Most hospital patients at risk for bacterial infection undergo an anesthetic: implications for infection control practices related to the anesthesia workspace.

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.

RéSUMé: OBJECTIF: Même avec un respect de près de 100 % des protocoles antibiotiques prophylactiques, bon nombre de patients et patientes en chirurgie (> 5 %) développent des infections du site opératoire, dont certaines sont causées par des agents pathogènes transmis par l'espace de travail anesthésique (p. ex. appareil d'anesthésie), y compris un staphylocoque doré multirésistant. La réduction de la contamination de l'espace de travail anesthésique réduit considérablement le risque d'infections du site opératoire. Nous avons estimé le pourcentage de patientes et patients hospitalisé·es à risque d'infections associées aux soins de santé qui pourraient bénéficier de l'application de mesures préventives de base sous le contrôle de praticiens et praticiennes d'anesthésie (par exemple, leur hygiène des mains). MéTHODE: Nous avons mené une étude de cohorte rétrospective qui comprenait toutes les personnes admises au Système de santé de l'Université de Miami d'avril 2021 à mars 2022 pour une hospitalisation, une intervention chirurgicale, des visites aux urgences ou des consultations externes. Des listes ont été créées pour la date et l'heure de début de chaque antibiotique parentéral administré et de chaque anesthésique. RéSULTATS: Parmi les 28 213 consultations avec les patient·es comprenant des antibiotiques parentéraux, plus de la moitié (64,3 %) comportaient également un anesthésique (intervalle de confiance à 99 %, 62,2 à 66,6). L'hypothèse selon laquelle la plupart des antibiotiques étaient administrés lors de rencontres lorsqu'une personne bénéficiait d'une anesthésie a été acceptée (P < 0,001). Cette observation peut sembler contre-intuitive, car des antibiotiques parentéraux ont été administrés pour moins de la moitié des 53 235 anesthésiques (34,2 %). En effet, la plupart des anesthésies (63,5 %) ont été administrées en dehors de la salle d'opération, et seulement 7,2 % de cette patientèle a reçu un antibiotique parentéral. CONCLUSION: Étant donné qu'environ les deux tiers des patientes et patients qui reçoivent un antibiotique par voie intraveineuse bénéficient également d'une anesthésie, une plus grande utilisation de mesures efficaces de contrôle des infections dans l'espace de travail anesthésique de la salle d'opération pourrait réduire considérablement les taux globaux d'infections hospitalières.

Infectious complications after intensive chemotherapy with CLAG-M versus 7+3 for AML and other high-grade myeloid neoplasms.

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.

Prevalence of Bacterial Urinary Tract Infection Among Patients With Type 2 Diabetes Mellitus on Sodium-Glucose Cotransporter-2 Inhibitors: A Prospective Real-World Setting Study.

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.

[What is the proportion of infectiology in the specialization urology? : A pilot study to underline the significance of Antibiotic Stewardship in urology]. / Welchen Anteil hat die Infektiologie am Fachgebiet Urologie? : Ein Pilotprojekt, zur Hervorhebung der Antibiotic-Stewardship-Bedeutung.

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.

Tocilizumab in critically ill COVID-19 patients: An observational study.

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.

Protective Effects of Statin Therapy in Cirrhosis Are Limited by a Common SLCO1B1 Transporter Variant.

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.

Glycogen synthase kinase-3ß (GSK-3ß) deficiency inactivates the NLRP3 inflammasome-mediated cell pyroptosis in LPS-treated periodontal ligament cells (PDLCs).

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-1ß, 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-3ß (GSK-3ß) was upregulated by LPS treatment, and inhibition of GSK-3ß by its inhibitor (GSKI) or GSK-3ß downregulation vectors was effective to restore normal cellular functions in LPS-treated PDLCs. Mechanistically, blockage of GSK-3ß 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-3ß/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.

Infections in patients with lymphoproliferative diseases treated with targeted agents: SEIFEM multicentric retrospective study.

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.

Dupilumab and the risk of conjunctivitis and serious infection in patients with atopic dermatitis: A propensity score-matched cohort study.

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.

Preventing infections in children and adults with asplenia.

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.

Proton pump inhibitor use is associated with a variety of infections in patients with liver cirrhosis.

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.

Efficacy and safety of two pegfilgrastim biosimilars: Tripegfilgrastim and pegteograstim.

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.

Treatment of Yersinia similis with the cationic lipid DOTAP enhances adhesion to and invasion into intestinal epithelial cells - A proof-of-principle study.

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.

Bacterial Infection Among Patients With Multiple Myeloma Treated With Bortezomib-based Induction Therapy: Real-World Experience in an Asian Cancer Center.

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.

[Proton pump inhibitors and cancers: A hazardous association?] / Inhibiteurs de la pompe à protons (IPP) et cancers : une association à risques ?

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.

Impact of microbial contamination of the islet product during total pancreatectomy with islet autotransplantation.

BACKGROUND: The combined use of interleukin-1ß 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-1ß 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.

Comparison of Total Anaerobic Microbiota in Periodontitis Before and After the Subgingival Irrigation with Chlorhexidine at 0. 12 % / Comparación de la Microbiota Anaerobia Total en Periodontitis antes y Después de la Irrigación Subgingival con Clorhexidina al 0, 12 %

ABSTRACT: The objective of this study was to determine the effect of the subgingival irrigation of chlorhexidine 0.12 % of the total anaerobic microbiota. Microbial sampling to 30 subjects with periodontitis stage II Grade B, in pockets with a periodontal probing depth > 4 mm. The subgingival irrigation was made with 5 mL of chlorhexidine in the test group and with 5 mL of distilled water in the control group. 24 hours after the procedure was obtained a second sample to compare. It was found that the subgingival irrigation with chlorhexidine at 0.12 % achieved a statistically significant decrease in anaerobic microbiota (p< 0.05).

RESUMEN: El objetivo del presente estudio fue determinar el efecto de la irrigación subgingival de la clorhexidina 0,12 % sobre la microbiota anaeróbica total. Se tomaron muestras microbiológicas a 30 sujetos con periodontitis estadio II grado B, en sacos periodontales con una profundidad de sondaje > 4 mm. Se realizó la irrigación subgingival con 5 mL. de clorhexidina en el grupo test y con 5 mL. de agua destilada en el grupo control. 24 horas después del procedimiento se obtuvo una segunda muestra a comparar. Se detectó que la irrigación subgingival con clorhexidina al 0,12 % logra disminuir en forma estadísticamente significativa la microbiota anaeróbica total (p< 0,05).

Predictive Model for Infection Risk in Myelodysplastic Syndromes, Acute Myeloid Leukemia, and Chronic Myelomonocytic Leukemia Patients Treated With Azacitidine; Azacitidine Infection Risk Model: The Polish Adult Leukemia Group Study.

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 × 109/L (OR, 3.03; 97.5% CI, 1.66-5.55), platelet count <50 × 109/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.

Efficacy of Combination Antibiotic Therapy for Refractory Pediatric Inflammatory Bowel Disease.

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.

Infectious complications and NK cell depletion following daratumumab treatment of Multiple Myeloma.

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.