in plating assays. Proteomic approaches confirmed the increased bacterial load on infected cells: analysis of protein extracts by two-dimensional difference gel electrophoresis (2D-DIGE) revealed higher amounts of bacterial proteins present in the cells infected with DOTAP-treated bacteria. MALDI-TOF mass spectrometry of selected spots from gel-separated protein extracts confirmed the presence of both bacterial and human cell proteins in the samples. Label-free quantitative proteomics analysis identified 1170 human cell proteins and 699 bacterial proteins. Three times more bacterial proteins (279 vs. 93) were detected in C2BBe1 cells infected with DOTAP-treated bacteria compared to infections with untreated bacteria. Infections with DOTAP-treated Y. similis led to a significant upregulation of the stress-inducible ubiquitin-conjugating enzyme UBE2M in C2BBe1 cells. This points towards a stronger impact of the stress and infection responsive transcription factor AP-1 by enhanced bacterial load. DOTAP-treatment of uninfected C2BBe1 cells led to a significant downregulation of the transmembrane trafficking protein TMED10. The application of DOTAP could be helpful for investigating the impact of otherwise low adherent or invasive bacteria on cultivated mammalian cells without utilisation of genetic modifications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Proton pump inhibitors, a major progress in gastro-enterology, are globally among the most widely prescribed drugs. But, due to their strong gastric acid inhibition, they can be responsible for side effects, particularly in cancer patients. They are involved in renal function impairment, bone fractures, digestive bacterial overgrowth, particularlyclostridium difficile infections, anemia and hypomagnesemia. Long term use can increase the risks of gastric, pancreatic and liver cancers. They decrease absorption of weak bases drugs, particularly tyrosine kinase inhibitors and capecitabine and are responsible for a poorer prognosis if taken concomitantly with erlotinib, gefitinib and pazopanib. Modification of cyclin dependent kinases is also possible as well as decrease of efficacy of immune check point inhibitors (microbiome modifications). Absoption and efficacy of capecitabine seem also poorer with negative prognosis effect on treatment of gastric and colon cancer. Their long term use, particularly in cancer patients, should probably be avoided., (Copyright © 2020 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background: The combined use of interleukin-1β and tumor necrosis factor-α blockers in the peritransplant period has improved outcomes of total pancreatectomy with islet autotransplantation (TPIAT). However, these drugs may suppress the immune system, resulting in severe infection., Methods: We retrospectively investigated the impact of microbial-contaminated islet product on posttransplant complications and metabolic outcomes of TPIAT patients receiving the IL-1β and TNF-blockade treatment at our center., Results: Among 108 TPIAT patients, 37 patients (34%) received contaminated products. Preoperative stent treatment and fibrosis score were independent risk factors for the contamination. There were no significant differences between the contaminated and noncontaminated product groups in posttransplant infectious complication rate, length of hospitalization, or readmission rate. However, islet equivalents (P < .0001) and insulin independence rate (P = .036) at 6 months were significantly lower for patients receiving contaminated product., Conclusions: These results suggest that combined anti-inflammatory drug use is safe and well tolerated in TPIAT patients who receive contaminated islet product and does not increase the rate of infectious complications; however, contaminated islet product is associated with poor metabolic outcomes., (© 2020 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: The treatment landscape for multiple myeloma (MM) has progressed significantly, and over the past decade, bortezomib-based induction therapy has been a standard of care. However, the practice of antibacterial prophylaxis during induction therapy has been diverse. The aim of our study is to evaluate the proportion of patients with febrile episodes and bacteremia among patients with MM, during the first 12 weeks of bortezomib-based induction therapy, without routine fluoroquinolone prophylaxis, but with routine Pneumocystis Carinii prophylaxis (mostly with trimethoprim-sulfamethoxazole), in a region with high fluoroquinolone resistance rate. Of note, these patients have direct access to health care facilities and timely supportive care., Patients and Methods: We evaluated newly diagnosed MM patients from 2014 to 2018 receiving bortezomib-based induction therapy for the proportion of patients who had febrile episodes and bacteremia in the first 12 weeks of bortezomib-based induction therapy. We also evaluated if there were factors associated with increased febrile episodes including age, absolute neutrophil count, creatinine clearance, M-band level at diagnosis, nadir platelet count, International Staging System, and Revised International Staging System., Results: Of the 108 evaluable patients, there were a total of 25 (23.1%) patients who had febrile episodes, and 1 (0.9%) patient who had bacteremia during the first 12 weeks of bortezomib-based induction therapy. All patients recovered well. No deaths were seen. Febrile episodes were associated with lower absolute neutrophil count (P = .036), renal impairment (P = .013), and ISS stage (P = .026)., Conclusion: The proportion of patients with significant bacterial infection during the first 12 weeks of bortezomib-based induction therapy without routine fluoroquinolone prophylaxis, but with routine Pneumocystis Carinii prophylaxis (mostly with trimethoprim-sulfamethoxazole), is low in a population with adequate access to health care facilities and timely supportive care., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Prophylaxis is strongly recommended in patients with hematological malignancy who are usually at higher risk for infection and neutropenic fever. It is still unclear whether or not there is a definite need for antimicrobial prophylaxis in intermediate-risk hematology patients such as those with lymphoma., Methods: A retrospective analysis was made of patients admitted from January 2009 to December 2017 to the Hematology Department of Diskapi Yildirim Beyazit Training and Research Hospital, a tertiary referral hospital in Ankara, Turkey. The study included patients who were diagnosed with any type of lymphoma and given chemotherapy. Routine antimicrobial prophylaxis was administered to 127 lymphoma patients, and not to 65 lymphoma patients. These two groups were compared in respect of the incidence of total infection episodes (IE), febrile neutropenia episodes, and nonneutropenic clinically documented infection episodes., Results: For all patients with lymphoma and subtypes of non-Hodgkin lymphoma or Hodgkin lymphoma, no significant difference was determined between the groups in respect of the total incidence of IE, febrile neutropenia and nonneutropenic clinically documented infection both during the first-line chemotherapy and throughout the total follow-up period ( p  > 0.05). Patients with prophylaxis had a higher incidence of IE, which was treated with parenteral antibiotics both during the first-line chemotherapy and throughout the total follow-up period ( p  < 0.05)., Conclusion: Antimicrobial prophylaxis was seen to have no effect on the total incidence of infection episode and febrile neutropenia. Therefore, the routine use of antimicrobial prophylaxis should not be recommended for patients with lymphoma.

Background: Recent studies have shown that oral combination antibiotics may improve disease course in refractory inflammatory bowel disease (IBD). Here, we describe the use of combination oral antibiotics as salvage therapy in refractory ulcerative colitis (UC), Crohn's colitis, and IBD-unclassified (IBD-U) at a large pediatric IBD center., Methods: Clinical response, disease activity indices, adverse events, and clinical outcomes were measured up to 1 year after antibiotic treatment in this retrospective cohort study of children with medically refractory IBD colitis., Results: Sixty-three patients with refractory UC, Crohn's colitis, and IBD-U (median age [interquartile range {IQR}], 15.3 [11.2-16.5] years; median disease duration [IQR], 1.2 [0.41-4.6] years) received a combination of 3 or 4 oral antibiotics (most commonly amoxicillin, metronidazole, and either doxycycline or ciprofloxacin) for a median (IQR) of 29 (21-58) days. Thirty-four patients (54%) were deemed corticosteroid-refractory or -dependent, with the majority (62/63) having a previous or present loss of response or primary nonresponse to anti-tumor necrosis factor alpha (anti-TNFα) therapy. Use of combination antibiotics led to a significant decrease in median Pediatric Ulcerative Colitis Activity Index (PUCAI) score (IQR) from 55 (40-65) to 10 (0-40; P < 0.0001) over 3 ± 1 weeks, with 25/63 (39.7%) patients achieving clinical remission (PUCAI <10 points). The clinical benefits of oral antibiotics were independent of anti-TNFα therapy optimization. Among children entering clinical remission (n = 25), only 1 patient required surgery at 1-year follow-up, vs 10 patients in the nonresponder group. Negative predictors of response to combination antibiotics were exposure to doxycycline (odds ratio [OR], 0.25; 95% CI, 0.08-0.76) and PUCAI ≥65 at baseline (OR, 0.2; 95% CI, 0.05-0.74)., Conclusions: Oral combination antibiotics appears to be an effective rescue and steroid-sparing therapy to induce remission in the short term in patients failing a biologic., (© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML) patients, including those treated with azacitidine, are at increased risk for serious infections. The aim of our study was to identify patients with higher infectious risk at the beginning of azacitidine treatment., Patients and Methods: We performed a retrospective evaluation of 298 MDS/CMML/AML patients and included in the analysis 232 patients who completed the first 3 cycles of azacitidine therapy or developed Grade III/IV infection before completing the third cycle., Results: Overall, 143 patients (62%) experienced serious infection, and in 94 patients (41%) infection occurred within the first 3 cycles. The following variables were found to have the most significant effect on the infectious risk in multivariate analysis: red blood cell transfusion dependency (odds ratio [OR], 2.38; 97.5% confidence interval [CI], 1.21-4.79), neutropenia <0.8 × 10 9 /L (OR, 3.03; 97.5% CI, 1.66-5.55), platelet count <50 × 10 9 /L (OR, 2.63; 97.5% CI, 1.42-4.76), albumin level <35 g/dL (OR, 2.04; 97.5% CI, 1.01-4.16), and Eastern Cooperative Oncology Group performance status ≥2 (OR, 2.19; 97.5% CI, 1.40-3.54). Each of these variables is assigned 1 point, and the combined score represents the proposed Azacitidine Infection Risk Model. The infection rate in the first 3 cycles of therapy in lower-risk (0-2 score) and higher-risk (3-5 score) patients was 25% and 73%, respectively. The overall survival was significantly reduced in higher-risk patients compared with the lower-risk cohort (8 vs. 29 months)., Conclusion: We selected a subset with high early risk for serious infection and worse clinical outcome among patients treated with azacitidine., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To investigate the rate of serious bacterial, viral or opportunistic infection in patients with rheumatoid arthritis (RA) starting tocilizumab (TCZ) versus tumour necrosis factor inhibitors (TNFi) or abatacept., Methods: Using claims data from US Medicare from 2010 to 2015, and IMS and MarketScan from 2011 to 2015, we identified adults with RA who initiated TCZ or TNFi (primary comparator)/abatacept (secondary comparator) with prior use of ≥1 different biologic drug or tofacitinib. The primary outcome was hospitalised serious infection (SI), including bacterial, viral or opportunistic infection. To control for >70 confounders, TCZ initiators were propensity score (PS)-matched to TNFi or abatacept initiators. Database-specific HRs were combined by a meta-analysis., Results: The primary cohort included 16 074 TCZ PS-matched to 33 109 TNFi initiators. The risk of composite SI was not different between TCZ and TNFi initiators (combined HR 1.05, 95% CI 0.95 to 1.16). However, TCZ was associated with an increased risk of serious bacterial infection (HR 1.19, 95% CI 1.07 to 1.33), skin and soft tissue infections (HR 2.38, 95% CI 1.47 to 3.86), and diverticulitis (HR 2.34, 95% CI 1.64 to 3.34) versus TNFi. An increased risk of composite SI, serious bacterial infection, diverticulitis, pneumonia/upper respiratory tract infection and septicaemia/bacteraemia was observed in TCZ versus abatacept users., Conclusions: This large multidatabase cohort study found no difference in composite SI risk in patients with RA initiating TCZ versus TNFi after failing ≥1 biologic drug or tofacitinib. However, the risk of serious bacterial infection, skin and soft tissue infections, and diverticulitis was higher in TCZ versus TNFi initiators. The risk of composite SI was higher in TCZ initiators versus abatacept., Competing Interests: Competing interests: SCK has received research grants to the Brigham and Women’s Hospital from Roche, Pfizer and Bristol-Myers Squibb. DHS has received research grants to the Brigham and Women’s Hospital from Pfizer, Genentech, Amgen, AbbVie, Bristol-Myers Squibb and Corrona. AP has nothing to disclose. AJSO has nothing to disclose. RJD reports serving as the principal investigator on research grants from Merck and Vertex to the Brigham and Women’s Hospital for unrelated projects. SG, MB and KS are employed by Genentech. SS is consultant to WHISCON and to Aetion, a software manufacturer of which he also owns equity. SS is the principal investigator of research grants to the Brigham and Women’s Hospital from Boehringer Ingelheim., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Infections represent a major cause of morbidity and mortality in multiple myeloma and are linked to both therapy- and disease-related factors. Although it has been suggested that the rate of infections increased since the introduction of novel agents, controversies still exist. To better assess the risk factors associated with infections in the era of novel agents, we conducted a large retrospective analysis of 479 myeloma patients treated at Jena University Hospital over a period of 12 years. During their disease history, 65% of patients developed at least one infection, and 37% of therapies were associated with at least one infectious episode. The rate of infections was constant over the years, with no increase in infectious complications after the routine implementation of novel agents. Infections were mainly bacterial and strongly associated with high disease burden, relapsed disease, and treatment with high-dose chemotherapy. Varicella zoster virus (VZV) reactivations occurred late during treatment (median time between high-dose chemotherapy and VZV reactivation 6 months, range 0-44 months), and fewer patients developed a VZV reactivation after 2009 (p = 0.001). Infections are still one of the major causes of morbidity in myeloma patients, and prophylactic measures are urgently needed to reduce this potentially lethal complication.

Treatment with Daratumumab (Dara), a monoclonal anti-CD38 antibody of IgG1 subtype, is effective in patients with multiple myeloma (MM). However, Dara also impairs the cellular immunity, which in turn may lead to higher susceptibility to infections. The exact link between immune impairment and infectious complications is unclear. In this study, we report that nine out of 23 patients (39%) with progressive MM had infectious complications after Dara treatment. Five of these patients had viral infections, two developed with bacterial infections and two with both bacterial and viral infections. Two of the viral infections were exogenous, i.e. acute respiratory syncytial virus (RSV) and human metapneumovirus (hMPV), while five consisted of reactivations, i.e. one herpes simplex (HSV), 1 varicella-zoster (VZV) and three cytomegalovirus (CMV). Infections were solely seen in patients with partial response or worse. Assessment of circulating lymphocytes indicated a selective depletion of NK cells and viral reactivation after Dara treatment, however this finding does not exclude the multiple components of viral immune-surveillance that may get disabled during this monoclonal treatment in this patient cohort. These results suggest that the use of antiviral and antibacterial prophylaxis and screening of the patients should be considered., Competing Interests: Genmab A/S, and Janssen Biotech, commercial companies, provided support by providing free materials for the study. There are no patents, products in development or marketed products to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Patients with haematological malignancies have a higher incidence of infection compared with the general population. Several factors contribute to this but specially chemotherapy drugs carry different and specific infectious risks. This protocol discusses the prevention of infections in patients who will undergo chemotherapy for the treatment of haematological malignancies. It is divided into: study prior to the initiation of chemotherapy; vaccination and eradication prior to initiation of chemotherapy; antimicrobial prophylaxis during chemotherapy; special situations. The main aims of this protocol are to serve as support to a more systematic and individualized approach to patients undergoing chemotherapy for the treatment of haematological malignancies and by doing so prevent the infectious complications that may arise.

Purpose To provide an updated joint ASCO/Infectious Diseases Society of American (IDSA) guideline on outpatient management of fever and neutropenia in patients with cancer. Methods ASCO and IDSA convened an Update Expert Panel and conducted a systematic review of relevant studies. The guideline recommendations were based on the review of evidence by the Expert Panel. Results Six new or updated meta-analyses and six new primary studies were added to the updated systematic review. Recommendation Clinical judgment is recommended when determining which patients are candidates for outpatient management, using clinical criteria or a validated tool such as the Multinational Association of Support Care in Cancer risk index. In addition, psychosocial and logistic considerations are outlined within the guideline. The panel continued to endorse consensus recommendations from the previous version of this guideline that patients with febrile neutropenia receive initial doses of empirical antibacterial therapy within 1 hour of triage and be monitored for ≥ 4 hours before discharge. An oral fluoroquinolone plus amoxicillin/clavulanate (or clindamycin, if penicillin allergic) is recommended as empirical outpatient therapy, unless fluoroquinolone prophylaxis was used before fever developed. Patients who do not defervesce after 2 to 3 days of an initial, empirical, broad-spectrum antibiotic regimen should be re-evaluated and considered as candidates for inpatient treatment. Additional information is available at www.asco.org/supportive-care-guidelines and www.asco.org/guidelineswiki .

Aim: Several systematic reviews have been performed to investigate whether intra-articular steroid injections can increase the risk of infection in subsequent arthroplasty. However, the conclusions of these systematic reviews are discordant. The purpose of the present study was to select best evidence and consider risk of bias of these systematic reviews and to provide recommendations through the best evidence., Methods: The systematic reviews that compared the infection rates of arthroplasty with or without previous intra-articular steroid injection were identified. The methodological quality and risk of bias of included systematic reviews were assessed by the AMSTAR instrument and ROBIS tool, respectively. Heterogeneity information within each variable was extracted from the included studies. The Jadad algorithm was then used to determine which systematic reviews can provide the best evidence., Results: Six systematic reviews were eligible for inclusion. The Jadad decision-making tool suggested that two reviews with highest AMSTAR score should be selected. According to the ROBIS tool, there were three systematic reviews with low risk of bias and three with high risk of bias. As a result, two systematic reviews conducted by Charalambous et al. and Marsland et al. with highest AMSTAR scores and low risk of bias were selected as the best evidence., Conclusions: The present study demonstrates that intra-articular steroid injections prior to arthroplasty did not increase infection rates severely after the operation. However, the strength of recommendation is weak due to the limitations of current evidence. Further high-quality primary studies are still required., (© 2018 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Lipopolysaccharide (LPS) treatment and stress may cause immune activation in the brain, an event which has been thought to play a role in mediating stress-induced cognitive dysfunction. However, the enduring impact of psychosocial stress on brain immune activation or cognitive deficits has not been well investigated. Likewise, it remains unexplored whether there exist synergistic effects of psychosocial stress and a weak systemic LPS treatment on brain immune activation and/or cognitive function. In this work, a 10-day social defeat regimen was used to model psychosocial stress and the number and density of ionized calcium-binding adaptor molecule 1 (Iba1)-stained microglia was used to reveal brain immune activation in male Balb/C mice. The social defeat regimen did not cause observable microglial activation in dentate gyrus (DG) 24 h after the conclusion of the regimen. Microglial activation peaked in DG 24 h following a single 1 mg/kg intra-peritoneal LPS injection. At this time point, DG microglial activation was not evident providing 0.125 mg/kg or lower of LPS was used, this dose of LPS was, thus, regarded as the “sub-threshold” in this study. Twenty-four h after the conclusion of the defeat regimen, mice received a social interaction test to determine their defeat stress susceptibility and a “sub-threshold” LPS injection. DG microglial activation was observed in the defeat-stress susceptible, but not in the resilient, mice. Furthermore, the stress-susceptible mice showed impairment in object location and Y maze tasks 24 and 72 h after the “sub-threshold” LPS injection. These results suggest that psychosocial stress, when combined with a negligible peripheral infection, may induce long-lasting hippocampus-related memory deficits exclusively in subjects susceptible to psychosocial stresses., Competing Interests: We declare no conflict of interest.

Background: Children, adolescents, and young adults with very high-risk (VHR) B acute lymphoblastic leukemia (B-ALL) have poor outcomes, and novel therapies are needed for this subgroup. The AALL1131 study evaluated postinduction therapy using cyclophosphamide (CPM), etoposide (ETOP), and clofarabine (CLOF) for patients with VHR B-ALL., Methods: Patients who were 1 to 30 years old and had VHR B-ALL received modified Berlin-Frankfurt-Münster therapy after induction and were randomized to 1) CPM, cytarabine, mercaptopurine, vincristine (VCR), and pegaspargase (control arm), 2) CPM, ETOP, VCR, and pegaspargase (experimental arm 1), or 3) CPM, ETOP, CLOF (30 mg/m 2 /d × 5), VCR, and pegaspargase (experimental arm 2) during the second half of consolidation and delayed intensification., Results: The rates of grade 4/5 infections and grade 3/4 pancreatitis were significantly increased in experimental arm 2. The dose of CLOF was, therefore, reduced to 20 mg/m 2 /d × 5, and myeloid growth factor was required after CLOF administration. Despite these changes, 4 of 39 patients (10.3%) developed grade 4 infections, with 1 of these patients developing a grade 5 acute kidney injury attributed to CLOF, whereas only 1 of 46 patients (2.2%) in experimental arm 1 developed grade 4 infections, and there were no grade 4/5 infections in the control arm (n = 20). Four patients in experimental arm 2 had prolonged cytopenias for >60 days, whereas none did in the control arm or experimental arm 1. Counts failed to recover for 2 of these patients, one having a grade 5 acute kidney injury and the other removed from protocol therapy; both events occurred 92 days after the start of consolidation part 2., Conclusions: In AALL1131, CLOF, administered with CPM and ETOP, was associated with unacceptable toxicity. Cancer 2018;124:1150-9. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Objectives: TNF-α inhibitors (TNFIs) have a black box warning for increased risk of serious infection that was based on evidence from studies of adults. Evidence of the association is lacking for children. We aimed to examine the risk of infection posed by TNFIs compared with DMARDs in children with JIA., Methods: We conducted a cohort study using the 2009-13 Truven MarketScan Commercial Claims and Encounters database. Children <16 years old with JIA who initiated monotherapy with TNFIs or DMARDs were identified and followed for occurrence of serious bacterial infection requiring hospitalization. Cox proportional hazard models were used to estimate hazard ratios for infection associated with TNFIs compared with DMARDs, adjusting for potential confounders with high-dimensional propensity scores and time-varying CS use., Results: We identified 2013 DMARD initiators and 482 TNFI initiators with a mean follow-up of 255 and 307 days, respectively. We identified 18 and 11 patients with a serious infection in the DMARD and TNFI groups, resulting in crude rates of 1.28 (95% CI 0.76-2.02) and 2.72 (95%CI 1.36-4.86) per 100 person-years, respectively. In adjusted models, TNFIs were associated with an increased risk of serious bacterial infection compared with DMARDs (adjusted hazard ratio 2.72, 95% CI: 1.08, 6.86)., Conclusion: Use of TNFIs poses a higher risk of serious infection compared with DMARDs in children with JIA. Our analysis confirms the US Food and Drug Administration warning about TNFI-associated infection in children with JIA., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Aim: To describe the prevalence, clinical characteristics and risk factors of opportunistic infection (OI) in a cohort of patients with inflammatory myopathies, and compare mortality rates between those with and without OIs., Methods: In total, 204 patients from our myositis cohort were reviewed to identify patients who had experienced an OI during the period 1986-2014. The patients' clinical characteristics, treatments received, and outcomes were systematically recorded. Disease activity at the OI diagnosis and the cumulative doses of immunosuppressive drugs were analyzed, as well as the specific pathogens involved and affected organs., Results: The prevalence of OI in the total cohort was 6.4%: viruses, 44.4% (varicella-zoster virus, cytomegalovirus); bacteria, 22.2% (Salmonella sp., Mycobacterium tuberculosis, M. chelonae); fungi, 16.7% (Candida albicans, Pneumocystis jirovecii); and parasites, 16.7% (Toxoplasmosis gondii, Leishmania spp.). Lung and skin/soft tissues were the organs most commonly affected (27.8%). Overall, 55.6% of OIs developed during the first year after the myositis diagnosis and OI was significantly associated with administration of high-dose glucocorticoids (P = 0.0148). Fever at onset of myositis (P = 0.0317), biological therapy (P < 0.001) and sequential administration of four or more immunosuppressive agents during myositis evolution (P = 0.0032) were significantly associated with OI. All-cause mortality in the OI group was 3.69 deaths per 100 patients/year versus 3.40 in the remainder of the cohort (P = 0.996)., Conclusions: The prevalence of OI was 6.4% in our myositis cohort, higher than the rest of the inpatients of our hospital (1.7%; P < 0.01). High-dose glucocorticoids at disease onset and severe immunosuppression are the main factors implicated., (© 2018 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Prostatitis is one of the most prevalent problems in andriatry and urinary surgery. In the present study, we evaluated the effect of procyanidin B2 (PB) on carrageenan-induced chronic nonbacterial prostatitis in rats. Results showed that PB significantly decreased the prostatic index and enhanced the body weight inhibited by carrageenan. Biochemical results revealed that PB significantly lowered the prostatic specific antigen (PSA) and alleviated oxidative stress in serum. The levels of TNF-α, IL-6, and IL-10 in prostatic homogenate were also significantly decreased after PB treatment. We also found evidence that PB treatment reversed the suppression of Nrf2 nuclear translocation, and increased the expressions of NQO1 and HO-1 in the prostate glands. In conclusion, treatment with PB attenuates carrageenan-induced chronic nonbacterial prostatitis via anti-inflammatory and activation of the Nrf2 pathway., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Biologic therapy is effective for treatment of moderate-to-severe psoriasis but may be associated with an increased risk for serious infection., Objective: To estimate the serious infection rate among patients with psoriasis treated with biologic as compared with nonbiologic systemic agents within a community-based health care delivery setting., Methods: We identified 5889 adult Kaiser Permanente Northern California health plan members with psoriasis who had ever been treated with systemic therapies and calculated the incidence rates and 95% confidence intervals (CIs) for serious infections over 29,717 person-years of follow-up. Adjusted hazard ratios (aHRs) were calculated using Cox regression., Results: Adjusting for age, sex, race or ethnicity, and comorbidities revealed a significantly increased risk for overall serious infection among patients treated with biologics as compared with those treated with nonbiologics (aHR, 1.31; 95% CI, 1.02-1.68). More specifically, there was a significantly elevated risk for skin and soft tissue infection (aHR, 1.75; 95% CI, 1.19-2.56) and meningitis (aHR, 9.22; 95% CI, 1.77-48.10) during periods of active biologic use., Limitations: Risk associated with individual drugs was not examined., Conclusion: We found an increased rate of skin and soft tissue infections among patients with psoriasis treated with biologic agents. There also was a signal suggesting increased risk for meningitis. Clinicians should be aware of these potential adverse events when prescribing biologic agents., (Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

We examine the infective complications occurring during azacitidine (AZA) therapy in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). A retrospective review of patients receiving ≥1 cycle of AZA for MDS or AML was performed. Patient demographics, infection prophylaxis/episodes and outcomes were evaluated. Sixty eight patients received 884 AZA cycles. Bacterial infections occurred in 25% of cycle-1 and 27% of cycle-2 AZA therapy. Febrile neutropenia complicated 5.3% of AZA cycles, bacteremia 2% and invasive Aspergillosis 0.3%. Using Poisson modeling, a very high IPSS-R (RR 10.26, 95% CI 1.20, 87.41, p= .033) was identified as an independent risk factor for infection. Infection-related attributable mortality was 23%. The burden of infection is high in AZA-treated patients, associated with high attributable mortality. Over 25% of AZA cycles 1 and 2 were complicated by infection, predominantly bacterial, rates dropping to <10% after cycle-5.

Azacitidine has become an available therapy for high-risk myelodysplastic syndromes. Infectious complications (IC) may impede the success of therapy. Since most patients are managed in an outpatient setting, often with low level of clinical and microbiological documentation, the impact of IC remains unclear. We retrospectively evaluated the clinical course of 77 patients with MDS treated with azacitidine between 2004 and 2015 (median age 69 years). Clinical workup included severity and type of IC, days in the hospital and with antimicrobial therapy, response to azacitidine, and overall survival (OS). In total, 614 azacitidine cycles were administered, 81 cycles with at least one IC. The median number of administered cycles was 6 (range 1-43). Median OS after the start of azacitidine was 17 months (range 1-103). Infection rates were higher in the first 3 cycles with bacterial infections leading. The better patients' hematological response to azacitidine with less IC occurred, and fewer days with antimicrobial treatment were needed. Compared to progressive disease, stable disease made no significant improvement in occurrence of IC and days in the hospital. Older age was associated with more IC and longer time in the hospital. Comorbidities or IPSS-R had no influence on IC. The incidence of IC correlated with hematological response and age. Stable disease led to longer OS, but incidence of IC was comparable to progressive disease and survival seemed to be bought by a considerable number of IC. IC rates were highest in the first 3 cycles. We recommend response evaluation after 4-6 cycles.

The wide burden of anaerobic bacteria colonizing human body comprises about 90% of its total biomass. The biotic relationship between humans and its microbiota sets reciprocal benefits, albeit with pathogenic potencial for the human being in particular dysbiosis situations. Infections adjacent to or originating from the skin or mucous membranes of the intestinal, genitourinary and upper respiratory tracts are often polymicrobial in nature, whereby should anaerobes be invariably included in the etiological differential diagnosis of these conditions. Gram negative bacilli such as Bacteroides fragilis group, Fusobacterium spp., Porphyromonas spp., Prevotella spp. and Gram positive cocci such as Peptostreptococcus spp. stand out for their high virulence and frequence of isolation in suppurative infections and abcesses with metastatic or contiguous relation to human microbiota. The fastidious nature of anaerobic bacteria, especially of less aerotolerant species, compels to particular techniques of sample collection, transport and cultural isolation that challenge clinicians and microbiologists for a full efficient practice. Such requirements bring on a poor identification of anaerobic bacteria in the clinical practice and undervaluation of its aetiopathogenic potential amongst common polymicrobial infections. An approach over microbial flora's composition in the different human anatomical sites is a primary goal of the present article. Clinicians are intended to recognize the variability and proportion of likely involved anaerobic microorganisms in certain infectious processes related to human microbiota, in order to optimize samples processing and the establishment of an appropriate empirical antibiotic therapy, mindful of anaerobic coverage and according to known susceptibility profiles.

Background & Aims: The purpose of this review is to evaluate the risks associated with long-term use of proton pump inhibitors (PPIs), focusing on long-term use of PPIs for three common indications: gastroesophageal reflux disease (GERD), Barrett's esophagus (BE), and non-steroidal anti-inflammatory drug (NSAID) bleeding prophylaxis., Methods: The recommendations outlined in this review are based on expert opinion and on relevant publications from PubMed, EMbase, and the Cochrane library (through July 2016). To identify relevant ongoing trials, we queried clinicaltrials.gov. To assess the quality of evidence, we used a modified approach based on the GRADE Working Group. The Clinical Practice Updates Committee of the American Gastroenterological Association has reviewed these recommendations. Best Practice Advice 1: Patients with GERD and acid-related complications (ie, erosive esophagitis or peptic stricture) should take a PPI for short-term healing, maintenance of healing, and long-term symptom control. Best Practice Advice 2: Patients with uncomplicated GERD who respond to short-term PPIs should subsequently attempt to stop or reduce them. Patients who cannot reduce PPIs should consider ambulatory esophageal pH/impedance monitoring before committing to lifelong PPIs to help distinguish GERD from a functional syndrome. The best candidates for this strategy may be patients with predominantly atypical symptoms or those who lack an obvious predisposition to GERD (eg, central obesity, large hiatal hernia). Best Practice Advice 3: Patients with Barrett's esophagus and symptomatic GERD should take a long-term PPI. Best Practice Advice 4: Asymptomatic patients with Barrett's esophagus should consider a long-term PPI. Best Practice Advice 5: Patients at high risk for ulcer-related bleeding from NSAIDs should take a PPI if they continue to take NSAIDs. Best Practice Advice 6: The dose of long-term PPIs should be periodically reevaluated so that the lowest effective PPI dose can be prescribed to manage the condition. Best Practice Advice 7: Long-term PPI users should not routinely use probiotics to prevent infection. Best Practice Advice 8: Long-term PPI users should not routinely raise their intake of calcium, vitamin B12, or magnesium beyond the Recommended Dietary Allowance (RDA). Best Practice Advice 9: Long-term PPI users should not routinely screen or monitor bone mineral density, serum creatinine, magnesium, or vitamin B12. Best Practice Advice 10: Specific PPI formulations should not be selected based on potential risks., (Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Part 3 of this 4-part continuing medical education series reviews several important infectious complications of corticosteroid use, including a focus on pneumocystis pneumonia (PCP) prophylaxis, tuberculosis, viral hepatitis, and other infections, followed by a discussion of vaccination recommendations in immunosuppressed patients., (Copyright © 2016 American Academy of Dermatology, Inc. All rights reserved.)

Introduction: To quantify the association between PPI use, type and dose and infectious gastroenteritis hospitalization in a population-based cohort of middle-aged and older adults., Methods: Prospective study of 38,019 concession card holders followed up over 6 years in the Sax Institute's 45 and Up Study. Data from the baseline questionnaire were linked to prescription medication, hospitalization, notifiable disease, cancer registry and death datasets from 2006-2012. Associations between PPI use and gastroenteritis hospitalization were examined using Cox regressions with age as the underlying time variable., Results: Among 38,019 participants, the median age was 69.7 years, and 57.3% were women. Compared to non-users, current PPI users were more likely to be older, and have a higher BMI. During follow-up there were 1,982 incident gastroenteritis hospitalizations (crude rate: 12.9 per 1000 person-years, 95% CI: 12.3-13.5). PPI use was significantly associated with infectious gastroenteritis hospitalization (aHR 1.4, 95% CI: 1.2-1.5). Among current users, a dose-response relationship was observed between the average daily dose (DDD) dispensed per day and infectious gastroenteritis hospitalization (Ptrend<0.001). We also observed higher rates of infectious gastroenteritis hospitalization and greater PPI use among participants with a history of chronic bowel problems (aHR 2.2, 95% CI: 1.9-2.5). There was no difference in risk by type of PPI. Recent use of H2 receptors was not associated with gastroenteritis hospitalization., Conclusion: PPI use is associated with an increased risk of infectious gastroenteritis hospitalization. Clinicians should be aware of this risk when considering PPI therapy., Competing Interests: The authors have declared that no competing interests exist.

Objective: To assess whether the time between the last rituximab infusion and initiation of a different biologic agent influenced infection risk in patients with rheumatoid arthritis (RA)., Methods: Patients with RA who newly initiated rituximab within the Consortium of Rheumatology Researchers of North America registry were included if they switched to a nonrituximab biologic agent and had ≥1 followup visit within 12 months of switching. Patients were categorized by duration of time between their last rituximab infusion and initiation of a subsequent biologic agent (≤5 months, 6-11 months, and ≥12 months). The primary outcome was time to first infectious event. Adjusted Cox regression models estimated the association between time to starting a subsequent biologic agent and infection., Results: A total of 44 overall infections (7 serious, 37 nonserious) were reported during the 12-month followup in the 215 patients included in this analysis (104 switched at ≤5 months, 67 at 6-11 months, and 44 at ≥12 months). Median (interquartile range) time to infection was 4 (2-5) months. Infection rates per patient-year in the ≤5-month, 6-11-month, and ≥12-month groups were 0.34 (95% confidence interval [95% CI] 0.22-0.52), 0.30 (95% CI 0.17-0.52), and 0.41 (95% CI 0.22-0.77), respectively. After adjustment, time to switch to a subsequent biologic agent was not associated with infection, which remained unchanged when number and rate of rituximab retreatments were included in the models., Conclusion: In this real-world cohort of patients with RA, infection rates ranged from 0.30 to 0.41 per patient-year, with no significant difference in the rate between patients who initiated a subsequent biologic agent earlier versus later after rituximab treatment., (© 2016, The Authors. Arthritis Care & Research published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.)

Unlabelled: Proton pump inhibitors (PPIs) may be a risk factor for hepatic encephalopathy (HE) in patients with cirrhosis, possibly through translocation of gut bacteria, which can also lead to spontaneous bacterial peritonitis (SBP). We examined the associations between PPIs and development of HE or SBP in patients with cirrhosis with ascites. We used data from three 1-year trials of satavaptan for ascites control. We used Cox regression to compare HE and SBP rates between users and nonusers of PPIs. At inclusion, 39% of the 865 patients with cirrhosis with ascites used PPIs, 52% used them at some point during the follow-up, and the proportion of current users was always in the 30%-39% range. There were 189 first-time HE episodes during the follow-up, and the cumulative 1-year risk was 31% for those who used PPIs at baseline versus 25% for those who did not. The confounder-adjusted hazard ratio (HR) of HE for current PPI use versus current nonuse was 1.36 (95% confidence interval [CI], 1.01-1.84). The HR for overt HE was higher (adjusted HR = 1.88; 95% CI, 1.21-1.91). During the follow-up, 86 patients developed SBP. The adjusted HR of SBP for current PPI users versus nonusers was 1.72 (95% CI, 1.10-2.69)., Conclusion: PPIs were used by 52% of this international cirrhosis cohort during a 1-year period and was a risk factor for developing HE and SBP. These findings are consistent with the hypothesis that PPIs may increase translocation of gut bacteria. (Hepatology 2016;64:1265-1272)., (© 2016 by the American Association for the Study of Liver Diseases.)

Several adverse effects associated with long-term PPI therapy have been reported. These potential risks or side effects have included hypergastrinemia, carcinoid formation, devel- opment of gastric cancer, bacterial overgrowth, Clostridium difficile infection, pneumonia, bone fracture and malabsorption of vitamin B12 and iron. I explain each of these adverse events based on the guideline for GERD in both Japan and US, multiple meta-analyses and systematic review previously published.

The purpose of this review is to establish whether there is a significantly increased incidence of serious infections during treatment for rheumatoid arthritis (RA) with etanercept, infliximab or adalimumab, to determine the background risk of serious infection in RA patients without treatment with any biological therapy and to ascertain which organisms are involved in serious infections in RA patients while being treated with etanercept, infliximab or adalimumab. Randomised controlled trials (RCTs), meta-analyses of RCTs, Cochrane reviews, national registry articles and case reports were identified using PubMed/MEDLINE, The Cochrane Library and Google Scholar. The medical subject heading "rheumatoid arthritis" was combined with "serious infection" or "infection" or "adverse drug events" with each of the three reference biological therapies separately: etanercept, infliximab and adalimumab. These electronic searches were limited to human studies, adult studies, those published in the last 10 years (2004-14) and in the English language. Studies which involved the tumor necrosis factor-α inhibitors certolizumab pegol or golimumab were excluded. The background risk of serious infection appears to be approximately two-fold more than non-RA patients before any treatment with biological therapy. The national registries, which may represent the typical RA patient more accurately than clinical trials, suggest a small but significantly increased incidence of serious infection ranging 1.2-2.78 times that of control (treatment with methotrexate). Mycobacteria spp., Staphyloccus aureus, Listeria monocytogenes, Varicella zoster virus and Leishmania species (spp.) repeatedly appear in the case report literature and should be in the mind of the clinician faced with a serious infection in a RA patient with an unknown pathogen who is being treated with either etanercept, infliximab or adalimumab., (© 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.)

Objective: to evaluate the incidence of bacterial aggravations and antibiotics administration with analysis of effectiveness of antiviral therapy in ambulatory patients with acute viral respiratory infection (ARVI) and influenza., Material and Methods: International cohort open non-interventional .study <

Anesthetics are known to modulate host immune responses, but separating the variables of surgery from anesthesia when analyzing hospital acquired infections is often difficult. Here, the bacterial pathogen Listeria monocytogenes (Lm) was used to assess the impact of the common anesthetic propofol on host susceptibility to infection. Brief sedation of mice with physiologically relevant concentrations of propofol increased bacterial burdens in target organs by more than 10,000-fold relative to infected control animals. The adverse effects of propofol sedation on immune clearance of Lm persisted after recovery from sedation, as animals given the drug remained susceptible to infection for days following anesthesia. In contrast to propofol, sedation with alternative anesthetics such as ketamine/xylazine or pentobarbital did not increase susceptibility to systemic Lm infection. Propofol altered systemic cytokine and chemokine expression during infection, and prevented effective bacterial clearance by inhibiting the recruitment and/or activity of immune effector cells at sites of infection. Propofol exposure induced a marked reduction in marginal zone macrophages in the spleens of Lm infected mice, resulting in bacterial dissemination into deep tissue. Propofol also significantly increased mouse kidney abscess formation following infection with the common nosocomial pathogen Staphylococcus aureus. Taken together, these data indicate that even brief exposure to propofol severely compromises host resistance to microbial infection for days after recovery from sedation.

We used a meta-analysis approach to investigate the association between proton pump inhibitor (PPI) use and risk of spontaneous bacterial peritonitis (SBP) in cirrhotic patients. We searched Ovid Medline, Embase, and the Cochrane Library to identify eligible studies. We included studies that compared cirrhotic patients who did or did not use PPIs. The primary outcome was SBP, and the secondary outcome was overall bacterial infection. Results were pooled using random-effect models. This process led to identification of 12 journal articles and 5 conference abstracts. The pooled data showed that PPI use in patients with cirrhosis and ascites was significantly associated with an increased risk of SBP [odds ratio (OR) = 2.17; 95% confidence interval (CI) = 1.46-3.23; P < 0.05; I2 = 85.6%] and overall risk of bacterial infection (OR = 1.98; 95%CI = 1.36-2.87; P < 0.05; I2 = 0). Subgroup analysis revealed that journal articles and studies reporting adjusted effect estimates demonstrated that PPI users had a significantly increased risk of SBP (OR = 2.13; 95%CI = 1.61-2.82; P < 0.05; I2 = 29.4%; and OR = 1.98; 95%CI = 1.42-2.77; P < 0.05; I2 = 67%, respectively). In conclusion, PPI use increased the risk of SBP and overall bacterial infection in patients with cirrhosis and ascites. PPIs should be administered after careful assessment of the indications in cirrhotic patients. Future well-designed prospective studies are warranted to clarify the dose relationships and to compare infection risks associated with different classes of PPIs.

Ulcerative colitis is a chronic, idiopathic, inflammatory bowel disease characterized by a relapsing and remitting course. A substantial proportion of patients fail conventional therapies despite therapy with immunosuppressives and tumor necrosis factor antagonists. Accordingly, newer therapeutic agents that target disease-specific inflammation and minimize adverse events are required. Central to the pathogenesis of ulcerative colitis is an aberrant host response to commensal microorganisms with a resultant dysregulation of gut immune homeostasis and lymphocyte trafficking. Recently, a newer biologic, vedolizumab, which blocks lymphocyte trafficking, has been developed for use in moderate to severe ulcerative colitis. The efficacy of this agent has been demonstrated to be similar to that of other currently available biologics, and the selectivity of this agent in blocking lymphocyte migration to the gut has substantially reduced treatment-related adverse events. The drug has now been approved for use in the United States and Europe, and, although the exact positioning of this biologic in clinical practice is yet to be defined, it represents an important new chapter in our armamentarium of treatment options for this population. In this review, we will highlight key considerations to be made by providers when using this agent in clinical practice., (© 2015 Pharmacotherapy Publications, Inc.)

Objective: There is little information regarding the incidence of bacterial infections as an adverse effect of telaprevir (TVR)-based triple therapy. This study was performed in order to evaluate the baseline and on-treatment predictors of bacterial infections in patients treated with TVR-based triple therapy., Methods: This multicenter study evaluated 430 patients with chronic hepatitis C who received 12 weeks of TVR in combination with 24 weeks of pegylated interferon α2b plus ribavirin. The occurrence of a bacterial infection during anti-viral treatment was defined as the onset of local or systemic inflammation as a result of pathogenic bacteria., Results: Bacterial infections occurred in 21 of the 430 (4.9%) patients during TVR-based triple therapy. Among these subjects, 71.4% (15 of 21) experienced bacterial infections during the initial eight weeks of treatment. Urinary tract infections were the most frequent infection, observed in 2.8% of cases (12 of 430). The rate of urinary tract infection among women (11 of 215, 5.1%) was significantly higher than that observed among men (1 of 215, 0.5%) (p<0.0001). According to a multivariable logistic regression analysis, the only significant independent predictor was the pretreatment serum albumin level (p=0.0008). Of the 21 patients who experienced bacterial infections, only one (4.8%) had to discontinue the treatment; however, the others were able to continue anti-viral treatment in combination with antibiotic treatment., Conclusion: Clinicians should be concerned regarding the incidence of bacterial infections among patients treated with TVR-based triple therapy, especially those with a low serum albumin level.