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.

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.

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.

The risk of infections in multiple myeloma before and after the advent of novel agents: a 12-year survey.

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.

Risk of serious infections in tocilizumab versus other biologic drugs in patients with rheumatoid arthritis: a multidatabase cohort study.

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.

Is antimicrobial prophylaxis necessary for lymphoma patients? A single centre, real-life experience.

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.

[Protocol for the Prevention of Infections Related to the Treatment of Hematological Malignancies]. / Protocolo de Prevenção de Infeções Relacionadas com o Tratamento de Neoplasias Hematológicas.

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.

Os doentes com doença hematológica neoplásica apresentam uma incidência de infeções superior à da população geral. Vários fatores contribuem para este aumento de incidência destacando-se os fármacos quimioterápicos que acarretam riscos infeciosos diferentes e específicos. Este protocolo versa a prevenção de infeções em doentes que vão ser submetidos a quimioterapia para tratamento de neoplasias hematológicas. Divide-se em: estudo prévio ao início de quimioterapia; vacinação e erradicações prévias ao início de quimioterapia; profilaxias antimicrobianas durante a quimioterapia; situações especiais. Pretende-se com este protocolo uma abordagem sistematizada e individualizada da situação clínica de cada doente de forma a prevenir de forma a prevenir de infeções emdoentes sob quimioterapia para tratamento de neoplasias hematológicas.

Outpatient Management of Fever and Neutropenia in Adults Treated for Malignancy: American Society of Clinical Oncology and Infectious Diseases Society of America Clinical Practice Guideline Update.

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 .

Risk of serious bacterial infection associated with tumour necrosis factor-alpha inhibitors in children with juvenile idiopathic arthritis.

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.