An international multicenter study comparing COVID-19 omicron outcomes in patients with hematological malignancies treated with obinutuzumab versus rituximab.

OBJECTIVES: Hematological malignancy (HM) patients treated with anti-CD20 monoclonal antibodies are at higher risk for severe COVID-19. A previous single-center study showed worse outcomes in patients treated with obinutuzumab compared to rituximab. We examined this hypothesis in a large international multicenter cohort. METHODS: We included HM patients from 15 centers, from five countries treated with anti-CD20, comparing those treated with obinutuzumab (O-G) to rituximab (R-G) between December 2021 and June 2022, when Omicron lineage was dominant. RESULTS: We collected data on 1048 patients. Within the R-G (n = 762, 73%), 191 (25%) contracted COVID-19 compared to 103 (36%) in the O-G. COVID-19 patients in the O-G were younger (61 ± 11.7 vs. 64 ± 14.5, p = 0.039), had more indolent HM diagnosis (aggressive lymphoma: 3.9% vs. 67.0%, p < 0.001), and most were on maintenance therapy at COVID-19 diagnosis (63.0% vs. 16.8%, p < 0.001). Severe-critical COVID-19 occurred in 31.1% of patients in the O-G and 22.5% in the R-G. In multivariable analysis, O-G had a 2.08-fold increased risk for severe-critical COVID-19 compared to R-G (95% CI 1.13-3.84), adjusted for Charlson comorbidity index, sex, and tixagevimab/cilgavimab (T-C) prophylaxis. Further analysis comparing O-G to R-G demonstrated increased hospitalizations (51.5% vs. 35.6% p = 0.008), ICU admissions (12.6% vs. 5.8%, p = 0.042), but the nonsignificant difference in COVID-19-related mortality (n = 10, 9.7% vs. n = 12, 6.3%, p = 0.293). CONCLUSIONS: Despite younger age and a more indolent HM diagnosis, patients receiving obinutuzumab had more severe COVID-19 outcomes than those receiving rituximab. Our findings underscore the need to evaluate the risk-benefit balance when considering obinutuzumab therapy for HM patients during respiratory viral outbreaks.

No changes in hemostasis after COVID-19-heterologous vaccination schedule: A subanalysis of the phase 2 CombiVacS study.

Background: Several cases of unusual thrombotic events and thrombocytopenia were described after vaccination with recombinant adenoviral vectors encoding the spike protein antigen of SARS-CoV-2. Objectives: The objective of this study was to elucidate the impact of a COVID-19 heterologous vaccination schedule, including priming with adenovirus vaccine, on hemostasis profiles. Methods: The present study is a subanalysis of the CombiVacS clinical trial initiated in April 2021 that included adult participants previously vaccinated with a single dose of ChAdOx1-S. Between 8 and 12 weeks after vaccination, they were randomly assigned (2:1) to receive either BNT162b2 vaccine (intervention group, n = 99) or continue observation (control group, n = 50). Samples drawn before and 28 days after a vaccination with BNT162b2 were analyzed for platelet count and markers of hemostasis (D-dimer, anti-PF4 antibodies, cfDNA, PAI-1, thrombin generation, and serum capacity to activate platelets). Results: Platelet count from all participants after receiving BNT162b2 was within the normal range. Anti-PF4 antibodies were present in 26% and 18% of the subjects from the control and intervention groups, respectively, at day 28. In most cases, the levels of anti-PF4 antibodies were high before receiving BNT162b2. Serum from these participants did not activate platelets from healthy controls. There were no differences between the groups in PAI-1 and cfDNA plasma levels. According to the D-dimer plasma concentration, the thrombin generation test showed that none of the participants had a procoagulant profile. Conclusion: Our data suggest that the heterologous vaccination against COVID-19 with ChAdOx1-S and a second dose with BNT162b2 might be safe in terms of haemostasis.

Bacterial co-infections in COVID-19 pneumonia in a tertiary care hospital: Surfing the first wave.

The aim of this study is to review bacterial isolates from respiratory samples of patients with severe COVID-19 disease during the first 2 months of the first wave in our hospital. A single-center retrospective observational study in critically ill adult patients was performed. A total of 1251 respiratory samples from 1195 patients were processed. Samples from 66 patients (5.52%) were determined to be microbiologically significant by a semi-quantitative culture. All patients received broad spectrum antibiotherapy as an empirical treatment. The isolated bacteria were mainly Enterobacterales followed by Staphylococcus aureus and Pseudomonas aeruginosa. Bacterial co-infections in ICU stay could seem not dependent on the virus that has produced the viral pneumonia similarly as with other respiratory viruses such as Influenza virus.

Characteristics of patients with suspected COVID-19 pneumonia and repeatedly negative RT-PCR.

OBJECTIVES: Challenges remain and there are still a sufficient number of cases with epidemiological, clinical features and radiological data suggestive of COVID-19 pneumonia that persist negative in their RT-PCR results. The aim of the study was to define the distinguishing characteristics between patients developing a serological response to SARS-CoV-2 and those who did not. METHODS: RT-PCR tests used were TaqPath 2019-nCoV Assay Kit v1 (ORF-1ab, N and S genes) from Thermo Fisher Diagnostics and SARS-COV-2 Kit (N and E genes) from Vircell. Serological response was tested using the rapid SARS-CoV2 IgG/IgM Test Cassette from T and D Diagnostics Canada and CMC Medical Devices and Drugs, S.L, CE. RESULTS: In this cross-sectional study, we included a cohort of 52 patients recruited from 31 March 2020 to 23 April 2020. Patients with positive serology had an older average age (73.29) compared to those who were negative (54.82) (P<0.05). Sat02 in 27 of 34 patients with positive serology were below 94% (P<0.05). There was a frequency of 1.5% negative SARS-CoV-2 RT-PCRs during the study period concurring with 36.7% of positivity. CONCLUSION: Clinical features and other biomarkers in a context of a positive serology can be considered crucial for diagnosis.

Intestinal loads of OXA-48-producing Klebsiella pneumoniae in colonized patients determined from surveillance rectal swabs.

OBJECTIVES: To determine quantitatively the extent of intestinal colonization by OXA-48-producing Klebsiella pneumoniae (KpOXA) in hospitalized patients. METHODS: The load of the OXA-48 ß-lactamase gene in rectal swabs from 147 colonized patients was measured by quantitative PCR. The load was calculated relative to the total bacterial population (represented by the 16S rRNA gene) using the ΔΔCt method and pure cultures of OXA-48-producing K. pneumoniae as reference samples. The relative loads of the epidemic K. pneumoniae clones ST11 and ST405 were also measured. RESULTS: The relative intestinal loads of the OXA-48 ß-lactamase gene, RLOXA-48, in hospitalized patients were high. The median RLOXA-48 was -0.42 (95% confidence interval (CI): -0.60 to -0.16), close to that of a pure culture of OXA-48-producing K. pneumoniae (RLOXA-48 = 0). In those patients colonized by the KpOXA clones ST11 (51/147, 34.7%) and ST405 (14/147, 9.5%), the relative loads of these clones were similarly high (median RLST11 = -1.1, 95% CI: -1.64 to -0.92; median RLST405 = -1.3, 95% CI: -1.76 to -0.96). Patients that had received previous antibiotic treatments and those that developed infections by KpOXA had significantly higher RLOXA-48 values: -0.32 (95% CI: -0.58 to -0.20) vs -1.07 (95% CI: -2.43 to -0.35) and -0.26 (-0.77 to -0.23) vs -0.47 (-0.74 to -0.28), respectively. CONCLUSIONS: Colonization by KpOXA in hospital patients involves intestinal loads much higher than the K. pneumoniae loads reported in the normal microbiota, reaching levels close to those of pure KpOXA cultures in many cases and largely replacing the host microbiota.

Proof-of-concept trial of the combination of lactitol with Bifidobacterium bifidum and Lactobacillus acidophilus for the eradication of intestinal OXA-48-producing Enterobacteriaceae.

BACKGROUND: The major reservoir of carbapenemase-producing Enterobacteriaceae (CPE) is the gastrointestinal tract of colonized patients. Colonization is silent and may last for months, but the risk of infection by CPE in colonized patients is significant. METHODS: Eight long-term intestinal carriers of OXA-48-producing Enterobacteriaceae (OXA-PE) were treated during 3 weeks with daily oral lactitol (Emportal®), Bifidobacterium bifidum and Lactobacillus acidophilus (Infloran®). Weekly stool samples were collected during the treatment period and 6 weeks later. The presence of OXA-PE was investigated by microbiological cultures and qPCR. RESULTS: At the end of treatment (EoT, secondary endpoint 1), four of the subjects had negative OXA-PE cultures. Three weeks later (secondary endpoint 2), six subjects were negative. Six weeks after the EoT (primary endpoint), three subjects had negative OXA-PE cultures. The relative intestinal load of OXA-PE decreased in all the patients during treatment. CONCLUSIONS: The combination of prebiotics and probiotics was well tolerated. A rapid reduction on the OXA-PE intestinal loads was observed. At the EoT, decolonization was achieved in three patients.Clinical Trials Registration: NCT02307383. EudraCT Number: 2014-000449-65.

Bacteriemia por enterobacterias productoras de carbapenemasas: el papel de Microbiología en su detección rápida / Carbapenem-producing enterobacteriaceae bloodstream infection: Microbiology's role in their rapid detection

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MALDI-TOF MS for rapid diagnosis of Anaerobiospirillum succiniciproducens, an unusual causative agent of bacteraemia in humans. Two case reports and literature review.

Anaerobiospirillum succiniciproducens is a gram-negative anaerobic spiral rod which is part of the normal flora of dogs and cats and can produce bacteraemia and diarrhoea in humans. In this report we describe two cases of bacteraemia caused by A. succiniciproducens which was successfully identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). We present a comprehensive literature review of 48 cases of A. succiniciproducens bacteraemia in which we describe previous underlying conditions, clinical presentations, identification methodology and antibiotic susceptibility data.

Ceftazidime-Avibactam as Salvage Therapy for Infections Caused by Carbapenem-Resistant Organisms.

Ceftazidime-avibactam (CAZ-AVI) is a recently approved ß-lactam-ß-lactamase inhibitor combination with the potential to treat serious infections caused by carbapenem-resistant organisms. Few patients with such infections were included in the CAZ-AVI clinical trials, and clinical experience is lacking. We present a case series of patients with infections caused by carbapenem-resistant Enterobacteriaceae (CRE) or Pseudomonas aeruginosa (CRPa) who were treated with CAZ-AVI salvage therapy on a compassionate-use basis. Physicians who had prescribed CAZ-AVI completed a case report form. We used descriptive statistics to summarize patient characteristics and treatment outcomes. We used the Wilcoxon rank sum test and Fisher's exact test to compare patients by treatment outcome. The sample included 36 patients infected with CRE and two with CRPa. The most common infections were intra-abdominal. Physicians categorized 60.5% of patients as having life-threatening infections. All but two patients received other antibiotics before CAZ-AVI, for a median of 13 days. The median duration of CAZ-AVI treatment was 16 days. Twenty-five patients (65.8%) concurrently received other antibiotics to which their pathogen was nonresistant in vitro Twenty-eight patients (73.7%, 95% confidence interval [CI], 56.9 to 86.6%) experienced clinical and/or microbiological cure. Five patients (20.8%) with documented microbiological cure died, whereas 10 patients (71.4%) with no documented microbiological cure died (P = 0.01). In three-quarters of cases, CAZ-AVI (alone or combined with other antibiotics) cured infections caused by carbapenem-resistant organisms, 95% of which had failed previous therapy. Microbiological cure was associated with improved survival. CAZ-AVI shows promising clinical results for infections for which treatment options are limited.

Infections caused by carbapenemase-producing Enterobacteriaceae: risk factors, clinical features and prognosis.

Infections caused by carbapenem-producing Enterobacteriaceae (CPE) can present as several infectious syndromes, but they primarily present as respiratory, urinary and blood stream infections (primary or catheter-related) that are usually found as nosocomial or healthcare-associated infections. The risk of CPE infection is influenced by individual factors, such as the length of the hospital stay and their exposure to invasive procedures and/or to antimicrobials. Of note, exposure to several antimicrobials, not only carbapenems, has been linked to CPE colonization; the duration of antibiotic exposure is one of the primary drivers of CPE acquisition. Individual risk factors must be considered jointly with the local epidemiology of these microorganisms in healthcare institutions. Overall, these infections have a high associated mortality. Mortality is influenced by host factors (e.g., age, comorbidity and immune deficiency), infection-related variables (e.g., type and severity of the infection) and treatment-related factors such as the delay in the initiation of appropriate antimicrobial therapy and the use or monotherapy or combined antimicrobial therapy. Gaining knowledge concerning the epidemiology, clinical features and prognostic features of CPE infection could be useful for improving infection prevention and for the management of patients with infections caused by these microorganisms.

Infections caused by carbapenemase-producing Enterobacteriaceae: Risk factors, clinical features and prognosis / Infecciones causadas por enterobacterias productoras de carbapenemasas: factores de riesgo, características clínicas y pronóstico

Infections caused by carbapenem-producing Enterobacteriaceae (CPE) can present as several infectious syndromes, but they primarily present as respiratory, urinary and blood stream infections (primary or catheter-related) that are usually found as nosocomial or healthcare-associated infections. The risk of CPE infection is influenced by individual factors, such as the length of the hospital stay and their exposure to invasive procedures and/or to antimicrobials. Of note, exposure to several antimicrobials, not only carbapenems, has been linked to CPE colonization; the duration of antibiotic exposure is one of the primary drivers of CPE acquisition. Individual risk factors must be considered jointly with the local epidemiology of these microorganisms in healthcare institutions. Overall, these infections have a high associated mortality. Mortality is influenced by host factors (e.g., age, comorbidity and immune deficiency), infection-related variables (e.g., type and severity of the infection) and treatment-related factors such as the delay in the initiation of appropriate antimicrobial therapy and the use or monotherapy or combined antimicrobial therapy. Gaining knowledge concerning the epidemiology, clinical features and prognostic features of CPE infection could be useful for improving infection prevention and for the management of patients with infections caused by these microorganisms (AU)

Las infecciones causadas por enterobacterias productoras de carbapenemasas (EPC) se pueden presentar con diferentes cuadros clínicos, aunque suelen ser más frecuentes las infecciones respiratorias, urinarias y la bacteriemia, ya sea primaria o asociada a catéter. Su adquisición es habitualmente nosocomial o relacionada con la asistencia sanitaria. El riesgo de presentar infección por EPC se relaciona con factores individuales como la duración del ingreso hospitalario y la exposición a procedimientos invasivos o antibióticos. El tratamiento previo con diversos antimicrobianos, además de carbapenemas, y en especial su duración son factores de riesgo esenciales para su adquisición. Estos factores individuales se deben valorar teniendo en cuenta la epidemiología local de las EPC en el medio sanitario. La mortalidad global de las infecciones causadas por EPC es generalmente elevada y se relaciona con factores del huésped (edad, inmunodepresión y enfermedades subyacentes), la infección (localización y gravedad) y el tratamiento antibiótico (retraso en el inicio de terapia adecuada y uso de monoterapia o terapia combinada). Un mayor conocimiento de la epidemiología, la presentación clínica y los factores pronósticos de las infecciones causadas por EPC debe contribuir a mejorar su prevención y manejo global (AU)

Meningitis aséptica y síndrome de Sweet / Aseptic meningitis and Sweet´s syndrome

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Hepatotoxicidad por clopidogrel / Clopidogrel-induced hepatoxicity

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Rotura esplénica espontánea como complicación de una pancreatitis aguda / Spontaneous splenic rupture as a complication of acute pancreatitis

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